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Biomedical subjects

C W Wu

Publications and source records attributed to C W Wu.

At least 163 records · Page 9Linked to original sources

Genetic polymorphism and activities of human colon alcohol and aldehyde dehydrogenases: no gender and age differences.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isoenzyme patterns from 69 (men, 47; women, 22) surgical colon mucosal specimens were identified by agarose isoelectric focusing. gamma-ADH was found to be the predominant form in the mucosa, whereas only beta-ADH was detectable in the muscle layer. ALDH1, ALDH2, and ALDH3 were detectable in the mucosa, with cytosolic ALDH1 being the major form. At pH 7.5, the ADH activities in the colon mucosae with the homozygous phenotype (exhibiting gamma 1 gamma 1) and the heterozygous phenotype (exhibiting gamma 1 gamma 1, gamma 1, gamma 2, gamma 2, gamma 2) were determined to be 183 +/- 13 and 156 +/- 30 nmol/min/g tissue, respectively. The ALDH activities in the ALDH2-active and ALDH2-inactive phenotypes were determined to be 40.2 +/- 2.3 and 34.6 +/- 2.0 nmol/min/g tissue, respectively. The lack of significant difference in the ALDH activities between these two phenotypic groups can be attributed to the very low expression of the mitochondrial ALDH2 in the colon mucosa. No significant differences in the ADH or the ALDH activities were found between the men and women studied and between the three age groups (20-40, 49-70, and 72-83 years). The ascending, transverse, descending, and sigmoid colons exhibited similar ADH and ALDH activities. The isoenzyme patterns of ADH and ALDH remained unaltered in colon carcinomas, except that a significant reduction of the enzyme activities was found in the cancer tissue as compared with the adjacent normal portions. it is concluded that human colon mucosa exhibits significant amounts of ethanol- and acetaldehyde-oxidizing activities.

Adult↗

Quantitative comparison of rate response and oxygen uptake kinetics between different sensor modes in multisensor rate adaptive pacing.

Although multisensor pacing may mitigate the inadequacy of rate adaptation in a single sensor system, the clinical role of multisensor driven rate adaptive pacing remains unclear. The cardiopulmonary performance of six patients (mean age 63.5 +/- 10 years) who had undergone the implant of combined QT and activity VVIR (Topaz) pacemakers was assessed during submaximal and maximal treadmill exercise with the rate response sensor randomly programmed to either single sensor mode, QT and activity (ACT), or dual sensor mode, with equal contribution of QT and ACT (QT = ACT). The rate of response, the proportionality, oxygen kinetics, and maximal exercise performance of the various sensor modes during exercise were measured and compared. The ACT sensor mode "overpaced" and the QT and QT = ACT sensor modes "underpaced" during the first three quartiles of exercise (P < 0.05). The ACT sensor mode also gave the fastest rate of response with the shortest delay (13 +/- 1.5 sec vs 145 +/- 58 sec and 41 +/- 17 sec, P < 0.05), time to 50% rate response (39 +/- 2.7 sec vs 275 +/- 48 sec and 203 +/- 40 sec, P < 0.05), and time to 90% of rate response (107 +/- 21 sec vs 375 +/- 34 sec and 347 +/- 34 sec, P < 0.05) and a smaller oxygen debt (0.87 +/- 0.16 L vs 1.10 +/- 0.2 L and 1.07 +/- 0.18 L, P < 0.05) compared to the QT and QT = ACT sensor modes, respectively. These differences were most significant at low exercise workloads. Thus, different sensor combinations result in different rate response profiles and oxygen delivery, especially during low level exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Nuclear mitotic apparatus protein (NuMA): spindle association, nuclear targeting and differential subcellular localization of various NuMA isoforms.

