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Biomedical subjects

S M Huang

Publications and source records attributed to S M Huang.

At least 91 records · Page 5Linked to original sources
PubMed1996

Overexpression of a Rrp1 transgene reduces the somatic mutation and recombination frequency induced by oxidative DNA damage in Drosophila melanogaster.

Recombination repair protein 1 (Rrp1) includes a C-terminal region homologous to several DNA repair proteins, including Escherichia coli exonuclease III and human APE, that repair oxidative and alkylation damage to DNA. The nuclease activities of Rrp1 include apurinic/apyrimidinic endonuclease, 3'-phosphodiesterase, 3'-phosphatase, and 3'-exonuclease. As shown previously, the C-terminal nuclease region of Rrp1 is sufficient to repair oxidative- and alkylation-induced DNA damage in repair-deficient E. coli mutants. DNA strand-transfer and single-stranded DNA renaturation activities are associated with the unique N-terminal region of Rrp1, which suggests possible additional functions that include recombinational repair or homologous recombination. By using the Drosophila w/w+ mosaic eye system, which detects loss of heterozygosity as changes in eye pigmentation, somatic mutation and recombination frequencies were determined in transgenic flies overexpressing wild-type Rrp1 protein from a heat-shock-inducible transgene. A large decrease in mosaic clone frequency is observed when Rrp1 overexpression precedes treatment with gamma-rays, bleomycin, or paraquat. In contrast, Rrp1 overexpression does not alter the spot frequency after treatment with the alkylating agents methyl methanesulfonate or methyl nitrosourea. A reduction in mosaic clone frequency depends on the expression of the Rrp1 transgene and on the nature of the induced DNA damage. These data suggest a lesion-specific involvement of Rrp1 in the repair of oxidative DNA damage.

Alkylating Agents↗
PubMed1996

Determination of XR510, a balanced angiotensin II receptor antagonist, in dog and rat plasma by combined liquid-liquid/solid-phase extraction and high-performance liquid chromatography.

A sensitive and selective high-performance liquid chromatographic method for the determination of XR510 (I), a new non-peptide angiotensin II (AII) receptor antagonist with balanced affinity for AT1 and AT2 receptor subtypes is described. I and the internal standard, XR513, were extracted from acidified plasma by combined liquid-liquid/solid-phase extraction and chromatographed on a phenyl column with ultraviolet absorbance detection at a wavelength of 272 nm. The mobile phase consisted of a mixture of acetonitrile and sodium phosphate buffer. For both rat and dog plasma, the limit of quantitation was 5 ng/ml. This method has been validated and successfully utilized to investigate the disposition of I.

Angiotensin Receptor Antagonists↗
PubMed1996

An alternative approach of choledocholithotomy via laparoscopic choledochotomy.

OBJECTIVE: To evaluate the safety and feasibility of laparoscopic choledocholithotomy via choledochotomy for the treatment of choledocholithiasis. DESIGN: A prospective series of 1332 consecutive patients who underwent laparoscopic cholecystectomies, with a mean follow-up of 21.2 months. SETTING: University-affiliated referral center. PATIENTS: Forty-three patients (3%) with documented common bile duct stones from January 1991 to February 1995. INTERVENTIONS: Laparoscopic choledocholithotomy with choledochotomy and T tube drainage were performed in 40 patients. Postoperative endoscopic sphincterotomy after laparoscopic cholecystectomy was performed in three patients. MAIN OUTCOME MEASURES: Documented removal of common bile duct stones and procedure-related complications. RESULTS: Laparoscopic choledocholithotomy via choledochotomy was successful in 35 (88%) of 40 patients in whom this procedure was attempted. The mean (+/- SD) operation time was 191.3 +/- 75.4 minutes, and the mean (+/- SD) length of postoperative stay was 10.4 +/- 2.7 days. Seven complications (18%) were recorded, including three major complications (8%) and two retained stones (5%). CONCLUSIONS: Laparoscopic choledocholithotomy via choledochotomy can be performed safely, without increasing the morbidity rate as compared with that of open choledocholithotomy. Thus, some of the advantages of minimally invasive surgery are preserved.

Aged↗
PubMed1996

Nonidentity of the cDNA sequence of human breast cancer cell malic enzyme to that from the normal human cell.

