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Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 1,063 records · Page 59Linked to original sources
PubMed1993

Theoretical conformational analyses of endothelin-1 in vacuum, aqueous, and lipid environments.

Endothelin-1 (ET-1) is a flexible molecule capable of existing in multiple shapes (conformations) depending on the surrounding molecular solvation. The conformational diversity of ET-1 was studied in three solvation spheres (gas phase, aqueous, and membrane lipid) with the new evolving biotechnology of computational biomolecular simulation. Simulations were performed using a combination of molecular mechanics, molecular dynamics, and semiempirical quantum mechanics calculations in a RISC architecture large-scale computing environment. Marked differences between the gas phase "folded" conformation and the membrane lipid "extended" conformation were identified.

Chemical Phenomena↗
PubMed1993

Successful treatment of adult T-cell leukemia/lymphoma with MACOP-B, M-FEPA and VEPP-B combination chemotherapy.

A 45-year-old man was referred to our department in March of 1989. Physical examination showed erythroderma, palmo-plantar hyperkeratosis, generalized lymphadenopathy, hepatosplenomegaly, and leukemic manifestation. The lymphocyte count in the peripheral blood before treatment was 1.7 x 10(4) cells/mm3. Atypical lymphocytes such as flower cells and lobulated cells were seen in the peripheral blood. A sample excised from a lymph node showed immunoblastic, pleomorphic T cells by a modified classification scheme of the Working Formulation. A high level of serum LDH was detected (2.1 times the upper normal limit). Anti HTLV-1 antibody was also detected in the serum. The atypical lymphocytes were positive for CD3, CD4, CD5, CD7 and HLA-DR, and negative for CD8. Thus, the clinical, pathologic and immunologic features were those of typical acute-type ATL. The patient was treated with VEPA-M for three months starting in March of 1989. Because of poor response, the patient was then treated with MACOP-B, M-FEPA, and VEPP-B for about one year from June of 1989 and has been free of disease up to the time of writing, March of 1993.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Effect of the platelet-activating factor antagonist, TCV-309, and the cyclo-oxygenase inhibitor, ibuprofen, on the haemodynamic changes in canine experimental endotoxic shock.

1. The present study was conducted in order to examine the effects of the platelet-activating factor (PAF) antagonist, TCV-309, and the cyclo-oxygenase inhibitor, ibuprofen, on the acute haemodynamic responses to endotoxin in anaesthetized dogs. 2. Endotoxin (2 mg kg-1, i.v.) induced a severe hypotension by decreasing both total peripheral resistance (TPR) and cardiac output. Endotoxin also decreased central venous pressure and increased effective vascular compliance (EVC), indicating a blood pooling in the capacitance vessels. 3. The endotoxin-induced hypotension but not the fall in cardiac output, was markedly attenuated by ibuprofen. Ibuprofen abolished the decrease in TPR and even caused a systemic vasoconstriction. Ibuprofen abolished the increase in EVC. 4. The hypotension caused by endotoxin was attenuated by TCV-309 to a lesser extent than ibuprofen. However, the reduction in cardiac output produced by endotoxin was markedly attenuated by the PAF antagonist. TCV-309 also abolished the increase in EVC. In contrast to ibuprofen, TCV-309 did not affect the decrease in TPR caused by endotoxin. 5. Combined treatment with ibuprofen and TCV-309 markedly attenuated the endotoxin-induced hypotension, but not the fall in cardiac output. Nevertheless, when compared with animals treated with ibuprofen alone, treatment with ibuprofen and TCV-309 partly attenuated the endotoxin-induced reduction in cardiac output and systemic vasoconstriction. 6. These data indicate that dilatation of both resistance vessels and capacitance vessels contributes to the endotoxin-induced hypotension. It is suggested that (i) both prostanoids and PAF are involved in dilatation of capacitance vessels, (ii) prostanoids, but not PAF cause dilatation of resistance vessels and(iii) PAF may partly contribute to prostanoid-independent reduction in cardiac output in acute canine experimental endotoxin shock.

Animals↗
PubMed1993

Differentiation-related expression of ICAM-1 by rat alveolar epithelial cells.

