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Biomedical subjects

B H Ruebner

Publications and source records attributed to B H Ruebner.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effect of selenium on aflatoxin hepatocarcinogenesis in the rat.

The effects of selenium (Na2SeO3) on aflatoxin B1 (AFB1)-induced hepatic neoplasia were studied in the rat. Putative preneoplastic foci and nodules composed of basophilic, eosinophilic, and clear cells developed early. Basophilic foci were seen first; in the later stages basophilic and eosinophilic nodules predominated. At each stage the AFB1 + Se groups showed fewer and smaller foci and nodules than the AFB1 - Se group. The number of foci in the AFB1 + 3 ppm Se group and their mean area were smaller than those in the 6 ppm Se + AFB1 group. At the end of the experiment hepatocellular carcinoma (HCC) was found in 11/18 rats (61%) of the AFB1 - Se group. HCC was not found in either of the groups given AFB1 + Se. We conclude that Se had an inhibitory effect on the initiation and promotion stages of AFB1-induced preneoplastic foci and nodules. Se also prevented progression of these nodules to HCC even after cessation of AFB1 administration. The inhibitory effect of Se at 3 ppm was greater than at 6 ppm. The 6 ppm Se group also showed evidence of toxicity.

Aflatoxin B1↗
PubMed1989

Immunochemical comparison of human and rhesus monkey liver microsomal and the hepatocellular carcinoma-induced human serum epoxide hydrolases (preneoplastic antigens): basis for an enzyme-linked immunoabsorbent assay.

An antibody (anti-EH) specific for microsomal epoxide hydrolase (mEH) from rhesus monkey liver has been used to test the immunochemical relationship between human liver mEH and the serum EH levels in human patients with hepatocellular carcinoma (HCC). Immunoblots of separated rhesus monkey and human liver microsomal proteins revealed that anti-EH was selective for a single polypeptide band of similar mol. wt, approximately 49 kd, in both species. Anti-EH was also able to precipitate 100% of the activity for two substrates specific in the mouse for mEH, cis-stilbene oxide and benzo[a]-pyrene-4,5-oxide, in solubilized human liver microsomes. In contrast, only 20% of the microsomal trans-stilbene oxide hydrolase activity was precipitated under similar conditions, providing immunochemical evidence that a distinct EH, with substrate selectivity similar to the cytosolic EH, resides in human liver microsomes. Immunoprecipitation of serum from a patient with elevated EH activity resulted in total precipitation of cis-stilbene oxide hydrolase activity. An enzyme-linked immunoabsorbant assay (ELISA) was developed using anti-EH with detection limits of 1 ng/ml. A high correlation between the enzymatically and immunochemically determined levels of serum EH provided further evidence for the immunochemical similarity of human liver microsomal and serum EH. In addition, the ELISA was equally capable of identifying elevated serum EH in patients with HCC, and should prove invaluable in evaluating the effectiveness of serum EH levels as a marker for HCC.

Animals↗
PubMed1988

Effect of total parenteral nutrition on hepatic histology.

We evaluated the effect of total parenteral nutrition (TPN) on abnormalities of hepatic histology. Liver biopsies of 93 patients who were concurrently receiving TPN were compared with a control group of 35 patients. The control patients were matched for extent of preexisting liver disease and degree of illness. The liver biopsy specimens were blindly graded on 19 histopathologic findings, including fatty change, portal inflammation, and cholestasis. Twenty-seven clinical variables, such as preexisting liver disease, the presence or absence of sepsis or shock, and number of days receiving TPN before biopsy, were recorded. Individual and partial correlations were established between the clinical variables and histopathologic findings. The control and TPN groups proved to have been closely matched regarding the extent of risk factors for hepatic histopathologic features. Positive correlations were repeatedly found between abnormal hepatic histologic features and preexisting liver disease, abdominal sepsis, renal failure, and blood transfusion but not with the administration of TPN. We conclude that clinical phenomena, such as existing liver disease, renal failure, and abdominal sepsis, rather than administration of TPN, had a predominant effect on histopathologic features in this group of patients.

Humans↗
PubMed1987

Carcinogenicity of dietary aflatoxin M1 in male Fischer rats compared to aflatoxin B1.

