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Biomedical subjects

M K Kim

Publications and source records attributed to M K Kim.

At least 181 records · Page 10Linked to original sources

Preferential infiltration of macrophages during early stages of insulitis in diabetes-prone BB rats.

The subpopulation of lymphoid cells at the different stages of insulitis in BB rats was determined by immunohistochemical techniques with various monoclonal antibodies, including the recently developed OX41, which distinguishes macrophages from T-lymphocytes, OX19 for pan-T-lymphocytes, W3/25 for both helper T-lymphocytes and macrophages, OX8 for cytotoxic T-lymphocytes and natural killer cells, and OX12 for B-lymphocytes. The major population of infiltrated cells found during the early stages of insulitis appeared to be macrophages. This preceded invasion by a mixed population of cells, including both T- and B-lymphocytes and/or natural killer cells. The preferential infiltration of macrophages during the early stages of insulitis strongly suggested that there might be an initial change in the target beta-cells that precedes their immune destruction, although the amplification of immune response by activated T-lymphocytes and natural killer cells at a later stage seemed to be required for the clinical expression of the disease.

Animals↗

Genetic control of organ-reactive autoantibody production in mice by obesity (ob) diabetes (db) genes.

Inbred strains of mice exhibited genetic and sex-dependent differences in spontaneous production of organ-reactive autoantibodies detected by indirect immunofluorescence. Antitestis autoreactivity was found primarily in sera from C57BL/6J (B6) mice, whereas antigastric autoreactivity was common to both CBA/J and 129/J strains. Autoantibodies against islet cell cytoplasmic antigens (ICAs) were uniquely expressed by C57BL/KsJ (BKs) males. Introduction of the diabetes (db) mutation into these various inbred-strain backgrounds induced expression of ICA, with stronger induction observed in males. The stress imposed by the db or obesity (ob) mutation induced ICA in BKs mice at a higher frequency than in B6 mice; this differential sensitivity was somehow related to a gene linked to the H-2 complex because BKs.B6 H-2b congenic mice resembled B6 mice. The db3J mutation increased the expression of these autoantibodies in 129/J mice, which, like B6, were H-2b and therefore presumably possessed the same H-2-linked inducibility allele as BKs. Cytotoxic autoantibodies against islet cell surface antigens were only observed in C3HeB/FeJ db/db males, and their presence was correlated with beta-cell necrosis. It is concluded that db and/or ob genes appear to play an important role in the production of autoantibodies to islet cells, and sex-linked factor(s) may modify the phenotypic expression of the autoantibodies.

Animals↗

Histopathologic and immunohistopathologic features of subretinal fibrosis and uveitis syndrome.

We studied histopathologic and immunohistopathologic features of an eye from a patient who had hypopigmented choroidal lesions with subsequent development of progressive subretinal fibrotic tissue associated with minimal signs of vitreal inflammation. A 24-year-old woman had a rapid and severe onset of the disease, which led to blindness within a few months despite treatment with corticosteroids and cyclophosphamide. Histopathologic studies disclosed a marked gliotic retina and thick subretinal fibrotic tissue as well as a granulomatous lymphocytic infiltration in the choroid. Electron microscopy demonstrated that the subretinal tissue was derived from retinal pigment epithelial cells. The immunoperoxidase staining showed similar proportions of T and B lymphocytes, indicating a relative increase of B cells. There was a predominance of the helper/inducer T lymphocyte subset in the infiltrating area. The Müller cells in the retina expressed class II antigens of the major histocompatibility complex.

Adult↗

A model to determine staff levels, cost, and productivity of hospital units.

A methodology is presented with examples of the productivity, the staffing required, the resultant productivity, and costs that can be obtained for hospital units that are subject to random work demands such as laboratory, radiology, physical therapy, and nuclear medicine. The methodology assumes that the hospital has a labor productivity system that produces the RVUs or earned hours of work accomplished daily by shift. Factors considered are the distribution of the capabilities of the work force, the fatigue and delay allowances of the work standards, the quality of the work standards, the maximum amount of overtime that people will be asked to work, staffing policies such as constant or different staffing levels for each day of the week, and worker selection processes. Predicted results are compared with present practice, which indicates that substantial cost reductions can occur with the use of the methodology.

Budgets↗

Pharmacologic effects on the expression of class II histocompatibility antigen in experimental endotoxin-induced uveitis.

Systemic dexamethasone, cyclosporine A, colchicine, indomethacin, and cobra venom factor were administered to Lewis rats that were then challenged with 100 micrograms of Salmonella typhimurium endotoxin. The effects of these five pharmacologic agents in endotoxin-induced uveitis were studied by analyzing their effects on ocular inflammation and on the expression of class II antigen of the major histocompatibility complex (MHC) on the epithelium of the ciliary body and iris. All the agents used in our study exhibited anti-inflammatory effects but only dexamethasone was able to inhibit significantly the expression of Ia antigen on the uveal epithelium. This demonstrates a dissociation between the inflammation and class II antigen expression and supports our previous data that class II antigen presentation may precede the inflammatory infiltrates. The alteration of ocular inflammation and especially the variation of Ia antigen expression in the uveal tissue may provide insight into the mechanism of action and the success of different pharmacologic agents used in the treatment of uveitis.

