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Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 1,207 records · Page 67Linked to original sources

Tissue and subcellular distributions of the smg-21/rap1/Krev-1 proteins which are partly distinct from those of c-ras p21s.

We have made a specific antiserum recognizing both smg p21A (the rap1A/Krev-1 protein) and -B (the rap1B protein), ras p21-like GTP-binding proteins having the same putative effector domain as ras p21s and have used this antiserum to study the tissue and subcellular distributions of smg p21s by immunoblot and immunocytochemical analyses. By immunoblot analysis, smg p21s were detected in various rat tissues and at the highest level in brain. By light microscopic immunocytochemical analysis, smg p21s were also detected in various rat tissues. Particularly, smg p21s in brain were found abundantly in the cytoplasmic region of most types of neuronal cell bodies and moderately in neuropil, whereas c-ras p21s were found more abundantly in neuropil than in the cytoplasmic region of most types of neuronal cell bodies. smg p21s in testis were found in spermatogenic cells, in which c-ras p21s were not significantly detected. By subcellular fractionation analysis of cerebrum, smg p21s were detected in all of the particulate fractions but not in the cytosol fraction. Among the particulate fractions, approximately 70% of smg p21s was recovered with the highest specific content in the fraction containing mainly synaptosomes, mitochondria, and myelin. In further fractionation of this fraction, approximately 40% of smg p21s was recovered in each of the synaptosome fraction and the mitochondrial fraction. This subcellular distribution of smg p21s in cerebrum was partly distinct from that of c-ras p21s, which were mainly recovered in the synaptosome and microsome fractions but present at very low levels in the mitochondrial fraction. These tissue and subcellular distributions of smg p 21s together with the fact that smg p21s have the same putative effector domain as ras p21s exert their own specific actions in addition to the actions similar or antagonistic to those of c-ras p21s.

Animals↗

Ongoing diversification of the rearranged immunoglobulin light-chain gene in a bursal lymphoma cell line.

The chicken immunoglobulin light-chain gene (IgL) encodes only a single variable gene segment capable of recombination. To generate an immune repertoire, chickens diversify this unique rearranged VL gene segment during B-cell development in the bursa of Fabricius. Sequence analysis of IgL cDNAs suggests that both gene conversion events derived from VL segment pseudogene templates (psi VL) and non-template-derived single-base-pair substitutions contribute to this diversity. To facilitate the study of postrecombinational mechanisms of immunoglobulin gene diversification, avian B-cell lines were examined for the ability to diversify their rearranged IgL gene during in vitro passage. One line that retains this ability, the avian leukosis virus-induced bursal lymphoma cell line DT40, has been identified. After passage for 1 year in culture, 39 of 51 randomly sequenced rearranged V-J segments from a DT40 population defined novel subclones of the parental tumor. All cloned V-J segments displayed the same V-J joint, confirming that the observed diversity arose after V-J rearrangement. Most sequence variations that we observed (203 of 220 base pairs) appeared to result from psi VL-derived gene conversion events; 16 of the 17 novel single nucleotide substitutions were transitions. Based on these data, it appears that immunoglobulin diversification during in vitro passage of DT40 cells is representative of the diversification that occurs during normal B-cell development in the bursa of Fabricius.

Alleles↗

Hemorrhagic fever with renal syndrome: MR imaging of the kidney.

Magnetic resonance (MR) imaging of the kidneys was performed in 14 patients with a severe form of hemorrhagic fever with renal syndrome (HFRS), a major public health problem in Far Eastern Asia. To the authors' knowledge, this is the first report of renal assessment with MR imaging in HFRS. Three MR imaging studies were done while patients were in the oliguric phase, 19 were done during the diuretic phase, and three were done during the convalescent phase. The authors differentiated the cortex and the medulla in all 21 T1-weighted examinations and all 25 T2-weighted examinations. Seven T1-weighted examinations (33%) and 20 T2-weighted examinations (80%) showed low signal intensity along the outer portion of the medulla, which thus enabled differentiation from the inner medulla. Low signal intensity along the medulla (especially the outer medulla) on T2-weighted images, possibly representing medullary hemorrhage, is fairly constant and characteristic on MR images of the kidneys in patients with HFRS.

