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Biomedical subjects

C C Hsieh

Publications and source records attributed to C C Hsieh.

At least 145 records · Page 8Linked to original sources

Collagen biosynthesis in human oral submucous fibrosis fibroblast cultures.

To investigate the mechanism of collagen accumulation in oral submucous fibrosis (OSF) tissues, we examined the biosynthesis of collagen in fibroblast cultures established from OSF lesions. Fibroblasts obtained from four of ten OSF specimens showed more than a 1.5-fold increase in the production of collagens compared with fibroblasts from age-, sex-, and passage-matched normal controls (p < 0.05). When the relative amounts of collagen synthesis were estimated by SDS polyacrylamide gel electrophoresis, it was found that both OSF and control cells produced about 85% type I collagen and 15% type III collagen. The ratio of alpha 1(I) to alpha 2(I) chains was about 3:1 in OSF cells instead of the 2:1 expected for type I collagen. The excess alpha 1(I) chains could mean that collagen type I trimer was synthesized by the fibroblasts. These findings suggest that collagen overproduction and a reduced degradation of the structure-stable collagen type I trimer synthesized by OSF fibroblasts might contribute to the accumulation of collagen in OSF lesions in vivo. The mechanism(s) of increased procollagen production were analyzed by Northern blot, slot blot, and Southern blot. The OSF fibroblast strains with elevated collagen production also contained higher-than-normal levels of procollagen mRNA, and the ratios of alpha 1(I), alpha 2(I), and alpha 1(III) procollagen mRNAs were compatible with the results of corresponding procollagen alpha chains. The gene copy number of pro alpha 2(I) collagen gene in OSF fibroblasts was about 1.05. No gene amplification was found. These results indicate that expression of these procollagen genes in cultured fibroblasts is regulated at the transcriptional level.

Case-Control Studies↗

Organochlorine compounds in relation to breast cancer, endometrial cancer, and endometriosis: an assessment of the biological and epidemiological evidence.

There is an increasing public and scientific concern that certain chlorinated compounds, recognized as environmental pollutants, may cause estrogen-related neoplastic disease in humans. The main hypothesis has been that certain organochlorines, through their estrogenic actions, might cause breast cancer. From experimental studies, both in vitro and in vivo, there is evidence that certain organochlorine compounds may cause estrogenic effects, whereas others may cause antiestrogenic effects. In limited studies, some of these compounds in high doses have also been shown to increase and reduce the frequency of estrogen-related tumors in animals. The epidemiological findings regarding the association between organochlorines and breast cancer are inconclusive. However, the largest and best designed study has been interpreted as negative with respect to DDT and polychlorinated biphenyls (PCB) in relation to breast cancer. Associations between organochlorine exposure and endometrial cancer or endometriosis have even more limited empirical basis. The hypothesis that human exposure to environmental levels or organochlorines would favor an estrogenic overactivity leading to an increase in estrogen-dependent formation of mammary or endometrial tumors is not supported by the existing in vitro, animal and epidemiological evidence. It can, however, not be conclusively rejected on the basis of available data.

Animals↗

Establishment of in vivo hepatoma models in rat and mouse from rodent hepatoma cell lines.

BACKGROUND: Hepatoma is one of the most common cancers in Southeast Asia and African countries. In Taiwan, it is the leading cause of death in male cancer patients. In order to examine the effect of various factors on the growth of hepatoma, in vivo hepatoma models such as carcinogen-induced hepatoma and subcutaneous implantation of hepatoma in nude mice have been used. However, there are disadvantages in these models. METHODS: Rats and mice were anesthetized by ketamine or ether, respectively. After a midline incision was made, N1S1 rat hepatoma cells were injected intrasplenically to partially hepatectomized or sham-operated rats, while BALB/c mice received intrasplenic injection of ML-2 and ML-3 mouse hepatoma cells. For direct tumor implantation, a 1mm3 N1S1 tumor piece was implanted in liver of Sprague-Dawley (SD) rat using a trocar. Animals were sacrificed at specific times after tumor implantation. Tumor incidence and the number of tumor nodules on the liver surface were recorded. Tumor samples were fixed and embedded for histological examination. RESULTS: After intrasplenic implantation of ML-2 cells, no tumor was observed on the liver in any of the 10 mice 40 days later. In comparison, rapid growth of hepatic ML-3 tumors was observed in all animals. Rat hepatoma cells RH-35, McA-RH7777 and McA-RH8994 cells did not form tumors in SD rats. The tumorigenicity of N1S1 cells in SD rats was dose-dependent on implanted tumor cells. In addition, hepatic N1S1 tumors could be obtained within a few weeks by homograft. CONCLUSIONS: We have successfully established in vivo hepatoma models in both the rat and the mouse. The murine ML-3 cells generated hepatoma in syngeneic BALB/c mice while the tumorigenicity of N1S1 cells in partially hepatectomized SD rats was dose-dependent on implanted tumor cells. These in vivo rodent models will be valuable tools for future studies of hepatoma.

