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Biomedical subjects

R M Silver

Publications and source records attributed to R M Silver.

At least 127 records · Page 7Linked to original sources
PubMed1985

Fibronectin distribution in nailfold biopsies of scleroderma (systemic sclerosis) patients.

The distribution of fibronectin (FN) was studied in skin biopsies of 13 patients with scleroderma (SD), 7 patients with dermatomyositis (D), and 10 normal controls (NC) by direct immunofluorescence. In normal tissues, continuous or segmental linear staining of the dermal-epidermal junction (DEJ) was seen. Papillary, subpapillary dermis, and papillary capillary loops showed a reticular pattern of deposition with fibronectin. Scleroderma patients revealed similar staining in the dermis and DEJ. The reticular distribution of FN appeared to stain more intensely in the dermis than in controls, especially in deeper layers. The amount of FN in walls of blood vessels from SD patients was markedly increased; all dermal vessels stained with FN and revealed considerably thicker walls and larger lumens. FN distribution in DM patients was similar to that seen in SD with an increased amount of FN staining in capillary walls.

Adolescent↗
PubMed1984

Interstitial lung disease in scleroderma. Analysis by bronchoalveolar lavage.

Interstitial pulmonary fibrosis is a common feature of scleroderma (systemic sclerosis) which may result in impairment of pulmonary function and may be a major determinant of morbidity and mortality. Clinicopathologic observations suggest that interstitial and alveolar inflammation may appear prior to fibrosis. Using the bronchoalveolar lavage (BAL) technique, we have characterized the nature of the inflammatory process in the lower respiratory tracts of 19 non-smoking scleroderma patients. Eleven of 19 patients (58%) had increased percentages of neutrophils and/or eosinophils in BAL fluid. Five of 10 patients (50%) had elevations of IgG in BAL fluid. The presence of neutrophils was associated with a decreased lung diffusing capacity for carbon monoxide (P less than 0.05) and with more advanced radiographic features of interstitial fibrosis in patients with disease of more than 1 year's duration. This study suggests that scleroderma lung involvement may be characterized by an inflammatory alveolitis and that the presence of such inflammation may relate to the severity of the pulmonary disease.

Adult↗
PubMed1984

Association between fluorescent antinuclear antibodies, capillary patterns, and clinical features in scleroderma spectrum disorders.

Antinuclear antibody and in vivo capillary patterns were studied in 33 patients with Raynaud's phenomenon only and in 68 patients with scleroderma spectrum disorders; the results were correlated with clinical and laboratory findings. In addition, antinuclear antibody results in the groups with Raynaud's phenomenon only and scleroderma spectrum disorders were compared with those found in 70 patients with systemic lupus erythematosus (SLE). Distinct antinuclear antibody profiles were observed in the three diagnostic groups. Comparison of patients with anticentromere antibodies with others in the group with scleroderma spectrum disorders demonstrated that anticentromere antibody-positive patients tended to have a milder disease: less skin and visceral involvement, less frequent presence of hypertension, anemia, and elevated sedimentation rate. These differences did not, however, reach statistical significance. Comparison of patients with scleroderma spectrum disorders according to in vivo capillary patterns revealed that those with an "active" pattern had significantly more extensive skin involvement than those with a "slow" pattern. Visceral involvement tended to be greater in all organ systems in the group with an "active" pattern and reached statistical significance for muscle and kidney. Hypertension was also significantly more frequent in the group with an "active" pattern than in the group with a "slow" one. The latter was positively correlated with the presence of anticentromere antibody.

Adolescent↗
PubMed1984

Immune complexes and antinuclear, antinucleolar, and anticentromere antibodies in scleroderma.