A cDNA coding for human breast cancer cell cytosolic NADP(+)-dependent malic enzyme was obtained. This cDNA is composed of a length of 2084 base pairs, with 1698 base pairs coding for 565 amino acid residues and a length of 386 base pairs representing a 3'-noncoding region. Comparing this nucleotide sequence with that from the normal human tissue [Loeber, G., Dworkin, M. B., Infante, A., and Ahorn, H. (1994), FEBS Lett. 344, 181-186] reveals that three nucleotides in the open reading frame and the length of 3'-noncoding region of the cDNA are different. One of the changes results in a substitution of serine at position 438 for proline, which, however, may not cause significant changes in the predicted secondary structure. A partial cDNA lacking the first 84 nucleotides in the open reading frame was successfully cloned and expressed functionally in Escherichia coli cells. Its Km value for L-malate (1.21 +/- 0.11 mM) is four times higher than that for the natural human breast cancer cell malic enzyme (0.29 +/- 0.04 mM) but similar to that for the full-length recombinant enzyme (1.06 +/- 0.07 mM). The Km values for Mn2+ and NADP+ (0.26 +/- 0.03 and 0.97 +/- 0.4 microM, respectively) are similar to those for the natural enzyme (0.12 +/- 0.02 and 1.9 +/- 0.3 microM, respectively) or the recombinant wild-type enzyme (0.56 +/- 0.04 and 0.44 +/- 0.02 microM, respectively). A recombinant pigeon liver malic enzyme without the first 13 amino acid residues was used for comparison. The Km values for L-malate and Mn2+ of the truncated enzyme (11.2 +/- 0.9 mM and 61.2 +/- 4.6 microM, respectively) are over 40 times larger than those for the natural pigeon liver malic enzyme (0.21 +/- 0.02 mM and 1.06 +/- 0.08 microM, respectively) or the recombinant wild-type enzyme (0.25 +/- 0.01 mM and 1.48 +/- 0.05 microM, respectively). We suggest that the N-terminus of malic enzyme may be required for the substrate binding during the catalytic cycle.

Amino Acid Sequence↗
PubMed1996

ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes.

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.

Aldehydes↗
PubMed1996

Surgical resection of primary hepatocellular carcinoma extending to adjacent organ(s).

Primary hepatocellular carcinoma (HCC) extending to the adjacent organ(s) is sometimes encountered in patients with large, peripherally located tumours. Over a 4-year period, a total of 151 patients received curative resection of HCC at the Surgical Department of Veterans General Hospital-Taipei, Taiwan. Of these patients, 21 underwent hepatic resection combined with en-bloc resection of the adjacent organ(s) because tumour extension was found during operation. Subsequent histological examination of the resected specimens found evidence of HCC invasion into the resected adjacent organ(s) in only nine patients (group I), and the remaining 12 patients showed no evidence of extrahepatic HCC invasion (group II). Twenty-seven HCC patients with clinico-pathologically matched tumours but without extrahepatic extension were selected as controls (group III). One patient in group I died of hepatic failure after the operation. The morbidity rate was 48% in group I and group II patients, and 30% in group III patients. The difference was not statistically significant. On evaluating the clinico-pathological factors, including DNA ploidy status of the tumours, there were no significant differences between tumours with and without extrahepatic invasion. Patients with locally invasive HCC (group I) had disease-free and overall survival rates comparable with those of the patients without local tumour invasion (group II and III). We conclude that HCC with invasion to the adjacent organ(s) does not seem to be directly related to the 'aggressiveness' of the tumour, and extrahepatic infiltration of the tumour does not preclude a chance of cure. Our results underscore the need for en-bloc resection as treatment of choice for these patients.

Carcinoma, Hepatocellular↗
PubMed1996

Effects of structural modifications on the intestinal permeability of angiotensin II receptor antagonists and the correlation of in vitro, in situ, and in vivo absorption.

