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Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 1,279 records · Page 71Linked to original sources

Fate of recombinant human renin administered exogenously to anesthetized monkeys.

Highly purified recombinant human renin (rh-renin), synthesized by Chinese hamster ovary cells, was labeled with iodine-125 and was given intravenously to pentobarbital-anesthetized common marmosets (Callithrix jacchus) to study the fate of the circulating renin. Specific anti-rh-renin antiserum was used to identify the 125I-rh-renin. Plasma disappearance of the exogenously administered 125I-rh-renin in marmosets (n = 6) showed two exponential components, with a half-life of 12.1 +/- 1.9 minutes for the rapid component and 120.3 +/- 16.4 minutes for the slow component. The metabolic clearance rate was 1.17 +/- 0.26 ml/min/kg. Thirty minutes after the injection of 125I-rh-renin, 43.1 +/- 0.9 and 3.5 +/- 0.5% of the injected dose had distributed to the liver and the kidneys, respectively. With time, the accumulated 125I-rh-renin in the liver and kidneys decreased. The accumulation of 125I-rh-renin was less than 1% of the dose injected in other organs such as lungs, heart, spleen, adrenal glands, testes, and ovaries. Analysis of liver and kidney extracts by high performance liquid chromatography at 30 and 120 minutes indicated that immunoreactive 125I-rh-renin decreased with time and was accompanied by an increase in nonimmunoreactive degradation products of a low molecular weight. The incubation of 125I-rh-renin with monkey or human plasma at 37 degrees C did not degrade the labeled renin. Therefore, rh-renin was rapidly cleared from the circulation by the liver and the kidney.

Anesthesia↗

Modulation by 1,25-dihydroxycholecalciferol of the acute change in cytosolic free calcium induced by thyrotropin-releasing hormone in GH4C1 pituitary cells.

Receptor-mediated regulation of prolactin synthesis by 1,25-dihydroxycholecalciferol (1,25(OH)2D3) in the pituitary cell strain GH4C1 is dependent on the concentration of extracellular calcium. We have now investigated the actions of 1,25(OH)2D3 on cytosolic free calcium concentrations [( Ca2+]i) in these cells using the fluorescent indicator quin2. Basal resting [Ca2+]i was unchanged in cells treated with 1 nM 1,25(OH)2D3 either acutely (from 0 to 15 min) or for periods of up to 48 h. However, the initial peak of the biphasic change in [Ca2+]i induced by thyrotropin-releasing hormone (TRH) was enhanced more than twofold in cells pretreated for 24 or 48 h with 1,25(OH)2D3. This 1,25(OH)2D3-enhanced calcium response was restricted to the initial phase of TRH action; the secondary plateau phase was unaffected. Neither the affinity nor number of TRH receptors nor the early time course of [3H]MeTRH binding to GH4C1 cells were affected by pretreatment with 1,25(OH)2D3. Because TRH binding was not altered, four sites along the intracellular signal transduction pathway of TRH action were examined. Neither protein kinase C activation nor inositol polyphosphate accumulation were enhanced in response to TRH, in 1,25(OH)2D3 pretreated cells, indicating that phosphatidylinositol hydrolysis was unchanged by pretreatment. A low concentration of ionomycin was used to probe the size of the nonmitochondrial intracellular calcium pool that is sensitive to TRH. Ionomycin was not able to mobilize more calcium from 1,25(OH)2D3 pretreated cells, indicating that TRH-responsive intracellular calcium stores were probably not enhanced by pretreatment. Chelation of extracellular calcium, however, did eliminate enhancement of the TRH response in 1,25(OH)2D3-pretreated cells. We conclude that 1,25(OH)2D3 modulates acute dynamic changes in [Ca2+]i induced by TRH without affecting basal [Ca2+]i. The mechanism of the enhanced response of 1,25(OH)2D3-pretreated cells to TRH appears to depend upon a postreceptor event independent of phosphatidylinositol hydrolysis that involves increased calcium conductance at the level of the plasma membrane. A less likely explanation involves enhancement of intracellular calcium stores in an ionomycin-resistant, EGTA-sensitive, TRH-mobilizable reservoir.

Animals↗

Quantitative differences in Ia antigen expression in the spleens of 15I5-B congenic and inbred chickens as defined by a new monoclonal antibody.

