Biomedical subjects

C C Hsia

Publications and source records attributed to C C Hsia.

At least 73 records · Page 4Linked to original sources

PubMed1992

Recruitment of diffusing capacity with exercise in patients after pneumonectomy.

Patients after pneumonectomy are severely limited upon exercise, but impairments in gas exchange are generally mild. One potential explanation of this observation is the existence of functional reserves of diffusing capacity (DLCO), which may be recruited during exercise, predominantly by increasing pulmonary blood flow (Qc). After pneumonectomy, DLCO reserves are recruited even at rest. To investigate if the pattern of recruitment of DLCO is altered and if reserves of DLCO are exhausted during exercise after pneumonectomy, DLCO, lung volume, and cardiac output were measured by the rebreathing method at rest and at multiple levels of steady-state exercise in eight subjects after pneumonectomy and in eight age- and sex-matched nonsmoking normal subjects. In patients after pneumonectomy, the slopes of increase in DLCO [ml.(min.mm Hg)-1.m-2] with respect to QC [ml.min-1.m-2] were normal (0.91 +/- 0.09 x 10(-3) in the pneumonectomy group, 1.16 +/- 0.12 x 10(-3) in the control group, mean +/- SE, p less than 0.05). Thus, the pattern of DLCO recruitment was not significantly affected by pneumonectomy. The ratio of DLCO/Qc fell more rapidly during exercise in patients after pneumonectomy, but the lowest value of the ratio achieved was relatively normal in all except one patient. Declines in arterial O2 saturation at exercise were mild and insufficient to explain the exercise limitation except in the patient whose DLCO/Qc fell below normal. There was no evidence that an upper limit of recruitment was approached. We conclude that the normal ability to recruit DLCO during exercise after pneumonectomy constitutes an important compensatory feature that prevents significant arterial O2 desaturation. In most patients, exercise is limited by a reduced maximal stroke index before reserves of diffusing capacity are exhausted.

Adult↗

PubMed1991

Estimation of diffusion limitation after pneumonectomy from carbon monoxide diffusing capacity.

In three foxhounds, diffusing capacity for carbon monoxide (DLCO) was reduced by 25-30% after left pneumonectomy. Based on previous morphometric data in animals and physiologic data in humans, this reduction should not result in any impairment in gas exchange. However, experimental evidence indicates that diffusion limitation develops during exercise after pneumonectomy. Our objective is to determine whether this diffusion limitation to gas exchange can be predicted from physiologic measurements of DLCO. DLCO measured by the rebreathing technique was translated into diffusing capacity for O2 (DLO2) using an average conversion factor for canids obtained morphometrically (Weibel et al., Respir. Physiol. 54: 173-188, 1983). Arterial O2 saturation (SaO2) at various intensities of steady state exercise was calculated from DLO2 and measured values of O2 consumption, alveolar PO2, hemoglobin and arterial pH, and compared to observed SaO2. After pneumonectomy, SaO2 declined progressively with increasing exercise load. In all dogs, the observed pattern of arterial O2 saturation could be predicted from DLCO measured at similar work loads. The relationship between predicted (Pr) and observed (Ob) SaO2 is: SaO2(Pr) = 22.73 + 0.77SaO2(Ob), r = 0.92. The slope is significantly less than 1.0 (P less than 0.005), indicating that other factors must also contribute to arterial desaturation. We conclude that physiologic measurement of DLCO is a meaningful indicator of diffusion limitation to gas exchange. In the foxhound, a modest reduction in DLCO significantly impairs O2 transport during exercise; but other gas exchange abnormalities, e.g. ventilation perfusion inhomogeneity, must also develop.

Animals↗

PubMed1991

Recruitment of lung diffusing capacity with exercise before and after pneumonectomy in dogs.