We have recently shown that the nuclear mitotic apparatus protein (NuMA) is composed of at least three isoforms that differ mainly at the carboxy terminus, and are generated by alternative splicing of a common mRNA precursor from a single NuMA gene (J. Cell Sci. (1993) 104, 249-260). Transient expression of human NuMA-1 isoform (T33/p230) in Chinese hamster ovary polyoma (CHOP) cells showed that NuMA-1 was present in interphase nuclei and was concentrated at the polar regions of the spindle apparatus in mitotic cells. However, expression of two other isoforms (NuMA-m and -s) revealed a distinct subcellular localization. NuMA-m (U4/p195) and NuMA-s (U6/p194) were present in the interphase cytosol and appeared to be mainly located at the centrosomal region. When cells entered into mitosis, however, NuMA-m and -s moved to the mitotic spindle pole. Analysis of a series of linker scanning-mutants and NuMA/beta-galactosidase chimeric proteins showed that residues 1972-2007 of NuMA-1 constitute a novel nuclear localization signal (NLS) and residues 1538-2115 are necessary and sufficient for spindle association. Further analysis of the NLS by site-specific mutagenesis indicated that Lys1988 is essential for nuclear targeting, whereas Arg1984 is not. These results have allowed us tentatively to assign specific biological activities to distinct structural domains of the NuMA polypeptide.

Amino Acid Sequence↗

Adenocarcinoma of midstomach. Clinical and pathoanatomic relation to lymph node metastases.

A detailed clinical and anatomic-pathological study of lymph node (LN) metastases from adenocarcinoma of the midstomach is lacking. To such an end, we prospectively evaluated 100 patients who underwent radical gastrectomy. A total of 3,394 LNs were removed with an average of 34 per specimen (range, 10-105). Forty-seven patients (47%) had involved LNs. The most frequent LNs involved were those along the lesser curvature (38%), greater curvature (23%), left gastric artery (19%), infrapyloric (16%), above the common hepatic artery (13%), suprapyloric (11%), and right paracardia (9%). When tumors involved the upper stomach, the frequency of LN metastases along the splenic artery and in the splenic hilum was 11.8%. Tumors along the lesser curvature or on the anterior or posterior walls had splenic hilar LN metastases in 10%, whereas of tumors involving the whole circumference, 16.7% showed with metastases. Four of 33 patients (12.1%) with early cancer had LN metastasis confined to the perigastric, left gastric artery, and above the common hepatic artery. The LN metastases were closely related to the depth of cancer invasion, location, size, gross appearance, and histology of the tumor.

Adenocarcinoma↗

Gastric cancer invading the lamina muscularis propria.

BACKGROUND: Gastric cancer invading the lamina muscularis propria is considered to be an intermediate stage between early and far advanced gastric cancer. This study evaluated the clinicopathological pictures of muscularis propria gastric cancer. METHODS: In the past 5 years, 407 patients with adenocarcinoma of stomach underwent radical gastrectomy in Department of Surgery, Veterans General Hospital-Taipei. Of them, 46 patients (11.3%) with gastric cancer invading the muscularis propria were studied. Their clinicopathologic features were further analyzed with special reference to the gross appearance of the tumor. RESULTS: Most muscularis propria gastric cancers occurred at lower stomach. Nodal spread accounted for 32.6% and was largely confined to n2 with limited involvement of n3. Borrmann type cancer comprised 63% (29/46) of cases and early-like type cancer comprised 37%. Early-like type cancer was smaller in size than Borrmann type cancer (p < 0.001). Nodal spread was more extent in Borrmann type cancer than in early-like type cancer. Other clinicopathologic features and survival were identical in both types of muscularis propria gastric cancer. CONCLUSIONS: Most muscularis propria gastric cancers were Borrmann type cancer grossly. Compared with the early-like type, the Borrmann type cancer was larger and had more extensive nodal spread.

Adenocarcinoma↗

Comparison of aged and young adult patients with cholelithiasis: a prospective controlled study.

