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Biomedical subjects

M H Kim

Publications and source records attributed to M H Kim.

At least 307 records · Page 17Linked to original sources
PubMed1987

Familial acanthosis nigricans. A longitudinal study.

The triad of hyperandrogenism, insulin resistance and acanthosis nigricans (HAIR-AN) is known to have a familial tendency. In order to better understand the natural history and possible treatment of this disorder, we studied the clinical course of two families in which all female progeny were affected. A rapid progression of the HAIR-AN syndrome was apparent during the peripubertal period and early reproductive years. Beyond this period, the progression of HAIR-AN appeared quite variable. Rapid weight gain was a major stimulant for increasing insulin resistance and hyperandrogenemia. In the one subject with a postmenarcheal onset of the syndrome, prolonged weight reduction was associated with an improvement in the dermatologic manifestation as well as in the hyperandrogenism and insulin resistance. Oral contraceptives appear to improve the dermatologic symptoms of the HAIR-AN syndrome.

Acanthosis Nigricans↗
PubMed1987

In vitro fertilization and embryo transfer as a treatment for male factor infertility.

In vitro fertilization was attempted in 25 consecutive cycles as a treatment for male factor infertility. These cycles were compared with 25 control cycles in which a male factor was not present. The fertilization rates for mature oocytes in male factor cases and controls were 17% and 70%, respectively (P less than 0.001). For immature oocytes, the fertilization rates for study patients and controls, respectively, were 16% and 57% (P less than 0.001). Embryos were available for transfer in 36% of study cycles and in 88% of control cycles (P less than 0.01). The pregnancy per transfer rate for study cycles was 33% and for control cycles was 32%. The hamster ova penetration assay was 100% specific and 50% sensitive in predicting fertilization in vitro among male factor patients.

Adult↗
PubMed1987

A rapid serum estrogen assay suitable for office use in monitoring follicular maturation.

Ovulation induction often requires the determination of serum estradiol levels. A rapid, sensitive, and simple non-radioactive serum estrogen assay was developed by modifying a hemagglutination-inhibition kit (Hi-Estrotec) originally designed to measure total urinary estrogens. With a minimum sensitivity of 100 pg of 17-beta-estradiol, the modified procedure generally takes less than 2.5 hours to complete and requires no special equipment or instrumentation. Randomly obtained serum samples assayed by both the hemagglutination-inhibition assay and radioimmunoassay achieved a correlation coefficient of 0.885 (P less than .001). Comparison of serum obtained from women undergoing ovulation induction with human menopausal gonadotropin-human chorionic gonadotropin measured by both techniques showed the same fluctuation pattern for serum estradiol levels during the stimulated cycles. The rapidity and reproducibility of this serum estrogen assay make it suitable for office use in monitoring ovulation induction and superovulation in in vitro fertilization-embryo transfer programs.

Estradiol↗
PubMed1986

Studies on the distribution of O6-methylguanine-DNA methyltransferase in rat.

O6-Methylguanine-DNA methyltransferase, a DNA repair enzyme which transfers the methyl group of O6-methylguanine residue to a cysteinyl residue in the methyltransferase itself, was examined in rat organs by quantifying the S-methylcysteine formed in the methyl acceptor protein. Among the various organs examined, the spleen exhibited the highest enzyme specific activity followed by the thymus, liver, lung and testis. Brain had the lowest activity. The patterns of subcellular distribution of the methyltransferase in spleen and liver were different: while 75-80% of the activity was present in the nuclear fraction of the spleen, 54% of the activity in the liver was found in the nuclei and 35% in the cytosolic fraction. Forty-five and thirty-five percent of the total nuclear enzyme activity could be extracted with 1 M and 2 M NaCl solutions, respectively, indicating that the repair enzyme is not tightly bound to the nuclear matrix. When isolated nuclei were incubated with [methyl-3H]DNA substrate and subsequently fractionated into histone and non-histone protein fractions, over 90% of the radioactivity was coeluted on a Bio-Rex 70 column with the non-histone fraction and only a negligible amount of radioactivity was found to be associated with the histone fraction. The molecular mass of the [methyl-3H]methyltransferase in the non-histone fraction was determined to be 23,000, and its pI value was found to be 6.6 by two-dimensional polyacrylamide gel electrophoresis.