Aflatoxin M1 (AFM), an hydroxy metabolite of the potent carcinogenic mycotoxin aflatoxin B1 (AFB) is frequently found in milk and other dairy products. Sufficient amounts of AFM were produced to study the carcinogenicity of this compound. AFM was fed to male Fischer rats starting at 7 weeks up to 21 months of age. Agar-based semisynthetic diets contained 0.0, 0.5, 5.0, and 50.0 micrograms/kg of AFM or 50 micrograms/kg of AFB. Hepatocellular carcinomas were detected in two of 37 rats and neoplastic nodules were found in six of 37 rats fed 50 micrograms/kg AFM between 19 and 21 months. No nodules or carcinomas were observed in the lower AFM dose groups. Nineteen of 20 rats fed a diet containing 50 micrograms/kg of AFB developed hepatocellular carcinomas by 19 months of age. Carcinogenic potency of the aflatoxins was reflected by morphometric quantitation of foci detected in hematoxylin and eosin stained sections. Three rats fed the diet containing 50 micrograms/kg AFM developed intestinal carcinomas. None were observed in other groups. Under the conditions of this experiment AFM was found to be a weak hepatic carcinogen compared to AFB and to possess intestinal carcinogenicity.

Aflatoxin B1↗
PubMed1987

Pathology of renal and hepatic anomalies in Meckel syndrome.

We describe 9 cases of Meckel syndrome (dysencephalia splanchnocystica), ranging in gestational age from 17 to 39 weeks. Five were liveborn, and the longest survival was 30 hours. Six of the 9 had all 3 elements of the classically defined triad, namely occipital encephalocele, renal cystic dysplasia, and postaxial polydactyly. The remaining 3 cases had only 2 elements of the triad. The renal abnormalities in the 9 cases resembled one another closely, varying only slightly in severity. They consisted of renal cystic dysplasia with different degrees of nephronic differentiation. The 8 available livers all contained intrahepatic bile duct anomalies. Seven of them had the classic "ductal plate malformation," as defined by Jorgensen [1977]; the remaining case had a less severe form of this malformation. The livers of the Meckel syndrome fetuses were compared to those of age-matched control fetuses, and it was concluded that the hepatic abnormality represents an arrested development of the intrahepatic biliary system at the stage of biliary cylinders with varying degrees of reactive bile duct proliferation, bile duct dilatation, portal fibrosis, and portal fibrous vascular obliteration superimposed on the arrested pattern. The case showing the least severe hepatic lesion also had the least severe renal lesion. The anomalies that were present are listed. The relationship of the different lesions to each other is briefly discussed. It was concluded that the hepatic lesion appears to be a consistent manifestation in Meckel syndrome and is of diagnostic value as the renal lesion has previously been shown to be.

Abnormalities, Multiple↗
PubMed1987

Hepatic fibrosis and cirrhosis in tropical countries (including portal hypertension).

The spectrum of diseases seen in patients from certain 'tropical areas' requires that a physician be aware of some of the syndromes discussed here. A high index of suspicion for less usual causes of cirrhosis is imperative when evaluating such patients presenting with hepatocellular disease. The differential must be expanded and the work-up complete. Liver biopsy should be performed as early in the course of disease as is feasible and will often provide valuable diagnostic information. It will not only facilitate treatment but allow for needed clinical trials and may help to increase our understanding of the various disease processes.

Anemia, Hemolytic↗
PubMed1987

What is new in epithelioid hemangioendothelioma of the liver?

An unusual hepatic vascular neoplasm has been delineated in recent years. It has characteristic morphologic features consisting of multiple nodules with relatively acellular centers which may be focally calcified. More peripherally there is a cellular zone containing elongated or plump tumor cells embedded in a fibromyxoid stroma. At the outer edge of the nodules, and particularly in vessels, the tumor cells may assume an epithelioid appearance. The tumor cells exhibit focally positive staining for Factor VIII related antigen and Weibel Palade bodies may be seen on electron microscopy. The tumor is malignant, but may have an indolent course over many years. It may be associated with hepatic cirrhosis and pulmonary osteoarthropathy. Other organs, particularly the lung and soft tissues are frequently involved.

Hemangioendothelioma↗
PubMed1987

Odontogenic tumors in Fischer rats.

