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F Stenbäck

Publications and source records attributed to F Stenbäck.

At least 19 recordsLinked to original sources
PubMed1995

Immunohistochemical study of type I collagen and type I pN-collagen in benign and malignant ovarian neoplasms.

BACKGROUND: Type I collagen is a major constituent of the interstitial connective tissue. Although ovarian carcinoma is known to induce the expression of type I collagen in the peritoneal cavity, the distribution and metabolic activity of this collagen in ovarian tumor tissue are not known. METHODS: The distributions and staining intensities of different molecular forms of type I collagen in ovarian neoplasms were studied immunohistochemically with antibodies to the aminoterminal propeptide of type I procollagen (PINP) and the cross-linked carboxyterminal telopeptide of type I collagen (ICTP), reflecting the presence of newly synthesized and old, cross-linked type I collagen, respectively. RESULTS: A regular pattern of moderately staining, relatively uniform fibers was observed in the stroma of benign serous and mucinous cystadenomas, indicating limited participation in tumor growth. The staining was accentuated subepithelially in borderline epithelial neoplasms and in well differentiated cystadenocarcinomas, suggesting induction of the stromal collagen synthesis by the tumor cells. Fewer degraded collagen fibers were found in moderately differentiated carcinomas, most likely because of enzymatic degradation of the stroma surrounding the neoplasms during tumor spread. Strongly staining, irregular collagen fibers occurred closely around islets of tumor cells in undifferentiated malignant neoplasms and in metastases of ovarian carcinomas; also, intracellular staining was present in part of the malignant cells. In most cases, the staining reactions obtained with the two different antibodies were similar, probably indicating rapid processing of the newly synthesized type I collagen (indicated by PINP) to a maturely cross-linked form (indicated by ICTP). CONCLUSIONS: Synthetic and degradative processes are typical of the collagenous matrix in malignant ovarian tumors. Aberrant expression of type I collagen may occur in anaplastic ovarian carcinomas.

Adult↗
PubMed1995

The role of CYP enzymes in cocaine-induced liver damage.

Cocaine is hepatotoxic in several species, including man. A high dose of cocaine produces metabolism-dependent, mainly pericentral, liver damage. At 24 h after a single dose of cocaine, mouse hepatic P450 content decreases but CYP2A activities; coumarin 7-hydroxylase and testosterone 15 alpha-hydroxylase increase concomitant with prominent diffuse cell necrosis. Repeated administration of cocaine for up to 5 days decreases CYP1A1/2, 2A4/5, 2Cx, and 2E1 related enzymatic activities. However, after five doses of cocaine, CYP2B10 increases in conjunction with the healing process. In the acute phase, the increased CYP2A activities do not participate in cocaine bioactivation. CYP3A enzymes are principally responsible for the cocaine N-demethylation in human and mouse liver microsomes. The hepatic metabolic CYP enzyme profile will change during prolonged cocaine intake, this being accompanied by altered cell morphology. Possible connections to cocaine toxicity in man are discussed.

Animals↗
PubMed1995

Cell proliferation markers and growth factors in ovarian cancer.

Results from our studies on the clinical applicability of proliferation markers and growth factors in the histopathological assessment of malignancy and prognosis of ovarian neoplasms are presented. Bromodeoxyuridine incorporation, Ki 67 antigen visualization and proliferation cell nuclear antigen expression indicated location and extent of cell proliferation, though not uniformly as compared to flow cytometry and mitotic counting. Clinicopathological correlations of the occurrence of programmed cell death, apoptosis, as indicated by morphology gave inconclusive results, as did analysis of Bcl-2 expression. Increased visualization of p53 protein was associated with increased degree of malignancy but was inconsistent in individual specimens. Growth factor expression, in particular transforming growth factor beta staining intensity, gave additional information on cell behaviour as did vascular endothelial growth factor distribution on vascularization and vessel neoformation when compared to platelet derived growth factor expression, useful in isolated specimens, and to basic fibroblast growth factor expression. The markers presented are indispensible in certain tumour types and give additional information improving our understanding of ovarian neoplasms and tumour classification in general but are mostly not yet reliable enough for clinically applicable conclusions of individual patients.

Apoptosis↗
PubMed1994

Modification of hepatic cytochrome P450 profile by cocaine-induced hepatotoxicity in DBA/2 mouse.

Previous studies in our laboratory have shown that a hepatotoxic dose of cocaine increases coumarin 7-hydroxylase activity in male DBA/2 mouse liver. In the present study, the dose- and time-dependent responses of the hepatic CYP2A4/5 complex to cocaine-induced liver damage were studied. Cocaine increased CYP2A4/5 levels in a dose-dependent manner. The maximal increases in coumarin 7-hydroxylase activity (4-fold), microsomal CYP2A4/5 content (3-fold) and steady-state mRNA levels (10-fold) were observed at 24 h after administration of a single dose of 60 mg/kg cocaine coinciding with morphologically detectable diffuse liver damage, while the total P450 content was not changed. 3 and 5 days after the daily administration of cocaine severe, mainly pericentral (zone III of Rappaport), liver damage was apparent in parallel with a clear decline in CYP2A4/5 mRNA, protein content and coumarin 7-hydroxylase activity. After 5 days of treatment, CYP2A5 still remained at a very low level but an induction in CYP2B10 protein and related pentoxyresorufin O-dealkylase activity was observed. No marked changes in microsomal CYP2Cx and CYP1A1/2 contents or associated activities were observed. Dimethylnitrosamine N-demethylase activity, a marker for CYP2E1, decreased in parallel with increased cocaine dose and time and the severity of liver damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The cerium-induced liver injury and oxidative drug metabolism in DBA/2 and C57BL/6 mice.

