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C C Hsia

Publications and source records attributed to C C Hsia.

At least 19 recordsLinked to original sources
PubMed1997

Binding of wild-type p53 by topoisomerase II and overexpression of topoisomerase II in human hepatocellular carcinoma.

In order to study the mechanisms by which p53 function is regulated, human wild-type p53 cDNA was cloned into a vaccinia virus vector and the expressed p53 protein was used to investigate binding of the p53 by cellular proteins from a cDNA expression library from human liver. One protein that bound wild-type p53 had > 99% homology with DNA topoisomerase IIb. p53 protein was coimmunoprecipitated from topoisomerase II-rich cell lysates (but not from topoisomerase II-deficient cell lysates) by an antibody to topoisomerase IIa and IIb. This binding was shown to occur without a dsDNA intermediary. Hepatocellular carcinomas (HCCs) and adjacent nontumorous liver tissues from ten patients were studied to determine the level of expression of topoisomerase II and p53. Overexpressed topoisomerase II proteins were detected by western blot in six of ten HCCs (60%), including several in which presumed wild-type p53 was detected by immunohistochemistry. No topoisomerase II expression was detectable in the ten nontumorous liver tissues from the same patients or in a sample of normal human liver.

Antibodies, Monoclonal↗
PubMed1997

In vivo assessment of changes in air and tissue volumes after pneumonectomy.

We examined the progression and topographical distribution of postpneumonectomy volume changes in immature foxhounds undergoing right pneumonectomy (R-Pnx, n = 5) or sham pneumonectomy (Sham, n = 6) at 2 mo of age and subsequently raised to maturity. Volumes of lung air (Vair) and tissue (Vti) were estimated by computerized tomography (CT) scan at 7, 22, and 52 wk after surgery at a transpulmonary pressure of 20 cmH2O. Estimates of Vti by CT scan included both septal tissue as well as nonseptal tissue (small- and medium-sized airways and blood vessels); these were compared with estimates of septal Vti by an acetylene rebreathing (Rb) method. We found significant correlations between these techniques (Vair(CT) = 0.83 Vair(Rb) + 275, R = 0.97; Vti(CT) = 1.62 Vti(Rb) - 30, R = 0.81). Extravascular septal Vti returned to normal 7 wk after R-Pnx and remained normal up to maturity. Nonseptal Vti remained significantly below normal. The greatest increase in Vti occurred in the midlung region just cephalad and caudal to the heart. After an early period of accelerated tissue growth after R-Pnx, the rate of septal tissue growth matched that of somatic growth, whereas nonseptal tissue growth lagged behind. Compensatory growth of the remaining left lung was not associated with selective alterations in thoracic development.

Acetylene↗
PubMed1996

Role of hematocrit in the recruitment of pulmonary diffusing capacity: comparison of human and dog.

In dogs, maximal O2 uptake (VO2max) per kilogram of body weight is two- to threefold that in humans; the difference cannot be explained solely by differences in structural features between species. We compared the functional recruitment of pulmonary diffusing capacity (DLCO) during exercise in dogs with that in humans to determine whether pulmonary gas exchange is matched to VO2max or the size of the lungs and to define the potential role of exercise-induced polycythemia in producing the superior aerobic capacity of the dogs. We compared the relationships of DLCO, membrane diffusing capacity (DMCO), and pulmonary capillary blood volume (Vc) with respect to pulmonary blood flow (Qc) by a rebreathing method during steady-state exercise in adult male human subjects and in conditioned adult male foxhounds. The slopes and intercepts of the relationships of DLCO and DMCO to Qc are significantly greater in dogs than in humans; the slopes of the relationship of Vc to Qc are similar. In dogs diffusive pulmonary gas transport is matched to the higher VO2max. The enhanced recruitment of DLCO and DMCO in dogs during exercise could potentially be explained entirely by the exercise-induced polycythemia, which is seen in dogs but not in humans.

Adult↗
PubMed1996

A modified rebreathing technique using an infrared gas analyzer.

