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Biomedical subjects

D K Kim

Publications and source records attributed to D K Kim.

At least 163 records · Page 9Linked to original sources
PubMed1999

Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.

OBJECTIVES: SS-cream is a topical agent made from the extracts of natural products for treating premature ejaculation (PE). To determine the optimal clinical dosage of SS-cream on PE, we investigated the safety and efficacy of SS-cream with various doses. A double blind, randomized placebo controlled clinical study was performed. METHODS: Fifty patients completed the study. Mean age of the patients was 37.1+/-1.O y and mean ejaculatory latency was 1.35+/-0.07 min. Sexual satisfaction rate of both the partner and patient was 16.2%. Each patient was instructed to apply the different cream (placebo, SS-cream 0.05, 0.10, 0.15, 0.20 g) on glans penis 1 h before sexual intercourse in random fashion. The ejaculatory latency was measured by stop watch and the satisfaction rate of both partner and patient was also recorded two times in the screening period and after the application of each test drugs. Clinical efficacy was considered if ejaculatory latency was prolonged more than 2 min and sexual satisfaction rate increased more than 20% than that of pretest values. RESULTS: The mean ejaculatory latencies were significantly prolonged after using various test drugs (placebo 2.27+/-0.32, SS-cream 0.05 g 4.47+/-0.81, 0.10 g 5.34+/-0.79, 0.15 g 6.22+/-0.87, 0.20 g 11.06+/-1.17 min, respectively). Clinical efficacies evaluated by ejaculatory latency were placebo 18%, SS-cream 0.05 g 30%, 0.10 g 60%, 0.15 g 54%, 0.20 g 84%, respectively. The satisfaction rate was also significantly increased dose-dependently (placebo 26%, SS-cream 0.05 g 60%, 0.10 g 70%, 0.15 g 78%, 0.20 g 90%, respectively). A side effect such as local mild burning sensation was noted in 35/250 times (14%) and no adverse effect on sexual function and no systemic side effects were observed. From the result of logistic regression analysis on clinical efficacy, the ED50 of SS-cream was obtained as 0.10 g. SS-cream 0.20 g was effective in 84% without any serious systemic side effects. CONCLUSION: From the above results, our conclusions are that SS-cream is effective on the treatment of PE with a few local side effects and that clinical optimal dose of SS-cream is 0.20 g.

Administration, Topical↗
PubMed1999

Antioxidative and proapoptotic effects of riluzole on cultured cortical neurons.

Riluzole is used clinically in patients with amyotrophic lateral sclerosis. As oxidative stress, in addition to excitotoxicity, may be a major mechanism of motoneuron degeneration in patients with amyotrophic lateral sclerosis, we examined whether riluzole protects against nonexcitotoxic oxidative injury. Probably reflecting its weak antiexcitotoxic effects, riluzole (1-30 microM) attenuated submaximal neuronal death induced by 24-h exposure to 30 microM kainate or NMDA, but not that by 100 microM NMDA, in cortical cultures. Riluzole also attenuated nonexcitotoxic oxidative injury induced by exposure to FeCl3 in the presence of MK-801 and CNQX. Consistent with its antioxidative effects, riluzole reduced Fe3+-induced lipid peroxidation, and inhibited cytosolic phospholipase A2. By contrast, riluzole did not attenuate neuronal apoptosis induced by staurosporine. Rather unexpectedly, 24-48-h exposure to 100-300 microM riluzole induced neuronal death accompanied by nuclear and DNA fragmentations, which was attenuated by caspase inhibitor carbobenzyloxy-Val-Ala-Asp-fluoromethyl ketone but not by protein synthesis inhibitor cycloheximide. The present study demonstrates that riluzole has direct antioxidative actions, perhaps in part by inhibiting phospholipase A2. However, in the same neurons, riluzole paradoxically induces neuronal apoptosis in a caspase-sensitive manner. Considering current clinical use of riluzole, further studies are warranted to investigate its potential cytolethal effects.