Adult↗

Conversion to renin of exogenously administered recombinant human prorenin in liver and kidney of monkeys.

Highly purified recombinant human prorenin, labeled with 125I (125I-prorenin), was intravenously given to monkeys to examine the possible in vivo conversion of this prorenin to renin. 125I-prorenin and 125I-renin were detected using specific anti-prorenin prosegment antibody and anti-renin antibody, respectively. The plasma disappearance of immunoreactive 125I-prorenin in marmosets showed two exponential components with a half-life of 10.4 +/- 0.2 min for the rapid component and 165.7 +/- 12.6 min for the slow component. Fifteen minutes after the injection of 125I-prorenin, 38.7 +/- 2.8 and 3.9 +/- 0.5% of the administered dose accumulated in the liver and kidney, respectively. Less than 1% of the dose injected distributed in the other organs, including the brain, submandibular gland, lung, heart, aorta, adrenal gland, spleen, uterus, ovary, and testis. Thus the labeled prorenin was predominantly taken up by the liver and kidney. Analysis of liver and kidney extracts and plasma, by both gel permeation high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, demonstrated that 125I-prorenin (Mr = 46,000) taken up by the liver and kidney was significantly converted to 125I-renin (Mr = 42,000), whereas only a negligible amount of 125I-renin (Mr = 42,000) was present in the plasma. Although there seems to be no activation of prorenin in the blood circulation, prorenin does seem to be activated by the liver and kidney.

Animals↗

Estrogen effects on lymph flow as a function of outflow pressure in ewes.

The purpose of the present study was to assess whether acute estrogen administration decreased the lymphatic vessel's "pumping" ability. An additional goal was to assess whether estrogen affected the capillary filtration (used here as the total transfer of fluid and protein across the capillaries evidenced by the thoracic duct lymph flow rate). We reasoned that if estrogen administration decreases the lymph pumping ability against outflow pressure, then this phenomenon could help to explain the interstitial fluid retention seen during chronic estrogen. In six nonpregnant ewes we studied the thoracic lymph flow rate measured at different outflow pressures, before and after the acute administration of 50 mg of Premarin (conjugated estrogenic hormones). We also continuously determined arterial and venous pressures and heart rate. The arterial pressure declined from a mean of 99 +/- 0.33 (SE) mmHg to 95.4 +/- 0.2 mmHg (P less than 0.05) after the administration of estrogen. Heart rate increased from 88.5 +/- 0.8 to 111.3 +/- 1.2 beats/min (P less than 0.01). Venous pressure, plasma and lymph protein concentrations, and hematocrit did not change significantly (P greater than 0.1). Lymph flow rate declined progressively when measured against positive outflow pressure, whereas it remained stable when measured against negative pressure. Lymph flow rate during negative outflow pressure was higher after the administration of estrogen 0.044 +/- 0.002 vs. 0.032 +/- 0.002 ml.min-1.kg-1 for the control period (P less than 0.05). The calculated outflow pressure at which lymph flow rate became zero was similar for the period before or after the estrogen administration (P greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cardiovascular changes after closure of uterine circulation during pregnancy.

To assess the effects of the presence of the uteroplacental circulation on the systemic arterial pressure, blood volume, and cardiac output during pregnancy, we measured those variables and plasma renin activity (PRA) during a 30-min period before and after occlusion of the uterine circulation. After uterine vascular occlusion, pregnant rabbits (n = 7) experienced a drop in mean arterial pressure of 8.7%, heart rate of 9.5%, cardiac output of 30.2%, and hematocrit of 18.2% (each with P less than 0.05). Stroke volume decreased an average of 29.7%; however, it did not reach significance. PRA and venous pressure did not change significantly from the control period (P greater than 0.1). Nonpregnant rabbits did not experience changes in arterial or venous pressures, hematocrit, heart rate, cardiac output, or PRA after closure of the uterine circulation. To exclude the possibility that the findings were secondary to the release of toxic products to the peritoneal cavity by the ischemic pregnant uterus, we also studied the effect of closure of the uterine circulation in five anesthetized pregnant guinea pigs. These animals' uteri were exteriorized and maintained in a sealed plastic container during the experiment. In these animals, arterial pressure decreased 15.6% by 10 min (P less than 0.05). The finding of a significant decrease in arterial pressure and heart rate is compatible with the idea that the uterine circulation produces a substance with a short half-life that has a significant direct effect on the heart and/or systemic vascular tone.