Although the left lung constitutes 42% of the total by weight and volume in dogs, carbon monoxide diffusing capacity (DL) after left pneumonectomy in adults falls less than 30% at rest, indicating a significant increase of DL in the remaining lung. DL normally increases during exercise, presumably by recruitment of alveolar capillaries and surface area as lung volume (Vs) and pulmonary blood flow (Qc) increase. We asked whether the increase of DL in the remaining lung after pneumonectomy in adult dogs could be explained by this kind of passive recruitment by the increased volume and Qc in the remaining lung. We measured the relationship between DL and Qc with a rebreathing technique at increasing treadmill loads in adult foxhounds, before and 6 mo after left pneumonectomy, and the relationship between DL and Vs by the same technique under anesthesia as Vs was expanded. DL was reduced by 29.1% at rest and 26.5% with heavy exercise after left pneumonectomy, indicating either recruitment or new growth in the right lung. With the assumption that the right lung normally receives 58% of the Qc and contains 58% of the DL, DL of the right lung increased with Qc in accordance with the following relationships before and after left pneumonectomy: right lung DL (before pneumonectomy) = 6.44 + 2.40(Qc) (r = 0.963) and right lung DL (after pneumonectomy) = 7.51 + 1.75(Qc) (r = 0.958). Only approximately 7% of the increase in DL from rest to peak exercise could be attributed to the increase in Vs during exercise before pneumonectomy and approximately 15% after pneumonectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Design and compliance of HBV vaccination trial on newborns to prevent hepatocellular carcinoma and 5-year results of its pilot study.

A large-scale, controlled study of universal immunization of newborns against HBV infection has been conducted in the high incidence area of hepatocellular carcinoma, Qidong County of China. This area has a stable population, standardized cancer registration system, and an epidemiological base for measurements of liver cancer prevention by vaccine. Randomization was done on the community level. The vaccination and the control group each will consist of 38,000 children by the end of 1990. It is anticipated that the design will provide high statistical power to detect 50% reduction in the prevalence rate of chronic hepatitis among the vaccinees vs. the controls at 6 to 10 years of age, and 50% reduction in the incidence rate of hepatocellular carcinoma at 35 to 40 years of age. The vaccine used is Hep-B Vax, donated by Merck and Co. through WHO. The vaccine was administered at 0, 1, and 6 months after birth, the dosage of 5 or 2.5 micrograms in the pilot study as used before 1985 and of 5 micrograms dose level during the main study starting from January 1, 1985. About 85% of the cohorts have now entered the protocol. The vaccination coverage during 1984 to 1989 was 98.0% (35,064/35,789). Follow-up of the vaccinees and the age-matched controls at 5 years has exceeded 97%. The cumulative mortality in the vaccinated group up to 1988 was 1.29% (354/27,450). No single death nor serious adverse reaction was found that was associated with vaccination. The use of HBV vaccine at a reduced dose was especially important for the developing countries at the present time in order to achieve widespread immunization. Five-year results of the pilot study of this vaccination project showed that significant protection against HBV infection was achieved with the 5 or 2.5 micrograms per dose regimen plus a booster of 5 micrograms given at 3.5 to 4 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular↗

PubMed1991

Expression of transforming growth factor-beta 1 during chemical hepatocarcinogenesis in the rat.

Cellular distribution of both transcripts and protein of transforming growth factor (TGF)-beta 1 was studied in preneoplastic nodules (6 cases) and primary hepatic carcinomas (16 hepatocellular carcinomas and 2 mixed tumors of hepatocellular carcinoma and cholangiocellular carcinoma) produced by Solt-Farber's protocol in rats using in situ hybridization and immunohistochemistry. The TGF-beta 1 transcripts were primarily observed in nonparenchymal cells, some of which were desmin-positive perisinusoidal cells, surrounding or within the preneoplastic nodules or carcinomas. The distribution of latent TGF-beta 1 protein was similar to the transcripts. However, mature TGF-beta 1, which was identified with CC-antibody, was only detected in nonparenchymal cells and connective tissue associated with carcinomas, but was not observed in preneoplastic nodules or in normal liver with the exception of the periportal space. There was no difference in TGF-beta 1 expression associated with tumor types or the differentiation status of primary hepatic carcinomas. The present study demonstrates that nonparenchymal cells, particularly desmin-positive perisinusoidal cells, are the principal source of TGF-beta 1 production during hepatocarcinogenesis. Furthermore, the data suggest that the close interaction between nonparenchymal cells and carcinoma cells may be necessary for the activation of latent TGF-beta 1. It is hypothesized that regulatory effects of TGF-beta 1 on growth of preneoplastic or carcinoma cells in the liver are exerted via paracrine mechanism.

Animals↗

PubMed1990

Cellular and molecular changes in the early stages of chemical hepatocarcinogenesis in the rat.