To lower the cost and improve accessibility of the rebreathing technique for measuring cardiopulmonary function during exercise, we implemented a fast-response infrared (IR) gas-analyzer system to simultaneously measure lung diffusing capacity, cardiac output lung tissue volume, and lung volume by a rebreathing technique in five healthy subjects at rest and during steady-state exercise. Interferences by water vapor and CO2 on the analyzer were determined and corrected for. During rebreathing, a gas mixture of 0.4% C2H2-0.3% CH4-9% He-30% O2, and either 0.3% C18O or 0.3% C16O in a balance of N2 was simultaneously sampled by both a mass spectrometer and the IR analyzer, permitting paired comparisons. Measurements obtained by the two devices were not significantly different. We conclude that this modified rebreathing technique using the IR analyzer is accurate for the measurement of cardiopulmonary function at rest and during exercise.

Adult↗
PubMed1996

Temporal course of gas exchange and mechanical compensation after right pneumonectomy in immature dogs.

To determine the temporal progression and magnitude of functional compensation in immature dogs raised to maturity after extensive lung resection, we performed right pneumonectomy (R-Pnx) or right thoracotomy without pneumonectomy (Sham) in matched foxhounds at 2 mo of age. At 4, 8, 20, 40, and 60 wk after surgery, static transpulmonary pressure-lung volume relationships were determined. Lung diffusing capacity, membrane diffusing capacity, pulmonary capillary blood volume, pulmonary blood flow, septal lung tissue volume, and lung volumes were measured simultaneously by a rebreathing technique. During maturation, total lung capacity, lung volume at a given distending pressure, and compliance were lower in the R-Pnx group than in the Sham group (P < 0.05). Pulmonary viscous resistance at maturity was elevated after R-Pnx. There were no significant differences in total lung diffusing capacity, membrane diffusing capacity, pulmonary capillary blood volume, pulmonary blood flow, and septal lung tissue volume between groups. Compensation of alveolar-capillary gas exchange was complete by 4-8 wk after R-Pnx, but compensation of mechanical properties remained incomplete throughout maturation. Relative magnitude of compensation after R-Pnx was greater in immature dogs than in adult dogs studied previously by similar techniques.

Airway Resistance↗
PubMed1995

Nodules of less-differentiated tumor within or adjacent to hepatocellular carcinoma: relative expression of transforming growth factor-alpha and its receptor in the different areas of tumor.

Expression of transforming growth factor-alpha (TGF-alpha) and its receptor, the epidermal growth factor receptor (EGFR), in hepatocellular carcinomas (HCCs) and adjacent nontumorous livers from 25 Japanese patients were examined using immunoperoxidase staining of paraffin-embedded sections. TGF-alpha was detected in 24 of 25 (96%) HCCs and 23 of 24 (96%) available adjacent nontumorous livers. EGFR was detected in 16 of 25 (64%) HCCs and 17 of 24 (71%) adjacent nontumorous livers. TGF-alpha and EGFR were not detected by immunohistochemical staining in normal livers. Fifteen of 25 HCCs contained an apparent area of a second tumor (two of the 15 also contained a third tumor) that had a less-differentiated histological grade developing within or adjacent to the first tumor. In those cases, staining in the less-differentiated area of tumor was usually less intense than in the more highly differentiated area (80% of cases for TGF-alpha; 91% for EGFR). These data confirm that increased expression of TGF-alpha and EGFR occur frequently in human HCC. Furthermore, the detection of greater staining in more highly differentiated portions of the tumors suggests that increased expression of TGF-alpha and EGFR may be events of the early stages of human hepatocarcinogenesis.

Adult↗
PubMed1995

Expression of transforming growth factor alpha in the liver before and after interferon alfa therapy for chronic hepatitis B.

