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Biomedical subjects

W C Williams

Publications and source records attributed to W C Williams.

13 recordsLinked to original sources
PubMed1992

Comparative immunosuppression of various glycol ethers orally administered to Fischer 344 rats.

Oral dosing of adult male F344 rats with the glycol ether 2-methoxyethanol (ME) or its principal metabolite 2-methoxyacetic acid (MAA) results in the suppression of the primary plaque-forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP-LPS). In the present study, the PFC response to TNP-LPS was used to evaluate the immunotoxic potential of ethylene glycol (EG) as well as the glycol ethers 2-methoxyethyl acetate (MEA), 2-(2-methoxyethoxy) ethanol, bis(2-methoxyethyl) ether, 2-ethoxyethanol and its principal metabolite 2-ethoxyacetic acid, 2-ethoxyethyl acetate, and 2-butoxyethanol relative to ME and MAA. Rats were immunized with TNP-LPS and then exposed 4 and 28 hr later to 50, 100, 200, or 400 mg/kg of glycol ether or EG. Three days following immunization, the PFC response to TNP-LPS was determined. In addition to ME and MAA, only MEA, which was as effective as ME, suppressed the PFC response to TNP-LPS. Concomitant administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole with ME or MEA prevented suppression of the PFC response by these glycol ethers. These results indicate that of the chemicals tested only ME, MEA, and MAA are immunosuppressive, and that oxidative metabolism via alcohol dehydrogenase is necessary for ME- and MEA-suppression of the response to TNP-LPS.

Administration, Oral↗
PubMed1992

Differences between rats and mice in the immunosuppressive activity of 2-methoxyethanol and 2-methoxyacetic acid.

Previous studies from this laboratory have demonstrated that 2-methoxyethanol (ME) and its principal metabolite 2-methoxyacetic acid (MAA) are immunosuppressive in young adult male Fischer 344 rats. In the present study, the immunosuppressive potential of ME and MAA was evaluated in young adult female Fischer 344 rats and C57BL/6J mice. Rats and mice were dosed by gavage with either ME or MAA in water, at dosages ranging from 50-400 mg/kg/day, for 10 consecutive days. Rats and mice were examined for alterations in body, spleen and thymus weights and mitogen-induced proliferation of splenic lymphocytes in vitro; separate groups were employed for the antibody plaque-forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP-LPS). Rats dosed at 100-400 mg/kg/day ME and rats dosed at 50-400 mg/kg/day MAA had decreased thymus weights in the absence of decreased body or spleen weights. Lymphoproliferative (LP) responses to concanavalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and Salmonella typhimurium mitogen (STM) were all reduced in rats treated with all dosages of ME. Rats treated with MAA displayed similar reductions in these LP responses except that the responses to PWM and STM in rats dosed at 50 mg/kg/day were not reduced. In contrast to the effects of ME and MAA on these end points in the rat, no thymic involution or suppression of LP responses were observed in mice dosed at 50-400 mg/kg/day. The PFC response to TNP-LPS was suppressed in rats dosed with either ME or MAA at dosages of 100-400 mg/kg/day. ME and MAA, however, failed to suppress the PFC response in mice immunized with TNP-LPS. These results indicate that unlike Fischer 344 rats, C57BL/6J mice are insensitive to the immunosuppressive effects of ME and MAA at the dosages employed in this study. Whether the different sensitivities of these two rodent species to ME- and MAA-induced immunosuppression are due to immunologic, pharmacokinetic or metabolic differences within each species remains to be determined.

Acetates↗
PubMed1991

Pathologic fibrosis and matrix connective tissue in the subaortic myocardium of patients with hypertrophic cardiomyopathy.

To evaluate scar-type and matrix connective tissue and to assess their role in the diastolic dysfunction of hypertrophic cardiomyopathy, surgically resected subaortic myectomy specimens and several autopsy hearts from patients with hypertrophic cardiomyopathy were studied. Eighteen specimens were differentially stained by a newly developed method that precisely determines relative collagen content; these tissues were compared with postmortem hypertrophied and normal control subaortic specimens. Quantitation revealed a 72% higher level (36.5 vs. 22.1 micrograms collagen/mg protein) of stainable collagen in the hearts with hypertrophic cardiomyopathy than in hypertrophied control hearts. The endocardial plaque was quantitated morphometrically, and it constituted only 4.6 +/- 1.7% of the total increased collagen content in the cardiomyopathy specimens. For the matrix studies, the cardiomyopathy specimens were stained by a silver impregnation technique that identifies connective tissue elements not normally visible with routine histologic methods. There was a marked increase in content of all matrix components, both in areas of pathologic scarring and in "normal" zones. Whorls of matrix connective tissue were noted in regions of myocyte whorls, as well as independent of them. Thus, these studies revealed a striking increase of both scar-type and matrix connective tissue in hypertrophic cardiomyopathy. The extensive scarring and the pronounced interstitial and intercellular matrix connective tissue may contribute to the increased ventricular chamber stiffness and impaired relaxation in this disease.

Cardiomyopathy, Hypertrophic↗
PubMed1991

The prevalence of Mycoplasma pneumoniae in ambulatory patients with nonstreptococcal sore throat.

