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Biomedical subjects

M Kim

Publications and source records attributed to M Kim.

At least 397 records · Page 22Linked to original sources
PubMed1988

Inherited superactivity of phosphoribosylpyrophosphate synthetase: association of uric acid overproduction and sensorineural deafness.

PURPOSE: Superactivity of 5-phosphoribosyl 1-pyrophosphate (PP-Rib-P) synthetase, inherited as an X chromosome-linked trait, has been reported in nearly 20 families in which overproduction of uric acid is invariably present in hemizygous affected males. Clinical manifestations of PP-Rib-P synthetase superactivity are mainly limited to gout in early adulthood. Neurologic deficits, including sensorineural deafness, have rarely been described. We herein document the association of PP-Rib-P synthetase superactivity, gout with excessive uric acid synthesis, and sensorineural deafness in an additional family. PATIENTS AND METHODS: Two members of a Spanish family were studied: an eight-year-old boy (Patient 1) with tophaceous gout, purine nucleotide and uric acid overproduction, and sensorineural deafness, and his 27-year-old mother (Patient 2), who had gout. Fibroblast cultures were initiated from skin biopsy specimens, and measurements of PP-Rib-P and purine nucleotide metabolism in the fibroblasts were performed. RESULTS: A labile but superactive PP-Rib-P synthetase was demonstrated in the fibroblasts cultured from both Patients 1 and 2. The kinetic basis of PP-Rib-P synthetase superactivity in this family was resistance to purine nucleotide inhibition of enzyme activity. More severe derangements in the enzyme and in PP-Rib-P and purine synthesis in Patient 1's cells than in Patient 2's cells suggest that Patient 1 is hemizygous and Patient 2 is heterozygous for an X chromosome-linked genetic defect. Limited pedigree data support this view. Compared with affected members of seven other families with PP-Rib-P synthetase superactivity, these patients are intermediate in the range of clinical expression and in the severity of the enzyme defect as measured by the degree of aberration of PP-Rib-P and purine nucleotide synthesis in fibroblasts. Metabolic abnormalities were more severe in Patient 1's cells than in the cells of most male patients (in whom clinical expression is limited to early adult-onset gout) but were less severe than in the cells of two patients in whom more complex enzyme defects were associated with uric acid overproduction and neurodevelopmental abnormalities (including deafness) in male children and adult women. CONCLUSION: Certain defects resulting in PP-Rib-P synthetase superactivity may be causally related to neurologic impairment, most commonly sensorineural deafness.

Adult↗
PubMed1988

Fluorescence assessment of skin perfusion after oral fluorescein.

This study evaluated oral ingestion as the route of fluorescein administration for fluorescence assessment of skin perfusion. In 10 anesthetized rats, dorsal pedicle flaps were raised to produce graded perfusion; then fluorescein (7.5 mg/kg) was administered via an oropharyngeal tube. Quantification of skin fluorescence, performed with the fiberoptic fluorometer 45 minutes after dye ingestion, delineated a significant difference between the perfusion of flap regions that remained viable and those that subsequently became dystrophic (p less than 0.05). The precision was equivalent to that previously reported after intravenous dye. In addition, the gradual delivery of dye after oral administration permitted monitoring of slope of uptake and time to peak. Each of these pharmacokinetic parameters delineated a significant difference between viable and nonviable sections. As measures of relative change in fluorescence, they are independent of skin color and thickness. This feature suggests that the oral route actually may improve the accuracy and reliability of the fluorescein test.

Administration, Oral↗
PubMed1987

Regulation of purine synthesis de novo in human fibroblasts by purine nucleotides and phosphoribosylpyrophosphate.