BACKGROUND: Surgical operations for gallstones are associated with increased perioperative mortality in the elderly. The presence of pre-existing cardiovascular disease and acute cholangitis might be the cause as found in the literature. METHODS: From August 1989 to December 1990, twenty-nine patients (Age > or = 70 years) with cholelithiasis undergoing biliary surgery in Veterans General Hospital-Taipei were collected as experimental group. Twenty-nine patients from 62 patients (Age < or = 50 years) with cholelithiasis were selected as control group. The basic data, symptomatology, blood biochemistry, peri-operative complications, mortality and gallstone compositions were analyzed and compared between both groups. RESULTS: There was a higher male to female ratio (4.8:1) in the aged group. Aged patients had higher incidence of common bile duct stone (11/29 versus 3/29, P < 0.025), while young adult patients had higher incidence of intrahepatic stone (1/29 versus 10/29, P < 0.05). The perioperative morbidity and mortality was higher in the aged group (37.9% and 3.4%) as compared with the young age group (3.4% and 0%, P < 0.005). CONCLUSIONS: Aged cholelithiatic patients were associated with male preponderance, more common bile duct stones, higher perioperative morbidity and mortality, as compared with the young adult cholelithiatic patients.

Adult↗

Mutagenicity and mutational spectrum of N-methyl-N'-nitro-N-nitrosoguanidine in the hprt gene in G1-S and late S phase of diploid human fibroblasts.

To investigate the effect of DNA replication on the mutation spectrum induced in diploid human fibroblasts by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), cells were synchronized and exposed to MNNG either at the G1-S border or in late S phase, and the mutations in the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene were examined. The coding regions of 92 independent mutants were characterized by direct sequencing of mRNA-polymerase chain reaction-amplified complementary DNA. While there was little difference in the sensitivity of the two populations to the cytotoxic effects of MNNG, the frequency of mutants induced in late S populations was significantly lower than that induced in G1-S populations. The majority of induced complementary DNA mutations were single base substitutions (54%) and splice site mutations (43%). Analysis of the intron-exon boundaries of more than one-half of the splicing mutants showed that almost all contained base substitutions in the hprt gene. A broad mutational spectrum was observed in low-dose (4, 6, or 8 microM) treatments; only 27% were G to A transitions, whereas 80% of base substitutions derived from the high-dose (10 or 12 microM) treatments were G to A transitions in G1-S populations. An intermediate frequency (64%) of G to A transitions was observed in late S populations exposed to MNNG. When the causative premutation lesion was O6-methylguanine, 75% of G to A transitions that were observed in G1-S populations clustered on both the transcribed and the nontranscribed strands of the 5' half of the hprt gene. In contrast, 50% of G to A transitions were located only on the nontranscribed strand of this region in late S populations. The results indicate that O(6)-alkylguanine-DNA-alkyltransferase may not efficiently remove O(6)-methylguanine from the 5' half of the gene but can repair lesions far away from this region during initiation of replication. Our results are consistent with the notion that the putative origin of replication is located at intron 1 of the hprt gene.

Amino Acid Sequence↗

Lymph node metastasis in patients with adenocarcinoma of gastric cardia.

BACKGROUND AND METHODS: Prospectively, a consecutive series of 42 patients undergoing extended radical total gastrectomies (R 3/4 lymph node dissection) for adenocarcinoma of the gastric cardia from January 1988 to June 1991 were studied. The aims of this study were to evaluate the status of lymph node metastasis and the relationship between the frequency of nodal involvement and the extent of the primary tumor invasion. The Japanese criteria was used for postoperative staging. RESULTS: The incidence of operative morbidity and mortality in the series were 40.5% and 9.5%, respectively. Twenty-two (52%) of the patients had lymph node metastasis. For those patients, the most common sites of nodal involvement were the lesser curvature (72.7%), pericardiac (68.2%), left gastric artery (45.5%), left greater curvature (31.8%), splenic artery (31.8%), and the hilum (22.7%), inferior paraesophageal (18.2%), and diaphragmatic (18.2%) regions. Only one skip lymph node metastasis was discovered. In addition, no lymph node metastasis was found in the following areas: hepatoduodenal ligaments, mesenteric root, right paraadrenal, and subcardial lymph nodes. CONCLUSIONS: The study's results demonstrate that there seemed to a correlation among the status of lymph node metastasis, tumor size, and the depth of tumor invasion. However, the depth of tumor invasion appears to be a more important factor than tumor size in influencing the status of lymph node metastasis. The local recurrence rate was 2.4%. Consequently, the authors recommend that for the tumor with mucosal invasion only, a relatively conservative lymphadenectomy may be sufficient, but for tumors that invade beyond the mucosal region, radical lymphadenectomy may be helpful in preventing local recurrence.