Animals↗

Heterogeneity of distribution pattern at the electron microscopic level of heparan sulfate in various basement membranes.

Using the high-iron diamine thiocarbohydrazide silver proteinate (HID-TCH-SP) staining technique and enzymatic digestion, we investigated the ultrastructural distribution pattern of heparan sulfate side chains of heparan sulfate proteoglycan (HSPG) in various basement membranes (nerve, capillary, oral epithelial, muscle, and dental basement membranes). Four different distribution patterns of stain deposits were identified as heparan sulfate on the basis of enzymatic degradation by heparitinase. In some basement membranes associated with tooth germs and oral epithelium, HID-TCH-SP stain deposits were regularly located at both sides of the lamina densa, but few were observed in the lamina densa itself. In nerve, muscle, and capillary basement membranes, the stain deposits were localized at the external side of the lamina densa adjacent to the underlying connective tissue, but were not found in the laminae lucida and densa. In the internal basal lamina of junctional epithelium of gingiva, the stain deposits were detected mainly in the lamina lucida region. Finally, in some dental and oral epithelial basement membranes, the stain deposits were randomly distributed throughout both laminae lucida and densa. Thus, the present study demonstrated distinct differences in heparan sulfate distribution pattern among various basement membranes, suggesting their architectural heterogeneity.

Animals↗

A phase II trial of intraperitoneal cisplatin and etoposide for primary treatment of ovarian epithelial cancer.

We conducted a phase II trial of intraperitoneal (IP) cisplatin (DDP) and etoposide (VP-16) in stage III and IV newly diagnosed ovarian carcinoma patients with residual disease of any size. Twenty-three patients were entered, 19 had stage III and four stage IV disease. DDP 200 mg/m2 and VP-16 350 mg/m2 were given in 2 L saline IP via a Port-A-Cath (Pharmacia-Deltec, St Paul, MN). Sodium thiosulfate 4 g/m2 was given intravenously (IV) just before the start of IP instillation, and continued as a constant IV infusion of 2 g/m2/hr IV for a total of 6 hours. Treatment was given once every 4 weeks; six cycles of therapy were planned. Thirteen patients (56%) were in complete clinical remission at the end of treatment (normal physical exam, computed tomographic [CT] scan, CA-125, and peritoneal cytology). Seven of these 13 underwent a second-look laparotomy: three (13%) were in pathologic complete remission and four (17%) had microscopic disease only. Projected survival is 68% at 27 months, with 10 patients being alive and continuously free of disease. There was a very rapid fall in mean CA-125 to within normal limits at the end of the second course of treatment. The major toxicity was myelosuppression with median nadir WBC, granulocyte, and platelet counts of 2,600, 896, and 205,000/microL, respectively. There was no cumulative renal damage, anemia, hypomagnesemia, or chemical peritonitis. Neurotoxicity was similar to that observed with IV dosing. We conclude that therapy with the IP DDP/VP-16/IV thiosulfate regimen, in which all cytotoxic drugs are given only by the IP route, produces less anemia and renal damage than standard IV DDP-containing regimens, and that survival with this regimen appears to be at least as good as that produced by IV programs.

Antineoplastic Combined Chemotherapy Protocols↗

A short-term outcome evaluation of the "I'm Special" drug abuse prevention program: a revisit using SCAT inventory.

