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R C Thompson

Publications and source records attributed to R C Thompson.

At least 91 records · Page 5Linked to original sources
PubMed1998

Identification and characterization of GFRalpha-3, a novel Co-receptor belonging to the glial cell line-derived neurotrophic receptor family.

A new family of neuronal survival factors comprised of glial cell line-derived neurotrophic factor (GDNF) and neurturin has recently been described (Kotzbauer, P. T., Lampe, P. A., Heuckeroth, R. O., Golden, J. P., Creedon, D. J., Johnson, E. M., Jr., and Milbrandt, J. (1997) Nature 384, 467-470). These molecules, which are related to transforming growth factor-beta, are important in embryogenesis and in the survival of distinct neuronal populations. These molecules signal through a novel receptor system that includes the Ret receptor tyrosine kinase, a ligand (i.e. GDNF or neurturin), and an accessory glycosyl-phosphatidylinositol-linked molecule that is responsible for high affinity binding of the ligand. Two accessory molecules denoted GDNF family receptor 1 and 2 (GFRalpha-1 and GFRalpha-2) have been described that function in GDNF and neurturin signaling complexes. We have identified a novel co-receptor belonging to this family based on similarity to GFRalpha-1, which we have named GFRalpha-3. GFRalpha-3 displays 33% amino acid identity with GFRalpha-1 and 36% identity with GFRalpha-2. Despite the similarity of GFRalpha-3 to GFRalpha-1 and GFRalpha-2, it is unable to activate Ret in conjunction with GDNF, suggesting that there are likely additional undiscovered ligands and/or Ret-like receptors to be identified. GFRalpha-3 is anchored to the cell membrane by a phosphatidylinositol-specific phospholipase C-resistant glycosyl-phosphatidylinositol linkage. GFRalpha-3 is highly expressed by embryonic day 11 but is not appreciably expressed in the adult mouse. In situ hybridization analyses demonstrate that GFRalpha-3 is located in dorsal root ganglia and the superior cervical sympathetic ganglion. Comparison of the expression patterns of GFRalpha-3 and Ret suggests that these molecules could form a receptor pair and interact with GDNF family members to play unique roles in development.

Amino Acid Sequence↗
PubMed1998

PCR detection of cryptosporidium: the way forward?

In this article, Una Morgan and Andrew Thompson briefly review the latest information on polymerase chain reaction (PCR)detection of Cryptosporidium parvum in both clinical and environmental samples. Current detection methods for Cryptosporidium are cumbersome, time-consuming and lack sensitivity. A variety of PCR tests have been described recently in the literature and this article discusses the advantages and disadvantages of each new technique and their potential for future diagnosis of Cryptosporidium.

Journal Article↗
PubMed1998

Molecular characterization of Cryptosporidium from various hosts.

A 298 bp region of the Cryptosporidium parvum 18S rDNA and a 390 bp region of the acetyl-CoA synthetase gene were sequenced for a range of human and animal isolates of Cryptosporidium from different geographical areas. A distinct genotype is common to isolates from cattle, sheep and goats and also an alpaca from Peru and is referred to here as the 'calf'-derived Cryptosporidium genotype. Another genotype of 'human'-derived isolates also appears to be conserved amongst human isolates although humans are also susceptible to infection with the 'calf' Cryptosporidium genotype. Mice and pigs carry genetically distinct genotypes of Cryptosporidium. Three snake isolates were also analysed, 2 of which exhibited C. muris genotypes and the third snake isolate carried a distinct 'mouse' genotype.

Acetate-CoA Ligase↗
PubMed1998

Molecular detection of parasitic protozoa.

The development of molecular diagnostic methods, particularly those utilizing PCR for the detection of parasitic protozoa will contribute greatly to the identification and control of these pathogens, by increasing speed of diagnosis, specificity and sensitivity, reproducibility and case of interpretation. PCR methods are not without their problems however, and there is a need for laboratory procedures to be refined before PCR-based assays are accepted as the tools of choice for the routine detection of protozoan parasites. The application of PCR detection to various parasites is discussed.

Animals↗
PubMed1998

Overview and significance of molecular methods: what role for molecular epidemiology?

In this chapter, the contribution of molecular tools in understanding the aetiology and ecology of infectious diseases is examined in the context of molecular epidemiology (ME). ME is seen as providing the 'tools', both laboratory and analytical, which have predictive significance in epidemiological investigations of the causation of disease. A diversity of questions can be addressed with these tools which can conveniently be viewed as particular regions of DNA and grouped according to the different hierarchical levels of specificity by which infectious agents can be characterized. These groupings and the applications of the different molecular tools are described, and consideration given to the most appropriate methods of analysing data from ME investigations.