Animals↗
PubMed1999

Phase II trial of a novel platinum analog, SKI 2053R, in patients with previously untreated extensive-stage small-cell lung cancer.

A phase II trial of a novel platinum analog, SKI 2053R, was performed in patients with previously untreated extensive-stage disease (ED) small-cell lung cancer (SCLC). SKI 2053R was administered at the dose of 400 mg/m2 every 3 to 4 weeks as a 1-h infusion. After the first cycle, the dose was escalated to 440 mg/m2 based on toxicity. Thirty-eight patients (31 male) were enrolled between June 1995 and August 1997. The median age was 61 years (range, 36-70 years). Six of 37 evaluable patients achieved a partial response (16.2%; 95% confidence interval [CI], 4.4-28.0%). The durations of response were 1.1, 1.5, 1.7, 1.9, 3.4, and 4.6 months. The estimated median survival time was 7.4 months (95% CI, 5.1-9.7 months). Grade 3 or 4 toxicities were not observed. Grade 1 to 2 leukopenia, anemia, and thrombocytopenia were seen in 5 of 68 cycles, 16 of 68, and 2 of 68, respectively. Nonhematologic toxicities included grade 1 to 2 nausea or vomiting (30 of 68 cycles), nephrotoxicity (27 of 68), and hepatotoxicity (13 of 68). SKI 2053R showed a modest antitumor activity with limited toxicities in patients with ED SCLC. Further clinical trials are warranted in SCLC with a higher dose of SKI 2053R.

Adult↗
PubMed1999

Bacterial meningitis associated with lumbar drains: a retrospective cohort study.

OBJECTIVES: The infective potential of lumbar drainage is an important topic deserving particular study. The aetiology, incidence, and clinical findings associated with bacterial meningitis are described in patients having continuous lumbar CSF drainage to treat communicating hydrocephalus after subarachnoid haemorrhage or CSF leaks after traumatic dural rents. METHODS: Retrospective review of the records of patients with a positive CSF bacterial culture who underwent lumbar drain placement over a 39 month period. RESULTS: Thirteen cases of bacterial meningitis occurred subsequent to the use of 312 lumbar drain kits (4.2%). All meningitic patients had CSF pleocytosis, but not all had peripheral leukocytosis. Fever, peripheral leukocytosis, and CSF pleocytosis did not help to differentiate the presence of bacterial meningitis from other infections. Eight patients had prior CSF drainage procedures, including ventriculostomy (n=5) or lumbar drain (n=5) placements; two patients received both procedures. Six of 13 patients developed their CSF infection within 24 hours of lumbar drain insertion. Six of 13 patients developed meningitis while receiving antibiotics for other reasons. CONCLUSIONS: External lumbar drainage seems to carry a low risk of infectious meningitis and offers a safe alternative to ventriculostomy or serial lumbar punctures. Antibiotics do not seem to protect completely against developing the infection. The infection happens most often with skin organisms. The meningitis often appears within 24 hours after lumbar drain placement. Daily CSF samples should include bacterial cultures but cell counts may not offer any additional useful information in diagnosing the complication. Lumbar drain insertion and management need not be confined to the intensive care unit.

Adult↗
PubMed1999

Pharmacokinetic imaging of 11C ethanol with PET in eight patients with hepatocellular carcinomas who were scheduled for treatment with percutaneous ethanol injection.

