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C B Smith

Publications and source records attributed to C B Smith.

284 records · Page 16Linked to original sources

DNA polymerase activity of cultured rheumatoid synovial cells.

Cultured synovial cells from 8 patients with rheumatoid arthritis (RA) and 7 subjects without joint disease were assayed and comapred for RNA-directed and DNA-directed DNA polymerase activity. No activity was found in either RA or control specimens using a synthetic RNA template that specificically detects oncornavirus RNA-directed DNA polymerase. The DNA-directed DNA polymerase activity of RA specimens was increased (P less than 0.10) in the high-speed pellet fraction of cell lysates. The possible relationship of these finding to virus infection in RA is disscussed.

Adult↗

Susceptibility of rheumatoid and nonrheumatoid synovial cells to antibody-dependent cell-mediated cytotoxicity.

Fibroblastic cells derived from rheumatoid (RA) and nonrheumatoid (N-RA) synovial tissue (synovial cells) were used as targets in assays of antibody-dependent cell-mediated cytotoxicity (ADCC). Synovial cells that had been pretreated with human alloantisera were rapidly lysed by normal human blood mononuclear cells. RA and N-RA synovial cells were equally susceptible to ADCC under these assay conditions. Antibody to autologous synovial cells was not detected in sera from 10 patients with RA by this method of assay.

Antibody-Dependent Cell Cytotoxicity↗

Effects of aging on regional rates of cerebral protein synthesis in the Sprague-Dawley rat: examination of the influence of recycling of amino acids derived from protein degradation into the precursor pool.

The quantitative autoradiographic L-[1-14C]leucine method for determination of regional rats of cerebral protein synthesis (1CPSleu) requires knowledge of the degree of recycling of leucine derived from protein degradation into the precursor pool of protein synthesis. The influence of recycling can be evaluated by measuring lambda, the steady state ratio of the leucine specific activity in the precursor amino acid pool (t-RNA-bound leucine) to that in the arterial plasma. To define the changes in 1CPS(leu) during the process of normal aging in the rat we have evaluated lambda in middle-aged (14 months) and aged (24 months) rats and compared its values with those obtained previously in young adult rats (two months of age). The results show that the value of lambda is the same in all three age groups, and that there is no change with aging in the fraction of leucine in the precursor pool derived from protein degradation. Our previously reported regional rates of protein synthesis in young adult and aged rats were based on the assumption that there was no recycling of leucine derived from protein degradation into the precursor pool of protein synthesis [Ingvar M.C., Maeder P., Sokoloff L. and Smith C.B. (1985) Brain 108, 155-170]. These values have been recalculated in the present study in order to take into account the appropriate correction for recycling. The recalculated rates are higher than those reported previously, but the effects of aging in the brain as a whole and in some specific brain regions are confirmed. Decreased 1CPS(leu) was observed by middle-age, and in this cross-sectional study did not appear to decrease further. Of the 39 brain regions examined decreases were found throughout the brain with some proclivity for the brain stem. In comparison with young adults the weighted average rate of protein synthesis in the brain as a whole was found to be decreased by 16 and 11% in the middle-aged and aged groups, respectively.

Aging↗

Effects of chronic dietary aluminum on local cerebral glucose utilization in rats.

Beginning at 4 weeks of age normal, male, Sprague-Dawley rats were reared on Purina Laboratory Chow and drinking water containing 100 microM AlCl3. After 2 years, local rates of cerebral glucose utilization were determined with the autoradiographic [14C] deoxyglucose method in the brain as a whole and in 25 brain regions in 6 treated rats and 4 age-matched controls. The results indicate that any effects of chronic aluminum in the diet on rates of cerebral glucose utilization are small. In the brain as a whole, the mean rate of glucose utilization in the aluminum-treated rats was 6% lower than that of the controls (p = 0.09). In 21 of the 25 brain regions examined mean rates of glucose utilization were generally lower in the aluminum-treated rats but in none of the region were the effects statistically significant.

Aging↗

Whisker follicle removal affects somatotopy and innervation of other follicles in adult mice.

The present study shows that in the whisker-to-barrel pathway of adult mice surgical removal of three whisker follicles leads to the expansion of the functional cortical representation of the whiskers adjacent to the lesion into the deprived barrels within 8 months. Concomitant with this enlargement, there is an increase in follicular innervation of the corresponding whiskers. This reorganization of the peripheral innervation may be important for the observed reshaping of cortical somatotopy.

Animals↗

Sympathetic inhibition with methyldopa in heart failure.

