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C C Hsia

Publications and source records attributed to C C Hsia.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1994

Cardiopulmonary adaptations to pneumonectomy in dogs. III. Ventilatory power requirements and muscle structure.

Static and dynamic mechanical characteristics of the respiratory system were measured in five adult foxhounds 6-15 mo after right pneumonectomy (R-PNX) and in five matched foxhounds that underwent right thoracotomy without pneumonectomy (Sham). In R-PNX dogs, elastic recoil was lower than that in the left lung of Sham dogs. On exercise, absolute ventilatory power requirements of the lung and its components were measured, i.e., power requirements to overcome elastic and viscous resistances of the lung as well as power requirements during inspiration and expiration. All components were higher for a given minute ventilation in R-PNX dogs than in both lungs of Sham dogs. Ventilatory power requirements after R-PNX were also higher than in three adult foxhounds after left PNX studied previously by the same techniques. After R-PNX, the mass of the right costal diaphragm and total mass of inspiratory muscles were greater than in Sham dogs. There were no significant differences in ultrastructural features of the costal diaphragm. The unilateral increase in muscle mass is likely the result of chronic elevation and stretch of the right costal diaphragm after R-PNX.

Air Pressure↗
PubMed1994

Cardiopulmonary adaptations to pneumonectomy in dogs. IV. Membrane diffusing capacity and capillary blood volume.

Lung diffusing capacity for carbon monoxide (DLco) and its components, membrane diffusing capacity (Dmco) and capillary blood volume (Vc), as well as pulmonary blood flow (Qc), were measured at rest at several lung volumes and during treadmill exercise by a rebreathing technique in four adult dogs after right pneumonectomy (R-PNX) and in six matched control dogs (Sham) 6-12 mo after surgery. In both groups, lung inflation at rest was associated with a small increase in DLco and Dmco but not in Vc. After R-PNX, total DLco was lower by 30% at peak exercise compared with control values. When compared with DLco in a normal left lung, DLco in the remaining lung continued to increase along the normal relationship with respect to Qc up to a cardiac output equivalent to 34 l/min through both lungs of the Sham dog. There was no evidence of an upper limit of DLco being reached. The augmentation of DLco from rest to exercise was associated with corresponding increases in Dmco and Vc; after R-PNX, both Dmco and Vc continued to increase with respect to Qc along similar relationships as in control dogs without reaching an upper limit, suggesting a much larger alveolar-capillary reserve for gas exchange by diffusion than previously recognized. At higher levels of blood flow through the remaining lung, DLco was greater in adult dogs after R-PNX than after left pneumonectomy (Carlin et al. J. Appl. Physiol. 70: 135-142, 1991), suggesting that additional sources of compensation, e.g., lung growth, exist after removal of > 50% of lung.

Animals↗
PubMed1994

Compensatory lung growth occurs in adult dogs after right pneumonectomy.

We investigated the structural changes in the left lung of five adult male foxhounds 5 mo (n = 2) or 16 mo (n = 3) after right pneumonectomy (approximately 54% of lung resected) and five sex- and age-matched foxhounds 15-16 mo after right thoracotomy without pneumonectomy. Lungs were fixed by intratracheal instillation of glutaraldehyde and analyzed by standard morphometric techniques. After right pneumonectomy, volume of the left lung increased by 72%. Volumes of all septal structures increased significantly and were more pronounced at 5 than at 16 mo after pneumonectomy. At 16 mo, the relative increases in volume with respect to the control left lung were as follows: epithelium 73%, interstitium 100%, endothelium 55%, and capillary blood volume 43%. Surface areas of alveoli and capillary increased significantly by 52% and 34%, respectively. At 5 mo after pneumonectomy, harmonic mean thickness of the tissue-plasma barrier was significantly greater but at 16 mo it was not different from controls. There was a significant increase in diffusing capacity for oxygen (33% above controls) at 16 mo after pneumonectomy. These data suggest that, in contrast to previous findings after left pneumonectomy, compensatory lung growth does occur in adult dogs after resection of > 50% of lung.

Animals↗
PubMed1993

Morphometric model for pulmonary diffusing capacity. I. Membrane diffusing capacity.

The pulmonary diffusing capacity is related to the quantitative design characteristics of the pulmonary gas exchanger. The current model for estimating DLO2 from morphometric data breaks the diffusion path for O2 into four steps, three of which represent the membrane part of DLO2. A critique of this model on the basis of newer evidence leads to a modification of the model where the path from the alveolar surface to the erythrocyte membrane is considered as a single step. The structural determinant of this model for DMO2 is the ratio of effective diffusion surface to effective total barrier thickness. The effective surface is formulated as a fraction of the alveolar surface area, the most robust measure of lung design, whereas the effective barrier thickness is the harmonic mean distance--or mean proximity--between alveolar surface and erythrocyte surface. The methods for obtaining the morphometric measurements are discussed. The results show that the new morphometric estimates of DMO2 are 33% lower than those obtained with the old model, resulting in a reduction of the estimates of DLO2 by 10-20%.