PURPOSE: To evaluate the carbon 11 ethanol kinetics with positron emission tomography after intratumoral injection of the tracer and assess its redistribution and dilution in patients who have hepatocellular carcinomas and who were scheduled for treatment with percutaneous ethanol injection. MATERIALS AND METHODS: The study included eight patients with hepatocellular carcinomas. 11C ethanol was administered via a puncture needle positioned with ultrasonographic guidance. Parametric images based on the Fourier transformation were created for further analysis of the local distribution patterns of the tracer. The ratio of the 45-minute postinjection standardized uptake value to the 5-minute postinjection standardized uptake value was used for the evaluation of ethanol dilution. RESULTS: Five of eight tumors demonstrated almost constant uptake values after the initial distribution phase. In contrast, a rapid elimination of the 11C ethanol from the tumor was documented in three of eight tumors. The 45 minute-to-5 minute ratio was 0.18-0.67 (median value, 0.56) in the tumors. The time-activity curves of the normal liver parenchyma increased slowly but steadily with time owing to a low ethanol elimination from the tumor. Fourier transformation demonstrated inhomogeneous parts on the amplitude images in seven of eight tumors and random redistribution on the phase images in six of eight tumors. CONCLUSION: Inhomogeneous drug distribution and drug dilution in the target area are likely to be the major limiting parameters for therapy response.

Aged↗
PubMed1999

Increased group IV cytosolic phospholipase A2 activity in lungs of sheep after smoke inhalation injury.

Increased phospholipase A2 (PLA2) activity was measured in cytosolic fractions of lungs from sheep exposed to smoke from burning cotton or to synthetic smoke consisting of carbon and acrolein, a cotton smoke toxin. Three peaks of PLA2 activity were identified by heparin-Sepharose chromatography. The heparin-nonbinding PLA2 activity was twofold higher in the extracts from lungs exposed to smoke than in normal lungs. This activity was identified as the group IV 85-kDa cytosolic PLA2 (cPLA2). The activities of the forms of PLA2 that bound to heparin did not change after smoke exposure. Those activities showed a pH optimum of 9.0, required a millimolar Ca2+ concentration for full activity, and were inhibited by 5 mM dithiothreitol. One activity eluted at an NaCl concentration typical for group Ib and V PLA2 and had the expected substrate specificity. The other form of lung PLA2 that bound heparin was a group II PLA2. Lung myeloperoxidase activity increased progressively with increased exposure to smoke. cPLA2 was identified in sheep neutrophils. With 30 breaths of smoke exposure, there was an increase in cPLA2 activity without a difference in immunoreactivity on Western blot, indicating that the increased activity was not due to increased amounts of protein. In conclusion, smoke induces increases in resident lung cell cPLA2 activity that is likely responsible for eicosanoid production, leading to lung inflammation and bronchoconstriction.

Animals↗
PubMed1999

Angiotensin II stimulates proliferation of adventitial fibroblasts cultured from rat aortic explants.

It has been proposed that the local renin-angiotensin system is activated in the adventitia after vascular injury. However, the physiological role of Angiotensin II (Ang II) in the adventitia has not been studied at a cellular level. This study was designed to assess the role of Ang II in the growth response of cultured adventitial fibroblasts (AFs). Adventitial explants of the rat thoracic aorta showed outgrowth of AFs within 5-7 days. Ang II caused hyperplastic response of AF cultures. The Ang II-induced mitogenic response of AFs was mediated primarily by the AT1 receptor. Ang II caused a rapid induction of immediate early genes (c-fos, c-myc and jun B). Induction of c-fos expression was fully blocked by an AT1 receptor antagonist but not by an AT2 receptor antagonist. Epidermal growth factor (EGF), platelet-derived growth factor-BB (PDGF-BB) and basic fibroblast growth factor (bFGF) induced DNA synthesis in AFs. Co-stimulation of AFs with the growth factors and Ang II potentiated the incorporation of 3H-thymidine into DNA. Results from this study indicate that Ang II causes mitogenesis of AFs via AT1 receptor stimulation and potentiates the responses to other mitogens. These data suggest that the Ang II may play an important role in regulating AF function during vascular remodeling following arterial injury.

Angiotensin II↗
PubMed1999

Correlation between EGFR and c-erbB-2 oncoprotein status and response to neoadjuvant chemotherapy in cervical carcinoma.