Animals↗
PubMed1986

The effects of enclomiphene and zuclomiphene citrates on mouse embryos fertilized in vitro and in vivo.

The ovulatory agent clomiphene citrate, a racemic mixture of the estrogenic zuclomiphene and antiestrogenic enclomiphene isomers, has been associated with gamete/embryo toxicity in various animal models. To assess the potential effects of these isomers on fertilization and early embryogenesis, 3200 embryos were obtained from mouse oocytes fertilized in vivo and in vitro and exposed to increasing concentrations of zuclomiphene, enclomiphene, and clomiphene citrate in culture. Fertilization rates (p less than 0.01), blastocyst formation rates (p less than 0.02), and degeneration rates (p less than 0.005) were all adversely affected in a dose-dependent fashion. There were no statistically significant differences between the two isomers. Preincubation with 17 beta-estradiol did decrease the degenerative changes induced by clomiphene citrate but did not improve the decreased rate of blastocyst formation. These findings suggest adverse effects of a high concentration of clomiphene citrate and its isomers on fertilization and early mouse embryo growth that may have implications in the clinical use of this drug.

Animals↗
PubMed1986

Conformations of complexes derived from the interactions of two stereoisomeric bay-region 5-methylchrysene diol epoxides with DNA.

The reaction mechanisms of two isomeric bay-region diol epoxides of 5-methylchrysene (trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (DE-I) and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene (DE-II) with double-stranded DNA in aqueous solutions were studied utilizing kinetic flow dichroism and fluorescence techniques. As in the case of the previously studied benzo(a)pyrene-7,8-diol-9,10-oxide isomers (BaPDE), both DE-I and DE-II rapidly form intercalation-type complexes (association constants K = 2700 and 1500 M-1 respectively in a neutral 5mM phosphate solution). The physically bound diol epoxide molecules react on time scales of minutes to form predominantly tetraols; a greater fraction (6 +/- 1%) of DE-I than of DE-II (2-3%) molecules react with the DNA to form covalent products. The DE-II isomer is characterized by a greater reactivity than DE-I, and the rates of reaction are markedly accelerated in the presence of DNA in both cases. The linear dichroism spectra of the covalent adducts reveal that the conformations of both types of adducts are similar, with the long axes of the phenanthrenyl chromophores tilted, on the average, at angles of 38-52 degrees with respect to the average orientations of the transition moments (at 260 nm) of the DNA bases. The conformations of the covalently bound DE-I and DE-II molecules resemble those observed in the case of the highly tumorigenic (+) enantiomer of anti-BaPDE.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1986

Reaction mechanisms of trans-9,10-dihydroxy-anti-7,8-epoxy-7,8,9,10-tetrahydro-3-methylcho lan threne with DNA in aqueous solutions. Conformation of adducts.

The reaction mechanisms of trans-9,10-dihydroxy-anti-7,8-epoxy-7,8,9,10-tetrahydro-3-methylcholanth rene (anti-3-MCDE) in aqueous phosphate buffer solutions (pH 7, 24 degrees C) containing double-stranded DNA, and the structure of the covalent adduct formed, were studied by utilizing the techniques of absorption, fluorescence and linear dichroism spectroscopy. The results were compared with those obtained with the widely studied trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaPDE). The reaction mechanisms are similar in both cases since 3-MCDE also appears to form physical complexes which give rise to an acceleration of the rate of reaction of the diol-epoxide (by as much as a factor of 30 at pH 7, depending on the DNA and salt concentrations). While in the case of 3-MCDE the physical association constant is about four times lower, and the overall rate of reaction is at least five times smaller (depending on the DNA concentration) than in the case of BaPDE, the level of covalent binding is two times higher (18 +/- 2% of the 3-MCDE molecules appear as covalent adducts, the remainder forming hydrolysis products). In a novel extension of flow linear dichroism techniques, it is shown that the orientations of small aromatic moieties bound to DNA whose absorption spectra overlap with those of the nucleic acid residues below 300 nm can be studied; the dichroism at 265 nm resulting from the anthracene-like aromatic residue of 3-MCDE covalently bound to DNA suggests that its long axis tends, on average, to be tilted away from the average orientations of the planes of the nucleic acids. This conformation is similar to the one observed with adducts derived from the covalent binding of the highly tumorigenic (+) enantiomer of BaPDE, while the adducts derived from other biologically less active stereoisomers of BaPDE are characterized by conformations in which the aromatic moieties tend to be more parallel to the planes of the nucleic acid bases. Differences in the biological activities of the various polycyclic aromatic diol-epoxides are discussed in terms of these conformations and the abilities of these molecules to bind covalently to DNA.