Animals↗
PubMed1993

Cardiopulmonary adaptations to pneumonectomy in dogs. II. VA/Q relationships and microvascular recruitment.

Ventilation-perfusion relationships, diffusing capacity for O2, and hemodynamic response were measured at rest and during exercise while five adult dogs breathed air and 15% O2 2 mo (Pnx-A, n = 2) or 12 mo (Pnx-B, n = 3) after right pneumonectomy (removal of 58% of lung tissue). Results were compared with those in five sham-operated controls. The multiple inert gas elimination technique was employed. Maximal O2 uptake was reduced by 50% in Pnx-A and by 15% in Pnx-B. Ventilation-perfusion matching was impaired in Pnx-A but not in Pnx-B. The increase in O2 diffusing capacity during exercise was significantly restricted in Pnx-A but was partially restored in Pnx-B. Mean pulmonary arterial pressure at a given blood flow through the remaining lung was normal in Pnx-A but lower than normal in Pnx-B compared with control values for a single lung. Stroke volume and cardiac output were lower in both Pnx-A and Pnx-B than in controls at a given exercise level. All functional abnormalities were more severe at 2 mo than at 12 mo postpneumonectomy. Gas phase diffusion resistance was present in both Pnx-A and Pnx-B but not in controls. We conclude that physiological compensation postpneumonectomy is progressive. Inability to recruit pulmonary vascular bed with incremental perfusion pressure or flow appears to be the major pathophysiological process that limits early functional capacity after right pneumonectomy.

Animals↗
PubMed1993

Respiratory muscle limitation in patients after pneumonectomy.

Exercise capacity is significantly impaired in postpneumonectomy patients who have relatively normal remaining lungs. Our objectives are to determine (1) the nature and extent of mechanical ventilatory abnormalities and oxygen cost of breathing in such patients, and (2) the efficacy of a selective respiratory muscle training program in improving ventilatory and exercise performance. A group of eight postpneumonectomy and eight normal subjects (mean ages 59 and 50 yr, respectively) were studied during steady-state exercise and resting voluntary hyperventilation. Ventilation, work of breathing, cardiac output, and oxygen costs of breathing were determined. Four postpneumonectomy and five normal subjects were studied before and after a respiratory muscle training program. In patients after pneumonectomy compared with normal control subjects, maximal oxygen uptake (VO2) was 56% lower (p < 0.001). Work of breathing was significantly higher at a given ventilation. Mechanical efficiency of ventilation was lower by 44% (p < 0.05). Near maximal VO2, 48% of any additional increment of total-body VO2 was required to sustain the associated increment in ventilatory work, compared with 28% in normal subjects (p < 0.05), suggesting that competition between respiratory and nonrespiratory muscles for oxygen delivery is a significant factor limiting exercise after pneumonectomy. After respiratory muscle training, maximal respiratory pressures improved but maximal sustained ventilation and maximal VO2 did not improve significantly, suggesting that selective respiratory muscle training is of limited utility in postpneumonectomy patients.

Analysis of Variance↗
PubMed1993

Structural changes underlying compensatory increase of diffusing capacity after left pneumonectomy in adult dogs.

To determine if the functional compensation in diffusing capacity of the remaining lung following pneumonectomy is due to structural growth, we performed morphometric analysis of the right lung in three adult foxhounds approximately 2 yr after left pneumonectomy (removal of 42% of lung) and compared the results to those in normal adult dogs previously studied by the same techniques. Diffusing capacity was calculated by an established morphometric model and compared to physiologic estimates at peak exercise in the same dogs after pneumonectomy. The major structural changes after left pneumonectomy are hyperinflation of the right lung, alveolar enlargement, and thinning of the alveolar-capillary tissue barrier. These changes confer significant functional compensation for gas exchange by reducing the overall resistance to O2 diffusion. The magnitude of compensation in diffusing capacity estimated either morphometrically or physiologically is similar. In spite of morphometric and physiologic evidence of functional compensation, there is no evidence of significant growth of structural components. After pneumonectomy, morphometric estimates of diffusing capacity are on average 23% higher than physiologic estimates in the same dogs at peak exercise. We conclude that the previously reported large differences between morphometric and physiologic estimates of diffusing capacity reflects the presence of large physiologic reserves available for recruitment.

