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Kindle Money Mastery

If you have ever wanted to be able to be an author for a living or as a side hobby, this is the online course for you! This course gives you access to all kinds of ebook and materials on how to make the most of the Amazon Kindle Store to make a huge amount of money! You don't need to be a creative genius, spend Hours on end writing, or even know how to use Kindle! All that you have to do is follow the instructions in this course by Stefan Pylarinos. Stefan built this course based on what he does for a living Every Single DAY. This is REAL information that has been perfected in a real business Why would this NOT work for you? This is how Stefan makes his money Why not you? Just think You can make living money writing Kindle books. And you can learn all about how to get started making money with K Money Mastery! Read more...

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Case Study Microvessel Density in Non Small Cell Lung Cancer

For systematic reviews based on published data, it is generally the aim to include as many studies as possible. For IPD systematic reviews, it is natural to adopt the same philosophy. However, identifying all relevant studies and obtaining the data can be very time-consuming, especially if efforts are made to obtain unpublished data, so that the goal of including data from all relevant studies may often be impossible to achieve. Emphasis should be placed on also trying to identify and include as many unpublished studies as possible, to try to reduce the impact of publication bias. Finding unpublished studies is not easy. An unpublished prognostic 'study' may be merely a set of data sitting on a computer, possibly with little documentation. Indeed, their existence may well be nearly forgotten. Unpublished studies can be identified through a variety of strategies including asking personal contacts, advertising the project on the Internet, on email lists, or at conferences, and writing...

Cold Spring Harbor

During the 1950s, I spent eight summers at the Cold Spring Harbor Laboratories on Long Island, New York. Dr. Barbara McClintock permitted me to use her greenhouses while she was working outdoors with corn (Zea mays). Each year at the end of August, Dr. Alfred Hershey organized a bacteriophage symposium for invited bacterial virologists. Although I did not work on bacteriophages, I was permitted to attend these meetings, where as yet unpublished findings were presented by the virologists. Throughout the summers, Drs. Max Delbruck, Salvator Luria, and Ernst Mayr were working in Cold Spring Harbor, lecturing, and socializing with the small group of scientists. Dr. Luria was working on his textbook on viruses and I was greatly impressed watching him dictate into a tape recorder each morning, and then mailing the tape to his secretary in Urbana for typing. When the typed version came back to Cold Spring Harbor, Dr. Luria made small corrections and each chapter was ready for publication....

Angiotensin Converting Enzyme

ACE is present at low to moderate levels in large areas of the brain, and in high levels in the nucleas tractus solitarii (NTS), and is likely to generate Ang II locally (82). Increasing the levels of ACE in the brain by transfection with a plasmid containing the human ACE gene caused an increase in BP, heart rate, and Ang II and ACE levels that lasted 2 wk (83). Unpublished results from our laboratory testing three different sequences of ACE-AS-ODNs showed a decrease in BP in hypertensive SHRs of 15-25 mmHg.

Other Amylinlike Molecular Forms

Several studies have addressed the possibility that type 2 diabetes melli-tus is associated with a mutation of the amylin gene. A polymorphism has been identified in studies of 155 Caucasians (Cook et al., 1991) and 119 south Indians (McCarthy et al., 1992), but no linkage with disease state was identified. In two studies, no abnormality of the amylin gene or promoter was identified in Japanese patients with NIDDM (Kajio et al. , 1992 Tokuyama et al., 1994). In another Japanese study of 540 individuals, a missense mutation was detected in 12 individuals in whom Gly replaced Ser-20 in the amylin molecule (Sakagashira et al., 1996 Sanke et al., 1996). This mutation was significantly overrepresented in patients with early onset NIDDM (10 of patients compared to 4 of all NIDDM patients and 0 of normal individuals). This mutant amylin molecule binds to amylin receptors in vitro (Moore et al., unpublished) and is active in vivo for inhibition of gastric emptying (Gedulin et al.,...

Immunohistochemical Localization of a2ARs in Rat Brain

Immunohistochemical distribution of the A subtype of a2-ARs at the light microscopic level in rat brain has been reported by our group (14,16,23) and by Aoki and colleagues (13). The A subtype shows an extensive distribution throughout the brain in perikarya and the neuropil. In contrast to the a2A-AR immunoreactivity, only perikaryal a2C-AR immunoreactivity is evident in the rat brain, though its distribution is also quite widespread (15). Localization of the B subtype has been described in kidney (19). However, we have not detected a2B-AR immunoreactivity in brain (Rosin and Okusa, unpublished observations). Indeed, there is no evidence to date for expression of a2B-AR protein in brain in adult animals or at best very, very low expression. Despite the discrete localization of mRNA for the a2B-AR in hypothalamus and thala-

Effects Of Acetaldehyde On Platelets

Agonists 39,40 , We have been recently performing studies on acetaldehyde, and find little if any effect of acetaldehyde, added in vitro, on human platelet aggregation at concentrations consistent with levels in humans after ethanol consumption (unpublished data from our laboratory). More work is needed in this area.

Extravesicular buffer and protein buffers

The protein sample should be in a buffer that is chloride free, if possible, and should also lack any compounds which would interfere with electrode response. (3-Mercaptoethanol has been found to especially perturb electrode response (S. L. Schendel and J. C. Reed, unpublished results).

Demographics And Epidemiology

The incidence and prevalence of the CBS and CBD are not known. Bower et al. did not identify any case of CBS or CBD in their analysis of parkinsonism in Olmsted County, Minnesota (14). However, in a review of the autopsy records of the Mayo Clinic from 1970 to 2000, two residents of Olmsted County, Minnesota, were found to have CBD pathology, with one exhibiting the CBS and the other exhibiting dementia of the Alzheimer type (B. Boeve, unpublished data). As of 2003, we are following 11 patients with the CBS in the Mayo Alzheimer's Disease Research Center who reside in the state of Minnesota. Considering there are approx 5 million residents in the state, a minimum prevalence estimate is at least 2 per million (B. Boeve, unpublished data). The rarity of the CBS and CBD will make more definitive incidence and prevalence estimates difficult.

Serotonin Antagonists

There is no specific treatment for the fatigue of cholesta-sis at present. The methodology to study fatigue is subjective thus, there is substantial uncertainty in interpreting any data on fatigue. Some patients with PBC report that taking naps during the day facilitates the performance of their daily activities (NV Bergasa, unpublished). The examination of patients with fatigue and liver disease includes the exclusion of conditions that have a negative impact on energy level, including anemia, thyroid dysfunction, adrenal and renal insufficiencies, and depression, in order for specific treatments to be prescribed if those conditions are present.

Management options

Ideally, women with a previous history of meningitis should be seen antenatally by the obstetric anaesthetist for assessment and reassurance. It is important to ascertain whether the meningitis was bacterial or viral as there is some evidence that those women who have had a bacterial meningitis have increased risk of accidental dural puncture (unpublished personal series), especially if the meningitis was caused by tuberculosis, and they can be advised of this risk. In general, most women can be reassured that they are not at extra risk from regional analgesia and anaesthesia.

Role Of Acetaldehydeprotein Adducts And Free Radicals

The liver is the main site of alcohol-derived acetaldehyde production, an extremely reactive metabolite. Acetaldehyde binds with proteins to form protein-adducts which may induce auto-immunogenic responses (as identified by raised serum antibodies) or render the affected protein functionally inoperative 74-82 , In rats subjected to 6 weeks ethanol feeding, ELISA showed increased amounts of reduced- and unreduced-acetaldehyde protein adducts as well as malondialdehyde-acetaldehyde protein adducts (Worrall S, Richardson PJ, Preedy VR, unpublished). However, there was no evidence of increased malondialdehyde and a-hydroxyethyl-protein adducts in hearts of ethanol fed rats compared to pair-fed controls (Worrall S, Richardson PJ, Preedy VR unpublished). Acetaldehyde may induce myocardial ischaemia and coronary vasospasm 50 , Elevations in circulating cardiac troponin-T occur after 2.5-6 hours in response to acute ethanol dosage in rats, suggestive of a membrane-mediated event 10,95 , We...

Choice of field strategies and additional practices

Msika, Zimbabwe, 1992, unpublished data), experiments at higher altitudes confirmed the difficulties of avoiding inducing high percentages of bolting while still making the best use of a potentially long growing season. Sowing in February in Marondera, Zimbabwe, in 1992, for example, resulted in high bolting in almost all cultivars except for the very early cvs 'Early Lockyer Brown' and 'Early Lockyer White' (Yates, Australia) and 'Ori' (Hazera, Israel) (R.L. Msika, Zimbabwe, 1992, unpublished data). In theory, it should be possible to control the factors that affect inflorescence induction by adjusting the sowing date (Castell, 1974 Abd El-Rehim et al., 1996). However, in practice it is not possible to forecast the coming night temperatures accurately historical records may allow them to be estimated as probabilities. Corgan and Kedar (1990) suggested that a low rate of bolting ( 10 ) in a subtropical onion crop showed that it had been sown at about...

The need for formal evidence syntheses of prognostic marker studies

The most commonly applied evidence synthesis method is a systematic review, which is a transparent framework for the collection, critical appraisal, and synthesis of the current evidence from published and (if possible) unpublished studies Egger, Davey Smith, and Altman (2001) . If appropriate, a meta-analysis can be performed at the end of a systematic review, which is a statistical approach that combines the quantitative evidence from all the individual studies (or the subset of better quality studies) to produce overall evidence-based results Egger, Davey Smith, and Altman (2001) . In order to facilitate a meta-analysis approach, it is common for a summary statistic (e.g., hazard ratio) of interest to be chosen and extracted, where possible, from each published (and unpublished) study. Alongside the estimate of the summary statistic chosen, one also requires a measure of the uncertainty about the estimate obtained e.g., standard error of the loge(hazard ratio) , so...