Previous studies of purine nucleotide synthesis de novo have suggested that major regulation of the rate of the pathway is affected at either the phosphoribosylpyrophosphate (PP-Rib-P) synthetase reaction or the amidophosphoribosyltransferase (amido PRT) reaction, or both. We studied control of purine synthesis de novo in cultured normal, hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient, and PP-Rib-P synthetase-superactive human fibroblasts by measuring concentrations and rates of synthesis of PP-Rib-P and purine nucleotide end products, proposed effectors of regulation, during inhibition of the pathway. Incubation of cells for 90 min with 0.1 mM azaserine, a glutamine antagonist which specifically blocked the pathway at the level of conversion of formylglycinamide ribotide, resulted in a 5-16% decrease in purine nucleoside triphosphate concentrations but no consistent alteration in generation of PP-Rib-P. During this treatment, however, rates of the early steps of the pathway were increased slightly (9-15%) in normal and HGPRT-deficient strains, more markedly (32-60%) in cells with catalytically superactive PP-Rib-P synthetases, and not at all in fibroblasts with purine nucleotide feedback-resistant PP-Rib-P synthetases. In contrast, glutamine deprivation, which inhibited the pathway at the amido PRT reaction, resulted in time-dependent nucleoside triphosphate pool depletion (26-43% decrease at 24 h) accompanied by increased rates of PP-Rib-P generation and, upon readdition of glutamine, substantial increments in rates of purine synthesis de novo. Enhanced PP-Rib-P generation during glutamine deprivation was greatest in cells with regulatory defects in PP-Rib-P synthetase (2-fold), but purine synthesis in these cells was stimulated only 1.4-fold control rates by glutamine readdition. Stimulation of these processes in normal and HGPRT-deficient cells and in cells with PP-Rib-P synthetase catalytic defects was, respectively: 1.5 and 2.0-fold; 1.5 and 1.7-fold; and 1.6 and 4.1-fold. These studies support the following concepts. 1) Rates of purine synthesis de novo are regulated at both the PP-Rib-P synthetase and amido PRT reactions by end products, with the latter reaction more sensitive to small changes in purine nucleotide inhibitor concentrations. 2) PP-Rib-P exerts its role as a major regulator of purine synthetic rate by virtue of its interaction with nucleotide inhibitors to determine the activity of amido PRT. 3) Activation of amido PRT by PP-Rib-P is nearly maximal at base line in fibroblasts with regulatory defects in PP-Rib-P synthetase.

Azaserine↗
PubMed1987

Mechanisms of accelerated purine nucleotide synthesis in human fibroblasts with superactive phosphoribosylpyrophosphate synthetases.

Concentrations and rates of synthesis of phosphoribosylpyrophosphate (PP-Rib-P) and purine nucleotides were compared in fibroblasts cultured from 5 males with PP-Rib-P synthetase superactivity, 3 normal individuals, and 2 children with severe hypoxanthine-guanine phosphoribosyltransferase deficiency. Although all cell strains with PP-Rib-P synthetase superactivity showed increased PP-Rib-P concentration and generation, increased rates of PP-Rib-P-dependent purine synthetic pathways, and increased purine and pyrimidine nucleoside triphosphate concentrations, two subgroups were discernible. Three fibroblast strains with isolated catalytic defects in PP-Rib-P synthetase showed milder increases in PP-Rib-P concentration (2.5-fold normal) and generation (1.6- to 2.1-fold) and in rates of purine synthesis de novo (1.6- to 2.2-fold) and purine nucleoside triphosphate pools (1.5-fold) than did cells from 2 individuals with combined kinetic defects in PP-Rib-P synthetase, both with purine nucleotide inhibitor-resistance. Values for these processes in the latter two strains were, respectively, 5- to 6-fold, 2.6- to 3.2-fold, 4- to 7-fold, and 1.7- to 2.2-fold those of normal cells. In contrast to cells with catalytic defects, these cells also excreted an abnormally high proportion of labeled purines and resisted purine base-mediated inhibition of PP-Rib-P and purine nucleotide synthesis. Hypoxanthine-guanine phosphoribosyltransferase-deficient cells showed normal regulation of PP-Rib-P synthesis and normal nucleoside triphosphate pools despite increased rates of purine synthesis de novo and of purine excretion. Cells with PP-Rib-P synthetase superactivity thus synthesize purine nucleotides at increased rates as a consequence of increased PP-Rib-P production, despite increased purine nucleotide concentrations. These and additional findings provide evidence that regulation of purine synthesis de novo is effected at both the PP-Rib-P synthetase and amidophosphoribosyltransferase reactions.