A monoclonal antibody (MAb), designated P2M11, that detects a monomorphic determinant of chicken class II antigens was produced from the fusion of P3X63 myeloma cells with spleen cells from BALB/c mice immunized with chicken splenic lymphocytes. Flow cytometric analyses of lymphocytes from the SC and FP strains of chickens showed 30 to 50% staining of bursa cells, 15 to 20% staining cells, and less than 5% staining of thymus cells. Addition of MAb P2M11 to splenic of T cell cultures stimulated with allogeneic cells or concanavalin A resulted in a significant inhibition of the T cell proliferation responses. Immunoprecipitation of 35S-methionine-labeled spleen cell extracts using MAb P2M11 identified molecules with apparent molecular weights of approximately 28,000, 30,000, and 32,000 by sodium dodecyl-polyacryl-amide gel electrophoresis. Taken together, these data indicate that the antigens detected by MAb P2M11 are similar in cell distribution and structure to chicken Ia antigens encoded by B-L genes. Using this MAb, a strain difference was demonstrated in the tissue distribution of Ia antigen positive lymphocytes in the spleens but not the thymuses of 15I5-B congenic and inbred strains of chickens. This difference may be due to the genes associated with B-complex genes.

Animals↗

Fibrinolysis in glomerulonephritis treated with ancrod: renal functional, immunologic and histopathologic effects.

The effects of a 14-day course of ancrod on fibrinolysis, renal function and structure, and immunologic findings are reported in 37 patients with glomerulonephritis. Patients were divided into two groups. In the first, the level of fibrin degradation products within 48 h was relatively low (less than 1 mg/ml). In these patients there was a linear relationship between changes in levels of fibrin degradation products and fibrinogen, suggesting that fibrin degradation products derived from ancrod-cleaved-fibrinogen in the circulating pool; in most, level of plasma alpha 2-antiplasmin before treatment was elevated. In the second, the level of fibrin degradation products within 48 h was high (greater than 1 mg/ml). Compared with the change in fibrinogen, a disproportionate increase in levels of fibrin degradation products suggested that a significant amount derived from sources other than plasmin digested ancrod-cleaved-fibrinogen, thus reflecting effective fibrinolysis, perhaps also in tissues; in most, the level of plasma alpha 2-antiplasmin was normal before treatment. In those with initial high levels of fibrin degradation products, higher levels persisted throughout treatment, changes in other fibrinolysis components were greater, and plasminogen activator inhibitor levels became normal. In patients with initial high but not with initial low response in fibrin degradation products renal function improved within 24 to 48 h and continued to improve thereafter; there was an immediate but temporary increase in proteinuria. Microvascular thrombosis decreased significantly, indicating effective removal of fibrin from glomeruli. The relation of early fibrinolysis to changes in immunologic and histopathologic findings was analyzed in patients with lupus nephritis. With ancrod, there was an increase toward normal of serum C3 and C4, a decrease in serum Igs, gamma globulin and anti-dsDNA antibody and in glomerular C3 and Ig deposits, suggesting that ancrod had favorable effects on immunologic factors. There were no clinical differences in patients with initial high and low responses, but the relationship of microvascular and inflammatory indexes before treatment differed. Initial renal biopsies and those after treatment were carried out on average 28 days apart. Inflammatory and microvascular indexes and glomerular thrombi decreased in patients with initial high levels of fibrin degradation products; fibrosclerosis index and glomerular sclerosis increased in patients with initial low levels of fibrin degradation products. Fibrinolysis expressed as the 48 h (fibrin degradation products/fibrinogen) ratio, correlated inversely with change in fibrosclerosis index and glomerular sclerosis in the whole group, and especially in those with initial high levels of fibrin degradation products.(ABSTRACT TRUNCATED AT 400 WORDS)

Ancrod↗

Diagnosis and management of intestinal endometriosis. A report of five cases.

Five cases of intestinal endometriosis presented with infertility and pelvic pain. Rectal bleeding occurred in two patients and diarrhea in one. A diagnosis was achieved with a barium enema study and colonoscopy. All the patients had pelvic endometriosis as documented by laparoscopy. Endometriosis was present in the sigmoid colon in three patients and in the cecum in one; it was pericecal in the fifth. Bowel resection and pathologic study are necessary to relieve the symptoms and avoid neglecting a malignant tumor or other lesions.

Adult↗

Bjork-Shiley cardiac valves long term results: Winnipeg experience.