PURPOSE: The effects of structural modifications on the membrane permeability of angiotensin II (Ang II) receptor antagonists and the usefulness of in vitro and in situ intestinal absorption models in predicting in vivo absorption or bioavailability were investigated. METHODS: Intestinal permeability was determined in vitro using Caco-2 cell monolayers and in situ using a perfused rat intestine method. Several physicochemical parameters were either measured or computed, and correlated with intestinal permeation. RESULTS: Permeation coefficients (Pa) across Caco-2 cell monolayers correlated well with both in situ absorption rate constants (ka) and in vivo bioavailability or % absorption. For these Ang II antagonists, Pa values larger than 3 x 10(-6) cm sec-1 and in situ ka values of 2 x 10(-4) min-1 cm-1 or above were associated with good in vivo absorption. Structural modifications at the R5 position, where a COOH group was substituted with either a CHO or CH2OH group, enhanced the permeability of the Ang II receptor antagonists up to 100-fold. There were good correlations between permeability and log P(octanol/buffer), log PHPLC, charge, solvation/desolvation energy and assigned hydrogen bonding potential. CONCLUSIONS: The correlations obtained in this study indicate that both the Caco-2 cell model and the in situ perfused rat intestine could be used to predict intestinal absorption in vivo. Structural modifications of the Ang II antagonists had a significant impact on the intestinal permeability. Charge, solvation energy, and hydrogen bonding are predominant determinants of intestinal permeability and oral bioavailability of these compounds.

Angiotensin Receptor Antagonists↗
PubMed1996

Transverse abdominis musculo-peritoneal (TRAMP) flap for the repair of large duodenal defects.

Definitive surgical management of major acute injuries to the second and third portions of the duodenum has been enigmatic. Sometimes, the defect is so large that it is unwise to do primary repair, and resection at this critical portion of the intestinal tract is technically hazardous or impossible. A serosal or mucosal patch technique has been used to repair this kind of duodenal defect with encouraging results. Since the use of this technique has proved effective, such a defect was not necessarily treated with the more complicated pancreaticoduodenectomy and was managed with less morbidity and mortality. But these techniques are still controversial. So, we tried a pedicle flap, called the transverse abdominis musculo-peritoneal (TRAMP) flap, for repair of large duodenal defect. We have used this flap in 25 rabbits, and the specimens were followed up to a period of 3 months. The flap showed satisfactory results and is presented as another option for repair of large duodenal defects.

Animals↗
PubMed1996

Pharmacokinetics and metabolism of EXP921, a novel cognitive enhancer, in rats.

EXP921, 5,5-bis(4-pyridinylmethyl)-5H-cyclopenta[2,1-b:3,4-b']-dipyridine, was a potential drug candidate for the improvement of cognitive performance in patients with Alzheimer's-type dementia. It has been shown to improve cognitive performance in rodent and primate models of learning and memory. To characterize the disposition of EXP921, the pharmacokinetics and metabolism of this compound were studied in rats after oral and intravenous administrations. EXP921 exhibited good bioavailability, 43% at 3 mg/kg and 61% at 10 mg/kg and was rapidly eliminated with a terminal half-life ranging from 1.28 to 2.29 hr after oral doses. Absorption from oral doses was rapid, as peak plasma levels were reached within 1 hr. A major metabolite was identified in plasma as the pyridinyl mono-N-oxide of EXP921. This metabolite (EXP696) was rapidly formed, and significant levels were detected in rat plasma after oral or intravenous administration. Its terminal half-life was slightly longer than that of EXP921. EXP696 was found to be reduced back to EXP921, demonstrating that the N-oxidation at the pyridyl ring is reversible. The interconversion favored the oxidation of EXP921 to EXP696. Two additional metabolites were identified in rat plasma at doses higher than or equal to 30 mg/kg. They result from despicolylation, followed by hydroxylation in the cyclopentane ring.

Administration, Oral↗
PubMed1996

A prospective randomised study of laparoscopic v. open cholecystectomy in aged patients with cholecystolithiasis.

Between August 1992 and July 1993, 27 patients aged 70 years of older with cholelithiasis were prospectively randomised into 2 groups. Fifteen patients underwent laparoscopic cholecystectomy and 12 patients underwent open cholecystectomy. Shorter operation time (93.3 +/- 25.3 minutes v. 176.3 +/- 26.1 minutes, P < 0.00001), fewer postoperative analgesic requirements (0.53 +/- 0.52 days v. 2.00 +/- 0.74 days, P < 0.00001), shorter postoperative hospital stay (3.93 +/- 1.71 days v. 7.92 +/- 0.79 days, P < 0.00001) and better cosmesis were found in the laparoscopic cholecystectomy group. The above data suggest that laparoscopic cholecystectomy is the treatment of choice for cholecystolithiasis in elderly patients.