In the previous evaluation of "I'm Special" (ISP) drug abuse prevention/education program, the long-term impact was reported. The current study examines the short-term outcome of the ISP to establish a conceptual link between what has been observed longitudinally to the short-term outcome. The evaluation instrument used is children's Self-Concept Attitudinal (SCAT) Inventory. Subjects are the third grade students in the Charlotte-Mecklenburg public schools located in Charlotte, North Carolina. The evaluation design employed is before and after-measurement without a control group. In the absence of a control group, the treatment effect of the ISP is estimated on the basis of individual growth curve models. Through the study, it has been learned that the ISP was able to generate positive changes along six attitudinal dimensions included in the SCAT Inventory. The six scales have shown close relationships to student performance at school: student-teacher relationship; self-esteem, attitude toward school, basic social values, advanced social values, and the perception of family cohesiveness. Of these, the first four scales have shown statistical significance at the .05 level. It is estimated that the ISP is capable of generating a significant amount of positive attitudinal changes on a short-term basis with a time span of about four months between pre- and posttests. These findings are consistent with the conclusions obtained from the longitudinal study where student alcohol and other drug using behavior and other related student problem behaviors were significantly lower among the ISP recipients than non-recipients of the program.

Child↗

Pulmonary diffuse alveolar septal amyloidosis--diagnosed by transbronchial lung biopsy.

Diffuse alveolar septal involvement is a rare form of pulmonary amyloidosis. Antemortem diagnosis is unusual, and most of the reported cases were diagnosed at autopsy. It has recently been reported that transbronchial lung biopsy via a flexible fiberoptic bronchoscope was a relatively safe method to confirm diffuse alveolar septal amyloidosis. We report a case of pulmonary diffuse alveolar septal amyloidosis confirmed by transbronchial lung biopsy. The patient's chief complaints were dyspnea on exertion and epigastric pain aggravated over a one-year period, while a chest roentgenogram showed bilateral diffuse interstitial infiltration. This case also showed nephrotic syndrome, cardiac arrhythmia, congestive heart failure, a tingling sensation in both hands and multiple nodules in the gastrointestinal tracts, suggesting involvement of the kidney, heart, peripheral nerves and gastrointestinal tracts. We propose that when diffuse interstitial lung disease is present with systemic signs such as nephrotic syndrome or cardiac arrhythmia, amyloidosis should be considered as a possible diagnosis. Also, transbronchial lung biopsy may be a useful confirmative diagnostic tool.

Amyloidosis↗

Nicorandil is a potent dilator of endothelin-induced vascular contraction.

Nicorandil, an antianginal drug, is known to open K+ channel and to increase cGMP production. The effects of nicorandil on vascular contraction induced by endothelin (ET), a potent newly discovered vasoconstrictor peptide, were investigated using helical strips from rat thoracic aorta. ET at a concentration of 5 x 10(-9) M induced strong and persistent contraction in the presence of extracellular Ca2+ and similar persistent but smaller contraction in the absence of extracellular Ca2+. Nicorandil at concentrations greater than 10(-7) M, strongly and dose-dependently inhibited ET-induced contraction in the presence of extracellular Ca2+. Nicorandil also suppressed ET-induced contraction in the presence of 10(-4) M methylene blue, an inhibitor of cGMP production, in the presence of extracellular Ca2+ but not in the absence of extracellular Ca2+. ET-induced contraction was also inhibited to lesser extents by the Ca2+ channel blockers nicardipine and verapamil. Nicorandil also strongly suppressed ET-induced increase in cytosolic free Ca2+ concentration in cultured vascular smooth muscle cells. These results suggest that nicorandil is a potent dilator of ET-induced vasoconstriction.

Animals↗

Endothelin stimulates Na+/H+ exchange in vascular smooth muscle cells.

The effect of endothelin (ET) on the intracellular pH (pHi) of vascular smooth muscle cells (VSMC), was investigated using a fluorescent pH indicator 2',7'-bis(carboxyethyl)carboxyfluorescein (BCECF). ET at concentrations of over 10(-9) M caused dose-dependent transient acidification followed by Na(+)-dependent and amiloride-sensitive alkalization of the cells due to stimulation of Na+/H+ exchange. The alkalization induced by ET was Ca2(+)-dependent and was inhibited by a calcium channel blocker, nicardipine. Pretreatment with H-7, an inhibitor of protein kinase C, also inhibited the ET-induced cell alkalization. These results indicate that ET stimulates Na+/H+ exchange, resulting in alkalization of VSMC and that this ET-induced cell-alkalization is probably linked to Ca2+ influx and activation of protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Changes in ultrastructural distribution of dental basement membrane heparan sulfate during early mouse tooth development.