The effect of interferon alfa (IFN-alpha) therapy on the expression of transforming growth factor alpha (TGF-alpha) in the liver during chronic hepatitis B was investigated. Serial liver biopsy specimens were evaluated from 35 patients who had participated in a randomized, controlled trial of recombinant human IFN-alpha for the treatment of chronic hepatitis B. Percutaneous liver biopsy specimens obtained before and 1 year after entry in the trial were sectioned and stained with a monoclonal antibody to TGF-alpha in an avidin-biotin-peroxidase-complex system. The expression of TGF-alpha in each section was evaluated blindly (with respect to treatment group and order of biopsies) and was numerically scored. There was no significant difference in TGF-alpha expression before or after therapy between 13 patients receiving daily IFN-alpha, 13 receiving alternate-day IFN-alpha, and 9 receiving no therapy. Sustained clearance of HBV-DNA and DNA polymerase activity occurred in 8 of 26 treated patients ("responders"); the 18 other patients were "nonresponders." Expression of TGF-alpha before IFN-alpha therapy was significantly higher in responders than in nonresponders; after IFN-alpha therapy, TGF-alpha expression decreased significantly among responders compared with nonresponders and untreated controls. Thus, the level of expression of TGF-alpha in the liver, which was correlated with the severity of inflammation in the liver in this study, appeared to be predictive of the response to IFN-alpha therapy in chronic hepatitis B, with a higher level of expression indicating a greater likelihood that the patient would respond.

Adult↗
PubMed1995

p53 in malignant and benign liver lesions.

p53 expression was studied by immunohistochemical methods in benign and malignant human epithelial liver lesions in 46 patients from Hungary. Positive immunostaining for p53 protein, indicating the overexpression or prolonged half-life of p53 protein, was detected in the nuclei of tumour cells of seven of the 16 hepatocellular carcinomas (HCC) (44%), including three HCC patients with hepatitis B virus infection. Immunostaining of p53 was seen in one of the seven hepatoblastomas, none of the 17 focal nodular hyperplasias, and none of the six hepatocellular adenomas. The detection of p53 in a relatively high percentage of the HCC cases in Hungary, a country in which aflatoxin contamination of the diet is rare, suggests that factors other than aflatoxin led to the accumulation or overexpression of p53 in these patients.

Adenoma, Liver Cell↗
PubMed1995

Cardiac output during exercise measured by acetylene rebreathing, thermodilution, and Fick techniques.

In dogs during exercise, respiratory rate can reach 200 breaths/min, blood temperature can exceed 42 degrees C, and hematocrit can approach 60%. To determine whether these changes significantly affect the measurement of cardiac output by the acetylene rebreathing method (QcRB), we compared estimates of QcRB with those measured by thermodilution and Fick (QcFI) techniques in nine dogs at rest and during steady-state exercise on a treadmill up to near-maximal workloads. Solubility of acetylene in blood was corrected to the simultaneously measured blood temperature and hematocrit. Results were also adjusted for mixing efficiency. Up to a QcFI of 20 l/min, QcRB was not significantly different from QcFI (P > 0.05). However, cardiac output measured by thermodilution was consistently higher than those measured by the other techniques (P < 0.0001). We conclude that the overall agreement between QcRB and QcFI estimates supports the validity of the rebreathing technique under exercise conditions where body temperature and hematocrit are changing rapidly and the breathing pattern is unrestrained. Systematic error by the thermodilution technique may be related to a variety of methodological issues as well as possible dissipation of cooling into the myocardial tissue and subsequent incomplete washout.

Acetylene↗
PubMed1995

Critique of conceptual basis of diffusing capacity estimates: a finite element analysis.

We present a simple geometric model of a pulmonary capillary segment containing a variable number of red blood cells. The pattern of CO transfer from alveolar air to capillary red blood cells in this model is accurately computed by a finite element method and used to explore conceptual flaws in the Roughton-Forster (RF) and morphometric methods of estimating pulmonary diffusing capacity for CO. The CO uptakes calculated by the finite element method at two alveolar O2 tensions are introduced into the RF model to determine whether the anatomically defined membrane component of diffusing capacity for CO (DmCO) and pulmonary capillary blood volume (Vc) are recovered. The same capillary model is also subjected to standard morphometric analysis. Results are compared at different levels of capillary hematocrit (Hct). The RF method accurately recovers DmCO and Vc at a low Hct but modestly overestimates DmCO and underestimates Vc at higher Hct; errors arise because conductance of the tissue-plasma membrane for CO varies with alveolar O2 tension. The morphometric method seriously overestimates DmCO because the true tissue-plasma resistance to diffusion is underestimated and the effective membrane utilized for diffusion is overestimated; these errors are accentuated by a low Hct.

