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Biomedical subjects

C R Wang

Publications and source records attributed to C R Wang.

At least 91 records · Page 5Linked to original sources

T cell receptor-mediated signaling events in CD4+CD8+ thymocytes undergoing thymic selection: requirement of calcineurin activation for thymic positive selection but not negative selection.

The goal of this study was to identify the differences of intracellular signals between the processes of thymic positive and negative selection. The activation of calcineurin, a calcium- and calmodulin-dependent phosphatase, is known to be an essential event in T cell activation via the T cell receptor (TCR). The effect of FK506, an inhibitor of calcineurin activation, on positive and negative selection in CD4+CD8+ double positive (DP) thymocytes was examined in normal mice and in a TCR transgenic mouse model. In vivo FK506 treatment blocked the generation of mature TCRhighCD4+CD8- and TCRhighCD4-CD8+ thymocytes, and the induction of CD69 expression on DP thymocytes. In addition, the shutdown of recombination activating gene 1 (RAG-1) transcription and the downregulation of CD4 and CD8 expression were inhibited by FK506 treatment suggesting that the activation of calcineurin is required for the first step (or the very early intracellular signaling events) of TCR-mediated positive selection of DP thymocytes. In contrast, FK506-sensitive calcineurin activation did not appear to be required for negative selection based on the observations that negative selection of TCR alpha beta T cells in the H-2b male thymus (a negative selecting environment) was not inhibited by in vivo treatment with FK506 and that there was no rescue of the endogenous superantigen-mediated clonal deletion of V beta 6 and V beta 11 thymocytes in FK506-treated CBA/J mice. DNA fragmentation induced by TCR activation of DP thymocytes in vitro was not affected by FK506. In addition, different effects of FK506 from Cyclosporin A on the T cell development in the thymus were demonstrated. The results of this study suggest that different signaling pathways work in positive and negative selection and that there is a differential dependence on calcineurin activation in the selection processes.

Animals↗

Thyroid peroxidase autoantibodies and their effects on enzyme activity in patients with systemic lupus erythematosus.

Thyroid microsomal antibodies (Ms-Ab) are recently proved to be directed to thyroid peroxidase (TPO). The aim of this study was to investigate whether the sera of patients with systemic lupus erythematosus (SLE) contain anti-TPO antibodies (TPO-Ab) and whether these antibodies influence enzyme activity. Sera from patient with Hashimoto's thyroiditis was also studied. Serum samples were obtained from 37 patients with SLE, 20 patients with Hashimoto's thyroiditis and 20 healthy subjects. TPO-Ab were detected by immunoprecipitation using crude microsomal preparations or enzyme-linked immunoabsorbent assay (ELISA) with recombinant TPO. Positive TPO-Ab by ELISA were found in 11 (61%) of 18 patients with lupus whose serum contained Ms-Ab. Low levels of TPO-Ab also were found in three (16%) of 19 lupus sera that did not contain Ms-Ab. All patients with Hashimoto's thyroiditis had high levels of TPO-Ab in serum. When measured by ELISA, TPO-Ab were highly correlated with the results of a TPO immunoprecipitation assay and with the titers of Ms-Ab in patients with lupus (r = 0.83, n = 18, P < 0.01; r = 0.63, n = 18, P < 0.01) and in Hashimoto's thyroiditis (r = 0.89, n = 20, P < 0.01; r = 0.75, n = 20, P < 0.01). When evaluating the direct influence of TPO-Ab on the activity of TPO, we found no significant inhibition of enzymatic activity in both guaiacol and iodide assays by lupus sera in contrast with sera from Hashimoto's thyroiditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Vallecular cysts: report of two cases.

A vallecular cyst is an unusual cause of inspiratory stridor in the infant. We report our findings in two infants with this lesion. Thorough diagnostic evaluation is mandatory in the pediatric patient with concomitant inspiratory stridor and respiratory distress or feeding difficulties.

Cysts↗

Anticardiolipin antisera from lupus patients with seizures reduce a GABA receptor-mediated chloride current in snail neurons.

The effects of circulating anticardiolipin (ACL) antisera in lupus patients on the LP5 central neuron of snail were studied. Both GABA and glutamate increased a chloride conductance of the LP5 neuron. The ACL antisera decreased the GABA-elicited responses in a concentration dependent manner while it had no effect on glutamate-elicited responses. The ACL antisera affected neither the resting membrane current, nor the membrane conductivity of neuron. Antisera without the activity of anticardiolipin did not decrease the GABA-elicited responses. The seizure incidence of the patients with higher ACL antisera levels is also higher. It is concluded that ACL antisera inhibited the GABA ionophore receptor complex in a snail central neuron.

Animals↗

The study of anticardiolipin antibodies and interleukin-6 in cerebrospinal fluid and blood of Chinese patients with systemic lupus erythematosus and central nervous system involvement.

