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Biomedical subjects

R L Wong

Publications and source records attributed to R L Wong.

At least 19 recordsLinked to original sources

A cytoplasmic activator of DNA replication is involved in signal transduction in antigen-specific T cell lines.

Cytoplasmic extracts prepared from T cell lines undergoing antigen-specific, interleukin-2 (IL-2)-dependent proliferation were tested for their ability to induce DNA synthesis in isolated, quiescent nuclei. A tetanus toxoid (TET)-specific T cell line, established from peripheral blood of a normal human volunteer, was stimulated in the presence of relevant antigen and 1 unit/ml IL-2. Cytoplasmic extracts prepared from these cells were capable of inducing DNA synthesis in isolated, quiescent nuclei. The ability of cytoplasmic extracts to induce DNA synthesis in isolated, quiescent nuclei. The ability of cytoplasmic extracts to induce DNA synthesis in isolated nuclei correlated positively with the degree of proliferation induced in these cells. In contrast, incubation of this T cell line in the absence of antigen failed to induce proliferation and cytoplasmic extracts prepared from these cells induced little to no DNA synthesis in isolated, quiescent nuclei. The factor present in the cytoplasm of T cells stimulated with relevant antigen in the presence of IL-2 is similar, if not identical, to a factor which we have previously demonstrated in cytoplasmic extracts prepared from transformed lymphoblastoid cell lines and from mitogenically stimulated normal human peripheral blood mononuclear cells. This factor, which we have called activator of DNA replication (ADR) is a heat-labile protein, and is inactivated by treatment with protease inhibitors, including aprotinin. The ability of cytoplasmic extracts from T cells undergoing antigen-specific, IL-2-dependent proliferation to induce DNA synthesis in isolated, quiescent nuclei was markedly inhibited in the presence of aprotinin, providing strong evidence that a cytoplasmic activator of DNA replication, ADR, is involved in the signal transduction process for antigen-specific, IL-2-dependent T cell proliferation. ADR may represent a common intracellular mediator of DNA synthesis in activated and transformed lymphocytes.

Aprotinin

Murine T helper cell clones secrete granulocyte-macrophage colony-stimulating factor (GmCSF) by both interleukin-2-dependent and interleukin-2-independent pathways.

Granulocyte-macrophage colony-stimulating factor (GmCSF) is a lymphokine secreted by class II major histocompatibility complex (MHC)-restricted T cells after lectin or antigen stimulation. To investigate the relationship between interleukin-2 (IL-2) and GmCSF production, we utilized long-term cultures of porcine myelin basic protein (PMBP)-specific T helper cell clones that were maintained with IL-2 in the absence of antigen or irradiated antigen-presenting cells (APC). We have found that supernatants of these T cell clones contained GmCSF activity after IL-2 stimulation. Inhibition of cell proliferation by irradiation failed to stop GmCSF production. When these clones were stimulated with PMBP and irradiated APC in the presence of anti-IL-2 receptor antibody, the T cell supernatants still contained GmCSF activity. These results indicate that (1) GmCSF production by T helper clones after IL-2 stimulation is independent of cell proliferation and (2) antigen/MHC-stimulated GmCSF production by T cell clones can occur by an IL-2-independent pathway.

Animals

Effects of H-7 are not exclusively mediated through protein kinase C or the cyclic nucleotide-dependent kinases.

Culturing murine T cell tumor lines in the presence of the protein kinase inhibitor H-7 for 4 days led to their dependence on H-7 for maximal constitutive proliferation. Withdrawal of H-7 from H-7-conditioned cells led to inhibition of proliferation and cell death. The mechanism underlying this H-7 dependence does not appear to be related to clonal selection or to effects on protein kinase C or the cyclic nucleotide-dependent kinases. This suggests that all the effects of the widely used H-7 may not be completely understood, and that H-7 may be useful in the dissection of the complex patterns of growth regulation in T cell malignancies.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Subtypes of helper cells. Non-inflammatory type 1 helper T cells.

