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Biomedical subjects

C L Williams

Publications and source records attributed to C L Williams.

At least 145 records · Page 8Linked to original sources
PubMed1993

Reversible lesions of the nucleus of the solitary tract attenuate the memory-modulating effects of posttraining epinephrine.

Rats implanted with cannula tips placed above the nucleus of the solitary tract (NTS) were trained to obtain food pellets placed in 2 arms of a Y maze and then given a footshock in 1 arm of the maze. The rats then received bilateral injections of lidocaine or buffer into the NTS and peripheral injections of saline or epinephrine (0.01 or 0.05 mg/kg ip). Two tests were given 24 and 48 hr after training to assess retention in the presence and absence of contextual cues (the stainless steel floor) associated with the footshock training trial. Epinephrine (0.05 mg/kg) produced a significant enhancement in retention, which was attenuated by injections of lidocaine into the NTS. These findings indicate that the NTS is involved in mediating the memory-modulating effects of peripheral epinephrine and that such effects are initiated at least in part by activation of vagal afferents projecting to the NTS.

Afferent Pathways↗
PubMed1992

Human monoclonal striational autoantibodies isolated from thymic B lymphocytes of patients with myasthenia gravis use VH and VL gene segments associated with the autoimmune repertoire.

The production of autoantibodies reactive with components of skeletal muscle is characteristic of myasthenia gravis (MG) and is strongly associated with the presence of thymic epithelial tumors in patients with MG. The nucleotide sequences of the heavy and light chain variable regions (VH and VL) of three human monoclonal striated muscle antibodies (StrAb) isolated from thymic B lymphocyte lines from two patients with MG and thymoma were analyzed. The VH and VL gene segments used by these anti-striated muscle antibodies appear to be derived from the same repertoire of gene segments as have been found in other autoantibodies isolated from patients with a number of different autoimmune diseases. While the IgM StrAb SA-1A is a direct copy of germ-line VH and VL gene segments, analysis of the IgG StrAb SA-4A and SA-4B, which may be more representative of antibodies found in the serum of MG patients, suggests that the processes of antigenic selection and somatic mutation may contribute to the generation of autoantibodies in MG.

Actins↗
PubMed1992

Subjective correlates of cigarette-smoking-induced elevations of peripheral beta-endorphin and cortisol.

Two experiments assessed subjective and hormonal effects of smoking cigarettes with three different nicotine deliveries. In experiment 1, 12 males smoked two cigarettes on three different occasions: (1) nicotine-free; (2) their own brand (1.0 mg FTC-estimated nicotine delivery); or (3) 2.4 mg FTC nicotine cigarettes. In experiment 2, 12 males smoked cigarettes of comparable nicotine yield using a quantified smoke delivery system (QSDS). Blood was sampled 2 min after each cigarette completion. Relative to nicotine-free smoking, plasma beta-endorphin (BE) and serum cortisol concentrations increased after quasi-ad libitum smoking of 2.4 mg, but not after 1.0 mg nicotine cigarettes. Self-reported malaise (nausea, sickness, and unpleasantness) also increased after smoking 2.4 mg nicotine cigarettes; subjective distress was correlated with changes in blood BE and cortisol. Smoking 1.0 mg cigarettes did not increase BE or cortisol, or subjective distress. QSDS smoking produced hormonal and subjective effects similar to quasi-ad libitum smoking; however, correlations between neuromodulator concentrations and mood were non-significant. These findings suggest that the elevated levels of plasma BE and cortisol reported in some smoking studies may not be characteristic effects of normal smoking.

Adult↗
PubMed1992

Reversible inactivation of the nucleus of the solitary tract impairs retention performance in an inhibitory avoidance task.

