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Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 1,009 records · Page 56Linked to original sources
PubMed1994

Changes of endothelin concentration in cerebrospinal fluid and plasma of patients with aneurysmal subarachnoid hemorrhage.

To investigate the clinical significance of endothelin (ET), a potent vasoconstrictor peptide, in subarachnoid hemorrhage (SAH) and SAH-related cerebral vasospasm, we measured the ET-like immunoreactivity (ET-LI) in plasma and cerebrospinal fluid (CSF) obtained serially from patients with SAH due to ruptured cerebral aneurysm who underwent aneurysmal surgery. The normal ET-LI levels in plasma and CSF (n = 24) were 12.4 +/- 2.0 (mean +/- s.d.) and 9.1 +/- 1.2 pg.ml-1, respectively. Plasma ET-LI levels in patients with SAH before surgery (16.8 +/- 7.8 pg.ml-1, n = 8) were higher than the normal values (P < 0.05), and became further elevated after surgery (22.5 +/- 9.4 pg.ml-1). ET-LI levels in plasma and CSF one day after surgery were 18.7 +/- 5.5 and 18.4 +/- 6.8 pg.ml-1 (P < 0.01 vs. normal values), respectively, and declined thereafter. The plasma and CSF ET-LI levels in patients who showed symptomatic vasospasm became concomitantly elevated again. These results suggest that ET is involved in SAH-related vasospasm and raise the possibility that surgical stress influences the vasospasm.

Adult↗
PubMed1994

AT1 receptor-mediated stimulation by angiotensin II of rat aortic fibronectin gene expression in vivo.

Fibronectin plays an important role in various vascular diseases. A subpressor (200 ng kg-1 min-1) or pressor (1000 ng kg-1 min-1) dose of angiotensin II was continuously infused into rats by osmotic minipump for various times, to investigate the effects on aortic fibronectin gene expression. In rats infused with a subpressor dose of angiotensin II in which blood pressure was normal for 3 days, aortic fibronectin mRNA levels started to increase by 1.4 fold at 12 h and reached the maximal levels (increased by 3.1 fold) at 3 days. Treatment with TCV-116 (3 mg kg-1 day-1), a non-peptide selective AT1 receptor antagonist, completely inhibited the angiotensin II-induced increase in aortic fibronectin mRNA, while hydralazine (10 mg kg-1 day-1) did not block this effect. Similar results were also obtained for a pressor dose of angiotensin II. Thus, angiotensin II directly stimulates aortic fibronectin gene expression in vivo, which is mediated by the AT1 receptor but not by blood pressure.

Angiotensin II↗
PubMed1994

Identification of signal sequences that control transcription of borna disease virus, a nonsegmented, negative-strand RNA virus.

Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that causes neurologic disorders in a wide range of animal species. Although the virus is unclassified, sequence analysis of the 8.9-kb viral genome has shown that it is related to rhabdoviruses and paramyxoviruses. We have mapped subgenomic RNAs of BDV strain He80-1 to the viral genome by determining the precise sequences at their 5' and 3' termini. This analysis showed that the genome contains three transcription initiation sites and four termination sites. A 14- to 16-nucleotide semiconserved sequence was present at the gene start sites and partially copied into the subgenomic RNAs. The termination sites contained a U-rich motif reminiscent of termination signals in rhabdoviruses and paramyxoviruses. In contrast to the genomes of other nonsegmented, negative-strand RNA viruses, the BDV genome lacked the typical configuration of termination signal, intergenic region, and initiation signal at the gene boundaries. Instead, transcription units and transcription signals frequently overlapped. These differences have implications for our understanding of the control of viral transcription and may relate to the low-level replication and persistence of BDV.

Animals↗
PubMed1994

Analysis of Tat function in human immunodeficiency virus type 1-infected low-level-expression cell lines U1 and ACH-2.

The U1 and ACH-2 cell lines are subclones of human monocytic and T-lymphoid cells, respectively, persistently infected with human immunodeficiency virus type 1. These cell lines harbor the viral genome but produce only very low levels of viral progeny, which can be increased by stimulation with agents such as phorbol ester and cytokines. As such, they provide an in vitro model for human immunodeficiency virus type 1 latency. In order to examine the basis for their latent state, we have analyzed the activity of endogenous Tat protein in these cells and investigated the effect on viral replication of the addition of exogenous Tat protein. We find that U1 cells seem to have levels of Tat protein that are suboptimal for long terminal repeat (LTR) transcription, because transcription from a transfected LTR-chloramphenicol acetyltransferase plasmid can be enhanced by cotransfection of a Tat expression plasmid. Furthermore, viral replication can be stimulated in this cell line by incubation with purified Tat protein. In contrast, ACH-2 cells are not limited for LTR-chloramphenicol acetyltransferase transcription by endogenous levels of Tat, and virus production is not increased by the addition of exogenous Tat protein. By semiquantitative PCR analysis of viral RNA, we have demonstrated that Tat protein caused an increase in human immunodeficiency virus RNA expression in U1 cells but had no effect in ACH-2 cells. This suggests that a different mechanism underlies the latent state in U1 and ACH-2 cells.

