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PubMedDate not supplied

Carcinogenesis in rats by nitrosodialkylureas containing oxygenated alkyl groups.

A number of asymmetric nitrosodialkylureas containing ethyl, hydroxyethyl, 2-hydroxypropyl, 2-oxopropyl or chloroethyl on one or the other side of the nitroso function were given to male and female F344 rats in drinking water. The two compounds containing a 2-oxopropyl group, ethylnitrosooxopropylurea and oxopropylnitrosochloroethylurea were also given by gavage at the same weekly doses as in drinking water. The effect was greater following gavage treatment, both in tumor incidence and in mortality rate. The most potent carcinogen was ethylnitrosooxopropylurea which induced a large variety of tumors, including lung, nervous system, colon, intestine, thyroid, skin and uterus tumors, mammary adenocarcinomas and mesotheliomas. A similar pattern of tumors was induced by ethylnitrosohydroxyethylurea and hydroxyethylnitrosoethylurea. Hydroxyethylnitrosochloroethylurea, hydroxypropylnitrosochloroethylurea and oxopropylnitrosochloroethylurea gave rise to tumors in fewer organs. Chloroethylnitrosohydroxypropylurea was very toxic to the kidneys and induced a few lung tumors. Skin tumors were commonly induced by the nitrosodialkylureas in drinking water, but not when given by gavage.

Administration, Oral↗
PubMedDate not supplied

[Intestinal pseudoobstruction in hypothyroidism].

Just as gastrointestinal functional diseases affect the thyroid, so thyroid disfunction affects the structure and function of almost all parts of the gastrointestinal tract. Hypothyroidism has frequently been associated with various gastrointestinal manifestations, including constipation, bloating, flatulence, atrophic gastritis, ileus, atony and dilatation of the oesophagus, stomach, gallbladder, small intestine and colon. Characteristic intestinal hypomotility in a severe hypothyroidism may progress to intestinal pseudoobstruction, paralytic ileus and megacolon. These rare but potentially serious complications must be recognized and treated promptly with adequate doses of thyroid hormone replacement therapy. The case history of a 64-year-old woman with hypothyroidism and intestinal pseudoobstruction is described.

Female↗
PubMed1990

[Radiotherapy-induced emergencies in the x-ray picture].

Acute symptoms have to be noted by the roentgenologist in diagnosis of emergency as direct consequence of irradiation. Above all they pertain to organs of thoracal area (lung, heart) and of abdomen (small intestine, colon). Roentgenologic pictures are presented with exemplary case reports.

Emergencies↗
PubMed1990

9 alpha,11 beta-prostaglandin F2 formation in various bovine tissues. Different isozymes of prostaglandin D2 11-ketoreductase, contribution of prostaglandin F synthetase and its cellular localization.

9 alpha,11 beta-prostaglandin F2 was formed from prostaglandin D2 by its 11-ketoreductases in 100,000 x g supernatants of various bovine tissues in the presence of an NADPH-generating system. The reductase activities were high in liver (51.09 nmol/h/mg of protein), lung (24.99), and spleen (14.20); moderate in heart and pancreas (3.09-3.61); weak in stomach, intestine, colon, kidney, uterus, adrenal gland, and thymus (0.11-2.63); and undetectable in brain, retina, carotid artery, and blood (less than 0.10). No formation of prostaglandin F2 alpha from prostaglandin D2 was detected in all tissues. In immunotitration analyses with a polyclonal antibody specific for prostaglandin F synthetase, the reductase activities in lung and spleen showed identical titration curves to that of the purified synthetase and decreased to less than 15% of the initial activity under the condition of antibody excess. Prostaglandin F synthetase-immunoreactive protein in these two tissues showed peptide fingerprints identical to that of the purified enzyme after partial digestion with Staphylococcus aureus V8 protease. The antibody was partially cross-reactive to the reductase in liver (about 20% of that to the synthetase) but not to the reductase(s) in other tissues. The Km value for prostaglandin D2 of the reductase activity was the same in lung and spleen as that of the purified prostaglandin F synthetase (120 microM) but differed in liver (6 microM), heart, and pancreas (15 microM). The predominant distribution of prostaglandin F synthetase in lung and spleen was confirmed by radioimmunoassay (2.8 and 1.0 micrograms/mg protein, respectively) and Northern blot analyses. In immunoperoxidase staining, this enzyme was localized in alveolar interstitial cells and nonciliated epithelial cells in lung, histiocytes and/or dendritic cells in spleen, and a few interstitial cells in kidney and adrenal cortex.

Animals↗
PubMed1989

Epidemiological studies on ingested mineral fibres: gastric and other cancers.

