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Biomedical subjects

S H Smith

Publications and source records attributed to S H Smith.

At least 73 records · Page 4Linked to original sources

Monoclonal antibody (UCHL1) that recognises normal and neoplastic T cells in routinely fixed tissues.

UCHL1 is a murine monoclonal antibody that recognises a 180-185 kD determinant on CD4 (72%) and CD8 (36%) positive T cells. This antibody is effective in formalin fixed and paraffin embedded tissues, using the immunoperoxidase method. One hundred and forty three cases of malignant lymphoma were examined. Neoplastic cells in 100% of cases of Mycosis fungoides (n = 10), 83% of cases of peripheral T cell lymphoma (n = 25), and 78% of cases of (T-ALL) T acute lymphoblastic lymphoma (n = 9) were stained by this antibody. In addition, staining was seen in 100% of cases of malignant histiocytosis of the intestine (n = 13), a condition now thought to be a T cell lymphoma. Two cases of true histiocytic lymphoma were also positive. This antibody stained neither the neoplastic cells in a wide range of B cell lymphomas (n = 62) nor Reed-Sternberg cells in 16 cases of Hodgkin's disease. UCHL1 also stained neoplastic cells in four cases of granulocytic sarcoma. A panel of normal tissues was similarly studied. Staining was seen in normal T cells and mucosal intraepithelial lymphocytes, macrophages, mature myeloid cells, and endometrial stromal granulocytes. UCHL1 is a monoclonal antibody that identifies T cells in formalin fixed paraffin embedded tissues, and should prove useful for diagnosing T cell lymphomas, especially when only formalin fixed tissue is available for diagnosis.

Animals↗

Selection criteria for drug-treated animals in two-kidney, one clip renal hypertension.

The two-kidney, one clip (2K1C) model of hypertension in the rat does not uniformly result in increased blood pressure. That is, the placement of a clip around one renal artery in a two-kidney rat will usually, but not always, produce hypertension. This is an important problem in studies designed to evaluate the ability of antihypertensive therapy to prevent hypertension. Therefore, an additional objective means other than blood pressure is needed to assess animals that are treated from the outset with antihypertensive therapy. The purpose of this study was to correlate the relative fresh weights of left (clipped)/right (nonclipped) kidneys (LK/RK) with tail-cuff systolic blood pressure in the 2K1C model of renal hypertension and to identify an LK/RK range that would exclude the animals least likely to become hypertensive (failures of the clipping procedure). On a scale of 0.0 to 1.0, an LK/RK ratio of 0.0 was present when the clipped kidney was completely infarcted or atrophied and a ratio of 1.0 was present when the clip did not cause sufficient renal artery stenosis to alter kidney weight. In a series of 72 untreated 2K1C male Sprague-Dawley rats examined 6 to 8 weeks after clipping, 100% of the animals with an LK/RK ratio of 0.5 to 0.8 (n = 19) and 75% with an LK/RK ratio of 0.4 to 0.9 (n = 38) had a blood pressure greater than 150 mm Hg. Less than 50% with an LK/RK ratio below 0.4 or above 0.9 (n = 34) were hypertensive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Coarctation of the abdominal aorta in a child: morphometric analysis of the arterial lesion.

Coarctation of the abdominal aorta with associated narrowing of the origin of major visceral arteries is a rare cause of life-threatening hypertension. We describe a 9-year-old male with hypertension and recent onset of headache and dizziness who was subsequently found to have a suprarenal coarctation with involvement of the proximal renal arteries. The patient died following a left cerebrovascular accident associated with recent thrombosis in the left middle cerebral and internal carotid arteries. Morphometric analysis of the aortic coarctation revealed that a reduction in outside diameter of the vessel was complicated by marked intimal thickening which caused further stenosis of the lumen. Medial thickness was constant, and elastic fibers of the media were intact at the level of coarctation.

Aorta, Abdominal↗

Functional subsets of human helper-inducer cells defined by a new monoclonal antibody, UCHL1.