Animals↗

Human and canine cardiac troponin T and creatine kinase-MB distribution in normal and diseased myocardium. Infarct sizing using serum profiles.

OBJECTIVE: Cardiac troponin T (cTnT) has been suggested as a new, more specific marker of myocardial cellular damage. The objectives of this study were to examine the distribution of cTnT and creatine kinase (CK)-MB in normal and diseased heart tissue of dogs and humans, and to assess the use of serum cTnT for the estimation of infarct size in dogs. DESIGN: Serial serum specimens over 7 days were obtained from normal dogs (controls, n = 3) and dogs that underwent surgical coronary artery occlusion (n = 6). Heart muscle samples were obtained from the controls and after 3 weeks of occlusion in experimental dogs. Diseased human heart muscle samples were obtained at autopsy from patients who had died of acute myocardial infarction (n = 3). Normal heart muscle samples (n = 3) were obtained at autopsy from patients who died of non-cardiac-related illnesses. Tissues were sectioned and homogenized to harvest both cytosolic and myofibril-bound proteins. Serum samples and tissue homogenates were assayed for cTnT, CK-MB, and myoglobin (humans only). Total protein was assayed on homogenate samples and results were reported as milligrams per gram of total protein. RESULTS: The distributions of cTnT, CK-MB, and myoglobin were equivalent across 14 sites within normal human heart. Creatine kinase-MB and myoglobin were more than 99% cytosolic. Cardiac troponin T was 92% myofibril bound and 8% cytosolic. In the control dog hearts, cTnT was higher and CK-MB was lower in the right ventricle than in the left ventricle. While CK-MB and myoglobin were more than 99% cytosolic, cTnT was 98% myofibril bound and 2% cytosolic. Infarct sizing in dog hearts initially did not correlate well with serum cTnT or CK-MB concentrations. However, when the data were separated by infarct location (right coronary artery; left circumflex coronary artery), the correlations improved dramatically. Differences in tissue concentrations of cTnT and CK-MB between the left and right ventricle might explain the change in correlations. Coronary artery occlusion in dogs and humans resulted in decreased cytosolic and myofibril cTnT and increased CK-MB and myoglobin in diseased myocardial tissue. CONCLUSIONS: Our observed biochemical alterations suggest that the energy-producing proteins CK-MB and myoglobin are upregulated following cellular damage, while the structural and regulatory protein cTnT does not have a mechanism for replacement of lost protein following cell injury and necrosis.

Animals↗

Congenital malformation in newborns. Analysis of 501 cases.

Over a 14-year period in Chang Gung Memorial Hospital, 510 out of 44, 362 newborns were found to have birth defects. Maternal age, gestational age, parity, infant sex and birth weight were analyzed for each anomaly and compared to normal newborns. The average maternal age and parity for newborns with congenital anomalies were not significantly different from normal newborns. Mothers giving birth to babies with chromosomal aberrations, however, had a significantly older maternal age than the normal population. The gestational age at delivery was significantly shorter for all except craniofacial anomaly. In addition, there was a high percentage of intrauterine growth retardation in congenital anomalies. The central nervous system, the musculoskeletal system and craniofacial systems were the most commonly involved. The leading anomalies included cleft lip, cleft palate, anencephaly, polydactyly, hydrops fetalis, trisomy 21 and cystic hygroma. With improved ultrasound equipment and other prenatal diagnostic procedures, many defects of the fetus can now be identified. If the fetus is diagnosed with a surgically correctable lesion like cleft lip, it can be kept to term, delivered, then managed postnatally. If life-incompatible malformations have been detected before the 24th week, physicians are in a good position to counsel the parents. After the 24th week termination is proscribed by law. Therefore, physicians must take special care to detect fetal abnormalities early.