Forty-one patients with various forms of systemic sclerosis (scleroderma) and positive antinuclear antibodies of nucleolar (ten patients), speckled (eleven patients), or centromere pattern (twenty patients) were selected for study of immune complexes by the radioisotope labeled Clq binding and the radioisotope labeled protein A binding methods. The presence of immune complexes was found by the Clq binding assay in sixteen patients (39%) and by a protein A binding assay in eight patients (20%). Overall, 46% of patients (19/41) had immune complexes. A lower incidence of organ involvement and fewer positive results in the screening of serum immune complexes were observed in patients with centromere antibody (35%) than in patients with nucleolar (60%) or speckled pattern (55%). Patients with immune complexes had higher frequencies of kidney, heart, and muscle involvement and digital ulceration than did patients with no detectable immune complexes, but the differences were not statistically significant. Diffuse skin involvement was not related to the presence of immune complexes.

Adult↗
PubMed1983

Studies of rheumatoid synovial fluid lymphocytes. II. A comparison of their behavior with blood mononuclear cells in the autologous mixed lymphocyte reaction and response to TCGF.

Synovial fluid lymphocytes (SFL) and peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis were compared for their response to lectin stimulation and for their behavior in the autologous mixed lymphocyte reaction (AMLR). The SFL proliferative response to phytohemagglutinin (PHA), as measured by tritiated thymidine incorporation at 72 hr, was lower than that of PBL (P less than 0.001). When T-cell growth factor (TCGF) was added to the medium, there was an increase in the SFL proliferative response to PHA (P less than 0.05). In contrast, TCGF did not alter significantly the PBL proliferative response to PHA. Mixing experiments were performed to determine whether the poor SFL proliferative response was due to passive absorption and removal of in situ-generated TCGF by "suppressor" cells. When cultured together, SFL did not suppress the PBL proliferative response to PHA, suggesting that decreased production of TCGF rather than competitive binding of TCGF results in the poor SFL proliferative response to lectin stimulation. In the AMLR, synovial fluid non-T cells were found to be more stimulatory to peripheral blood T cells than were peripheral blood non-T cells (P less than 0.001). In comparison to peripheral blood T cells, synovial fluid T cells were poor responders in the AMLR. Repetitive in vitro autologous stimulation of peripheral blood T cells resulted in proliferative responsiveness analogous to that of SFL, i.e., a relatively poor proliferative response in the AMLR and a poor response to PHA. The latter could be augmented by TCGF. The SFL requirement for exogenous TCGF is consistent with a state of immune activation. In vivo stimulation by non-T cells may play an important role in the immune activation which characterizes rheumatoid SFL.

Adult↗
PubMed1983

Pulmonary function in mechanically-ventilated patients during 24-hour use of a hygroscopic condensor humidifier.

Hygroscopic condensor humidifiers (HCH) are reportedly capable of humidifying even the driest of ventilator source gases with at least 30 mg H2O/liter of ventilation. To assess the adequacy of the HCH during mechanical ventilation, we studied 26 patients over a 72-hour period (alternating 24-hour periods of humidification by a conventional cascade and the HCH). In these patients, we found no significant difference in static lung compliance, airway resistance, PaO2, and PaCO2 on either system. Additionally, estimates of sputum volume (over a four-hour collection period) and clearance of aerosolized 99mTc labelled DTPA (in five of these patients) also showed no significant differences between the two systems. We conclude that the HCH is capable of supplying necessary heat and moisture to most mechanically-ventilated patients for at least a period of 24 hours.

Adult↗
PubMedDate not supplied

Cognitive deficits in a murine model of the eosinophilia-myalgia syndrome: a preliminary report.