The monoclonal antibody UCHL1 identified an antigen present on most thymocytes, a subpopulation of resting T cells within both the CD4 and CD8 subsets, and on mature activated T cells. The UCHL1 determinant is also present on cells of the myeloid lineage, but not normal B cells or NK cells. Functionally, UCHL1 identifies a subpopulation of T cells which proliferates maximally to soluble antigen and provides maximum help for PWM-stimulated immunoglobulin synthesis. In contrast, the UCHL1- cells do not induce immunoglobulin synthesis and do not proliferate in the presence of soluble antigen, although both the UCHL1- and the UCHL1+ fractions of T cells proliferate well in the presence of PHA. By standard immunoprecipitation techniques and SDS page, the antigen recognized by UCHL1 was found to have a molecular weight of 180,000-185,000. Preclearing experiments using antibodies identifying the leucocyte common antigen, LCA, and the lymphocyte function-associated antigen, LFA-1, which have similar molecular weights to UCHL1, showed that the UCHL1 determinant is not biochemically related to these antigens.

Animals↗

Chemotaxis of nurse shark leukocytes.

Studies were conducted to determine the ability of leukocytes from the nurse shark to migrate in an in vitro micropore filter chemotaxis assay and to determine optimal assay conditions and suitable attractants for such an assay. A migratory response was seen with several attractants: activated rat serum, activated shark plasma, and a pool of shark complement components. Only the response to activated rat serum was chemotactic, as determined by the checkerboard assay.

Animals↗

Regional myocyte size in compensated right ventricular hypertrophy in the ferret.

The effect of pressure-induced right ventricular hypertrophy on regional myocyte size and shape and regional myocardial wet weight was studied by comparing 20 ferrets which underwent pulmonary artery banding at a weanling age to 19 non-operated siblings. Using isolated myocyte preparations from six myocardial regions in 10 banded and seven non-banded ferrets, a 60% increase in cell volume in the right ventricular outflow tract and the right ventricular free wall was shown to be due primarily to an increased cross-sectional area of individual myocytes. The right side of the interventricular septum exhibited an intermediate increase in cell volume, while the left side of the interventricular septum did not respond to the pulmonary artery banding procedure. These findings confirm that localized hemodynamic changes produce hypertrophy of individual myocytes in selected regions of the heart and that a pressure-induced model of hypertrophy involves an increased cross-sectional area of myocytes, with minimal change in cell length.

Animals↗

The electrocardiogram of normal ferrets and ferrets with right ventricular hypertrophy.

Sixty-eight electrocardiograms were recorded on ferrets (Mustela putorius furo). These represent 29 normal weanling males, 19 normal adult males and 20 adult males with right ventricular hypertrophy (RVH). Analyses of rate, rhythm, axis and total voltage were used to define the normal electrocardiogram (ECG) and to identify changes seen in RVH. The normal ferret has a heart rate of about 300 beats per minute and a mean electrical axis of + 86 degrees +/- 6.6 (SD). A 56% increase in right ventricular weight to body weight ratio was not associated with right axis deviation. The overall voltage produced on the ECG was increased in the group with RVH as compared to the normal group (p less than 0.030).

Animals↗

Morphology of saphenous vein-coronary artery bypass grafts: Seven to 116 months after surgery.

Morphologic changes in saphenous vein-coronary artery bypass grafts in 24 cases (51 grafts) seven to 116 months after surgery were studied. Four pathologic changes were found (1) Fibrous cord lesions were present that represented early postoperative thrombotic occlusion and organization. (2) Diffuse intimal thickening was present in all grafts maintaining long-term patency. (3) Atherosclerosis identified as intimal foam cell accumulation or frank plaques was found only in cases 39 or more months postoperative and was present in 79% of such cases (71% of the vein grafts). (4) Late vein thrombosis was found in three cases and was the presumed cause of death. We concluded that atherosclerosis occurs with a high incidence in vein grafts after three years, and plaque rupture with thrombosis can be a cause for vein occlusion.

Arteriosclerosis↗

Tritiated thymidine incorporation does not measure DNA synthesis in ribavirin-treated human cells.

When the incorporation of tritiated thymidine into acid insoluble material was measured, ribavirin appeared to be a potent inhibitor of DNA synthesis in KB cells and human lymphocytes. Inhibition was nearly 100-fold less, however, when DNA synthesis was measured by incorporation of phosphorus-32-labeled phosphate or by DNA fluorescence. The potent inhibition detected by incorporation of tritiated thymidine into DNA actually was the result of a potent effect on the labeling of deoxythymidine triphosphate, not on the synthesis of DNA.

