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Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

1,575 records · Page 88Linked to original sources

Coagulopathy in hemorrhagic fever with renal syndrome (Korean hemorrhagic fever).

The pathophysiology of bleeding manifestations in hemorrhagic fever with renal syndrome (HFRS) was elucidated by serially evaluating coagulation and fibrinolytic profiles and complement alterations in patients with HFRS. In the early stage of the disease, platelet counts, platelet survival time, and platelet aggregation in vitro decreased. Prolongation of bleeding time, prothrombin time, and activated partial thromboplastin time was noted, with decreases in coagulation factors II, V, VIII, IX, and X. Levels of fibrinogen were decreased, and those of fibrinogen-fibrin degradation products in serum and urine were increased. Concentrations of plasminogen, alpha 2-plasmin inhibitor, and antithrombin III in plasma were depressed. Procoagulant activity was present in plasma. Circulating immune complexes were found, whereas serum levels of C3 were decreased. In the early stage of HFRS, thrombocytopenia, defects in platelet function, and disseminated intravascular coagulation may play central roles in the pathogenesis of bleeding manifestations. Vasculopathy and immunologic aberrations also may play a role.

Antigen-Antibody Complex↗

Multivesicular liposomes containing cytarabine entrapped in the presence of hydrochloric acid for intracavitary chemotherapy.

For a full exploitation of the 1000-fold ip pharmacokinetic advantage obtained when cytarabine is administered ip, the drug exposure must be prolonged because the drug is a cell cycle phase-specific agent. Multivesicular liposomes made from nontoxic components were studied as biodegradable, slow-release microcapsules for intracavitary therapy. No attempt was made to increase efficacy by fusing liposomal membrane with that of tumor cells or by selective targeting of liposomes to cancer cells other than simple administration into a cavity. The presence of HCl with cytarabine at the time of encapsulation was found to decrease the leakage rate in human plasma dramatically. After ip administration of encapsulated cytarabine to mice, the total intracavitary drug concentration initially increased tenfold in 15 hours, then fell to the original concentration at 87 hours. The total amount of the drug in the peritoneal cavity decreased with a 21-hour half-life. All mice treated 24 hours after ip inoculation with 1 X 10(6) L1210 cells were cured when 32 mg/kg or 16 mg/kg of cytarabine in liposomes was given ip every 4 days for a total of three doses. Multivesicular liposomes do prolong intracavitary exposure to cytarabine and are efficacious in this model system.

Animals↗

Possible involvement of calpain in the growth of estrogen receptor positive breast cancer cells.

Calpain (Ca2(+)-activated neutral protease, EC 3.4.22.17) has been reported to hydrolyze the estrogen receptor (ER). However, there has been no report available regarding the role of calpain in the growth of breast cancer cells. To investigate the role of calpain in the growth of various breast cancer cell lines, we employed a synthetic peptide, calpeptin, which is a cell permeable specific inhibitor of calpain. Calpeptin inhibited the cell growth of ER positive breast cancer cells, such as MCF-7, T-47D, and ZR-75-1 in a dose dependent manner in the presence of E2. However, the growth of ER negative breast cancer cells, MDA-MB-231, was not inhibited by calpeptin. It is suggested that calpain plays an important role in the growth of ER positive breast cancer cells.

Animals↗

Mycobacterium tuberculosis infection in a corticosteroid-treated rheumatic disease patient population.

OBJECTIVE: To investigate the incidence and risk factors of Mycobacterium tuberculosis infection in longterm corticosteroid treated rheumatic disease patients. METHODS: We assessed retrospectively the incidence of active tuberculosis and its risk factors in 269 rheumatic disease patients treated with moderate to high doses of corticosteroid for an evaluation period representing 1,035 corticosteroid years of therapy. RESULTS: The mean daily dose of steroid was 18.7 mg prednisolone and the mean daily dose during the first year of treatment was 20.4 mg prednisolone. 21 of these patients developed active tuberculosis resulting in an incidence rate of 20/1,000 patient-years. Cumulative and mean daily steroid doses during the follow-up period and during the first year of treatment, and a history of steroid pulse therapy were significantly correlated with the development of tuberculosis. A past history of tuberculosis, initial chest P-A abnormality, the starting dose of steroid, a history of more than 30 mg/day of prednisolone for more than one month, and a history of cytotoxic therapy were not related to the development of tuberculosis. CONCLUSION: The incidence of active tuberculosis is increased in rheumatic patients on moderate-to-high dose steroid treatment. Its risk factors are the cumulative and mean daily steroid doses during the follow-up period and during the first year of steroid treatment, and a history of steroid pulse therapy.

Adolescent↗

Growth inhibition induced by Ro 31-8220 and calphostin C in human glioblastoma cell lines is associated with apoptosis and inhibition of CDC2 kinase.

Protein kinase C (PKC) is a central component in signal transduction and growth control and might be an appropriate target for the chemotherapy of human brain tumors. This study demonstrates that the staurosporine derivative Ro 31-8220, a potent PKC inhibitor, inhibited the growth of 7 human brain tumor cell lines with an IC50 of about 2 microM. Calphostin C, a structurally unrelated PKC inhibitor, inhibited the growth of two of these cell lines with an IC50 of about 100 to 300 nM. Drug withdrawal and clonogenicity assays indicated that the growth inhibition by both of these compounds was irreversible. Morphologic studies, DNA fragmentation studies and flow cytometric assays showed that the treated glioblastoma cells underwent apoptosis. Treatment of glioblastoma cells with Ro 31-8220 lead to a rapid decline in the level of the anti-apoptosis protein bcl-2. At least three of the glioblastoma cell lines carried mutant p53 alleles with missense mutations in the DNA binding domain of p53. Therefore, the induction of apoptosis in these cell lines occurred through a p53-independent mechanism. Furthermore treatment of these glioblastoma cell lines with Ro 31-8220 or calphostin C led to an increase of cells in the G2-M phase of the cell cycle. This correlated with a decrease in CDC2-associated histone H1 kinase activity, as well as a decrease in the level of the CDC2 protein as shown by immunoblotting. When added to subcellular assays Ro 31-8220 markedly inhibited CDC2 histone H1 kinase activity with an IC50 of 100 nM, but calphostin C directly inhibited this kinase activity only at very high concentrations (above 100 microM). Thus these compounds inhibit the growth of glioblastoma cells through novel mechanisms. Ro 31-8220, in particular, might be a useful agent for the treatment of human brain tumors.

Anticarcinogenic Agents↗

Bone scan appearance of renal osteodystrophy in diabetic chronic renal failure patients.

To investigate Tc-99m methylenediphosphonate (MDP) bone scan appearance in diabetic chronic renal failure patients, we compared the bone scan images of chronic renal failure patients with and without diabetes. The number of patients studied was 134, of whom 43 had diabetes. Two nuclear medicine physicians read Tc-99m MDP bone scan images and for six areas - the axial skeleton, long bone, skull and mandible, periarticular areas, costochondral junction, and sternum - assigned a score of either 1 or 0. The sums of scores were compared. We also performed multivariate analysis including sex, age, and serum creatinine level using analysis of covariance. DM group patients scored significantly lower (2.01+/-0.95) than those of the non-DM group (3.26+/-1.16). Analysis of covariance revealed that the lower DM group score was independent of sex, age, and serum creatinine level. The bone scans of diabetic chronic renal failure patients showed less Tc-99m MDP uptake than those of non-diabetic patients. Thus, diagnosing renal osteodystrophy in diabetic chronic renal failure patients on bone scan images could be difficult.

Adult↗