Animals↗

Immunopathology of ocular onchocerciasis. 2. Anti-retinal autoantibodies in serum and ocular fluids.

Ocular fluids and sera from 12 onchocerciasis patients and nine age-matched controls living in Tamale, Ghana, were examined for the presence of anti-retinal autoantibodies by the indirect immunoperoxidase technique. Antibodies directed against autoantigens of the inner retina (nerve fiber, ganglion cell, and Müller cell) were found in the sera of 10 of 12 patients, but in only three of nine controls (P less than 0.003). Autoimmune antibodies against the outer segment of the photoreceptor were noted in 7 of 12 patients, in contrast to only one of nine controls (P less than 0.02). Findings with the ocular fluids generally mirrored those with the sera. These autoantibodies could not be absorbed by conventional techniques using either retinal S-antigen (S-Ag) or the interphotoreceptor retinoid binding protein, an observation suggesting that other ocular antigens are involved. Such anti-retinal antibodies, especially those directed against the inner retina, may play a significant role in the pathogenesis of the retinal degeneration and optic atrophy that occur as a consequence of onchocerciasis.

Adult↗

Bromocriptine and low dose cyclosporine in the treatment of experimental autoimmune uveitis in the rat.

The immunologic effects of bromocriptine and low dose cyclosporine on experimental autoimmune uveitis (EAU) induced in Lewis rats by S-antigen immunization were studied. Rats treated with a sub-optimal dose (low dose) of cyclosporine (2 mg/kg per d), bromocriptine (1.8 mg/kg per d), or both drugs were compared with untreated rats in regard to the development of EAU, lymphocyte proliferative responses, and anti-S-antigen serum antibodies. Bromocriptine alone decreased the incidence of EAU only in female rats (P less than 0.01), did not effect the lymphocyte proliferative response, but did significantly decrease antibody titers in both males (P less than 0.004) and females (P less than 0.0005). Low dose cyclosporine also partially decreased the incidence of EAU in female rats, but did not decrease antibody titers or lymphocyte proliferative responses. Bromocriptine plus low-dose cyclosporine led to more marked decreases in the incidence of EAU and anti-S-antigen antibody titers as well as in the lymphocyte proliferative assay (P less than 0.01 for males, P less than 0.0005 for females). This study suggests that bromocriptine can enhance the immunosuppression of low dose cyclosporine.

Animals↗

Presence of HTLV-III in tears and cells from the eyes of AIDS patients.

Tears, conjunctival epithelium, and corneoscleral tissue from AIDS patients were used for the isolation of HTLV-III and also for identifying cell types which support its replication. HTLV-III was isolated from tears of AIDS patients (66.6%) by cultivation of cells and fluid from patients' eyes with fresh human mononuclear cells. The cells from the conjunctival scrapings of these patients (33.3%) revealed HTLV-III antigens by indirect immunofluorescence (IF) using anti-P24 and P15 monoclonal antibodies. HTLV-III from the cell-free supernatant of the infected mononuclear cells from two patients' cocultures were further transmitted into fresh cells. The cells from right and left central cornea, as well as limbal cornea from an asymptomatic HTLV-III antibody-positive individual and one AIDS patient revealed HTLV-III upon cocultivation. HTLV-III P15 and P24 antigens were detected in cultured primary cornea epithelial cells. The tears and conjunctival cells from a control group were found to be free of HTLV-III. Although no documented cases of AIDS have been reported in corneal transplant recipients, serologic screening of donors prior to the use of the tissues for transplantation is advisable. Our data also raises important questions regarding possible transmission of virus during ophthalmologic examination by way of examiner's hands, through instruments and during contact lens fittings. Moreover, these findings indicate the need for testing various eye disinfectants for virus inactivation and/or inhibition.

Acquired Immunodeficiency Syndrome↗

Neovascular glaucoma after helium ion irradiation for uveal melanoma.

Neovascular glaucoma developed in 22 of 169 uveal melanoma patients treated with helium ion irradiation. Most patients had large melanomas; no eyes containing small melanomas developed anterior segment neovascularization. The mean onset of glaucoma was 14.1 months (range, 7-31 months). The incidence of anterior segment neovascularization increased with radiation dosage; there was an approximately three-fold increase at 80 GyE versus 60 GyE of helium ion radiation (23% vs. 8.5%) (P less than 0.05). Neovascular glaucoma occurred more commonly in larger tumors; the incidence was not affected by tumor location, presence of subretinal fluid, nor rate of tumor regression. Fifty-three percent of patients had some response with intraocular pressures of 21 mmHg or less to a combination of antiglaucoma treatments.

Anterior Eye Segment↗

Expression of class II antigen in endotoxin induced uveitis.