Differential scanning calorimetry DSC

(ii) to construct a state-phase diagram in which the glass transition temperature (Tg) and the ice formation melting temperature are plotted as a function of moisture content (Vertucci, 1990 Leprince and Vertucci, 1995 Buitink et al., 1996). The calorimetric behaviour of the glass transition can be characterized although DSC does not give direct access to the physical and biological properties of glasses. Sometimes, the heat released during the glass transition is below the sensitivity of the equipment. For example, in seed species such as rice and tobacco, Tg cannot be detected by DSC (O. Leprince and J. Buitink, unpublished data). Furthermore, in oily seeds such as neem and Impatiens, the lipid melting transitions often mask the thermal events associated with water,

Designs For Twochannel Arrays

A condition for this approach is that the arrays are spotted in the same batch so the array to array variation is as small as possible. It is also important to use signal-dependent normalization before comparing between slides (arrays). Figure 13.1 shows a comparison of within-slide fold changes to between-slide fold changes for an experiment comparing a TnrA mutant in Bacillus subtilis to its wild type using spotted cDNA arrays with 12 replicates and 4111 genes (unpublished data). There are only a few genes out of the 4111 where there is a significant difference between the two ratios.

Recent studies of Rhinocyllus 19861999 Variation in phenology

In North America, recent work supports the hypothesis of latitudinal variation in activity and development of R conicus. For example, in Virginia the activity of overwintered adult weevils was observed to start in mid to late April in Virginia, USA weedfeeders rhinocyllus_c.html) and in Nebraska on 13 May in 1998 (S.M. Louda, unpublished results). Also, newly developed teneral adults were observed in Colorado, USA, in June and July (http www.ag.state.co.us DPI publications muskthistle.html). However, further north in south-central Alberta, Canada, overwintered adults appeared only in early June and newly emerged adults were seen in August (A.S. McClay, Alberta, 1999, personal communication). Thus, geographical differences in activity pattern can have an environmental component. Furthermore, in Europe, Aeschlimann (1999) confirmed Zwolfer's (1967) observation that the activity period of the R. conicus in the more southern Mediterranean climatic region was earlier than that in the more...

Technical Considerations 251 Biopsy Time

It is still unclear in humans what impact biopsying embryos with four to five cells has in humans. In a study carried out by Tarin et al. (44), embryos biopsied on day 2 after insemination showed a great degree of retarded cleavage rates after biopsy as well as low cell numbers in resulting blastocysts (44). In contrast, pregnancies have been reported from embryos biopsied at the four-cell stage (A. Thornhill, unpublished data).

Cryopreservation of Biopsied Embryos

Cryopreservation of biopsied embryos is becoming a necessity with patients who have a greater number of normal embryos than those transferred. Experiments in mice have shown promising results in achieving successful cryopreservation of biopsied embryos (51, 53, 93). Cryopreservation of biopsied human embryos would not be as simple as methods applied for unbiopsied embryos due to the presence of a hole in the zona (which acts as a protective barrier to regulate the inflow of toxic cryoprotectant). To date, few groups have attempted freezing biopsied embryos. One of the first reports by Joris et al. (74) tried freezing biopsied day 3 embryos using a slow freeze thaw procedure with DMSO. Survival in the biopsied group was significantly lower than in intact controls. Nevertheless, in biopsied embryos that did survive the freeze thaw procedure, blasto-cyst formation was seen in a small percentage. Similar results were confirmed by Magli et al. (95). This suggests that although survival...

Pharmacological Studies For Validation Of The Animal Model

Because myoclonus is often considered a component of an epileptic syndrome, antiepileptic drugs may be potentially useful for the treatment of this condition. Indeed, patients with myoclonus do respond to an array of antiepileptic agents. For example, clonazepam and val-proate, two classical antiepileptic agents, can help reduce symptoms of post-hypoxic myoclonus in at least 50 of patients (Fahn, 1978 Fahn, 1986). In order to examine the validity of our model, we examined whether the rats with myoclonus also responded to antiepileptic agents. Results showed that both clonazepam and valproate significantly reduced myoclonus, as indicated by decreased myoclonus scores (Figure 2). The therapeutic effects of these two agents on myoclonus in this model occurred in a dose-related manner (Truong et al., 1994). Piracetam (2-oxo-1-pyrrolidine acetamide), a nootropic agent with an unknown mechanism of action, has also been shown to be effective in human myoclonus. Piracetam is found to be...

Hyperekplexia Models To Develop And Test Therapeutic Intervention

In order to understand the pathological mechanisms acting in GlyR disease, pharmacological treatments have been applied to some of the animal models described above. For example, it has been shown in transgenic animals over-expressing the glycine receptor mutation (S267Q) that this mutant GlyR renders mice more resistant to ethanol (Findlay et al., 2002) these results provide in vivo evidence for the hypothesis that the GlyR is an important target for motor incoordination and anesthetic properties of ethanol action (Mihic, 1999 Mihic et al., 1997 Sebe et al., 2003). Quinlan and associates have found modified ethanol responses in mice with mutant GlyR (Quinlan et al., 2002). Application of cannabinoids to GlyR mutant mice have so far not produced evidence for a potential benefit of such agents in GlyR disease (D. Baker, unpublished observation). The use of such models to develop and test therapeutic intervention has just begun. Thus, we have recently shown that the anesthetic propofol,...

Preparation of Purified Virus Material

The external glycoprotein of retroviruses are essential for their binding to the target cell. However, these are usually not recovered to a high extent with conventional virus purification protocols. To overcome this problem, we have studied the behavior of several retroviruses in polymer phase systems. Feline and bovine leukemia viruses (19,20), as well as human immunodeficiency viruses (HIV-1 and HIV-2), and simian immunodeficiency virus (SIVmac), were all recovered from culture supernatant with retained external glycoproteins (19-22). With HIV-2 (unpublished results) and SIVmac, the method was scaled up to 25 L of culture supernatant (7,22,23) and the purified viruses used as source for the preparation of highly purified external glycoproteins (22,23). One may also mention the report by Andrews, Huang, and Asenjo (24), which points to the usefulness of the polymer phase-extraction method for the separa

Ribozymes Targeted To A Secreted Fgfbinding Protein

The originally described characteristics of FGF-BP (62) make this protein an excellent extracellular carrier molecule for immobilized and hence inactivated FGFs. In studies addressing this hypothesis, we found that expression of FGF-BP in cell lines that express bFGF leads to a tumorigenic and angiogenic phenotype of these cells (63). We also found that FGF-BP-transfected cells release the protein into their media together with bFGF in a noncovalently bound form. This released bFGF is biologically active. Based on these observations, we speculated that spontaneously expressed FGF-BP in human cancer may play a role for the tumorigenic phenotype through its activating effect on locally stored and ubiquitously present bFGF or lesser abundant aFGF. Indeed, we found FGF-BP expressed in SCC cell lines from different organs and at very high levels in almost all SCC tumor tissue specimens from patients (63) as well as in some colon cancer samples and cell lines (unpublished data). In...

Antisense Oligonucleotide Chemistries

Several different chemistries have been used to induce exon skipping in the dystrophin gene, including oligodeoxynucleotides (Pramono et al. 1996), 2'-O-methyl and 2'-O-(2-Methoxy)ethyl modified bases (Wilton, unpublished data), all on phosphorothioate backbones, chimeric 2'-O-methyl ethylene bridged nucleic acids (Surono et al. 2004 Yagi et al. 2004), locked nucleic acids (Aartsma-Rus et al. 2004b), morpholino oligonucleotides (Aartsma-Rus et al. 2004b Gebski et al. 2003), and peptide nucleic acids (Aartsma-Rus et al. 2004b).

Implications for testing the role of PHFs in cell and animal models

Although the structure of PHFs is interesting from a biological point of view, the overriding goal is to use the structural information for preventing the neuronal degeneration in AD. The current insights can be used in two ways. First, one of the main obstacles to generating cell or animal models has been the exceptional solubility of tau (mentioned above), which means that simple overexpression of the protein (or modification by phosphorylation) is usually not sufficient to generate neurofibrillary tangles in a reasonable time frame. This problem can be overcome by using mutations that are known to enhance -structure. Examples are the P301L and AK280 mutations, both known as FTDP-17 mutations, which modify the vicinity of the hexapeptide motifs to allow more extensive -conformation (von Bergen et al. 2001). In both cases, transgenic mice readily develop neurofibrillary tangles (Lewis et al. 2000 and own observations, unpublished). With these models, it is possible to test hypotheses...

Antisense Studies in Animal Models of Muscular Dystrophy

The mdx mouse offers only one target for antisense oligonucleotide evaluation. Interestingly, targeting the same coordinates in the human dystrophin gene transcript that induced exon skipping in the mouse (that is, the last 2 bases of exon 23 and the first 18 bases of intron 23), resulted in no detectable skipping of human exon 23 (Mann, Wilton, Fletcher, unpublished observations). Although the coordinates are the same, the target sequence is different and this suggests that each exon must be addressed on a case by case basis. The canine model of muscular dystrophy requires that exons 6 and 8 be removed to restore the frame-shift induced by exon 7 exclusion. Our laboratory has been able to induce efficient skipping of these exons in cultured cells and we have detected induced dystrophin by western blotting in vitro and in vivo (McClorey, Fletcher, and Wilton, unpublished observations). Cultured GRMD myoblasts are not robust, and the difficulty in detecting dystrophin may be a...

Tumor Cells Subvert Host Defenses Designed To Suppress Angiogenesis

Ately activated, are able to arrest the growth or kill neoplastic and transformed target cells. Although there is substantial in vitro evidence supporting the antitumor activity of activated M0, the in vivo relevance of these observations has not been unequivocally demonstrated even under conditions in which M0 are likely to have antitumor activity. M0 express diverse functions that are essential for tissue remodeling, inflammation, and immunity. Analyses of tumor-associated M0 (TAM) functions suggest these multifunctional cells have the capacity to affect diverse aspects of neoplastic development, including vascularization, growth rate and metastasis, stroma development, and remodeling. There is evidence that in some neoplasms, including human cancers, the protumor functions of M0 prevail. The importance of a sustained influx of activated TAM to tumor neovascularization has been recently investigated by Lingen, Bouck, and Polverini (unpublished observations). They recently found that...