With the invagination of the deep surface of the tooth buds of mouse embryos (15 days of gestation), heparan sulfate in the region of the lamina lucida of the dental basement membrane began to disappear. Subsequently, as the outline of the future dentino-enamel junction, which elaborates the molar cusp pattern, was formed (16-17 days of gestation), heparan sulfate disappeared not only in the lamina lucida but also at the external side of the lamina densa. However, prior to or during predentin matrix deposition (18 days of gestation), heparan sulfate reappeared in the dental basement membrane.

Amelogenesis↗

Small molecular weight GTP-binding proteins and signal transduction.

We have separated multiple GTP-binding proteins (G proteins) having Mr values of about 20,000 (small Mr G proteins) from bovine brain membranes, purified to near homogeneity and characterized two novel G proteins designated as smg p25A and smg p21, the c-Ki-ras protein (c-Ki-ras p21) and the two rho proteins (rho p20 and rho p21). smg p25A is present abundantly in brain and adrenal medulla. This G protein is also found in rat pheochromocytoma PC-12 cells, and its mRNA level increased after differentiation of the cells into neuron-like cells in response to nerve growth factor or dibutyryl cyclic AMP. These results suggest that smg p25A plays an important role in the regulation of neuronal functions. In contrast, smg p21 is found in most tissues. This G protein has the same putative effector domain as ras p21s, suggesting that smg p21 exerts the actions similar and/or antagonistic to those of ras p21s. In fact, smg p21 has been found to be identical with the protein encoded by the Krev-1 gene recently isolated as a gene suppressing the transforming action of Ki-ras p21 in NIH/3T3 cells. On the other hand, rho p20 and rho p21 are ADP-ribosylated by an ADP-ribosyltransferase contained or contaminated in botulinum toxin type C1, presumably C3. Botulinum ADP-ribosyltransferase C3 has recently been shown to induce morphological changes similar to those induced by ras p21 in fibroblasts. Thus, small Mr G proteins are part of a huge network of intracellular regulatory systems and play important roles in the regulation of various cell functions including cell transformation, proliferation and differentiation.

Amino Acid Sequence↗

Comparison of effects of a potassium channel opener BRL34915, a specific potassium ionophore valinomycin and calcium channel blockers on endothelin-induced vascular contraction.

The effects of a potassium (K+) channel opener BRL34915 and a specific K+ ionophore valinomycin on vasoconstriction induced by endothelin (ET) were compared with those of calcium (Ca2+) channel blockers, nicardipine and verapamil, using helical strips from rat thoracic aorta. ET induced potent and persistent contraction in control solution and similar but smaller contraction in Ca2+-free solution. BRL34915 and valinomycin inhibited the ET-induced contraction dose-dependently in control solution, but not in Ca2+-free solution. The ET-induced contraction was also inhibited by nicardipine and verapamil, though less strongly. On the other hand, high K+ (35 mM)-induced vasoconstriction was strongly inhibited by nicardipine and verapamil, but not by BRL34915 or valinomycin. These results support the idea that the extracellular Ca2+-dependent component of the ET-induced contraction may be mediated by Ca2+ influx by a route other than voltage-dependent Ca2+-channels.

Animals↗

Tissue distribution of smg p25A, a ras p21-like GTP-binding protein, studied by use of a specific monoclonal antibody.

We made a monoclonal antibody specifically recognizing smg p25A among many ras p21-like GTP-binding proteins and investigated the tissue distribution of smg p25A by use of this antibody. By immunoblot analysis, smg p25A was detected in rat brain and bovine adrenal medulla but not in bovine adrenal cortex or other rat tissues including thymus, spleen, lung, heart, liver and kidney. However, by immunocytochemical studies, smg p25A was detected not only in the synaptic areas of rat brain and the chromaffin cells of bovine adrenal medulla but also in the endocrine cells of rat pancreatic islets, the acinar cells of rat exocrine pancreas and the exocrine cells of rat submaxillary gland. These results suggest that smg p25A is involved in the regulation of secretory processes not only in synapses but also in other endocrine and exocrine secretory cells.

Adrenal Medulla↗