Uveitis can be induced by systemic or intravitreal administration of endotoxin (lipopolysaccharide, LPS). In this study we correlated the expression of class II antigens (la in rat) of the Major Histocompatibility Complex (MHC), with this experimental model of uveitis. Ia antigen was detected by immunohistochemistry using the Avidin-Biotin-Peroxidase Complex (ABC) method and the monoclonal antibody OX6. Ia antigen was not expressed in normal eyes. However, Ia was expressed in the anterior uvea epithelial cells in all eyes with LPS induced uveitis. This study demonstrates that the ocular Ia expression is a localized process in the anterior uvea in response to systemic or intravitreal LPS. This response appears to be distinct from the action of LPS on macrophage Ia expression, where LPS has been shown to inhibit the induction of Ia antigen in macrophages by gamma interferon.

Animals↗

Purification and characterization of a low molecular weight transforming growth factor from the urine of melanoma patients.

A low Mr human transforming growth factor (TGF) present in melanoma patients' urine has been purified approximately 200,000-fold to apparent homogeneity. Initial purification of an acid-soluble fraction of urine was achieved by Bio-Gel P-30 gel filtration chromatography in 1 M acetic acid. TGF activities were demonstrated in the Mr ranges of 30,000 and 6,000-10,000. These competed with epidermal growth factor (EGF) for binding to A431 membrane receptors and induced anchorage-independent growth of untransformed fibroblasts. The low Mr TGF activity obtained from P-30 chromatography was purified to apparent homogeneity by two sequential reverse-phase high performance liquid chromatography steps with a mu Bondapak C18 column first using a linear gradient of acetonitrile going from 0-60% in 120 min and then by rechromatography of the activity over the same column using a shallower gradient of acetonitrile going from 20-40% in 160 min. The isoelectric point of the melanoma patient-derived urinary TGF was determined to be 6.2, which is distinct from that for human EGF. Amino acid composition analysis of the purified urinary TGF (uTGF) revealed that it is composed of at least 42 amino acid residues with a minimum estimated Mr of 4,545. Compositional analysis further revealed distinct similarities and differences between the uTGF, human EGF and TGFs secreted by various transformed human and rodent cell lines.

Amino Acids↗

Inhibitory effect of hyperosmolality on catecholamine secretion from the bovine adrenal medulla.

We examined the effect of hyperosmolality on exocytotic catecholamine secretion in isolated-perfused bovine adrenals, in both the absence and presence of Ca2+ in the extracellular medium. Exposure of adrenal glands to hyperosmotic media (600 mOsm/Kg H2O) for 20 minutes significantly decreased spontaneous catecholamine output, and was independent of extracellular Ca2+ concentration. Adrenal glands were exposed to a hyperosmotic Locke solution (600 mOsm/Kg H2O) for 10 minutes and then stimulated with acetylcholine. Hyperosmolality produced a significant, reversible inhibition of acetylcholine-evoked catecholamine secretion. As the osmotic strength of the perfusion fluid was increased, either by addition of sucrose or NaCl, there was a progressive reduction in the acetylcholine response. Hyperosmolality also decreased catecholamine release induced by 56 mM K+ and by removal of NaCl from the perfusion medium. Similar results were seen in glands exposed to a NaCl-free solution in the absence of extracellular Ca2+. These results suggest that inhibitory effects of hyperosmolality on stimulus-secretion coupling in the adrenal medulla are exerted after Ca2+ enters the chromaffin cells, and support one of the primary criteria of the chemiosmotic hypothesis.

Acetylcholine↗

Vasoactive effect of sera from preeclamptic patients.

Investigated was a bioassay method for measurement of vasoactivity in the serum of preeclamptic patients. Intravital microscopy was used to measure the diameter of the principal arteriole and venule in the gastrolienal mesentery of mice before (VD1) and after (VD2) the intravenous injection of sera from preeclamptic primigravid patients and from preeclamptic primigravid patients after treatment with magnesium sulfate (MgSO4). A vasoactive index (VI) was calculated as VD2/VD1. The VIa (vasoactive index for arteriole) of preeclamptic primigravid patients (0.64 +/- 0.39, mean +/- SD) was significantly different (p less than 0.01) from the VIa of normal primigravid patients (0.91 +/- 0.08) and from the VIa of saline controls (0.99 +/- 0.02). Four of the seven preeclamptic primigravid patients had a duration of signs and symptoms dating from the antepartum period (VIa = 0.53 +/-. 0.42), and for three, the diagnosis was made only in the intrapartum period (VIa = 0.77 +/- 0.38). Sera from the MgSO4-treated preeclamptic patients yielded a VIa of 0.91 +/- 0.14, which was not significantly different from that for either the normal primigravid patients or the saline controls. This VIa value was significantly different (p less than 0.01) from the VIa of the untreated preeclamptic patients. These results suggest that here is a vasoactive substance(s) in the sera of preeclamptic patients which may contribute to their arteriolar vasospasm. The magnitude of vasoactivity appears to be related to the duration and severity of preeclampsia but is masked or disappears after treatment of the patient with MgSO4.

Animals↗