The formation of odontogenic tumors in rats is rare unless they are treated with known carcinogens. In this study, male Fischer rats were continuously fed aflatoxins M1, B1, or control diets, then killed at 1, 6, 10, 16, 17, 19 and 21 months. Of the 186 rats fed aflatoxin M1 at 3 concentrations, 12 developed odontogenic tumors; 7 of 63 rats fed an agar-based diet also developed odontogenic tumors in 17-21 months. The purpose of this study is to describe these tumors. All the tumors were located in the upper jaw associated with the incisor teeth. The tumors developed in the periodontal ligament area and were composed mainly of highly cellular fibrous connective tissue. The fibroblastic nuclei were clustered in poorly defined swirls in areas and were evenly scattered in a myxomatous stroma in other areas. Within this tissue were ovoid sometimes coalescing, calcified bodies resembling cementum. Occasional inclusions of solid epithelial cell nests were present. Scattered nests were composed of ovoid epithelial ghost cells. Acellular cementum-like material surrounded many of these nests. An inductive phenomenon was present around occasional epithelial nests. Rare structures composed of globular dentin with irregular tubules were also observed. These tumors caused distortion of the facial areas and disruption of incisor tooth development. No metastatic lesions were noted but other neoplastic lesions occurred in these animals.

Aflatoxin B1↗
PubMed1985

Cancer risks posed by aflatoxin M1.

The suspect milk-borne carcinogen, aflatoxin M1 (AFM), was produced and isolated from the rice culture of the fungus Aspergillus flavus NRRL3251 for confirmation and determination of the potency of its carcinogenicity in the male adult Fischer rat. The carcinogen was mixed into an agar-based, semisynthetic diet at 0, 0.5, 5, and 50 ppb (microgram/kg) and was fed to groups of animals continuously for 19-21 months. Aflatoxin B1 (AFB), of which AFM is a metabolite, at 50 ppb was used as a positive control. Hepatocarcinogenicity of AFM was detected at 50 ppb, but not at 5 or 0.5 ppb, with a potency of 2-10% that of AFB. A low incidence of intestinal adenocarcinomas was found in the AFM 50 ppb group, but not in any other groups. At 0.5 ppb, the action level enforced by the U.S.A. Food and Drug Administration, AFM induced no liver lesions in the rats but stimulated the animals' growth. On the average, the rats in the 0.5 ppb group weighed 11% (p less than 0.001) more than those in the control group. This increased growth was associated with increased feed intake. Based on the biological activity of AFM at the relevant low doses and the estimated level of human exposure to AFM through consumption of milk, the cancer risk posed by this contaminant for human adults is assessed to be very low. For infants, further studies are warranted because milk constitutes the major ingredient of the infant diet and because infant animals have been shown to be more sensitive to the carcinogenicity of AFB than adult animals.

Aflatoxin M1↗
PubMed1984

Irreversibility of liver tumors in C3H mice.

The present study was designed to test the possibility that spontaneous regression of hepatocellular tumors might be observed in mice. This problem was studied by sequential liver biopsies in C3H male mice that had been treated with dieldrin (CAS: 60-57-1) as well as in animals treated with N-diethylnitrosamine (CAS: 55-18-5) and in untreated control mice. Adenomas were seen in some animals at the second laparotomy when there had been no tumor at the first laparotomy. In a few mice there was histologic progression from adenoma to carcinoma. A change in predominant cell type in adenomas from clear to basophilic or eosinophilic was also observed in some cases. Additional hepatocellular carcinomas were observed in some animals necropsied at 2 years of age. These observations suggest that spontaneous hepatic tumors and tumors in mice treated with either complete carcinogens or nongenotoxic compounds have a strong tendency to progress. Tumor regression in mice appears to be unusual. No consistent relationship of histologic grade of hepatocarcinoma to the type of chemical employed was observed.

Animals↗
PubMed1982

Enzyme histochemical characteristics of spontaneous and induced hepatocellular neoplasms in mice.

Hepatocellular neoplasms are known to differ in enzyme activity from the surrounding non-neoplastic liver. We have compared histochemically the enzyme activity of spontaneous hepatocellular tumors in mice with tumors induced by diethylnitrosamine and dieldrin. Some neoplasms had increased activity, others had decreased enzyme activity, yet other had the same activity as the surrounding liver. Alkaline phosphatase, glucose-6-phosphatase, succinic dehydrogenase and adenosine triphosphatase, as well as glycogen levels were studied. Carcinomas differed from adenomas in having elevated enzyme activity significantly more often than adenomas. However, the carcinomas showed elevated glycogen levels less frequently than adenomas. Histochemically, pulmonary metastases resembled the primary hepatocellular carcinomas from which they were derived. Tumors of dieldrin animals were notable in having increased activity of all the enzymes which we studied more frequently than tumors of diethylnitrosamine animals or of controls. Differences in enzyme activity between the three mouse strains were slight.

