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Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 991 records · Page 55Linked to original sources
PubMed1994

Occupancy of the serotonin transporter by fluoxetine, paroxetine, and sertraline: in vivo studies with [125I]RTI-55.

[125I]RTI-55 was used tracer doses to label serotonin (5-HT) transporters in vivo in the mouse brain. Fluoxetine, paroxetine, and sertraline, potent antidepressants and selective inhibitors of serotonin transporter sites, were administered in various doses and at various times. The doses and times that result in significant binding of the drugs to transporters correspond to doses and times where they are reported to have physiological effects. Estimates of occupancy rate and duration of binding to serotonin transporters were made. The rate of occupancy of the 5-HT transporter site was fastest for sertraline, intermediate for paroxetine and slowest for fluoxetine. Similarly, the duration of occupancy was significantly shorter for sertraline and paroxetine (approximately 10 h) than for fluoxetine (approximately 50 h). The results indicate that in competition studies, [125I]RTI-55 can be used to identify doses of drugs that are physiologically effective, to determine their relative rate of occupancy, and most importantly, to measure the residency time on the central serotonin transporter in vivo.

1-Naphthylamine↗
PubMed1994

A comparison of intravenous versus intraperitoneal chemotherapy for the initial treatment of ovarian cancer.

A phase III study was conducted comparing intraperitoneal (ip) versus intravenous (iv) cisplatin-based therapy for patients with newly diagnosed ovarian cancer to determine if the pharmacologic advantage of ip delivery could be translated into an improved response and survival rate. Twenty-nine patients were randomized to receive six cycles of ip cisplatin 200 mg/m2 plus ip etoposide 350 mg/m2 with iv thiosulfate protection given every 4 weeks; thirty-three patients were randomized to receive six cycles of iv cisplatin 100 mg/m2 plus iv cyclophosphamide 600 mg/m2 administered every 3 weeks. Patients were stratified by stage (IIC-IV) and size of residual disease (> or < or = 1 cm). The study was conducted in a community-wide setting. The complete response in evaluable patients was 48% in the ip group and 52% in the iv group. The surgical complete response rate for all patients on study, underestimated because not all patients in complete clinical remission had a second-look laparotomy, was 31% in the ip group and 33% in the iv group. There was no difference in the response rates between the treatment arms as a function of residual disease < or = or > 1 cm. With a median follow-up of 46 months (range 21-70 months) there is no difference in response duration or survival. Both regimens were well tolerated with comparable hematologic and nonhematologic toxicity.

Adult↗
PubMed1994

Phase I trial of cisplatin in combination with glutathione.

We treated 16 patients in a phase I trial of escalating doses of intravenous cisplatin in combination with the chemoprotectant glutathione given every 21 days. Forty-three of 44 cycles (98%) were evaluable, 85% of cycles were given on time, and the median number of cycles per patient was 2. Dose-limiting nephrotoxicity was reached at a dose of 175 mg/M2 of cisplatin. Other toxicities included ototoxicity in 7 patients (44%) and grade 3 to 4 nausea and vomiting in 15 evaluable cycles (34.9%). Myelosuppression was infrequent. An increase to 175% of standard cisplatin dose intensity is attainable with the administration of glutathione; however, toxicity is substantial and the number of tolerated cycles is limited. Alternatives to the single bolus dose schedule studied in the present trial should be explored in order to better define the clinical utility of glutathione in combination with high-dose cisplatin.

Adult↗
PubMed1994

Effect of electrical tooth stimulation on blood flow, interstitial fluid pressure and substance P and CGRP-immunoreactive nerve fibers in the low compliant cat dental pulp.