Immunity and resistance

One significant problem associated with disease resistance is differentiation between resistant and uninfected bivalves. Neither show clinical signs of disease or, for most cases, readily detectable evidence of the infectious agent (see 'Control and treatment' section below). The persistence of infectious organisms in resistant (subclinical) bivalve populations is also noteworthy. The period in between epizootics of Malpeque disease averaged 15 years, until the last outbreak in the 1960s. Recent experiments with a historically susceptible population of C. virginica have shown that the pathogen is still present, and virulent, in endemic areas, despite no recorded mortalities or clinical signs of the disease in the resident oyster populations for over 25 years (S.E. McGladdery, unpublished data).

Responses of gas exchange and volatile emission to drying

A wide variety of gaseous metabolites can be studied in drying tissues O2 and CO2 exchange as markers of respiration or photosynthesis, ethanol and acetaldehyde as markers of fermentation, alkanes, alkones, alkenes, aldehydes (volatile) as markers of oxidative stress. Several instruments such as infrared CO2 analysers, gas-phase O2 electrodes or O2 analysers can detect and analyse CO2 and O2 exchanges. These types of analysers have mainly been used to describe the effects of desiccation on photo-synthetic activities of resurrection plants (Schwab et al., 1989) and photosymbiotic lichens (Nash et al., 1990 Scheidegger et al., 1995). However, they are not always suited to assaying low respiration rates from nearly dried material because of their low sensitivity (O. Leprince, unpublished data).

Nontarget feeding on Cirsium species in North America

To date, R conicus has been reared from flowerheads of native Cirsium species in every extensive survey of native Cirsium species in the USA in California (Goeden and Ricker, 1986a,b, 1987a,b Turner et al., 1987 Turner and Herr, 1996 Palmisano and Fox, 1997), in Colorado (Louda et al., 1997), in Montana (Rees, 1977, 1991), in Nebraska (Louda et al., 1997 Louda, 1998), as well as South Dakota and Wyoming (Louda et al., 1997). Because of ongoing studies of thistle-insect interactions in prairie grasslands, Louda and colleagues were the first to be able to quantify (i) the population dynamics of host range expansion by R conicus (Louda, 1998, 2000a) (ii) the consequences of feeding by native floral insect herbivores on the population dynamics of a native thistle, Cirsium canescens Nutt., before the host range expansion of R conicus (Louda et al., 1990, 1992 Louda and Potvin, 1995) (iii) the demographic effects of accelerated seed loss caused by R conicus for C. canescens after the...

Antisense Oligonucleotide Modification of Splicing Patterns

Since the most common consequences of a splice site mutation are either exon skipping or the activation of a cryptic splice site, the application of antisense oligonucleotides to a particular splicing motif should also result in either exon skipping or activation of a cryptic splice site. Now, with some experience in this area, several investigators have found the most likely consequence to be exon removal (Aartsma-Rus et al. 2004b Errington et al. 2003 Gebski et al. 2003 Mann et al. 2001 Mann et al. 2002 Pramono et al. 1996 Takeshima et al. 2001 van Deutekom et al. 2001 Wilton et al. 1999). Activation of cryptic splice sites in the dystrophin gene has only occurred in a few cases, and these cryptic splice sites could be suppressed by a second antisense oligonucleotide (Dominski and Kole 1993). Alternately, we have found that redesigning the first antisense oligonucleotide to a different motif within the same exon resulted in precise exon skipping (Wilton, Fletcher, and McClorey,...

The Coffee botanical family Rubiaceae

Such as the Tea plant family (Theaceae), the Guarana plant family (Sapinidaceae) and the Cola plant family (Sterculiaceae). The plants of the Guarana family have one additional alkaloid, guaranine (Table 10). Purine alkaloids have a biological and according to recent (still unpublished) clinical results, also a positive and prophylactic effect in decreasing the risk of Parkinson's disease, for example in the case of caffeine. From Waltheria douradinha St. Hill belonging to the Cola family, walterione A, a tryptophan-derived alkaloid, has been discovered147. This alkaloid has important biological potential. Staerk et al.50 noted five alkaloids isolated from the species Corynanthe pachyceras K. Schum., a member of the Rubiaceae family. Corynantheidine, corynantheine, dihydrocorynantheine, a-yohimbine and corynanthine were isolated from the bark of this species and all these alkaloids demonstrate powerful bio and ecoimpacts (leishmanici-dal, antiplasmodial and cytotoxic activity). Other...

Prevention of amyloidogenesis in an AD mouse model by the asecretase ADAM10

In a first step, mice were generated that overexpressed either ADAM10 to different extents or the catalytically inactive ADAM10 mutant. Overexpression of the transgenes was under control of the neuron-specific, postnatally active thy1 -promoter. Neuronal overexpression of ADAM10 had no detrimental effects on ADAM10 single-transgenic mice these animals exhibited normal behavioral abilities (Schmitt et al. 2004). This finding was promising given that ADAM10 is also involved in the cleavage of membrane proteins other than APP, such as Notch, EGF, and cadherins. We examined whether Notch signalling was affected by analyzing the expression level of Hes5, a gene affected downstream of Notch, and we found no significant difference between Hes5 transcript levels of adult non-transgenic mice and ADAM10-overexpressing mice. Gene profiling studies of transgenic mice recently showed that overexpression of ADAM10 does not lead to an increased expression of genes coding for pro-inflammatory or...

Thalidomide And Analogs In Angiogenesis And Cancer

Gordon et al. provided evidence for the conversion of thalidomide to a toxic arene oxide metabolite by liver microsomes (10), possibly by the action of cytochrome P-450 (42). Since both a 3- and a 4-hydroxy metabolite of thalidomide have been detected, it was hypothesized that a reactive 3,4-epoxy form of thalidomide may mediate its teratogenic action (10). Interestingly, tetrafluorothalidomide, a fluorinated analog of thalidomide that cannot be hydroxylated or converted into an epoxide (43), inhibited angiogenesis comparable to thalidomide at its maximum tolerated dose (unpublished data). This suggests that neither epoxide formation nor hydroxylation of the pthalimide ring is essential for inhibiting angiogenesis. Other metabolites of thalidomide and EM-12, including 3-hydroxyphthalmide, 4-hydroxythalidomide, EM-27, and EM-356, were also tested but did not inhibit corneal neovascularization (20). S ince PG-acid and EM-138 inhibited angiogenesis in both the chick CAM assay and in...

Human Angiostatin Protein Derived from Elastase Cleavage of Human Plasminogen

The fact that mouse and human recombinant AP expressed in Escherichia coli is active in vivo (Lin et al. Zhou et al., unpublished) argues against this possibility, because E. coli-derived proteins are expressed without posttranslational modifications, including glyco-sylation. However, the role of the carbohydrate chains, with respect to the specificity of activity, and in vivo clearance time, among others, remains to be defined.

Modulation of TSP1 Production During Tumor Development

Essential changes in secretion of TSP-1, as well as in the production of other inducers and inhibitors of angiogenesis, are a result of the same genetic changes that drive carcinogenesis, the activation of oncogenes, and the inactivation of tumor-suppressor genes (3). TSP-1 production can be regulated by a variety of oncogenes and tumor-suppressor genes, and, in contrast to the mitogenic effects of oncogene activation and tumor suppressor gene loss, which often can have a broad tissue range, the effects of these mutations on angiogenic agents are often strikingly tissue-specific. The activation of a variety of oncogenes can depress the production of TSP-1, and thus presumably enhance the angiogenic potential of a developing tumor. Activated ras is effective in several different cells (97,98), as is src (98,99). V-myc (100) and c-jun (101) also downmodulate TSP-1. Only in the case of v-myc has it been shown that the angiogenic phenotype of the cells switches from antiangiogenic to...

Education Level and VP for Brain Damaged Samples

Herring and Reitan (1986) also noted the same type of relationship between level of education and V-P discrepancy indicated in Table 8.22 for patients with left lesions, based on unpublished studies in their laboratory P ersons with lower educational levels and left cerebral hemisphere lesions had relatively low VIQ compared with PIQ, whereas VIQs were only slightly lower than PIQs for persons with left cerebral hemisphere lesions when educational levels were higher (p. 540).

Prospective dorsal views

Unequal cell divisions in the embryo of Helobdella fall into two categories (Scott Settle, unpublished observations) (Fig. 2). Slightly unequal divisions, defined as those that are clearly unequal but in which the ratio of sister cell diameters is less than 3, are seen among the large yolk-rich blas-tomeres beginning with first cleavage, and also in the stereotyped cell lineages leading from micromeres and blast cells to their definitive prostomial and segmental progeny, respectively. Highly unequal divisions, defined as those in which the ratio of sister cell volumes is greater than 3, consist of the micromere-forming divisions scattered throughout cleavage, and the production of blast cells by the repeated stem-cell divisions of the teloblasts. As will be illustrated below, the categorization of two different cell division as slightly unequal for example does not mean that they employ the same mechanism for regulating the position of the spindle apparatus, but nonetheless it's a...

Results And Discussion

Although the increased CSF-phospho-tau in AD suggests that abnormal phosphorylated tau in CSF is a marker for tau pathology in the brain, CSF-phospho-tau levels in FTD or CBD were only moderately increased. Furthermore CSF-phospho-tau levels are normal in PSP, a condition pathologically characterized by abnormal phosphorylated tau deposition (Flament et al., 1991). This indicates that either phosphorylation at threonine 181 is less specific for tau pathology in FTD or CBD or that other phosphorylation sites on tau might be more important (Ishiguro et al., 1999). Alternatively, an increase of the tau phospho-tau ratio might be related to other pathological mechanisms it has been suggested that an increase in CSF levels of cytoskeletal proteins is related to differential involvement of these proteins in the pathophysiology of AD and FTD (Sjogren et al., 2000). Very high levels of CSF-tau in stroke (Hesse et al., 2000) and Creutzfeldt-Jakob disease (Otto et al., 1997) are not accompanied...