Animals↗
PubMed1998

The management of patients with arteriovenous malformations and associated intracranial aneurysms.

OBJECTIVE: Few published studies have focused specifically on the unique management issues encountered in treating patients with arteriovenous malformations (AVMs) and associated intracranial aneurysms. The primary objective of this study was to retrospectively review the clinical and radiographic features of these patients. METHODS: Medical records of all patients seen at Stanford University Hospital between 1988 and 1996 with a diagnosis of AVMs were retrospectively reviewed. Aneurysms were identified by conventional angiography and characterized by size, number, and location relative to the AVMs. AVMs were graded according to the Spetzler-Martin scale. Odds ratios were calculated for the risk of intracranial hemorrhage. Variables included age, sex, number of aneurysms, and AVM grade. RESULTS: Forty-five of 600 patients (7.5%) were identified as having coexisting intracranial aneurysms. All 45 patients had high-flow malformations, and 58% had AVMs of Spetzler-Martin Grade IV or higher. A majority of patients had multiple aneurysms. There was a statistically significant increase in AVM hemorrhage in female patients (odds ratio, 8.53 [1.87-38.98]; P < 0.005). There was no statistically significant correlation between the development of hemorrhage and either age, AVM grade, or the number of aneurysms. Twenty-three patients (51%) presented with intracranial hemorrhage: bleeding occurred from the AVMs in 15 and from ruptured aneurysms in 5, and the source of the bleeding could not be determined in 3. Overall, nine patients (20%) bled from ruptured aneurysms: five at presentation, two during or within 3 weeks of AVM treatment, and two from new aneurysms. Two of these nine patients died as a direct result of aneurysmal subarachnoid hemorrhage. Five patients (11%) developed new aneurysms. CONCLUSION: Aneurysms associated with AVMs are at risk for rupture before, during, and immediately after treatment of the AVMs. New aneurysms may arise in patients with high-flow AVMs. The risk of intracranial hemorrhage from either source is higher in female patients. To reduce the complications of intracranial hemorrhage in these patients, we recommend a management protocol designed to treat the aneurysms by surgical or endovascular means before administering definitive therapy for the AVMs. Meticulous intraoperative blood pressure control and fluid management during aneurysm surgery is critical to avoid hemorrhage from the AVMs.

Adolescent↗
PubMed1998

Radiation hybrid mapping of the two highly homologous human-variant pMCHL genes by PCR-SSCP.

When gene loci are very similar in sequence, as in gene families or multiple pseudogenes, it is difficult to determine the specific location of the individual genes. We show here that applying PCR-SSCP to a radiation hybrid panel allowed mapping and specific sequencing of two genes with only a few sequence differences. Human-variant forms of the promelanin-concentrating hormone (pMCH) gene are found in two locations in the genome, previously localized by FISH to 5p14 and 5q12-q13. Without prior knowledge of sequence variation between the loci, we observed a difference in migration pattern in PCR-SSCP, indicating the presence of at least one point of sequence divergence. PCR-SSCP of 93 samples from a human-hamster radiation hybrid panel revealed the location of the genes to be between markers WI-4804 and AFM225YC5 on chromosome 5p, and between markers WI-3133 and WI-4225 on chromosome 5q. Sequencing of the two 680-bp PCR products from the hybrid panel demonstrated 3 bases of sequence difference between the 5p and 5q locations.

Alleles↗
PubMed1998

Comparison of PCR and microscopy for detection of Cryptosporidium parvum in human fecal specimens: clinical trial.

PCR technology offers alternatives to conventional diagnosis of Cryptosporidium for both clinical and environmental samples. We compared microscopic examination by a conventional acid-fast staining procedure with a recently developed PCR test that can not only detect Cryptosporidium but is also able to differentiate between what appear to be host-adapted genotypes of the parasite. Examinations were performed on 511 stool specimens referred for screening on the basis of diarrhea. PCR detected a total of 36 positives out of the 511 samples, while routine microscopy detected 29 positives. Additional positives detected by PCR were eventually confirmed to be positive by microscopy. A total of five samples that were positive by routine microscopy at Western Diagnostic Pathology but negative by PCR and by microscopy in our laboratory were treated as false positives. Microscopy therefore exhibited 83.7% sensitivity and 98.9% specificity compared to PCR. PCR was more sensitive and easier to interpret but required more hands-on time to perform and was more expensive than microscopy. PCR, however, was very adaptable to batch analysis, reducing the costs considerably. Bulk buying of reagents and modifications to the procedure would decrease the cost of the PCR test even more. An important advantage of the PCR test, its ability to directly differentiate between different Cryptosporidium genotypes, will assist in determining the source of cryptosporidial outbreaks. Sensitivity, specificity, ability to genotype, ease of use, and adaptability to batch testing make PCR a useful tool for future diagnosis and studies on the molecular epidemiology of Cryptosporidium infections.

