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Biomedical subjects

M Kim

Publications and source records attributed to M Kim.

At least 505 records · Page 28Linked to original sources
PubMedDate not supplied

Direct effects of cyclosporin A on proliferation of hematopoietic stem and progenitor cells.

Cyclosporin A (Cy A) has been reported to both stimulate and inhibit bone marrow colony assays in a dose-dependent manner. The observation that anti-gamma-IFN antibodies stimulate hematopoiesis to the same degree as Cy A has led several groups to propose that the stimulatory effects of Cy A are due to inhibition of gamma-IFN production by T cells. In this study we observed that cultures of highly enriched hematopoietic stem/progenitor cells (HSPC), devoid of CD3/5/8+ T cells, also exhibit enhanced cloning efficiency when cultured in the presence of Cy A. Normal bone marrow cells or Thy-1.1lowSca-1+Lin(neg) HSPC were incubated in methylcellulose cultures and stimulated with various combinations of steel factor (SF), interleukin (IL)-3, IL-6, granulocyte colony stimulating factor (G-CSF), and erythropoietin (EPO) in the presence of increasing concentrations of Cy A. HSPC cultures with SF, IL-3, and IL-6 stimulation and low Cy A concentrations had from 24% to 78% higher cloning efficiencies than did parallel cultures without Cy A, and did not fall below control levels until the Cy A concentration was increased to more than 1.25 microg/ml. The addition of EPO and G-CSF abrogated the Cy A stimulation observed with SF, IL-3, and IL-6. These results were reflected in whole bone marrow, but with a higher range of variability. Cultures in which FK-506 replaced Cy A showed no consistent stimulation or inhibition of colony formation. These studies show that Cy A can stimulate hematopoietic stem cell growth independent of mediation by T cells. Consequently, these results argue for a direct positive effect of Cy A on the signal transduction pathways in HSPC.

Animals↗
PubMedDate not supplied

The public versus the World Health Organization on health system performance.

The World Health Organization (WHO) ranked health systems in 191 countries based on measures developed by public health experts. This paper compares the WHO rankings for seventeen industrialized countries with the perceptions of their citizens. The results show little relationship between WHO rankings and the satisfaction of the citizens who experience these health systems. The health systems of some top WHO performers are rated poorly by their citizens, including the low-income and elderly. The two rated most highly by the public rank at the bottom of the WHO ratings. These findings suggest that both public and expert views should be considered in international rankings.

Consumer Behavior↗
PubMedDate not supplied

Americans' health priorities: curing cancer and controlling costs.

In this paper we provide a comprehensive examination of Americans' priorities within both health and health care. We find that Americans do have a clear set of priorities in each of these areas. Americans rated cancer, human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), and heart disease, and medical research to address these conditions, as top priorities among eighty health problems. However, they did not rank many leading causes of death very high as serious problems. On the issue of health care, problems of costs, prescription drugs, and the uninsured top the list. Americans are very concerned about emerging international infectious diseases that they believe threaten their health.

Attitude to Health↗
PubMedDate not supplied

Resumption of home activities following cardiac events.

Patients resume home activities at different paces after uncomplicated cardiac events, and respond to education in a variety of ways. Forty patients recovering from either myocardial infarction (MI) and coronary artery bypass surgery, or MI with coronary angioplasty who were enrolled in a randomized clinical study were interviewed and completed questionnaires regarding their experience resuming home activities. Responses indicated that uncomplicated patients can easily resume those activities important to them. Based on these findings, a Home Activity Assessment Tool was finalized to provide the practicing nurse with practical ways to guide discharge teaching. Use of this tool may facilitate patient's resumption of home, social and work activities.

Activities of Daily Living↗
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Electrophysiological effects of cyclazocine on rat cerebellar Purkinje neurons: comparison with phencyclidine.

Cyclazocine is a benzomorphan which, in addition to more classical opiate properties, binds to the sigma opiate receptor site. Recently, it has been suggested that the sigma opiate receptor is identical to the binding site responsible for the actions of phencyclidine (PCP). Since the electrophysiological actions of PCP have already been demonstrated on rat cerebellar Purkinje neurons, the effects of cyclazocine were also studied in this system with the goal of comparing the electrophysiological effects of cyclazocine to those of PCP. Cyclazocine inhibited the spontaneous firing rates of Purkinje neurons. These responses were stereospecific and qualitatively appeared similar to the effects of PCP. Antipsychotic drugs, haloperidol and fluphenazine, partially antagonized the actions of cyclazocine, suggesting a catecholaminergic involvement similar to the mechanism proposed for PCP. Unlike PCP, the effects of cyclazocine were also partially reversed by the opiate antagonist, naloxone. Taken together, these results suggest that in the rat cerebellum cyclazocine may be interacting with at least two receptor mechanisms: a naloxone-sensitive opiate site, and a naloxone-insensitive site which might involve catecholaminergic mediation similar to the PCP mechanism of action. The naloxone-sensitive effects of cyclazocine, however, may be related to an interaction of the drug with kappa receptors rather than with the more classical mu or delta opiate mechanisms.