TSP1 Is a Potent Inhibitor In Vivo

TSP-1 is effective at inhibiting angiogenesis induced by living tumor cells in several settings. Small pieces of mouse melanoma, or human colon carcinoma cut from tumors growing in nude mice and implanted directly into rat corneas, induce vessel ingrowth that is blocked when a pellet containing TSP-1 is interposed between the tumor fragment and the vascular limbus (P. J. Polverini and N. Bouck, unpublished data). Systemic treatment of mice with purified TSP-1 can also be anti angiogenic and inhibit tumor growth. High levels of TSP-1 in the circulation render mice unable to mount a corneal angiogenic response to a pellet containing stimulatory bFGF and halt the growth of experimental lung metastases (19). There is a single report of TSP-1 failing to inhibit angiogenesis in an in vivo assay (20). When incorporated into Elvax-40 pellets, human platelet thrombospondin was slightly angiogenic when tested alone, and enhanced, rather than inhibited, angiogenesis stimulated by bFGF or by LPS....

Changes In M0 Tsp1 Expression Levels Influence Tumor Neovascularization

The importance of how alterations in the expression of TSP1 by TAM can affect tumor angiogenesis is best exemplified by recent studies by Ling en et al. (68,69). These workers have demonstrated that retinoic acid, a chemopreventive agent currently used to reduce the incidence of secondary tumor growth in patients with head and neck squamous cells carcinoma, does so in part by inducing tumor cell to produce inhibitors of angiogenesis and by rendering endothelial cells refractory to proangiogenic mediators. In addition, Lingen, Bouck, and Polverini (unpublished observations) have found that human squa-mous carcinoma treated with the chemopreventive agent retinoic acid failed to activate M0, resulting in a diminished capacity to express angiogenic activity in vitro and in vivo. Moreover, when these cells were phenotyped for expression of proangiogenic and angioinhibitory molecules, the most dramatic change observed was marked increase in the level of TSP1 production. These results...

Pathogenesis of atypical Aeromonas salmonicida

As salmonid culture represents an important asset in several countries, several non-salmonid isolates have been tested for their possible virulence in salmonids. There is no doubt that one goldfish isolate can be highly virulent for salmonids after i.p. injection, with LD50 values ranging from 1 x 102 to 1 x 103 injected cells. This has been confirmed by other studies, in which goldfish isolates were found to be virulent for Atlantic salmon, brook trout and rainbow trout under different challenge conditions, including i.p. injection and bath challenge, with or without prior skin abrasion, and by cohabitation (Carson and Handlinger, 1988 Whittington and Cullis, 1988). In addition, a sand eel isolate killed 50 of rainbow trout injected i.p. with 8 x 106 cfu (Dalsgaard and Paulsen, 1986). Isolates from other species, including flounder, turbot, wrasse and cod, were not found to be virulent for salmonids (Pedersen et al., 1994). Even if some atypical strains isolated from non-salmonids...

Presenilin mutations selectively increase A042 in plasma

As we watched the color come up at the end of the assay, it was immediately obvious by eye that there were some samples with a distinctly higher level of Ap40. When we broke code, every one of those samples was from a carrier the Ap40 levels in the carriers were completely separated from those in the non-carriers. We thought our ability to distinguish both pre-symptomatic and symptomatic carriers so clearly in human plasma was exciting news. The reviewers of the manuscript that was submitted disagreed, arguing that finding elevated Ap in the plasma of carriers wasn't novel since we and others had already shown the same effect in transfected cultured cells. Because of this, the finding went unpublished until we included it in the manuscript focused primarily on PS1 2 mutations (Scheuner et al. 1996) that is the subject of this commentary. The result from the Swedish APP mutation was critically important for our work on PS1 2 mutations because it gave us confidence that we would...

Ist In A Number Of Experimental Settings

The abundance and localization of influenza A virus specific CD 8+ T cells in lymph nodes and lung tissue was studied in influenza A infected mice 3. IST was used to characterize LCM virus specific CTLs in peripheral lymphoid and brain tissues in mice (9), and used to characterize simian immunodeficiency virus (SIV) specific T cells in lymph nodes, spleen, vagina, cervix, and rectum, colon, ileum and jejunum in SIV infected macaques (10-13 Skinner et al., unpublished data).

Possible Mechanisms Involved In Papio Papio Myoclonus

The question as to whether or not Papio papio ILSM and MIM are linked remains open. Of 106 baboons tested for this purpose, 41 (39 ) presented with ILSM, of which six also displayed MIM. Of the remaining 65 baboons, four had MIM (our unpublished observations). Statistical analysis of these data indicated that the two types of myoclonus are independent of each other. It is thus probable that brainstem dysfunction, even if it may be suspected in both cases, could implicate different circuits responsible for the two different types of myoclonus.

Discrimination and memory processes

In an unpublished dissertation, Paletz identified an effect of developmental exposure to MeHg (0.5 and 5 ppm) on spatial and visual discrimination reversal performance. MeHg impaired the acquisition of the first reversal, a pattern often seen in such procedures. The pattern of errors was nonrandom and was consistent with perseveration on the lever associated with extinction.

Interactions Between Food Energy Consumption Tumor Growth And Angiogenesis

Thus far, few studies have focused on the role of energy intake and tumor vascular biology. A recent report showed that the transplantable Englebreth-Holm-Swarm (EHS) sarcoma (46), grown in young mice fed reduced-energy intake, contained fewer blood vessels and increased matrix, compared to those fed ad libitum (47). These observations are supported by the authors' recent unpublished experiments. The authors have completed a series of studies employing total diet or energy restriction with a variety of rodent tumor models, and assessed tumor growth and its relationship to microvessel density, based on factor VIII staining. These studies show that energy or diet restriction significantly reduces microvessel density in several transplantable tumor models, including murine MB49 bladder cancer, RT2 rat glioma, Dunning R3327H rat prostate cancer, and LNCaP human prostate carcinoma grown in nude mice (48).

Proposed Mechanism Of Angiostatin Protein Generation

What is the mechanism for the phenomenon of the inhibition of tumor growth by tumor mass The working hypothesis put forward by O'Reilly and Folkman proposes that the presence of the primary tumor inhibits the growth of metastases. This occurs because the primary tumor generates the inhibitors of metastases. Attempts at detecting AP transcripts in LLC-LM cells, freshly resected from mice or after 4 passages in vitro by RT-PCR, or by Northern blotting, have been unsuccessful, indicating that primary LLC-LM tumors do not express AP per se (Sim et al., unpublished). Recent work by Gately et al. (19) and Dong et al. (20), provided an explanation for the hypothesis that tumors could generate their own inhibitors of angiogenesis. Metalloelastase produced by tumor-infil

How adult salmonid fish are becoming infected

Water-borne IHNV can result in horizontal transmission between adult salmonids. Field observations showed that yearling fish cohabiting with sockeye salmon adults became infected with IHNV (Mulcahy et al., 1983a) and waterborne virus potentially spread from adult chinook salmon to adult coho salmon at the Trinity River hatchery in California (LaPatra et al., 1987, 1989b). Laboratory data have confirmed that spawning fish can be infected by waterborne IHNV. Sexually mature kokanee salmon were infected after only 30 min immersion in a low dose of IHNV and viral titres in pooled spleen and gill increased over an 8-day period (Yamamoto et al., 1989). Immersion of sexually mature kokanee salmon in 103 pfu ml-1 of RB-1 (type 1) or 104 pfu ml-1 of WRAC (type 2) IHNV isolates for 1 h resulted in infection of 11 organs per fish and the reproductive products, with mortalities reaching 94 and 72 , respectively. Control fish had a mortality of 60 , attributable to natural causes (H.V. Lorz, L.M....

Animal Models of Human Prostate Cancer

Our studies suggest that the native PSA enhancer and promoter inserted into Ad can direct tissue-specific and androgen-inducible expression in LNCaP cells, but the transcriptional activity is 50-fold lower than the constitutive CMV promoter Wu et al., unpublished data . By exploiting the known properties of the native PSA control regions, we have improved the activity and specificity of the prostate-specific PSA enhancer (Wu et al. unpublished data). Previous studies had established that AR molecules bound cooperatively to AREs in the PSA enhancer core ( 4326 to 3935) act synergistically with AR bound to the proximal promoter to regulate transcriptional output 177, 178 . To exploit the synergistic nature of AR action, we generated chimeric enhancer constructs by (1) insertion of a synthetic element containing four tandem copies of the proximal PSA promoter AREI (ARE4) element or (2) duplication of enhancer core and (3) removal of intervening sequences ( 3744 to 2875) between the...

Digested P vs P equivalency value of phytase

Yi and Kornegay (Virginia Polytechnic Institute and State University, 1998, unpublished data) developed and organized equivalency values from several published broiler studies. For broilers, usually from hatch to 3 weeks of age, the average mean P equivalency of 500 U phytase kg-1 was 0.70 g inorganic P based on body-weight (BW) gain and toe ash percentage. In a 3-week starter turkey trial, the average P equivalency of 500 U phytase kg-1 was 0.82 g inorganic P based on BW gain and toe ash. If the 0.70 g P and 0.82 g P are multiplied by 46.2 (0.462 g P retained per 1 g inorganic P), the products are 0.32 g P (0.7 X 0.462) and 0.38 g P (0.082 X 0.462). A value of 0.37 g retained P (0.037 ) was obtained in the poultry data set for 500 U phytase kg-1 (Table 10.4).