Congenital Abnormalities↗

Prenatal diagnosis of tetralogy of fallot by Doppler color flow mapping.

The prenatal diagnosis of tetralogy of Fallot (TOF) can be difficult, as the routine sonographic four-chamber view may be normal before birth. Unlike the normal fetus, in which blood flows adjacent to the left side of the interventricular septum, on color Doppler mapping a fetus with TOF also demonstrates antegrade flow along the right side of the interventricular septum. This Y-shaped ventricular outflow passing through the dilated aortic tract is confluent at the level of the ventricular septal defect during the systolic phase. In the past 3 years, three cases of TOF have been diagnosed prenatally at the Chang Gung Memorial Hospital. In each case, the above picture was demonstrated. 2-Dimensional Doppler color flow mapping may be helpful in the prenatal diagnosis of TOF.

Adult↗

Serum activity of angiotensin converting enzyme (ACE) is not affected by hepatitis B viral infection.

Activity of angiotensin converting enzyme (ACE) in the serum from healthy and hepatitis B-infected subjects were examined. Preservation of the serum samples for 32 days at -80 degrees C did not significantly alter the activity of ACE. We have determined the ACE activity in three groups: healthy subjects with negative hepatitis B surface antigen (HBsAg) and normal liver function or the (-,N) group, subjects exhibiting positive HBsAg and normal liver function or the (+,N) group, as well as subject with positive HBsAg and abnormal liver function or the (+,Ab) group. The healthy group (-,N) exhibited serum activity of ACE of 31.5 +/- 1.2(25) nmoles/min/ml serum. There was no difference in ACE activity whether surface antigen was present, i.e., between (-,N) and (+,N) groups. Although a slight (about 10%) elevation of ACE activity was observed in the third group (+,Ab), it was not significantly different from either (-,N) or (+,N) group. These results suggest the lack of association between the serum activity of ACE and hepatis B, however, further studies are required to clarify whether correlation exists between serum activity and liver function.

Adult↗

Purification of glucosyltransferases (GtfB/C and GtfD) from mutant strains of Streptococcus mutans.

Streptococcus mutants constitutively expresses three glucosyltransferases (GTFs), i.e., GtfB, GtfC, and GtfD, which synthesize glucan polymers from sucrose. Two genetically constructed mutants of S. mutans which stably expressed either the cell-associated or the extracellular GTFs were selected for purification and characterization of these enzymes. The cell-associated GtfB and GtfC from strain GS-5DD lacking the gtfD gene expression were extracted by urea, renatured by dialysis in sodium phosphate buffer and then separated from the other wall-associated components by column chromatography. The extracellular GtfD was purified from the culture supernatant of strain NHS1 lacking gtfB and gtfC gene expression. The molecular weights of the purified GTFs was similar (150-160 kDa), as determined by SDS-polyacrylamide gel electrophoresis. The GtfB/C preparation synthesized primarily water-insoluble glucan in a primer independent manner. However, the presence of the dextran enhanced the enzymatic activities of the GtfB/C. GtfD synthesized water-soluble glucan exclusively in a primer dependent manner. Purified GtfD had a pH optimum of 5.5, and a K(m) value of 4.35 mM for sucrose. These results indicated that the mutated strains served as an efficient and specific host to obtain native GTFs.

Glucosyltransferases↗

Purification and characterization of Streptococcus mutans glucosyltransferase (GtfC) expressed in Escherichia coli.

