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Biomedical subjects

H Lee

Publications and source records attributed to H Lee.

At least 883 records · Page 49Linked to original sources
PubMed1981

Immunochemical characterization of antibodies to factor VIII in hemophilic and nonhemophilic patients.

Plasma samples from eighteen patients (9 hemophilic, 9 nonhemophilic) with antibodies to Factor VIII were purified by protein A gel chromatography. This procedure separates the IgG3 from the IgG1, IgG2, and IgG4 subclasses. The partially purified anti--Factor VIII fractions were typed for their heavy and light chain composition by immunoneutralization assay. Residual anti--Factor VIII activity was revealed by inhibition of fibrin formation in agarose gel plates. The combination of these two techniques permitted the study of a relatively large number of partially purified samples, at several dilutions of each, against each anti-heavy or anti-light chain antiserum obtained from various sources. A high degree of subclass and light chain restriction was found in the antibodies from the hemophilic patients, eight were predominantly of IgG4 kappa type, the ninth was IgG4 but of mixed light chains. In contrast, a heterogeneous distribution was found in the ten nonhemophilic patients: two IgG4 kappa, one IgG4 lambda, one IgG4 with both kappa and lambda, two a mixture of IgG1 and IgG4 with only kappa light chains, and three a mixture of IgG1 and IgG4 as well as both light chains.

Antibodies, Anti-Idiotypic↗
PubMed1981

The in vitro effect of ticlopidine on fibrinogen and factor VIII binding to human platelets.

The mode of action of the antiplatelet agent ticlopidine is not yet fully understood. Its multiple effects on platelet function include prolongation of the bleeding time, reduction in primary and secondary waves of ADP-induced aggregation and inhibition of collagen and thrombin-induced aggregation. We have studied the in vitro effects of ticlopidine on fibrinogen binding induced by ADP and adrenaline as well as factor VIII/vWF binding induced by ristocetin. 125I-fibrinogen binding was measured in suspensions of freshly-washed normal platelets stimulated by 10 microM ADP or 10 microM adrenaline. The binding of 125I-factor VIII/vWF in the presence of 1 mg/ml ristocetin was measured in both washed and paraformaldehyde-fixed platelets. Ticlopidine at final concentrations of 200, 100, 50 and 25 microM inhibited both ADP and adrenaline-induced fibrinogen binding in a dose-dependent manner. The mean % inhibition of ADP-induced fibrinogen binding was 82, 73, 42 and 32 respectively. The mean % inhibition of adrenaline-induced fibrinogen binding was 86, 82, 60 and 35 respectively. In contrast, the factor VIII/vWF binding was unaffected by ticlopidine at all concentrations except at 200 microM using fresh platelets where a slight inhibition (19%) was observed. These results suggest that ticlopidine either inhibits platelet activation and consequently fibrinogen binding, or inhibits the binding directly, presumably by having an effect on the specific configuration of the platelet membrane required for normal fibrinogen binding.

Anticoagulants↗
PubMed1980

Evidence of clastogens in acute leukemia. Chromosomal abnormalities in healthy parents of congenital leukemic patients.

If leukemia is caused by an "agent" which can pass through the placenta, it could produce leukemic transformation in the maternal cells. Cytogenetic studies were carried out in 5 acute lymphoblastic leukemic children and their parents. Significant abnormalities were found in 3 of the fathers, 4 of the mothers, and all the leukemic children. All but one abnormal metaphase from the mothers of the 2 leukemic boys had a XX sex pattern, indicating that these abnormal metaphases originated in the mother and probably were caused by a chromosomal breaking agent. The abnormal metaphases found in the fathers suggests that they too were exposed to this agent. Therefore, this agent must be present in the immediate environment, and this can pass from the material circulation to the fetus through the placenta and effect the fetus cells. The failure of the infant to eradicate these abnormal cells results in the phenotypical expression of clinical leukemia.

Acute Disease↗
PubMed1980

Carbocyclic analogs of arabinosylpurine nucleosides.

Carbocyclic analogs of arabinofuranosylguanine (VII) and 2,6-diamino-9-beta-arabinofuranosylpurine (VIII) and the corresponding 8-azapurine analogs, 5-amino-7-hydroxy-3-[2 alpha,3 beta-dihydroxy-4 alpha-(hydroxymethyl)cyclopent-1 alpha-yl]-v-triazolo[4,5-d]pyrimidine (X) and 5,7-diamino-3-[2 alpha,3 beta-dihydroxy-4 alpha-(hydroxymethyl)cyclopent-1 alpha-yl]-v-triazolo[4,5-d]pyrimidine (XI), were prepared. Carbocyclic nucleoside analogs VII and X exhibited significant cytotoxicity against P-388 mouse leukemia cells in culture. In vitro testing against herpes simplex type 1 (strain HF) indicated that only VIII exhibited significant antiviral activity.

