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Biomedical subjects

F Stenbäck

Publications and source records attributed to F Stenbäck.

At least 73 records · Page 4Linked to original sources

Toxicity of plant material used as emergency food during famines in Finland.

The use of natural plants as emergency food in Finland and northern Europe has been described. The chemical contents of the commonly used "pettu" (pine bark), lichen (Cetraria islandica, Cladonia sp.) and water plants (Calla palustris, Menyathes trifoliata, Nymphea sp. and Nuphar luteum) are described and their toxicity after traditional pretreatments were studied in mice and rats. As 50% w/w mixture in normal food none of them were tolerated by mice. However, rats tolerated 25% of "pettu" and ash-treated C. islandica in 3-month tests rather well, although the body weight did not increase as much as in controls. At the end of experiment in the lichen group, the rats had proteinuria, and on autopsy some tubular changes were found probably due to high concentrations of lead in the lichen and kidneys. All the rhizomes studied contain toxic compounds, but they, particularly calla, would be nutritionally valuable. Boiling poorly eliminated their toxicity, but after baking at 180-200 degrees C the most toxic Nuphar and calla were well tolerated as 25% mixture during a 6-week test. It is possible that poorly selected or poorly pretreated emergency food have sometimes contributed to the death of famine victims in the olden times. Unqualified simplification of the traditional precautions for their treatment may be dangerous.

Animals↗

Fibrotic process and drug metabolism in alcoholic liver disease.

The effect of fibrosis on drug metabolism in alcoholic liver disease was evaluated in a comparison of the concentrations of serum aminoterminal propeptide of type III procollagen and basement membrane (BM; 7S domain of type IV collagen and laminin) antigens with in vitro (cytochrome P-450) and in vivo (antipyrine) drug metabolism in 67 alcoholics classified by liver histology. Alcoholics with intact or fatty liver had rapid or normal drug metabolism and normal collagen metabolism. Alcoholics with a fatty liver plus fibrosis or active cirrhosis had reduced drug metabolism and elevated levels of serum markers for collagen and BM metabolism. Alcoholics with inactive cirrhosis who had received therapy with enzyme inducers had a tendency toward normal drug and collagen metabolism parameters. Antipyrine metabolism, but not P-450 content, was related to the levels of serum type III collagen and BM markers. The fibrotic process, especially BM formation, creates a mechanical barrier that may prevent contact between blood and hepatocytes, thus delaying substrate availability.

Adult↗

Basement membranes in experimentally induced skin tumors.

Basement membrane changes in the epidermis and hair follicle apparatus resulting from topical 9,10-dimethylbenzanthracene applications were studied in mice, rats, and hamsters by light and electron microscopy and using antibodies to human collagen type IV and laminin. The basement membrane was distinct in epidermal hyperplasia, dysplasia, and papillomas, as well as around most of the keratoacanthomas and squamous cell carcinomas, which showed basement membrane irregularities, thickening, and reduplication in some areas. The invading edges of the squamous cell carcinomas with inflammatory infiltrates were devoid of laminin and collagen. Collagen IV and laminin-positive structures were observed around preserved follicular structures in rat: hair nevi and hair-follicle nevi, but partly absent around trichoepitheliomas and trichofolliculomas. Basal cell tumors were usually surrounded by a distinct basement membrane, which was lacking around some tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗

Occurrence of basement membranes in pigment cell tumors of the skin, relation to cell type and clinical behavior.

The occurrence, location and intensity of the basement membrane (BM) components collagen IV and laminin in benign and malignant pigment cell tumors was studied by immunohistochemical methods. The results seemed to establish the following findings: junctional nevi display varying continuity of BM; nevus cells in the dermis display more continuous and thicker BM superficially (associated with epithelial type nevus cells); superficial spreading melanoma displays discontinuity of BM, and nodular melanoma and metastatic melanoma display variable BM around tumor aggregates. The variable expression of BM components in this study showed an apparent relationship to tumor cell type and laminin and collagen IV production, partly related to clinical behaviour.

Basement Membrane↗

Insulin-mediated glucose metabolism is related to liver structure and microsomal function.

The role of the liver in glucose metabolism was investigated in 24 consecutive patients undergoing diagnostic liver biopsy by comparing hepatic morphometry and microsomal enzyme activity in vivo (antipyrine) with fasting blood glucose (BG) and immunoreactive insulin (IRI) levels and with the metabolic clearance rate of insulin and the insulin sensitivity index. The patients had elevated BG and IRI levels and reduced insulin-mediated glucose metabolism, insulin sensitivity index, and microsomal enzyme activity as compared with controls. The insulin metabolic clearance rate did not diverge among the groups. Patients with fatty liver had a high BG associated with a reduced glucose disposal rate, whereas fasting IRI did not diverge when compared with other liver patients. Glucose disposal rate was related to the amount of unaltered liver (r2 = 0.640; p less than 0.001) and antipyrine metabolism (r = 0.631; p less than 0.01) and inversely related to the amount of fat (r2 = 0.585; p less than 0.01). The findings demonstrate that insulin-mediated glucose metabolism is related to liver structure and microsomal function. Accumulation of fat in the liver seems to be a major factor associated with reduced insulin sensitivity and glucose tolerance.

