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Biomedical subjects

H J Kim

Publications and source records attributed to H J Kim.

At least 19 recordsLinked to original sources

The use of a spectrophotometric assay to study the interaction of S-adenosylmethionine synthetase with methionine analogues.

We have developed a continuous spectrophotometric assay for S-adenosylmethionine synthetase and, using this assay, have examined the interaction of five potential inhibitors with the E. coli enzyme. S-Vinylhomocysteine and S-allylhomocysteine were found to be substrates, while S-(methanethio)cysteine and S-(methanethio)homocysteine were found to be competitive inhibitors. S-Cyanohomocysteine is neither a substrate nor an inhibitor.

Bacterial Proteins

Mutation creates an open reading frame within the 5' untranslated region of macaque erythrocyte carbonic anhydrase (CA) I mRNA that suppresses CA I expression and supports the scanning model for translation.

A variant allele at the CA I locus that produces a deficiency of erythrocyte-specific CA I occurs as a widespread polymorphism in pigtail macaques from southeast Asia. Sequence analyses revealed a C----G substitution 12 nucleotides downstream of the cap site in the variant erythrocyte CA I mRNA. This mutation forms a new AUG start site and an open reading frame coding for 26 amino acids that terminates 6 nucleotides before the normal AUG initiation codon for CA I. It appears that the presence of this upstream open reading frame greatly diminishes reinitiation of translation from the normal start site, resulting in trace levels of CA I in erythrocytes. Preferential use of the first AUG codon supports the scanning model for translation initiation in eukaryotes.

Animals

Tissue sulfate determination by ion chromatography.

The application of controlled-flow anion chromatography to assay inorganic sulfate in biological fluids and tissues is described. The eluent used in previous methods for analyzing sulfate in biological fluids has been modified by adding 4.5% acetonitrile to separate sulfate from a co-eluting peak. To markedly increase the life of the column, the tissue samples were further diluted, extracted with chloroform, and analyzed at a lower detection range (0.3 microS). The method has been shown to be applicable for determining sulfate in tissues as well as biological fluids.

Animals

1,25-Dihydroxy-vitamin-D3 enhances antiproliferative effect and transcription of TGF-beta1 on human keratinocytes in culture.

Both TGF-beta and 1,25-dihydroxy-vitamin-D3 (1,25(OH)2D3) have been reported to decrease the proliferation of normal human keratinocytes. The effect and expression of TGF-beta in keratinocytes treated with 1,25(OH)2D3 was investigated. Human keratinocytes were grown in the presence of various concentrations of TGF-beta and/or 1,25(OH)2D3 prior to enumeration. TGF-beta, alone, has a half maximal dose of inhibition (ED50) of approximately 750 pg/ml after seven days in culture in Keratinocyte Growth Medium (KGM; Clonetics) supplemented with 1.5 mM calcium. When 1,25(OH)2D3 (10(-7)M) was also added to cultures with various concentrations of TGF-beta, the ED50 shifted an average of 2-fold less. The presence of TGF-beta (10 pg/ml) augmented the potency of 1,25(OH)2D3 by at least 10-fold. In keratinocyte cultures, the antiproliferative effect of the two compounds together is synergistic. In keratinocytes grown for 1 week in the presence of 1,25(OH)2D3 at 10(-6)M, the TGF-beta 1 message increased approximately 5-fold. An increase is detected within 2 hours of exposure to 1,25(OH)2D3. There was only a 50% increase in the levels of TGF-beta 2 and no detection of TGF-beta 3. When keratinocyte cultures were treated with 1,25(OH)2D3 and neutralizing antibodies to TGF-beta, the induced-antiproliferative activity was blocked by more than 50%. The keratinocytes produced more active than latent TGF-beta after growth with high doses of 1,25(OH)2D3.

Antibodies

Clinical application of arterialization of portal vein in living related donor partial liver transplantation.

Arterialization of the portal vein was employed during hepatic arterial reconstruction in our first few clinical experiences of partial liver transplantation using liver grafts obtained from living related donors. This procedure reduced the time required for revascularization of the grafts to about 25 min, and could in fact reduce the ischemic phase of the grafts. Repeated practice of the clinical transplantation technique has shortened the time needed to complete vascular reconstruction, eliminating the need for this procedure in most of our subsequent cases. In many clinical cases, however, there may be emergency situations which require vascular reconstruction, resulting in a prolongation of ischemic phase and the deterioration of the cellular viability of the graft. In such situations, arterialization of the portal vein can be a useful way to prevent the prolongation of the ischemic phase and to rescue the graft.