The early cellular and molecular changes in the Solt-Farber model of hepatocarcinogenesis with and without initiation was studied by using histochemical, immunohistochemical, and in situ hybridization techniques. Increased cellularity was observed in the periductal space in both models 32 to 56 h after partial hepatectomy. These periductal cells and Ito cells were the only cells that became labeled with tritiated thymidine in the uninitiated liver model. Forty-five to 60% of the labeled periductal cells were positive for gamma-glutamyltranspeptidase. From the periductal area the cells that were positive for antibody raised against oval cells (OV-6) infiltrated into liver parenchyma and were followed by desmin-positive Ito cells. The number of Ito cells in the uninitiated model 6 days after partial hepatectomy was 3.5 times higher in the area occupied by oval cells than elsewhere in the liver. The first alpha-fetoprotein (AFP)-positive cells appeared either as individual cells or as pseudoductal formations 32 or 56 h after partial hepatectomy at the periphery of the periductal space in both initiated and uninitiated animals. A combination of in situ and immunohistochemistry revealed that the OV-6-positive cells were AFP positive, whereas desmin-positive cells were AFP negative. Glutathione S-transferase P (GST-P) transcripts could be found mainly in OV-6-positive oval cells. Bile duct cells were positive for GST-P and negative for transforming growth factor beta 1, whereas cells in the periductal space were positive for both of these transcripts. The GST-P-positive early preneoplastic lesions showed a similar distribution pattern as that of oval cells; the preexisting hepatocytes became trapped between small basophilic hepatocytes that showed either irregular or pseudoalveolar arrangement. This raises the question as to whether cells which are stem cell-like are among the target cells in the Solt-Farber model of hepatocarcinogenesis. Proliferation of transforming growth factor beta 1-producing, desmin-positive cells (Ito cells) and multipotent oval cells in a close proximity to each other indicates an intricate relationship between Ito cells and oval cells in liver that warrants further investigation.

2-Acetylaminofluorene↗

PubMed1990

Gas exchange abnormalities after pneumonectomy in conditioned foxhounds.

Loss of a major portion of lung tissue has been associated with impaired exercise capacity, but the underlying mechanisms are not well defined. We studied the alterations in gas exchange during exercise before and after left pneumonectomy in three conditioned foxhounds. After pneumonectomy, minute ventilation and O2 consumption at comparable submaximal work loads were unchanged but arterial PCO2 at any work load was higher, implying that ventilatory response to CO2 was impaired. Arterial hypoxemia and an elevated alveolar-arterial O2 tension difference (AaDO2) developed during heavy exercise. Using the multiple inert gas elimination technique, we determined the distributions of ventilation-perfusion (VA/Q) ratios postpneumonectomy. Significant increase in VA/Q inequality developed during exercise while the foxhounds were breathing room air, accounting for an average of 42% of the total increase in AaDO2 while diffusion limitation accounted for 58%. While the animals were breathing hypoxic gas mixture, diffusion limitation accounted for an average of 88% of the total increase AaDO2. Cardiac output and O2 delivery were reduced at a given O2 consumption after pneumonectomy. After pneumonectomy, the animals reached O2 consumptions close to the maximum expected for normal dogs. Compensation for the impairment in O2 delivery post-pneumonectomy occurred mainly by an increase in hemoglobin concentration. Training probably played an important role in returning exercise capacity toward prepneumonectomy levels. We conclude that significant abnormalities in gas exchange develop during exercise after loss of 42% of lung tissue, but the animals demonstrate a remarkable ability to compensate for these changes.

Animals↗

PubMed1990

Hemodynamic changes after pneumonectomy in the exercising foxhound.

Pulmonary arterial pressure is higher during exercise after pneumonectomy than before. Several factors may contribute to the elevation, e.g., loss of vascular bed, overinflation of the remaining lung, and active pulmonary vasoconstriction. We measured hemodynamic changes during graded exercise in conditioned foxhounds and compared pulmonary pressure-flow relationships before and after left pneumonectomy. Pulmonary arterial pressure-flow relationship in the remaining lung is not altered by pneumonectomy, suggesting that the increase in pulmonary vascular resistance post-pneumonectomy is largely the passive consequence of increased pulmonary blood flow to the remaining lung. The potential for chronic hyperinflation of the remaining lung to increase pulmonary resistance after pneumonectomy may have been counterbalanced by a concomitant reduction in lung elastic recoil. Unexpectedly, both mean systemic blood pressure and hematocrit were higher with respect to cardiac output after pneumonectomy. Cardiac output and stroke volume at any given work load were lower after pneumonectomy than before, and heart rate response was unaltered. This pattern of responses suggests that increases in left and right ventricular afterload may have contributed to the reduction in cardiac output.

Animals↗

PubMed1990

Cellular distribution of transforming growth factor-beta 1 and procollagen types I, III, and IV transcripts in carbon tetrachloride-induced rat liver fibrosis.

