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J C Schultz

Publications and source records attributed to J C Schultz.

At least 37 records · Page 2Linked to original sources

Synergistic and antagonistic effects of combinations of cyclosporine A and its metabolites on inhibition of phytohemagglutinin-induced lymphocyte transformation in vitro.

Cyclosporine A (CsA) and purified CsA metabolites were tested alone and in combination in cell culture to determine their effects on phytohemagglutinin (PHA)-induced lymphocyte proliferation. CsA was significantly more inhibitory than its metabolites at all concentrations tested (0-1000 ng/mL). CsA exerted maximum inhibition (70% decrease in [methyl-3H]thymidine incorporation) at concentrations of 300 ng/mL or greater; metabolites M1, M17, and M21 depressed the response 46, 39, and 23%, respectively, at 300 ng/mL. Metabolites M8, M18, M26, M25, M13, and M203-218 were non-inhibitory. When combinations of M17 and CsA were tested for the effects on PHA-induced lymphocyte transformation, a synergistic effect occurred at combinations of low concentrations of M17 and CsA and an antagonistic effect at the higher concentrations. Of the 49 combinations of CsA and M17 tested, 30 were antagonistic, 16 synergistic and 3 undecided (approaching addition). When 49 combinations of CsA and the non-immunosuppressive metabolite M8 were tested, 29 of the 49 combinations were synergistic, 17 antagonistic, 1 additive and 2 undecided (approaching addition). Of the 29 synergistic combinations, 14 were strongly synergistic. The importance of the interaction of CsA and metabolites to the immunopharmacology of CsA therapy is discussed.

Cell Division↗

Specificity and sensitivity of esophageal motor abnormality in systemic sclerosis (scleroderma) and related diseases: a cineradiographic study.

Using cineradiography, we studied esophageal peristalsis in patients with suspected systemic sclerosis and related diseases, and in patients without known esophageal disease who had been referred for upper gastrointestinal series. Patterns of peristaltic abnormality were identified, and specificity and sensitivity values calculated. Esophageal aperistalsis was 100% specific, and consistently weak peristalsis after all, swallows was 88% specific for systemic sclerosis. Specificity decreased to 70% in patients over age 60. Abnormal peristalsis after some, but not all, swallows had only 52% specificity. Consistently abnormal peristalsis (absent or diminished) was 67% sensitive for scleroderma. Although a high sensitivity value (87%) for cineradiography can be obtained by considering any peristaltic abnormality as a sign of scleroderma, this is achieved at the price of an undesirably high number of false positives (specificity 40%).

Adolescent↗

Mutagenicity tests with gallic and tannic acid in the Salmonella/mammalian microsome assay.

Gallic acid, tannic acid mixture and a purified fraction of tannic acid were evaluated for possible mutagenic activity in three strains of Salmonella typhimurium, TA98, TA100, and TA1535. These chemicals were not mutagenic either before or after activation with rat and woodchuck microsomal and cytosolic enzymes. However, tannic acid mixture and tannic acid fraction both gave a significantly (p = 0.05) dose-related reduction in the number of the revertant colonies, compared to the normal spontaneous revertants with no apparent toxic effects in the background lawn. With an agar diffusion assay, the chemicals exhibited toxic effects at 5000 micrograms/disc.

Animals↗

Inhibitory effect of leukemic plasma on periodate-induced lymphocyte transformation.

Plasma from nine out of 18 patients with untreated acute lymphoblastic leukemia (ALL) depressed the transformation of normal blood lymphocytes induced by sodium periodate (NaIO4) as judged by reduction of blast cell formation and [3H]thymidine and [3H]uridine incorporation into DNA and RNA respectively. The depressed mitogen responsiveness of lymphocytes cultured in the presence of leukemic plasma was due to the presence of inhibitory factor(s) present in the plasma rather than the absence of components present in normal plasma. The inhibitory effect of leukemic plasma on periodate-induced cell stimulation indicated that the leukemic plasma inhibitory factor(s) exert their action very rapidly and directly on the cell. Transfer of the inhibitory factor(s) from the leukemic plasma to the cultured cells was supported by the finding that the depressive action of leukemic plasma on lectin and non-lectin mitogen-induced transformation of lymphocytes was reduced if the leukemic plasma was preincubated with either resting or mitogen-treated lymphocytes prior to testing with lymphocytes not previously exposed to leukemic plasma or mitogen.

Cell Division↗

Recategorizing childhood acute lymphoblastic leukemia with monoclonal antibodies to human T cells.

The lymphoblasts of three patients with childhood acute lymphoblastic leukemia (ALL) were analyzed for their immunologic surface markers. Blasts from two of these patients did not form rosettes with sheep erythrocytes and the third did so marginally, suggesting these patients had non-T-cell leukemia. These blasts were also tested with monoclonal antibodies that detect thymocyte differentiation markers, and all three patients were highly reactive with at least two of these reagents. We anticipate the availability of multiple standardized monoclonal reagents will necessitate a recategorization of ALL phenotypes. Some of these leukemic phenotypes may not correspond to normal stages of lymphoid differentiation. Therefore, we suggest that it may be inappropriate to attempt to identify and categorize leukemic cells by the pathways of normal differentiation.

Adolescent↗

Tomography in expansile lesions of the nasal and paranasal sinuses.