Neoadjuvant chemotherapy prior to definitive radical surgery or radiotherapy may be effective in reducing tumor volume or clinical stage and may even enhance pelvic control and survival. However, there are significant limitations to the use of neoadjuvant therapy in the non-responder group. They include delayed total treatment course, the presence of drug resistant clones which result in accelerated tumor growth, and limited bone marrow reserve for subsequent definitive therapy. Thus, there is a need to identify parameters providing a more precise indication of the response to neoadjuvant chemotherapy in patients with invasive cervical cancer. From Jan. 1995 to Jan. 1996, neoadjuvant chemotherapy with 3 courses of cisplatin and vincristine was used in 32 patients with invasive cervical cancer (FIGO stage Ib to IIIb; tumor size greater than 2 cm). Prior to chemotherapy, quantitative tissue levels of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene protein were measured by using an enzyme-linked immunosorbent assay (ELISA). Tumor size was estimated before and after chemotherapy. Relations between oncoproteins and reductions of tumor size were evaluated. Tumor size prior to neoadjuvant chemotherapy did not show any correlation with either the concentrations of EGFR or c-erbB-2 oncoprotein. As well, the tumor reduction index did not manifest any correlation with EGFR, it did had an inverse linear correlation with the c-erbB-2 oncoprotein levels (Rs = -0.71, P < 0.05). The results of this study suggest that c-erbB-2 oncoprotein is associated with a reduced response to neoadjuvant chemotherapy in primary treatment of invasive cervical cancer and may be useful in directing therapeutic approaches.

Adult↗
PubMed1999

Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells.

Ginsenoside Rh2 (G-Rh2) isolated from the root of Panax ginseng has been shown to have anti-cancer proliferation, differentiation and chemopreventive effects in certain cancer cell types. We investigated the mechanism of G-Rh2-induced growth inhibition in MCF-7 human breast carcinoma cells. G-Rh2 significantly inhibited the cell growth in a concentration-dependent manner, which effect was reversible, and induced a G1 arrest in cell cycle progression. G-Rh2 treatment down-regulated the protein level of cyclin D3 but upregulated the expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1. The increased levels of p21 were associated with increased binding of p21 and Cdk2 concomitant with marked decrease in Cdk2 and cyclin E-dependent kinase activities with no changes in Cdk2 and cyclin E expression. G-Rh2 markedly reduced the phosphorylated retinoblastoma protein (pRb) and enchanced association of unphosphorylated pRb and the transcription factor E2F-1. These data suggest that G-Rh2 inhibited the growth of MCF-7 cells, by inducing protein expression of p21 and reducing the protein levels of cyclin D which resulted in the down-regulation of cyclin/Cdk complex kinase activity, decreasing phosphorylation of pRb, and inhibiting E2F release.

Antineoplastic Agents↗
PubMed1999

Enhanced secretory group II PLA2 activity in the tears of chronic blepharitis patients.

PURPOSE: Phospholipase A2 (PLA2) hydrolyzes phospholipids, one of the important constituents of human meibomian gland secretions. This study was performed to investigate PLA2 type and activity in the tears of chronic blepharitis patients compared to those of normal persons. METHODS: Tear samples of 36 patients and 10 normal persons were collected in non-heparinized microcapillary tubes. PLA2 activity in the tears was measured by Dole's method, and the results of the blepharitis patients were compared to those of the normal persons. The characterization of PLA2 was performed by the head group preference test and the dithiothreitol (DTT) sensitivity test. The classification of PLA2 type was done using Western blot analysis with anti-human secretory PLA2 antibody. RESULTS: No statistically significant differences were found among the six categories of chronic blepharitis. However, the mean PLA2 activity in the tears of the chronic blepharitis patients was about two times higher than that of the normal controls with statistical significance (P < 0.05). The PLA2 substrate specificity test revealed group II PLA2 activity. Furthermore, the group II PLA2 was identified as a 14 kDa band in Western blot analysis using an antibody raised against human secretory group II PLA2. CONCLUSIONS: Secretory group II PLA2 activity was significantly enhanced in the tears of the chronic blepharitis patients compared with that of the normal controls. It is suggested that this increased enzymatic activity may decrease the tear film stability through increased hydrolysis of phospholipids.