Biopsy↗
PubMed1987

Differential polarization imaging. I. Theory.

A theory of differential polarization imaging is derived using Mueller calculus. It is shown that, for any arbitrary object, 16 images (in general different) can be obtained by combining different incident polarizations of light and measuring the specific polarization components transmitted or scattered by the object. These are called the Mueller images of the object. Mathematical expressions of these images for an object of arbitrary geometry are derived using classical vector diffraction theory and the paraxial and thin lens approximations. The object is described as a collection of point polarizable groups. The electromagnetic fields are calculated using the first Born-Approximation, but extension of the theory to higher-order approximations is shown to be straightforward. These expressions are obtained for the transmission, or bright-field, geometry, and the scattering, or dark-field, configuration. In both cases, the contributions of scattering, absorption, and background illumination to the Mueller images are characterized. The contributions of linear dichroism, circular dichroism, and linear and circular intensity differential scattering to certain Mueller images are established. It is shown that the Mueller images represent a complete two-dimensional mapping of the molecular anisotropy of the object.

Mathematics↗
PubMed1987

Differential polarization imaging. II. Symmetry properties and calculations.

Various differential polarization images or Mueller images of model objects are generated using the equations derived in the previous paper (paper I of this series). These calculated images include models of the higher-order organization of metaphase chromosomes, and show the applicability of the differential polarization imaging method to the elucidation of complex molecular organizations. Then, the symmetry behavior of the Mueller matrix elements upon infinitesimal rotations of the optical components about the optical axis of the imaging system is presented. It is shown that the rotational properties of the Mueller images can be used to eliminate the linear polarization contributions to the M14 and M44 images, which appear when these images are generated with imperfect circular polarizations. The relationships between the 16 bright-field Mueller images for four different media, i.e., linearly and circularly isotropic, circularly anisotropic, linearly anisotropic, and linearly and circularly anisotropic, are also derived. For the first three cases simple relationships between the Mueller images are found and phenomenological equations in terms of the optical coefficients are derived. In the last case there are no specific relationships between the Mueller images and instead we briefly present Schellman and Jensen's method for treating this type of medium. The criterion of spatial resolution between adjacent domains of different optical anisotropy is then derived. It is found that in transitions between domains of opposite anisotropy the classical Rayleigh limit must be replaced by a magnitude criterion which depends on the limits of the sensitivity of the detection. Finally, the feasibility of optical sectioning in differential polarization imaging is demonstrated.

Mathematics↗
PubMed1987

In vitro fertilization and embryo transfer in patients with one ovary.

The purpose of this investigation was to compare follicular response and pregnancy rates in patients with one and two ovaries who have undergone in vitro fertilization (IVF). No statistically significant difference was found in serum estradiol levels on the day of human chorionic gonadotropin administration, mean number of follicles (greater than 15 mm), mean total number of oocytes recovered, mean number of mature oocytes recovered, or number of pregnancies per transfer. The total number of oocytes recovered in the one- and two-ovary groups was 47 and 123, respectively. There was a significantly greater mean number of immature oocytes recovered (1.5 +/- .03 versus 0.5 +/- 0.2, P less than 0.01) and embryos transferred (2.7 +/- 0.3 versus 1.7 +/- 0.3, P less than .04) in patients with two ovaries. Though not statistically significant, a trend was noted in the two-ovary group for a greater number of pregnancies per transfer (9:25 versus 2:14). The authors conclude that single-ovary patients may have a reduced outcome with IVF compared with patients with two ovaries.

Adult↗
PubMed1987

Burn-induced alterations in feeding, energy expenditure, and brain amine neurotransmitters in rats.

