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Biomedical subjects

M Williams

Publications and source records attributed to M Williams.

At least 19 recordsLinked to original sources
PubMed1992

A-77636: a potent and selective dopamine D1 receptor agonist with antiparkinsonian activity in marmosets.

A-77636, ((1R,3S) 3-(1'-adamantyl)-1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1H-2-benz opyran hydrochloride), is a selective dopamine D1 receptor agonist. In a battery of receptor binding assays, A-77636 shows the highest affinity (pKi = 7.40 +/- 0.09; Ki = 39.8 nM) for the dopamine D1 receptor. A-77636 is an agonist at the dopamine D1 receptors in the fish retina (pEC50 = 8.13; EC50 = 1.1 nM; intrinsic activity = 102% of dopamine) and the rat caudate-putamen (pEC50 = 8.97; intrinsic activity = 134% of dopamine). The compound is functionally inactive at dopamine D2 receptors (EC50 > 10 microM). In rats with unilateral 6-OHDA (6-hydroxydopamine) lesions of the nigro-striatal dopaminergic pathway, A-77636 elicits prolonged (> 20 h) contralateral turning that is blocked by SCH 23390, a D1 receptor antagonist, but not by haloperidol at doses selective for the dopamine D2 receptor. Higher doses of A-77636 produce forelimb clonus in rats and mice. When tested in marmosets treated with MPTP to induce a parkinsonian-like state, A-77636 increases locomotor activity and decreases the severity of the parkinsonian-like symptoms: the compound is active after either subcutaneous or oral administration. A-77641, the optical antipode of A-77636, has a lower affinity towards the dopamine D1 receptor (pKi = 5.14, Ki = 7200 nM), is less potent as a dopamine D1 receptor agonist (pEC50 = 5.65; EC50 = 2200 nM), fails to elicit turning in the 6-OHDA-lesioned rat, and lacks antiparkinsonian efficacy in the MPTP-treated marmoset.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Toxic dark effects of protoporphyrin on the cytochrome P-450 system in rat liver microsomes.

In erythropoietic protoporphyria, accumulation of protoporphyrin has been found in various tissues and liver cirrhosis occurs frequently in this disease, probably due to toxic dark effects of protoporphyrin. We have studied the effect of porphyrins on various enzymic functions in rat liver microsomes. Incubation of microsomes with protoporphyrin resulted in a concentration-dependent inhibition of the oxidation of 7-ethoxycoumarin and aminopyrine by the cytochrome P-450 system. Kinetic analysis showed a decrease in Vmax., whereas the Km was not affected (non-competitive inhibition). Furthermore, reduction of cytochrome c by the NADPH-cytochrome P-450 reductase and by the NADH-cytochrome b5 reductase was inhibited. However, the activity of the reductases was only affected when the microsomes were pre-incubated with protoporphyrin, and it was found that the inhibition was dependent on the duration of the pre-incubation. Kinetic analysis again revealed non-competitive inhibition. When these experiments were repeated with uroporphyrin, no inhibition could be observed. With Stern-Volmer plots it was demonstrated that this was most likely caused by the localization of the porphyrins: protoporphyrin is localized in the membrane, whereas uroporphyrin remains in solution. From these results it is concluded that accumulation of protoporphyrin in the liver may markedly affect the cytochrome P-450 system and thus its detoxification function.

Aminopyrine↗
PubMed1992

European brown hare syndrome in the U.K.; a calicivirus related to but distinct from that of viral haemorrhagic disease in rabbits.

The virus recovered from cases of European brown hare syndrome in the U.K. contains one major capsid protein of approximately 60 k molecular weight and morphologically resembles known caliciviruses. It has been compared with a European isolate of rabbit haemorrhagic disease calicivirus and, although it shows some antigenic similarity, it is not identical. In transmission and protection studies the virus from U.K. hares failed to produce disease in rabbits and did not effectively protect against subsequent challenge with the rabbit calicivirus.

Animals↗
PubMed1992

Responses of enterocyte microvilli in experimental diabetes to insulin and an aldose reductase inhibitor (ponalrestat).

The small intestine of 12-week-old streptozotocin-diabetic rats was examined by light and transmission electron microscopy in order to study the effects of alternative treatments on microvillous morphology. Four groups were examined: untreated diabetic rats, insulin-treated diabetics and rats treated with an aldose reductase inhibitor (ponalrestat) given with and without insulin. Numbers and dimensions of microvilli at the apex of columnar absorptive epithelial cells (enterocytes) were estimated using stereological principles. Values were obtained for the organ as a whole as well as for different sites along its length. In the untreated diabetic intestine, the mean (standard error of mean) number of microvilli was 4.5 (0.8) x 10(12) with a total surface area of 1.9 (0.50) m2. On average, the microvilli were 1.1 (0.08) microns long, 104 (3.8) nm in diameter and packed on the villous surface at a density of 3400 (50) per 100 microns 2. Their length at least varied with intestinal location. Significant effects of insulin therapy were detected. In contrast, the study failed to find any significant effect of aldose reductase inhibition on any variable except microvillous packing density.