Perspectives on the Kinetics of Desiccation Damage

Hypothesis, the concentration of reacting phospholipids is reduced by inserting sugars between head groups (Clegg, 1986 Hoekstra et al., 1989, 1991 Crowe and Crowe, 1992 Hoekstra and Golovina, 1999). Alternatively, vitrification between bilayer interfaces provides a mechanical resistance to the compression of bilayers (Wolfe and Bryant, 1999 Koster et al., 2000 Bryant et al., 2001). According to these two hypotheses, more tolerant organisms have either proportionally more sugars to insert (Hoekstra et al., 1989) or more strength to repel (Wolfe and Bryant, 1999). Continuing this line of thinking may help to further distinguish between the two hypotheses. According to the Water Replacement Hypothesis, once a finite number of sites is filled, the membrane or cell should be able to tolerate complete drying and maintain structure through time since reactive sites are protected. On the other hand, vitrification is likely to provide imperfect protection, and macromolecular structures will...

Postembedding Colloidal Gold PEG

Successful dual localization of the two receptor subunits to single PSDs and at sites away from synapses has been achieved by using two sizes of colloidal gold for PEG labels and or by combining PEGs with SIG (35). These studies indicate that PEG is applicable for the precise localization of neurotransmitter receptors. Moreover, the PEG procedure can, in some cases, be applied to osmium-fixed tissue for combining with HRP-DAB (HRP-DAB requires osmium treatment for rendering the label electron-dense for EM) (Erisir et al., unpublished observations). Results from these studies indicate that not only double, but also triple, EM-ICC is a possibility by combining SIG, HRP-DAB, and one or two PEG labels.

Evolutionary Implications

Characters, but only a single character related to the anterior end was used (Whittington and Cribb, 1999). Furthermore, the anterior character that was incorporated into Boeger and Kritsky's (1997) phylogeny was the 'circum-oral sucker', an organ sensu stricto that, according to some studies, may not be present in any monogenean (e.g. Whittington et al., 1989, and Section 5.1, p. 148) It is apparent, therefore, that a wealth of potentially useful information about the anterior region of the Monogenea has been ignored to date. Our investigations, and many of the studies reviewed above, demonstrate that a variety of anterior adhesive structures and secretions exist. We think that future attention paid to these characters will provide useful additional morphological data of the kind suggested by Littlewood et al. (1999) to add to the 'total evidence' approach to help assess phylogeny for the Monogenea. We have pointed out (Whittington and Cribb, 1999) that our future studies will...

Common Honey Bee Viruses

DWV appears to be the most prevalent infection in A. mellifera in recent years. Our 5-year field survey carried out in Beltsville, MD showed that DWV infection occurred in 100 of the apiaries investigated (Y. P. C., unpublished observation). Similar results were reported previously by Tentcheva et al. (2004b) who observed that DWV was detected in over 97 of French apiaries when the adult bee population was examined. A study on the prevalence and distribution pattern of viruses in Austria demonstrated that DWV was present in 91 of tested bee samples (Berenyi et al., 2006). Although high prevalence of DWV is not geographically related, some seasonal variation in virus incidence was observed and the frequency of DWV infection in both adult bees and pupae increased considerably from summer to autumn during the year (Tentcheva et al., 2004a,b). The striking high incidence of DWV infection in honey bees obtained from these studies indicate that DWV is prevalent over a wide range of...

Pathogenesis Of Motor Response Complications In Nonhuman Primates

In the non-Parkinsonian brain, the nigrostriatal pathway is usually tonically active, leading to relatively constant dopaminergic stimulation of striatal dopamine receptors (Bunney et al. 1973 Schultz 1994). In the striatum of MPTP-lesioned Parkinsonian primates, dopamine synthesis from exogenous levodopa largely takes place in non-dopaminergic cells containing dopa-decarboxylase that are not equipped to store and release dopamine in a controlled fashion (Melamed et al. 1980). As a result, striatal intrasy-naptic dopamine levels no longer remain constant but mirror the broad swings in plasma levodopa levels associated with the intermittent administration of this rapidly metabolized prodrug. Dopaminergic transmission is thus converted from a tonic to a phasic process (Chase et al. 1996). In Parkin-sonian primates, the periodic high intensity stimulation of striatal postsynaptic dopamine receptors is believed to contribute to the development of the motor response complication syndrome...

Our Advice About The Dyskinesia Test

We are often approached by colleagues asking for practical advice about how to set up the rat dyskinesia test in their laboratories. A matter of concern pertains to the confidence with which the rat dyskinetic movements can be distinguished from naturally occurring behaviors. Overt dyskinesia that includes severe dystonic postures of the trunk and ample flexion-extension movements of the fore-limb are unequivocally abnormal, and do not require any particular familiarity with the rat behavioral repertoire to be detected and rated. Some mild, borderline forms of dys-kinetic movements, however, may require some experience to be detected and scored in a consistent way. Incipient dyskinesia of the forelimb may go unnoticed, as it may either appear to be an oscillatory movement of low amplitude (resembling tremor) or may manifest as a repeated stepping movement of the limb against the floor (A1 in box 1). However, ignoring this type of dyskinesia would not necessarily affect the...

Fourcell Clones in Slice Culture

A-D P N and P P divisions observed in E13-14 mouse cerebral wall slice culture A Two distinct types of P N division observed at the apical surface (Miyata et al. 2001) are schematically illustrated with developmental stage and brain thickness increasing towards the right side of the panel. In each case, a single DiI-labeled progenitor cell generated a daughter cell that remained in the VZ and divided at the apical surface (white, judged to be a progenitor cell, PS-div their mitoses are omitted for clarity) while the other daughter cell (black) exited the VZ without exhibiting any signs of mitosis (judged to be a neuron, N). Both daughter neurons, having inherited the basal process from their progenitor cells (therefore this division pattern is designated as P BPN+PS-div), are initially bipolar-shaped resembling their progenitor cells, but they exit the VZ after loosing their apical attachment. The daughter neuron born in an early and thin cerebral wall (leftpart), which...

Drosophila Stem Cell Self Renewal and Tumor Suppression

In the typical neuroblast lineage proliferation paradigm, an asymmetrically dividing neuroblast gives rise to another neuroblast and a GMC, which in turn terminally divides to generate differentiating, postmitotic ganglion cells (Fig. 2A). It is therefore conceivable, that neuroblasts mutant for Numb, Mira, or Pros divide symmetrically generating two daughter neuroblasts as is the case for impaired apical complex formation, or that neuroblasts carry on dividing asymmetrically but limitless beyond the normal number of times they divide. Yet, in wildtype, the total number of times a neuroblast stem cell divides is limited since cessation of proliferation in the developing Drosophila CNS occurs during puparium formation and metamorphosis (Ito and Hotta, 1992 F. Hirth, unpublished observation). The underlying genetic mechanisms are currently unknown, although for a subset of actively dividing larval neuroblasts, it has recently been shown that they are eliminated by programmed cell death,...

Mechanisms for leukocyte rolling through PSGL1

They might contribute to the location of PSGL-1 in microvilli of resting cells and to the redistribution of PSGL-1 to the uropods of polarized, activated cells 80 . Based on experiments with transfected cells, the cytoplasmic tail of PSGL-1 was reported to be essential for rolling on P-selectin 81 . However, our unpublished data indicate that deletion of the cytoplasmic domain of PSGL-1 causes at most modest defects in cell rolling. Interactions of other membrane proteins with the cortical cytoskeleton may regulate tether extensions even if the cytoplasmic domain of PSGL-1 is deleted 82 .

The Evolution Of Parasitism

Critical evaluation to exclude the possibilities of laboratory cross-contamination or superinfection of leishmanial lesions by monogenetic trypanosomatids - the characterization of such parasites with independent gene markers before firm conclusions can be drawn is essential. For example, one of the best documented of these parasites was isolated from a patient with acquired immune deficiency syndrome in Martinique and was described as a lower trypanosomatid on the basis of its highly distinctive isoenzyme profile and unusual morphology in the patient (Dedet et ai, 1995). However, sequences of the ssu rRNA gene and RNA and DNA polymerase genes indicate that this parasite was in fact a divergent member of the genus Leishmania (H.A. Noyes, unpublished observations). If any of these sporadic infections are proven to be due to members of the monogenetic trypanosomatid genera, it would indicate that there must be both biochemical and ecological barriers to these infections developing into...

Unequal Cell Divisions at Second Cleavage

For Tubifex, an obvious difference between the mitotic apparatus in AB and CD cells is that the latter has gamma-tubulin reactive centrosomes and normal asters, while the former has neither of these (Shimizu, 1996). It is tempting to think that this may be important in determining the properties of the microtubules, but from the work in Helobdella, it seems that the AB mitotic apparatus has nice asters (Scott Settle, unpublished observations) and presumably centrosomes as well, since it inherits one from the first mitosis (Ren 2005). Other possibilities would be that the PARI immunore-activity we see in the domain of cell-cell apposition is actually confined to cell CD, something that cannot be distinguished by current immunofluores-cence observations, or that some other factor, possibly related to the telo-plasm and thus present only in cell CD, is required for the mitotic apparatus to respond to the PAR1 and PAR6 domains. A related possibility is that the delay in mitosis of cell AB...

Molecular Mediators of Inflammation

MCP-1 was not elevated at 6 h after adenovirus lung infection but progressively increased thereafter and was still at the highest value 3 days after infection. This pattern of expression is different from the immediate cytokines because it is of substantially longer duration. In fact, a decline in expression after adenovirus lung infection has not been defined. MCP-1 is capable of recruiting multiple mononuclear cell subsets, however, its precise role in adenoviral infection is currently unclear. In other lung inflammation models (e.g., silicosis) a network of cytokine chemokine signaling has been observed linking TNFa expression to MCP-1 production and T-cell recruitment (Tamez and Shanley, unpublished observations). MCP-1 is also important in recruitment of monocytes. Thus, MCP-1 may have multiple roles in adenoviral lung infection. Interestingly, overexpression of MCP-1 in the lung results in skewing toward Th2 development with increased IL-10 and IL-13 levels and decreased IL-12...