Adult↗
PubMed1999

Automation and integration of components for generalized semantic markup of electronic medical texts.

Our group has built an information retrieval system based on a complex semantic markup of medical textbooks. We describe the construction of a set of web-based knowledge-acquisition tools that expedites the collection and maintenance of the concepts required for text markup and the search interface required for information retrieval from the marked text. In the text markup system, domain experts (DEs) identify sections of text that contain one or more elements from a finite set of concepts. End users can then query the text using a predefined set of questions, each of which identifies a subset of complementary concepts. The search process matches that subset of concepts to relevant points in the text. The current process requires that the DE invest significant time to generate the required concepts and questions. We propose a new system--called ACQUIRE (Acquisition of Concepts and Queries in an Integrated Retrieval Environment)--that assists a DE in two essential tasks in the text-markup process. First, it helps her to develop, edit, and maintain the concept model: the set of concepts with which she marks the text. Second, ACQUIRE helps her to develop a query model: the set of specific questions that end users can later use to search the marked text. The DE incorporates concepts from the concept model when she creates the questions in the query model. The major benefit of the ACQUIRE system is a reduction in the time and effort required for the text-markup process. We compared the process of concept- and query-model creation using ACQUIRE to the process used in previous work by rebuilding two existing models that we previously constructed manually. We observed a significant decrease in the time required to build and maintain the concept and query models.

Abstracting and Indexing↗
PubMed1998

Takayasu's arteritis presenting with focal periostitis affecting two limbs.

Takayasu's arteritis (TA) is a vasculitis of large and medium sized arteries. Involvement of bone in TA is very rare. We report a case of young woman who presented with multiple painful bone lesions which were identified as periostitis with new bone formation associated with TA. Our case is unique in that bony involvement in TA could occur independent of vascular stenosis.

Adult↗
PubMed1998

Evidence for a voltage-dependent enhancement of neurotransmitter release mediated via the synaptic protein interaction site of N-type Ca2+ channels.

Secretion of neurotransmitters is initiated by voltage-gated calcium influx through presynaptic, voltage-gated N-type calcium channels. These channels interact with the SNARE proteins, which are core components of the exocytosis process, via the synaptic protein interaction (synprint) site in the intracellular loop connecting domains II and III of their alpha1B subunit. Interruption of this interaction by competing synprint peptides inhibits fast, synchronous transmitter release. Here we identify a voltage-dependent, but calcium-independent, enhancement of transmitter release that is elicited by trains of action potentials in the presence of a hyperosmotic extracellular concentration of sucrose. This enhancement of transmitter release requires interaction of SNARE proteins with the synprint site. Our results provide evidence for a voltage-dependent signal that is transmitted by protein-protein interactions from the N-type calcium channel to the SNARE proteins and enhances neurotransmitter release by altering SNARE protein function.

Action Potentials↗
PubMed1998

Caffeine causes glycerophosphorylcholine accumulation through ryanodine-inhibitable increase of cellular calcium and activation of phospholipase A2 in cultured MDCK cells.