A 30% body surface area, open-flame, full-thickness burn of adult rats induced a 4-day period of anorexia that was followed by hyperphagia beginning on postburn day 10. The hyperphagic burned rats also exhibited increased resting energy expenditure and no gain in body weight, suggesting hypermetabolism. Plasma levels of immunoreactive insulin and albumin were decreased in both groups of burned rats; immunoreactive pancreatic glucagon concentrations were elevated only in the anorectic burned rats. Plasma levels of epinephrine were elevated in the hyperphagic burned rats. In the brain, dopamine metabolism appeared to be increased in the corpus striatum, nucleus accumbens, and amygdala of anorectic burned rats; norepinephrine levels were elevated in the hypothalamus and nucleus accumbens of the hyperphagic-hypermetabolic rats. These data indicate that this animal model of major burn trauma exhibits anorexia, hyperphagia, catabolism, and hypermetabolism. Furthermore, elevated dopamine metabolism appears to be associated with the anorexia, while the hyperphagia-hypermetabolism may be mediated by norepinephrine.

Animals↗
PubMed1986

[Correlations between depression and work problem of workers].

Recent increase of depressive patients visiting psychiatric clinics have been attributed to social and other environmental factors including those related to work environment. A questionnaire study was carried out in a Tokyo-based company which manufactures desk calculators and other electronic devices, to investigate associations between psychiatric symptoms related to depression and 32 items on work and work environment. Depression was found associated with aforementioned clusters middle-aged employees and executives, whereas it showed little association in young employees, a result suggesting relative vulnerability of the former.

Adult↗
PubMed1986

Surgical clinicopathologic study of malignant fibrous histiocytoma.

Fifteen men and six women, ranging in age from 20 to 79 years, with malignant fibrous histiocytoma comprised this series. Amputation of the right lower extremity was performed in one patient, wide resection in 7 and marginal excision in 9, respectively. In the other 4 patients, a non-curative resection was carried out. Adjuvant chemotherapy was prescribed post-operatively for 12 patients. Histologic grade of the surgical specimens was Stage I in 3, II in 6, III in 8 and IV in 4. Among fourteen patients living from 10 months to 9 years and 9 months after the operation, the 7 subjected to a wide resection are all disease free. Seven patients died of a local recurrence or a distant metastases. The survival rate of the patients with Stages I, II is significantly higher than those with Stages III, IV. These results show that a wide resection is to be favored and that staging is useful to estimate the prognosis.

Adult↗
PubMed1986

O6-methylguanine methyltransferase increases before S phase in normal human cells but does not increase in hypermutable Bloom's syndrome cells.

The regulation of the O6-methylguanine methyltransferase was examined during cell proliferation in hypermutable Bloom's syndrome fibroblasts and normal human skin fibroblasts. During synchronous growth following serum stimulation normal human cells enhanced methyltransferase activity 2.4-fold in the absence of exogenous damage as a normal regulatory event during the cell cycle. Methyltransferase activity was increased prior to the induction of DNA replication and of DNA polymerase and was diminished when each replicative activity was maximal. In contrast, although methyltransferase levels in quiescent cells are equivalent, hypermutable Bloom's syndrome cells did not increase methyltransferase at any interval in the cell cycle.

Bloom Syndrome↗
PubMed1985

Oral mucositis in patients undergoing bone marrow transplantation.

Thirty patients who received bone marrow transplantation treatment from HLA identical sibling donors for immunologic and malignant diseases were studied. In essentially all of the patients oral changes developed during the first 30 days following transplant. Oral symptoms frequently constituted the major complaints of the patients during the follow-up period. The oral changes included mucositis, xerostomia, pain, and bleeding. Mucositis was more severe and of longer duration when associated with herpes simplex infections and when optimal oral hygiene was not maintained. Xerostomia which accompanies engraftment was an early sign of acute graft-versus-host disease. A nonbrushing method of oral hygiene was effective in reducing the severity and duration of mucositis. This technique offers a short-term alternative to brushing in pancytopenic patients who are susceptible to bleeding or trauma.