Alanine Transaminase↗

Pathogenesis of dimethylnitrosamine-induced hepatocellular cancer in hamster liver and lack of enhancement by phenobarbital.

The early stages of dimethylnitrosamine (CAS: 62-75-9)-induced liver cancer and the effect of administration of phenobarbital (CAS: 50-06-6) after dimethylnitrosamine were studied in Syrian golden hamsters. A single ip injection of 6 mg dimethylnitrosamine/kg (body wt) induced hepatocellular altered foci by 6 months. Most foci were composed mainly of large clear glycogen-containing cells, while smaller numbers were formed by cells with abnormally acidophilic or basophilic cytoplasms. Biliary cysts, but not biliary neoplasms, also occurred. A few neoplastic (hyperplastic) nodules and hepatocellular carcinomas developed by 12 months. gamma-Glutamyltranspeptidase activity was not present in any of the hepatocellular lesions, but foci of all types, neoplastic nodules, and carcinomas were characterized by a lack of iron accumulation. Phenobarbital at 0.05% in the diet for up to 12 months did not increase the number of lesions of any type, indicating a lack of promoting effect under these conditions.

Animals↗

Sulphonylureas and glucose metabolism in phenobarbital induced rats.

The addition of phenobarbital (PB) to a sulphonylurea (SU) regimen may improve glycemic control in patients with non- insulin dependent diabetes mellitus (NIDDM, type II). Since SU reactions may be modified, we investigated glucose metabolism in rats with combined PB and SU treatment. Chlorpropamide (CHL) and glibenclamide (GB) were selected as SU drugs. The combination of PB to the CHL or GB regimens induced the drug metabolism enzymes excluding aminopyrine N-demethylase activity, which was enhanced by GB but not CHL. The CHL and GB treatments lowered blood glucose (BG) concentration and decreased hepatic glucose-6-phosphate phosphohydrolase (G6P hydrolase) activity and glycogen reserves in the rats. The concomitant administration of PB and the SUs decreased hepatic G6P hydrolase activity and glycogen content in the animals, whereas the BG level remained unaltered. The hepatic glycogen content was decreased more markedly in the CHL plus PB than in the CHL alone treated animals. The findings suggests that enzyme inducers modify the action of SU in rats. Hepatic drug and glucose metabolizing enzymes seems also to respond to distinct PB plus SU combinations in different ways.

Aminopyrine N-Demethylase↗

Short-term effects of danazol and medroxyprogesterone acetate on cytosol and nuclear estrogen and progestin receptors, 17 beta-hydroxysteroid dehydrogenase activity, histopathology, and ultrastructure of human endometrial adenocarcinoma.

We measured concentrations of cytosol and nuclear estrogen, as well as progestin receptors and activities of 17 beta-hydroxysteroid dehydrogenase (17-HSD), and examined histopathology and ultrastructure of endometrial carcinoma specimens taken before and after one-week danazol (200 mg, 3 times daily) or medroxyprogesterone acetate (MPA, 100 mg daily) treatments in 14 and 16 patients, respectively. A typical progestin effect, a significant increase in the activity of 17-HSD, was observed after both treatments. The post-therapy 17-HSD activities correlated significantly with the pretreatment cytosol progestin receptor concentrations in both treatment groups. Both MPA and danazol decreased the proliferative activity and increased the secretory activity of the malignant epithelial endometrial cells. These biochemical and morphological results support the concept that danazol has progestin-like actions on the human endometrium, and might therefore be an alternative for hormonal treatment of endometrial carcinoma.

17-Hydroxysteroid Dehydrogenases↗

Basement membrane structures in tumors of the ovary.

The location and amount of the basement membrane (BM) components collagen IV and laminin were studied in ovarian epithelial, sex cord-stromal and germ cell tumors. BM structures were found in the epithelial stromal interface of benign surface epithelial tumors and, though discontinuous, around well-differentiated tumor islets, being less well developed in invasive undifferentiated neoplasms. The stromal components in Müllerian mixed tumors had less distinct BM structures, a finding useful for the classification of these neoplasms. Thecomas and fibromas had scanty collagen IV and laminin; granulosa cell tumors contained large amounts of BM material. A fine diffuse BM-positive pattern occurred in dysgerminomas and endodermal sinus tumors; BM structures in cystic teratomas were distinct. Collagen IV and laminin were well-developed in benign and slow-growing tumors with epithelial components and in their metastases, but less distinct in stromal tumors and highly malignant undifferentiated tumors, showing the usefulness of this method for the clinical and biological classification of such tumors.

Adenocarcinoma↗

Cell structure and function and response to chemotherapy in tumors heterotransplanted into the subrenal capsule of mice and rats.