Several peripherally acting hormones and drugs are known to modulate memory storage processes, yet the mechanisms which permit these agents to influence memory is not well understood since they do not freely enter the brain. The nucleus of the solitary tract (NTS) is one brainstem structure which receives important neural input from the periphery. Therefore, the objective of this experiment was to determine whether the NTS is involved in modulating processes contributing to memory formation. Male Sprague-Dawley rats were trained in a one-trial inhibitory avoidance task (0.35 mA, 0.5 s footshock). Immediately or 2 h after training microinjections of 2% lidocaine hydrochloride (20 mg/kg) or a phosphate buffer solution were administered bilaterally into the NTS. Two other groups received microinjections of lidocaine into the fourth ventricle or cerebellum. On retention tests given 48 h after training the latency to reenter the dark compartment of the apparatus was recorded. The retention latencies of rats receiving bilateral microinjections of 0.5 microliter of lidocaine hydrochloride into the NTS were significantly shorter than those of animals given injections of a buffer solution (0.5 microliter), delayed injections of buffer or lidocaine, or control injections of lidocaine into the cerebellum or fourth ventricle. These findings suggest that memory storage processes are impaired by reversible inactivation of the NTS after training. The implications of these findings in terms of a possible role of the NTS in modulating brain processes involved in memory storage are discussed.

Amygdala↗
PubMed1992

Paraneoplastic IgG striational autoantibodies produced by clonal thymic B cells and in serum of patients with myasthenia gravis and thymoma react with titin.

Autoantibodies with heterogeneous specificities for contractile elements of striated muscle are found in 80 to 90% of patients who have myasthenia gravis (MG) with thymoma. The stimulus for production of these paraneoplastic striational autoantibodies (StrAb) is unknown. One approach to understanding their association with MG and thymoma is to define the antigenic specificities of monoclonal StrAb secreted by B cell lines established from patients who have MG and thymoma. Here, we report the isolation from a single patient of two independent thymic B cell clones secreting StrAb of IgG isotype. In immunoblots, both StrAb bound monospecifically to an antigen of human skeletal muscle that comigrated with the high molecular weight protein, titin. The pattern of immunofluorescence staining yielded by both antibodies in cultured human muscle cells was similar to that produced by rabbit polyclonal anti-titin antibodies. Each monoclonal antibody bound to a different region of the sarcomere in stretched myofibrils; these corresponded to sites previously reported to bind murine anti-titin monoclonal antibodies. The pattern of sarcomere immunostaining produced by combining the two human monoclonal antibodies was indistinguishable from that produced by serum IgG from the patient whose thymus yielded the B cell clones. Thus, the monoclonal antibodies appear to identify two epitopes of titin that are recognized by IgG StrAb in serum. The finding that IgG anti-titin autoantibodies are restricted to serum of MG patients who have thymoma suggests that titin is a major specificity of IgG StrAb. Our additional finding that anti-titin IgG binds to striated elements in medullary myoid cells of the human thymus supports the hypothesis that StrAb represent an intrathymic B cell immune response that is initiated by autoantigens that are rendered immunogenic for helper T cells in the course of noeplastic transformation to thymoma.

Adult↗
PubMed1991

The organizational effects of gonadal steroids on sexually dimorphic spatial ability.

Numerous studies have provided evidence that both human and nonhuman males reliably outperform females on tasks that require spatial ability. Because most of the research on this topic has utilized hormonally normal adults as subjects, it is still not known to what extent, if any, sex differences in spatial ability can be attributed to hormonally organized dimorphisms in neural structures subserving cognitive function. The purpose of this paper is to address this critical issue in three areas: (1) Research that demonstrates that male rodents initially outperform females on maze tasks that utilize visuospatial representation will be reviewed. (2) New data which provide strong evidence for the organizational effects of gonadal steroids will be described. The timing of the sensitive period for hormone action, the specific hormones involved and their possible sites of action will be discussed. (3) The question of what behavioral processes hormones might be affecting to cause differential performance on spatial tasks will be examined. The studies described in this review suggest that gonadal steroids, probably the testosterone metabolite estradiol, cause organizational effects during perinatal development which have multiple effects on the associational-perceptual-motor biases that guide visuospatial navigation.

Animals↗
PubMed1991

Primary prevention of acculturative stress among refugees. Application of psychological theory and practice.