The effect of vasodilation on simultaneously measured interstitial fluid pressure (IFP, micropuncture) and blood flow (laser-Doppler) in the low compliant pulpal connective tissue was investigated in 10 cats. Vasodilation was induced by electrical stimulation of the tooth after pretreatment with the sympathetic blocker guanethidine. Visualization of the sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) was performed using immunocytochemistry. The study was designed to answer the following questions. (1) Does vasodilation promptly increase IFP in low compliant tissues? (2) Does an increase in IFP counteract the blood flow increase? (3) Does repeated electrical stimulation cause reduced staining of CGRP- and SP-immunoreactive nerve fibers in the dental pulp? Electrical stimulation resulted consistently in a nearly synchronous increase in both blood flow and IFP. IFP was nearly doubled, from 6.3 +/- 0.18 mm Hg in control to 11.7 +/- 0.44 mm Hg, whereas blood flow increased by 28%. However, despite continued vasodilation the IFP fell to control level, or even lower, within 1-5 min. The results indicate that the increased IFP will promote fluid absorption into the blood, counteracting a further IFP increase in low compliant tissues during vasodilation. Accordingly, transmural pressure is only transitorily reduced and compression of vessels does not take place. There was considerably less CGRP- and SP-immunoreactive fibers in the stimulated teeth than in the contralateral controls, suggesting that the vasodilation was caused by liberation of these sensory neuropeptides.

Animals↗
PubMed1994

The role of activation of the sympathetic nervous system in the central pressor action of calcitonin gene-related peptide in conscious rats.

The effects of intracerebroventricular (i.c.v.) administration of calcitonin gene-related (CGRP) on blood pressure and heart rate (HR), and the underlying mechanisms were studied in conscious rats. CGRP (0.1-3.0 nmol i.c.v.) increased mean arterial blood pressure (MABP) and HR. CGRP (3.0 nmol i.c.v.) also significantly increased both plasma norepinephrine and epinephrine concentrations. Pretreatment with 16.5 nmol i.c.v. CGRP(8-37), a specific CGRP receptor antagonist, significantly inhibited the i.c.v. CGRP (1.0 nmol)-induced increases in MABP and HR. Phenoxybenzamine inhibited the i.c.v. CGRP-induced increase in MABP, while propranolol suppressed the tachycardiac response to i.c.v. CGRP. Chemical sympathectomy by 6-hydroxydopamine inhibited the increases in MABP and HR produced by i.c.v. CGRP. These results suggest that the central pressor and tachycardiac effects of i.c.v. CGRP are mediated by catecholamine release due to stimulation of sympathetic nervous system activity, possibly via specific CGRP receptors in the central nervous system.

Animals↗
PubMed1994

An extended-release formulation of methotrexate for subcutaneous administration.

Methotrexate is a cell-cycle phase-specific antimetabolite that requires prolonged exposure for optimal efficacy. However, the in vivo half-life is short, and repeated administrations are required for optimal efficacy. Methotrexate was encapsulated into a lipid-based drug-delivery system to create an extended-release formulation (Depo/methotrexate) for subcutaneous administration. Pharmacokinetics and efficacy studies were done in BDF1 mice. Depo/methotrexate increased the methotrexate plasma half-life by a factor of 190, from 0.53 to 100 h. Plasma peak levels of the encapsulated drug were 120-fold lower than those of unencapsulated methotrexate, whereas the AUCs (areas under the concentration-time curve) were similar. As a consequence of the extended drug release, the single-dose potency of methotrexate against the L1210 leukemia model was increased by a factor of about 130 without producing significant changes in the therapeutic index. In conclusion, Depo/methotrexate appears to have potential usefulness as an extended-release formulation of methotrexate.

Animals↗
PubMed1994

Cardioprotective effect of the angiotensin II type 1 receptor antagonist TCV-116 on ischemia-reperfusion injury.

We investigated the protective effect of angiotensin II (Ang II) type 1 receptor antagonist on myocardial ischemia-reperfusion injury and the role of exogenous Ang II to this injury in perfused hearts. We orally administered TCV-116 (Ang II type 1 receptor antagonist) and delapril (angiotensin converting enzyme inhibitor) to Wistar rats for 1 week and measured the immunoreactive cardiac Ang II. Immunoreactive cardiac Ang II (pg/gm tissue) was 14.3 +/- 2.0 in control group, 11.8 +/- 0.8 in TCV-116-treated group, and 7.3 +/- 0.6 in delapril-treated group (p < 0.05 compared to TCV-116-treated group; p < 0.01 compared to control group). The 15 hearts (five rats in each group) were perfused by a langendorff method and global ischemia was maintained for 30 min. Both TCV-116 and delapril were found to improve postischemic cardiac function and decrease reperfusion creatine kinase (CK) release. Ang II injection before ischemia worsened postischemic cardiac function and increased reperfusion CK release. Only TCV-116 prevented this injury. These data indicated that TCV-116 Ang II type 1 receptor antagonist was effective against myocardial ischemia-reperfusion injury, and exogenous Ang II accelerated this injury through Ang II type 1 receptor.