Aldehyde Reductase↗
PubMed1992

Angiographic restenosis after successful Wallstent stent implantation: an analysis of risk predictors.

Follow-up angiographic study was performed in 86 patients after initially successful Wallstent stent (Medinvent, Lausanne, Switzerland) implantation between April 1986 and October 1990. The stent angiographic restenosis rate was 16% at a mean of 8 months after stenting despite the inclusion of a substantial number of patients at high risk of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Of a total 15 variables analyzed, only suboptimal stent placement was found to be a significant predictor of stent restenosis. Age; gender; baseline New York Heart Association functional class; previous PTCA; indication for stenting; left ventricular ejection fraction; preangioplasty and immediate postangioplasty diameter stenosis severity; stented vessel site, lesional morphology; number, diameter, and length of stents implanted; and the interval between stenting and follow-up angiographic restudy were not significant risk factors of stent restenosis. Our study suggests that intracoronary stent implantation with the Wallstent may be a useful and promising adjunctive option after PTCA, particularly in patients at high risk of restenosis after PTCA. However, because of the significantly enhanced risk of restenosis after suboptimal stent implantation, we strongly recommend the selection and placement of Wallstent stents that adequately cover the entire length of the dilated coronary segment.

Adult↗
PubMed1992

DNA sequence analysis and comparison of the variable heavy and light chain regions of two IgM, monoclonal, anti-myelin associated glycoprotein antibodies.

The complete variable heavy and light chain gene sequences of two monoclonal, IgM, anti-myelin associated glycoprotein (MAG) antibodies associated with peripheral neuropathy, are presented. Comparative analysis of the two VH regions has revealed that they are 88% homologous to one another and are both members of the VH3 gene family. They are also highly homologous to a gene which is frequently utilized in the fetal B-cell repertoire. The V kappa light chain gene of one of the antibodies is 99% homologous to a V kappa II gene and the V lambda light chain gene of the other antibody is only 72% homologous to other known V lambda genes. Further analysis of V genes utilized by anti-MAG antibodies should reveal the structural basis for their binding activity.

Amino Acid Sequence↗
PubMed1992

Expression of IGF-1 mRNA in the murine subventricular zone during postnatal development.

Insulin-like growth factor-1 (IGF-1) stimulates the proliferation and maturation of neuroglia in vitro. To further investigate its role in gliogenesis, in situ hybridization was utilized to determine whether IGF-1 mRNA was expressed in the subventricular zone (SVZ) of the postnatal mouse forebrain. The SVZ is a transient germinal zone and in the neonate is the principle source of oligodendroglia for myelinating fiber tracts of the forebrain. Strong hybridization signal was detected over cells in the SVZ at postnatal day (PND) 4, the earliest time point examined. Positive signal persisted in the SVZ at PND 8, however, the number of IGF-1-labeled cells declined rapidly during the second postnatal week. IGF-1 mRNA was not uniformly distributed throughout the SVZ and the majority of labeled cells were located within its so-called 'border' region. In contrast to the SVZ, IGF-1 mRNA-expressing cells were only rarely found in forebrain fiber tracts. IGF-1 transcripts were not detected in ependymal lining or choroid plexus of the lateral ventricle. In light of its known gliotrophic activity, the localization of IGF-1 mRNA in the SVZ suggests that locally produced IGF-1 may act as a mitogen or differentiation-inducing agent during gliogenesis.

Aging↗
PubMed1992

Behavioral asymmetries of psychomotor performance in rhesus monkeys (Macaca mulatta): a dissociation between hand preference and skill.

Hand preferences were recorded for 35 rhesus monkeys (Macaca mulatta) as they manipulated a joystick in response to 2 computerized tasks. These preferences were then used to contrast 8 left- and 10 right-handed subjects on performance measures of hand skill. Individual hand preferences were found, but no significant population asymmetry was observed across the sample. However, the performance data reveal substantial benefits of right-handedness for joystick manipulation, as this group of monkeys mastered the 2 psychomotor tasks significantly faster than did their left-handed counterparts. The data support earlier reports of a right-hand advantage for joystick manipulation and also support the importance of distinguishing between hand preference and manual performance in research on functional asymmetries.