Gene Products, tat↗
PubMed1994

Interferons block protein kinase C-dependent but not-independent activation of Raf-1 and mitogen-activated protein kinases and mitogenesis in NIH 3T3 cells.

Interferons (IFNs) exert antiproliferative effects on many types of cells. The underlying molecular mechanism, however, is unclear. One possibility is that IFNs block growth factor-induced mitogenic signaling, which involves activation of Ras/Raf-1/MEK/mitogen-activated protein kinase. We have tested this hypothesis by using HER14 cells (NIH 3T3 cell expressing both platelet-derived growth factor [PDGF] and epidermal growth factor [EGF] receptors) as a model system. Our studies showed that IFNs (alpha/beta and gamma) blocked PDGF-and phorbol ester- but not EGF-stimulated DNA synthesis and cell proliferation. While the ligand-stimulated receptor tyrosine phosphorylation and interaction with downstream signaling molecules, such as GRB2, were not affected, IFNs specifically blocked PDGF- and phorbol ester- but not EGF-stimulated activation of Raf-1, mitogen-activated protein kinases, and tyrosine phosphorylation of an unidentified 34-kDa protein. This inhibition could be detected as early as 5 min after IFN treatments and was insensitive to cycloheximide, indicating that de novo protein synthesis is not required. The IFN-induced inhibition acted upstream of Raf-1 kinase and downstream of diacyl glycerol/phorbol ester, suggesting that protein kinase C (PKC) is the potential primary target. Consistently, downregulation of PKC by chronic phorbol myristate acetate treatment or inhibition of PKC by H7 and staurosporine blocked PDGF- and phorbol myristate acetate- but not EGF-induced signaling and DNA synthesis. Moreover, incubating cells with antisense oligodeoxyribonucleotides of PKC delta eliminated production of PKC delta protein and specifically blocked PDGF- but not EGF-stimulated mitogenesis in these cells. Thus, these studies have elucidated a major difference in the early events of EGF-and PDGF-stimulated signal transduction and, more importantly, revealed a novel mechanism by which IFNs may execute their antiproliferative function.

3T3 Cells↗
PubMed1994

Role of angiotensin II in renal injury of deoxycorticosterone acetate-salt hypertensive rats.

To investigate the role of angiotensin II (Ang II) in hypertension-induced tissue injury, we gave TCV-116 (1 mg/kg per day PO), a nonpeptide Ang II type I receptor antagonist, or enalapril (10 mg/kg per day PO) to deoxycorticosterone acetate (DOCA)-salt hypertensive rats for 3 weeks and examined the effects on tissue mRNA levels for transforming growth factor-beta 1 (TGF-beta 1) and extracellular matrix components. Tissue mRNA levels were measured by Northern blot analysis. Renal mRNA levels for TGF-beta 1; types I, III, and IV collagen; and fibronectin in DOCA-salt hypertensive rats were increased by severalfold (P < .01) compared with sham-operated rats. In the aorta of DOCA-salt hypertensive rats, TGF-beta 1 and fibronectin mRNA levels were increased, but types I, III, and IV collagen mRNAs did not increase. In the heart, increased mRNA was found only for fibronectin. Thus, these gene expressions are regulated in a tissue-specific manner. TCV-116 or enalapril did not lower blood pressure in DOCA-salt hypertensive rats. However, the increase in renal mRNAs for TGF-beta 1 and extracellular matrix components in DOCA-salt hypertensive rats was significantly inhibited by treatment with TCV-116 or enalapril, which was associated with a significant decrease in urinary protein and albumin excretions and histological improvement of renal lesions. In contrast, in the aorta and heart these gene expressions were not affected by TCV-116 or enalapril. Thus, local Ang II may contribute to renal injury of DOCA-salt hypertension by stimulating the gene expression of TGF-beta 1 and extracellular matrix components.

Angiotensin II↗
PubMed1994

The deleterious effects of exogenous angiotensin I and angiotensin II on myocardial ischemia-reperfusion injury.