Of 35 nasal and paranasal sinus masses examined by radiography and tomography, 22 malignant tumors showed purely destructive growth. Bone expansion was observed in 13 benign, and 2 slowly growing malignant masses. Pluridirectional tomography in carefully selected projections is often necessary to reveal expansile growth. The 13 expansile lesions, including mucocele, neurofibroma, dermoid, epidermoid, cementifying fibroma, angiofibroma, inverting papilloma, and cylindroma, are briefly described. Tomographic appearance alone did not characterize histopathologic entities. However, distinctions may be made between fibro-osseous and epithelial tumors, and between fast growing and slowly growing tumors.

Adolescent↗

Enzymatic synthesis of 2-O-alpha-D-mannopyranosyl-methyl-alpha-D-mannopyranoside by a cell-free particulate system of Mycobacterium smegmatis.

A cell-free particulate enzyme preparation of Mycobacterium smegmatis ATCC 607 catalyzed the transfer of labeled mannose from GDP[14C] mannose to methyl-alpha-D-mannopyranoside (an exogenously added acceptor) to form a product that was characterized to be 2-O-alpha-D[14C] mannopyranosyl-methyl-alpha-D-mannopyranoside. This transmannosylase activity was specific for both the sugar nucleotide donor and methyl monosaccharide acceptor. The reaction was stimulated by the addition of various metal ions and had a pH optimum of 6.0. The apparent Km of this transmannosylase reaction for methyl-alpha-D-mannopyranoside was 35 mM. The possible relationship between this "artificial" mannosyl-transfer system and the "natural" system which leads to the formation of the oligomannosides and glycoproteins is discussed.

Cell-Free System↗

The role of mannosylphosphorylpolyisoprenol in glycoprotein biosynthesis in Mycobacterium smegmatis.

A particulate enzyme preparation of Mycobacterium smegmatis catalyzes the transfer of labeled mannose from GDP-[14C] mannose into several endogenous acceptors. In one of these transfer reactions, the radioactivity is incorporated into an insoluble polymeric product that is present at the interphase after extraction of reaction mixture with chloroform-methanol. Solubilization of this product was achieved by digestion with proteolytic enzymes or treatment with 0.1 M NaOH indicating that the material was glycoprotein in nature. The solubilized material obtained after proteolytic digestion followed by treatment with alkali (representing 80-93% of the total interphase product) was shown to consist of a series of small molecular weight [14C] mannose containing oligosaccharides and glycopeptides by Bio-Gel column chromatography. A kinetic study of the enzymatic transfer of [14C] mannose from GDP-[14C] mannose into the glycoprotein suggested that the mannosylphosphorylpolyisoprenols are the obligatory mannosyl donor.

Carbon Radioisotopes↗

Biosynthesis of glycosyldiglycerides in Mycobacterium smegmatis.

A particulate enzyme preparation from Mycobacterium smegmatis catalyzes the transfer of [(14)C]galactose from uridine 5'-diphosphate (UDP)-[(14)C]galactose and of [(14)C]glucose from UDP-[(14)C]glucose into chloroform-soluble products. The radioactive neutral lipids were purified by passage through diethylaminoethyl-cellulose, followed by thin-layer chromatography. When UDP-glucose was used as substrate, two major radioactive lipids were obtained; one had a hexose-glucose-glycerol ratio of 1:1:1. The second product had a hexose-glycerol ratio of 2:1 and, in addition to glucose, contained lesser amounts of mannose and galactose. With UDP-galactose as substrate, two radioactive products were observed that were chromatographically indistinguishable from the [(14)C]glucosyl-labeled mono- and diglycosyldiglyceride. Palmitate and oleate were the predominant fatty acid constituents in these lipids and were present in equimolar amounts in all of the products examined. The products have thus been identified as monoglycosyldiglyceride and a diglycosyldiglyceride containing glucose as the major hexose along with mannose and galactose. Properties of the galactosyl and glucosyl transferases are described.

Carbon Radioisotopes↗

Biosynthesis of glycogen and starch in Cryptococcus laurentii.

Cells of Cryptococcus laurentii, when grown in liquid culture on 2% glucose close to neutral pH, showed glycogen granules throughout the cytoplasm. Glycogen levels of C. laurentii cells reached maximal levels just before onset of stationary phase. Concomitantly, a sharp rise in total and specific activity of glycogen synthetase was observed. Conversely, glycogen phosphorylase reached its highest specific activity approximately 3 hr after the glycogen peaked and remained high until most of the endogenous glycogen was utilized. Uridine diphosphoglucose pyrophosphorylase activity was always an order of magnitude higher than glycogen synthetase during log phase, but fell off rapidly after the cells reached stationary growth. Kinetic properties of the glycogen synthetase showed that the enzyme is always activated by glucose-6-phosphate, although the degree of activation by glucose-6-phosphate was found to be somewhat variable. The accelerated uptake of glucose commencing with the onset of stationary phase is explained by the rapid formation of extracellular acidic polysaccharide, which continues as long as there is glucose in the medium. In cells grown at pH 3.4, where no detectable extracellular acidic polysaccharide was formed, glucose uptake drastically declined when the cells reached stationary phase. These cells also contained glycogen-like granules in the cytoplasm. The evidence presented indicates that these granules are in fact glycogen, and that its structure does not resemble that of the starch excreted by cells grown at acidic pH.

Carbon Isotopes↗