PubMed Health⌕ Search

Biomedical subjects

C L Williams

Publications and source records attributed to C L Williams.

At least 19 recordsLinked to original sources
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

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↗
PubMed1979

Selected chronic disease 'risk factors' in two elementary school populations. A pilot study.

Ninety-five first-grade elementary school students (aged 5 to 6 years) in two New York City area schools participated in a pilot test of a chronic disease primary prevention program stressing nutrition, antismoking, and physical activity. Program components included a health knowledge questionnaire; measurement of height, weight, skin-fold thickness, total serum cholesterol level, and blood pressure; and a modified Harvard step test of pulse rate recovery after exercise and subsequent classroom health education. The proportion of students with test values higher than specified critical levels was much greater in school M compared with school S. These measures will be repeated after one year to determine the feasibility and potential effectiveness of certain classroom health education activities.

Blood Pressure↗
PubMed1979

Reducing adolescent obesity through a school health program.

The feasibility and effectiveness of conducting a school-based multi-component behavioral weight reduction program was tested on 119 overweight junior high school students. Four schools in the metropolitan New York area were randomly assigned to either the experimental or control conditions. After participating in a school-wide health-profile screening, students in the experimental group were invited to participate in a ten-session weight reduction program that included behavior modification, nutrition education, and exercise management. Comparison of the experimental and control groups with respect to changes on weight and triceps skinfold measures indicated significant differences between the two groups. Although the long-term effectiveness of the weight reduction program cannot be determined, the present study clearly demonstrates the short-term effectiveness and feasibility of conducting such a program in a school setting.

Adolescent↗
PubMed1979

Inhibition of suckling in weaning-age rats: a possible serotonergic mechanism.

The nature, development, and specificity of serotonergic involvement in the control of suckling behavior in rat pups from 10 to 35 days of age were studied. During development, suckling normally declines after 10 days and is abandoned after 30 days. It was found that (a) methysergide, a serotonin (5-HT) receptor blocker, reinstated suckling behavior in pups 15 days of age and older but had no effect on the suckling of 10-day old pups, (b) quipazine, a 5-HT receptor agonist, inhibited suckling of pups 10 days of age and older, (c) methysergide pretreatment blocked the quipazine inhibition of suckling, and (d) metergoline, another 5-HT blocker, also stimulated suckling, and fenfluramine, a 5-HT releaser, blocked suckling in deprived pups. Together, these data support the hypothesis that a serotonergic inhibitory mechanism modulates the suckling of weaning-age rats. These pharmacological manipulations of 5-HT appear to alter specific components of suckling behavior involved in its initiation and maintenance but do not appear to alter a general hunger system.

Animal Population Groups↗
PubMed1979

Validation of students' self-reported cigarette smoking status with plasma cotinine levels.

Plasma cotinine levels were measured in 137 students (ages 14 to 17 years), as an independent validation of self-reported cigarette smoking status. Ninety-five per cent of the students who reported daily cigarette smoking had detectable cotinine levels. In contract, only 2 per cent of students who reported that they never smoke cigarettes had detectable levels of plasma cotinine. Results suggest that adolescents can report accurately on their smoking status if sufficient assurance of confidentiality is stressed.

Adolescent↗
PubMed1978

Suckling behavior of the infant rat: modulation by a developing neurotransmitter system.

Drugs which alter serotonin receptor activity modified the suckling behavior of 20-day-old rat pups. Suckling could be reinstated in nondeprived pups, which normally do not suckle, by blockade of serotonin receptors with methysergide. Stimulation of serotonin receptors with quipazine inhibited suckling in deprived pups, and this effect was prevented by methysergide pretreatment. This evidence suggests that suckling in weaning age pups is controlled by a serotonergic inhibitory mechanism.

Animals↗