Cells, Cultured↗

Effects of cannabinoids on host resistance to Listeria monocytogenes and herpes simplex virus.

Previous investigations from our laboratories have demonstrated that cannabinoids possess immunosuppressive properties. The present studies were designed to determine whether these agents decrease host resistance to infections with Listeria monocytogenes and herpes simplex virus type 2. Host resistance was measured by changes in the 50% lethal dose of the pathogen in cannabinoid-treated and control mice. The effect of cannabinoids on resistance to L. monocytogens was dose dependent. Delta-9-tetrhydrocannabinol at doses of 38, 75, and 150 mg/kg suppressed resistance to infection by 10-, 17-, and 657-fold, respectively. Marijuana extract was less active but significantly reduced resistance to L. moncytogenes at all tested doses. Resistance to systemic herpes simplex virus type 2 infection was decreased 96-fold by delta-9-tetrahydrocannabinol, although marijuana extract was inactive. The doses and regimen of treatment with cannabinoids that produced significant decreases in host resistance were similar to those which caused suppression of delayed-type hypersensitivity to sheep erythrocytes. The possible mechanisms and public health aspects of the decreased host resistance produced by marijuana extract and its cannabinoids are discussed.

Animals↗

Deoxyadenosine antagonism of the antiviral activity of 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosylhypoxanthine.

Deoxyadenosine but not adenosine reversed the antiviral activity of 9-beta-D-arabinofuranosyladenine (ara-A) and 9-beta-D-arabinofuranosylhypoxanthine (ara-H) when used in the presence of coformycin, an inhibitor of adenosine deaminase. In suspension cultures of KB cells, 10 muM ara-A inhibited the replication of herpes simplex virus type 1 by 80%. Concomitant addition of 50 muM deoxyadenosine reduced the antiviral activity of 10 muM ara-A to only 40% inhibition. Adenosine failed to antagonize the antiviral activity. In monolayer cultures of KB cells, the 50% inhibitory concentration of ara-A was increased from 1.5 to 2.9 muM by 2 muM deoxyadenosine and to 8.5 muM by 10 muM deoxyadenosine. Analysis of the dose-response data by a double reciprocal plot method indicated that the antagonism was competitive. The antiviral activity of ara-H also was antagonized by deoxyadenosine. The 50% inhibitory concentration of ara-H was increased from 42 muM to 70, 91, or 121 muM by the concurrent addition of 5, 10, or 20 muM deoxyadenosine. Competitive antagonism could not be demonstrated. In the absence of the adenosine deaminase inhibitor, neither ara-A nor ara-H was antagonized by deoxyadenosine. Since such inhibitors were not available unitl recently, previous investigators were unable to observe the antagonistic capacity of deoxyadenosine.

Adenosine↗

Structure-activity relationships of natural and synthetic cannabinoids in suppression of humoral and cell-mediated immunity.

Delta-9-Tetrahydrocannabinol (delta-9-THC) a psychoactive constituent of marihuana, has been shown in previous studies to suppress humoral and cell-mediated immunity. The objective of this study was to determine whether structural modification of delta-9-THC would result in a more potent immunosuppressant agent devoid of central nervous system activity. The ED50 for reduction of the humoral immune response to sheep erythrocytes as measured by spleen plaque forming cells/10(6) spleen cells was 70 mg/kg for delta-9-THC. Delta-8-THC, 1-methyl delta-8-THC and abnormal delta-8-THC were more potent with ED50 values of 14, 13 and 8 mg/kg, respectively. Cell-mediated immunity was evaluated by a delayed-type hypersensitivity response to sheep erythrocytes. At doses of 100 mg/kg s.c. for 4 days, the cannabinoids suppressed the delayed-type hypersensitivity response from 35 to 64%. These data show that the cannabinoids can cause immunosuppression which is not related to central nervous system activity since 1-methyl delta-8-THC and abnormal delta-8-THC have minimal central nervous system activity.

Animals↗