Aged↗
PubMed1995

Effects of phosphodiesterase inhibitors on spontaneous electrical activity (slow waves) in the guinea-pig gastric muscle.

1. The effects of the phosphodiesterase inhibitors caffeine, theophylline, isobutylmethylxanthine (IBMX) and rolipram on spontaneous electrical activity (slow waves) were studied in the circular muscle of the guinea-pig gastric antrum. 2. All the inhibitors reduced slow wave frequency without changing the membrane potential and the slow wave configuration, but at higher concentrations they blocked the slow waves and caused membrane hyperpolarization. In the presence of the inhibitors a low level of irregular electrical activity could be observed in many preparations. 3. Isoprenaline, forskolin, dibutyryl cAMP and 8-bromo-cAMP all produced effects essentially similar to those of phosphodiesterase inhibitors. K+ (12 mM) and removal of K+ both depolarized the membrane and these were not affected by IBMX (1-3 microM). A decrease in frequency caused by IBMX was also not significantly affected by 12 mM K+ or K+ removal and only partially antagonized by TEA or 4-aminopyridine. 4. These results suggest that an increase in intracellular cAMP inhibits pacemaker activity of slow waves. An increase in K+ conductance does not seem to be a major factor in this inhibition. Slow waves appear to be a compound electrical activity in a group of muscle cells and are likely to be disintegrated by xanthine derivatives.

4-Aminopyridine↗
PubMed1995

Characterization of the nuclease activity of Drosophila Rrp1 on phosphoglycolate- and phosphate-modified DNA 3'-termini.

Drosophila Rrp1 includes a carboxy-terminal region homologous to Escherichia coli exonuclease III which is sufficient to repair both oxidative and alkylation damage to DNA. An apurinic/apyrimidinic endonuclease activity intrinsic to Rrp1 was characterized previously. In this work, the 3'-phosphodiesterase and 3'-phosphatase activities of Rrp1 are demonstrated and characterized. Phosphoglycolate- and phosphate-modified DNA 3'-termini are formed by oxygen radical induced DNA cleavage. To demonstrate the 3'-phosphodiesterase activity of Rrp1, a 3'-phosphoglycolate-terminated oligonucleotide substrate was generated by site-specific cleavage of a unique GpC dinucleotide by iron(II) bleomycin. Removal of the terminal phosphoglycolate is detected by mobility shift on a DNA sequencing gel. Rrp1 cleaves the phosphoglycolate and releases a product with a 3'-hydroxyl terminus. Phosphoglycolate is removed more readily than the 3'-terminal dGMP residue. Rrp1 phosphodiesterase activity is not inhibited by 120 mM NaCl, while the 3'-exonuclease is reduced 25-fold. Using a 3'-phosphate-terminated oligonucleotide, the phosphatase activity of Rrp1 is at least 25-fold lower than its phosphodiesterase or apurinic endonuclease, and 56-fold lower than exonuclease III activity on the identical substrate. Rrp1 3'-phosphatase is reduced 25-fold by 80 mM NaCl. These results were confirmed using an assay that measures the ability of Rrp1 to stimulate DNA synthesis on circular DNA substrates nicked by various DNA damage treatments. In that assay, Rrp1 poorly repairs 3'-phosphate-terminated nicks introduced by micrococcal nuclease. The significance of these enzymatic properties for the biological of Rrp1 is discussed.

Animals↗
PubMed1995

Sustained contraction produced by caffeine after ryanodine treatment in the circular muscle of the guinea-pig gastric antrum and rabbit portal vein.