Arteriovenous Shunt, Surgical

Pharmacokinetic simulations of SPECT quantitation of the M2 muscarinic neuroreceptor subtype in disease states using radioiodinated (R,R)-4IQNB.

Alzheimer's disease (AD) involves selective loss of muscarinic M2, but not M1, subtype neuroreceptors in the posterior parietal cortex of the human brain. Emission tomographic study of the loss of M2 receptors in AD is limited by the fact that there is currently no available M2-selective radioligand which can penetrate the blood-brain barrier. However, by taking advantage of the different pharmacokinetic properties of (R,R)-[123I]IQNB for the M1 and M2 subtypes, it may be possible to estimate losses in M2. It has previously been hypothesized that the difference between an early study and a late study should provide information on the M2 receptor population. In order to test this hypothesis, we present here the results of pharmacokinetic simulations of the in vivo localization of (R,R)-[123I]IQNB in brain regions containing various proportions of M1 and M2 subtypes. These results permit us to conclude that SPECT imaging of (R,R)-[123I]IQNB localization can potentially be used to quantitate changes in the M2 subtype in a disease state within a brain region for which the ratio M2/M1 is sufficiently high in normal individuals.

Alzheimer Disease

Retinoids for the future: investigational approaches for the identification of new compounds.

One desired goal for future retinoid development is the dissociation of therapeutic benefit from teratogenic risk. It is not known if this result can be achieved, but increasing our understanding of the molecular mechanisms of retinoid action offers rational approaches to the attainment of this goal. The basis for these new approaches is the recent discovery of nuclear receptors for all-trans-retinoic acid and for the 9-cis form of retinoic acid. These receptors, like the steroid hormone receptors, are ligand-dependent transcription factors. Retinoids act by binding to these receptors and modulating specific gene pathways that ultimately control cell differentiation and development. Retinoic acid is required for normal embryonic development, and retinoic acid concentrations are regulated in the developing embryo. The malformations associated with in utero exposure to retinoids might be the result of inappropriate activation of specific receptors and inappropriate modulation of specific gene pathways. At least three nuclear receptors for all-trans-retinoic acid and three nuclear receptors for the 9-cis form of retinoic acid are known to exist, with the two receptor subfamilies interacting to form heterodimers. This multiplicity of receptors and receptor interactions suggests that differences may exist among receptors in the biologic effects they mediate. Although some retinoid ligands are not specific, others are highly selective for one particular receptor. Contrasting the effects of ligands with different specificities should increase understanding of the biologic responses associated with specific receptors and efforts to dissociate therapeutic activity from undesired effects.

Animals

Effect of topical retinoic acids on the levels of collagen mRNA during the repair of UVB-induced dermal damage in the hairless mouse and the possible role of TGF-beta as a mediator.

Topically applied retinoic acids have been found to enhance the gene expression for collagen types I and III in the skin of UVB-irradiated hairless mice. Prior damage is required because the effect is not observed in the skin of age-matched, non-irradiated control animals. Immunochemical methods have shown an increase in TGF-beta 1 and, to a lesser extent, of TGF-beta 2 in the epidermis following retinoic acid treatment. There were no changes in mRNA levels for any of the isotypes of TGF-beta induced by retinoic acid treatment. This study suggests that TGF-beta may mediate the effect of retinoic acids on dermal repair through the stimulation of collagen gene expression.

Administration, Topical

Acquired tufted angioma associated with pregnancy.

Acquired tufted angioma is a distinctive condition that is different from other types of acquired vascular proliferation. Despite the progressive spread of these angiomas, they appear to be benign, and malignant change has not been encountered. We describe a case of recurrent acquired tufted angioma associated with pregnancy, an association which has not been previously recorded.

Adult

Intraventricular neurocytoma: clinicopathological analysis of seven cases.

A retrospective analysis of seven patients with intraventricular neurocytoma is presented. Patient age at diagnosis ranged from 15 to 38 years (mean 24.6 years) and the male:female ratio was 6:1. Raised intracranial pressure due to hydrocephalus was the main cause of the clinical manifestations. An isodense mass with multiple intratumoral cysts and homogeneous contrast enhancement was the characteristic computerized tomography finding. The lesions commonly involved the lateral ventricle with or without extension to the third ventricle. Cerebral angiography showed homogeneous vascular staining in five patients. Magnetic resonance images revealed a mass isointense with the cerebral cortex on both T1- and T2-weighted images. Gadolinium-diethylenetriaminepenta-acetic acid-enhanced images showed homogeneous enhancement. Total removal of the tumor was possible in four patients. Pathologically, six cases were initially diagnosed as oligodendroglioma and the remaining case as ependymoma. However, immunohistochemical studies demonstrated strong positivity for neuron-specific enolase in all seven cases and for synaptophysin in five cases. On electron microscopy, three cases showed well-defined neurosecretory granules and 10-nm microtubules in their cytoplasm and cytoplasmic processes. One patient developed a recurrent tumor 18 months after surgery. The remaining six patients are free of recurrent tumors at 2 to 62 months after surgery. It is suggested that neurocytoma must be included in the differential diagnosis of intraventricular lesions, and that electron microscopic and immunohistochemical studies should be undertaken.