Animals↗
PubMed1995

Reference values of pulmonary diffusing capacity during exercise by a rebreathing technique.

Normal reference values of the pulmonary diffusing capacity for carbon monoxide (DLCO), diffusing capacity of the membrane (DMCO), and pulmonary capillary blood volume (VC) were derived by a rebreathing technique in 44 normal, healthy, nonsmoking individuals ranging from 17 to 68 yr of age. Simultaneous measurements of DLCO, lung volumes, pulmonary blood flow, and septal tissue volume were determined at rest and during steady-state exercise of 25, 50, and 80% of maximal workload and at two levels of alveolar O2 tension. DMCO and VC were calculated using the Roughton-Forster relationship. Using stepwise regression analysis, DLCO and DMCO (in ml CO/min/mm Hg) were found to be significantly related to pulmonary blood flow (Qc in L/min), age (in years), and body surface area (BSA in square meters). VC (in ml) was found to be significantly related to QC and BSA. Normalization of measured data with respect to these variables largely eliminated male versus female differences. We conclude that QC is the most important determinant of the recruitment of diffusing capacity. From rest to near-maximal exercise, DLCO, DMCO, and VC increase linearly with respect to QC without evidence of reaching a plateau.

Adolescent↗
PubMed1994

Expression of hepatitis B surface and core antigens and transforming growth factor-alpha in "oval cells" of the liver in patients with hepatocellular carcinoma.

Recent studies have identified epithelial cell populations in human livers that are similar to the "oval cells" and "transitional cells" seen in rat livers during the early stages of chemical carcinogenesis. It has been suggested that these cells might be precursors of hepatocytes and theoretically could be involved in hepatocarcinogenesis. The hepatitis B virus (HBV) also is believed to play a role in the etiology of hepatocellular carcinoma (HCC). Therefore, a study was conducted in nontumorous livers adjacent to HCCs obtained from 26 patients from China to determine whether HBV antigens could be identified in oval cells and transitional cells using an immunohistochemical technique. Hepatitis B surface antigen (HBsAg) was detected in the nontumorous livers of 22/26 (85%) patients. HBsAg was detected in oval cells in 18/26 (69%), in transitional cells in 21/26 (81%), and in mature hepatocytes in 22/26 (85%), but not in bile duct or ductule cells. Transforming growth factor-alpha (TGF-alpha) was expressed in oval cells, transitional cells, and bile duct cells in 24/26 (92%) patients, an in mature hepatocytes in 25/26 (96%). Coexpression of HBsAg and TGF-alpha was identified in the same cells in populations of oval cells and transitional cells of selected patients. Because of the possibility that oval cells could be a source of evolving HCC, these findings suggest that expression of TGF-alpha associated with HBV infection of oval cells could be a mechanism of human hepatocarcinogenesis. Thus, oval cells could be a site (or one of the sites) where HBV participates in the development of HCC.

Adult↗
PubMed1994

RB tumor suppressor gene expression in hepatocellular carcinomas from patients infected with the hepatitis B virus.