Local regulation of immune and inflammatory responses within the alveolar space is a critical aspect of normal pulmonary host defense. The type I and type II epithelial cells that line the alveolar space are in intimate contact with lymphocytes and macrophages within the alveolar space and are ideally situated to provide regulatory signals to these effector cells. The present studies were undertaken to investigate the expression by rat alveolar epithelial cells in vitro and in vivo of intercellular adhesion molecule-1 (ICAM-1), an adhesion molecule that is involved in migration and activation of T cells and macrophages. An antibody specifically blocking rat ICAM-1 (mAb 1A29) inhibited the adherence of activated T lymphoblasts to monolayers of type II alveolar epithelial cells. The expression of ICAM-1 protein by alveolar epithelial cells in vitro was confirmed both by immunofluorescence microscopy and by Western blot analysis. However, in each instance, ICAM-1 was not detected in type II cells the day of isolation, but appeared at low levels after 1 day and in abundance throughout the monolayer after 2 days, with sustained expression thereafter. This suggested that ICAM-1 expression might be a type I cell feature, which was induced as isolated type II cells underwent transformation towards the type I cell-like phenotype in vitro. Using immunofluorescence microscopy on frozen sections of normal lung, ICAM-1 was found in a linear distribution along the alveolar space, consistent with expression on type I cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Extended CSF cytarabine exposure following intrathecal administration of DTC 101.

PURPOSE: The aims of the present study were to determine ventricular and lumbar CSF pharmacokinetics and the maximum-tolerated dose (MTD) of DTC 101 (DepoFoam; DepoTech Corp, La Jolla, CA) following intraventricular administration. PATIENTS AND METHODS: Twelve patients with neoplastic meningitis were treated with escalating doses of DTC 101. CSF samples were obtained from the right lateral ventricle or from the lumbar subarachnoid space and cytarabine concentrations were determined by high-performance liquid chromatography. RESULTS: Therapeutic ventricular CSF concentrations were maintained for 9 +/- 2 days following administration of a single dose of DTC 101 into the lateral ventricle. Lumbar cytarabine concentrations became equal to those in the ventricle within the first 6 hours after intraventricular injection, and the subsequent decay in concentrations of free and total cytarabine were the same at both sites. Following intralumbar administration, the peak ventricular concentration of free cytarabine was reached within 1 day, and therapeutic ventricular CSF levels were maintained for several days. Therapeutic intralumbar concentration of free cytarabine was maintained for up to 14 days. The MTD was 75 mg of DTC 101, and seven of nine patients manifested cytologic responses. CONCLUSION: Extended CSF exposure to therapeutic cytarabine concentrations was achieved after a single intraventricular or intralumbar dose of DTC 101, permitting drug administration once every 2 weeks.

Adolescent↗
PubMed1993

Phase I/pharmacokinetic study of high-dose progesterone and doxorubicin.

PURPOSE: We developed a new formulation of progesterone that permits administration of up to 10 g of progesterone as a continuous intravenous infusion over 24 hours and conducted a phase I clinical trial to determine whether progesterone could modulate the in vivo cytotoxicity of the P-glycoprotein substrate doxorubicin. PATIENTS AND METHODS: Thirty-four patients with advanced malignancies were treated with increasing doses of progesterone and a fixed dose of 60 mg/m2 of doxorubicin given as an intravenous bolus 2 hours after starting a 24-hour intravenous infusion of progesterone. RESULTS: Progesterone enhanced doxorubicin-induced myelotoxicity in a dose-dependent fashion without altering the pharmacokinetics of doxorubicin. The steady-state plasma concentration of progesterone at a dose level of 4 g was 4.1 +/- 0.9 mumol/L, which was higher than the minimal concentration required to reverse multidrug resistance (MDR) in vitro. CONCLUSION: Progesterone enhanced the hematologic toxicity of doxorubicin without altering its pharmacokinetics, suggesting that progesterone could modulate P-glycoprotein at the level of pluripotent hematopoietic stem cells. Adequate tissue concentrations of progesterone could be achieved in vivo to modulate doxorubicin toxicity in the bone marrow and thus potentially in tumor tissue as well. Selectivity may potentially be gained by using hematopoietic growth factors to offset the enhanced hematologic toxicity of doxorubicin while leaving the enhancement of toxicity to tumor cells unchanged.

Adult↗
PubMed1993

Effect of NG-nitro-L-arginine on effective vascular stiffness in dogs.