Neural And Behavioral Mechanisms

The behavioral significance of these effects has been demonstrated using drug challenges in behaving animals. Developmental exposure to methylmercury (relatively high levels compared with contemporary exposure protocols) affect sensitivity to amphetamine, a dopamine and noradrenergic agonist in relatively young animals 17, 18, 47, 80, 153 . Moreover, these effects are specific to certain drug classes, extend into fully adult animals, and arise with dosing protocols involving relatively low exposure levels, suggesting that they represent permanent changes in the neu-rochemical tone of the intact nervous system under physiologically relevant conditions 142 . Adult rats exposed during gestation to MeHg (0.5 and 6 ppm, resulting in 40 and 500 g kg day) were especially sensitive to amphetamine when tested as adults 142 . They were also relatively insensitive to pentobarbital, a GABA agonist. No specific sensitivity was demonstrated to a cholinergic or glutamatergic antagonist. An...

Natural Killerlymphokineactivated Killer Cells

AData obtained in previous studies (Albright JW and Albright JF, unpublished) similar data may be found in publications by others (e.g., Saxena RK et al. Immunology. 1984 51 719). 6Mouse spleen cells placed in culture and not further stimulated or stimulated either with IL-2 (200 U mL for 3 d) or poly I poly C (20 g for 3 d).

Phosphorodiamidate Morpholino Oligomers

The studies presented in this chapter utilized phosphorodiamidate morpholino oligomer (PMO) antisense agents. The chemistry of PMO overcomes some of the major shortcomings of phosphorothioate oligonucleotides (see Chapter 13). The PMO backbone is nonionic at physiological pH and consists of a six-membered morpholine ring instead of a deoxyribose sugar, and the charged phosphodiester internucleoside linkage is replaced by an uncharged phosphorodiamidate linkage (52). PMOs are highly resistant to various nucleases and proteases (53), as well as extremely efficient inhibitors of translation via a non-RNase H (54), sequence-specific steric-blockade process (55). PMOs also have favorable organ distribution following systemic administration at all organ sites rich in CYP activity, namely the liver (56,57), kidneys (58), and small intestines (unpublished data). PMOs have been successfully used to inhibit CYP3A4 in primary human hepatocytes (59) and CYP3A2 in rats in vivo following ip, oral...

Epigenetic Influences On Maintenance Of Mature Vagal Afferent Neurons

Helke and Verdier-Pinard (Reference 81 and unpublished data) used cultures of dissociated mature nodose and petrosal ganglia neurons to evaluate the presence of neuropeptide (VIP, CGRP, and NPY)-containing neurons in vitro in the absence of neurotrophic factors. At each time point in culture (20 of labeled neurons in culture (elevated at all time points in culture, including

Serological characteristics

Several investigators have developed monoclonal antibodies (MAbs) to aquatic birnaviruses (Caswell-Reno et al., 1986 Wolski et al., 1986 Christie et al., 1988 Lipipun, 1988 Chi et al, 1991 Shankar, 1991). These MAbs were used to classify aquatic birnaviruses. The patterns of reactivity in binding tests with MAbs fairly closely follow the neutralization-based serotyping scheme as outlined by Hill and Way (1988a, 1995). One of the MAbs (AS-1), generated against a Canadian A1 isolate, reacted with all of the more than 200 aquatic birnaviruses isolates tested, while others were isolate specific (Caswell-Reno et al., 1986, 1989 Reno et al, 1994). None of the MAbs reacted with TV-2, an isolate from serogroup B (P. Caswell-Reno, P.W. Reno and B.L. Nicholson, unpublished results). polyclonal antibodies and reactions in MAb tests. There are studies which suggest epitope variation within serotypes. In a study which included the nine serotypes of serogroup A as well as other isolates,...

Quantitative Analysis Of Cfse Data

One of the most striking features of experiments using CFSE is the spread of cells in different divisions at each time point as noted in Figure 2, 3 and 4. Put more simply, lymphocytes are not all behaving identically, even when the stimulus is polyclonal and growth factors such as IL-2 are provided in saturating concentrations. What is the source of the variability Experiments using BrDU pulsing show that the division rates of cells after their first entry to division are relatively constant. Similarly, when cells were sorted from different divisions (1-7) and placed back in culture, they underwent a uniform progression through division (Gett and Hodgkin unpublished). Thus, once T cells are stimulated into division they divide at a relatively even rate. These experiments indicate that the major source of

Baculoviral and baculoviruslike viruses

Ultrastructure Hepatopancreas

The first baculovirus described from shrimp was baculovirus penaei (BP) in Penaeus duorarum from Florida (Couch, 1974a,b). J.-R. Bonami, L.D. Bruce, B.T. Poulos and D.V. Lightner (unpublished, cited in Bruce et al., 1993) propose changing BP to 'PvSNPV' ('the most characterised variant, from Penaeus vannamei, in the singly enveloped nuclear polyhedrosis virus group'), in compliance with the guidelines for virus nomenclature designated by the International Committee on Taxonomy of Viruses. For the sake of consistency with previous descriptions, however, the acronym BP is used here.

Androgen Receptor GGC Repeats

In addition to containing a polymorphic CAG repeat in the transactivation domain, exon one of the androgen receptor also contains a polymorphic GGC repeat. The GGC repeat encodes for a variable number of glycines and is located approximately 1.1 kilobases 3' of the CAG repeat. The variable GGC repeat (4 to 24 triplets) follows an invariant (GGT)3GGG(GGT)2 repeat that also encodes for six consecutive glycines. The median and mean GGC repeat length are both approximately 16.9,10 Unpublished observations by Barrack and colleagues indicate that the GGC repeat length is shorter in African Americans as compared to Caucasians. Functional consequences, if any, have yet to be ascertained for variations in androgen receptor GGC length.

Adhesion at the Anterior End of Monopisthocotylean Monogeneans

Secretion Needle Microscopy

Considerably, especially in regions where the apertures or outlets of the anterior gland ducts are located (e.g. Cribb et al., 1998). The inference is that the surface area of the anterior end of the parasite increases where the adhesive secretions are released and provides, therefore, a larger area of contact at the interface between worm and host. It was noted above that six apertures for release of adhesive secretions is a common arrangement. We have observed that specimens of Benedenia spp. (see Whittington and Cribb, 1999) can achieve firm attachment to glass and to host surfaces using adhesive secretions from only a single 'attachment zone' on their disc-like anterior attachment organs, even in the presence of considerable water currents. Attachment involving some, but not all, of the anterior apertures was also noted in Monocotyle spiremae (see Cribb et al., 1997). We have made similar observations for other monogenean species from the Capsalidae, Dactylogyridae, Dionchidae,...

Abnormal Anourogenital Development

Anorectal Malformation Embrio

Again the findings in the embryos treated with terato-gens at embryo day 9 in mice is that of a deficiency of the dorsal cloacal membrane and the adjacent dorsal cloaca 32 . In addition, etretinate also has an effect on the proliferation of neuroepithelial cells in the pre-sacral region, resulting in anterior sacral myelome-ningocele. These animals also developed significant abnormalities in the sacral vertebrae and short or absent tails. Most of the ARM that developed were high lesions with rectourethral fistulas in males or cloacal malformations in the females. Embryos exposed to etretinate at an earlier stage of development have more severe deformities and many do not survive, but of those that are not resorbed, many display sy-ringomyelia, with the total absence of lower midline trunk and genital structures and fusion of the lower limb anlage (unpublished data). This would support the suggestion by Liu et al. 32 that the effects of etretinate are initiated by its effects on the...

Influence of SMN2 Copy Number on the SMA Phenotype

The main cause for this fact is the variable number of SMN2 copies which directly correlates with the disease severity (Burghes 1997 Brahe 2000 Feldkotter et al. 2002). According to this observation, the majority of type I SMA patients carry two SMN2 copies, type II SMA patients three SMN2 copies, type III SMA patients three or four copies, and type IV four to six SMN2 copies (Feldkotter et al. 2002 Wirth et al. 2006). Analysis of FL-SMN2 versus SMN2 A7 transcripts of type I-III SMA patients showed a ratio of about 20 80 in type I, 30 70 in type II, and 40 60 in type III SMA patients (Helmken et al. 2003). On the protein level, there are significant differences, especially between type I and II SMA patients versus type III patients and controls (Coovert et al. 1997 Lefebvre et al. 1997 Helmken et al. 2003). Individuals carrying 5-6 SMN2 copies develop very mild SMA symptoms (type IV SMA Wirth, unpublished results) whereas 8 SMN2 copies fully protect from developing SMA (Vitali et al....

Elegans Parkinson Disease Models Generated By Transgenic Manipulations

Elegans Twitching

Researchers have also applied transgenic approaches to C. elegans (Mello and Fire 1995). We have produced a trans-genic Parkinson disease model in C. elegans using overexpression of a-synuclein (Lakso et al. 2003). The product of this gene is found in Lewy bodies, the pathological hallmark of Parkinson disease (Spillantini et al. 1997). Mutations in this gene lead to familial forms of Parkinson disease (Poly-meropoulus et al. 1997). Some of the biochemical features of Parkinson disease were recapitulated in our model. For example, loss of dopaminergic neurons and processes was observed when a-synuclein was overexpressed under control of a dopaminergic neuron-specific promoter. Cellular inclusions consisting of a-synuclein protein were also observed although these events were rare. With regard to movement deficits, a thrashing assay was used. We observed that transgenic C. elegans overexpressing a-synuclein under a pan-neuronal promoter had thrashing values 50 less than transgenic...