Adenocarcinoma↗

Protection of a rat tracheal epithelial cell line from paraquat toxicity by inhibition of glucose-6-phosphate dehydrogenase.

Transformed rat tracheal epithelial cells (U2) were found to be 3.6-fold more sensitive than lung fibroblasts (RLF) to paraquat. Although the toxic effects of paraquat are associated with the generation of very active superoxides, U2 cells contained higher levels of superoxide dismutase and catalase than RLF cells. On the other hand, the specific activities of both NADPH-cytochrome c reductase and glucose-6-phosphate dehydrogenase (G6DP) were 3- to 4-fold higher in U2 cells than in RLF cells. Treatment with dehydroepiandrosterone (DHEA) and epiandrosterone (EPI), G6PD inhibitors, significantly decreased the intracellular NADPH and protected U2 cells from paraquat toxicity. Since DHEA and EPI treatment did not affect the uptake of paraquat, our results suggest that paraquat sensitivity may depend on the redox cycling-associated activities of paraquat.

Androsterone↗

Bile duct injury and bile leakage in laparoscopic cholecystectomy.

Between January 1991 and July 1992, 350 laparoscopic cholecystectomies were performed. There were six biliary complications (1.7 per cent): common bile duct (CBD) injury (one patient), delayed CBD necrosis (one), immediate postoperative bile leakage (one) and delayed bile leakage (three). All six patients required laparotomy. Primary repair with long-arm T tube splinting for 3 months was performed for the CBD injury. Religation of the cystic duct was carried out after immediate postoperative bile leakage. Laparotomy with T tube choledochostomy only was performed in the three patients with delayed bile leakage, and hepatojejunostomy Roux-en-Y was undertaken for CBD necrosis. The patient with primary repair of the CBD injury required choledochojejunostomy Roux-en-Y 18 months later for stenosis. Episodes of intermittent cholangitis occurred in the patient with CBD necrosis. The outcome for the four patients with bile leakage was good. There were no deaths.

Adult↗

Cytomegalovirus recurrence in seropositive pregnant women attending obstetric clinics.

To understand reasons for cytomegalovirus (CMV) recurrence, a cohort of 350 CMV-seropositive pregnant women attending obstetric clinics in Taiwan was examined for cervical or urinary CMV shedding. Urine specimens were collected from 350 women and cervical secretion specimens were collected from 220 women. We measured the association of various factors with CMV recurrence, which was defined as viral shedding identified by the presence of a CMV-specific gene sequence amplified by the polymerase chain reaction in seropositive individuals. CMV recurrence status was independently associated with a sexual activity composite variable, which was defined by three sexual activity indicators: age at first sexual intercourse, total years of sexual experience, and average frequency of sexual intercourse prior to pregnancy. Pregnant women with a history of genital tract infection were more likely than women without such history to experience cervical CMV recurrence. Similarly, pregnant women with previous urinary tract infections were more likely to experience urinary CMV recurrence. The findings indicate that multiple exposure to CMV by sexual activity prior to pregnancy is an important determinant of CMV recurrence during pregnancy.

Antibodies, Viral↗

High rate of concurrent genital infections with human cytomegalovirus and human papillomaviruses in cervical cancer patients.