The described study was to determine the effects of chronic exposure to 1,1'-ethylidenebis[L-tryptophan] (EBT), a tryptophan contaminant, on cognitive behavior of female C57BL/6 (C57) mice. EBT (also designated as "peak E" or "peak 97") is one of several compounds that are suspect in the eosinophilia-myalgia syndrome (EMS). Groups of female C57 mice (12/group) were injected IP with saline (SAL), tryptophan (TRY), EBT, or an EBT + tryptophan combination (EBT + TRY) over a 6-week period. Previous experiments established that the dosing conditions produce several characteristics of EMS, including dermal inflammation and fibrosis, increased dermal mast cells, and increased levels of quinolinic acid. The mice exposed to EBT + TRY were abnormal during the solution of a Morris water maze problem. First, they had a shorter latency to locate the submerged platform goal during the initial day of training compared to SAL or TRY mice; secondly, they did not show the systematic reduction in latency to locate the platform goal across days of training noted for SAL or TRY mice. These abnormalities occurred in the absence of altered body weight or gross motor activity during the treatment procedure, or in the animal's swim speeds at the time of testing, 3 days after termination of treatment. The results suggest that prolonged exposure to EBT + TRY can alter the reaction to a stressful environment and can alter cognitive behavior.

Analysis of Variance↗
PubMedDate not supplied

Pregnancy specific beta 1 glycoprotein (SP-1) in maternal serum and amniotic fluid; pre-eclampsia, small for gestational age fetus and fetal distress.

Pregnancy specific beta 1 glycoprotein (SP-1) levels have been suggested to correlate with certain obstetrical complications. We compared maternal serum SP-1 levels in normal pregnancies (N = 82), and pregnancies complicated by pre-eclampsia (N = 37), small for gestational age fetuses (N = 8) and fetal distress (N = 13). We also compared levels of this protein in mid-trimester amniotic fluid samples obtained from normal (N = 47) and small for gestational age fetuses (N = 25). Despite trends towards low maternal serum and amniotic fluid SP-1 values in complicated pregnancies, there were no statistically significant differences in their levels as compared with normal gestational age matched controls (P > 0.05). These data do not support the use of SP-1 values in clinical practice.

Adult↗
PubMedDate not supplied

Mechanism of interleukin-1 beta stimulation of human amnion prostaglandin biosynthesis: mediation via a novel inducible cyclooxygenase.

We have evaluated the mechanism by which interleukin-1 beta (IL-1 beta) increases amnion cell PGE2 production in a concentration-dependent manner. IL-1 beta-stimulated amnion cell PGE2 biosynthesis was time-dependent, and significant stimulation occurred within 2 h of incubation. IL-1 beta stimulation occurred in the presence of added arachidonic acid but was abrogated by treatment with cycloheximide and actinomycin D. Amnion cells treated with IL-1 beta recovered rapidly from aspirin pretreatment suggesting an action on fatty acid cyclooxygenase (COX). Increased amounts of COX protein were demonstrated by Western blot analysis within 2 h of IL-1 beta treatment of amnion cells. Northern blot analysis using a probe specific for a novel form of COX (COX-II) showed an increase in mRNA for this COX within 30 min. This finding using a homologous detection system and human cells of fetal origin in primary culture provides strong support for a physiological role for COX-II in man.

Amnion↗
PubMedDate not supplied

Cyclosporin A attenuates increased prostaglandin and thromboxane production in response to various stimuli in human decidua.

PROBLEM: This study was undertaken to evaluate the effects of cyclosporin A on prostanoid (prostaglandin and thromboxane) production by human decidua. METHOD: Decidual cells were isolated from term placentae obtained at elective cesarean section before the onset of labor. Cells were grown to confluence and then incubated for 16 h with cyclosporin A (0.1-100 ng/ml) in the presence and absence of interleukin 1 beta (IL-1 beta, 10 ng/ml), phorbol 12-myristate 13-acetate (PMA, 10(-7) M) and ionomycin (0.5 micron). Prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) were measured by radioimmunoassay, and cellular protein was determined. RESULTS: IL-1 beta, PMA, and ionomycin all stimulated decidual PGE2 and TXB2 production as expected. However, these stimulatory actions were attenuated by 20% when cells were coincubated with cyclosporin A (100 ng/ml). All concentrations of cyclosporin A tested were within the therapeutic range. CONCLUSIONS: Our results indicate that cyclosporin A does not stimulate decidual prostanoid production and is probably unrelated to preterm labor and delivery in allograft recipients.