Glycerophosphrylocholine (GPC) is a renal medullary compatible organic osmolyte that is derived from choline via phosphatidylcholine, which is catalyzed in part by phospholipase A2 (PLA2) and its degradation by GPC: choline phosphodiesterase (GPC: choline PDE). We found that caffeine elevated intracellular free calcium ([Ca2+]i) and GPC level in cultured MDCK cells, canine kidney epithelial cells, and propose a possible biochemical mechanism. When MDCK cells were incubated for 3 h with 1 to 10 mM caffeine, cellular GPC was elevated in a dose-dependent manner, and this occurred independently of the extracellular osmolality. Caffeine stimulated the rate of [14C]choline incorporation into [14C]GPC and PLA2 activity. Whereas, GPC: choline PDE activity was accompanied by less of increase. These enzyme changes demonstrate the increased net synthesis of MDCK GPC. In order to identify what triggers the PLA2 activation, [Ca2+]i was measured by using a fluorescence dye, Fura-2. Caffeine (10 mM) resulted in a typical transient increase in MDCK [Ca2+]i concentration, and this increase was greatly inhibited by pretreatment of MDCK cells with 10 mM ryanodine for 5 min. Ryanodine (10 mM) also inhibited the caffeine-induced stimulation of PLA2 activity. These findings provide the first evidence that caffeine in MDCK cells causes a ryanodine-inhibitable increase of [Ca2+]i and PLA2 activity, resulting in cellular GPC accumulation.

Animals↗
PubMed1998

Nickel (II)-induced apoptosis and G2/M enrichment.

Treatment with certain DNA-damaging agents induce a complex cellular response comprising pertubation of cell cycle progression and/or apoptosis on proliferating mammalian cells. Our studies were focused on the cellular effects of nickel (II) acetate, DNA-damaging agent, on Chinese hamster ovary (CHO) cells. Fragmented DNAs were examined by agarose gel electrophoresis and cell cycle was determined by DNA flow cytometry using propidium iodide fluorescence. Apparent DNA laddering was observed in cells treated with 240 microM nickel (II) and increased with a concentration-dependent manner. Treatment of nickel (II) acetate resulted in apoptosis which was accompanied by G2/M cell accumulation. Proportion of CHO cells in G2/M phase was also significantly increased in cells exposed to at least 480 microM nickel (II) from 57.7% of cells in the G0/G1 phase, 34.7% in the S phase, and 7.6% in the G2/M1 phase for 0 microM nickel (II), to 58.6%, 14.5%, and 26.9% for 640 microM nickel (II). These findings suggest that nickel (II) can modulate cellular response through some common effectors involving in both apoptotic and cell cycle regulatory pathways.

Animals↗
PubMed1998

Impaired expression of integrin alpha-4 subunit in cultured mast cells derived from mutant mice of mi/mi genotype.

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). We have reported that expression of several genes was impaired in cultured mast cells (CMCs) of mi/mi mice due to a defective transactivation ability of mutant MITF (mi-MITF). Because attachment of mi/mi CMCs to fibroblasts is impaired, we examined the expression of integrin genes in mi/mi CMCs in the present study. Among the integrin genes examined, the expression of integrin alpha4 subunit was barely detectable in mi/mi CMCs, and the alpha4 protein was not detected by flow cytometry either. The specific adhesion to vascular cell adhesion molecule-1 (VCAM-1), the ligand for alpha4 subunit, was observed in +/+ CMCs but not in mi/mi CMCs, indicating that the expression of integrin alpha4 subunit at a functional level did not occur in mi/mi CMCs. In the promoter region of the alpha4 subunit gene, there was a CACTTG motif to which normal MITF (+- MITF) bound. The coexpression of +-MITF but not of mi-MITF transactivated the promoter of the alpha4 subunit gene. The deletion or mutation of the CACTTG motif abolished the transactivation by +-MITF, suggesting that +-MITF directly transactivated the gene encoding alpha4 subunit of integrin.

Animals↗
PubMed1998

Takayasu arteritis presented with acute febrile pericardial effusion.

We report the clinical and radiographic findings of Takayasu arteritis (TA) presented with acute febrile pericardial effusion. Our case is unique in that acute pericardial effusion developed in the absence of other intracardiac abnormalities as an initial manifestation of TA. While pericardial effusion is infrequently related with TA, TA should be considered as one of causes of acute febrile pericardial effusion in especially young women.

Acute Disease↗