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Biomedical subjects

W V Williams

Publications and source records attributed to W V Williams.

124 records · Page 7Linked to original sources

The role of cellular proliferation in the induction of experimental autoimmune thyroiditis (EAT) in mice.

Experimental autoimmune thyroiditis (EAT) can be induced in susceptible strains of mice by injection of mouse thyroglobulin (MTg) and adjuvant. Lymphocytes from immunized mice develop a proliferative response to MTg which generally correlates with the development of EAT. We utilize a cell transfer system wherein spleen cells from CBA/J mice primed with MTg and lipopolysaccharide (LPS) in vivo are activated by culture with MTg in vitro to transfer EAT to naive recipients. In vivo priming of CBA/J mice is required to develop an antigen specific proliferative response to MTg. This response is optimal between 48 and 90 hr of culture at an MTg concentration of 125-250 micrograms/ml. The correlation between proliferation and transfer of EAT is not absolute as primed Balb/c X CBA/J F1 and AKR lymphocytes do not proliferate detectably in response to MTg but can be activated to transfer EAT; primed Balb/c lymphocytes neither proliferate nor transfer EAT. Proliferation per se is not sufficient to activate cells to transfer EAT as culture with nonspecific mitogens is not effective in activating primed CBA/J spleen cells to transfer EAT. However, lymphoblasts generated during in vitro culture of primed CBA/J spleen cells with MTg are responsible for transfer of EAT; small lymphocytes are ineffective. We conclude that antigen specific proliferation in response to MTg is essential in activating lymphocytes in vitro to transfer EAT.

Animals↗

The clinical significance of the in vivo antinuclear antibody phenomenon.

We describe a patient with systemic lupus erythematosus (SLE) with demonstrated direct immunofluorescent staining of epidermal nuclei in a rim pattern, the second case of in vivo antinuclear antibody (ANA) producing a rim pattern in normal epidermis. A review of the literature showed that 258 cases have been reported of in vivo ANA deposition in epidermal nuclei from nonlesional skin. This phenomenon, which is most common in patients with mixed connective tissue disease, SLE, and scleroderma, correlates frequently with antibodies to extractable nuclear antigens. In vivo ANA have also been described in renal and pulmonary tissue from patients with SLE. In most cases, the pathogenic significance of the phenomenon is unknown.

Antibodies, Antinuclear↗

Redundancy and complexity of information in cognitive performances of schizophrenic and normal individuals.

Examined cognitive performance of schizophrenic and normal Ss matched on age, education, and intelligence (N = 120). Complexity of information and redundant cues were manipulated systematically in a concept identification (CI) task. Schizophrenics were not impaired compared to normals in solution of problems with low redundancy. Whereas normals' performance was facilitated by redundant information, schizophrenics demonstrated marked deficit in CI as a function of that information. Results were interpreted in terms of schizophrenics' inability to filter out irrelevant information, in addition to their deficit in channel capacity for utilizing relevant-redundant cues, which have been shown to reliably facilitate normals' CI.

Adult↗

Cognitive deficit in schizophrenia. Subvocal mediation, rigidity, and complexity parameters.

This study investigated the effects of problem complexity on cognitive performance of 96 schizophrenic and nonpsychiatric inpatients. Subvocal activity (mediation) and three rigidity parameters were examined in relation to performance. The major findings were: a) with increased problem complexity, schizophrenics demonstrated relatively greater difficulty in performance than controls; b) subvocal activity was greater in schizophrenics than controls and was positively related to both the complexity of the problem and the inability to respond correctly; c) motor-cognitive rigidity was higher in schizophrenics and positively correlated with cognitive errors, as well as with the subvocal activity--this was not so in controls, demonstrating the differential role of the rigidity dimension in the two populations.

Adult↗

Follow-up research in primary prevention: a model of adjustment in acute grief.

Investigated the effects of preventive intervention that followed the life crisis of sudden death in the family. Two bereaved groups of families (one of which received preventive intervention service) and one non-bereaved group were compared in an outcome design and were assessed for indices of illness, psycho-social disturbance, and general quality of life. The results revealed that sudden death has a two-stage impact upon family survivors and that subsequent adjustment can be predicted from a knowledge of facts at the time of death. A preventive intervention service had little or no impact and may have been harmful. Discussion centered on possible intervention strategies with a focus upon the complex determinants of environmental stresses and family/individual variables.

Acute Disease↗

Cognitive rigidity in information processing of chronic undifferentiated schizophrenics.