The cellular distribution and temporal expression of transcripts from transforming growth factor-beta 1 (TGF-beta 1) and procollagen alpha 1(I), alpha 1(III), and alpha 1(IV) genes were studied in carbon tetrachloride (CCl4)-induced rat liver fibrosis by using in situ hybridization technique. During the fibrotic process, TGF-beta 1 and procollagen genes were similarly and predominantly expressed in Desmin-positive perisinusoidal cells (e.g., fat-storing cells and myofibroblasts) and fibroblasts and their expression continued to be higher than those observed in control rats. These transcripts were also observed in inflammatory cells mainly granulocytes and macrophage-like cells at the early stages of liver fibrosis. The production of extracellular matrix along small blood vessels and fibrous septa coincided with the expression of these genes. Expression of TGF-beta 1 and procollagen genes were not detected in hepatocytes throughout the experiment. No significant differences in cellular distribution or time course of gene expression among procollagen alpha 1(I), alpha 1(III), and alpha 1(IV) were observed. Desmin-positive perisinusoidal cells and fibroblasts appeared to play the principal role in synthesis of collagens in CCl4-induced hepatic fibrosis. The simultaneous expression of TGF-beta 1 and procollagen genes in mesenchymal cells, including Desmin-positive perisinusoidal cells, during hepatic fibrosis suggests the possibility that TGF-beta 1 may have an important role in the production of fibrosis.

Albumins↗

PubMed1990

Transforming growth factor-beta 1 and type I procollagen transcripts during regeneration and early fibrosis of rat liver.

The temporal and cellular distribution of transforming growth factor (TGF)-beta 1 and procollagen alpha 1(I) transcripts were examined during regeneration and early fibrosis of rat liver using in situ hybridization and Northern blot analyses. Surgical two-thirds partial hepatectomy (mechanical partial hepatectomy (PH)) and carbon tetrachloride administration (chemical PH) were used to initiate liver regeneration and fibrosis, respectively. Enhancement of TGF-beta 1 gene expression appeared as early as 4 hours after mechanical PH and reached maximum at 12 hours, which preceded the peak of DNA synthesis. However, the peak of TGF-beta 1 expression after carbon tetrachloride administration was observed after 2 days. The increase in expression of the procollagen alpha 1 (I) gene followed that of TGF-beta 1 after both mechanical and chemical PH. Increases in TGF-beta 1 and procollagen alpha 1 (I) transcripts were observed primarily in periductal and periportal cells, as well as in endothelial cells of the portal and central veins after mechanical and chemical PH. In the centrilobular necrotic areas after chemical PH, TGF-beta 1 and procollagen alpha 1 (I) transcripts were observed first in inflammatory cells and then in desmin-positive perisinusoidal cells and resulted in the accumulation of connective tissues. These data suggest that TGF-beta 1 derived from inflammatory cells may have enhanced the expression of the procollagen alpha 1 (I) gene as well as that of the TGF-beta 1 gene itself in desmin-positive perisinusoidal cells by paracrine mechanisms. This sequence of events may represent the initial stages of liver fibrogenesis.

Albumins↗

PubMed1988

Natural occurrence and clastogenic effects of nivalenol, deoxynivalenol, 3-acetyl-deoxynivalenol, 15-acetyl-deoxynivalenol, and zearalenone in corn from a high-risk area of esophageal cancer.

This is the first report of the natural coexistence of a group of Fusarium mycotoxins (nivalenol [NIV], deoxynivalenol [DON], 3-acetyl-deoxynivalenol [3-ADON], 15-acetyl-deoxynivalenol [15-ADON], and zearalenone [ZEN]) in corn from Linxian, China, an area with a high risk of esophageal cancer. Using thin layer chromatography (TLC), high pressure liquid chromatography (HPLC), and gas chromatography (GC), 107 corn samples from Linxian were analyzed. The average levels of NIV and DON were 757 +/- 707 (54-2,760) ng/g and 5,376 +/- 4,460 (360-12,670) ng/g, respectively, with 100% positivity in 24 corn samples consumed as staple food by esophageal cancer patients and their families. Other corn samples collected from five villages in Linxian at different seasons in 1984-1986 also revealed high levels of NIV and DON contamination, with 100% positivity, suggesting that they are consistently and widely present in corn in that area. Levels of 3-ADON and 15-ADON in Linxian corn were 113 +/- 57 and 495 +/- 538 ng/g, respectively. Crude extracts of corn samples collected from esophageal cancer patients' families and the HPLC-purified NIV and DON fractions induced significant chromosome aberrations in V79 cells. Pure toxins of NIV, DON, T-2, and 3-ADON also induced chromosome aberrations in V79 cells at very low concentrations (ng levels/ml medium). Cytotoxic effects were observed at slightly higher concentrations. The levels and kinds of trichothecenes were in positive co-relation with the incidence of esophageal cancer. The data suggest that trichothecenes in food may possibly be associated with esophagitis and esophageal cancer in Linxian.