Angiotensin II↗
PubMed1994

Ultrastructure of quick-frozen secretory ameloblasts of the rat molar tooth.

Ameloblasts in molar tooth germs from 4 to 12-day-old neonatal rats were quick-frozen and then freeze-substituted in acetone-tannic acid and acetone-osmium tetroxide. Following quick freezing and freeze-substitution, the preservation of ameloblasts was principally the same as seen in conventionally-fixed ones. Several differences, however, became apparent between two methods. Concerning enamel formation, the quick-freezing procedure greatly improved the preservation including that of the extrusion of secretory granules into the extracellular space. The exocytosis is a type of merocrine secretion. The precursor stippled material was demonstrated at the front of Tomes' processes and in the intercellular space of the distal terminal junction. In the more advanced stage, the stippled material tended to decrease gradually in amount. Prior to the formation of the typical Tomes' process, large secretory granules fused directly with the distal plasma membrane, which plays a role in the formation of prismless enamel. After the typical Tomes' process had formed, secretory granules containing electron-dense material instead of the large secretory granules accumulated in the distal portion of the Tomes' process. These latter secretory granules had two different destinations; i.e. the granules discharged their contents into the infoldings of the distal part of Tomes' process and into the infoldings of the lateral cell membrane. These types of secretion seem to have a functional role in the rod or inter-rod enamel formation. The ultrastructure of the stippled material consisted of 3-dimensionally interconnected strands after quick freezing, which is different from the appearance of granules embedded in amorphous material after conventional fixation. The stippled material was seen in the intercrystal space among the newly formed crystals. Also, an extensive tubulo-vesicular structure was preserved in both the cell body and Tomes' process. The present data suggest that the membrane of this structure showed a smooth contour opening to the extracellular space, and also an intimate relationship with the secretory granules.

Ameloblasts↗
PubMed1994

Ethnic identity, role integration, quality of life, and depression in Korean-American women.

Little is known about how living between two cultures affects the mental health of immigrant women. This study examined the relationships between ethnic identity, role integration, quality of life, and depression in 76 Korean-American women. Quality of life was positively associated with role integration (r = .68, p < .01). Role integration and quality of life were negatively and significantly associated with depression (r = -.59 and r = -.72, p < .01, respectively). An exploratory path analysis was performed to examine the relationships between demographics and conceptual variables. Only quality of life and length of residence in the United States were strongly associated with depression. Findings have implications for psychiatric nursing practice.

Adult↗
PubMed1994

Cystosolic chaperonin subunits have a conserved ATPase domain but diverged polypeptide-binding domains.

CCT (also called the TCP-1 complex or TriC) is a chaperonin found in the eukaryotic cytosol, and has unique structural and functional features. Unlike homo-oligomeric chaperonins, CCT comprises at least eight different subunits, and appears to have a limited range of physiological substrates. We have analysed CCT sequences in light of the recent determination of the crystal structure and mutational identification of the functional domains of the bacterial chaperonin GroEL. A high level of identity among all chaperonin subunits is observed in those regions that correspond to the ATP-binding site of GroEL. By contrast, no significant identity is shared in the region corresponding to the polypeptide-binding region of GroEL, either between CCT subunits or between CCT subunits and GroEL. This suggests that the polypeptide-binding sites of CCT subunits have diverged both from each other and from GroEL, which may explain the apparently different range of substrates recognized by CCT.

Adenosine Triphosphatases↗
PubMed1994

Contribution of renal angiotensin II type I receptor to gene expressions in hypertension-induced renal injury.