Several studies have implicated Mycoplasma pneumoniae as an important cause of nonstreptococcal pharyngitis in certain clinical settings. This study was performed to determine the prevalence of M. pneumoniae infection in family practice patients with sore throats and to identify patient characteristics predictive of this infection. M. pneumoniae throat cultures were obtained from 419 patients aged five years or older who were seen in one of four family practice offices with a complaint of sore throat. The overall prevalence of M. pneumoniae infection was 13%. It was characterized by more frequent hoarseness and less frequent complaint of postnasal drip when compared with other nonstreptococcal infections. Compared to patients with streptococcal pharyngitis, M. pneumoniae patients revealed a strikingly dissimilar clinical presentation. In particular, while pharyngitis is predictive of streptococcal infections, its presence did not predict M. pneumoniae infection. Recently developed rapid office-based tests for M. pneumoniae may allow timely diagnosis of this common and formerly elusive pathogen. Further study is required to validate the utility of such methods and to evaluate the efficacy of treatment.

Adolescent↗
PubMed1990

Vaginal intraepithelial neoplasia: methodologic problems in a case-control study.

Vaginal Intraepithelial Neoplasia (VAIN) has recently received increased attention as a precursor to vaginal cancer, yet its natural history remains largely obscure. Several case series have implicated hysterectomy as a risk factor for the subsequent development of vaginal neoplasia. A recent case-control study failed to support an association with vaginal cancer when controlling for age, sex, and prior cervical dysplasia or neoplasia. In order to further investigate the possible association of hysterectomy with vaginal neoplasia, we performed the following retrospective case-control study. We compared 39 cases of VAIN with 39 controls matched for age, race, and prior cervical dysplasia or neoplasia. Matched-pair analysis yielded an odds ratio of 7.0 with a 95% confidence interval of 1.7 to 28. This would suggest that previous hysterectomy is indeed associated with the development of VAIN. However, several potential sources of systematic error were identified in the study design. Thus this association can not be supported. Further, this study exemplifies the difficulty of generalizing study results from a tertiary care population to primary care settings.

Bias↗
PubMed1975

A bone calcium index based on partial-body calcium measurements by in vivo activation analysis.

Measurements of partial-body calcium by in vivo neutron activation analysis have been carried out on normal and osteoporotic subjects. Based on measurements on 16 normal subjects (volunteers less than 55 years of age), a calcium index has been established that takes into account variation in skeletal frame size. On the basis of this index, all osteoporotic patients have bone mineral content less than any of the normal subjects. The normal calcium indices range from 0.9 to 1.2, and the osteoporotic indices ranged from 0.41 to 0.83. Thirteen of 22 volunteers over 55 years of age had calcium indices less than 0.9 in agreement with the expected loss of calcium with age. Measurements of total-body potassium were also made on these same subjects and the calcium/potassium ratios calculated. Although as groups the older volunteers and older osteoporotic subjects had mean calcium/potassium ratios similar to the mean for the normal subjects, the osteoporotic subjects under 55 years of age had a mean calcium/potassium ratio significantly lower, indicationg that for this latter group the loss in bone mineral was not associated with a corresponding loss in muscle mass.

Activation Analysis↗
PubMed1975

Conditioned response-contingent delays of the unconditioned stimulus in human aversive conditioning.

Four groups of subjects were given either 0. 100, 500, or 1,000 msec delays of the unconditioned stimulus (UCS) contingent upon the occurrence of a conditioned response (CR) and were given a UCS 515 msec after conditioned stimulus (CS) onset when a CR did not occur. A fifth group received standard classical conditioning trials with an interstimulus interval of 515 msec. Overall performance decreased as CR-contingent UCS delay increased, with the classical conditioning group approximating the performance of the group receiving the 100-msec delay. The data were analyzed with the two-phase model of conditioning and the following results were obtained: The duration of Phase 1 of the model increased with contingent delay; operator limits associated with CR trials or with combined CR-CR (CR absent) trials decreased as a function of delay; and operator limits associated exclusively with CR trials were unaffected by the delay. Subjects receiving a contingent delay of 0 msec gave the shortest latency responses and exhibited reliable latency decreases across trials, suggesting an attempt to "beat" the UCS. The results were interpreted as contrary to what would be expected from low-of-effect theories which postulate that reinforcement results from a CR-UCS interaction, although they could be subsumed under a drive or an associative strength theory in which the aversive, or CR-supportive, strength of the UCS is assumed to be negatively correlated with contingent UCS delay.

Adult↗
PubMed1975

Classical skin conductance response conditioning: effects of intermittent reinforcement and information about schedule contingencies.

Skin conductance responses were differentially conditioned using reinforcement schedules of 25%, 50%, 75%, and 100%, manipulated between subjects. Half of the subjects were informed about schedule contingencies, and half were uninformed. The interstimulus interval was 6 sec. Discrimination of first-interval responses (1.0-3.5 sec after conditioned stimulus [CS] onset) by informed subjects did not vary with the ratio variable, but that by uninformed subjects improved with increasing reinforcement ratio because of diminished response levels to the nonreinforced CS (CS-). Discrimination of second-interval responses (3.6-7.0 sec after CS onset) improved as a function of increasing reinforcement ratio because of elevated response levels to the reinforced CS (CS+), but the effect was not persistent across trials in informed subjects. Performance in the first and second intervals did not reflect sequential increments and decrements as a function of reinforced and nonreinforced trials. Third-interval responses (7.1-9.9 sec after CS on nonreinforced trials) were not affected by schedule manipulations, but unconditioned responses diminished with increasing reinforcement ratio. Information about schedule contingencies led to superior discrimination of first-, second-, and third-interval responses and to suppression of unconditioned responses.

Adolescent↗