Animals↗
PubMed1998

Evidence for GnRH regulation by leptin: leptin administration prevents reduced pulsatile LH secretion during fasting.

Administration of leptin during undernutrition improves reproductive function, but whether this occurs at the level of the brain, pituitary, or gonads is not yet clear. The present study tested the hypothesis that one important mechanism is the control of pulsatile gonadotropin-releasing hormone (GnRH) secretion. Our approach was to determine if leptin could prevent the marked suppression of pulsatile luteinizing hormone (LH) secretion which occurs during fasting. Leptin (3 micrograms/g i.p.; three times/48 h) or vehicle was administered during a 48-hour fast in adult ovariectomized and estrogen-treated ovariectomized rats (n = 5-7/group). LH was measured in blood samples collected every 6 min for 2 h before and after fasting. In vehicle-treated animals, plasma insulin and leptin levels decreased after fasting. As expected, the LH pulse frequency also decreased markedly. When circulating leptin remained artificially elevated during fasting, the suppression of LH pulse frequency did not occur. Leptin treatment maintained a high LH pulse frequency in the presence or absence of estrogen. The finding that leptin modulates LH pulse frequency indicates that this fat-derived hormone conveys information about nutrition to mechanisms which regulate pulsatile gonadotropin-releasing hormone secretion. Because this occurs in the absence of estrogen, the mechanism does not necessarily involve modulation of negative feedback.

Animals↗
PubMed1998

Novel glycopeptide antibiotics: N-alkylated derivatives active against vancomycin-resistant enterococci.

LY264826 (A82846B) is a naturally-occurring glycopeptide antibiotic, differing from vancomycin in the stereochemistry of the amino-sugar of the disaccharide function, and the presence of a third sugar attached at the benzylic position of amino acid residue 6. Despite these seemingly subtle differences, LY264826 is approximately 10 times more active than vancomycin against the enterococci. In the pursuit of new antibiotics active against multiresistant Gram-positive organisms, an extensive side chain SAR was developed focusing on the reductive alkylation of LY264826 at the amino function of the disaccharide moiety. A new series of derivatives having varying degrees of structural diversity in the side chain (e.g. varying lengths and degrees of rigidity) was found to have potent activity against vancomycin-resistant enterococci (MIC's < 1.0 microgram/ml) as well as activity against staphylococci and streptococci as good or better than vancomycin.

Alkylation↗
PubMed1998

Aneurysms and arteriovenous malformations.

Patients with arteriovenous malformation (AVM)-associated aneurysms are a well-recognized subset of the cerebrovascular disease population. The origin of these dual lesions is likely multifactorial, with hemodynamic stresses having a dominant influence. In most patients who present with hemorrhage, the aneurysm is the usual source. Since aneurysm rupture continues to carry a more significant morbidity and mortality when compared to AVM hemorrhage, the authors recommend that the aneurysm be treated first or simultaneously with the AVM in the majority of cases. Treatment of the AVM first is primarily reserved for patients who have suffered bleeds from resectable AVMs.

Aneurysm, Ruptured↗
PubMed1998

Factors influencing the development and carbohydrate metabolism of Echinococcus granulosus in dogs.

Echinococcus granulosus adult worms, 35 days postinfection, were measured for dispersion in the intestines of 10 dogs, a range of morphological characters, and the excreted end products of carbohydrate catabolism following 4 hr incubation in vitro. Most worms were found in the proximal sections of the small intestine, but the pattern of dispersion differed between dogs. Worm development varied both between dogs and between different regions of the small intestine of individual dogs. Overall there was a high level of variability with no simple patterns. Worm metabolism was related to worm development and, also independently, to local population density within the intestine. Larger, more mature worms produced less lactate and, at higher densities, worms tended to produce more acetate and succinate (pathways with a higher energy yield than lactate) and less ethanol. Thus, both more developed worms and high population density are associated with a shift from cytosolic to mitochondrial metabolism. The variation between worm populations along the small intestine along with the observed variation between worm populations from sibling dogs infected with genetically identical parasites suggests that the local host environment has a significant effect on parasite development.

