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Biomedical subjects

J Vickers

Publications and source records attributed to J Vickers.

At least 37 records · Page 2Linked to original sources

Correlation of CSF 5-HIAA concentration with sociality and the timing of emigration in free-ranging primates.

OBJECTIVE: The purpose of this study was to examine the relationship between behavior and serotonin in nonhuman primates. METHOD: During a routine capture and medical examination, 26 adolescent male rhesus macaques (Macaca mulatta) were selected as subjects from a free-ranging population of 4,500 rhesus monkeys inhabiting a 475-acre sea island. Blood samples (N = 23) and CSF samples (N = 22) were obtained, and each subject was fitted with a radio transmitter collar for rapid location. The subjects were released into their social groups, and quantitative behavioral observations were made over a 3-month period. RESULTS: CSF 5-hydroxyindoleacetic acid (5-HIAA) concentration was positively correlated with three measures of sociality: 1) total time spent grooming others, 2) total time spent in close proximity to other group members, and 3) mean number of neighbors within a 5-m radius. In addition, CSF 5-HIAA concentration was positively correlated with age at emigration from the natal group (in months). CONCLUSIONS: In adolescent male rhesus macaques living in naturalistic settings, CSF 5-HIAA concentration is positively correlated with affiliative sociality. Rhesus males with low CSF 5-HIAA concentrations exhibit less social competence and emigrate from their social groups at a younger age than do males with higher concentrations of CSF 5-HIAA.

Age Factors↗

Hepatitis B outbreak in a drug trials unit: investigation and recommendations.

In autumn 1990 three young men developed acute hepatitis B. They belonged to a group of 24 young male volunteers who had taken part in a trial in a residential unit for drug trials in July and August 1990. A further case of acute hepatitis B and a carrier of hepatitis B e antigen (HBeAg) were detected by serological testing of the volunteers. Volunteers, in two groups of twelve, had occupied the unit at different times during the trial. The four cases occurred in the group that contained the HBeAg positive carrier. The carrier had also taken part in two trials on the unit in 1989. He was HBeAg positive then, but transmission of hepatitis B virus (HBV) did not occur. Although blood samples were taken in each of the three trials, intravenous cannulas were used only in the 1990 trial. It is likely that HBV was transmitted by blood to blood contact between volunteers when blood was sampled through cannulas during the trial. This outbreak might have been prevented. If an infection control policy had been applied to avoid hazardous practices, and volunteers had been screened for HBV before entry and the carrier excluded (as recommended by the Association of Independent Clinical Research Contractors), the outbreak would not have occurred. Volunteers for drug trials in residential units should be screened for HBV, human immune deficiency virus (HIV) and hepatitis C virus (HCV), and those found to be infected should not be accepted.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

Abnormalities in p53 and DNA content in transitional cell carcinoma of the bladder.

OBJECTIVE: To determine if transitional cell tumours of the bladder which contain mutations in the p53 gene have alterations in their DNA content. MATERIALS AND METHODS: In 33 transitional cell tumours of the bladder, DNA content was determined by flow cytometry and compared with expression of mutant p53 as assessed by immuno-histochemistry. RESULTS: Abnormal DNA content was associated with increased staining for p53 (P < 0.05), high tumour stage (P < 0.001) and increased histological grade (P < 0.01). Although positive staining for p53 was frequently associated with abnormal DNA content, a significant number of non-diploid tumours stained negatively for mutant p53. CONCLUSION: These data demonstrate that increased staining for p53 is associated with abnormalities in DNA content suggesting that mutation of the p53 gene is associated with an increased rate of chromosomal abnormalities and an increased rate of cell proliferation.

Carcinoma, Transitional Cell↗

Inhibition of platelet aggregation by transdermal glyceryl trinitrate.

OBJECTIVE: To determine the optimum conditions for the demonstration of an antiplatelet effect of nitric oxide and to use these conditions to elucidate the effects of a transdermal glyceryl trinitrate patch on platelet aggregation in normal volunteers. METHODS: An open prospective crossover study. The effects of nitric oxide on platelet aggregation in whole blood and platelet rich plasma as stimulated by adenosine diphosphate and U46619 was assessed in the presence and absence of iloprost and MB22948. Optimum conditions for the demonstration of an antiplatelet effect of nitric oxide were then applied to whole blood from normal volunteers in the presence and absence of a transdermal glyceryl trinitrate patch. SETTING: University hospital. SUBJECTS: Eight normal volunteers. MAIN OUTCOME MEASURES: Platelet aggregation in the presence and absence of transdermal glyceryl trinitrate. RESULTS: The optimum conditions for the demonstration of an antiplatelet effect of nitric oxide in whole blood were collecting blood into a tube containing MB22948 and citrate and stimulating platelet aggregation with adenosine diphosphate in the presence or absence of iloprost. Using this method a significant effect of transdermal glyceryl trinitrate on platelet aggregation was shown (P < 0.03) in the presence and absence of iloprost. CONCLUSIONS: These results are consistent with an inhibitory effect on platelet aggregation of nitric oxide liberated by transdermal glyceryl trinitrate. Optimum test conditions are needed to show this effect. The clinical significance of the antiplatelet effect of transdermal glyceryl trinitrate is unknown.

Adenosine Diphosphate↗

Low CSF 5-HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates.