Animals↗
PubMed1992

Mutations of p53 gene in hepatocellular carcinoma: roles of hepatitis B virus and aflatoxin contamination in the diet.

BACKGROUND: Mutations of the p53 tumor suppressor gene have been reported in 50% of patients with hepatocellular carcinoma (HCC) from China and South Africa. These reports suggested an association of p53 mutations with high levels of aflatoxin in the diet. Most studies of p53 and HCC, however, have not fully evaluated the possible role of the hepatitis B virus (HBV). Aflatoxin is a substance produced by food mold that is known to cause HCC in experimental animals. PURPOSE: The purpose of this study was to evaluate the relationship of p53 gene mutation to high or low levels of aflatoxin in the diet and to HBV infection. METHODS: p53 protein and hepatitis B surface antigen (HBsAg) were evaluated by immunohistochemistry using the avidin-biotin-peroxidase system in paraffin-embedded specimens of HCC and of adjacent nontumorous liver tissue from 43 patients. Tissue specimens from three normal human livers were also evaluated. HCCs and adjacent nontumorous liver tissues were obtained from 23 patients from Qidong, China, where aflatoxin levels in the diet are high, and from 20 patients from two regions in the United States (patients from the National Institutes of Health, Bethesda, Md., and Kuakini Medical Center, Honolulu, Hawaii), where aflatoxin levels in the diet are low. RESULTS: Mutant p53 protein was detected in the nuclei of HCCs from 14 (61%) of 23 patients from China and from three (30%) of 10 patients and six (60%) of 10 patients, respectively, from the two regions of the United States. A statistically significant association between detection of mutant p53 protein in HCC cells and the detection of HBsAg in hepatocytes of the adjacent nontumorous liver tissue was observed in patients from China and the United States considered together. CONCLUSION: Mutations of the tumor suppressor gene p53 in hepatocellular carcinomas are not limited to patients from geographic regions where the ingestion of aflatoxin is high. In many patients, these mutations may be associated with HBV infection. IMPLICATIONS: The possible interaction of chronic HBV infection and p53 gene mutation, suggested by these data, indicates a mechanism by which HBV infection beginning early in life could contribute to the subsequent development of HCC.

Adult↗
PubMed1992

Transforming growth factor-alpha in human hepatocellular carcinoma and coexpression with hepatitis B surface antigen in adjacent liver.

BACKGROUND: Hepatitis B virus (HBV) infection is closely associated with the development of hepatocellular carcinoma (HCC) in many patients, but the mechanisms by which HBV contributes to HCC are not known. Transforming growth factor-alpha (TGF-alpha), a regulator of growth and regeneration in rat liver that can be found in high levels in some human cancers, theoretically could play such an intermediate role in the development of HCC. METHODS: The expression of TGF-alpha and its relation to the HBV antigens were evaluated in human HCC and adjacent nontumorous livers from 33 patients from the United States and China using immunoperoxidase staining of paraffin-embedded sections. RESULTS: TGF-alpha was detected in HCC from 27 of 33 (82%) patients; the frequencies were similar in patients from the United States and China. TGF-alpha was detected in HCC more frequently in patients whose adjacent nontumorous livers had detectable hepatitis B surface antigen (HBsAg) and/or hepatitis B core antigen (HBcAg) than in those whose adjacent livers lacked HBsAg and HBcAg. Detection of TGF-alpha was not affected by tumor size, histologic type, or grade. TGF-alpha was detected in adjacent nontumorous livers from 31 of 33 patients (94%). Coexpression at a high intensity of TGF-alpha and HBsAg in the same hepatocytes could be demonstrated by specific staining of consecutively cut sections for 17 of 33 patients (52%). CONCLUSIONS: TGF-alpha is expressed at a high level in 82% of human HCC. Localization of HBsAg within the same hepatocytes as TGF-alpha suggests a possible interaction between HBV and TGF-alpha during hepatocarcinogenesis in humans. Stimulation of TGF-alpha expression could be part of a chain of events by which HBV contributes to the development of HCC in some patients.

Adult↗
PubMed1992

Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis.

Proliferation of a new population of epithelial cells with distinct structure, as well as cytokeratin and alpha-fetoprotein expression, was observed in nonneoplastic liver tissues from 14 cases (13 hepatitis B virus-positive) of human hepatocellular carcinoma. These cells were characterized by oval nuclei; scant, pale cytoplasm; small cell size; and cross-reaction with a monoclonal antibody against rat oval cells. These putative human oval cells were strongly positive for cytokeratin 19 and displayed considerable heterogeneity in alpha-fetoprotein and albumin expression. The oval cells were most prominent in actively regenerating nodules and in liver tissue surrounding the cancer. Oval cells and transitional types of cells appear to be the principal producers of alpha-fetoprotein in the regenerating liver. Cancer cells positive for cytokeratins 8, 18 and 19 were observed in half the hepatocellular carcinomas studied. The data suggest that a new cell population structurally similar to oval cells seen in early stages of chemical hepatocarcinogenesis in rats is consistently present in regenerating liver lesions associated with human hepatocellular carcinoma. Furthermore, it is possible that the proliferation of these oval-type cells may partly account for the elevation of serum alpha-fetoprotein frequently seen in precancerous stages of hepatitis B virus-associated human hepatocellular carcinoma.