Animals↗
PubMed1980

Conditions for measuring DNA synthesis in PHA stimulated human lymphocytes in 20 microliters hanging drops with various cell concentrations and periods of culture.

We have studied conditions for measuring the uptake of [3H]thymidine ([3H]Tdr) by human lymphocytes in inverted microcultures, varying cell concentrations and periods in culture. Analysis of variance of the log values for [3H]Tdr uptake may be used to separate effects of variables and their interactions. A pulse time of 2 h, a total thymidine concentration of about 1 microgram/ml and a specific activity of [3H]Tdr of 2 Ci/mmole were optimal. Variables such as cell concentration, period of culture, type of serum and dose of PHA were shown to interact, suggesting that these variables should be examined together especially when comparing different samples of lymphocytes. Conditions for doing this simply in small volumes are now available for culturing, thymidine pulsing, harvesting and analysis of data.

Cell Division↗
PubMed1980

Acute myelogenous leukemia with megakaryocytic myelosis.

A case of acute myelogenous leukemia terminating in megakaryocytic myelosis is reported. There was a severe, apparently neoplastic proliferation of megakaryocytes so different from that seen in acute granulocytic leukemia or myelofibrosis that a diagnosis of acute megakaryocytic myelosis was warranted. The clinical and pathologic findings of the case are presented in detail. The literature of this extremely rare hematologic disease is reviewed, and differentiation from chronic and malignant myelosclerosis is discussed.

Aged↗
PubMed1980

The influence of chronic ethanol feeding to rats on liver mitochondrial membrane structure and function.

Arrhenius plots were generated on the activity of rat liver mitochondrial cytochrome c oxidase from Metrecal-sucrose fed controls and Metrecal-alcohol fed experimentals. Chronic alcohol feeding resulted in diminished specific activity of cytochrome c oxidase and abolition of the discontinuity temperature at 17.5 degrees C found in the controls. Twenty-four hours after alcohol withdrawal, a discontinuity temperature reappeared at 14.4 degrees C; at 48 h it increased to 22.6 degrees C and returned to normal (17.4 degrees C) at 72 h. Such liver mitochondria also showed a decreased capacity to oxidize the acetyl group of acetyl carnitine immediately following prolonged alcohol feeding. When the assay was performed following withdrawal from alcohol 24 h later, oxidation was enhanced and this effect persisted for another 48 h. These latter results revealed a diminished capacity of such mitochondria to oxidize short chain fatty acids during alcohol feeding and the reverse during alcohol withdrawal. These results, complemented by thermographic data obtained through differential scanning calorimetry (DSC) reinforced the view that chronic alcoholic feeding induced adaptive changes in the fluidity of rat liver mitochondrial membrane lipids. Moreover, they demonstrated that in the microenvironment of the membrane-bound enzymes on withdrawal from ethanol, the membrane readapts to the new conditions without alcohol. This involved modulation of membrane structure and function and at the same time demonstrated a role for the membrane in the expression of tolerance and functional dependence on alcohol.

Acetylcarnitine↗
PubMed1979

Neural tube closure defects caused by papaverine in explanted early chick embryos.

Papaverine (50 micrograms/ml) preferentially inhibited uplifting of neural folds in explanted stage 8 chick embryos. Affected neuroepithelial cells often lost their wedge-shaped and elongated appearance. Also, luminal surfaces of most affected cells were smoother than usual as evidenced by the marked decrease in the number of cytoplasmic extensions, but the integrity of other structures (including cytoskeletal components) was not noticeably affected. The observed changes in cell surface topography were due, at least in part, to the imparied ability of apical microfilaments to contract and their eventual relaxation. The "relaxing" effect of papaverine on neural folds could be reversed by subsequent treatment with ionophore A23187. Since papaverine and ionophore A23187 are known to alter the normal distribution of intracellular Ca2+ and changes in cell surface topography are correlated with contractile activities of apical microfilaments, papaverine elicits neural tube closure defects by lowering intracellular free Ca2+ levels, thereby relaxing contracted apical microfilaments in neuroepithelial cells.

Abnormalities, Drug-Induced↗
PubMed1979

Danazol binding to rat androgen, glucocorticoid, progesterone, and estrogen receptors: correlation with biologic activity.

Danazol was found to possess androgenic and glucocorticoid activity in rat bioassays. In contrast, danazol displayed no significant estrogenic activity. In support of these findings, danazol bound to the 8 S androgen receptor of rat prostate cytosol and to the glucocorticoid receptor of rat liver cytosol, but danazol did not bind well to the estrogen receptor of the rat uterus. Finally, danazol bound to the progesterone receptor of the rat uterus, but controversy continues as the whether danazol possesses progestational, antiprogestational, or no progestational effects.

Animals↗
PubMed1979

A method for preparing and handling cross-sections from early chick embryos for scanning electron microscopy.

A method is described for processing multiple cross-sections from early chick embryos for scanning electron microscopy. Embryos are cut through the desired regions. Sections are affixed to a coverslip with Duco cement and critical point dried by Freon 13 or liquid CO2. This method provides a reliable means for preparing multiple cross-sections from single embryos and eliminates the need for direct handling of brittle tissues after drying.

Animals↗
PubMed1979

Progesterone receptor in the hypothalamic cytosol of female rats.

A progesterone (P)-binding component with a sedimentation coefficient of 8S has been demonstrated in hypothalamic cytosol from ovariectomized, estrogen-primed rats using both [H]P-containing sucrose-glycerol gradient analysis and dextran-coated charcoal adsorption of the preisolated 8S component. The association rate constant (K+1) was determined to be 1.90 +/- 0.38 (SD) X 10(6) M-1 min-1 at 0-2 C. The dissociation rate constant (K-1) was 1.86 x 10(-2) min-1, as calculated from the half-dissociation time [37.0 +/- 7.3 (SD) min]. The apparent dissociation constant (Kd) at 0-2 C was determined to be 6-10 nM by Scatchard plot analysis of data obtained from either direct [3HA]P binding or competition of the [3H]P binding by nonradioactive P and by calculating from K-1/K+1. The 8S binding component was protein in nature, and the concentration of binding sites was 12 fmol/mg cytosol protein. On a per U cytosol protein basis, the relative capacities of the specific 8S binding components were: uterus greater than pituitary greater than hypothalamus greater than hippocampus/amygdala greater than cerebral cortex. Competition studies showed a high specificity for P and 5 alpha-dihydroprogesterone. Corticosterone (C), although competing for the binding, had an affinity 8-fold less than P. Implantation of C in adrenalectomized, ovariectomized, estrogen-implanted rats suppressed the 8S binding of [3H]C without affecting the [3H]P binding. The binding of [3H]P to the cytoplasmic 8S component of hypothalamus was greater than that of combined hippocampus and amygdala, while the reverse was observed for the binding of [3H]dexamethasone. These results demonstrate in rat hypothalamic cytosol a tissue and hormone-specific, high affinity, 8S progesterone-binding protein which has many of the properties expected of a hormone receptor.

Animals↗
PubMed1979

Survival of frozen mouse embryos after rapid thawing from -196 degrees C.

The effect of the rate of rewarming on the survival of 8-cell mouse embryos and blastocysts was examined. The samples were slowly cooled (0.3--0.6 degrees C/min) in 1.5 M-DMSO to temperatures between -10 and -80 degrees C before direct transfer to liquid nitrogen (-196 degrees C). Embryos survived rapid thawing (275--500 degrees C/min) only when slow cooling was terminated at relatively high subzero temperatures (-10 to -50 degrees C). The highest levels of survival in vitro of rapidly thawed 8-cell embryos were obtained after transfer to -196 degrees C from -35 and -40 degrees C (72 to 88%) and of rapidly thawed blastocysts after transfer from -25 to -50 degrees C (69 to 74%). By contrast, for embryos to survive slow thawing (8 to 20 degrees C/min) slow cooling to lower subzero temperatures (-60 degrees C and below) was required before transfer to -196 degrees C. The results indicate that embryos transferred to -196 degrees C from high subzero temperatures contain sufficient intracellular ice to damage them during slow warming but to permit survival after rapid warming. Survival of embryos after rapid dilution of DMSO at room temperature was similar to that after slow (stepwise) dilution at 0 degrees C. There was no difference between the viability of rapidly and slowly thawed embryos after transfer to pseudopregnant foster mothers. It is concluded that the behaviour of mammalian embryos subjected to the stresses of freezing and thawing is similar to that of other mammalian cells. A simpler and quicker method for the preservation of mouse embryos is described.

Animals↗