Adhesive And Other Gland Cells In The Cestodes

Larve Phyllobothrium

It seems to us unlikely that most metacestode stages would require any adhesive secretions or an attachment mechanism of any kind when their biology is considered. Most procercoids and plerocercoids reside in the body cavity of their hosts, they may be encapsulated, encysted or neither, and they have no need for an attachment mechanism because they generally lie loose in the capsule or cyst, or in or on the viscera. Their requirement for movement is necessary only when they, together with their host, are eaten by a subsequent host. The only exceptions to this general scheme are the plerocercoids of some tetraphyllideans, or so-called 'scolex polymorphus', many of which live actively, moving using their anterior suckers, in the intestines of their squid (Stunkard, 1977) and teleost hosts (unpublished observation, I.D. Whittington). These plerocercoids are similarly awaiting ingestion by the elasmobranch definitive host. Figure 20 Transmission electron micrograph of the tentacles of an...

Stem cells of the adult liver

WB-F344 cells share some phenotypic traits with both hepatocytes and biliary epithelial cells, but their overall phenotype differs distinctively from either differentiated cell type (20). Most notably, WB-F344 cells are null for the major antigens that typify and distinguish hepatocytes or biliary epithelial cells (198 A. E. Wennerberg and J. W. Grisham, 1993, unpublished observations).

Hosttargeted acaricides

A pesticide self-application device for the control of ticks on white-tailed deer has been developed and patented by scientists at the US Department of Agriculture Livestock Insects Research Laboratory in Kerrville, Texas (US patent no. 5,367,983). The topical pesticide self-application device, termed the 4-poster, consists of a central bin that contains bait to attract deer with one trough and two vertical pesticide impregnated rollers on each end (Pound et al., 1994). Deer contact one of the rollers as they feed, treating the head, neck and ears with an acaricide (Fig. 12.3). Ninety-two and 94 control of nymphal and larval lone star ticks on deer in a large (22.3 ha) deer-fenced pasture in comparison with an untreated pasture was obtained with 2 amitraz (an acaricide with no withdrawal period) applied to deer during the tick season over 3 consecutive years (Pound et al., 2000). The efficacy of the 4-poster and amitraz in controlling I. scapularis feeding on deer and free-living...

Example ABBA crossover design

We illustrate the AB BA cross-over design with results from an unpublished study comparing two diuretics in the treatment of mild to moderate heart failure. After initial screening for suitability, there was a period of not less than one day, and not more than seven days, where diuretic treatment was withheld. Immediately prior to randomisation to either the AB sequence of treatment, or the BA sequence, baseline observations were taken. Each treatment period lasted for five days, with an immediate transfer to the second treatment after the first treatment period was completed. As a washout was not employed between treatments, observations made in the first two days of each treatment period were not utilised in the analysis of the trial. The primary outcome measures were the frequency of micturition and the subjective assessment of urgency. As neither of these are suitable for illustrating the analysis of normally distributed data, we will use instead a secondary effectiveness...

Primary and recurrent rectal cancer

Shadow Pelvis Mri Due Scar Tissue

Pathologic specimens, two radiologists in consensus achieved an overall accuracy of only 65 in determining involved mesorectal lymph nodes, with a good interobserver agreement (k 0.64, unpublished data). false-positive rate was 15.58 and the false-negative rate was 4.58 (Figs. 32-34) (Lawrence Schwartz, unpublished data). Prediction of invasion of the bladder, prostate, and sacral periosteum when not grossly obvious can be limited. Seminal vesicle invasion may be the easiest to predict because of replacement of high-signal T2 fluid by tumor (Fig. 35).

Antiangiogenic Activity Of Interferon

In order to evaluate the effect of IFN on angiogenesis specifically, the authors trans-fected a human metastatic bladder carcinoma (253J-BVR, resistant to the antiproliferative effects of IFN) with the human IFN-P gene, and injected the cells orthotopically into nude mice. Although parental cells and control-transfected cells were able to grow rapidly and produce highly vascular tumors that metastasized to regional lymph nodes, the IFN- -transfected cells were weakly tumorigenic (Bielenberg et al., unpublished data). In vitro, IFN- -transfected cells constitutively produced less bFGF and collagenase type IV than parental or control-transfected cells. These experiments suggest a causal role for IFN-P in suppressing tumor-derived angiogenic factors and thus inhibiting angiogenesis and metastasis.

Gene Targeting Method

Gene targeting relies on homologous recombination whereby a piece of DNA containing the mutated gene fragment flanked by large stretches of unaltered DNA is introduced into the ES cell through electroporation which is then incorporated into the genome at a targeted site. With the help of endogenous recombinases, the flanking unaltered sequences that line up with the homologous chromosomal DNA switch places with the genomic segment, taking along the mutated fragment between the arms. A wild-type allelic fragment is thus replaced with an altered version from the DNA construct. Incorporation of the transgene in these ES cells mainly occurs randomly, but in one out of every 105 to 107 ES cells, homologous recombination occurs (Vasquez et al. 2001). The efficiency of homologous recombination depends on several factors. The first factor is the similarity between the construct DNA and its corresponding endogenous counterpart (te Riele et al. 1992). Using DNA for the construct that comes from...

Species of fish affected and geographical distribution

However, CCVD could not be induced in these fish by oral administration of virus or by cohabitation with infected channel catfish. White catfish (Ictalurus catus) is susceptible to experimental infection, but disease incidence and mortality are low (Plumb, 1971a N. Fijan, unpublished data). Fingerlings of brown bullhead (Ameiurus nebulosus) and yellow bullhead (Ameiurus natalis) did not develop disease after injection of the virus (Plumb, 1989). Sheatfish, the African catfish (Clarias gariepinus), the Asian catfish (Clarias batrachus) and the bluegill (Lepomis macrochirus) are resistant to CCV (Plumb et al., 1985 Boon et al., 1988 Chumnongsitathum et al., 1988) the virus was detected in some specimens of these resistant species only within a few days of infection.

Adhesion at the Posterior End of Monopisthocotylean Monogeneans

Kearn Capsalidae

Another monogenean family for which haptoral hooks appear to be ineffective is the Microbothriidae which live attached to the hard, enamel-like placoid scales of sharks (Kearn, 1965). The small haptor of L. minor attaches to host denticles by an adhesive secretion (termed 'cement' by Kearn, 1965) and an adhesive residue remains on glass surfaces where attached parasites were located. Observations by Kearn (1965) showed that L. minor can move in a leech-like fashion using adhesive glands at the front and back of the animal, but detachment of the haptor took several seconds as it stripped away slowly from the host denticle. This may be consistent with detachment occurring simply by secretion of fresh adhesive to permit the slow withdrawal of the attached haptor from a substrate. An unpublished study by Rees (1986) suggested that the posterior adhesive secretion in L. minor is produced by a single type of gland cell. The slowness of the detachment process by the posterior end of L. minor...

IA2 ICA512 and Phogrin IA2j

As is the case for GAD, the availability of human monoclonal autoantibodies from diabetic patients and structural modeling of the IA-2 PTP domain based on crystal structures of other PTPs have assisted the definition of major disease-associated antibody epitopes. A number of human monoclonal antibodies have been obtained by Epstein-Barr virus transformation of B lymphocytes from type 1 diabetic patients, and these bind epitopes within the juxtamembrane and PTP domains of the IA-2 molecule 101 . One of these monoclonal antibodies, termed 96 3, was shown to effectively compete for IA-2 binding with serum antibodies from a majority of patients with type 1 diabetes, and this antibody binds to an epitope within a region (amino acids 795-889) that is frequently targeted by antibodies in type 1 diabetes. Peptide phage display and molecular modeling have identified potential 96 3 antibody contact residues at positions 799, 836, and 858 within the PTP domain of IA-2, and substitution of each...

Methods for Combining Studies Metaanalysis Basis of Metaanalysis

The first step in a meta-analysis is to identify the relevant studies. Systematic, explicit criteria must be established for including studies in a meta-analysis. The establishment of explicit criteria distinguishes meta-analysis from a qualitative literature review. Identifying relevant studies usually involves searching personal reference lists, computerized sources such as Medline, lists of references in other relevant original articles and review articles, the contents of journals in which relevant articles are likely to be published, and doctoral dissertations on the topic. Experts in the area are usually consulted to determine if they know of articles that have been missed through the other sources. In addition, it is important to try to identify unpublished studies, because of publication bias the greater tendency of research with statistically significant results to be submitted and published than results that are not statistically significant and or...

Activitydependent Neuronal Growth

Growth cone behavior and the underlying Ca2+ dynamics during nerve terminal arborization may be altered in hyper-excitable K+ channel mutants. Giant neuron cultures made from cytokinesis-arrested neuroblasts (Wu et al., 1989) can facilitate analysis of the contributions made by individual K+ channel subunits in growth cones and other cellular regions in activity-dependent growth. For example, K+ channel mutations including Sh indeed alter the size of growth cones in culture (Figure 10A). In addition, Sh and slo mutations lead to excessive spontaneous Ca2+ increases in the growth cone (Figure 10B). A role for action potentials is suggested in triggering spontaneous Ca2+ transients and in the enlarged growth cones because both can be suppressed by TTX (Berke and Wu, unpublished observations). Mutants of the Sh and erg genes have revealed differential defects in K+ currents, reflecting the in vivo function of individual K+ currents. Investigators have identified four K+ current...

Types of DNA fragmentation

Very recently, a caspase-activated DNase (CAD) has been reported by S. Nagata and co-workers (33). CAD is a 40 kDa protein that induces internucle-osomal DNA cleavage in isolated nuclei in the presence of Mg2+. CAD activity does not require Ca2+, and CAD forms a complex and co-purifies with an inhibitor of CAD (ICAD) that can be cleaved by caspase-3 during apoptosis (33, 34). CAD and ICAD have been isolated independently by X. Wang and co-workers who showed that DNA fragmentation and chromatin condensation depend on a heterodimeric protein composed of two DNA fragmentation factors of 45 and 40 kDa (DFF45 and DFF40 corresponding to ICAD and CAD, respectively) (35, 36). In our laboratory, we purified a 34 kDa Mg2+-dependent and Ca2+-independent endonuclease from etoposide-treated HL60 cells undergoing apoptosis (37), and designated this 34 kDa Mg2+-dependent endonuclease, AN34 (apoptotic nuclease 34 kDa) (37). AN34 introduces single-and double-strand breaks in purified DNA and...