Recent evidence indicates that transforming growth factor-beta 1 (TGF-beta 1) plays an important role in renal fibrosis via stimulation of extracellular matrix synthesis. The present study was undertaken to investigate the role of angiotensin II type I receptor (AT1 receptor) in hypertension-induced renal injury. Twenty-two-week-old stroke-prone spontaneously hypertensive rats (SHRSP), which had established hypertension and moderate renal damage, were orally given TCV-116, a selective non-peptide AT1 receptor antagonist (0.1, 1 or 10 mg/kg/day), enalapril (10 mg/kg/day) or vehicle once a day for 10 weeks. At the end point of the treatment, we examined renal function, the gene expressions of TGF-beta 1 and extracellular matrix components in the interstitium [collagen types I (COI) and III (COIII), fibronectin (FN)] and the basement membrane (COIV and laminin), and renal microscopic morphology in rats aged 32 weeks. In vehicle-treated 32 week-old SHRSP with renal dysfunction and nephrosclerosis, renal mRNA levels for TGF-beta 1, COI, COIII, FN, COIV were all several-fold higher than in WKY. Thus, renal TGF-beta 1 gene expression was enhanced in SHRSP, which may contribute to the increased renal expressions of COI, COIII, FN, COIV in SHRSP. Treatment with TCV-116 (0.1 mg/kg/day) in SHRSP, in spite of no reduction of blood pressure, decreased renal mRNA levels for TGF-beta 1, COI, COIII, FN, COIV, being accompanied by the significant decrease in urinary protein and albumin excretion, blood urea nitrogen and plasma creatinine. Treatment with TCV-116 (10 mg/kg/day) in SHRSP decreased mRNAs for TGF-beta 1, COI, COIII, FN and COIV to almost the same levels as WKY, being associated with normalization of urinary protein and albumin excretion and the prevention of nephrosclerosis, as judged by microscopic histological observations. On the other hand, the effects of enalapril (10 mg/kg/day) on the above mentioned mRNA levels, renal function and renal morphology were weaker than those of TCV-116 (10 mg/kg/day) and were as much as TCV-116 (1 mg/kg/day). These results suggest that independently of hypotensive action, AT1 receptor antagonist has a potent renal protective effect by inhibiting the gene expression of renal TGF-beta 1 and extracellular matrix components.

Angiotensin II↗
PubMed1994

Localization and quantitation of active renin in monkey kidney by radioinhibitor binding and in vitro autoradiography.

We developed an in vitro autoradiographic method to localize and quantify active renin in primate tissues. Active renin in monkey kidney sections was labeled with the primate specific renin inhibitor, 3H-CGP29287, and quantitated with autoradiography and computerized densitometry. Microscopic emulsion autoradiography was carried out to clarify the detailed localization of the binding. Non-specific binding to aspartyl proteases other than renin was blocked using 1 mumol/L of N-acetyl-pepstatin. To assess the usefulness of this procedure, binding of 3H-CGP29287 was examined both by film and emulsion autoradiography in the kidneys of monkeys (Macaca fuscata) that were given chronically either an angiotensin converting enzyme inhibitor (trandolapril), an angiotensin II receptor antagonist (E4177), or vehicle. 3H-CGP29287 was found to bind very selectively to the juxtaglomerular apparatus (JGA) under control conditions. In monkeys treated with trandolapril or E4177, 3H-CGP29287 binding was increased in proportion to the increase in renal renin concentration determined enzymatically; in these kidneys, emulsion autoradiography revealed radioinhibitor binding extending far from the JGA. The potency of a series of unlabeled renin inhibitor in competing for 3H-CGP29287 binding in the autoradiographic system closely paralleled their potencies, as determined in inhibiting renin by an enzymatic assay. This technique permits specific labeling of the catalytic site of renin in the monkey kidney sections.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Transforming growth factor beta 1 and extracellular matrix gene expression in isoprenaline induced cardiac hypertrophy: effects of inhibition of the renin-angiotensin system.