Acetates↗
PubMed1997

The interaction of the zone of calcified cartilage and subchondral bone in osteoarthritis.

The zone of calcified cartilage (ZCC) forms an important interface between cartilage and bone for transmitting force, attaching cartilage to bone, and limiting diffusion from bone to the deeper layers of cartilage. The height of the ZCC is a relatively constant percent of articular cartilage and the height is maintained by a balance between progression of the tidemark into the unmineralized cartilage and changing into bone by vascular invasion and bony remodeling. During its formation, the cells that form the ZCC have properties similar to the cells of the growth plate. In the adult, the ZCC becomes quiescent but not inactive. The ZCC may be reactivated in osteoarthritis and may progressively calcify the unmineralized cartilage. This might contribute to cartilage thinning which would increase the concentration of forces across the uncalcified cartilage leading to more damage. Although the subchondral bony plate remodels extensively in osteoarthritis, there is little evidence that a change in the biomechanics of the plate directly initiates the osteoarthritic process in cartilage. However, increased repair by endochondral ossification of vertical cracks in the ZCC that penetrate into the marrow space could contribute to progression via changes in the ZCC.

Animals↗
PubMed1997

Intraspecific variation of Echinococcus granulosus and related species with emphasis on their infectivity to humans.

Four species are presently recognised within the genus Echinococcus, namely Echinococcus granulosus, E. multilocularis, E. oligarthrus and E. vogeli, which are infective to humans. Evidence for strain diversity within the species E. granulosus, previously mainly based on morphological, biological and biochemical features, has been principally confirmed by recent genetic studies. Several molecular techniques are now available which allow the identification of E. granulosus strains. Epidemiological evidence and molecular studies indicate that the so-called sheep, cattle and cervid strains of E. granulosus are infective to humans, while the horse, camel and pig strains may be less or not infective, but this question warrants further studies. A recent study indicates that E. granulosus infecting patients in Poland shares close molecular affinity with a genotype of pig origin (G7) but exhibits some clear differences. Therefore, it may represent a previously undescribed genotype of E. granulosus, designated as G9. Phylogenetic analysis of molecular data has demonstrated the need to reappraise the taxonomic status of currently recognised strains. Clear evidence for strain variation in the other species of Echinococcus does not exist at present.

Animals↗
PubMed1997

The prevalence of hookworm infection, iron deficiency and anaemia in an aboriginal community in north-west Australia.

OBJECTIVE: To determine the prevalence of hookworm infections, iron deficiency and anaemia in an Aboriginal community in the north of Western Australia. DESIGN AND SETTING: A cross-sectional survey conducted in 1992, examining faecal specimens and blood samples from Aboriginals and non-Aboriginals in a remote coastal community in the north of Western Australia. PARTICIPANTS: All those living in the community at the time of the survey. MAIN OUTCOME MEASURES: Parasite status and haematological values for haemoglobin, serum iron, ferritin, transferrin and mean red cell volume. RESULTS: Infections with hookworm were present throughout the Aboriginal population (77%; n = 243), with the highest prevalence in children aged 5-14 years (93%; n = 74). Hookworm was not detected in non-Aboriginals (n = 24). Iron deficiency was common throughout the Aboriginal population, especially in children aged 5-14 years (79%; n = 68) and women aged over 14 years (72%; n = 65). Anaemia was highly prevalent among Aboriginal children aged 5-14 years (84% in hookworm-positive children, 75% in hookworm-negative) and women aged over 14 years (63% in hookworm-positive women, 31% in hookworm-negative). Aboriginals over 14 years of age who had hookworm (n = 82) had significantly lower levels of haemoglobin, serum iron and serum ferritin, a lower mean red cell volume and significantly higher transferrin levels than uninfected Aboriginals (n = 38) and non-Aboriginals (n = 19) in the same age group. Hookworm infections were associated with anaemia (P < 0.01) and iron deficiency (P < 0.01) in people over 14 years of age. The species of hookworm, determined after examining 13 larval cultures and two adult worms, was found to be Ancylostoma duodenale. CONCLUSION: Infections with A. duodenale are endemic in Aboriginals in this community, and are likely to contribute to the high prevalence of iron deficiency and anaemia observed in the Aboriginal population, particularly in children and women.

Adolescent↗