Animals↗
PubMed1992

Antibody to hepatitis C virus in selected groups of a Canadian urban population.

In an anonymous survey, 433 sera from Canadian individuals of selected categories were tested for the presence of antibody to hepatitis C virus (HCV) using a recombinant antigen-based immunoassay. About 50% of intravenous drug abusers (IVDA), 10% of transfusion recipients and an overall average of 7.9% of male homosexuals were reactive for antibody to HCV. Individuals with jaundice and negative hepatitis B virus (HBV) serology were not reactive for antibody to HCV compared with 26.7% of those with positive HBV serology. Similarly 58% of male Federal prisoners with positive HBV serology were also HCV-antibody reactive compared with 15% of those with negative HBV serology. A prevalence of 1.2% was recorded for individuals not in any of the above groups. Of 433 sera, 92 were reactive and the discrimination in absorbance values between reactive and not reactive samples was good except for 13 sera, eight of which gave values considerably higher than the average negative value and five which were just above the positive threshold.

Alberta↗
PubMed1992

Recovery of artificially inseminated spermatozoa from the fallopian tubes of a woman undergoing total abdominal hysterectomy.

Investigation of the process of sperm transport within the human female reproductive tract must involve the recovery of spermatozoa from the oviducts of women post-coitum or insemination. This case report describes the insemination of a 40-year-old woman with her partner's semen and the subsequent recovery of spermatozoa from her Fallopian tubes, removed at hysterectomy, 2 days post-ovulation. The number of spermatozoa present within the tubes and their location was ascertained using a flushing technique and scanning electron microscopy (SEM). The total number of spermatozoa present within the flushed tube was calculated to be 142, whilst the total number of spermatozoa calculated to be present within the scanned tube was 673. The proportional distribution of spermatozoa within the tubes was virtually identical by the two techniques used. The largest population of spermatozoa resided within the ampulla (66.1% SEM, 68.3% flush), and the smallest population resided within the intramural region (14.9% SEM, 13.4% flush).

Adult↗
PubMed1992

Psychiatric epidemiology of an Indian village. A 19-year replication study.

This 1988 study reports the point and lifetime prevalence of psychiatric disorders, using DSM-III-R criteria, of a sample (approximately 25%) of adult members of an Indian village previously studied in 1969. The basic instrument was the Schedule for Affective Disorders and Schizophrenia, augmented by available medical information and administered by experienced psychiatrists. Subjects were interviewed and results were weighed for the age- and sex-distributed population. The results indicated a high point prevalence of alcohol dependence (32.8%), with a lifetime prevalence of 72.8%, among males. The lifetime prevalence of affective disorders among women was also high (36.8%), but less so among men (19.3%). When compared with the DSM-III-R diagnoses of the 1969 study, the point prevalence rates of alcohol dependence and abuse disorders fell from 39% to 21%. Also, fewer subjects were judged to be psychiatrically impaired. Even though the prevalence of psychiatric disorders was lower in the current study, the rates for alcohol disorders and affective disorders were still far higher than those reported in Epidemiologic Catchment Area studies. Alcohol dependence (especially among young men) and affective disorder (among women) were major problems.

Adult↗
PubMed1992

Acoustic analysis and perception of vowels in children's and teenagers' stuttered speech.

The syllable repetitions of 24 child and eight teenage stutterers were investigated to assess whether the vowels neutralize and, if so, what causes this. In both groups of speakers, the vowel in CV syllable repetitions and the following fluent vowel were excised from conversational speech samples. Acoustic analyses showed the formant frequencies of vowels in syllable repetitions to be appropriate for the intended vowel and the duration of the dysfluent vowels to be shorter than those of the fluent vowels for both groups of speakers. The intensity of the fluent vowels was greater than that of the dysfluent vowels for the teenagers but not the children: For both age groups, excitation waveforms obtained by inverse filtering showed that the excitation spectra associated with dysfluent vowels fell off more rapidly with frequency than did those associated with the fluent vowels. The fundamental frequency of the children's dysfluent speech was higher than their fluent speech while there was no difference in the teenager's speech. The relationship between the intensities of the glottal volume velocities was the same as that of the speech waveforms. Perceptual tests were also conducted to assess whether duration and the differences found in the source excitation would make children's vowels sound neutral. The experiments show that in children neither vowel duration nor fundamental frequency differences cause the vowels to be perceived as neutral. The results suggest that the low intensity and characteristics of the source of excitation which cause vowels to sound neutral may only occur in late childhood. Furthermore, monitoring stuttered speech for the emergence of neutral vowels may be a way of indexing the progress of the disorder.

Adolescent↗