Primary prevention in refugee mental health requires information from clinical, health, and cross-cultural psychology. Primary prevention's roots are in public health, which is distinguished by a communitywide perspective for addressing mental health concerns. This article summarizes research suggesting that refugees are an at-risk population, making them especially suitable for public health interventions. Research on stress and acculturation is highlighted, given its importance to prevention in refugee mental health. The opportunities for primary prevention programs and policies at 3 levels (i.e., local community, national, and international) are illustrated with case examples from both the United States and Canada. Prevention at the international level is highlighted by a World Health Organization Mental Health Mission to camps on the Thai-Cambodian border.

Acculturation↗
PubMed1991

Activation of muscarinic acetylcholine receptors inhibits cell cycle progression of small cell lung carcinoma.

We previously reported that activation of muscarinic acetylcholine receptors (mAChR) of M3 subtype causes hydrolysis of phosphoinositides and inhibits voltage-gated Ca2+ channel activity in small cell lung carcinoma (SCLC) cells. We now report that mAChR activation causes exponentially growing SCLC cells to arrest in S and G2/M phases of the cell cycle, concomitant with a decrease in DNA synthesis. Cell cycle progression and DNA synthesis resume when mAChR are down-regulated. In serum-starved SCLC cells, mAChR activation inhibits DNA synthesis induced by serum, bombesin, insulin, or insulin-like growth factor-I. The finding that DNA synthesis is inhibited even when mAChR are activated after exposure of cells to growth factors indicates that decreased signal transduction by growth factor receptors is not the mechanism of mAChR-mediated growth inhibition. Our data suggest that mAChR activation disrupts a common event that is induced by different growth factors and is fundamental for cell cycle progression.

Bombesin↗
PubMed1991

Induction of tubules in rat metanephrogenic mesenchyme in the absence of an inductive tissue.

Differentiation of metanephrogenic mesenchyme to renal tubular epithelium requires induction by the ureteric bud in vivo or any of several embryonic tissues in vitro. In an effort to eliminate the tissue requirement in embryonic induction, extracellular matrices and soluble factors were analyzed individually or in combination for their ability to stimulate tubulogenesis in uninduced metanephrogenic mesenchyme from 13-gestation-day rat embryos. These evaluations have established that pituitary extract and epidermal growth factor (EGF) in concert with a matrix can promote morphogenesis of mesenchymal rudiments in culture. While type I collagen, laminin, or fibronectin matrices all promoted tubulogenesis in the presence of pituitary extract and EGF, type IV collagen proved the most effective. Under these conditions, tubules were induced in 23/24 mesenchymal rudiments by 9 days in culture. Mesenchyme was not induced prior to explanation since it formed no tubules when cultured in a medium that allowed tubulogenesis in intact embryonic kidneys. Preliminary characterization of the undefined factor in pituitary extract was consistent with a protein of molecular weight greater than 100,000 but less than 300,000. When uninduced metanephrogenic mesenchyme from mouse was used instead of rat tissue, a similar pattern of morphogenesis was not observed, suggesting that the described medium is inappropriate for promoting differentiation in mouse or, less likely, that different mechanisms mediate differentiation in rat and mouse. These studies show that embryonic induction can occur in explanted rat renal mesenchyme in an appropriate environment and does not require the presence of an inductive tissue.

Animals↗
PubMed1991

Growth and branching morphogenesis of rat collecting duct anlagen in the absence of metanephrogenic mesenchyme.

The growth and differentiation of the epithelium in many tissues is mediated by interactions with the adjacent mesenchyme, but the mechanisms responsible remain undefined. To identify the factors involved in the growth and branching morphogenesis of ureteric bud, which is the collecting duct anlagen, buds from 13-gestation-day rat embryos were separated from the metanephrogenic mesenchyme and explanted to culture dishes coated with gelled type I collagen in a defined medium. Under these conditions buds attached to the substrate and grew out without indication of cell senescence. When buds were instead suspended in gelled type I collagen, branching morphogenesis was observed despite the absence of mesenchyme although it was not as extensive as in vivo. Since growth occurred much more slowly in culture than expected, culture conditions were varied in attempts to accelerate the process. Despite extensive screening of matrices and growth factors, only epidermal and endothelial cell growth factors stimulated growth to a significant extent. Transforming growth factor-beta, on the other hand, was a potent inhibitor of growth. Homogenates from tumors that caricature metanephrogenic mesenchyme were highly mitogenic for bud cells and, thus, will be a source of material for characterizing regulatory factors involved in renal growth. These studies show that growth and branching morphogenesis of the ureteric bud can occur without direct cell-cell interactions with the metanephrogenic mesenchyme and that matrices and factors secreted by the mesenchyme may mediated these activities in vivo.