It has been reported that there is a continuous release of nitric oxide (NO) that contributes to the regulation of vascular tone in the arterial system. In contrast, the role of NO on vascular tone in the venous system is controversial. We examined the effect of NG-nitro-L-arginine (LNNA), an NO synthase inhibitor, on venous tone in dogs. Venous tone was evaluated by effective vascular stiffness (EVS), which was calculated from the changes in central venous pressure recorded simultaneously with changes in blood volume. LNNA (10 mg/kg, i.v.) increased EVS from 0.21 +/- 0.04 to 0.30 +/- 0.03 mmHg.kg/ml as well as increasing the systemic vascular resistance. NG-Nitro-D-arginine had no effect on EVS. The LNNA-induced increase in EVS was partly reversed by L-arginine, but not by D-arginine, indicating that the increase in EVS was attributable to a blockade of NO synthesis. Since the present study was conducted under ganglion blockade, nitroxidergic nerve terminals do not seem to be the source of NO in this case. These findings suggest that NO (endothelium-derived relaxing factor) is constantly released in the venous system and contributes to the regulation of total systemic venous tone.

Animals↗
PubMed1993

Is ST/HR slope a predictor of coronary artery lesion in effort angina pectoris? A comparison of exercise hemodynamic variables.

This study evaluated the clinical value of the ST/HR slope and exercise hemodynamic variables for the severity of coronary artery lesions. Twenty-nine patients with effort angina pectoris underwent ergometer exercise during right side heart catheterization. The ST/HR slope failed to differentiate three groups stratified by the number of involved coronary vessels. The ST/HR slope was uncorrelated with the Gensini score (r = 0.24). By contrast, pulmonary capillary pressure (PCP), cardiac output index (CI) and CI/PCP at peak exercise correlated significantly with the Gensini score (r = 0.73, 0.53 and 0.69, respectively). We conclude that the ST/HR slope is not a useful predictor of the severity of coronary artery lesions, while exercise hemodynamic variables measured by right side heart catheter are useful.

Adult↗
PubMed1993

Liposomes as carriers of cancer chemotherapy. Current status and future prospects.

Chemotherapy is a modality of cancer therapy that needs much improvement. Development of a new chemical entity is very costly and time consuming, but improvements in delivery of existing agents may yield more rapid clinical results. Liposomes and other lipid-based drug delivery systems have the advantage, in this context, of utilising no new chemical entities. In terms of mechanism of action, tumour targeting has been the focus of much work in liposomal drug delivery. The recent development of liposomes with longer circulation times has led to improved tumour targeting in animal studies. Other mechanisms of action, such as release from drug depot formulations, heat-triggered local drug release, and transfection of genetic materials, may prove to be useful in humans. Liposomal formulations of more than a dozen antineoplastic agents have shown promise in vitro and in animal models. Somewhat mundane, but nevertheless crucial, issues of medical rationale and formulation engineering, and commercial considerations, have slowed testing in patients with cancer. However, 3 antineoplastic agents, doxorubicin, daunorubicin and cytarabine, are in advanced stages of clinical testing in humans. One or more of these should prove to be a medically useful and commercially viable product within the next few years.

Antibiotics, Antineoplastic↗
PubMed1993

An outcome evaluation of Here's Looking At You 2000.

This study reports outcome evaluation results from a segment of one of the most widely used drug education/prevention programs entitled "Here's Looking At You 2000." HLAY 2000 was offered to the seventh and eighth grade students (n = 463) by regular classroom teachers of Yadkin County Schools located in one of the rural areas in North Carolina. Six schools served as the experimental group while two randomly selected schools served as a control group. The program was implemented during the 1990-91 school year.

Adolescent↗
PubMed1993

Central neural mechanism contributing to attenuation of angiotensin II-induced hypertension in rats on dietary calcium supplementation.

The effect of dietary calcium (Ca) supplementation on blood pressure (BP) and the central nervous system (CNS) mechanism underlying this effect were studied in angiotensin II (Ang II)-induced hypertensive rats. The effects of dietary Ca (0.5, 2, 4%) on systolic blood pressure (SBP), ionized Ca concentration (Ca++) in cerebrospinal fluid (CSF) and central norepinephrine (NE) turnover were investigated in male Wistar rats receiving subcutaneous infusion of Ang II (100 ng/min). Central NE turnover was studied by measuring 3-methoxy-4-hydroxyphenylglycol (MHPG) concentration in CSF with multiple electrode liquid chromatography. Ang II significantly increased SBP, and dietary Ca dose-dependently attenuated the increase. SBP inversely correlated with Ca++ and MHPG in CSF. Intracerebroventricular injection of CaCl2 more markedly reduced BP in Ang II-treated rats than that in control rats. These results suggest that modulation of central NE turnover possibly caused by the increase in CNS Ca++ is involved in the anti-hypertensive mechanism of dietary Ca supplementation in Ang II-induced hypertensive rats.