The epidemiological studies of ingested asbestos fibres conducted world-wide are reviewed and evaluated. Most of the studies have been done in the United States and Canada and have involved community exposures via natural contamination of drinking-water supplies. One or more studies found associations between asbestos fibres in drinking-water supplies and cancer incidence or mortality associated with many body sites, including oesophagus, stomach, small intestine, colon, rectum, gall-bladder, lungs, pancreas, peritoneum, pleura, prostate, kidneys, brain and thyroid. Each study has methodological limitations or weaknesses that limit the ability to assess risk from ingested asbestos. There is no agreement between the results of the various studies, but an association between ingested asbestos fibres and cancer of the stomach and pancreas has been found with some degree of consistency.

Asbestos↗
PubMed1987

Analysis of the tissue-specific expression, developmental regulation, and linkage relationships of a rodent gene encoding heart fatty acid binding protein.

The rat contains at least three homologous cytosolic proteins that bind long chain fatty acids, termed liver (L-), intestinal (I-), and heart (H-) fatty acid binding protein (FABP). I-FABP mRNA is confined to the gastrointestinal tract while L-FABP mRNA is abundantly represented in hepatocytes as well as enterocytes. We have isolated a rat heart FABP cDNA clone and determined the pattern of H-FABP mRNA accumulation in a wide variety of tissues harvested from late fetal, suckling, weaning, and adult rats. RNA blot hybridizations and primer extension analysis disclosed that the distribution of H-FABP mRNA in adult rat tissues is different from that of I- or L-FABP mRNA. H-FABP mRNA is most abundant in adult heart. This mRNA was also present in an adult slow twitch (type I) skeletal muscle (soleus, 63% of the concentration in heart), testes (28%), a fast twitch skeletal muscle (psoas, 17%), brain (10%), kidney (5%), and adrenal gland (5%). H-FABP mRNA was not detected in adult small intestine, colon, spleen, lung, or liver RNA. Distinct patterns of developmental change in H-FABP mRNA accumulation were documented in heart, placenta, brain, kidney, and testes. Myocardial H-FABP mRNA levels rise rapidly during the 48 h prior to and after birth, reaching peak levels by the early weaning period. The postnatal increase in myocardial H-FABP mRNA concentration and its relative distribution in adult fast and slow twitch skeletal muscle are consistent with its previously proposed function in facilitating mitochondrial beta-oxidation of fatty acids. However, the presence of H-FABP mRNA in brain, a tissue which does not normally significantly oxidize fatty acids in late postnatal life, suggests that H-FABP may play a wider role in fatty acid metabolism than previously realized. Mouse-hamster somatic cell hybrids were utilized to map H-FABP. Using stringencies which did not produce cross-hybridization between L-, I-, and H-FABP DNA sequences, we found at least three loci in the mouse genome, each located on different chromosomes, which reacted with our cloned H-FABP cDNA. None of these H-FABP-related loci were linked to the gene which specifies a highly homologous adipocyte-specific protein termed aP2 or to genes encoding two other members of this protein family, cellular retinol binding protein and cellular retinol binding protein II.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1988

Radiation dose and second cancer risk in patients treated for cancer of the cervix.

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.

Female↗
PubMed1988

The good ol' days is now: trends in operative experience of general surgical residents over 25 years.

To define the changing trends in operative experience of general surgery residents, the records of all residents completing our training program from 1964-1987 were reviewed. Except for a slight decline in operative experience in head and neck and gastric surgery, the experience in other primary component procedures either remained stable (major breast, esophagus, intestine, colon, pancreas, spleen and endocrine) or increased (minor breast, anorectal, hernia, biliary, vascular and trauma). A rich experience in secondary component procedures was maintained in thoracic, pediatric and plastic surgery, all of which are services within the department of surgery. A relatively low but stable experience in gynecology, neurosurgery, orthopaedics and urology has been reported, which did not change when these disciplines became separate departments. Finally, there has been a dramatic increase in endoscopic procedures performed in the surgery department despite the presence of endoscopic services in other departments. It is believed that such an institutional review of surgical resident caseload over time will be of help not only to program directors but also to accrediting and certifying organizations concerned with surgical training programs and their graduates.

Arkansas↗
PubMed1987

Granulocytic sarcoma of the intestine as a primary manifestation nine months prior to overt acute myelogenous leukemia.

A case of granulocytic sarcoma is reported. A 51-year-old male was found, upon laparotomy, to have a tumor mass in the terminal ileum. Nine months later, acute myelogenous leukemia (AML) was diagnosed upon a peripheral blood and bone marrow examination showing an increased number of abnormal myeloblasts. Scattered lesions of granulocytic sarcoma were found in the intestine, colon, testis, skin, gingiva and bone marrow. Chemotherapy, with multiple regimens for leukemia in combination, did not affect the tumor and the patient died 10 months following his development of overt leukemia. Detailed pathological findings are presented because of the difficulty in differentiating granulocytic sarcoma from non-Hodgkin's lymphoma.

Humans↗
PubMed1980

Effect of dioctyl sodium sulfosuccinate feeding on rat colorectal 1,2-dimethylhydrazine carcinogenesis.