Angiotensin II is well known to have a cardiotoxic effects. However, it is still unclear whether exogenous angiotensin I or angiotensin II has a deleterious effect on myocardial ischemia-reperfusion injury. To examine this deleterious effects, we administered angiotensin I and angiotensin II to perfused hearts before ischemia, and measured creatine kinase (CK) release and cardiac function during subsequent reperfusion. Wistar Kyoto rats were used and the hearts were perfused by the Langendorff technique at a constant flow (10 ml/min). Seven hearts were perfused for 20 min and then subjected to 15 min of global ischemia (Control). In the experimental groups, during the 5 min before ischemia, we administered 100 ng/ml angiotensin I (Ang I; n = 9), 1 microgram/ml enalaprilat (ACEI; n = 5), both agents (ACEI + Ang I) (n = 6), or 10 ng/ml angiotensin II (Ang II; n = 6). The perfusates were then sampled to measure angiotensin II. After 15 min of ischemia, the hearts were reperfused with control perfusate. Throughout the 20 min of reperfusion, the effluent was collected to measure cumulative CK release. Angiotensin I increased coronary perfusion pressure (CPP) by 32 +/- 4 mmHg, however, the angiotension converting enzyme inhibitor inhibited the increase of CPP by angiotension I (11 +/- 1 mmHg) (p < 0.01). The contents of angiotensin II in the effluent in Ang I and Ang I + ACEI were 11.5 +/- 1.9 ng/ml and 4.0 +/- 0.5 ng/ml (p < 0.01). After 20 min of reperfusion, the left ventricular developed pressure was unchanged in all of the groups. CPP was also unchanged by ischemia in all of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗
PubMed1994

[Pharmacology of the renin-angiotensin system].

Recent developments in the techniques of molecular biology and the availability of inhibitors of the renin-angiotensin system have provided new insight into renin-angiotensin research. The control mechanism of renin release and the metabolism of circulating renin have been well characterized on the molecular level. Angiotensin II has been shown to play an important role not only in the regulation of blood pressure but also in cell growth and hypertrophy. ACE inhibitors are effective for the treatments of hypertension and heart failure. Furthermore, recent studies suggest that ACE inhibitors may prevent atherosclerosis and glomerulosclerosis. Angiotensin II receptor antagonists have similar beneficial effects. These effects of ACE inhibitors and angiotensin II-receptor antagonists may be mediated by growth factors and the extracellular matrix.

Angiotensin II↗
PubMed1994

Effect of erythrocyte mass on arterial blood pressure in dialysis patients receiving maintenance erythropoietin therapy.

Treatment of renal anemia with recombinant human erythropoietin (rEPO) frequently raises arterial blood pressure. The objective of this study was to determine whether this is a direct effect of rEPO or a consequence of the expansion of erythrocyte mass. Twenty-three chronic hemodialysis patients receiving maintenance rEPO therapy who had uncontrolled anemia due to iron deficiency were studied. It was anticipated that repletion of iron stores with iv iron dextran would restore rEPO responsiveness, leading to a gradual rise in hematocrit to the target values (0.30 to 0.33). The effect of the increase in hematocrit on arterial blood pressure could then be dissected from the direct effect of rEPO in patients receiving constant doses of rEPO throughout the study period. To this end, arterial blood pressure, iron indices, hematocrit, and measures of fluid balance were monitored at baseline and for a 10-wk period after iron repletion. In eight patients, the hematocrit transiently rose above 0.33, triggering a reduction in rEPO dosage. In the remaining 15 patients, rEPO dosage was held constant during the study period. In this subgroup, repletion of iron stores led to a rise in hematocrit from 0.25 +/- 0.04 to 0.32 +/- 0.04 (P < 0.001) within 4 wk. Despite the significant rise in hematocrit, both systolic and diastolic blood pressure values remained virtually unchanged. Likewise, body weight and interdialytic fluid gain were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Poor renal uptake of technetium-99m-DMSA and technetium-99m-MDP in a patient with Fanconi syndrome and near normal glomerular filtration rate.

We present a patient with Fanconi syndrome who demonstrated poor renal uptake of 99mTc-DMSA and high urinary concentration of the tracer. A 99mTc-DTPA scan was normal and the creatinine clearance only minimally decreased. These findings suggest that 99mTc-DMSA may be accumulated in the kidney by glomerular filtration and subsequent tubular reabsorption, with the nonabsorbed fraction appearing in the urine. In Fanconi Syndrome the tubular reabsorption of DMSA may also be reduced, thus explaining the poor renal uptake in this patient. A 99mTc-MDP bone scan showed faint renal uptake and diffuse high uptake mainly in the spine, demonstrating that the metabolic bone disease associated with Fanconi Syndrome can be another mechanism for poor renal visualization on bone scan.

Fanconi Syndrome↗
PubMed1994

Cepacidine A, a novel antifungal antibiotic produced by Pseudomonas cepacia. I. Taxonomy, production, isolation and biological activity.

Cepacidine A is a potent antifungal antibiotic produced by Pseudomonas cepacia AF 2001. The compound was isolated from the fermentation broth with 1 vol isopropyl alcohol, followed by the collection of the precipitation formed upon concentration of the extract. Purification was effected by chromatography on Diaion HP-20, alumina and reversed phase C18 followed by TLC on silica gel. These techniques afforded the two closely related compounds, cepacidine A1 and cepacidine A2. A mixture of these two compounds called capacidine A, showed high in vitro antifungal activity against the various animal and plant pathogenic fungi. The activity was diminished by the presence of serum. No antibacterial activity was demonstrable.

Anti-Bacterial Agents↗
PubMed1994

Cepacidine A, a novel antifungal antibiotic produced by Pseudomonas cepacia. II. Physico-chemical properties and structure elucidation.

Cepacidine A is a novel glycopeptide with a potent antifungal activity, which is produced by Pseudomonas cepacia AF 2001. Its molecular weight was determined by FAB-MS (m/z 1215). The compound is comprised of glycine (1), serine (2), 2,4-diaminobutyric acid (1), aspartic acid (1), beta-hydroxy tyrosine (1), beta-hydroxy asparagine (1), xylose (1) and 5,7-dihydroxy-3,9-diamino-octadecanoic acid (1). Unfortunately, cepacidine A is a mixture of A1 and A2, either of which is barely distinguishable. Cepacidine A2 includes asparagine (1) instead of beta-hydroxy asparagine (1) of cepacidine A1. The MS data and the NOESY, TOCSY and HMBC spectra show that cepacidine A is a cyclic peptide and xylose is connected to 5,7-dihydroxy-3,9-diaminooctadecanoic acid.

Anti-Bacterial Agents↗
PubMed1994

Renal protective effect of TCV-116 in stroke-prone spontaneously hypertensive rats.

We examined the effects of TCV-116, a non-peptide selective AT1 receptor antagonist, on cellular phenotype and on the expression of the transforming growth factor-beta 1 (TGF-beta 1) and extracellular matrix genes in the kidneys of stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were given vehicle or TCV-116 (10 mg/kg/day) by gastric gavage for 10 weeks (from the age of 22 to 32 weeks). Renal mRNA levels were measured by Northern blot analysis. In vehicle-treated 32-week-old SHRSP, urinary albumin excretion per 24 h was about 26-fold greater than that in age-matched Wistar-Kyoto (WKY) rats, and the mRNA levels of renal TGF-beta 1, fibronectin and collagen types I and III in SHRSP were all several-fold higher than those in WKY. Immunohistochemical studies showed the prominent presence of alpha-smooth muscle actin-expressing glomerular cells in SHRSP, in contrast to their absence in WKY. Treatment of SHRSP with TCV-116 decreased urinary albumin excretion and renal mRNA levels for TGF-beta 1 and for the above-mentioned extracellular matrix components. TCV-116 prevented the phenotypic modulation of glomerular cells in SHRSP. These results suggest that AT1 receptor antagonists may have powerful renal protective effects.

Albuminuria↗
PubMed1994

Keratinocyte growth factor causes cystic dilation of the mammary glands of mice. Interactions of keratinocyte growth factor, estrogen, and progesterone in vivo.

Keratinocyte growth factor (KGF) is a paracrine mediator of epithelial cell proliferation that has been reported to induce marked proliferation of mammary epithelium in rats. In this study, systemic administration of KGF into naive and oophorectomized mice causes mammary gland proliferation, as evidenced histologically by the appearance of cysts lined by a single layer of epithelium and by hyperplastic epithelium. Whole mount preparations of the mammary glands reveal that the histologically noted cysts are actually ducts that are dilated along much of their length. The histology of the mammary glands of KGF-treated mice is similar to the histology of fibrocystic disease in the human female breast. The response in mice differs significantly from the appearance of the mammary glands in KGF-treated rats in which ductal epithelial proliferation is most prominent. Estrogen and progesterone when administered in combination but not alone cause the development of numerous endbuds in the mouse mammary gland. KGF in estrogen- and progesterone-pretreated mice causes the growth of dilated ducts, hyperplastic epithelium within ducts and endbuds, and a fibrous metamorphosis of periductal adipose tissue. The mammary epithelial hyperplasia caused by KGF is rapidly reversible in both mice and rats after cessation of KGF treatment. The spectrum of KGF-, estrogen-, and progesterone-induced mammary histopathology in mice provides a model for the study of fibrocystic and hyperplastic breast disease.

