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Biomedical subjects

M Williams

Publications and source records attributed to M Williams.

At least 451 records · Page 25Linked to original sources
PubMed1992

Physiological response to cycling with both circular and noncircular chainrings.

The purpose of this study was to compare physiological variables of endurance-trained cyclists riding with four different chainring designs: round, Shimano Biopace, and two engineered ellipse designs. The ellipse designated Eng10 had the crank arm oriented 10 degrees forward of the major (i.e. longer) axis. Eighty degrees further forward, along the minor axis, was the crank arm orientation for the second ellipse, Eng90. With the major to minor axis ratio of 22.9 cm/16.8 cm (1.36), both ellipses imposed a crank angular velocity variation of 27% relative to the highest velocity assuming constant chain velocity. Best described as a skewed ellipse (i.e., major and minor axes not perpendicular), the Biopace had a major to minor axis ratio of 1.09 thus giving a crank angular velocity variation of 8%. Eleven male cyclists rode at a high (80% of maximum VO2) and a low (60% of maximum VO2) workrate using each chainring. The study was conducted over four consecutive days with the presentation order of the chainrings randomized. Open circuit spirometry was used to collect continuous respiratory data. Heart rate, blood lactate, and cadence values also were measured. None of the physiological variables including rates of oxygen consumption showed significant differences among the chainrings. Thus, the gross efficiency of cycling was not improved by any of the noncircular chainrings. For cycling events where efficiency is a determinant of performance, the noncircular chainrings do not offer any advantage over round chainrings.

Adult↗
PubMed1992

Clinical research and statistical analysis of a visual field awareness system.

This article discusses the clinical research and applications of the statistical analysis of a system called "The Visual Field Awareness System." This medical lens system allows patients with a visual field loss to 1) scan toward area of the loss, to see objects sooner and more clearly, and 2) demonstrate increased function and safety. Seventy-nine percent (27 of 34) of the patients in the sample received and accepted the prism treatment. Of this group, a minimum of 70 percent (19 of 27) continue to benefit from this treatment strategy. Statistically significant predictors of success are discussed. This study demonstrates that patients suffering visual field loss may show functional benefit by the utilization of this prism treatment along with vision rehabilitation.

Adult↗
PubMed1992

Ovarian hyperstimulation and follicular aspiration. Effect on ovulatory function.

The return of normal function of the reproductive axis immediately after hyperstimulation and follicular aspiration is of both physiologic and clinical interest. These cycles may be utilized for the replacement of cryopreserved embryos, for repeated ovarian stimulation or for any alternative treatment that relies upon normal ovulatory function. Thirty-five women were randomly assigned to be monitored in the first (n = 11), second (n = 13) or third (n = 11) menstrual cycle after in vitro fertilization (IVF). Five of 35 patients (14.3%) failed to ovulate, 2 in each of the first and second menstrual cycles and 1 in the third cycle after IVF. Six (20%) ovulatory cycles demonstrated luteal phase deficiencies. The defective luteal phases were evenly distributed between cycles immediately after IVF and those more remote in time from the procedure.

Academic Medical Centers↗
PubMed1991

Vaccine-induced CD4+ T cells against the simian immunodeficiency virus gag protein. Epitope specificity and relevance to protective immunity.

We have examined the induction and epitope specificity of T cells for the simian immunodeficiency virus (SIV) gag p27 protein in macaques immunized with either a recombinant SIV gag protein or an inactivated SIV vaccine. CD4+ MHC class II-restricted T cell lines and clones derived from five immunized macaques recognized a total of seven peptides in three immunodominant regions of p27. Two T cell clones generated from one of the lines, recognized a single 20 amino acid peptide that overlapped with a region previously shown to include a CTL epitope from SIV-infected macaques. Although this epitope is in a conserved region of the gag protein of SIV, its recognition by a CD4+ T cell clone was abrogated by sequence variation in the equivalent HIV protein. The specificity of the T cell lines for synthetic peptides demonstrated considerable overlap between T cells generated by immunization with the recombinant gag protein and inactivated SIV. However, in contrast to the protective efficacy of the whole virus vaccine in the syntex adjuvant formulation, immunization with the p27 protein with alum failed to generate a protective immune response. Furthermore, despite the consistent gag-specific T cell responses induced by the recombinant protein, there was no evidence of an enhanced antibody response to envelope (env) after live SIV challenge.

Amino Acid Sequence↗
PubMed1991

[3H]CGP 39653: a new N-methyl-D-aspartate antagonist radioligand with low nanomolar affinity in rat brain.

CGP 39653 (D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid) was initially discovered to inhibit the binding of [3H]L-glutamate and [3H]3-[+/-)2-carboxypiperazin-4-yl)-propyl-1- phosphonic acid [( 3H]CPP) with Ki values of 230 and 5 nM, respectively. The radiolabeled compound [3H]CGP 39653 binds to rat frontal cortical membranes in a saturable and reversible manner. Analysis of saturation experiments revealed that the ligand labels one binding site with a Kd value of 6 nM. Competition experiments indicated that the order of potency of a number of competitive excitatory amino acid agonist and antagonist compounds was similar to that found previously for other N-methyl-D-aspartate (NMDA) receptor ligands. In contrast to these competitive inhibitors, which produced steep inhibition curves, glycine inhibited binding in a complex manner. When the functional activity of the unlabeled compound was explored, CGP 39653 blocked NMDA-evoked depolarizations in the rat cortical wedge in vitro and inhibited L-glutamate stimulated [3H]N(1-[2-thienyl]cyclohexyl)3,4-piperidine [( 3H]TCP) binding in cortical membranes. These results suggest that [3H]CGP 39653 selectively binds to the NMDA receptor as an antagonist with high affinity and is currently the ligand of choice for labeling the NMDA receptor.

2-Amino-5-phosphonovalerate↗
PubMed1991

Down-regulation of protein kinase C blocks 5-HT-induced enhancement in Hermissenda B photoreceptors.

Light paired with serotonin (5-HT) in vivo produces both short and long-term enhancement of generator potentials in identified B-photoreceptors in Hermissenda. The contribution of protein kinase C to the induction of enhancement was assessed by pretreatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which produces a depletion or down-regulation of protein kinase C. Presentation of light and 5-HT after an 8 h pretreatment with TPA blocked the induction of enhancement of light-evoked generator potentials. Typical enhancement produced by light and 5-HT was observed after pretreatment with an inactive phorbol (4 alpha-phorbol). These results indicate that activation of protein kinase C is an important step in the induction of enhancement.

Animals↗
PubMed1991

Confirmed rabies exposure during pregnancy: treatment with human rabies immune globulin and human diploid cell vaccine.

A review of the literature shows 24 cases of pregnant human exposure to rabies virus through confirmed rabid animal bites. Historically, these patients received passive immunization with equine rabies immunoglobulin and/or purified vero cell vaccine or duck embryo vaccine. With the recent development of human-derived rabies vaccines, we report an additional case of human gestational rabies exposure, which was treated with human rabies immune globulin and human diploid cell vaccine.

Adult↗
PubMed1991

Localization of insulin-like growth factor-1 mRNA in murine central nervous system during postnatal development.

Insulin-like growth factor-1 (IGF-1) is believed to play a role in the regulation of brain growth. The identity of cells responsible for its synthesis in the immature brain, however, has not been established. To identify potential sites of IGF-1 synthesis, in situ hybridization has been utilized to localize IGF-1 mRNA in the murine brain during the first postnatal month. Although IGF-1 mRNA was detected in all regions of the neonatal brain, there was considerable regional variation in the level of expression. Neurons were the principle sites IGF-1 mRNA expression and expression was typically restricted to one or two neuronal cell types within each region. In the cerebellar cortex, for example, only Purkinje cells hybridized to the IGF-1 probe. In contrast to gray matter, IGF-1 labeled cells were rarely found in presumptive white matter tracts of the forebrain. The hybridization signal was most prominent in regions where neurogenesis persisted after birth, including the cerebellum, olfactory bulb, and hippocampal complex. The timing of IGF-1 mRNA expression appeared to be temporally related to local neuronal proliferation. The number of labeled cells and intensity of hybridization signal was greatest during the first 2 postnatal weeks, a period of rapid neuronal proliferation in these regions. At the end of the first month, when neurogenesis had essentially ceased, IGF-1 signal strength had declined to background levels. The temporal and spatial pattern IGF-1 mRNA expression in the immature CNS was consistent with a role for locally produced IGF-1 in the regulation of brain development.

Aging↗
PubMed1991

Effect of verapamil on the uptake and efflux of etoposide (VP16) in both sensitive and resistant cancer cells.

The effect of calcium antagonist verapamil on the uptake and efflux of Etoposide (VP16), a semi-synthetic derivative of podophylotoxin and a broad spectrum antineoplastic agent, has been investigated and compared in sensitive (UM-UC-2) and resistant (UM-UC-9) human bladder cancer cells, and L1210 leukemia cells, by using both radioisotope (3[H]-VP16) liquid scintillation and high performance liquid chromatography assay with electrochemical detection. The uptake of VP16 was rapid in all three cell lines, showing an initial rapid linear phase followed by a second slower phase, but at steady state the ratios of intracellular to extracellular VP16 concentrations were only 0.004-0.006. No significant difference in drug uptake was observed in sensitive UM-UC-2 and resistant UM-UC-9 cells at all concentrations studied. Verapamil at a concentration of 10 microM enhanced the intracellular VP-16 levels in all sensitive and resistant cell lines. The increments were 21.5% for UM-UC-2, 11.8% for UM-UC-9, and 31.0% for L1210 cells after 30 minutes incubation with 1 microM VP16. A slower efflux of VP16 was observed in verapamil treated cells in all three cell lines. There was a small increase in the nonexchangeable components in verapamil treated cells, although only 5-10% of VP16 was retained. No peak other than that of VP16 was detected in the HPLC chromatogram of extracts from both cell pellet and influx or efflux medium.

Animals↗
PubMed1991

Gene rearrangements in the diagnosis of lymphoma/leukemia. Guidelines for use based on a multiinstitutional study.

The demonstration of immunoglobulin or T-cell receptor gene rearrangements in human lymphoproliferative processes with the use of DNA hybridization has gained great popularity as a sensitive laboratory adjunct to diagnostic hematopathology. The fact that nearly all B- or T-cell malignant lymphomas and leukemias have one or more rearranged antigen receptor genes provides a biologic basis for a diagnostic test. To formally analyze the sensitivity, specificity, and reproducibility of gene rearrangements in the diagnosis of human lymphoproliferative disease, the authors conducted a large, multiinstitutional study. Through a blinded, controlled approach, gene rearrangement analysis of 275 cases was shown to carry a high correlation with conventional phenotyping and histologic diagnosis, with only minor false-positive and false-negative rates. Significantly, no rearrangements were detected in normal lymphoid tissues or carcinomas, sarcomas, or melanomas. In a randomized study of 50 cases, laboratory results showed a high rate of interlaboratory agreement, regardless of the level of previous experience. Furthermore, the reproducibility of interpretation of data (Southern blot autoradiograms) of 192 cases showed high concordance among 11 observers from multiple laboratories. Based on these findings, the authors propose a set of guidelines for interpretation of gene rearrangement analysis that, if carefully followed, renders this a highly reproducible, safe, and accurate addition to the diagnostic regimen for human lymphoproliferative processes.

B-Lymphocytes↗
PubMed1991

Sodium nitroprusside degenerates cultured rat striatal neurons.