Animals↗
PubMed1986

The acute effects of exercise on prolactin and growth hormone secretion: comparison between sedentary women and women runners with normal and abnormal menstrual cycles.

Acute exercise may stimulate PRL secretion, which, in turn, may contribute to exercise-associated menstrual dysfunction. We compared the response of PRL secretion in sedentary women and women runners with normal and abnormal menstrual cycles. We also studied the GH response to acute exercise, as GH may bind to lactogenic receptors. Five nonrunning women, 5 eumenorrheic running women, four oligomenorrheic running women, and six amenorrheic running women were studied on 2 consecutive days. On day 1, the women cycled on a bicycle ergometer against an increasing workload until total exhaustion. Serum PRL and GH increased several-fold in response to acute exercise in all three groups of running women. On day 2, the women simulated a daily training run by enduring a designed submaximal exercise regimen. In response to submaximal exercise, no group had a significant elevation of PRL or GH. Therefore, a threshold of exercise intensity exists that must be achieved before a significant increase in PRL or GH secretion occurs in women runners; serum PRL and GH in the nonrunning group did not increase significantly even in response to acute maximal exercise. The transient elevations in PRL and GH in women runners probably do not contribute to their menstrual dysfunction unless individual hypersensitivity of the hypothalamic-pituitary-ovarian axis to such intermittent elevations is present.

Adult↗
PubMed1985

Parallel inactivation of alpha 2-adrenergic agonist binding and Ni by alkaline treatment.

Alpha 2-Adrenergic receptor-mediated inhibition of adenylate cyclase requires the guanine nucleotide-binding protein, Ni. This protein may also be required for stabilization of high-affinity alpha 2-adrenergic agonist binding. Human platelet membranes treated under alkaline conditions (pH 11.5) exhibited a selective loss of high-affinity agonist binding as measured by p-[3H]aminoclonidine and [3H]UK 14,304. Binding of the antagonist [3H]yohimbine was largely unaffected with retention of greater than 60% of control binding sites. Ni, determined by pertussis toxin-catalyzed [32P]ADP-ribosylation of cholate extracts from alkaline-treated membranes, was also markedly reduced. The parallel loss of alpha 2-agonist binding and Ni provides additional evidence that Ni is required for alpha 2-adrenergic agonist binding.

Adenylate Cyclase Toxin↗
PubMed1985

Embryo toxicity of clomiphene citrate on mouse embryos fertilized in vitro and in vivo.

The effect of the ovulatory agent clomiphene citrate on fertilization and early embryogenesis was investigated with the use of in vitro fertilized mouse oocytes. Alterations in early embryogenesis with clomiphene citrate exposure were further studied with the use of embryos obtained from mouse oocytes fertilized in vivo. In the nontreated group, the fertilization rate was 81%, and 61% of the oocytes reached the blastocyst stage by 96 hours. Both fertilization and blastocyst formation declined in a dose-dependent fashion when clomiphene citrate was added to the culture media in concentrations greater than or equal to 10 micrograms/ml (p less than 0.001). The rate of progressive embryo cleavage was also slower at 48 and 72 hours after drug exposure. Mouse embryos fertilized in vivo demonstrated similar findings, with decreased blastocyst formation and increased degeneration rates, again at clomiphene citrate concentrations greater than or equal to 10 micrograms/ml (p less than 0.01). Exposure to the drug beyond 24 hours had no additional effect. It appears that clomiphene citrate-exposed embryos may undergo subtle changes that later manifest themselves in the form of decreased embryo growth rates and increased embryo degeneration rates.

Animals↗
PubMed1985

Serum testosterone concentrations in the evaluation of androgen-producing tumors.