Animals↗
PubMed1991

Use of low-dose trimethoprim-sulfamethoxazole thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.

We conducted an open prospective clinical trial to evaluate the efficacy and toxicity of trimethoprim-sulfamethoxazole given as one double-strength tablet thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus-infected (HIV+) patients. A total of 104 HIV+ patients were evaluated, with 74 being in the primary prophylaxis group and 30 being in the secondary prophylaxis group. All except six patients received concomitant zidovudine; five patients on primary prophylaxis and one patient on secondary prophylaxis refused zidovudine. There were 70 patients evaluated for the efficacy of primary prophylaxis. The mean CD4 count was 124.4 +/- 110.1 cells per microliter. The mean follow-up time was 11.8 +/- 5.8 months (median, 12 months; range, 1 to 32 months). Two noncompliant patients developed PCP after 1 and 3 months of chemoprophylaxis. The failure rate (under the intention to treat principle) was 2 of 70 patients (2.9%; 95% confidence interval, 0.35 to 10%), or 1 per 413 patient-months of observation. There were 27 patients evaluated for the efficacy of secondary prophylaxis. The mean follow-up time was 12.4 +/- 7.2 months (median, 11 months; range, 1 to 29 months). Two patients, one of whom was noncompliant, were treatment failures, developing PCP after 14 and 15 months of chemoprophylaxis; this gave a failure rate of 2 of 27 patients (7.4%; 95% confidence interval, 0.9 to 24.3%), or 1 per 167 patient-months of observation. Adverse reactions sufficient to permanently terminate therapy occurred in 9 of 104 patients (8.7%; 95% confidence interval, 4 to 15.7%) overall. The serum trimethoprim, sulfamethoxazole, and N4-acetyl-sulfamethoxazole concentrations measured by high-pressure liquid chromatography were uniformly low. One double-strength tablet of trimethoprim-sulfamethoxazole taken weekly on Monday, Wednesday, and Friday appeared to be well tolerated and efficacious for the prophylaxis of PCP in HIV+ patients at high risk and deserves further investigation.

Adult↗
PubMed1991

Pharmacokinetics and adverse effects of 20-mg/kg/day trimethoprim and 100-mg/kg/day sulfamethoxazole in healthy adult subjects.

The pharmacokinetics of trimethoprim-sulfamethoxazole were studied in 12 healthy adult subjects receiving trimethoprim at 20 mg/kg of body weight per day and sulfamethoxazole at 100 mg/kg/day, which is the conventional dose for treating Pneumocystis carinii pneumonia (PCP). Daily doses were evenly divided and orally administered every 6 h for 3 days. Trimethoprim, sulfamethoxazole, and N4-acetylsulfamethoxazole concentrations in serum and urine were measured by high-performance liquid chromatography. Five subjects withdrew from the study because of intolerable gastrointestinal and central nervous system toxicities. In the seven subjects that completed the study, the mean maximum serum drug concentrations after the last dose were 13.6 +/- 2.0, 372 +/- 64, and 50.1 +/- 10.9 micrograms/ml for trimethoprim, sulfamethoxazole, and N4-acetylsulfamethoxazole, respectively. The mean half-lives were 13.6 +/- 3.5, 14.0 +/- 2.3, and 18.6 +/- 4.3 h, respectively. Changes in absolute neutrophil count were significantly correlated with the minimum concentrations of trimethoprim and sulfamethoxazole in serum and trimethoprim area under the concentration-time curve (for all three parameters, r2 = 0.6 and P less than 0.05). Our findings add to the evidence that serum drug concentrations in adults following the conventional dose of trimethoprim-sulfamethoxazole for PCP are excessive and contribute to certain adverse reactions. Further studies are indicated in patients to optimize the dosing regimen of trimethoprim-sulfamethoxazole in the treatment of PCP.

Administration, Oral↗