China↗

PubMed1986

Induction of chromosome aberrations by fusarium T-2 toxin in cultured human peripheral blood lymphocytes and Chinese hamster fibroblasts.

T-2 toxin is an important representative of trichothecenes produced by various species of imperfect fungi, mainly Fusarium genus. It is a naturally occurring toxin that can cause severe diseases in human and animals. No definite data demonstrating the carcinogenic potential of T-2 toxin had been reported up to now. We demonstrated that T-2 toxin reproducibly induced chromosomal structural aberrations both in cultured human peripheral blood lymphocytes as well as in V79 Chinese hamster fibroblasts. The mean percentage of cells with aberration of human lymphocytes from normal individuals induced by T-2 toxin is 49-fold (9.8%) of the mean percentage of corresponding control cultures without T-2 toxin (0.2%). T-2 toxin induced chromosome type (76%) as well as chromatid type (24%) of aberrations; among them, acentric fragment (46%) was the most common type, and chromatid gap, deletion, and chromosome gap were the next most common. T-2 toxin can induce aberrations in cells at different phases of the cell cycle. There are definite dose-effect relationships within a certain range of dosage of T-2 toxin in experiments with both human peripheral blood lymphocytes and V79 cells. T-2 toxin exhibited three types of effects on cells, namely, mitogenic at lowest concentration, clastogenic (chromosome aberration) at median concentration, and cytotoxic at higher concentration. The dose-effect curves of these three effects are partly overlapping. There is some interindividual difference in sensitivity of response for the clastogenic effect of T-2 toxin, but no resistant individual was observed. Sex or age effect was not observed. The above results suggest that T-2 toxin has carcinogenic potentials. The dosage of aflatoxin that can induce chromosomal aberration of human peripheral blood lymphocytes is thousands-fold of the dosage of T-2 toxin as shown in this report. T-2 toxin might have more hazardous potentials than had been previously considered. The carcinogenic potential of T-2 toxin and related trichothecenes and their possible roles in carcinogenesis of upper gastrointestinal (G.I.) tract cancers need to be further investigated.

Animals↗

PubMed1986

[Studies on the relationship of duck hepatoma and duck hepatitis B virus in a high incidence area of human hepatoma].

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Animals↗

PubMed1984

Activation of chemical carcinogens by cultured human fetal liver, esophagus and stomach.

Cultured fetal human stomach, esophagus and liver activated benzo[a]pyrene (BP), aflatoxin B1 (AFB) and certain N-nitrosamines into metabolites that bound to cellular DNA. When the 3 organs were compared the highest level of activity was observed in the stomach. The interindividual variation was 10-fold and the amount of carcinogen-DNA adducts did not correlate with the sex or age of the fetus. The reaction products between BP or AFB and cellular DNA were investigated in liver explants. The carcinogen-DNA adduct patterns were identical to those observed in adult human tissues; BPDEI-Gua being the major adduct formed by BP and 2,3-dihydro-2-(7'-guanyl)-3-hydroxy-AFB by AFB. The results indicate that fetal organs can metabolize those oncogenic compounds at an early stage of the development, and that the metabolic pathways and DNA adducts are quite similar to those in experimental animals in which the compounds are carcinogenic.

Aflatoxin B1↗

PubMed1983

Proliferative and cytotoxic effects of Fusarium T2 toxin on cultured human fetal esophagus.

In an area with high incidence of esophageal cancer, Linxian, staple food is heavily contaminated by fungi of the Fusarium genus. We have found that T-2 toxin produced by Fusarium has both direct cytotoxic and proliferative effects on fetal esophageal epithelium. At higher dosage of T-2 toxin (4 ng/ml for 6 days) the cultured epithelium became necrotic. At a lower dosage range of 0.2-1.2 ng/ml, T-2 toxin caused mitogenic effects including focal basal cell hyperplasia, dysplasia, and increased number of mitoses. Atypical mitoses were also seen. These changes are very similar to the premalignant lesions seen in epithelium adjacent to human esophageal carcinoma. These observations suggest that Fusarium mycotoxin can have a role in human esophageal carcinogenesis and should be further investigated.

