Search PubMed⌕ Search

Biomedical subjects

C Y Ho

Publications and source records attributed to C Y Ho.

At least 55 records · Page 3Linked to original sources
PubMed1996

Linkage of a familial platelet disorder with a propensity to develop myeloid malignancies to human chromosome 21q22.1-22.2.

Linkage analysis was performed on a large pedigree with an autosomal dominant platelet disorder and a striking propensity in affected family members to develop hematologic malignancy, predominantly acute myelogenous leukemia. We report the linkage of the autosomal dominant platelet disorder to markers on chromosome 21q22. Four genetic markers completely cosegregate with the trait and yield maximum logarithm of difference scores ranging from 4.9 to 10.5 (theta = .001). Two flanking markers, D21S1265 and D21S167, define a critical region for the disease locus of 15.2 centimorgan. Further analysis of this locus may identify a gene product that affects platelet production and function and contributes to the molecular evolution of hematologic malignancy.

Acute Disease↗
PubMed1996

Effect of electrical stimulation on postmortem titin, nebulin, desmin, and troponin-T degradation and ultrastructural changes in bovine longissimus muscle.

Electrical stimulation (ES) of bovine carcasses is usually done to increase tenderness and has been hypothesized to increase the activity of proteolytic enzymes that may degrade structural proteins in muscle cells and cause fractures and breaks in muscle fibers, thus enhancing meat tenderness. Our objective was to compare postmortem (PM) changes in the muscle proteins, titin, nebulin, alpha-actinin, desmin, and troponin-T and in myofibrillar structure in nonstimulated (NS) and ES bovine skeletal muscle. One side of eight beef carcasses was stimulated within 1 h of death, and the other side was the NS control. Myofibrils for SDS-PAGE and samples for transmission electron microscopy were prepared from the longissimus muscle at 0, 1, 3, 7, 14, and 28 d PM. In SDS-PAGE, titin migrated as three bands in both NS and ES 0-d samples. The slowest migrating band, T1 (intact titin), decreased slightly faster in ES samples from five animals. The fastest migrating band, T2 (degraded titin), increased in amount through 3 d and was still present at 28 d. A titin monoclonal antibody (mAb) identified a large family of degradation products that migrated faster than myosin heavy chains and that was more heavily labeled in Western blots of ES samples than in NS samples. In SDS-PAGE of NS samples, intact nebulin disappeared by 3 d in three animals, by 7 d in four animals, and by 14 d in one animal, but in ES samples the nebulin band was absent by 3 d in three animals and by 7 d in five animals. SDS-PAGE showed that the amount of intact desmin decreased slightly sooner in two ES samples and was absent earlier in one ES sample than in the corresponding NS control samples. Blots labeled with a polyclonal antibody to desmin showed that a more heavily labeled 38-kDa desmin degradation product was present in ES than in NS samples. Postmortem degradation of alpha-actinin was not detected. Contraction node (CN) formation, stretching of conjoined sarcomeres adjacent to the nodes, increased frequency of I-band fractures and accelerated appearance of wide I-band fractures adjacent to the Z-line, and, in some animals, slightly accelerated degradation of titin, nebulin, and troponin-T were characteristics of ES muscle.

Actin Cytoskeleton↗
PubMed1995

Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo-[4,5,1-jk][1,4]benzodiazepin- 2(1H)-one (TlBO) derivatives. 4.

In previous papers, we have described the discovery of a new series of compounds, 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1 H)- ones, TlBO (1 and 1a), with potent anti-HIV-1 activity and the synthesis of analogues to better define the structure-activity relationships (SAR) in terms of changes in substituents at the N-6 position and variations of the five-membered urea ring as well as the seven-membered diazepine ring. This paper describes the synthesis of TlBO analogues with various substitutents on the aromatic ring and their SAR in terms of anti-HIV-1 properties. Substituents on the 8-position furnished the most rewarding results and gave a large improvement in potency versus the parent compound. These included halogen, thiomethyl, and methyl. Analogues like 8-cyano, -methoxy, and -acetylene were equipotent, while 8-amino, -acetylamino, -dimethylamino, and -nitro were inactive (Table 1). Substituents at the 9-position tended to have little effect on activity, and 10-substituents decreased activity. The 8-chloro compound 6a with IC50 = 0.0043 microM is currently under clinical development.

Antiviral Agents↗
PubMed1995

Relationship between nasal resistance and airway hyperreactivity following nasal provocation with Dermatophagoides pteronyssinus in allergic rhinitis.

To determine whether nasal allergic symptoms can cause bronchial hyperresponsiveness to methacholine, 30 subjects with allergic rhinitis (22 with allergic rhinitis and 8 with allergic asthmatic rhinitis) were studied. All subjects were skin test positive to Dermatophagoides pteronyssinus (DP) and underwent nasal allergic provocation with DP. After provocation, there was a severe nasal allergic reaction in the challenged nostril with a significant increase in nasal resistance both immediately and long (7 h) after DP exposure. There were no significant changes in the forced expiratory volume in 1 s and the forced expiratory flow rate between 25 and 75% of the forced vital capacity and in both allergic rhinitis and allergic asthmatic rhinitis patients. There was also no change in bronchial hyperresponsiveness to methacholine. The eosinophil counts, leukotriene B4, leukotriene C4 and platelet-activating factor levels in nasal discharges also showed no differences in both groups of patients. Our studies suggest that nasal provocation with limited allergen is a safe diagnostic technique. However, the relationship between nasal resistance and airway hyperreactivity is not obvious in this study. The similar concentrations of nasal inflammatory mediators in both allergic rhinitis and allergic asthmatic rhinitis indicate that bronchial hyperreactivity is not solely due to nasal drainage of inflammatory mediators.

Adolescent↗
PubMed1994

Heterodimerization of the yeast MATa1 and MAT alpha 2 proteins is mediated by two leucine zipper-like coiled-coil motifs.

The yeast Saccharomyces cerevisiae has three cell types distinguished by the proteins encoded in their mating type (MAT) loci: the a and alpha haploids, which express the DNA binding proteins a1 and alpha 1 and alpha 2, respectively, and the a/alpha diploid which expresses both a1 and alpha 2 proteins. In a/alpha cells, a1-alpha 2 heterodimers repress haploid-specific genes, while alpha 2 homodimers repress a-specific genes, indicating a dual regulatory function for alpha 2 in mating type control. a1 does not form homodimers. We have identified two sequences in the alpha 2 N-terminal domain which contain the 3,4-hydrophobic heptad repeat pattern characteristic of coiled-coils. Mutational analyses show that both sequences are important to a1-alpha 2 heterodimerization. We propose that these two sequences associate in a coiled-coil-like manner with a sequence within a1 which bears two adjacent, overlapping 3,4-hydrophobic heptad repeats. This model, which describes a novel dimerization motif for homeodomain proteins, also provides a mechanism by which a1-a1 homodimerization is prevented.

Amino Acid Sequence↗
PubMed1994

Identification of the 30 kDa polypeptide in post mortem skeletal muscle as a degradation product of troponin-T.

Although a 30 kDa polypeptide frequently is seen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of post mortem (pm) skeletal muscle and in turn is used as an indicator of proteolysis, its origin has not been conclusively identified. We used antibodies to selected myofibrillar proteins, including some known to be degraded pm, to identify this polypeptide. The left side of eight beef carcasses was electrically stimulated (ES) within 1 h after slaughter, and the right side served as the non-stimulated (NS) control. The longissimus lumborum (LL) muscle was removed from the carcass at 24 h pm and was stored at 2 degrees C. Myofibrils were prepared from the LL muscle immediately after stimulation (0 day) and from the stored muscle sample at 1, 3, 7, 14 and 28 days pm for analysis of SDS-PAGE and Western blots. By SDS-PAGE, troponin-T (TN-T) decreased in amount more rapidly pm in ES samples than in NS samples. By SDS-PAGE, a 30 kDa band increased and became a prominent band by 7 days pm in both NS and ES samples. A monoclonal antibody (mAb) to TN-T labeled purified TN-T, as well as the TN-T in myofibrils, a prominent 30 kDa polypeptide and a family of lower molecular mass polypeptides in pm muscle. This mAb also labeled a 30 kDa band that had been electrophoretically purified from pm muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Use of a ligand-screening procedure to study the interaction of S. cerevisiae alpha 2 repressor with its operator sequence.

A simple and rapid screening procedure was developed to study the interaction of the S. cerevisiae alpha 2 repressor with its operator sequence. An E. coli expression vector was constructed in which the alpha 2 coding sequence was placed under control of the lac promoter. Bacterial colonies containing this vector could be lysed and assayed directly for binding of wild-type and mutant operator sequences when grown on nitrocellulose filters. alpha 2 assayed in this way showed the same sequence specificity as determined in vivo. Pools of mutant alpha 2 repressors in which the codons for Arg185 or Ser181 in the homeodomain region were randomized were created by cassette mutagenesis. These pools of mutants were screened with the wild-type operator sequence to determine allowed amino acid substitutions at each position. Results suggest that both Arg185 and Ser181 have a role in high affinity operator binding.

Amino Acid Sequence↗
PubMed1991

Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-on e (TIBO) derivatives. 2.

In the first paper of this series a new structure with anti-HIV-1 activity was disclosed and analogues were synthesized to explore the structure-activity relationship of changes in the substituent (R) attached at the N-6 position of 9. This study describes the syntheses and anti-HIV-1 testing of analogues with variations of the five-membered urea ring of the 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk] [1,4]benzodiazepin-2(1H)-one (TIBO) structures. Although many different rings were synthesized to replace the cyclic urea of TIBO, most were found to be inactive in inhibiting the replication of the HIV-1 virus in MT-4 cells. The exceptions were replacement of the urea oxygen with sulfur or selenium to give the corresponding thio- or selenoureas. These were found to be more active than the oxygen counterparts. A small series of analogues was synthesized and tested which allowed direct comparison of urea and thiourea derivatives. Without exception, the latter were always more active than the former. The most active compound of this series (8d) was found to inhibit the HIV-1 virus with an IC50 of 0.012 microM which is comparable to that of AZT.

Antiviral Agents↗
PubMed1990

Personal exposure to nitrogen dioxide and its association with respiratory illness in Hong Kong.

In 1985, 362 primary schoolchildren and their 319 mothers were surveyed in Hong Kong to study the possible relationship of air pollution to respiratory illnesses. Using nitrogen dioxide (NO2) measured by personal samplers as a measure of air pollution, the study aimed to identify the major sources of NO2 in the indoor environment and see whether its increased presence was associated with respiratory symptoms. The levels of NO2 among the mothers was found to increase by 21% if dust exposure was reported from the workplace, 18% if they used such cooking fuels as liquid petroleum gas or kerosene, 11% when kitchens did not have ventilating fans, and 10% when incense was burned at home. In terms of respiratory symptoms, an increase in NO2 levels of 19% was reported among those with allergic rhinitis and 18% among those with chronic cough. The levels of NO2 among children were correlated with levels measured in classrooms, all of which had opened windows so that the NO2 came from outdoors. No association was found between children's NO2 levels and respiratory symptoms. With the exception of smoking by the father and the children's NO2 levels, no association was found between smoking at home and NO2 levels.

Adult↗
PubMed1988

Inhibition of leukotriene and thromboxane biosynthesis by a 9-(4-chlorophenyl) analogue of arachidonic acid.

The synthesis of 9-(4-chlorophenyl)-7,7-dimethyl-5(Z), 8-nonadienoic acid (7) and its methyl ester 6, and their effects on arachidonic acid metabolism in vitro are described. The IC50 values of 19.6 and 20.6 microM were observed for inhibition of leukotriene synthesis in human granulocytes for 6 and 7, respectively. Additionally, the compounds inhibited thromboxane B2 (TxB2) synthesis, with respective IC50 values of 6.1 and 20 microM, while producing pronounced 3-8-fold increases in PGE2 synthesis in human mononuclear cells. Increased PGE2 synthesis may have reflected shunting of free arachidonic acid substrate at the thromboxane synthetase and endoperoxide E isomerase branchpoint of arachidonic acid metabolism.

Animals↗
PubMed1987

Measurements of passive smoking and estimates of lung cancer risk among non-smoking Chinese females.

Lifetime exposures to environmental tobacco smoke from the home or workplace for 88 "never-smoked" female lung cancer patients and 137 "never-smoked" district controls were estimated in Hong Kong to assess the possible causal relationship of passive smoking to lung cancer risk. Relative risks based on the husband's smoking habits, or lifetime estimates of total years, total hours, mean hours/day, or total cigarettes/day smoked by each household smoker did not show dose-response results. Similarly, when such categories as mean hours/day, or earlier age of initial exposure, were combined with years of exposure, there were no apparent increases in relative risk. However, when the data were segregated by histological type and location of the primary tumor, it was seen that peripheral tumors in the middle or lower lobes, or, less strongly, squamous or small-cell tumors in the middle or lower lobes, had increasing relative risks that might indicate some association with passive smoking exposure.

China↗
PubMed1987

Hepatic metabolism and secretion of a cholesterol-enriched lipoprotein fraction.

A potentially important source of cholesterol secreted in bile is cholesterol-rich lipoproteins. However, the fate of the cholesterol carried in these lipoproteins after hepatic uptake has not been investigated. We harvested an apoE- and cholesterol-rich lipoprotein fraction (d 1.02-1.06 g/ml) from hypercholesterolemic rats and examined the acute effects of these lipoproteins on hepatic cholesterol metabolism, very low density lipoprotein (VLDL) secretion, and biliary lipid secretion. Administration of a lipoprotein bolus (20 mg of cholesterol) to rats resulted in a significant decrease in 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and a significant increase in acyl-coenzyme A:cholesterol acyltransferase activity over controls at 1 hr. Hepatic cholesteryl ester content increased 400% with no change in hepatic free cholesterol content or biliary cholesterol secretion. These cholesterol-rich lipoproteins delivered in the isolated perfused liver effected a fivefold increase in hepatic VLDL secretion with no change in composition. Therefore, cholesterol-rich lipoproteins do not acutely alter biliary cholesterol secretion. Rather, the majority of the cholesterol delivered to the liver in these lipoproteins is either esterified and stored as cholesteryl ester or resecreted as free and esterified cholesterol in hepatic VLDL.

Animals↗
PubMed1986

Experience with polytetrafluoroethylene grafts in children with cyanotic congenital heart disease.

Survival and event-free rates of 47 polytetrafluoroethylene (PTFE) (Gore-Tex) shunts for severe cyanotic congenital heart defects were studied in 42 children from April, 1981, to March, 1983. Retrospective actuarial analysis was conducted over the 27 months of the study in 3-month intervals of the follow-up. The estimated actuarial patient survival at two years was 86% with an estimated actuarial event-free rate of 57.2%. The grafts were found to be patent in 89% (42/47) of the grafts. Complications associated with PTFE grafts were thrombosis, infections, heart failure, shunt stenosis, and deformity of the pulmonary arteries. Polytetrafluoroethylene grafts for systemic-pulmonary shunts offer good palliation, but the frequency of complications indicates that close follow-up is mandatory to avoid or treat serious sequelae of the complications.

Actuarial Analysis↗
PubMed1986

Indolo[2,1-c][1,4]benzodiazepines: a new class of antiallergic agents.

A series of 12-(cyclic alkylamino)-6H-indolo[2,1-c][1,4]benzodiazepines were synthesized that possess antihistamine and antiserotonin activities as well as ability to inhibit mediator release. Compound 6a, 12-(4-methyl-1-piperazinyl)-6H-indolo[2,1-c][1,4]benzodiazepine was a more potent inhibitor of serotonin release than disodium cromoglycate (DSCG) and ketotifen and approximately equivalent to oxatomide. In the in vivo tests (PCA and ALA), compound 6a was equivalent or superior to DSCG and oxatomide. These agents have potential for the treatment of a variety of allergic conditions.

Anaphylaxis↗
PubMed1985

Effects of diethylhydroxylamine on hepatic microsomal lipid peroxidation and glutathione S-transferases.

The effects of diethylhydroxylamine (DEHA), a potent free-radical scavenger, on lipid peroxidation of rat liver microsomes were investigated in vitro. DEHA strongly inhibited ascorbate-dependent nonenzymatic microsomal lipid peroxidation. DEHA also completely inhibited nonenzymatic lipid peroxidation of heat-denatured microsomes, indicating that inhibition is protein-independent. DEHA only moderately inhibited NADPH-dependent enzymatic microsomal lipid peroxidation. DEHA has been shown to exhibit antitumorogenic properties. However, it had no significant effect on hepatic glutathione S-transferase, selenium-independent glutathione peroxidase, or selenium-dependent glutathione peroxidase activity in the DEHA-treated CD-1 (lCR) Br male mouse. This suggests that the mode of action of DEHA as an antitumorogenic agent may be different from that of butylated hydroxyanisole, whose antitumor function is attributed to induction of glutathione S-transferase activity.

Animals↗
PubMed1984

The effect of dietary fat saturation on plasma and hepatic lipoproteins in the rat.

Semipurified diets containing 10% kilocalories from either safflower oil (SO), corn oil (CO), olive oil (OO) or palm oil (PO) were fed to weanling male rats for 2 weeks. The effects of dietary fat saturation on plasma lipids and lipoproteins were: 1) Nonfasted plasma cholesterol concentration was higher in rats fed OO (mean +/- SEM = 81.0 +/- 2.9 mg/dl) vs. CO (67.5 +/- 2.9); 2) plasma chylomicron cholesterol concentration was higher in rats fed OO vs. SO and CO, with PO values in between; and 3) the cholesterol concentration of plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) did not differ among groups. The effects of dietary fat saturation on hepatic lipoproteins (determined by liver perfusion techniques) were: 1) hepatic higher density lipoprotein (d = 1.006-1.21 g/ml) cholesterol production was greater in rats fed SO and CO vs. PO [19.1 +/- 1.2, 17.2 +/- 0.8 and 13.7 +/- 1.6 micrograms/(g liver X 1.5 hour), respectively]; 2) there was no difference in hepatic VLDL cholesterol production among groups; and 3) the ratio of cholesterol to protein of hepatic VLDL and the higher density lipoprotein fraction was higher in rats fed diets rich in polyunsaturated fatty acids versus saturated fatty acids. Dietary fat saturation had no effect on carcass and liver cholesterol concentrations. Since differences in hepatic lipoprotein production were not reflected in plasma lipoprotein patterns, these results suggest that extrahepatic lipoprotein metabolism differs in rats fed diets containing fatty acids of varying saturation.

Animals↗