OBJECTIVE: The aim was to investigate changes in cardiac transforming growth factor beta 1 (TGF-beta 1), fibronectin, and collagen types I and III mRNA levels in isoprenaline induced cardiac hypertrophy, and the effects of delapril, an angiotensin converting enzyme inhibitor, and TCV-116, an angiotensin II type 1 receptor antagonist, on this hypertrophy. METHODS: Rats were continuously infused with saline and low or high dose of isoprenaline (0.5 or 3 mg.kg-1.d-1) by an osmotic minipump for 24 h, 48 h or 7 d. Treatment with delapril (100 mg.kg-1.d-1) or TCV-116 (10 mg.kg-1.d-1) was started from 1 d before the implantation of minipump to the end of experiments. After the experimental periods, left ventricular weight was measured and the mRNA was extracted and measured by northern blot hybridisation. RESULTS: Both low and high doses of isoprenaline infusion resulted in increased left ventricular weight. With low dose infusion, cardiac TGF-beta 1 mRNA was not stimulated throughout the infusion, while fibronectin mRNA and collagen types I and III mRNAs began to increase at 24 h and 48 h, respectively, after the infusion. In high dose isoprenaline infusion, not only was extracellular matrix mRNA but also TGF-beta 1 mRNA in the ventricle significantly increased. TCV-116 prevented isoprenaline induced left ventricular hypertrophy as much as delapril. However, with delapril or TCV-116, the time course of TGF-beta 1 and ECM mRNA expression was almost similar to isoprenaline infusion only. CONCLUSIONS: The extracellular matrix mRNA expressions are enhanced in myocardial hypertrophy by a low dose of isoprenaline, which is probably not mediated by TGF-beta 1. The preventive effects of TCV-116 on this hypertrophy indicate that the inhibitory effects of angiotensin converting enzyme inhibitor on cardiac hypertrophy are due to the inhibition of angiotensin II and that angiotensin II type I receptor plays an important role in isoprenaline induced left ventricular hypertrophy. However, the renin-angiotensin system may play a minor role in isoprenaline induced cardiac fibrosis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Analysis of a recombination hotspot for gene conversion occurring at the HIS2 gene of Saccharomyces cerevisiae.

The properties of gene conversion as measured in fungi that generate asci containing all the products of meiosis imply that meiotic recombination initiates at specific sites. The HIS2 gene of Saccharomyces cerevisiae displays a high frequency of gene conversion, indicating that it is a recombination hotspot. The HIS2 gene was cloned and sequenced, and the cloned DNA was used to make several different types of alterations in the yeast chromosome by transformation; these alterations were used to determine the location of the sequences necessary for the high levels of meiotic conversion observed at HIS2. Previous work indicated that the gene conversion polarity gradient is high at the 3' end of the gene, and that the promoter of the gene is not necessary for the high frequency of conversion observed. Data presented here suggest that at least some of the sequences necessary for high levels of conversion at HIS2 are located over 700 bp downstream of the end of the coding region, extend over (at least) several hundred base pairs, and may be quite complex, perhaps involving chromatin structure. Additional data indicate that multiple single base heterologies within a 1-kb interval contribute little to the frequency of gene conversion. This contrasts with other reports about the role of heterologies at the MAT locus.

Amino Acid Sequence↗
PubMed1994

A case of the 'dapsone syndrome'.

The 'dapsone syndrome' developed in a 44-year-old woman who was treated for pyoderma gangrenosum with 100 mg/day dapsone for about 5 weeks. Symptoms included fever, malaise, jaundice with hepatic dysfunction, lymphadenopathy, mononucleosis and dermatitis. These symptoms disappeared with 30 mg/day of oral prednisolone. A lymphocyte stimulation test with dapsone was positive, as was the delayed-type intradermal skin test with 0.5 and 0.05% dapsone in saline. Immunohistochemical studies of the rash and skin test reaction revealed that the dominant infiltrating T cells in the upper dermis were of the Leu 2a+ cytotoxic/suppressor-type rather than the Leu 3a+ helper/delayed hypersensitivity-type.

Adult↗