Adolescent↗
PubMed1985

Selective expression of phosphoribosylpyrophosphate synthetase superactivity in human lymphoblast lines.

Phenotypic expression of 5-phosphoribosyl 1-pyrophosphate (PRPP) synthetase superactivity was examined in lymphoblast lines derived from six unrelated male patients. Fibroblasts from these individuals have increased rates of PRPP and purine nucleotide synthesis and express four classes of kinetic derangement underlying enzyme superactivity: increased maximal reaction velocity (catalytic defect); inhibitor resistance (regulatory defect); increased substrate affinity (substrate binding defect); and combined catalytic and regulatory defects. Lymphoblast lines from three patients with catalytic defects and from three normal individuals were indistinguishable with respect to enzyme activities, PRPP concentrations and generation, and rates of purine synthesis. Enzyme in lymphoblasts from a patient with combined defects also showed normal maximal reaction velocity but expressed purine nucleotide inhibitor resistance. A second regulatory defect and a substrate binding defect were also demonstrable in lymphoblasts and were identical to the enzyme defects in fibroblasts from the respective patients. Regulatory and substrate binding defects in lymphoblasts were accompanied by increased rates of PRPP and purine nucleotide synthesis. Among explanations for selective expression of enzyme superactivity, reduced concentrations of catalytically superactive enzymes seemed unlikely: immunoreactive PRPP synthetase was comparable in normal-derived and patient-derived cells. Activation of normal enzyme in transformed lymphocytes was also unlikely because absolute specific activities of lymphoblast PRPP synthetases corresponded to those of normal fibroblast and erythrocyte enzymes. Abnormal electrophoretic mobilities and thermal stabilities, identified in certain catalytically superactive fibroblast PRPP synthetases, were not found in the corresponding lymphoblast enzymes. Thus, lymphoblast PRPP synthetases from patients with catalytic superactivity appeared to differ structurally and functionally from their fibroblast counterparts.

Allosteric Regulation↗
PubMed1985

The natural history of idiopathic hyperprolactinemia.

Idiopathic hyperprolactinemia (IH) can be defined as the presence of elevated serum PRL levels in a patient in the absence of demonstrable pituitary or central nervous system disease and of any other recognized cause of increased PRL secretion. This study examined the long term clinical outcome of 41 patients (mean age, 26 yr) with IH followed for up to 11 yr (mean, 5.5 yr). Initial and final PRL levels were determined by RIA in the same laboratory. A correction factor was used to obviate periodic changes in the potency of the NIH standards used in the PRL assay, so that all results are expressed in terms of the original VLS no. 1 standard. The initial serum PRL levels ranged from 27.2-243 ng/ml, with a mean of 57 ng/ml. Only three patients had initial serum PRL levels greater than 100 ng/ml. All had a normal skull x-ray and/or brain computed tomographic scan during their initial visit. All 41 patients had galactorrhea and/or amenorrhea. Serum PRL levels remained the same, decreased, or returned to normal in 34 of 41 patients. The mean PRL level at the time of reevaluation was 35 ng/ml. Thirty-four percent of the patients had a normal serum PRL level. Only 17% of the patients had serum PRL levels that were significantly higher (greater than 50% of their original value). Six of 9 patients with an initial serum PRL level less than 40 ng/ml had normal levels. One patient developed a pituitary tumor (initial PRL, 150 ng/ml). All patients reevaluated with brain computed tomographic scans had normal pituitary size. No patient reported a worsening of signs or symptoms, and in many, improvement (n = 16) or complete resolution (n = 8) of the amenorrhea and/or galactorrhea occurred. Twenty-seven spontaneous or bromocriptine-induced normal pregnancies and deliveries occurred without development of a pituitary tumor. Therefore, our data clearly challenge the use of ablative pituitary therapy for IH and raises questions of the benefit of chronic medical therapy for this condition.

Adult↗