Hepatitis B virus (HBV) infection is closely associated with the development of hepatocellular carcinoma (HCC), but definite mechanisms by which it could play an etiologic role have not yet been identified. Modifications of the function of the RB tumor suppressor gene, which regulates the cell cycle, could provide such a mechanism. In the present study, the expression of the protein product of RB, pRB, was evaluated by immunohistochemical staining in HCC tissues from 25 patients from China and the United States, adjacent nontumorous liver from 19 of those patients, five human HCC cell lines, three human hepatoblastoma cell lines, and five specimens of normal human liver. Representative samples were also evaluated by western blot. Altered expression of RB was detected in eight HCC tissues (pRB undetectable in five HCCs and detected in < 1% of nuclei of HCC cells in three others); all eight had detectable hepatitis B surface or core antigen in the adjacent nontumorous liver, indicating active HBV infection. pRB was detected in 10-95% of nuclei (normal expression) in the remaining 17 HCCs, and in many nuclei in all 19 nontumorous livers, and in the 5 normal livers. No pRB staining was detected in the nuclei of three HCC cell lines, but pRB was detected in > 90% of nuclei of the other HCC and hepatoblastoma cell lines. The relationship of pRB expression to mutations of the p53 tumor suppressor gene was also examined. The absence of detectable nuclear pRB by immunohistochemical staining was associated with the presence of presumed mutant p53 detected by immunohistochemical staining in four out of five HCC cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Overexpression of transforming growth factor-alpha in hepatocellular carcinoma and focal nodular hyperplasia from European patients.

The expression of transforming growth factor-alpha (TGF-alpha) was studied in 33 surgically excised human hepatocellular carcinomas (HCCs), focal nodular hyperplasias (FNHs), and the surrounding liver tissue from patients who were life-long residents of Hungary. Monoclonal antibodies were used to localize TGF-alpha and hepatitis B surface antigen (HBsAg) using an avidin-biotin-peroxidase immunohistochemical method on paraffin-embedded sections. Transforming growth factor-alpha was detected in the tumor tissue in 13 of 16 patients with HCC (81%) and in 12 of 17 patients with FNH (71%). Three patients with HCC were actively infected with hepatitis B virus, indicated by the detection of HBsAg in the serum and in adjacent nontumorous liver. Transforming growth factor-alpha was detected in the same nontumorous hepatocytes as HBsAg, often in areas of the hepatocyte cytoplasm, with a "ground glass" appearance. Bile duct cells were stained for TGF-alpha in the surrounding nontumorous liver tissue and a more intensive immunostaining was observed in the proliferating bile ducts in the FNH cases, which suggests that TGF-alpha may participate in the growth regulation of bile ducts.

Adolescent↗
PubMed1994

Southwestern Internal Medicine Conference: pulmonary complications of high-altitude exposure.

The primary physiologic disturbance at high altitude is hypoxemia, which leads to a cascade of secondary changes in each step of the oxygen-transport chain. The author, in this review, focuses on the alterations in ventilatory control and alveolar-capillary gas exchange at high altitude and discusses the clinical pulmonary complications associated with these alterations, as well as their prevention and management.

Acclimatization↗
PubMed1994

Alterations of the RB tumour suppressor gene in hepatocellular carcinoma and hepatoblastoma cell lines in association with abnormal p53 expression.

Alterations in the expression of the RB tumour suppressor gene were found by Western immunoblot in three of seven hepatocellular carcinoma and hepatoblastoma cell lines. Abnormalities were detected by single-strand conformation polymorphism (SSCP) within exons 17-21 in RB cDNA from two of these three cell lines and within exons 20-21 in the third cell line. In these three cell lines with abnormal RB expression, abnormal expression of the p53 tumour suppressor gene was also found, apparently the product of a mutant gene. Thus, mutations within the RB gene (or splice-site mutations with exon-skipping) and apparent mutations of the p53 gene together may have contributed to the development of three of these tumours or to the establishment of these cell lines.

Base Sequence↗
PubMed1994

Histochemical and immunohistochemical similarities between hepatic tumors in two chimpanzees and man.

A well-differentiated trabecular hepatocellular carcinoma (HCC) and a well-differentiated tumor resembling HCC from each of two chimpanzees were found to have histochemical and immunohistochemical staining characteristics similar to those in human HCCs. Transforming growth factor alpha was overexpressed in both tumors. Oval cells, thought to be liver stem cell progeny with a possible role in hepatocarcinogenesis, were observed among nontumorous hepatocytes, particularly near the tumors. Hepatic tumors are rare in chimpanzees but their similarities to human HCC provides a useful research model.

Animals↗