OBJECTIVE: The purpose of this study was to examine the relationship between behavior and serotonin by using a nonhuman primate model of aggression and impulse control. METHOD: During a routine capture and medical examination, 26 adolescent male rhesus macaques (Macaca mulatta) were selected as subjects from a free-ranging population of 4,500 rhesus monkeys inhabiting a 475-acre sea island. Physiological data were obtained from 22-23 of the subjects. Blood and CSF samples were obtained, and each subject was fitted with a radio transmitter collar for rapid location. The subjects were released into their social groups, and quantitative behavioral observations were made over a 3-month period. RESULTS: CSF 5-hydroxyindoleacetic acid (5-HIAA) concentrations were inversely correlated with "escalated" aggression, i.e., a measure of more intense or severe aggression as defined by the ratio of chases and physical assaults to all aggressive acts. CSF 5-HIAA concentrations were significantly lower in those subjects who showed evidence of physical wounding than in subjects with no wounds. Low CSF 5-HIAA concentrations were also correlated with greater risk-taking as determined by an analysis of leaping behaviors in the forest canopy. The ratio of long leaps (leaps that traversed the longest distances at dangerous heights) to all leaps was negatively correlated with CSF 5-HIAA concentrations. CONCLUSIONS: Adolescent male rhesus macaques with low CSF 5-HIAA concentrations are at risk for 1) exhibiting more violent forms of aggressive behavior and 2) loss of impulse control as evidenced by greater risk taking during movement through the forest canopy.

Aggression↗

Glutathione-S-transferase pi expression in transitional cell carcinoma of the bladder.

Glutathione-S-transferase pi (GST pi) is a multifunctional protein that acts as an enzyme, involved in the detoxification of drugs and carcinogens. It has been implicated both in drug resistance and malignant transformation of epithelium. Using an indirect immunohistochemical technique, we have evaluated cytoplasmic and nuclear staining in normal urothelium, 23 superficial bladder tumours and 26 invasive tumours. All 26 invasive tumours had been treated with platinum-based chemotherapy. Cytoplasmic staining was seen in normal urothelium and all bladder tumours. Nuclear staining was seen in 1 superficial tumour and in 13 invasive tumours. There was no association between nuclear staining and response to chemotherapy. Nuclear staining was seen in 1 area of dysplasia and in 2 of 3 areas of carcinoma in situ. GST pi expression is not a predictor of response to chemotherapy. Increased intra-nuclear expression of GST pi may be associated with progression of transitional cell carcinoma of the bladder.

Carcinoma, Transitional Cell↗

Histopathology of melanocytic lesions in goats and establishment of a melanoma cell line: a potential model for human melanoma.

Melanocytic cells from white Angora goats were studied in vivo and in vitro. The histopathology of pigmented areas of skin from the most common sites of melanoma (solar-exposed areas of the ear, face, and perineum) resembled that of the epidermal melanocytes in Hutchinson's melanotic freckle in humans. Seven melanoma biopsies from 6 Angora goats showed histopathological features in common with human melanoma. A melanoma cell line, GM-1, was established in culture from a lymph node metastasis obtained from an animal that had a primary tumor excised and later developed extensive metastatic disease. GM-1 cells were mainly diploid, amelanotic, proliferated rapidly, spontaneously formed vacuolated cells, and were tumorigenic in nude mice. The species of origin of the GM-1 line was confirmed by isozyme profiles. GM-1 cultured cells and the original biopsy both expressed S-100 protein and tyrosinase antigen. Using GM-1 cells as the immunogen, a monoclonal antibody (MoAb 1F1) was derived that reacted strongly with a 116 kDa antigen in 50% of the GM-1 cells, but had little activity with goat fibroblasts (GM-F) or with human melanoma cells. GM-F, on the other hand, yielded more intense staining than GM-1 with an intermediate filament antibody (IFA), reacting with a 58 kDa antigen in both cell lines. The sensitivity of GM-1 to anticancer agents was similar to that of human melanoma cells. The pathology of caprine melanoma and its association with sun-exposed sites in relatively young animals suggest that it may be a suitable model for studying induction of melanoma by natural sunlight.

Animals↗

Development of synaptic currents in immobilized muscle of Xenopus laevis.

The effect of chronic immobilization on the development of synaptic currents was studied in myotomal muscle of Xenopus laevis. Embryos and tadpoles were immobilized by rearing them in the presence of tetrodotoxin (TTX) after removal of the egg membranes. Immobilization did not affect the developmental change in duration of miniature end-plate currents (m.e.p.c.s). Rise times decreased from about 3 to 0.6 ms in both immobilized and control muscle, and decay constants decreased from about 7 to 1 - 2 ms in both conditions. M.e.p.c.s with double exponential decays were recorded in both immobilized and control muscle at intermediate and late developmental stages. The fast and slow decay constants were 0.7 ms and slightly less than 3 ms in older muscle of both groups. These values are comparable to the apparent open times of fast and slow ACh receptors present on Xenopus muscle. Application of an anticholinesterase (methanesulphonyl fluoride) lengthened the duration of m.e.p.c.s comparably in immobilized and control muscle. These data indicate that the deposition of junctional acetylcholinesterase and the reduction in open time of acetylcholine receptor channels in developing Xenopus myotomal muscle are independent of contractile activity of muscle and TTX-blockable action potentials in muscle or motoneurones.

Acetylcholinesterase↗