Class II MHC-restricted T cells recently have been characterized as being either type 1 (Th1) or type 2 (Th2) based on their ability to both secrete different lymphokines and perform different functions. Characterization of these subtypes to date have indicated that Th1 cells secrete IL-2, IFN-gamma, lymphotoxin, and IL-3, whereas Th2 cells secrete IL-4, IL-5, and IL-3. Functionally, Th1 cells mediated cytotoxicity and delayed-type hypersensitivity, and have been termed "inflammatory cells," whereas Th2 cells mediate helper function for Ig secretion and have been termed, "regulatory cells." We now present evidence that not all Th1 clones are inflammatory and capable of mediating cutaneous delayed-type hypersensitivity. We have generated a number of myelin basic protein-specific Th1 clones that do not mediate swelling when injected together with myelin basic protein directly into the footpads of syngeneic mice. These results suggest that Th1 cells can be further subdivided based on their ability to mediate delayed-type hypersensitivity, and that the Th1/Th2 characterization of Th cells may be insufficient to adequately characterize all functional subtypes of class II MHC-restricted T cells.

Animals

Inhibition of nuclear DNA synthesis by an autoantibody to proliferating cell nuclear antigen/cyclin.

Proliferating cell nuclear antigen (PCNA) is expressed in the nuclei of proliferating cells, but is not detected in resting cells. The kinetics of PCNA expression suggest that it is associated with a phase preceding active DNA synthesis. DNA synthesis is under cytoplasmic control, and there is a cytoplasmic protein, ADR (activator of DNA replication), that induces DNA synthesis in isolated quiescent nuclei. We now report that a human antibody preparation monospecific for PCNA, but not two monoclonal antibodies directed against different epitopes on PCNA, can inhibit the ability of ADR to induce DNA synthesis in isolated quiescent nuclei. This effect is not due to inhibition of DNA polymerase alpha activity. Thus, the anti-PCNA antibody exerts its effect either by directly influencing the initial interaction of ADR with the nucleus, or by inhibiting subsequent synthetic events.

Antigen-Antibody Reactions

Induction of DNA synthesis in isolated nuclei by cytoplasmic factors: inhibition by protease inhibitors.

Cytoplasmic extracts from spontaneously proliferating and mitogen-activated lymphoid cells contain a protein factor called ADR (activator of DNA replication) that induces DNA synthesis in isolated quiescent nuclei. ADR-containing preparations have proteolytic activity, as indicated by their ability to degrade fibrin in a plasminogen-independent and plasminogen-dependent manner. In addition, aprotinin, a nonspecific protease inhibitor, abrogates ADR-induced DNA synthesis in a dose-dependent fashion. Preincubation studies demonstrated that the effect of aprotinin is not due to its suppressive effects on the nuclei themselves. Other protease inhibitors such as leupeptin, p-aminobenzamidine, and N-alpha-tosyllysine chloromethyl ketone are also inhibitory, but soybean trypsin inhibitor is without effect. ADR activity can be removed from active extracts by adsorption with aprotinin-conjugated agarose beads and can be recovered by elution with an acetate buffer (pH 5). These findings are consistent with the interpretation that the initiation of DNA synthesis in resting nuclei may be protease dependent and, further, that the cytoplasmic stimulatory factor we have called ADR may be a protease itself.

Animals

Temporal arteritis without an elevated erythrocyte sedimentation rate. Case report and review of the literature.

An elevated erythrocyte sedimentation rate is regarded as a hallmark of temporal arteritis. Thirty-five cases of biopsy-proved temporal arteritis without an elevated erythrocyte sedimentation rate are identified, and a 36th case is described. All patients had age-adjusted normal Westergren sedimentation rates, 16 with sedimentation rates of 20 mm per hour or less and 20 with sedimentation rates of 21 to 40 mm per hour. Twenty-two patients had sufficient clinical information for analysis and comparison with reported series of patients with biopsy-proved temporal arteritis with an elevated Westergren sedimentation rate. Headache (41 percent), temporal artery abnormalities (41 percent), and visual symptoms (36 percent) were the most common manifestations in patients without an elevated sedimentation rate. Headache (41 percent versus 75 percent, p less than 0.05) and jaw claudication (9 percent versus 43 percent, p less than 0.025) were found less often in the patients without an elevated sedimentation rate. History and physical examination are essential in the diagnosis of temporal arteritis with a normal Westergren sedimentation rate.

