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Biomedical subjects

A Silverman

Publications and source records attributed to A Silverman.

At least 37 records · Page 2Linked to original sources

Characterization of T-cell clones generated from skin of patients with psoriasis.

BACKGROUND: The infiltrating cells in psoriasis include a subpopulation of autoreactive T cells. OBJECTIVE: The aim of this study was to further characterize skin-infiltrating T lymphocytes in patients with psoriasis. METHODS: Forty-five T-cell clones were generated from skin biopsy specimens from two patients. RESULTS: Phenotypic studies on 25 of 45 clones revealed that 19 (76%) of the clones were CD4+, 5 (20%) were CD8+, and 1 (4%) clone was CD4- and CD8-. Twenty-three clones were stained for identification of T-cell receptors. Twenty-two clones expressed alpha/beta T-cell receptors and one clone (CD4-/CD8-) expressed no T-cell receptor. Nineteen clones (42%) were autoreactive with no restriction to class I or class II HLA antigens. By contrast, proliferation of two of the seven clones was inhibited by class I monoclonal antibody, whereas proliferation of four of seven clones was inhibited by class II monoclonal antibody. CONCLUSION: These data suggest that skin-infiltrating lymphocytes in patients with psoriasis may recognize HLA-associated molecules, perhaps the peptide of the HLA groove. The recognition of the peptide is presumably inhibited when monoclonal antibody is bound to the HLA molecule.

CD4 Antigens↗

Association of 70-kilodalton heat-shock cognate proteins with acclimation to cold.

Exposure of young spinach seedlings (Spinacia oleracea L. cv Bloomsdale) to 5 degrees C leads to an increase in the synthesis of several 79-kilodalton proteins that are present in leaf tissue grown at 20 degrees C. Protein sequence analyses and immunological cross-reactivity indicate that this group of proteins belongs to the 70-kilodalton heat-shock family. Steady-state transcript levels and protein synthesis are increased two- to threefold within 1 day, but immunoblot analyses suggest that the steady-state concentration of this protein group in leaf tissue only gradually accumulates at low temperature. It is proposed that the increased synthesis of several members of the 70-kilodalton heat-shock family could result from an influence of low temperature on protein folding and/or assembly processes.

Journal Article↗

Hematologic changes during and after cardiopulmonary bypass and their relationship to the bleeding time and nonsurgical blood loss.

The hemostatic dysfunction induced by cardiopulmonary bypass is due, in part, to a platelet dysfunction evidenced by a postoperative extension of the bleeding time; it leads to increased postoperative blood loss and morbidity. This study, which was conducted in 85 patients undergoing cardiopulmonary bypass, was designed to characterize the hematologic changes during and after cardiopulmonary bypass and to elucidate the relationships between these changes, the extension of the bleeding time, and the magnitude of the postoperative nonsurgical blood loss. Variables were measured before, during, and 2, 24, 48, and 72 hours after cardiopulmonary bypass. Univariate and multivariate analyses were performed with either the 2-hour postbypass bleeding time or the 4-hour postbypass blood loss as the dependent variables. The reversal of the extension of the bleeding time in the postoperative period was accompanied by a significant increase in the mean platelet volume and by a significant increase in the level of thromboxane B2 measured in the blood shed from the site of the bleeding time determination. The postoperative bleeding time correlated with the postoperative blood loss, and both parameters were dependent on the duration of cardiopulmonary bypass. In addition, the postoperative bleeding time correlated with the skin temperature and the plasma level of D-dimer, while the postoperative blood loss also correlated with temperature and the plasma levels of C3. These data establish a direct relationship between the postoperative bleeding time, the postoperative blood loss, and temperature. They indicate that the reversal of the postoperative extension of the bleeding time is due in part to rewarming and to the release of larger platelets into the circulation, and they suggest that hyperfibrinolysis and complement activation may play an important role in the cardiopulmonary bypass-induced platelet dysfunction.

Bleeding Time↗

Liver involvement in Alpers disease.

Alpers disease consists of diffuse cerebral degeneration manifested as developmental delay, seizures, vomiting, and progressive neuromuscular deterioration, with liver disease and death. We report the clinical course of the liver disease, histologic progression of the hepatic lesions, and etiologic investigations in five patients (four girls, three kinships). All had grown and developed normally until seen at 6 to 36 months of age (mean 20 months), with vomiting (n = 5), progressive hypotonia (n = 3), or seizures (n = 2). All had been given anticonvulsants, including valproic acid in three. Liver disease was noted at a mean age of 35 months (range 9 to 67 months), with hepatomegaly (two patients), abnormal hepatic synthetic function (three) or transaminase values (three), and cirrhosis in one. Patients survived for a mean of 4.6 weeks (range 1 to 8 weeks) after the identification of liver disease; all died of hepatic failure. Results of evaluation for infectious and metabolic causes of liver disease and causes of degenerative neuromuscular disease were negative in all patients. Premortem liver biopsy specimens (n = 3) demonstrated an early lesion consisting of lobular disarray, microvesicular steatosis, periportal acute and chronic inflammation, and individual hepatocyte necrosis. Autopsy findings (n = 5) consisted of macrovesicular steatosis, massive hepatocyte dropout, and proliferation of bile ductular elements, with almost complete replacement of hepatocytes by proliferating bile ductular elements in two patients. Brain showed characteristic neuronal degeneration. We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction.