1. Caffeine inhibited spontaneous mechanical activity at 0.3-1 mM, but produced a tonic contraction at concentrations higher than 3 mM in the circular muscle of the guinea-pig gastric antrum. In the circular muscle of the rabbit portal vein, caffeine at concentrations higher than 1 mM produced an early phasic contraction followed by a small tonic component. The caffeine-induced contraction was abolished by removal of the external Ca2+ more rapidly in the gastric antrum than the portal vein. 2. When the preparations were pretreated with ryanodine (1 microM) a sustained contraction developed on wash-out of caffeine (10 mM) both in the gastric antrum and portal vein. This contraction was not affected by nicardipine (3 microM) or verapamil (3 microM), but was readily abolished by removal of the external Ca2+ or by addition of cobalt (1 mM). Spontaneous electrical activity, the slow wave, in gastric muscles was blocked in the presence of 10 mM caffeine, but reappeared during the sustained contraction. 3. Both the contractions induced directly by caffeine and those produced following caffeine wash-out after ryanodine treatment were accompanied by a maintained increase in intracellular Ca2+ concentration measured with fura-2. 4. The presence or absence of Ca2+ during the application of ryanodine did not affect the ability of caffeine to initiate sustained contractions, provided Ca2+ was present during the exposure to caffeine. 5. It is concluded that caffeine can induce a sustained contraction after ryanodine treatment both in the guinea-pig gastric antrum and rabbit portal vein, by activating a Ca2+ influx pathway insensitive to organic Ca2+ channel blockers. No clear evidence was obtained for involvement of the Ca2+ influx pathway activated through depletion of intracellular Ca2+ stores. A hypothesis is proposed that the plasma membrane of these preparations is similar to the sarcoplasmic reticulum membrane in that Ca2+permeability can be increased almost irreversibly by a combination of caffeine and ryanodine in the presence of the external Ca2+.

Animals↗
PubMed1995

Pharmacology and pharmacokinetics of a novel nonpeptide angiotensin II receptor antagonist--DMP 811.

DMP 811 exhibited high binding affinity for the angiotensin II subtype receptor AT1 in rat adrenal tissues with an IC50 of 6 nM, but not for the subtype receptor AT2. In the isolated rabbit aorta, DMP 811 inhibited the contractile response to angiotensin II selectively and noncompetitively with a KB value of 0.1 nM. In conscious renal hypertensive rats, DMP 811 decreased blood pressure with i.v. and p.o. ED30s of 0.005 and 0.03 mg/kg, respectively (p.o. ED30 for losartan = 0.59 mg/kg). In conscious furosemide-treated dogs, DMP 811 given either at 0.3 or 1 mg/kg p.o. decreased blood pressure. DMP 811 has oral bioavailabilities of 7 and 29% in rats and dogs, respectively, after a solution dose and 8 and 13%, respectively, after a suspension or capsule dosing. Our study indicates that DMP 811 is a selective and insurmountable AT1 receptor antagonist and is a 20-fold more potent orally-active antihypertensive agent than losartan.

Angiotensin Receptor Antagonists↗
PubMed1995

Application of ABO genotyping using polymerase chain reaction method to assess engraftment in bone marrow transplantation--a case report.

We described a case of acute promyelocytic leukemia with O blood type who received bone marrow transplantation during a second remission from his HLA identical, B blood type sibling. Using PCR genotyping of the ABO group and analysis of the variable number of tandem repeats of the D1S80 locus, we could quickly document the successful early engraftment in this patient. We emphasize that the use of PCR ABO genotyping is a quick and valuable method which could be applied to assess the engraftment and its follow up in those transplant cases with donors of mismatched blood groups.

ABO Blood-Group System↗
PubMed1995

MDR1 gene expression in acute myeloid leukemia: clinical correlation.

Acute myeloid leukemia (AML) has a poor long-term prognosis, with a disease-free survival rate of only 20%. Drug resistance remains the major obstacle in this disease, although relatively little data are available on the correlation of multi-drug resistance (MDR) and clinical outcome. We examined 28 bone marrow samples from 24 patients with AML. The MDR1 RNA levels were determined by slot blot analysis. The incidence of positive expression of MDR1 mRNA in patients was 64.7% in samples from newly-diagnosed patients and 85.7% in relapse samples. The overall complete remission rate was 45%. However, the complete remission rate was lower for patients in the MDR1 RNA positive group than in the negative group. In three cases, the MDR1 RNA expression steadily rose during the period of disease progression and after several courses of chemotherapy. We suggest that a high frequency of MDR1 gene expression in patients with AML and higher MDR1 RNA levels are associated with a lower incidence of complete remission as well as a shorter disease-free time. The expression of MDR1 is a poor prognostic factor for AML treatment and it may play an important role in resistance to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