Adult↗
PubMed1992

Increased expression of transforming growth factor alpha after transfection of a human hepatoblastoma cell line with the hepatitis B virus.

The expression of transforming growth factor alpha (TGF-alpha) was examined in a human hepatoblastoma cell line, Hep G2, which does not contain hepatitis B virus (HBV) DNA, and in the cell line 2.2.15, which was formed by the transfection of Hep G2 cells with the complete HBV DNA, to study the possibility that HBV and TGF-alpha could function as co-factors in hepatocarcinogenesis. Northern blot hybridization of RNA extracted from these cell lines, with densitometric analysis, revealed expression of the TGF-alpha gene in the transfected cells at a level three times higher than in the nontransfected cells. Staining of the cells using a monoclonal antibody to TGF-alpha and the avidin-biotin-peroxidase immunohistochemical method revealed a much higher intensity of TGF-alpha staining in the transfected cell line. These findings show that the presence of HBV DNA appears to cause a significant up-regulation of the TGF-alpha gene. This effect on the TGF-alpha gene may be a mechanism by which HBV contributes to the etiology of hepatocellular carcinoma in some patients.

Carcinoma, Hepatocellular↗
PubMed1992

Respiratory muscle blood flow in exercising dogs after pneumonectomy.

In three foxhounds after left pneumonectomy, the relationships of ventilatory work and respiratory muscle (RM) blood flow to ventilation (VE) during steady-state exercise were examined. VE was measured using a specially constructed respiratory mask and a pneumotach; work of breathing was measured by the esophageal balloon technique. Blood flow to RM was measured by the radionuclide-labeled microsphere technique. Lung compliance after pneumonectomy was 55% of that before pneumonectomy; compliance of the thorax was unchanged. O2 uptake (VO2) of RM comprised only 5% of total body VO2 at exercise. At rest, inspiratory muscles received 62% and expiratory muscles 38% of the total O2 delivered to the RM (QO2RM). During exercise, inspiratory muscles received 59% and expiratory muscles 41% of total QO2RM. Blood flow per gram of muscle to the costal diaphragm was significantly higher than that to the crural diaphragm. The diaphragm, parasternals, and posterior cricoarytenoids were the most important inspiratory muscles, and internal intercostals and external obliques were the most important expiratory muscles for exercise. Up to a VE of 120 l/min through one lung, QO2RM constituted only a small fraction of total body VO2 during exercise and maximal vasodilation in the diaphragm was never approached.

Animals↗
PubMed1992

Cardiopulmonary adaptations to pneumonectomy in dogs. I. Maximal exercise performance.

Maximal exercise performance was evaluated in four adult foxhounds after right pneumonectomy (removal of 58% of lung) and compared with that in seven sham-operated control dogs 6 mo after surgery. Maximal O2 uptake (ml O2.min-1.kg-1) was 142.9 +/- 1.9 in the sham group and 123.0 +/- 3.8 in the pneumonectomy group, a reduction of 14% (P less than 0.001). Maximal stroke volume (ml/kg) was 2.59 +/- 0.10 in the sham group and 1.99 +/- 0.05 in the pneumonectomy group, a reduction of 23% (P less than 0.005). Lung diffusing capacity (DL(CO)) (ml.min-1.Torr-1.kg-1) reached 2.27 +/- 0.08 in the combined lungs of the sham group and 1.67 +/- 0.07 in the remaining lung of the pneumonectomy group (P less than 0.001). In the pneumonectomy group, DL(CO) of the left lung was 76% greater than that in the left lung of controls. Blood lactate concentration and hematocrit were significantly higher at exercise in the pneumonectomy group. We conclude that, in dogs after resection of 58% of lung, O2 uptake, cardiac output, stroke volume, and DL(CO) at maximal exercise were restricted. However, the magnitude of overall impairment was surprisingly small, indicating a remarkable ability to compensate for the loss of one lung. This compensation was achieved through the recruitment of reserves in DL(CO) in the remaining lung, the development of exercise-induced polycythemia, and the maintenance of a relatively large stroke volume in the face of an increased pulmonary vascular resistance.

Animals↗