Anticardiolipin (ACL) antibodies and interleukin-6 (IL-6) in cerebrospinal fluid (CSF) may be involved in the mechanism of lupus patients with central nervous system (CNS) involvement. ACL antibodies of 3 isotypes and IL-6 were measured in paired CSF and serum samples from 14 lupus patients with CNS involvement, 5 lupus patients without CNS involvement and 7 patients with non-inflammatory neurological diseases. ACL antibodies, IgG and IgM isotypes, and IL-6 were significantly increased in CSF from lupus patients with CNS involvement as compared with other 2 groups of patients. Both ACL antibodies and IL-6 decreased after neurological activity subsided. These results suggest increased ACL antibodies and IL-6 in CSF are involved in immune responses within CNS in lupus patients. Quantitation of CSF ACL antibodies may be helpful in evaluating neurological activity of lupus patients with CNS involvement.

Adolescent↗

HMT, encoded by H-2M3, is a neoclassical major histocompatibility class I antigen.

H-2M3 encodes HMT, the major histocompatibility complex (MHC) class I heavy chain of the maternally transmitted antigen (Mta). Like classical MHC class I genes, the expression of M3 can be stimulated by gamma-interferon and its message can be detected from mid-gestational embryos (day 8) through adulthood. HMTb, a nonimmunogenic allelic form of HMT, differs from the common HMTa molecule by four amino acids, of which only two (residues 31 and 95) are located in the alpha 1 and alpha 2 domains that form the peptide-binding groove. Recognition of site-directed mutants by Mta-specific cytotoxic T lymphocytes was hardly affected by the substitution of Met for Val31 but was abolished by the substitution of Gln for Leu95, which is located in the beta-sheet floor of the peptide-binding groove. Thus a single amino acid difference is responsible for the immunological silence of HMTb.

Animals↗

Organization and structure of the H-2M4-M8 class I genes in the mouse major histocompatibility complex.

We have cloned and characterized five new class I genes from the M region at the distal end of the H-2 complex of the BALB/c mouse. M4, M5, and M6 are clustered on two overlapping cosmids, and M7 and M8 are located on another cosmid together with the previously cloned M1 gene, to which they are most closely related. M4, M6, and M7 are full-length class I genes (exons 1 through 5 were identified) but with stop codons or frameshifts that mark them as pseudogenes, and only exons 4 and 5 remain of M8. M5 has complete open reading frames in exons 1 through 5 and intact splice signals; it has the potential to encode a divergent class I major histocompatibility molecule, but no transcripts were found. These genes provide probes for studying the evolution of class I genes in rodents and for the mapping and cloning of genes at the end of the distal inversion in t haplotype chromosomes.

Amino Acid Sequence↗

Thyroid disorders in Chinese patients with systemic lupus erythematosus.

To clarify the prevalence of thyroid disorders in Chinese patients with systemic lupus erythematosus (SLE), 45 SLE patients not receiving corticosteroid therapy for at least 6 months were selected over a period of 1 year. They were investigated by utilizing thyroid ultrasonography and by determinations of thyroid antibodies and thyroid function. Of these patients, 24 (53.3%) showed abnormal sonographic findings. Thyroid antibodies (microsomal and/or thyroglobulin) were detected in 21 patients (46.7%), but a low index of thyrotropin-binding inhibitory immunoglobulin (TBII) was found in only one euthyroid patients with a normal echogram. Ten patients (22.2%) had abnormal thyroid function. The mean disease duration was longer in patients with thyroid anomalies (p < 0.05). Hashimoto's thyroiditis was found in four patients (8.8%), two of whom had hypothyroidism. We concluded that thyroid anomalies are frequently found in patients with SLE in the area of this study. The possibility of the coexistence of thyroid disorders in systemic lupus erythematosus should be carefully considered throughout the course of patients' follow-up, especially in those with a long disease duration.

Adult↗

Circulating intercellular adhesion molecules-1 and autoantibodies including anti-endothelial cell, anti-cardiolipin, and anti-neutrophil cytoplasma antibodies in patients with vasculitis.

Circulating intercellular adhesion molecule-1 (ICAM-1) and 3 types of autoantibodies were measured in 30 patients with angiographical or pathological proved vasculitis. There were 18 patients with systemic vasculitis and 12 patients with cutaneous vasculitis. The measured antibodies included anti-endothelial cell antibodies (AECA), anti-cardiolipin (ACL) antibodies of 3 isotypes and anti-neutrophil cytoplasma antibodies (ANCA). The results showed that patients with systemic vasculitis had elevated levels of ICAM-1, AECA and IgG isotype antibody as compared with none or lower in patients with cutaneous vasculitis. Levels of ICAM-1 and IgG isotype ACL antibodies also decreased significantly after disease activity subsided in patients with systemic vasculitis. Measurement of ICAM-1 and autoantibodies may be useful in evaluating the extent of involvement and in following the disease activity of patients with vasculitis.

Adolescent↗

Lupus patients with peripheral vascular thrombosis: the significance of measuring anticardiolipin antibody.

The purpose of this study was to determine the significance of measuring anticardiolipin (ACL) antibodies in Chinese lupus patients with peripheral vascular thrombosis. A total of 252 lupus patients were evaluated prospectively for the presence of peripheral vascular thrombosis in a 3-year period. Tests of ACL antibodies with three isotypes were done serially during follow-up. There were 10 lupus patients with five episodes of arterial thrombosis and seven episodes of venous thrombosis by the evidence of angiographical and/or pathological findings. The ACL antibody status was negative (< 2 standard deviation [SD]), low (2 to 5 SD) and high (> 5 SD) for 43.3%, 22.6%, and 34.1% patients, respectively. Patients with high levels (> 5 SD) of ACL antibodies had a high frequency of peripheral vascular thrombosis than patients with negative levels (> 2 SD) of ACL antibodies (P < .05). It is concluded that serial measurement of ACL antibodies in lupus patients is useful in predicting the occurrence of peripheral vascular thrombosis. Clinicians should be alert to the possibility of such complication in lupus patients with high ACL antibodies levels when visiting the emergency service.

Adolescent↗

Acute pancreatitis related to anticardiolipin antibodies in lupus patients visiting an emergency department.

Four patients with systemic lupus erythematosus visiting an emergency department were reported with clinical presentation of acute pancreatitis. All had high levels of anticardiolipin antibodies (aCL); at autopsy, one had multiple thrombi within the blood vessels of the pancreas. The aCL antibody might play an important role in the pathogenesis of acute pancreatitis. Three patients had multiple organ involvement, especially the central nervous system, concomitant with an acute attack of pancreatitis; all died from these complications. Thus it was suggested that initial acute pancreatitis is an omnious prognostic factor in lupus patients visiting an emergency department. When evaluating lupus patients visiting an emergency department, clinicians should be alert to the status of aCL and the possibility of pancreatitis in these patients.

Acute Disease↗

Circulating intercellular adhesion molecule-1 and lymphocyte subsets involved in immune response of breast cancer.

To understand the immune responses of patients with breast cancer, circulating intercellular adhesion molecules-1 (ICAM-1) and lymphocyte subsets were measured in patients with breast cancer and in healthy persons. There were 10 patients of with metastasis, 11 patients breast cancer without metastasis and 9 age-and-sex matched healthy persons. Their serum samples were counted for circulating ICAM-1 levels, and blood cells were calculated for lymphocyte subpopulation including CD3, CD4, CD8 and CD19 by using flow cytometry. Higher levels of circulating ICAM-1 were noted in patients with breast cancer and metastasis than those without metastasis (p < 0.01). Lower percentage of CD8 lymphocyte subset were found ih patients with breast cancer and metastasis than those without metastasis (p < 0.05). Shedding of ICAM-1 antigens from the tumor may block the attachment of cytotoxic T cells, and decreased numbers of cytotoxic T cells may be unable to inhibit the spread of cancer cells. Immune responses of patients with breast cancer may be different between metastatic status and limited status. Further investigations should correlate the results of tissue stains of breast cancer with ICAM-1 and lymphocyte markers with those from peripheral blood.

Adult↗

Successful treatment of Kaposi's sarcoma with interferon-alpha in a patient with acquired immunodeficiency syndrome.

Although combined therapy with interferon-alpha and zidovudine may be safely administered to some patients with the acquired immunodeficiency syndrome (AIDS) and Kaposi sarcoma, no ethnic Chinese patient has been successfully treated before in this area. This case report concerns a 47-year-old male with a history of bisexuality who had suffered from oral ulcers for half a year, Human immunodeficiency virus (HIV) serology was positive, and pathology of the oral ulcers disclosed Kaposi sarcoma. Combination therapy with zidovudine and interferon-alpha was initiated. The patient received a low-dose regimen of 5.0 million U interferon-alpha s.c. per day for 8 weeks and 5 million U twice a week for another 8 weeks. The oral ulcers faded away without recurrence. This report also reviews the literatures on treatment of AIDS-related Kaposi sarcoma with interferon.

Acquired Immunodeficiency Syndrome↗

Salbutamol in treatment of bronchial asthma--comparison of controlled release tablet with standard tablet.

Salbutamol in controlled release tablet form was compared to salbutamol in standard tablet form for the management of patients with bronchial asthma. A total of twenty asthmatic patients enrolled in the study were classified into two groups, ten patients each, for a cross-over study. Group 1 received controlled release tablets for a 2 to 3 week period, and were then shifted to standard tablets for another similar period. Group 2 received standard tablets first and was then shifted to controlled release tablets. Patients were required to record symptom scores during therapy, including sleep disturbance, chest tightness, wheezing, cough, sputum production and inhalational bronchodilator use. Measurements of peak expiratory flow rate (PEFR) were also done, as well as record made of side effects experienced. The result showed that a lower symptom score was found in patients receiving controlled release tablets than in patients receiving standard tablets (p < 0.001 for sleep disturbance, p < 0.005 for sputum formation and p < 0.001 for total score). There was a higher PEFR in patients receiving controlled-release tablets than in patients receiving standard tablets (p < 0.001). Side effects with tremor were observed in 30% of both groups of patients with a slightly higher degree in the patients receiving standard tablets (statistically not significant). In conclusion, salbutamol of controlled release tablet form obtains a better therapeutic response than standard tablets in the management of patients with bronchial asthma.

Adult↗