Biomedical subjects
Publications and source records attributed to H Lee.
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The beta-globin gene from a patient with homozygous beta-thalassemia in Taiwan was cloned and extensively sequenced. Four nucleotides in the codon for amino acids, 41 and 42, are deleted. This change generates a frame-shift mutation and a termination codon in the new 59th codon. Some changes in nucleotide sequence were also found in intervening sequences IVS1 and IVS2, and Exon3, and were considered to be sequence polymorphisms.
The intestinal absorption of L-lysine-p-nitroanilide, L-alanine-p-nitroanilide, and glycine-p-nitroanilide was studied in perfused rat intestine in the presence of a variety of potential competitive inhibitors. The results indicate that the hydrolysis site(s) show side-chain specificity, and that inhibitors require a free amino group in the alpha-position and must be in the L-configuration to be effective. Glycyl-L-proline, a peptide transport inhibitor, had no effect on the absorption rate.
We report the successful management by CT-guided percutaneous catheter drainage of a lymphocele complicating a Warren-Zeppa distal splenorenal venous anastomosis. The early postoperative course of this 31-year-old male with homozygous alpha 1-antitrypsin deficiency was complicated by chylous ascites and a large lymphocele demonstrable on CT scanning. The persistent 10.5 cm diameter lymphocele was drained percutaneously 5 weeks later by a CT-guided catheter. Drainage of lymph continued at decreasing rates for 13 days when the catheter was removed. Complete resolution of the lymphocele was confirmed at 2 1/2 months. The successful treatment of a lymphocele by percutaneous catheter drainage may obviate major surgery and has not been previously documented.
Diazepam (Valium/Roche), a benzodiazepine derivative, reversibly inhibited the spreading of chick embryo fibroblasts in a dose-related manner. This inhibition was accompanied by: 1 Fewer and less organized microfilament bundles. 2 A reduction in myosin fluorescence along these structures. 3 A reduction in the total myosin content of cells compared to corresponding controls. Overall results suggest that myosin plays an active role in the spreading of chick embryo fibroblasts.
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The conformations of the adducts derived from the covalent binding of the two enantiomeric forms of 9,10-epoxy-9,10,11,12-tetrahydrobenzo(e)pyrene (BePE) with native DNA were investigated by the electric linear dichroism technique. Both enantiomers give rise to two major adducts, one of which appears to be a quasi-intercalative site (I) while the other one is an external binding site (II). While the overall linear dichroism spectra are similar, in the case of the (-) enantiomer there is a greater contribution of site II adducts. These results are markedly different from the ones obtained with the two enantiomers of anti-benzo(a)pyrene-7,8-diol-9,10-epoxide (BaPDE), where the (+) enantiomer gives rise almost exclusively to site II binding, while the (-) enantiomer gives rise to both site I and site II covalent binding. The differences in the heterogeneity of binding between BePE and anti-BaPDE enantiomers may be due to the absence of hydroxyl groups in BePE which, in the case of BaPDE, are an important factor in determining the stereoselective properties of the covalent binding to double-stranded DNA.
Synthesis is described of trans-7,8-dihydroxy-7,8-dihydro-8-methylbenzo[a]pyrene and trans-7,8-dihydroxy-anti-9,10-epoxy-8-methyl-7,8,9,10-tetrahydrobenzo[a] pyrene, potential proximate and ultimate carcinogenic metabolites, respectively, of 8-methylbenzo[a]pyrene.
Synthesis is described of trans-1,2-dihydroxy-1,2-dihydro-5-methylchrysene and trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene, implicated as the proximate and ultimate carcinogenic metabolites, respectively, of the potent environmental carcinogen 5-methylchrysene.
A method utilizing polyethylene glycol (PEG) as an extractable embedment for electron microscopy is described. Tissues are fixed according to conventional protocols, embedded in PEG, and sectioned. Sections (ranging from 100 to 500 nm in thickness) are mounted on grids, divested of their PEG matrix, critical-point-dried, and examined stereoscopically. This method greatly facilitates studies on the three-dimensional organization of cytoskeletal and cytoplasmic contractile systems in both muscle and nonmuscle cells.
Two murine monoclonal antibodies (E11-1 and MR4-130) agglutinated all samples of human red cells except those of the Ge (-1, -2, -3) phenotype. It was possible to demonstrate that these antibodies recognize two different epitopes of the Gerbich antigen.