The 1,2-dimethylhydrazine (DMH) rodent model for colorectal carcinogenesis was used to explore the effect of dietary dioctyl sodium sulfosuccinate (DSS) on carcinogenesis. Inbred male F344 rats were divided into two groups of 84 each and fed the following diets: ground chow and 5% corn oil (control group) and ground chow, 5% corn oil, and 1% DSS (experimental group). All rats received high-dose DMH base, 20 mg/kg/week sc for 20 weeks. Twenty rats per group were killed after 3, 4, 5, and 6 months. Duodenum, small intestine, colon, and rectum were dissected out. Each tumor was measured for size and location and evaluated histologically. The percentage of rats bearing tumors in the control and experimental groups did not differ significantly. In each rat there were fewer gastrointestinal tumors in the DSS-fed group of all histologic types combined, at all organ sites, at 5 and 6 months. This difference between the control and DSS-fed rats reached the level of statistical significance for tumors of the duodenum, colon, and rectum and for total gastrointestinal tumors at the 5th month.

Animals↗
PubMed1983

Wide-range linear dose-response curve for DNA binding of orally administered benzo(a)pyrene in mice.

The binding of p.o. benzo(a)pyrene (BP) to the DNA of mice was investigated. With a single dose of 1 microgram, levels of DNA binding were highest in the liver, followed by the intestine, colon, and stomach. In all organs, the majority of DNA-associated radioactivity was in the form of adducts which did not release ethyl acetate-soluble BP tetrols on acid hydrolysis. In both stomach and liver, the formation of acid-hydrolyzable and non-acid-hydrolyzable BP-DNA adducts was linearly related to dose, over a carcinogen dosage range of 10(-8) to 10(-3) g (liver) or 10(-7) to 10(-3) g (stomach). Repair or removal via cell turnover of liver BP-DNA adducts over a period of 7 days proceeded with the same efficiency when the dose of the administered carcinogen was varied over a range of 100,000-fold. These results suggest that in vivo the initial interaction between DNA and ingested BP takes place in the same manner both at high doses typical of laboratory carcinogenesis experiments and at low doses typical of human exposure.

Administration, Oral↗
PubMed1984

The immune response of the mammary gland and its significance for the neonate.

The immune response of the mammary gland is dominated by local production of secretory IgA antibodies (SIgA). These milk antibodies, amounting to about 0.5-1 g/day throughout lactation, are directed against food proteins and microorganisms often present in the intestine. This is presumably explained by the enteromammaric link: after antigenic exposure in the Peyer's patches of lymphoid cells they home to various exocrine glands, including the mammary gland. Similarly, lymphoid cells from the bronchial mucosa, may contribute to the antibody-producing cell population in the mammary gland. SIgA antibodies against common foods like cow's milk and soy proteins are regularly found in milk if such proteins are part of the mother's diet. It is possible, but unproven, that milk antibodies can decrease the exposure of the infant's intestinal mucosa to foreign food proteins introduced during continued breast-feeding. Milk SIgA antibodies do not prevent intestinal colonization by microorganisms, against which the milk antibodies are directed. The SIgA antibodies are thought to exert protection primarily by preventing contact between the microorganisms and the mucosal membranes. In this manner, human milk blocks attachment of otitis media-causing strains of pneumococci and H. influenzae to retropharyngeal cells, possibly explaining why breast-feeding may prevent otitis media. Milk antibodies have anti-attachment capacity, but there is also low molecular weight material in the milk with this capacity. It probably consists of analogues to the oligosaccharide receptor for pneumococci on the retropharyngeal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Prostaglandin endoperoxide synthetase and the activation of benzo(a)pyrene to reactive metabolites in vivo in guinea pigs.

The role of prostaglandin endoperoxide synthetase in the in vivo activation of benzo(a)pyrene to reactive metabolites capable of interacting irreversibly with cellular macromolecules was studied in guinea pig liver, lung, kidney, spleen, small intestine, colon, and brain. DNA and protein covalent binding experiments were made after systemic administration of acetylsalicylic acid (200 mg/kg) followed by radiolabeled benzo(a)pyrene (4 microgram/kg). Results are compared with a control situation in which the prostaglandin endoperoxide synthetase inhibitor (acetylsalicylic acid) was not administered. No decrease in the level of DNA or protein benzo(a)pyrene-derived covalent binding was observed in any of the tissues studied.

Animals↗
PubMed1984

[In vivo testing of a peroral theophylline depot preparation with zero-order release].

A theophylline depot preparation on the basis of microcapsules (multiple-units principle) with an initial dose Di = 133 mg and a maintenance dose Dm = 217 mg (kof = 22.8 mg/h) is examined after single application to 7 volunteers in comparison with the aqueous solution. The relative bioavailability of the depot preparation is about 92%. Curve fitting shows that the liberation in vivo is clearly slower (kof = 15.6 mg/h) than in vitro. This could be of general importance for the development of peroral depot preparations. Furthermore the data suggest considerable absorption from the large intestine (colon). This is of interest for the conception of peroral preparations with exceptionally long action.

Biological Availability↗