This study investigated Concept Identification (CI) performance and hypothesis behavior of 100 chronic undifferentiated schizophrenic and matched normal Ss as functions of motor-cognitive, personality-perceptual, and psychomotor speed parameters of rigidity. The CI task was designed to test the effects of five levels of information complexity and to examine 10 categories of hypothesis strategies utilized in conceptual problem solving. It was found that normals were superior to schizophrenics in CI and that schizophrenics performed more poorly than normals at higher complexity levels. Normals were markedly less rigid on the motor-cognitive dimension than were schizophrenics. Correlational analysis revealed a number of reliable relationships between the three rigidity measures and the 10 hypothesis categories. Some insight was gained about the role of rigidity in utilization of effective strategies in problem solving; the psychomotor speed factor emerged as the best predictor of schizophrenics' hypothesis behavior.

Adaptation, Psychological↗

Crisis intervention: effects of crisis intervention on family survivors of sudden death situations.

A controlled study that examined the effects of a short-term crisis service given to a group of families recently bereaved through a sudden death within the family is reported. The results reveal that sudden death does have a major impact on recently bereaved families in terms of increased risk of ill health, poor coping behavior, and disturbed social functioning when compared to nonbereaved families. However, the short-term crisis service appeared to have no major impact upon postbereavement adjustment. Discussion centered around possible reasons for failure of the short-term crisis services.

Adaptation, Psychological↗

Prevention in mental health: a controlled study.

The authors conducted a controlled study in which families who had experienced the sudden death of a family member were given crisis intervention services and compared at follow-up with two untreated control groups. Results did not support the hypothesis that such services decrease the risk of psychiatric illness, disturbed family functioning, or increased social cost to the families. The authors suggest that environmental and social systems factors and individual variables are powerful predictors of outcome in bereavement.

Adaptation, Psychological↗

Synovial T cell receptor heterogeneity in early arthritis.

Rheumatoid arthritis (RA) has been postulated to result from a synovial immune response to an unidentified antigen(s), which should be mirrored by the T cell response. Here we investigate the T cell receptor (TCR) repertoire in the synovial tissue of patients with arthritis of early to moderate duration. We developed a nested polymerase chain reaction (PCR) technique to examine the TCR repertoire of small biopsy specimens, and show that the method is highly sensitive. We apply this technique to synovial biopsies obtained from the knee joints of patients with early to moderate duration arthritis (average duration of arthritis 1 year, range 0. 02-2.75 years). We examined biopsies from 5 normal individuals, 32 RA patients, 7 patients with seronegative spondyloarthropathy (Sp), and 12 patients with undifferentiated arthritis (UA). TCR message was detectable in 4/5 normals, 15/32 RA, 5/7 Sp, and 8/11 UA biopsies, with sampling error likely accounting for most negative biopsies. The average numbers of TCR Vbetas detected per TCR-positive biopsy were 5.0 +/- 3.7 for normals, 12.7 +/- 8.4 for RA, 18.0 +/- 7.4 for Sp patients, and 14.4 +/- 10.2 for UA. Examination of TCR messages by single-stranded conformational polymorphism analysis showed similar proportions of dominant clones in the normals compared with the patients with inflammatory arthritis. Sequence analysis was performed on 33 dominant clones from 16 patients. Sequence alignment of the third hypervariable regions showed some evidence of disease-specific sequence clustering for Sp, while some RA sequences showed similarity to previously described motifs. These data indicate greater TCR heterogeneity in early Sp and UA compared with normal synovium. Disease-specific TCR sequences may occur in early RA and Sp.

Adult↗

Development of GM-CSF antagonist peptides.

Granulocyte/macrophage colony stimulating factor (GM-CSF) is both a hematopoietic growth factor and a cytokine implicated in inflammatory disease. The development of GM-CSF antagonist peptides corresponding to the GM-CSF native sequence should allow their modification into higher affinity analogs, but this is hampered by the low affinity of linear peptides. To adequately evaluate such low affinity peptides, the use of several independent assays should allow specific versus nonspecific inhibitors to be distinguished. In this study, inhibition of GM-CSF-dependent cell growth, inhibition of GM-CSF binding and immunologic cross-reactivity between GM-CSF-derived peptides and native protein by neutralizing antibodies have been used to evaluate peptide analogs with potential bioactivity. The GM-CSF sequence was divided into 6 peptides ranging in size from 15-24 amino acids. Antisera were raised to these peptides in mice and assayed for immunologic cross-reactivity. 4/6 anti-peptide antisera bound GM-CSF on ELISA and 3/6 on immunoprecipitation. Antisera to two of the peptides (corresponding to residues 17-31 and 96-112) inhibited GM-CSF-dependent cellular proliferation in two cell lines, with one peptide derived from residues 17-31 demonstrating inhibition of GM-CSF binding and direct biological inhibitory activity. A peptide that did not elicit native GM-CSF reactive antibodies, corresponding to residues 54-78, was recognized by two neutralizing monoclonal antibodies. It exhibited inhibition of GM-CSF binding and direct biological antagonist activity. These studies implicate two sites in mediating GM-CSF biological activity, and indicate that biological antagonists can be developed based on these sites.

Amino Acid Sequence↗