Adolescent

POEMS syndrome--a case report.

POEMS syndrome is a multisystem disorder associated with polyneuropathy, organomegaly, endocrinopathy, a monoclonal protein (M-protein), and skin changes. The authors describe a patient with POEMS syndrome who had osteosclerotic myeloma confirmed by open bone biopsy. Magnetic resonance imaging (MRI) showed discrete lesions of low signal intensity in both T1 and T2-weighted images. This patient is now being successfully treated with melphalan and prednisone with much improvement in skin thickening and sensory change in the lower extremities.

Adult

[Comparative study on the effectiveness of modified Kato's cellophane thick smear and Stoll's dilution egg counting technique for quantitative fecal examination of helminth eggs].

A total of 197 fecal specimens was prepared for quantitative examination of helminth eggs by modified Kato's cellophane thick smear (M.C.T.S.) and Stoll's dilution egg counting technique (D.E.C.T.). The comparative effectiveness of two techniques was evaluated and conversion function was deduced. The average time required for the microscopic examination on one slide by M.C.T.S. was 12.6 minutes and that of D.E.C.T. was 14.6 minutes. M.C.T.S. showed lower false negative rate than D.E.C.T. in light worm burden cases. Functions to convert the counts obtained by M.C.T.S. to E.P.G. by Stoll's dilution egg counting technique were 47.86 x 10(0.87) logM.C.T.S. in A. lumbricoides, 41.69 x 10(0.82) logM.C.T.S. in T. trichiura and 63.10 x 10(0.85) logM.C.T.S. in C. sinensis. It was suggested M.C.T.S. be better than D.E.C.T. for the quantitative examination of intestinal helminthiases such as A. lumbricoides, T. trichiura, and C. sinensis infections even in the cases with low worm burden.

Cellophane

Compartmental analysis of RBC circulation through the rabbit kidney.

This experiment involved 12 rabbits of both sexes, weighing 2.1 kg. After anesthesia, the kidneys were exposed, isolated and cannulated in the renal artery, ureter and sometimes in the vein as well. The kidney were perfused through the renal artery with Krebs-Henseleit solution, which were then filtered to be free of particles, gased with 95% O2-5% CO2, and kept at 37 degrees C. We measured RBCs concentrations by means of Coulter Counter in the venous outflow collected, and plotted them against the volume perfused. Using 2 different flow rates, 9 ml/min (group I) and 19 ml/min (group II), we found that the RBCs decreased in a multiexponential decay fashion and a biophysical model for each flow rate was constructed. These models indicated that there were more cell stores (2.20 x 10(10)) in the fast compartment of group II than in group I (1.72 x 10(10)). This difference is not statistically significant, but certainly coincides with urine flow collected from ureter cannula during perfusion. Our present data clearly suggest that in order to clear 99% blood cells out of 10-12 gm rabbit kidneys, at least 3-6 ml of cell free perfusate is required while clearing the whole blood cells out of human kidneys (200-240 gm) may need 600 ml or more. Thus, we recommend that at least 600 ml of perfusate should be used to clear most of the blood cells in the renal vasculature before renal transplantation is performed.

Animals

Heterogeneous changes of serum potassium levels in NIDDM patients on oral glucose load.

Ten noninsulin dependent diabetic patients (NIDDM) without baseline hyperkalemia and with normal aldosterone levels when given 100 g of glucose orally revealed heterogeneous responses in serum potassium changes. Six diabetics had paradoxical increases in serum potassium levels averaged 0.44 mEq/L (range, 0.1 to 1.1 mEq/L) and were accompanied by increases in plasma aldosterone levels. On the contrary, four other noninsulin dependent diabetics and four nondiabetic control subjects had gradual decreases in serum potassium levels with simultaneous decreases in plasma aldosterone levels. These rises and falls in serum potassium concentrations coincided with changes in serum osmolality related mostly to the degree of increases in serum glucose following oral glucose administration. pH of venous blood didn't show any relevant and significant changes with changes of serum potassium levels following oral glucose load. This finding suggests that osmotic mechanisms with various degree of well known abnormal insulin secretion and resistance to insulin action in target tissues in NIDDM patients may account for these heterogeneous responses in serum potassium changes after glucose load, and normal aldosterone levels may not be sufficient to prevent glucose induced increases in serum potassium in NIDDM patients.