Incubation of a primary culture of rat striatal neurons with sodium nitroprusside (SNP), a known source of nitric oxide (NO), showed a concentration-dependent increase in cyclic GMP levels with an EC50 value of 13.7 microM. Twenty-four hours following incubation with 10 microM SNP, striatal neurons underwent degeneration as assessed immunohistochemically and biochemically. In contrast, potassium ferricyanate at concentrations up to 1 mM had no effect on striatal neuron viability. These results indicate that SNP has neurotoxic actions in-vitro, an effect that may involve NO as a second messenger.

Animals↗
PubMed1991

LR1, a lipopolysaccharide-responsive factor with binding sites in the immunoglobulin switch regions and heavy-chain enhancer.

In nuclear extracts of primary murine B lymphocytes cultured with LPS we have identified an inducible DNA-binding activity that is a candidate regulator of isotype-switch recombination. This LPS-responsive factor, which we refer to as LR1, is induced in LPS-cultured primary cells with kinetics that parallel isotype-switch recombination. LR1 binds sequences from the S gamma 1, S gamma 3, and S alpha switch regions, as well as the heavy-chain enhancer, and these binding sites define a consensus that occurs in each of the murine switch regions. LR1 activity is present in pre-B and B-cell lines but absent from primary B cells that have not been cultured with mitogen and from highly differentiated B-cell lines. LR1-binding activity depends on phosphorylation and is lost following incubation of nuclear extracts with acid phosphatase. The LPS inducibility and phosphorylation dependence of LR1 activity suggest that this factor monitors kinase-dependent events in cell development and communicates them to the chromosome. The locations of its binding sites and the kinetics of its induction are consistent with a role for LR1 in regulation of isotype switching.

Animals↗
PubMed1991

Is GIFT (gamete intrafallopian transfer) the best treatment for unexplained infertility?

OBJECTIVE: To compare the cumulative pregnancy rates after gamete intrafallopian transfer (GIFT) with the cumulative spontaneous pregnancy rates in couples with unexplained infertility. DESIGN: A contemporaneous study in a single group of patients. SETTING: Northern Regional Fertility Centre. SUBJECTS: 76 couples with unexplained infertility of more than 3 years duration. INTERVENTIONS: Successful pregnancies were recorded during at least 3 months before GIFT and up to 21 months after a maximum of three cycles of GIFT treatment. MAIN OUTCOME MEASURES: Pregnancy resulting in a live birth. RESULTS: Average monthly fecundability without treatment was 0.021 and after GIFT was 0.14 (P less than 0.001). This was reflected as a cumulative pregnancy rate of 52% after three cycles of GIFT and 30% after 24 months without treatment. CONCLUSIONS: The chance of having a baby after one cycle of GIFT is significantly greater than the chance in a spontaneous cycle. However, considering the cumulative pregnancy rates, we suggest that if GIFT is to be a realistic treatment option, it should be offered for more than one cycle.

Adult↗
PubMed1991

Gamete intrafallopian transfer (GIFT) compared with intrauterine insemination in the treatment of unexplained infertility.

OBJECTIVE: To compare GIFT, intrauterine insemination (IUI) with, and without, ovarian hyperstimulation in the treatment of unexplained infertility. DESIGN: Women randomly allocated to one of three treatment protocols. SETTING: Northern Regional Fertility Centre. SUBJECTS: 59 couples with unexplained infertility of more than 3 years duration. INTERVENTIONS: Three cycles of either GIFT, IUI after ovarian hyperstimulation or IUI in a spontaneous cycle. MAIN OUTCOME MEASURES: Pregnancy resulting in a live birth. RESULTS: Fecundabilities were 0.12 after GIFT, 0.018 after ovarian hyperstimulation and IUI, and 0.018 after IUI in a spontaneous cycle. The fecundability after IUI was no different from that which would be expected without treatment in these couples but fecundability was significantly better (P greater than 0.02) after GIFT. CONCLUSIONS: This trial does not support the use of IUI in the treatment of unexplained infertility but confirms the value of GIFT.

Adult↗