The relative therapeutic effects of vidarabine (9-beta-D-arabinofuranosyladenine), cyclaradine (the adenosine deaminase-resistant carbocyclic analog of vidarabine), and cyclaradine-5'-methoxyacetate in the parenteral treatment of systemic herpes simplex virus type 1 infections in Swiss mice were determined. Among control mice inoculated intraperitoneally with virus, a mortality rate of 95% was observed. The intraperitoneal administration of nontoxic doses of vidarabine (125 to 250 mg/kg per day) or cyclaradine (113 to 450 mg/kg per day), by daily injections for 7 days beginning 4 h after virus inoculation, reduced mortality to 0 to 10%. Among control animals inoculated intracerebrally with 32 50% lethal doses of virus, 100% mortality was observed, with a mean survival time of 4.6 days. Treatment with either drug at equimolar dose levels ranging from ca. 32 to 750 mg/kg per day produced significant (P less than 0.0005), dose-dependent increases in the mean survival time of animals dying of herpesvirus encephalitis. Mice inoculated intracerebrally with 10 50% lethal doses of virus exhibited 97% mortality and a mean survival time of 5.5 to 6.4 days. Treatment with vidarabine, cyclaradine, or cyclaradine-5'-methoxyacetate significantly increased the mean survival time of dying animals and, at doses ranging from 250 to 750 mg/kg per day, produced significant increases in survival. The three drugs displayed equivalent antiviral efficacy in vivo. Drug toxicity (measured by weight loss) was not detected in mice treated with cyclaradine or cyclaradine-5'-methoxyacetate at 750 mg/kg per day, whereas severe toxicity (weight loss of greater than or equal to 3 g) was observed in mice treated with vidarabine at an equivalent dose level. Thus, cyclaradine or its 5'-methoxyacetic acid ester may possess some advantage over vidarabine in the treatment of severe herpesvirus infections and should therefore be considered for clinical trials in humans.
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Spleens from high responder Biozzi mice immunized with purified HBsAg of adw2, adw4 and ayw3 subtypes respectively were fused with N5-1 mouse myeloma cells. Over 30 clones with anti-alpha activity were obtained (principally from fusion adw2) as well as numerous clones with restrictive anti-HBs reactivity. The aim of this study was to characterize 9 different monoclonal antibodies with restrictive reactivity in comparison to a monoclonal anti-alpha antibody. Two different techniques were used: immunodiffusion and enzymoimmunoassay. Already known specificities or common reactivity between some subtypes were found, as w4, subdivision of ayw3 subtype, antigenic determinant common to w4 and adr, absence of the same determinant in adw2 and ayw1, the 2 subtypes having the highest capacity to absorb anti-alpha. Other monoclonal antibodies indicated the presence of previously unidentified subtype specificities: one of them recognized all HBsAg with d determinant but also ayw4, another recognized all HBsAg with y determinant but also adr, 2 others recognized determinants present completely or partially (spur formation) in many subtypes, another one recognized ayw4 and adw4 but also adw2. The combination of new tools such as monoclonal antibodies and synthetic peptides should facilitate the analysis of HBsAg.
Five cases of gastrointestinal perforation are presented in which computed tomography (CT) successfully demonstrated the abnormalities directly related to the perforation. In all cases, CT played a significant role in establishing a correct diagnosis, and in four cases permitted precise localization which facilitated the surgical approach. We believe that in cases where conventional radiographic examinations are not diagnostic, CT is particularly valuable because of its superior ability to depict anatomic abnormalities in the mesentery and surrounding tissue planes to suggest bowel perforation.
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The toxic and teratologic effects of caffeine on chick embryos explanted at stages 4-7 and cultured for 19-22 hours were investigated. Caffeine, at 200-300 micrograms/ml, significantly increased the incidence of neural tube defects regardless of the developmental stage at treatment. Concentrations of 500 micrograms/ml or higher inhibited morphogenesis of nearly all organ primordia. In general, the effects of caffeine were concentration dependent and younger embryos were more susceptible to treatment than their older counterparts. Microscopic studies confirmed that the developing neuroepithelium was most sensitive to treatment. Caffeine, at concentrations sufficient to inhibit neural tube closure, caused no apparent alteration in the ultrastructure of cellular components except that apical microfilament bundles were thinner and less conspicuous than usual. Furthermore, caffeine (400 micrograms/ml) selectively inhibited uplifting of neural folds (and hence, closure of the neural tube) in embryos explanted at stage 8 and cultured for 4-6 and 16 hours. Affected neuroepithelial cells lacked the typical bottle-shaped characteristic and folded apical surfaces. Overall results of this study suggest that caffeine causes neural tube defects, at least in part, through its inhibitory action on the contractile activity of apical microfilament bundles in developing neuroepithelial cells.
When boiled pork extract was heated under reflux at 102 degrees C for 4 hr mutagens, which were detected using Salmonella typhimurium strains TA98 and TA1538, were formed. The level of mutagenicity was dependent on the concentration of pork in the extract, the duration of boiling and on pH; the optimum pH for mutagen formation was found to be 9 to 11. Thin-layer chromatographic analysis showed that the mutagens formed in boiled pork extract were chromatographically distinguishable from benzo[a]pyrene and from the primary mutagenic pyrolysis products of tryptophan (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and of glutamic acid (2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole).