Biomedical subjects

H Cheng

Publications and source records attributed to H Cheng.

530 records · Page 30Linked to original sources

PubMedDate not supplied

An autosomal genetic linkage map of the chicken.

We have developed an autosomal genetic linkage map of the chicken genome using a subpanel of 52 DNAs from a previously described reference backcross mapping population. The population derived from a cross of an inbred Red Jungle Fowl male and a highly inbred White Leghorn female. The backcross subpanel used was made up of offspring of a single F1 male with four White Leghorn females. Ninety-eight markers consisting of classical and erythrocyte antigen genes, restriction fragment length polymorphisms, random amplified polymorphic DNA, and chicken CR1 repeat-element polymorphisms were typed. Seventy-two of these markers were resolved into 19 linkage groups. Four of the linkage groups were assigned to chromosomes 1, 4, and 17. Four linkage groups were associated with linkage groups published earlier. Linkages within approximately 27 cM can be detected with a lod score of 3 with the panel used. The preliminary map contains approximately 590 cM within the linkage groups, and approximately 70% of the randomly selected markers fell in one of the groups; however, a considerable portion of the genome may remain outside of the existing linkage groups. These markers greatly expand the existing linkage map of the chicken genome.

Animals↗

PubMedDate not supplied

Characterization of differentially expressed genes in ovarian cancer by cDNA microarrays.

The molecular events leading to the development and progression of ovarian carcinoma are not completely understood. We performed a large-scale survey for the identification of differentially expressed genes between ovarian carcinoma and normal ovarian tissue by using cDNA microarray analysis. We utilized 512 member human novel putative oncogene and tumor suppressor gene cDNA microarrays to study the differences in gene expression between ovarian carcinoma and normal ovarian tissues. Some differentially expressed genes have been further confirmed by immunohistochemical analysis. A total of 39 differentially expressed genes were identified, of which 16 and 23 were specifically expressed in ovarian cancer and normal ovarian tissue, respectively. The comparison of average signal of differentially expressed genes exhibited at least a twofold difference in expression. The differentially expressed genes may be related to the carcinogenesis and progression of the malignant growth. The use of cDNA microarrays allows simultaneous monitor of the expression of many genes, thereby it speeds up the identification of differentially expressed genes. It is essential for further exploration of the mechanisms of the disease.

Adenocarcinoma↗

PubMedDate not supplied

Coupling of beta2-adrenoceptor to Gi proteins and its physiological relevance in murine cardiac myocytes.

-Transgenic mouse models have been developed to manipulate beta-adrenergic receptor (betaAR) signal transduction. Although several of these models have altered betaAR subtypes, the specific functional sequelae of betaAR stimulation in murine heart, particularly those of beta2-adrenergic receptor (beta2AR) stimulation, have not been characterized. In the present study, we investigated effects of beta2AR stimulation on contraction, [Ca2+]i transient, and L-type Ca2+ currents (ICa) in single ventricular myocytes isolated from transgenic mice overexpressing human beta2AR (TG4 mice) and wild-type (WT) littermates. Baseline contractility of TG4 heart cells was increased by 3-fold relative to WT controls as a result of the presence of spontaneous beta2AR activation. In contrast, beta2AR stimulation by zinterol or isoproterenol plus a selective beta1-adrenergic receptor (beta1AR) antagonist CGP 20712A failed to enhance the contractility in TG4 myocytes, and more surprisingly, beta2AR stimulation was also ineffective in increasing contractility in WT myocytes. Pertussis toxin (PTX) treatment fully rescued the ICa, [Ca2+]i, and contractile responses to beta2AR agonists in both WT and TG4 cells. The PTX-rescued murine cardiac beta2AR response is mediated by cAMP-dependent mechanisms, because it was totally blocked by the inhibitory cAMP analog Rp-cAMPS. These results suggest that PTX-sensitive G proteins are responsible for the unresponsiveness of mouse heart to agonist-induced beta2AR stimulation. This was further corroborated by an increased incorporation of the photoreactive GTP analog [gamma-32P]GTP azidoanilide into alpha subunits of Gi2 and Gi3 after beta2AR stimulation by zinterol or isoproterenol plus the beta1AR blocker CGP 20712A. This effect to activate Gi proteins was abolished by a selective beta2AR blocker ICI 118,551 or by PTX treatment. Thus, we conclude that (1) beta2ARs in murine cardiac myocytes couple to concurrent Gs and Gi signaling, resulting in null inotropic response, unless the Gi signaling is inhibited; (2) as a special case, the lack of cardiac contractile response to beta2AR agonists in TG4 mice is not due to a saturation of cell contractility or of the cAMP signaling cascade but rather to an activation of beta2AR-coupled Gi proteins; and (3) spontaneous beta2AR activation may differ from agonist-stimulated beta2AR signaling.

Adrenergic beta-Agonists↗

PubMedDate not supplied

Characterization of a fibrin glue-GDNF slow-release preparation.

One novel method to deliver trophic factor locally in the CNS is to mix it into fibrin glue. In the present studies, [125I]-labeled GDNF-containing fibrin glue balls were used to determine binding and spread of the trophic factor. First, the binding of different concentrations of [125I]-labeled GDNF in fibrin glue was determined in vitro. Within the six concentrations used (from 200 nM to 0.004 nM, 0 M as control), there was a strong linear correlation between the [125I]-GDNF concentration and the recovered radioactivity (r = 0.992). The mean bound radioactivity in 16 samples with 4 nM [125I]-GDNF was 71262 +/- 2710 CPM, and accounted for 89.8% of the mean initial count of free [125I]-GDNF (79369 +/- 3499 CPM). Second, [125I]-GDNF-containing glue balls were implanted into the anterior chamber of adult rats. The implanted fibrin glue balls decreased in size with time, but could still be identified on the irises 2 wk after implantation. Radioactivity was concentrated at the implantation sites in the early stages with a distribution in the surrounding iris tissue, which became separated into focal radioactive spots at the third week. Counts of radioactivity were significantly higher in the [125I]-GDNF glue ball-implanted irises than controls until 14 days after implantation. A study of the [125I] decay over time using least-squares linear regression demonstrated first-order kinetics (r = -0.98, p <0.02) with k = 0.0091 and T 1/2 = 76 h. Finally, [125I]-GDNF-containing glue balls were implanted in the spinal cord of adult rats. Radioactivity was concentrated at the implantation sites in the early stages and was later distributed more widely in the surrounding thoracic cord. The [125I]-GDNF-containing glue degraded over time and became a porous meshwork with decreasing radioactivity at the later time points. Radioactivity in the spinal cords subjected to implantation of [125I]-GDNF-containing glue balls was higher than in controls for 14 days. Study of the [125I] decay by time with least-squares linear regression demonstrated first-order kinetics (r = -0.97, p = 0.001) with T 1/2 = 75.6 h. We conclude that the trophic factor GDNF becomes bound in the fibrin glue matrix from which it is gradually released. Our results suggest that fibrin glue is an effective substrate for keeping a trophic factor localized in situ for a finite period, protected from the circulation, surrounding aqueous humor or CSF.

Animals↗

PubMedDate not supplied

Characterization of Bovidae sex-determining gene SRY.

In mammals, testis determination is under the control of the sex-determining gene SRY. This Y-linked gene encodes a protein with a DNA binding domain similar to those found in high-mobility-group proteins. Here we report the cloning and sequences of the SRY genes of yak and Chinese native cattle. Our data show that SRY genes in Bovidae are less divergent, especially in the coding and 3' regions.

3' Untranslated Regions↗

PubMedDate not supplied

Identification of urinary metabolites of 8-methyl-8-azabicyclo-[3,2,1] octan-3-yl 3,5-dichlorobenzoate (MDL 72,222) in the dog and monkey.

The metabolism of 8-methyl-8-azabicyclo- 3,2,1]octan-3-yl 3,5-dichlorobenzoate (MDL 72,222) was studied in the dog and monkey. Four urinary metabolites were detected by HPLC, HPLC/MS, and GC/MS, and were identified by comparison to authentic standards. The major metabolite in the dog, approximately 41% of the administered dose excreted between 0 and 120 hr, was the MDL 72,222-N-oxide. On the other hand, the major metabolite in the monkey was the glycine conjugate of 3,5-dichlorobenzoic acid (greater than 56% of the dose). Seven percent of the dose in the monkey urine was free 3,5-dichlorobenzoic acid. N-Desmethyl MDL 72,222 was present at 2.5 and 1% in the dog and monkey, respectively. Very little (less than 1%) of the parent compound was found in urine. The major pathways of metabolism of MDL 72,222 are N-oxidation, N-demethylation, ester hydrolysis, and amino acid conjugation.

Animals↗

PubMedDate not supplied

Disposition and metabolism of the angiotensin-converting enzyme inhibitor [4S-[4 alpha, 7 alpha, (R*), 12b beta]]-7-[S-(1-ethoxycarbonyl-3- phenylpropyl)amino]-1,2,3,4,6,7,8,12b-octahydro-6-oxo- pyrido[2,1-a][2]benzazepine-4-carboxylic acid in monkeys and dogs.

[4S-[4 alpha, 7 alpha, (R*),12b beta]]-7-[S- (1-ethoxycarbonyl-3-phenylpropyl)amino]-1,2,3,4,6,7,8, 12b-octahydro-6-oxo-pyrido[2,1-a][2]benzazepine-4-carboxylic acid (MDL 27,210) is the ethyl ester prodrug of a potent angiotensin-converting enzyme inhibitor, MDL 27,088. After a single dose of [14C]MDL 27,210 (3 mg/kg iv), MDL 27,210 was rapidly eliminated from the plasma of monkeys and dogs with a terminal half-life of approximately 0.3 hr. The steady-state volume of distribution was 0.15 liter/kg in dogs and 0.28 liter/kg in monkeys. Monkeys excreted 52% of the 14C dose in the feces and 41% in the urine; dogs excreted 80% of the 14C dose in the feces and 14% in the urine. The presence of a large fraction of the 14C dose in the feces of both species following iv administration suggests that significant biliary excretion occurred. MDL 27,210 administered iv to monkeys and dogs was rapidly and extensively (greater than 99.9%) metabolized, primarily to its diacid metabolite, MDL 27,088. The half-life of MDL 27,088 was 2.2 hr in dogs and 3.6 hr in monkeys.

Angiotensin-Converting Enzyme Inhibitors↗

PubMedDate not supplied

Metabolic disposition of simvastatin in patients with T-tube drainage.

A study to investigate the disposition and biliary excretion of simvastatin (SV) was conducted in four cholecystectomy patients with T-tube drainage. Each patient received a single oral dose of 100 mg of [14C]SV (20 microCi). Of the 14C-labeled dose, approximately 35% was excreted in urine, 25% in bile, and 20% in feces. Thus, at least 60% of the oral dose was absorbed from the gastrointestinal tract. Of the AUC for radioactivity in plasma, 13% was contributed by the HMG-CoA reductase inhibitors. In addition, only 2% of the 14C-dose was eliminated in urine as HMG-CoA reductase inhibitors. Thus, most of the SV-related compounds in plasma and urine have little or no HMG-CoA reductase inhibitory activity. The same is probably true for these compounds in bile. Two major active metabolites were present in the bile. Based on HPLC and MS/MS data, they were identified as 6' beta-COOH-SVA and 6'-OH-SVA. In general, the majority of the radioactivity in the bile and urine was excreted within 24 hr postdose. Of the radioactivity excreted in the 0- to 24-hr bile, on average, approximately 30% was contributed by 6' beta-COOH-SVA and 6'-OH-SVA. These two metabolites accounted for the majority of HMG-CoA reductase inhibitory activity in the bile. Little or SV or no SVA was present in the bile.

Adult↗