Action Potentials↗
PubMedDate not supplied

[Effect of dietary protein content on the structure of blood vessels].

It has been demonstrated in experiments on rats that prolonged (for 1-6 months) use of the diet with protein deficiency or excess (5 and 30% respectively as regards caloricity) determines the development of injuries to the aortal wall and arteries of the heart and kidneys. Vascular elasticity shows abnormality, which is the most pronounced if the animals are given the low-protein diet including butter. Sunflower oil has a protective effect which becomes manifest provided that the animals receive the high-protein diet.

Animals↗
PubMedDate not supplied

Traumatic ventricular septal defect with tricuspid incompetence. Surgical treatment.

The authors report a case of traumatic ventricular septal defect associated with tricuspid incompetence after blunt injury of the chest. This case is the third one described in the literature. This case includes several unusual features: (1) the patient was a 52 year old man. Wounds of the heart usually happen to younger people; (2) clinical manifestations were immediately important; (3) there was a left bundle branch block on the electrocardiogram; (4) surgical treatment was performed as an emergency (less than a fortnight after the accident).

Bioprosthesis↗
PubMedDate not supplied

[Ophthalmological manifestations in AIDS: evaluation of 445 patients in one year].

The authors prospectively evaluated 445 HIV positive patients for the presence of ophthalmological manifestations. PURPOSE--To evaluate patients HIV positive with or without AIDS and correlate the data with the ocular findings mentioned in the literature. METHODS--445 HIV positive patients (66% with AIDS) were evaluated in one year at the Paulista School of Medicine, São Paulo Hospital, Brazil. There was a predominance of males (87%) and homosexuals (58.2%). RESULTS--Of the 445 patients, 52% presented ocular findings secondary to HIV infection at the first examination. The diagnosis included: CMV retinitis (25%), ocular toxoplasmosis (8.5%), herpes retinitis (3.6%), papilledema (2.2%), optic atrophy (1.6%), phthisis bulbi (1.5%), multifocal choroiditis (1.2%), retinal hemorrhages (0.9%), syphilitic uveitis (0.6%) and central vein occlusion (0.2%). CONCLUSION--The incidence of ophthalmic manifestations of AIDS in Brazil is similar to that found in the international literature. We found though a higher incidence of ocular toxoplasmosis than that in other countries. No ocular pneumocystosis was presents in the population evaluated by us.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Pharmacokinetic evaluation of aconiazide, a potentially less toxic isoniazid prodrug.

STUDY OBJECTIVE: To determine the bioavailability and renal elimination of isoniazid, acetylisoniazid, monoacetylhydrazine, diacetylhydrazine, aconiazide, and 2-formylphenoxyacetic acid. STUDY DESIGN: Randomized, double-blind, two-period, crossover phase I study. SETTING: Pharmacokinetics unit at a referral hospital that specializes in the treatment of mycobacterial infections. SUBJECTS: Twelve healthy volunteers selected from the hospital staff. INTERVENTIONS: Subjects received aconiazide tablets 650 mg (containing isoniazid 300 mg) and isoniazid tablets 300 mg. Blood and urine samples were collected over 24 hours after the dose. MEASUREMENTS AND MAIN RESULTS: Intact aconiazide and 2-formylphenoxyacetic acid were not detected in the serum. Compared with isoniazid tablets, aconiazide's relative bioavailability (based on the area under the serum concentration-time curve) was 50.7%; its relative maximum serum concentration was 13.4%. CONCLUSIONS: Isoniazid is less bioavailable after aconiazide tablets than after isoniazid tablets. The optimum dose of aconiazide remains to be determined.

Adult↗
PubMedDate not supplied

Inhibition of the enantioselective oxidative metabolism of metoprolol by verapamil in human liver microsomes.