Biopsy↗

Noninfectious colitis associated with short gut syndrome in infants.

We describe noninfectious bloody diarrhea in 13 of 16 infants referred for management of short bowel syndrome and parenteral nutrition during a 33-month period. The condition was characterized by bloody, watery stools associated with carbohydrate malabsorption. Colitis occurred at a mean age of 4.2 months during periods of advancing enteral feedings of a hydrolyzed protein- or amino acid-containing formula. Sigmoidoscopy performed in nine patients revealed edema, patchy erythema, loss of normal vascular pattern, and mucosal friability without ulcerations or pseudomembranes. Colonic biopsy specimens demonstrated edema and mixed hypercellularity of the lamina propria, with prominent eosinophilia. Rectal bleeding ceased if formula feedings were decreased or withheld. Of multiple medications administered, sulfasalazine seemed to improve rectal bleeding most effectively in our patients and allowed for more rapid reintroduction of enteral feedings.

Carbohydrate Metabolism↗

Safety, efficacy, and tolerance of intestinal lavage in pediatric patients undergoing diagnostic colonoscopy.

In an open-label prospective study the safety, efficacy, and patient tolerance of an enterally administered isotonic intestinal lavage solution containing polyethylene glycol-3350 was evaluated in 20 pediatric patients (ages 1 1/2 to 19 years) undergoing diagnostic colonoscopy. After an oral dose of metoclopramide, lavage solution was administered by mouth or nasogastric tube at a rate of 40 ml/kg per hour until stools were clear. Emesis occurred in 4 patients, nausea in 11, and abdominal distension in 5. Clear stools were produced in a mean (+/- SE) time of 2.6 +/- 0.3 hours. The volume of lavage solution delivered, which ranged from 15.6 to 183.3 ml/kg, varied inversely with the weight (and age) of the patient. Preparation of the colon was considered optimal in 11 patients, satisfactory in 7, and suboptimal in 2. Small but significant decreases in urine osmolality, blood urea nitrogen, serum glucose, and potassium values were noted at the termination of perfusion. Postperfusion serum glucose concentration in the smallest patient (11.4 kg) was 61 mg/dL (3.4 mmol/L). Mean (+/- SEM) change in weight after perfusion was 0.14 +/- 0.05 kg (range -0.2 to +0.6 kg). Of 20 patients, 11 required or requested nasogastric administration of the lavage solution because of its unpleasant taste. We conclude that whole intestinal perfusion with a balanced electrolyte solution containing polyethylene glycol is safe, acceptable, and efficacious in children.

Adolescent↗

Characterization of skin-infiltrating lymphocytes in patients with psoriasis.

In this study, skin-infiltrating cells in psoriasis patients were characterized in biopsies from both involved and uninvolved skin. Histologic examination of biopsies showed the presence of both CD4+ and CD8+ T cells and the lack of B lymphocytes. Skin biopsies were also placed in tissue culture medium supplemented with human serum, interleukin-2 (IL-2), and irradiated autologous blood lymphocytes. T lymphocytes grew from both plaques and univolved skin biopsies and consisted of a heterogeneous population of T-cell subsets. The immunophenotypic analysis of cultured cells was comparable to the histologic examination on frozen section, i.e., there was a greater number of CD4/CDw29+ cells than CD8+/CD45+ cells. Cultures were tested in the primed lymphocyte test (PLT) and cell-mediated lympholysis (CML) assays. All cultures tested demonstrated secondary proliferative but not cytolytic reactivity. The PLT results indicate that the cell cultures generated are autoreactive. This autoreactivity was found to be directed against non-human leukocyte antigens (HLA), i.e., minor HLA with some restriction to major HLA antigens.

Antigens, CD↗

Methotrexate-induced cirrhosis requiring liver transplantation in three patients with psoriasis. A word of caution in light of the expanding use of this 'steroid-sparing' agent.

Methotrexate has been used for many years to treat refractory psoriasis. Three cases of methotrexate-induced cirrhosis requiring orthotopic liver transplantation are presented to emphasize the importance of strict adherence to published criteria for patient selection, monitoring of cumulative drug dosages, and the performance of serial liver biopsies. Each patient had been treated with long-term methotrexate therapy (cumulative doses far in excess of 1.5 g) without undergoing serial liver biopsies, contrary to well-established treatment guidelines. Caution must be exercised in using methotrexate as a steroid-sparing agent in the treatment of inflammatory diseases because of its potential to cause severe hepatotoxic effects with long-term usage and cumulative doses above 1.5 g. Patients easily become psychologically dependent on the drug, and physicians need to guard against the false sense of security engendered by normal results on liver function studies.

Adult↗