First Causal Therapy for SMA Patients

Clinical picture after 5-6 months of treatment was observed in about 50 of the patients (Wirth, unpublished data). Some patients presented decreased L-carnitin levels which were compensated by substitution with acetyl-carnitin. Observation of patients with unchanged decreased FL-SMN2 transcript levels underscores the need for a biomarker. However, so far we do not know if SMN expression in blood reflects SMN expression in a-motor neurons and correlates with muscle strength. Therefore, long-term clinical trials in SMA patients that correlate SMN expression in blood with individual motor function tests are required. Two large trials with VPA L-carnitin are in progress in type I SMA patients in Germany (www.initiative-sma.de), and in type II and III SMA patients in the United States (www.FSMA.org).

Host management reduction and exclusion

The incremental removal of deer has been shown to reduce tick abundance (Deblinger et al., 1993 K. Stafford, unpublished data). A gradual reduction in deer densities over a 7 year period at a 567 ha site in Ipswich, Massachusetts, reduced the abundance of I. scapularis larvae and nymphs on white-footed mice by roughly one-half, although the density of female ticks on deer increased four-to sixfold during the 7 year reduction of deer at Crane's Beach (Deblinger et al., 1993). Similarly, the reduction of deer from 97.3 km-2 to 13.1 km-2 over a 7 year period on a 176 ha forested, fenced property in Connecticut, resulted in an almost fivefold reduction in nymphal tick abundance (K. Stafford, unpublished data). The virtual elimination of deer from Great Island, a 240 ha coastal peninsula near Cape Cod, Massachusetts, produced a dramatic reduction in the subadult population of this tick (Wilson et al., 1988a,b), although adult tick abundance initially seemed to increase after deer became...

Correction For The Dmso Effect By The Ashift Method

The ''A shift'' Avdeef, unpublished . It is thought to be caused in some cases by DMSO binding to the drugs. Just as the equilibrium model in Section 6.1.3 was expanded to allow for the salt solubility equilibrium, Eq. (6.4), the same can be done with a binding equation based on DMSO (e.g., in 0.5 v v)

Comparison Of Platyhelminth Adhesives With Temporary Adhesives In Other Marine Macroinvertebrates

For the Monogenea, there has been no chemical characterization of putative adhesive secretions beyond histochemistry, except for work in progress by Hamwood, Cribb, Halliday, Kearn and Whittington (unpublished data), but some useful comparisons with echinoderms can be drawn. Within the Monogenea, histochemical data tell us that some monopisthocotyleans use a posterior adhesive secretion which is a tyrosine-rich lipoprotein (Rand et al., 1986), but it is the anterior adhesive system of monogeneans which is most reminiscent of the echinoderm adhesive system. Similarities evident are the presence of multiple secretions released from ducts which may mix to form the adhesive and or a separate de-adhesive secretion the ultrastructure of puta-tively adhesive spherical secretions may differ across monogenean taxa (Kritsky, 1978 El-Naggar and Kearn, 1980, 1983 Rees and Kearn, 1984 Yuan and Long, 1996 Yuan and Lang, 1997 Cribb et al., 1998 Whittington and Cribb, 1998a, 1999) adhesive prints...

Vertical transmission and the carrier state

Survivors of IPN epizootics remain carriers for up to 6 years (Wolf, 1966 Yamamoto,1975a Reno, 1976). In a given population, the proportion of fish from which virus can be isolated varies drastically. In naturally infected brook trout, the prevalence ranged from 99 to less than 5 (Reno, 1976 unpublished observations). The latter is the prevalence used in fish health inspections for the

Area application of acaricides

The principal acaricides used for the control of I. scapularis were cyfluthrin, chlorpyrifos and carbaryl. A more recent survey in the heavily populated southeastern portion of the state found that the pyrethroid cyfluthrin was used by over half of the commercial applicators (K. Stafford, unpublished data). It is unknown how many homeowners apply acaricides to control ticks, but only 22.5 of 402 respondents in an LB survey of two Connecticut towns indicated that they had used acaricides and of those 16.9 indicated someone in their household had applied the chemical, while 75.6 used a commercial business to perform the acaricide application (Connecticut Department of Public Health, unpublished data). With the phase-out of residential use of the organophosphates chlorpyrifos and diazinon by the US Environment Protection Agency, fewer products will be available to individual homeowners for the control of ticks. With the effectiveness of synthetic...

Relationship of Islet Autoantibodies to Tcell Responses in Type 1 Diabetes

Contrast, T cells from individuals already undergoing insulin therapy for type 1 diabetes, and therefore responding to exogenous injected insulin, exhibited increased production of the Th1 cytokine IFN-y 181 . Recent results from our own laboratory also reveal a positive association between T-cell responses to peptides representing residues 831-860 of IA-2 and autoantibodies to the 96 3 epitope region of the molecule (residues 795-889 of the IA-2 PTP Fig. 15.1) that overlaps this region (S. Weenink, unpublished observations). Diabetic patients with higher levels of autoantibodies to the 96 3 epitope region were found by ELISPOT to have increased frequency of T cells secreting IL-10 in response to synthetic peptides spanning the 831-860 region.

Differentiation potential of dpscs in vitro and in vivo

Dpsc Stem Cells

Collagen fibers in the dentin was characteristic of ordered primary dentin, perpendicular to the odontoblast layer. Backscatter EM analysis demonstrated that the dentinlike material formed in the transplants had a globular appearance consistent with the structure of dentin in situ (unpublished observations). Moreover, the presence of human DSPP detected in the transplants confirmed the ability of DPSCs to regenerate a human dentin-pulp microenvironment in vivo.

Pathways to the discovery of the neuronal origin and proteolytic biogenesis of Ap amyloid of Alzheimers disease

Masters first saw this paper when travelling to an EMBO-sponsored meeting on the Transmissible Spongiform Encephalopathies being organized by Alan Dickinson in Edinburgh. At this meeting, Konrad Beyreuther and Stan Prusiner were present Beyreuther attended because of his association with Heino Diringer who had interested him in some of the properties of scrapie fibrils isolated in Diringer's Berlin laboratories Prusiner was there with some important unpublished information on the N-terminal sequence of PrP. Masters approached Beyreuther, known for his expertise in amino acid sequencing, to help with his studies on the AD amyloid plaque cores. By that time, Masters had also determined their solubility in strong chaotropes, such as guanidine, and had discovered formic acid to be the most effective solvent (a tip derived from the previous generation of Australian wool protein chemists). Beyreuther readily agreed to collaborate, and Masters sent purified AD-APC to him and Gerd Multhaup...

Theories Of Arsenic Mobilization

Other reasons for rejecting pyrite oxidation as a mechanism are as follows. The sediments contain too little arsenical pyrite for this mechanism to be important. Measured sulfur concentrations in aquifer sediments represent both pyritic and organic sulfur but allow upper limits to be placed on pyrite abundance of 0.3 (Nickson et al., 2000), 0.02 (AAN, 1999), 0.1 (J.M. McArthur, unpublished) and 0.06 (DPHE, 1999). Were arsenic to be released by partial oxidation of arsenical pyrite, Bangladesh groundwaters, which are anoxic, would have an iron sulfate molar ratio of 0.5 from the stoichiometry of the reaction

Pharmacotherapy Of Motor Response Complications In Mptp Nonhuman Primates

Studies in Parkinsonian primates further revealed that not all noncompetitive NMDA-receptor antagonists have the same effects on motor behavior, despite a generally similar subunit-nonselective profile (Papa et al. 1996). No definite anti-Parkinsonian or anti-dyskinetic activity was observed with remacemide, which is also a noncompetitive and subunit-nonselective NMDA-receptor antagonist with relatively low affinity, in MPTP-lesioned monkeys (Blanchet and Chase unpublished observation). Taken together, these findings suggest a possibility that high NMDA-receptor binding affinity might be required for the genesis of motoric effects in this model. Amantadine is an aminoadamantane that has a long history in the treatment of PD. The NMDA antagonist property of amantadine, however, was recognized only recently (Kornhuber et al. 1991), providing a safe opportunity to evaluate the hypothesis that NMDA antagonists diminish dyskinesias in nonhuman primates....

Peri Infarct Depolarisations PIDS

Fall in net ATP yield per mole glucose utilised from 38 to 2 moles. Glucose utilisation increases to compensate 101 this is possible despite presence of ischaemia, due to the remarkable effectiveness of the capillary glucose uptake transport mechanism. This concept is based on several lines of evidence. Hansen showed that following cardiac arrest in rats, delay before terminal ischaemic depolarisation was proportional to plasma glucose, indicating an inverse relationship between depolarisation rate (the dependent variable) and glucose availability in the brain 23 . In 1986, Nedergaard and Astrup showed in rats (MCAO) that hyperglycaemia reduced the frequency of PIDs (although a plasma level in excess of 30 mmol L was needed to achieve this) 102 . They also showed an increase in phosphorylation of 14C 2-deoxyglucose (an index of metabolic rate) that was related to frequency of PIDs, and predicted that with ischaemia accompanied by PIDs the brain free glucose pool would tend towards...

The Role of Selective Mixing

May and Anderson (1987) cite data documenting the enormous variability in the numbers of sexual partners per year found among homosexual or bisexual men, both in the United States and in the United Kingdom. For example, unpublished data from London in 1984 indicated that nearly half the men surveyed had reported between 6 and 50 partners per year. However, about 3 reported no partners and about 5 reported more than 100 partners per year.

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