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Biomedical subjects

C Sokol

Publications and source records attributed to C Sokol.

7 recordsLinked to original sources
PubMed2000

The origin of anti-nuclear antibodies in bcl-2 transgenic mice.

bcl-2 transgenic mice develop anti-double-stranded (ds) DNA antibodies similar to those present in systemic lupus erythematosus. To begin to understand where a breakdown in the regulation of autoreactive lymphocytes is occurring, we have used a bcl-2 transgene (Tg) in conjunction with an Ig Tg that allows us to identify and track anti-dsDNA B cells. Previously, we have shown that anti-dsDNA B cells are actively tolerized in BALB/c mice as manifested by their developmental arrest, follicular exclusion, increased in vivo turnover rate and lack of their antibody in the serum. The bcl-2 Tg mice increased the lifespan of anti-dsDNA B cells, but did not alter the other features of tolerance, indicating that the anergy of the anti-dsDNA B cells is independent of their reduced lifespan. Furthermore, these data suggest that the serum anti-dsDNA antibodies in bcl-2 transgenic mice are not due to a breakdown in the induction or maintenance of B cell anergy; rather they may originate from B cells that have transited through a germinal center.

Animals↗
PubMed1999

MRL-lpr/lpr mice exhibit a defect in maintaining developmental arrest and follicular exclusion of anti-double-stranded DNA B cells.

A hallmark of systemic lupus erythematosus and the MRL murine model for lupus is the presence of anti-double-stranded (ds)DNA antibodies (Abs). To identify the steps leading to the production of these Abs in autoimmune mice, we have compared the phenotype and localization of anti-dsDNA B cells in autoimmune (MRL+/+ and lpr/lpr) mice with that in nonautoimmune (BALB/c) mice. Anti-dsDNA B cells are actively regulated in BALB/c mice as indicated by their developmental arrest and accumulation at the T-B interface of the splenic follicle. In the MRL genetic background, anti-dsDNA B cells are no longer developmentally arrested, suggesting an intrinsic B cell defect conferred by MRL background genes. With intact Fas, they continue to exhibit follicular exclusion; however, in the presence of the lpr/lpr mutation, anti-dsDNA B cells are now present in the follicle. Coincident with the altered localization of anti-dsDNA B cells is a follicular infiltration of CD4 T cells. Together, these data suggest that MRL mice are defective in maintaining the developmental arrest of autoreactive B cells and indicate a role for Fas in restricting entry into the follicle.

Animals↗
PubMed1999

Characterization of anergic anti-DNA B cells: B cell anergy is a T cell-independent and potentially reversible process.

Anti-single stranded DNA (ssDNA) and anti-double stranded DNA (dsDNA) B cells are regulated in non-autoimmune mice. In this report we show that while both anti-ssDNA and anti-dsDNA B cells are blocked in their ability to differentiate into antibody-secreting cells, other phenotypic and functional characteristics distinguish them from one another. Splenic anti-ssDNA B cells are found distributed throughout the B cell follicle, and are phenotypically mature and long-lived. On the other hand, splenic anti-dsDNA B cells are short-lived, exhibit an immature and antigen-experienced phenotype, and localize to the T-B interface of the splenic follicle. Functionally, anti-ssDNA B cells proliferate, albeit suboptimally, in response to anti-IgM, lipopolysaccharide (LPS) and CD40L/IL-4 + anti-IgM stimulation, and tyrosine phosphorylate intracellular proteins upon mIgM cross-linking. Anti-dsDNA B cells, on the other hand, are functionally unresponsive to anti-IgM and LPS stimulation, and do not phosphorylate intracellular proteins, including Syk, upon mIg stimulation. Importantly, anti-DNA B cell anergy is maintained in the absence of T cells since both anti-ssDNA and anti-dsDNA B cells are as efficiently regulated in RAG2(-/-) mice as in their RAG2(+/+) counterparts. Interestingly, the severely anergic state of anti-dsDNA B cells is partially reversible upon stimulation with CD40 ligand and IL-4. In response to these signals, anti-dsDNA B cells remain viable, up-regulate cell surface expression of B7-2 and IgM, and restore their ability to proliferate and phosphorylate Syk upon mIg cross-linking. Collectively, these data suggest that anti-DNA B cell anergy encompasses distinct phenotypes which, even in its most severe form, may be reversible upon stimulation with T cell-derived factors.

Animals↗
PubMed1997

Immunolocalization of basic fibroblast growth factor in porcine epiphyseal growth plate.

Recent evidence clearly indicates that basic fibroblast growth factor (bFGF) signal transduction is essential for normal skeletal development. Here, we report that bFGF and its receptor are specifically localized in the terminal hypertrophic chondrocytes of the porcine epiphyseal growth plate, the tissue responsible for longitudinal bone growth. Similar observations were obtained with the chondrocytes immediately adjacent to resorbing blood vessels in the secondary center of ossification of the epiphysis. These results are consistent with a recent proposal that bFGF functions in coupling osteogenesis with chondrogenesis by attracting the vascular invasion of cartilage from adjacent trabecular bone.

Animals↗
PubMed1994

Effect of lesion size on the metabolic activity of tibial dyschondroplastic chondrocytes.

Experiments were conducted to determine the influence of lesion size and method of producing tibial dyschondroplasia on metabolic activity of cultured chondrocytes. Genetic selection was one method used to produce a high incidence of tibial dyschondroplasia. Chondrocytes obtained from severe lesions exhibited reduced mitogenic activity (3H-thymidine incorporation) and ability to synthesize matrix proteoglycans (35SO4 incorporation) when compared with normal growth plate and smaller lesions. When a commercial broiler strain was used, all chondrocytes isolated from lesions induced by feeding thiram had reduced metabolic activity. Similar results were observed with severe lesions obtained from copper-deficient chicks. It is concluded that lesion size is an important factor in determining subsequent metabolic activity of chondrocytes isolated from tibial dyschondroplastic lesions.

Animals↗
PubMedDate not supplied

Implementing preventive health measures: a pilot study.

OBJECTIVE: Implementation of preventive services guidelines is performed inconsistently. In an attempt to reduce variation in guideline implementation, we developed a patient questionnaire based on the US Preventive Services Task Force Guide and the Health Plan Employer Data and Information Set 3.0 performance measures of the National Committee on Quality Assurance. SUBJECTS: 100 hospitalized patients of five primary-care physicians. METHODS: In a pilot study, 100 hospitalized patients of five primary-care physicians were questioned about their compliance with evidence-based, preventive healthcare recommendations. Information was requested on blood pressure measurement, cholesterol screening, fecal occult blood testing, smoking-cessation counseling, Pap testing, mammography, postmenopausal hormonal replacement therapy counseling, prostate examination and prostate-specific antigen (PSA) testing, use of aspirin and beta-blockers following an acute myocardial infarction, testing of diabetics for hemoglobin A1c and retinal eye examinations, questioning of the elderly for auditory and visual problems, and receipt of influenza and pneumococcal vaccines. Information on variations from the recommended preventive service was fed back to their physicians. Six months after the initial survey, the patients were requestioned to determine if compliance had improved with the recommendations. RESULTS: We found significant improvement in fecal occult blood testing, smoking cessation, Pap smear testing, mammography use, prostate examinations and PSA testing, hemoglobin A1c testing, seeing or hearing loss follow-up, and the administration of influenza and pneumococcal vaccines. CONCLUSIONS: Improving implementation of preventive services recommendations is a challenge. This pilot study suggests that involving the patient more in the process and informing the physician of the results may improve the process.

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