Adenosine Triphosphatases↗
PubMed1982

Transplantation and metastasis of NB rat prostate neoplasia in congenitally athymic (nude) mice, nude mice treated with antilymphocyte sera and congenitally athymic rats.

The androgen-dependent NB rat prostate adenocarcinoma 2PR 129 and the autonomous tumor 102PR were transplanted into groups of both male and female nude mice, nude rats, and NB rats. Significant growth of the 2PR 129 tumor at the site of transplantation was noted in male but not female nude mice, nude rats or NB rats. Indeed, successful transplantation of 2PR 129 was not achieved in female nude mice even with usage of antilymphocyte sera. In contrast, the autonomous tumor 102PR grew at a significant rate at the local site of transplantation in mice and rats of both sexes. Although significant tumor masses were found at the injection site of male nude mice transplanted with 2PR 129 and in both male and female nude mice injected with 102PR, metastasis was not found. Further, antilymphocyte sera increased the rate of growth of both tumors in nude mice but did not change the apparent metastatic potential. Nonetheless, metastasis was readily observed in male nude rats transplanted with 2PR 129 and nude rats of both sexes transplanted with 102PR. Such metastatic lesions of nude rats were found in lung, liver and kidney with a similar frequency and histologic profile as NB rats. These results suggest that the nude rat, at least for this rat tumor system, is a more versatile and biologically relevant system than nude mice and further cautions against use of xenotransplants as models of tumor natural history. Moreover, it suggests the possible relationship between host recognition of species-determined genetic loci and metastatic potential.

Animals↗
PubMed1981

Mallory body formation in hepatic nodules of mice ingesting dieldrin.

Mallory bodies (MBs) were observed in hepatic nodules induced by long-term administration of a diet containing 10 p.p.m. of dieldrin to C57BL/6 mice. MBs were first detected after 46 weeks and were seen in 26 of 41 mice which developed hepatic nodules. The MBs were limited to the nodules in 25 mice. Twenty-one of the nodules were carcinomas and 20 of those contained MBs. Our observations suggest that MBs may be a marker for neoplastic transformation and may prove useful in experimental studies of carcinogenesis.

Animals↗
PubMed1981

Gastric tumors in patients with pulmonary chondroma or extra-adrenal paraganglioma: an ultrastructural study.

The histogenesis of a distinctive metastasizing intramural gastric tumor found in patients with extra-adrenal paragangliomas, pulmonary chondromas, or both, is unknown. By light microscopy, it has appeared to be of smooth-muscle derivation, and it has been interpreted as being epithelioid leiomyosarcoma. For further clues to its nature, we studied three examples by electron microscopy (two obtained from patients with extra-adrenal paragangliomas and one from a patient with pulmonary chondroma). Ultrastructurally, they were characterized by interdigitating cytoplasmic processes, plasma membrane-associated dense patches, an incomplete basement membrane, junctional complexes, randomly oriented filaments without periodicity, cytoplasmic dense bodies, pinocytotic vesicles, clustering of mitochondria, and rare cilia-features of normal smooth muscle or of smooth-muscle tumors with classic histologic patterns. Thus, the findings suggest that the three tumors we studied are of smooth-muscle derivation.

Adolescent↗
PubMed1980

Changes in bilirubins in human prenatal development.

1. A densitometric method has been developed for the quantification of azodipyrroles derived from dog bile pigments treated with diazotized ethyl anthranilate. 2. This method was used to estimate the bilirubins in bile and meconium from foetuses of 14-36 weeks gestation. 3. The proportion of the bilirubins in foetal bile changed during gestation. (a) No bile pigments were found until 14 weeks. (b) Between 14 and 15 weeks bilirubin-IX beta was the only bile pigment detected. (c) At 16-17 weeks some unconjugated bilirubin-IX alpha was found in the bile, but up to 20 weeks bilirubin-IX beta was the predominant bilirubin in the bile. (d) At about 20 weeks glucose, xylose, and an unidentified bilirubin-IX alpha monoconjugate were found in the bile. (e) Between 20 and 23 weeks bilirubin-IX alpha glucuronide appeared in the bile. (f) At 30 weeks monoconjugates of bilirubin-IX alpha were the predominant bilirubins in the bile. (g) Only in full-term foetuses was bilirubin-IX alpha monoglucuronide the major bilirubin derivative.

Azo Compounds↗