Streptococcus mutans constitutively expresses three glucosyltransferases, i.e., GtfB, GtfC, and GtfD; which synthesize glucan polymers from sucrose. To obtain individual GTF without complexing with one another, a purification strategy was developed to recover recombinant GTF expressed from Escherichia coli. The recombinant GtfC was aggregated and associated with the insoluble fraction in E. coli homogenates. GtfC was solublized with the 8M urea, renatured to its biologically active form by serial dialysis against sodium phosphate buffer, and subsequently purified to homogeneity by DEAE-Sephacel and hydroxylapatite column chromatography. The GtfC enzyme preparation was purified 16.3-fold and the molecular weight was estimated to be 140 kDa. GtfC synthesized water insoluble glucan in a primer independent manner and its enzymatic activities could be enhanced by dextran. Purified GtfC had a pH optimum of 6.5, a K(m) of 9.26 mM for sucrose and a pI of 5.5. Distinct from the previous reports, results from this study offers an alternative for the purification of the recombinant GTFs free from any detergent contamination to make it more suitable for utilization in vivo.

Escherichia coli↗

Parity, age at first childbirth, and risk of ovarian cancer.

Increasing parity is associated with a reduction in the risk of ovarian cancer, but it is not clear whether this association applies to different histopathological types and to borderline tumours. Moreover, the temporal relations are poorly understood, and the possible role of age at first birth remains unequivocal. We have investigated these issues in a case-control study nested in a nationwide cohort of women born between 1925 and 1960 in Sweden. During follow-up until 1984, 3486 invasive ovarian cancers (2992 epithelial, 330 stromal, 149 germ-cell, 15 not classifiable) and 510 tumours of borderline malignant potential were diagnosed. 5 individually age-matched controls (total 19,980) were selected for each case woman. After simultaneous adjustment for parity and age at first birth, increasing parity was associated with a pronounced consistent decrease in relative risk of all invasive cancers (odds ratio for each additional birth 0.81 [95% Cl 0.77-0.85]), epithelial cancer (0.81 [0.77-0.86]), stromal cancer (0.84 [0.72-0.98]), and germ-cell cancer (0.71 [0.48-1.05]), but a less consistent decrease for borderline tumours (0.92 [0.81-1.04]). The risk of ovarian cancer decreased by about 10% for each 5-year increment in age at first childbirth (odds ratios 0.89 [0.84-0.94] epithelial cancer, 0.92 [0.77-1.10] stromal cancer, 0.92 [0.65-1.32] germ-cell cancer, 0.93 [0.80-1.09] borderline tumours). Because our findings cannot be readily explained by theories involving incessant ovulation or high serum concentrations of gonadotropins, new aetiological hypotheses are needed. Pregnancy-dependent clearance from the ovaries of cells that have undergone malignant transformation could explain the reproductive risk factors for ovarian cancer.

Adolescent↗

Reduced rate of disease development after HIV-2 infection as compared to HIV-1.

Human immunodeficiency virus type-2 (HIV-2) is a close relative of the prototype acquired immunodeficiency syndrome (AIDS) virus, HIV-1. HIV-2 is biologically similar to HIV-1, but information is lacking concerning clinical outcomes of HIV-2-infected individuals. From 1985 to 1993, a prospective clinical study was conducted in women with HIV-2 and HIV-1 infection to determine and compare rates of disease development. HIV-1-infected women had a 67% probability of AIDS-free survival 5 years after seroconversion in contrast with 100% for HIV-2-infected women. In addition to having significantly less HIV-related disease outcome in HIV-2 enrollees compared to HIV-1 enrollees, the rate of developing abnormal CD4+ lymphocyte counts with HIV-2 infection was also significantly reduced. This natural history study demonstrates that HIV-2 has a reduced virulence compared to HIV-1.

Acquired Immunodeficiency Syndrome↗

Transport of 2-aminoisobutyric acid in cultured endothelial cells.

Conflicting reports exist concerning the presence of a Na(+)-coupled amino acid transport system in cultured endothelial cells. We have employed a non-metabolizable analog, 2-aminoisobutyric acid (AIB), to investigate the activity of Na(+)-dependent amino acid transport in cultured human umbilical vein endothelial cells (HUVEC). We found a pronounced saturable, Na(+)-dependent component of AIB uptake in 'fresh' (non-starved) HUVEC. The Na(+)-dependent component accounted for 78% of total AIB uptake with a high sensitivity to external Na+. The accumulation of AIB was inhibited by ouabain preincubation, consistent with the energetics of Na(+)-coupled transport. Amiloride, an epithelial Na+ channel blocker, also inhibited AIB transport at high concentration. The results strongly support the presence of a Na(+)-coupled transport system of amino acid in HUVEC.