Specimens from 16 freshly biopsied human tumors, two mammary adenocarcinomas, ten ovarian adenocarcinomas, two squamous cell carcinomas, one malignant histiocytoma and one chondrosarcoma of the bone, two human ovarian adenocarcinomas established by transplantation into nude mice and two adenocarcinomas induced in rat mammary gland were transplanted under the renal capsule of 510 normal immunocompetent mice and 180 rats and the effects of chemotherapy were evaluated. The results showed successful transplantation of all types of tumors in both animal species. Morphological analysis revealed preserved glandular structures with surface microvilli, mucin and CEA production and partially preserved basement membranes. Treatment with cyclophosphamide, vinblastine, adriamycin and cisplatin caused cell shrinkage, degradation and partial or total disappearance of the tumor cells. Vascularization was distinct in all specimens. A cellular infiltrate was found frequently but not consistently. A common end stage was a fibrotic scar with no cellular activity, occasionally giving a misleading impression of a growing tumor on gross observation. The results were obtained rapidly and suggest that the subrenal capsule assay would be useful for evaluating the sensitivity of human tumors to therapeutic manipulation, but needs supplementary histological examination.

Animals↗

Basement membrane laminin and type IV collagen in endometrial adenocarcinoma: relation to differentiation and treatment.

Changes in basement membrane (BM) structure were studied in functioning and hyperplastic endometrium, in adenocarcinomas with various degrees of differentiation and in progesterone-treated adenocarcinomas using electron microscopy and immunohistochemical staining with antibodies against human type IV collagen and laminin. These BM components were distinctly visualized as narrow, continuous bands beneath the epithelium and around the endometrial glands in functioning, atrophic and hyperplastic endometrium. In well-differentiated endometrial carcinomas there was mostly a continuous BM, though occasional disruptions were seen. The undifferentiated tumors, on the other hand, were characterized by the absence of a continuous BM structure, although irregular patches of BM material were found within the neoplasm. Hormonal treatment caused the reappearance of the BM structures. According to these results, the visualization of the BMs in the endometrium not only increases our understanding of tumor behavior, but can also be used as an aid for the classification and treatment of endometrial neoplasms.

Adenocarcinoma↗

Basement membranes in progressing intraepithelial cervical neoplasia. An ultrastructural and immunohistochemical study with antibodies against human type IV collagen and laminin.

The occurrence and location of basement membranes (BM) and their constituents were studied in benign, inflammatory, dysplastic and malignant conditions of the uterine cervix by light and electron microscopy and by immunohistochemical analysis with antibodies against human laminin and type IV collagen. The normal squamous epithelium showed a thin subepithelial BM band, which was preserved in dysplasia. Severe inflammatory conditions affecting the epithelium caused disruption and fragmentation of the BM. Well-differentiated carcinomas were frequently surrounded by a BM, whereas anaplastic tumors had a disrupted and fragmented BM, and similar material was also seen in the tumor tissue itself. Thus the presence of a continuous BM seems to be only a relative criterion in distinguishing between benign and malignant conditions.

Basement Membrane↗

Medroxyprogesterone acetate and phenobarbital induce NADPH producing enzyme activities in rats with a chemical liver injury.

The administration of medroxyprogesterone acetate (MPA) and phenobarbital (PB) improves liver function in rats with liver damage. This was seen here as increased aryl hydrocarbon hydroxylase (AHH) activity after therapy with MPA or PB in rats with a chemical liver injury, produced by dimethylnitrosamine (DMN). Hepatic glucose-6-phosphatase (G6Pase) activity, an index of glucose metabolism was also normalized in the MPA treated rats. The present study further shows that MPA induced hepatic malic enzyme (ME) and isocitrate dehydrogenase (ICDH) activities and PB enhanced glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and ME activities in the DMN pretreated rats. This suggests that MPA and PB enhanced the capacity of altered liver tissue to generate NADPH, a cofactor in the monooxygenase system, which may, in part, enhance the restoration of drug hydroxylation in the rats. Since G6PDH, 6PGDH and ME participate in glucose metabolism, the finding that the compounds influenced these enzymes in distinct ways, may explain the different effects of MPA and PB on the restoration of glucose metabolism.

Animals↗

Morphology of transplanted tumours and drug induced regression in the subrenal capsule assay (SRCA) of mice and rats.

Specimens from freshly biopsied human mammary and ovarian tumours and DMBA-induced rat mammary tumours were transplanted under the renal capsule of normal, immunocompetent mice and rats. The growth of the tumour and the effects of chemotherapy to the host animals were evaluated by measuring the growth of the implanted tumour specimens. Morphological analysis of the tumours showed preserved histological structures and cellular function, as evidenced by the basement membrane component production seen using immunohistochemical stains and by the surface specialized structures, cell-to-cell contact and secretory activity observed in ultrastructural studies. Treatments with different types of drugs yielded tangible results within 6 days of transplantation, showing lymphoid infiltration and scar formation, but preserved vascular structures. The results suggest that tumours subjected to subrenal capsule assay retain their structure and function when transplanted, thus enabling the evaluation of their sensitivity to therapeutic manipulation.

Animals↗