Animals↗
PubMed1994

Hepatocarcinogenesis is the sequel to hepatitis in Z#2 alpha 1-antitrypsin transgenic mice: histopathological and DNA ploidy studies.

Z mutant-associated alpha 1-antitrypsin deficiency in human beings leads to hepatitis and, in some cases, hepatocellular carcinoma. To begin to delineate the molecular basis for the development of hepatocellular carcinoma in alpha 1-antitrypsin deficiency, we previously developed transgenic mice using human alpha 1-antitrypsin M and Z genomic clones. High-copy Z lineage mice (12 gene copies/haploid mouse genome; "Z#2") had hepatocytes distended with human alpha 1-antitrypsin deficiency globules. Hepatitis was present, and the morphological changes mimicked those observed in human alpha 1-antitrypsin deficiency-related liver disease. The numbers of hepatocytes containing alpha 1-antitrypsin globules decreased with age, and alpha 1-antitrypsin-negative nodular aggregates of hepatocytes increased in number and size. Hepatocytic dysplasia occurred as early as 6 wk and was almost universally present at 1 yr. Nodules of dysplastic cells demonstrating aneuploidy were seen as early as 10 wks. These became persistent, proliferative lesions. Dysplasia and aneuploidy distinctly increased with time and advancing microscopic stage as lesions progressed to malignancy. Tumors were seen after 1 yr as adenomas, which are aneuploid and most likely well-differentiated hepatocellular carcinoma, and borderline malignant lesions; and, in 82% of Z#2 mice 16 to 20 mo old, as invasive hepatocellular carcinoma. These observations suggest but do not conclusively prove that hepatocellular carcinoma in alpha 1-antitrypsin deficiency and other hepatic disorders arises as a result of a common, endogenously stimulated pathway for hepatocellular carcinogenesis.

Adenoma↗
PubMed1993

C-terminal peptide appendix in a class I tRNA synthetase needed for acceptor-helix contacts and microhelix aminoacylation.

The 10 class I tRNA synthetases have an N-terminal nucleotide-binding fold which contains the catalytic center. Insertions into the nucleotide-binding fold provide contacts for acceptor-helix interactions, which stabilize the amino acid acceptor end of the tRNA substrate in the active site. A separate and largely nonconserved C-terminal domain provides contacts with distal parts of the tRNA, including the anticodon. For Escherichia coli methionyl tRNA synthetase, whose structure is known, the C-terminal domain is predominantly alpha-helical and forms a loop which interacts with the anticodon trinucleotide located about 76 A from the amino acid attachment site. Fused to the end of this helical domain is a peptide which curls back into the N-terminal nucleotide-binding fold and region of the active site. We show here that mutations in this peptide appendix disrupt aminoacylation and binding of a 7 base pair microhelix substrate based on the acceptor stem of tRNA(fMet), without affecting interactions with ATP or methionine or with the tRNA(fMet) anticodon. The impairment of acceptor-helix interactions by mutation of the C-terminal peptide can offset favorable anticodon interactions and severely reduce aminoacylation of tRNA(fMet). Thus, in addition to, or as an alternative to, acceptor-helix-binding insertions into the N-terminal nucleotide-binding fold, C-terminal peptide epitopes in some class I enzymes may provide a mechanism for facilitating RNA microhelix interactions with the catalytic site.

Amino Acid Sequence↗
PubMed1993

Diversified sequences of peptide epitope for same-RNA recognition.

We replaced an essential RNA-binding, 30-amino acid helix-loop in an Escherichia coli tRNA synthetase with an inactive and simplified "generic" sequence having 23 of the 30 amino acids as alanine and serine. Wild-type residues were restored in random combinations to generate a library with a sequence complexity of about 1.9 x 10(7). Active molecules were obtained by genetic selection at a frequency of approximately 1% and contained variants with as many as 11 alanine/serine replacements and a total of 17 alanine/serine residues. These variants have activities which are thermodynamically competitive with that of the native protein and therefore are functionally and, most likely, conformationally equivalent.

Anticodon↗