Angiotensin II↗
PubMed1993

[Two elderly cases of megacolon associated with cerebral infarction and diabetes mellitus].

The authors experienced two elderly patients of megacolon associated with cerebral infarction and diabetes mellitus. The first patient was a 66-year-old female who was admitted to our hospital for rehabilitation with a complaint of knee pain. She had suffered from diabetes mellitus since she was 30 years old and multiple cerebral infarction since age 62. Two months after admission, she had an episode of abdominal distension and obstructive symptoms. The roentgenograms of her abdomen showed diffuse dilatation of the colon. The second patient was a 78-year-old female admitted to our hospital with complaints of abdominal pain, distension of the abdomen and vomiting. Her abdomen was severely distended and plain roentgenograms of the abdomen, X-ray studies of the colon with the aid of contrast medium and CT scan of the abdomen showed striking dilatation of the colon. Megacolon may be congenital or acquired, and in acquired forms the conditions are secondary to organic diseases, smooth muscle atrophy, metabolic and neurological diseases, ulcerative colitis or psychogenic origin (idiopathic). The two patients in this series were suffered from cerebral infarction and diabetes mellitus. The mechanisms of megacolon seen in these two patients are not known, but involvement of the visceral autonomic innervation is presumed. Some elderly patients have chronic constipation, and dilatation of the colon may not be uncommon due to underlying diseases or drugs. Therefore, when examining elderly patients, careful attention should be paid to their bowel movement.

Aged↗
PubMed1993

An outbreak of Heinz body positive hemolytic anemia in chronic hemodialysis patients.

During the four month period, from December 1988 to March 1989, there was an outbreak of Heinz body positive hemolytic anemia in 34 patients undergoing hemodialysis in a 500-bed hospital, Seoul, Korea. The episodes of hemolysis were not reduced by changing the charcoal column and reverse osmosis system, or by adding ascorbic acid to the dialysate. The concentrations of nitrate, copper, aluminum and zinc in the treated water were all within the standards for hemodialysis. The chloramine concentration of the treated water was over 0.6 mg/L, markedly exceeding the allowable level of 0.1 mg/L. This high level of chloramine was proved to be due to the contamination of the water source by raw sewage. After we changed the source of water supply to another, no more episodes of hemolytic anemia occurred. It is concluded that chloramine is one of the major contaminants causing dialysis-induced hemolytic anemia and regular determinations are necessary, especially during winter and dry seasons.

Anemia, Hemolytic↗
PubMed1993

[Immunohistochemical analysis of cell surface markers in leprosy patients].

Nine biopsy specimens from 3 tuberculoid (TT), 1 borderline tuberculoid (BT), 2 borderline (BB), 2 borderline lepromatous (BL), and 1 lepromatous (LL) patients were studied using immunoperoxidase procedures with monoclonal antibodies. In TT patients 4B4+, TCR alpha beta+, CD4+ T cells were dominant in dermal granulomas. In LL patient, dermal granulomas with 4B4+, TCR alpha beta+, CD4+ T cells and 2H4+, TCR alpha beta+, CD4+ T cells also had CD8+ T cells. The proportion of 4B4+ T cells increased in granulomas from LL to TT and 2H4+ T cells proportionately increased from TT to LL. TCR gamma delta+ T cells were detected only in BB and BL patients. However, there is no difference of staining pattern of ICAM-1 or LFA-1 antigen in any type of leprosy. These results indicate that the immunohistochemical pattern of T cells (CD4, CD8, 4B4, 2H4, TCR) may be useful in the diagnosis of the spectrum of leprosy.

Adult↗
PubMed1993

Mechanisms of the inhibition of reverse transcription by unmodified and modified antisense oligonucleotides.

We have demonstrated that the synthetic oligonucleotides, either unmodified or phosphorothioates, prevent cDNA synthesis by the AMV or HIV reverse transcriptases. The RNA was truncated at the antisense oligonucleotide-RNA duplex during the reverse transcription. Th blockage involves the degradation of the RNA fragment bound to the antisense oligonucleotide by the reverse transcriptase associated RNase H activity. However, in the case of phosphorothioate oligomer, the production of cDNA would be inhibited by a hybrid formed between the AMV RT and phosphorothioate oligomer than arrested elongation of the cDNA strands, whereas arrest of a growing cDNA strand by HIV RT can be blocked by an oligonucleotide complementary to a region downstream from the primer.

Animals↗