Cell Division↗

PubMed1981

Enhancement of formation of the esophageal carcinogen benzylmethylnitrosamine from its precursors by Candida albicans.

Previous studies in Linxian, an area of China with a high incidence of esophageal carcinoma, showed that fungal infections are common in the esophageal epithelium of patients with either premalignant changes or early esophageal carcinoma. Fungi of the genus Candida were the most frequent invaders. In these areas nitrate and nitrite are often present in high concentrations in drinking water and staple grains. The present studies have established the ability of Candida albicans to augment the nitrosative formation of the esophagus-specific carcinogen, benzylmethylnitrosamine (NBMA; N-nitroso-N-methylbenzylamine). Stationary C. albicans cultures, with pH held at 6.8, were incubated with the precursors of NBMA, benzylmethylamine (BMA; N-methylbenzylamine) and NaNO(2). There was a significant increase in the amount of NBMA formed in these cultures, compared to precursors-only controls. The amount of NBMA synthesized depended on fungal cell number. Exponentially growing cultures were also able to cause NBMA formation. The identity of the NBMA was confirmed by high-performance liquid chromatographic coelution with authentic NBMA in three solvent systems and by mass spectroscopy. Boiled cells and conditioned medium in which cells had been incubated were not effective in enhancing nitrosation. Cultured Candida released acidic metabolites that reduced the pH of the medium when only a low concentration of buffer was present. Spontaneous nitrosation of BMA was enhanced under these acidic conditions. Thus, C. albicans infecting the esophageal epithelium could cause local formation of NBMA by both cell-mediated catalysis and extracellular decrease in pH.

Benzylamines↗

PubMed1981

Antibodies reactive with murine mammary tumor virus in sera of patients with breast cancer: geographic and family studies.

Sera of patients with breast cancer, of healthy women from the United States, East India, East Africa, and China, and of healthy women of American and Parsi families in which breast cancer occurred in several family members were assayed for levels of antibody reactive with the murine mammary tumor virus (MuMTV) by an enzyme-linked immunosorbent assay. Increased levels of antibody to MuMTV (absorbance greater than or equal to 0.4) were found in sera of 18.6% of American patients with breast cancer and of 2.8% of healthy American women and in 38% of patients from India and 61.9% from East Africa (healthy, 26.9%). In contrast, antibody reactive with MuMTV was found in less than 5 of women with breast cancer from mainland China (healthy Chinese, 5.0%). Differences in serum MuMTV antibody levels between breast cancer patients in the four groups were found to be significant (P less than 0.0001). Studies of two families from the United States and of one Parsi family from India with genetic propensity to breast cancer showed that high levels of antibody to MuMTV were found in 33%, 71%, and 23% of healthy family members, respectively. The antibody to MuMTV was readily absorbed with purified MuMTV and gp52. In contrast, fetal calf serum, murine type c retroviruses, or erythrocytes from various species failed to absorb the antibody.

Animals↗

PubMed1980

Geographic and family studies of immunological responses to antigens of the murine mammary tumor virus in sera of patients with breast cancer.

Sera of breast cancer patients from the United States, India, East Africa and China as well as from their families and from healthy women were assayed for antibodies reactive with the murine mammary tumor virus (MuMTV). Detection was by an enzyme-linked immunoassay recently developed in our laboratory. In the women with breast cancer, 62% of the East Africans, 28% of the Indians, 19% of the Americans but only 5% of the Chinese had antibody to MuMTV. Among healthy women, 21% of the Africans, 3% of the Americans and 5% of the Chinese possessed this antibody. Several family members of breast cancer patients, males as well as females, had increased levels of MuMTV antibody. The MuMTV-reactive antibody was removed by absorption with MuMTV, deglycosylated MuMTV and gp52, the major MuMTV envelope protein. It was not absorbed out by murine leukemia viruses, red blood cells from various species, fetal calf serum or carbohydrates. The results suggest that there may be more than one form of breast cancer, definable by reactivity to MuMTV. The murine mammary tumor virus (MuMTV) is the etiological agent of breast cancer in mice. The induction of mammary tumorigenesis, however, is dependent upon the genetic makeup, hormonal status, and diet of the infected mouse. Thus, even in a situation where a known single cause for breast cancer exists, disease manifestation is subordinate to diverse factors in the individual host.

Africa, Eastern↗