Cells, Cultured↗
PubMedDate not supplied

Thrombin-mediated cellular events in pulmonary fibrosis associated with systemic sclerosis (scleroderma).

The vascular hypothesis for the pathogenesis of systemic sclerosis was perhaps Professor LeRoy's most important scientific contribution. One early and important consequence of vascular injury is the release of activated thrombin. In this manuscript we present our data and review the current understanding of the role played by thrombin in the process of fibrosis, particularly as it relates to scleroderma lung disease. Thrombin's cellular effects are intimately involved in promoting myofibroblast differentiation, endothelial cell activation, extracellular matrix protein deposition, and the induction of important profibrotic factors. Such studies confirm that thrombin is one of the major mediators in the development and progression of pulmonary fibrosis. Therefore, targeting the major receptor of thrombin, PAR-I, and its downstream signaling molecules may lead to novel therapeutic approaches for the management of scleroderma lung fibrosis. We are indebted to Dr LeRoy for his many contributions to the field of scleroderma, and for all that he did to stimulate our interest in these studies.

Apoptosis↗
PubMedDate not supplied

Myofibroblast induction and microvascular alteration in scleroderma lung fibrosis.

OBJECTIVE: Scleroderma (SSc) is an autoimmune connective tissue disorder characterized by progressive fibrosis of the skin and internal organs. The leading cause of death in SSc patients is pulmonary dysfunction as a result of interstitial fibrosis and pulmonary vasculopathy. Our objective was to evaluate histopathological abnormalities associated with the development of pulmonary fibrosis in SSc. METHODS: Postmortem SSc lung tissue from various stages of fibrosis and tissue from normal lung were analyzed by Masson's trichrome staining and immunohistochemistry. Monoclonal antibodies against smooth muscle-alpha actin (myofibroblast marker), von Willebrand Factor, platelet endothelial cell adhesion molecule-1 (endothelial cell markers), or caldesmon (smooth muscle cell marker) were employed. RESULTS: We found that in the early active stages of SSc lung fibrosis two major types of cellular abnormalities occur. One is the induction of a large number of smooth muscle alpha-actin-positive myofibroblasts in interstitia. The other is the excessive formation of alveolar capillaries (hypervascularity) accompanied by an increase in the number of microvascular endothelial cells. The vascular abnormality also involves the development of microvessels that are irregular in size and shape. However, the population of myofibroblasts and capillary endothelial cells decline as the fibrosis progresses to its most marked, later stages. CONCLUSION: We conclude that the induction of myofibroblasts and the overdevelopment of capillary microvessels characterize the progression of lung fibrosis in SSc. Using these histological alterations as criteria, therefore we have divided the fibrosis formed in the SSc lungs into four pathological stages. These results suggest that both fibroblast overproliferation and vascular abnormality play an important role in the pathogenesis of lung fibrosis in SSc.

Adult↗
PubMedDate not supplied

Lymphokine activated killer (LAK) cell activity in the peripheral blood lymphocytes of systemic sclerosis (SSc) patients.

Lymphokine activated killer (LAK) cells, which arise from interleukin-2 (IL-2) activation of natural killer (NK) cells, are capable of lysing NK-resistant cell targets, including endothelial cells (EC). Since EC cytotoxicity is postulated to play a role in the pathogenesis of systemic sclerosis (SSc), experiments were performed to measure LAK activity in the peripheral blood lymphocytes (PBL) of 10 SSc patients and 10 normal controls. SSc patients had no significant spontaneous cytotoxicity against NK-resistant cell targets, including EC. After IL-2 stimulation in vitro, SSc patients and normal controls demonstrated cytotoxicity toward NK-resistant cell targets, including EC. This LAK-mediated EC cytotoxicity was actually lower for SSc patients than for normal controls. These studies do not preclude a role for LAK-mediated EC cytotoxicity in the pathogenesis of SSc, but demonstrate that LAK cells are not spontaneously present in circulating PBL.

Adult↗