Aged

Dermatomyositis and Hodgkin's disease. Case report and review of the literature.

The association between dermatomyositis and Hodgkin's disease has been infrequently reported. A patient with advanced Hodgkin's disease and dermatomyositis is presented and an additional 11 cases obtained from the world literature are reviewed. The clinical features, response to treatment, and outcome of these diseases are discussed.

Adult

A comparison of the specificity of the 1971 and 1982 American Rheumatism Association criteria for the classification of systemic lupus erythematosus.

The specificity of the preliminary and the revised American Rheumatism Association criteria for the classification of systemic lupus erythematosus (SLE) was tested in 207 of our patients with other rheumatic diseases which were considered to be important in the differential diagnosis of SLE. Using the preliminary criteria, the data revealed that 5 patients were falsely classified as having SLE (2 with scleroderma, 2 with Raynaud's disease, and 1 with systemic necrotizing vasculitis), whereas using the revised criteria, only 2 patients (1 with scleroderma and 1 with systemic necrotizing vasculitis) were falsely classified. The calculated specificity was 99% for the revised criteria and 98% for the preliminary criteria. Thus, the data revealed that the specificity of the revised criteria is high and comparable with that of the preliminary criteria when applied to a group of patients with related rheumatic diseases.

Adolescent

Monocyte function in cervical carcinoma: plasma inhibitor of monocyte chemotaxis.

Blood monocyte function was tested in 43 untreated patients with carcinoma of the cervix (stages Ib to IIIb) and 50 age-matched controls. Monocyte counts, adhesion to glass, spreading on glass, phagocytosis and killing of Candida albicans, and chemotaxis under agarose were not significantly different between the patient and control groups. In 65% of a further series of 17 patient/control pairs, the plasma of cervical carcinoma patients was shown to contain a cell-directed inhibitor of monocyte chemotaxis. The accumulated evidence indicates that production of such factors by malignant tumors is an important mechanism in counteracting mononuclear phagocyte defense.

Candida albicans

Folate status in pregnant Chinese women in Hong Kong.

Hematologic and folate studies were carried out in 116 pregnant Chinese women in Hong Kong. Mean serum folate values fell progressively with pregnancy reaching subnormal levels during the puerperium. Mean red-cell folate values remained normal or high throughout, but showed a significant fall after delivery in women who carried out breast-feeding. Individually, 18 women showed hematologic abnormalities compatible with folate deficiency, but only four had subnormal red-cell folate values satisfying the strict criterion of folate deficiency, giving an overall frequency of 3.4%. Compared to primigravidae and other multiparae, gravida 2 women appeared to be at highest risk of folate deficiency.

China

Human colostral and breast milk cells. A light and electron microscopic study.

Colostrum and breast milk samples were obtained from 74 women, 18 of whom gave sequential samples. The mean total leukocyte count in colostrum was 3190 cells/mm3. Proportions of macrophages, polymorphs and lymphocytes varied widely; macrophages usually predominated. Serial sampling showed (1) a small fall in total counts through delivery, (2) a fall in total counts and the proportion of PMNs at the onset of lactation, (3) after 1 to 2 weeks of lactation the appearance of cytoplasmic fragments together with epithelial cells which later constituted the main cell type. It was estimated that the total number of leukocytes available to the neonate remained approximately constant during the first 2 weeks of lactation and fell thereafter. Functionally, morphologically and histochemically macrophages in colostrum and breast milk resembled macrophages elsewhere. Their ultrastructure was characterized by filiform surface projections, numerous endocytic vacuoles and lipid droplets in the cytoplasm.

Colostrum

Interferon synthesis by human colostral leucocytes.

The antiviral potential of human colostral leucocytes was assessed by their capacity to produce interferon. Leucocytes cultured from colostrum were stimulated by mitogens or Newcastle disease virus (NDV) to produce interferon which, by metabolic and physicochemical criteria, corresponded to normal human leucocyte interferon. Prepartum cells produced higher levels than postpartum cells. Colostral cells were less efficient producers than blood leucocytes.

Cells, Cultured