Amiloride↗

Slower heterosexual spread of HIV-2 than HIV-1.

Because of the similar virological properties of HIV types 1 and 2, HIV-2 was assumed to be as infectious and capable of inducing AIDS as HIV-1. Seroepidemiological studies have shown significant rates of HIV-2 infection in West Africa, and surveys from other regions of the world indicate that the spread of HIV-2 infection continues. However the pathogenic potential of HIV-2 is considered to be lower than that of HIV-1. It is therefore important to understand the transmission properties of HIV-2 and its contribution to the AIDS pandemic. Since 1985, we have prospectively studied 1452 registered female prostitutes in Dakar, Senegal, with sequential evaluation of their antibody status to HIV-1 and HIV-2. During the study the overall incidence of HIV-1 and HIV-2 was the same (1.11 per 100 person-years of observation [pyo]). However, the annual incidence of HIV-1 increased substantially: there was a 1.4-fold increased risk per year and thus a 12-fold increase in risk over the entire study period. The incidence of HIV-2 remained stable, despite higher HIV-2 prevalence. In our population the heterosexual spread of HIV-2 is significantly slower than that of HIV-1, which strongly suggests differences in the viruses' infectivity potential.

Adult↗

Epidemiologic correlates of breast cancer laterality (Sweden).

Breast cancer laterality was studied in relation to age in 80,784 cases of invasive and 3,835 cases of pre-invasive breast cancer in women and 548 cases of invasive breast cancer in men reported to the Swedish Cancer Registry, 1970-89. In a subset of 11,274 women with invasive disease, data on parity were available through the Swedish Fertility Registry. Laterality also was evaluated in relation to age and reproductive variables in 3,986 cases from an international study from the 1960s. The overall incidence of pre-invasive and invasive cancer was higher in the left than in the right breast among both women and men. The excess incidence of invasive cancer in the left breast was evident only after the age of 45 years in women; a similar phenomenon may exist with pre-invasive disease in women and in men. The age-dependent laterality pattern did not appear to be confounded by menopausal status. Among women younger than 45 years, nulliparity, right handedness, and late age at menarche was associated with a somewhat higher incidence of cancer in the right breast. The laterality findings are likely to be due to factors operating early in the carcinogenic process, perhaps at the pre-initiation stage.

Adult↗

Rising incidence rate of esophageal adenocarcinoma and use of pharmaceutical agents that relax the lower esophageal sphincter (United States).

Primary adenocarcinoma of the esophagus, previously considered a rare neoplasm, has shown a dramatic increase in its incidence rate among White men in the United States since 1970. The reason for this increase is unknown. Since the presence of Barrett's esophagus is essential for the development of most esophageal adenocarcinomas, the increasing incidence of esophageal adenocarcinoma may be related to an increasing prevalence of Barrett's esophagus, and its precursor, gastroesophageal reflux. An association between this increasing incidence and an increasing use of pharmaceutical agents that relax the lower esophageal sphincter is proposed. The data on the dollar amount and approximate quantity in milligrams purchased per capita through retail pharmacies and hospitals in the United States from 1957 to 1986 are presented for four categories of such agents. An upward trend is observed for all four categories.

Adenocarcinoma↗

Season of birth and breast cancer risk in Sweden.

Recent research suggests that intrauterine exposures, perhaps factors that influence birth weight and other indicators of fetal growth, may affect future breast cancer risk. Because birth weight shows seasonal variation in Sweden, we assessed whether risk for breast cancer is associated with month of birth. The analyses included all 115,670 women, born between 1858 and 1968, who were reported to the Swedish Cancer Registry in 1958-89 as having breast cancer. Poisson regression models were used to examine the data. After adjustment for seasonality of number of live births in the population at risk, a significant seasonal pattern was identified for women born between 1880 and 1920. Women born in June had a 5% higher risk of breast cancer than those born in December. By contrast, there was no evidence of birth seasonality among 440,948 women with cancer at other sites. Exposures relevant to breast cancer risk later in life are unlikely to be related to month of birth. Thus, prenatal or early post-natal factors influence breast carcinogenesis, but the seasonal variation in these factors must have decreased over time.

Breast Neoplasms↗