In an effort to investigate the metabolic basis of previously reported pharmacokinetic interactions between beta-adrenergic antagonists and calcium channel blockers, the effects of verapamil on the oxidative metabolism of metoprolol were studied in microsomes isolated from four human livers. Deuterium-labeled pseudoracemic metoprolol was used to characterize the substrate stereoselectivity of this metabolic interaction. Biphasic kinetics were observed for both the alpha-hydroxylation and O-demethylation of metoprolol, suggesting that multiple P-450 enzymes with differing KMs are involved in the formation of these oxidative metabolites. alpha-Hydroxylation showed a slight preference for S-(-)-metoprolol, and it was largely mediated by a high-affinity enzyme over a wide range of substrate concentrations. The high-affinity component of the O-demethylation reaction exhibited significant selectivity for the R-(+)-enantiomer. The opposite enantioselectivity was observed for the low-affinity component of O-demethylation. Racemic verapamil inhibited both the alpha-hydroxylation and the O-demethylation of metoprolol. The kinetics of inhibition were consistent with competitive effects of verapamil on the high-affinity components of both oxidative pathways, which previously had been suggested to be mediated by CYP2D6. Potent inhibition of the low-affinity component of O-demethylation was also observed. The inhibitory effect of verapamil on the alpha-hydroxylation of metoprolol was not enantioselective. On the other hand, verapamil preferentially inhibited the O-demethylation of R-(+)-metoprolol compared with S-(-)-metoprolol at low substrate concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytochrome P-450 Enzyme System↗
PubMedDate not supplied

Evidence for indirect involvement of the H-2Kb gene in the regulation of natural killer sensitivity of BL6 melanoma cells.

We have previously demonstrated that transfection of BL6-8 melanoma cells with the H-2Kb gene increased their sensitivity to natural killer (NK)- and natural cytotoxic (NC) cell-mediated cytotoxicity, and resulted in alterations of various cell characteristics such as the loss of melanoma-associated antigen (MAA), and the appearance of Griffonia simplicifolia 1B4 (GS1B4)- and soybean agglutinin (SBA)-lectin-binding sites. In the present study the BL6-8 melanoma clone was transfected with the H-2Kb gene without cotransfection of the neomycin resistance (neor) gene, and transfected cells were isolated on the basis of their low sialylation and ability to bind to SBA-agarose beads. 38 out of 47 analyzed clones were morphologically distinguishable, expressed the H-2Kb gene, lost the MAA and gained SBA- and GS1B4-lectin-binding sites (H-2Kb+, MAA-, SBA+, GS1B4+), whereas only 5 clones were morphologically and phenotypically unchanged (H-2Kb-, MAA+, SBA-, GS1B4-). The remaining 4 clones were morphologically changed, lost MAA and gained SBA- and GS1B4-binding epitopes, but did not express H-2Kb antigen (H-2Kb-, MAA-, SBA+, GS1B4+). Analysis of the NK sensitivity of H-2Kb-gene-transfected clones revealed that H-2Kb+, MAA-, SBA+, GS1B4+ clones were highly sensitive to NK cell lysis, whereas H-2Kb-, MAA+, SBA-, GS1B4- clones were NK resistant. It is of particular note that the 4 clones that did not express H-2Kb antigen but had other phenotypic changes (H-2Kb-, MAA-, SBA+, GS1B4+) were also highly sensitive to NK cells. The NK sensitivity of H-2Kb-transfected cells was closely associated with their increased ability to compete with YAC-1 cells for effector cells in a cold-target inhibition assay. Thus, the data obtained indicate that H-2Kb molecules in BL6-8 melanoma cells are not required for interaction with the effector cells, and H-2Kb-induced alterations in membrane carbohydrates and/or expression of the retrovirus-associated MAA might be important for the increase NK sensitivity of BL6-8 melanoma cells.

DNA, Neoplasm↗
PubMedDate not supplied

A recombinant adenovirus expressing wild type p53 induces apoptosis in drug-resistant human breast cancer cells: a gene therapy approach for drug-resistant cancers.

The cytotoxicity of a recombinant adenovirus expressing the wild type tumor suppressor gene p53 (AdWTp53) was studied in two human breast cancer MCF-7 sublines selected for resistance to adriamycin (MCF-Adr) and mitoxantrone (MCF-Mito). Although the levels of wild type p53 protein following infection with AdWTp53 are comparable in all cell lines, the two drug-resistant MCF-7 sublines were 300- and 18-fold more sensitive to killing by AdWTp53 compared with the drug-sensitive parental MCF-7 cell lines. In each cell line, AdWTp53 infection led to cell cycle arrest, and reduction of Cdk2 and cyclin B1-Cdc2 activity. Nucleosomal DNA fragmentation analysis (as a function of apoptosis) following AdWTp53 infection revealed that, while the parental MCF-7 cells failed to undergo apoptosis, both drug-resistant cell lines showed distinct DNA laddering. In MCF-Adr cells, a combination treatment of AdWTp53 and adriamycin was much more toxic than either of the reagents used individually. Finally, exposure of a mixed population of MCF-Adr and CD34+ cells to AdWTp53 selectively prevented MCF-Adr cell colony formation, while there was no inhibition of CFU-GM colony formation from CD34+ cells. These findings suggest that some drug-resistant human breast cancers may be effectively treated with adenovirus expressing wild type p53.

Adenoviridae↗