The hypothesis that withdrawal of increased sympathetic activity may be beneficial in heart failure was tested by administration of the centrally acting adrenergic inhibitor methyldopa. Fourteen subjects with chronic, stable New York Heart Association Functional Class 2 or 3 heart failure receiving digitalis and diuretics were randomized to methyldopa (n = 8) 500-1000 mg daily or placebo (n = 6). Clinical, hemodynamic, neurohumoral, and platelet alpha 2-receptor effects were studied after chronic (3 weeks) administration. Sympathetic inhibition did not alter symptom status or exercise duration but reduced plasma norepinephrine concentration during exercise and permitted the same level of exercise to be attained at a lower pressure-rate product, indicating reduced myocardial oxygen consumption. Left ventricular ejection fraction and stroke volume tended to increase, and systemic vascular resistance tended to decrease during exercise after methyldopa administration, suggesting enhanced vasodilation. Upright plasma renin activity increased from 8.2 +/- 2.2 to 13.3 +/- 3.0 ng/nl/h (p = 0.03) after methyldopa, but plasma antidiuretic hormone concentration changed insignificantly. In a subset of patients, platelet alpha 2-receptor density and affinity were unaltered. Renal function was also unchanged. Thus, sympathetic inhibition induced by methyldopa in selected patients with chronic, stable heart failure does not worsen symptom status or exercise performance, and may produce a beneficial effect by withdrawal of excess sympathetic activity with reduction of plasma norepinephrine levels.

Adult↗

Platelet alpha 2-adrenoreceptors, catecholamines, hemodynamic variables, and anxiety in panic patients and their asymptomatic relatives.

The objectives of this study were to a) replicate our prior finding of a decreased number (Bmax) of platelet alpha 2-adrenoreceptors in panic disorder, b) determine if binding is also decreased in asymptomatic first-degree relatives of panic patients (known to be at increased risk for developing panic), and c) evaluate the effect of treatment on the presumptive decrease in binding (i.e., is the decrease a state or a trait marker for panic?). Panic patients had clonidine and yohimbine platelet-binding assays, symptom ratings, and measurement of lying and standing plasma epinephrine, norepinephrine, systolic and diastolic blood pressure, and heart rate before treatment, after approximately 2 months of medication (fluoxetine, tricyclics, or alprazolam) and/or cognitive behavioral treatment, and after symptom remission while drug free; normal subjects had determinations of the same measures at approximately the same time intervals. Relatives of both groups had one determination only of all measures. Tritiated clonidine binding was decreased and lying heart rate was increased in patients before treatment. Magnitude of binding decrease was correlated with symptom severity and standing norepinephrine. No binding abnormality was seen in first-degree relatives of patients. Treatment increased clonidine binding in patients. Both patients and relatives of patients showed significantly increased standing plasma norepinephrine in comparison to controls. There is a state-related decrease in binding, associated with symptom severity and norepinephrine, in panic disorder. Abnormal reactivity of norepinephrine to standing might be a marker for increased likelihood of panic development in individuals at risk.

Adult↗

Treatment of cytomegalovirus pneumonia in heart transplant recipients with 9(1,3-dihydroxy-2-proproxymethyl)-guanine (DHPG).

Cytomegalovirus (CMV) infection is a frequent cause of serious illness in heart transplant patients and may cause life-threatening pneumonia, with a reported mortality of greater than 50%. We investigated the clinical efficacy of a new antiviral agent, 9(1,3-dihydroxy-2-proproxymethyl)-guanine (DHPG) in the treatment of CMV pneumonia in heart transplant patients. Four of these patients with biopsy-proved CMV pneumonia were treated with DHPG, with resolution of pneumonia and no relapse at a mean follow-up period of 21 weeks. DHPG may be useful in the treatment of CMV pneumonia in heart transplant patients.

Acyclovir↗

Lack of antibody in rheumatoid sera to autologous synovial macrophages and dendritic cells by antibody-dependent cellular cytotoxicity assays (ADCC).

We tested the hypothesis that antigens which stimulate the chronic immune reactivity in rheumatoid synovia might be associated with synovial macrophages and dendritic cells. ADCC assays were used to test sera from 15 RA patients and 8 non-RA controls for antibody to autologous primary and secondary cell cultures prepared by enzymatic digestion of synovial tissue. Such autoantibody was not detected in any of the 23 patients using assay conditions which minimized potential ADCC blocking effects of immune complexes and multinuclear giant cells. Collagenase producing dendritic and multinuclear giant cells. Collagenase activity and dendritic cells occurred with equal frequency in both RA and non-RA primary monolayers.

Antibodies↗