During a 5-year study period 18 women with a serum testosterone concentrations of greater than 2 ng/ml were evaluated for a possible androgen-producing tumor. All subjects were hirsute and had menstrual irregularities, with the exception of one postmenopausal woman. The majority of the women were obese and 72% were greater than 50% over ideal body weight. Only two of 11 women undergoing operative and histologic evaluation of the ovaries were found to have an androgen-producing neoplasm. Seven additional women with serum testosterone concentration of greater than 2 ng/ml have been followed for over 1 year with no additional evidence of an androgen-producing neoplasm. The poor predictive value of a serum concentration of greater than 2 ng/ml in identification of an androgen-producing neoplasm is partially explained by the apparent prevalence of high testosterone concentrations in chronically anovulatory, hyperandrogenic obese women and by the large coefficient of variation observed in this study when analyzing testosterone concentrations were analyzed over an 8-hour interval (range, 3% to 42%). In the absence of an adnexal mass or rapidly progressive virilization, it is suggested that the use of venography or operative exploration to diagnose an androgen-producing neoplasm be reserved for women with a mean testosterone concentration derived from three daily samples that is at least 2.5 times greater than the upper range of normal in the given laboratory.

Androgens↗
PubMed1985

Reaction mechanisms of trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene with DNA in aqueous solutions.

Reactions of trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (anti-5-MeCDE) with DNA and the effects of ionic strength on the reaction were studied in aqueous buffer solution (5 mM sodium phosphate, pH 7) by means of absorption and fluorescence spectroscopy. The results are compared with those obtained with the widely studied metabolite model compound trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaPDE). The rate constant of hydrolysis of 5-MeCDE is k = 1.0 X 10(4)/S, which is approximately 35 times smaller than the value of k for BaPDE under similar conditions. As in the case of BaPDE, the rate of reaction of 5-MeCDE is accelerated in the presence of DNA. This effect is attributed to the rapid formation of physical association complexes (binding constant K) and the subsequent slower formation (rate constant k3) of carbocations at DNA binding sites, which in turn decay rapidly via hydrolysis to tetraols (1,2,3,4-tetrahydroxytetrahydro-5-methylchrysene, 5-MeCT) and to covalent adducts. The values of K and k3 are 2800 +/- 300/M and 8.7 X 10(-3)/S respectively, and are reduced to 450 +/- 100/M and 1.8 X 10(-3)/S in the presence of 0.1 M NaCl. The fraction of 5-MeCDE molecules which bind covalently to DNA is, on the other hand, constant under these conditions and lies in the range of 5-8%. Similar values for the covalent binding are observed for BaPDE, even though the physical association constant K is approximately 10 times larger than for 5-MeCDE under similar conditions. This difference in the values of K are attributed to the larger aromatic ring system in BaPDE which allows for a higher interaction of this molecule with the bases of DNA. Finally, the tetraol derived from the hydrolysis of 5-MeCDE also binds non-covalently to DNA, but the value of K is approximately 3 times smaller than for the diol epoxide.

Carcinogens↗
PubMed1985

Mutational mechanisms by which an inactive replication origin of bacteriophage M13 is turned on are similar to mechanisms of activation of ras proto-oncogenes.

M13 viral strand synthesis is initiated by nicking of the viral strand of the duplex replicative form by the M13 gene II initiator protein at a specific site within a sequence of about 40 base pairs having dyad symmetry. Efficient replication of the M13 viral strand also requires the presence of an adjacent sequence of ca. 100 base pairs. Together these sequences constitute the minimal origin for M13 viral strand synthesis. A pBR322 derivative having a 182-base-pair insert of M13 DNA contains a functional M13 viral strand origin and, when provided with M13 gene functions in trans, replicates under conditions nonpermissive for the parent plasmid. Chimeric plasmids containing deletions within the sequence flanking the viral strand origin are unable to replicate under these conditions. We isolated spontaneous mutants of M13 based on their ability to activate replication of such plasmids. The mutations found in these strains, as well as several produced by oligonucleotide-directed mutagenesis, all result in the substitution of any of at least four different amino acids for a specific glycine residue near the amino-terminal end of the initiator protein. Other studies have shown that overproduction of the wild-type initiator protein also restores replication. These alternate mechanisms are discussed in terms of their striking similarity to the mechanisms of activation of the ras proto-oncogenes which can be activated either by increased expression of the wild-type protein or by substitution of any of several amino acids for a glycine residue near the amino terminus.

Bacteriophages↗