Between April 1970 and December 1984, 1183 Bjork-Shiley cardiac valve prostheses were implanted in 915 patients (470 males, 445 females). Four types of valves were used; Delrin disc prostheses in 75 patients, pyrolytic carbon spherical disc valves in 645 patients, the 60 degrees convexo-concave disc model in 197 patients and the 70 degrees model in seven patients. Isolated mitral valve replacement was performed in 278 patients, isolated aortic valve replacement in 363 and double valve replacement in 153. Concomitant surgery was performed in 121 patients, including a modified Bentall procedure in 15. Perioperative mortality was 6.4% (nine patients undergoing isolated aortic valve replacement; 16 in mitral valve group, 18 with double valve replacement and 16 undergoing concomitant surgery). The cumulative follow-up was 4592 patient-years, to a maximum of 15 years. There were 130 late deaths, 60% due to cardiac events. Actuarial survival for the mitral valve group was as follows: four of six patients with Delrin disc valves were alive at 13.4 years; in the pyrolytic group, survival was 82% at 10 years; in the 60 degrees convexo-concave group survival was 87.5% at seven years. In the aortic valve replacement group, 83% of patients with pyrolytic valves were alive at 10 years and 85.7% of the 60 degree convexo-concave group were alive at seven years. For patients undergoing double valve replacement, 72% were still alive after seven years. Thromboembolic events averaged 1.4 per 100 patient-years. There were seven complete valve thromboses in the mitral position requiring reoperation; six of these patients were long term survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Enzymatic methylation of in vitro synthesized apocytochrome c enhances its transport into mitochondria.

The gene for iso-1-cytochrome c from Saccharomyces cerevisiae was recloned into a pSP65 vector containing an active bacteriophage SP promoter. The iso-1-cytochrome c gene was cloned as an 856-base pair XhoI-HindIII fragment. When the resulting plasmid was digested at the HindIII site 279 bases downstream from the termination codon of the gene and transcribed in vitro using SP6 RNA polymerase, full length transcripts were produced. The SP6 iso-1-cytochrome c mRNA was translated using a rabbit reticulocyte lysate system, and the protein products were analyzed on sodium dodecyl sulfate-polyacrylamide gels. One major band with a molecular weight of 12,000 was detected by autofluorography and coincided with the Coomassie staining band of apocytochrome c from S. cerevisiae. The product was also shown to be identical with that of standard yeast apocytochrome c on an isoelectrofocusing gel. The in vitro synthesized iso-1-apocytochrome c was enzymatically methylated by adding partially purified S-adenosyl-L-methionine:cytochrome c-lysine N-methyltransferase (protein methylase III, EC 2.1.1.59) from S. cerevisiae along with S-adenosyl-L-methionine to the in vitro translation mixtures. The methylation was shown to be inhibited by the addition of the methylase inhibitor S-adenosyl-L-homocysteine or the protein synthesis inhibitor puromycin. The principal type of methylated amino acid in the protein was found to be epsilon-N-trimethyllysine which accounted for 77% of the total. Finally, the methylation of in vitro synthesized iso-1-apocytochrome c was found to increase its import into mitochondria isolated from S. cerevisiae 2-4-fold over unmethylated protein, but not into rat liver mitochondria. This suggests that methylation facilitates the import of apocytochrome c into mitochondria by a specific receptor mechanism.

Apoproteins↗

Ovarian renin gene expression is regulated by follicle-stimulating hormone.

The regulation of renin and renin messenger RNA (mRNA) in the rat ovary was examined to test the hypothesis that the expression of renin gene and the secretion of renin in the ovary is the estrogen-mediated process that responds to follicle-stimulating hormone (FSH). In the ovary of the immature 25-day female rats, the concentration of renin mRNA was comparatively low, but 36 h after injection of FSH, the renin mRNA content showed a three-fold increase compared to the basal level. This increase was consistent with the stimulation of the total renin concentration in the ovary. On the other hand, the total renin concentration in the rat uterus gradually decreased, suggesting that the enhancement of the contents of renin and renin mRNA by FSH is an ovary-specific phenomenon. In hypophysectomized rats, the total renin concentration in the rat ovary was stimulated by the estrogen as well as FSH. These findings suggest that the production of ovarian renin is regulated by the pituitary hormone, particularly FSH.

Animals↗

Multivesicular liposomes containing 1-beta-D-arabinofuranosylcytosine for slow-release intrathecal therapy.

Optimal anticancer treatment with cell cycle-specific antimetabolites requires maintenance of a cytotoxic drug level for a prolonged period of time. We explored the use of multivesicular liposomes as a slow-release depot of 1-beta-D-arabinofuranosylcytosine for intrathecal administration. The intrathecal half-life of the liposome-encapsulated drug was 148 h, in contrast to the half-life of 2.7 h for the unencapsulated free drug, in a Sprague-Dawley rat model. The prolonged maintenance of a therapeutic drug level may increase efficacy, and the elimination of the very high peak level may decrease toxicity.

Animals↗