A case-control study evaluated a possible association between infection with human papillomavirus (HPV) or cytomegalovirus (CMV) and cervical cancer. Seventy-eight patients with cervical cancer (cases) were compared with 55 age-compatible patients with uterine leiomyoma (controls). Genital CMV and HPV infections were diagnosed by polymerase chain reaction amplification of viral DNA in cervical tissues. Smoking, first coitus or pregnancy before age 20, multiple sex partners, history of multiple pregnancies, and frequent sexual intercourse were important factors associated with cervical cancer. Only 9% of the cases versus 29.1% of the controls did not have genital infection with either virus. Concurrent genital CMV and HPV infection was noted in 51.3% of the cases but in none of the controls. HPV infection alone occurred in 15.4% of the cases but in only 5.5% of the controls. CMV infection alone was associated with no increased risk for cervical cancer. These data suggest that a synergistic interaction may occur between these two viral infections in the oncogenesis of cervical cancer.

Adult↗

Alcohol and aldehyde dehydrogenases in human esophagus: comparison with the stomach enzyme activities.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isoenzymes from surgical esophageal and gastric mucosa were compared by agarose isoelectric focusing. Two prominent ADH forms, designated mu 1 (equivalent to the recently reported mu-form) and mu 2, were expressed in all the 15 esophagus specimens studied, whereas only four of seven examined gastric specimens exhibited a weak to moderately strong mu 1-ADH activity band on the isoelectric focusing gels. pI values of the esophageal mu 1-ADH and mu 2-ADH, and the liver pi-ADH were determined to be 8.61, 8.13, and 8.90, respectively. mu-ADHs exhibited high Km for ethanol (12 mM) and low sensitivity to 4-methylpyrazole inhibition. ALDH3 (BB form) and ALDH1 were the major high- and low-Km aldehyde dehydrogenase in the esophagus, respectively. The ADH and ALDH activities were determined at pH 7.5 to be 751 +/- 78 and 29.9 +/- 3.0 nmol/min/g tissue, respectively (measured at 500 mM ethanol or at 200 microM acetaldehyde; mean +/- SEM; N = 15). The esophageal ADH activity was approximately 4-fold and the ALDH activity 20% that of the stomach enzyme. Because the presence of high activity and high Km mu-ADHs as well as low-activity ALDH1 were found in human esophageal mucosa, it is suggested that there may exist an accumulation of intracellular acetaldehyde during alcohol ingestion. This reactive and toxic metabolite may be involved in the pathogenesis of alcohol-induced esophageal disorders.

Aged↗

Cytomegalovirus excretion in pregnant and nonpregnant women.

Cervical and urinary excretion of cytomegalovirus by Taiwanese women was identified by the presence of a cytomegalovirus-specific immediate-early gene sequence amplified by the polymerase chain reaction. Excretion rates during the first trimester of pregnancy resembled rates for nonpregnant women. As pregnancy proceeded, the cervical excretion rate increased from 13 to 40% and the urinary excretion rate increased from 1 to 13%.

Adult↗

Can daily dietary arginine supplement affect the function and subpopulation of lymphocytes in patients with advanced gastric cancer?

Since arginine can stimulate lymphocyte proliferation in the healthy human, its effect on lymphocyte proliferation in vitro was studied in 7 patients with far advanced gastric cancer. These patients with normal nourishment were ambulatory and could consume a regular diet. A daily dietary supplement of 30 g arginine for 7 days did not alter the total lymphocyte counts or the T/B cell ratio in the peripheral blood. Enhancement of lymphocyte proliferation in response to mitogen stimulation was not observed. Furthermore, an in vitro study on the effect of arginine on phytohemagglutinin-stimulated lymphocyte proliferation showed that lymphocytes from gastric cancer patients had poorer responses than those obtained from normal subjects, despite the supplement in the culture medium with normal serum, patient serum, or fetal bovine serum. Arginine ingestion did not impair liver function and had no detectable side effects except transient nausea in 1 patient. These results indicate that dietary arginine supplement appears safe but does not stimulate lymphocyte function in far advanced gastric cancer patients. The suppressed immune function in gastric cancer patients may be the result of their intrinsic lymphocyte defect.

Adenocarcinoma↗