Administration, Oral

Simultaneous expression of keratin and glial fibrillary acidic protein by the same cells in epiretinal membranes.

The identification of cells comprising epiretinal membranes is difficult because of the phenotypic changes that occur. Examination of intermediate filament protein content by immunocytochemical analysis can help to identify some cells with altered ultrastructure but is not always definitive because altered expression of intermediate filament proteins can also occur. To examine this issue further, the authors utilized a postembedding immunocytochemical technique with epiretinal membranes in which they were able to double label for keratin, a useful marker for identifying retinal pigment epithelial cells, and glial fibrillary acidic protein (GFAP), a useful marker for identifying glial cells. Nine of ten idiopathic epiretinal membranes contained cells that labeled for GFAP and not keratin. Two of these membranes also contained cells that labeled only for keratin and one membrane contained cells that simultaneously labeled for both GFAP and keratin. Other types of epiretinal membranes had an equal participation by cells that expressed only GFAP or keratin (12 of 17 membranes contained cells positive for keratin; 13 of 17 contained cells positive for GFAP). Ten of 17 nonidiopathic membranes contained cells simultaneously expressing GFAP and keratin, although they comprised only a minor subpopulation of the total number of cells present. These findings demonstrate that keratin and GFAP are not mutually exclusive intermediate filament proteins in cells of epiretinal membranes and that, although each may provide a helpful adjunct for cell type identification, neither is an absolutely specific marker.

Eye Diseases

Effect of phenylpropanolamine hydrochloride on blood pressure in Korean patients with hypertension controlled by hydrochlorothiazide.

The effect of 10 oral doses of phenylpropanolamine hydrochloride 25 mg four times a day on blood pressure and heart rate in Korean patients with hypertension controlled by hydrochlorothiazide was studied. A randomized, placebo-controlled, crossover, double-blind study design was used. Twenty Korean patients with mild hypertension controlled by hydrochlorothiazide were recruited from an ambulatory-care clinic. Blood pressure and heart rate were measured in triplicate before treatment, after a five-day washout period between phases of treatment, and two hours after the last dose in each phase of treatment. Eighteen patients completed both phases of treatment, and one patient completed only the placebo phase. Mean baseline values for systolic and diastolic blood pressures and heart rate before the placebo phase did not significantly differ from mean baseline values before the phenylpropanolamine phase. Comparison of mean baseline values for systolic and diastolic blood pressures and heart rate with mean after-treatment values showed no clinically relevant or statistically significant changes for the 19 patients who completed the placebo phase or the 18 patients who completed the phenylpropanolamine phase. There was no significant difference between the mean change in systolic blood pressure, diastolic blood pressure, or heart rate when the phenylpropanolamine phase was compared with the placebo phase. Phenylpropanolamine hydrochloride 25 mg p.o. four times a day (total, 10 doses) given to Korean patients with hypertension controlled by hydrochlorothiazide did not affect blood pressure or heart rate according to single-point outcome measurements.

Administration, Oral

Compensation for three-dimensional detector response, attenuation and scatter in SPECT grey matter imaging using an iterative reconstruction algorithm which incorporates a high-resolution anatomical image.

The use of SPECT to diagnose physiological alterations in disease states depends on the potential of SPECT to provide a quantitatively accurate reconstructed image. However, the reconstructed values depend upon the shape and size of the brain region as strongly as they depend upon true radioactivity concentration. We report here the results of applying an iterative reconstruction algorithm (IRA) to compensate for shape- and size-dependence, as well as for attenuation and scatter. The IRA is designed only for the reconstruction of images for which the true radioactivity in the white matter within the actual brain is negligible compared with the true radioactivity in the grey matter within the actual brain. The IRA incorporates an accurate three-dimensional model of detector response and utilizes an MRI image which defines the anatomical features of the brain being imaged by segmenting the grey, white and ventricular regions. It is the assumption of radioactivity localization exclusively in the grey matter which permits the efficient incorporation of the MRI image. The IRA was validated by simulation studies that utilized a slice through the basal ganglia in the realistic Hoffman three-dimensional mathematical brain model. FBP images deviate significantly from true radioactivity distribution, whereas IRA images are nearly identical to true radioactivity distribution, except for random fluctuations due to the presence of statistical noise. These results indicate that the application of the IRA will permit SPECT to distinguish deficits due to true physiological changes from apparent deficits due to imaging/reconstruction artifacts.

Algorithms