The influence of the known hepatotoxic agent, cerium (Ce) on the activity of liver microsomal monoxygenases, especially coumarin 7-hydroxylase (COH) was investigated in two inbred strains of male mice, DBA/2N and C57BL/6N. Ce was injected intravenously in three doses (0.5, 1.0 and 2.0 mg/kg body wt) and the animals were killed 24 or 72 h later. On the basis of histological assessment of the liver, C57BL/6N mice are apparently more resistant to the hepatotoxic effect of Ce. At 24 h, COH activity was increased in a dose-dependent manner in DBA/2 animals, whereas no change was seen in C57BL/6N animals. A significant increase in all other enzymes studied, cytochrome P-450 (P450), ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase, was seen in DBA/2 mice injected with the highest dose of Ce. At 72 h Ce increased CON activity, as well as other enzymes, in C57BL/6N mice in a dose-dependent manner, whereas in DBA/2 mice the increase was only seen after the two lower doses, the highest dose causing severe morphological changes in the liver structure and a clear decrease in COH and other activities. The distribution studies with Ce-141 showed that C57BL/6N livers contained more Ce than DBA/2 livers after the highest dose.

Animals↗
PubMed1991

Immunohistochemical localization of syndecan in mouse skin tumors induced by UV irradiation. Loss of expression associated with malignant transformation.

Immunoreactivity for syndecan, a cell surface proteoglycan, which binds extracellular matrix molecules and growth factors, was studied in hairless (hr/hr) mice exposed to UV-A and UV-B irradiation. Positive staining was observed at the surface of normal epidermal cells as well as in the dermal abortive hair follicle cysts characteristic to this mouse strain. Early reaction to UV-irradiation showing hyperplastic epidermis with slight cellular atypia showed also positive, although reduced, staining of epidermal cell surfaces. Specimens with severe dysplasia showed weak staining in the granular cell layer, whereas the basal cell layer was negative. In papillomas and keratoacanthomas, immunoreactivity for syndecan was observed in the benign hyperplastic epidermal cells as well as in the proliferating epidermal cells of the horn cysts. Malignant transformation of epithelium, expressed as the formation of early invasive and anaplastic squamous cell carcinomas, was uniformly associated with loss of syndecan staining. These results are consistent with the previous findings of reduced expression of syndecan associated with malignant transformation of cultured epithelial cells, but also suggest an important role for syndecan in the maintenance of normal tissue architecture and differentiation pattern of the skin.

Animals↗
PubMed1991

Time dependent effects of medroxyprogesterone acetate on hepatic ultrastructure in rats.

The present study demonstrates that MPA treatment may alter liver ultrastructure in rats. This was seen as a slight cytoplasmic vacuolization in light microscopy. In electron microscopy the most striking findings were the increase in the size of hepatocytes, the volume of smooth endoplasmic reticulum (SER) and the number of mitochondria. Minor changes in mitochondrial size and structure, and SER outline were also obtained. The amount of rough endoplasmic reticulum was decreased and bleb formation was common. The effect of MPA on liver ultrastructure was time-dependent. The main changes were found in rats receiving MPA daily for seven days. Most of the observed changes disappeared within 17 days after the cessation of the regimen. MPA induced alterations in liver morphology may partly be due to induction phenomenon although the hormonal property of MPA also may play some etiological role.

Animals↗
PubMed1990

UVA irradiation increases the incidence of epithelial tumors in UVB-irradiated hairless mice.

The interaction of UVA and UVB radiation in tumorigenesis in lightly pigmented hairless hr/hr mice was studied. Seventy-eight tumors (5 sarcomas, 4 squamocellular carcinomas, 1 carcinosarcoma, 63 papillomas, 2 keratoacanthomas, 1 fibrous polyp and 2 adnexal tumors) occurred in 12 mice receiving high UVA (582 J/cm2) plus high UVB(EE) (erythemally effective) (1.0 J/cm2) doses, whereas only 28 tumors (6 sarcomas, 1 carcinosarcoma, 20 papillomas and 1 keratoacanthoma) were found in 12 mice receiving low UVA (71 J/cm2) plus high UVB(EE) (0.8 J/cm2) doses. In 12 mice receiving low doses of both UVA and UVB(EE), only 2 tumors (sarcomas) occurred. The predominantly epidermal tumor response in the high UVA-high UVB group suggests that UVA irradiation increases the number of epithelial tumors when given together with carcinogenic doses of UVB radiation.

Animals↗
PubMed1989

Collagen type III in ovarian tumors. Histological, immunohistochemical and ultrastructural findings.

The occurrence and location of interstitial collagen amino-terminal propeptide type III procollagen (PIIIP) and fibronectin was studied in 123 ovarian tumors of different types and related to the histological type and clinical behavior of the neoplasm. The purpose was to further our understanding of the development and classification of these tumors and to determine characteristics of diagnostic and prognostic significance. PIIIP-positive fibers were common in the stroma of all types of neoplasms, condensation of fibres occurred at the epithelial-stromal interface of surface epithelial tumors, and disintegration and discontinuation of fibers around invasive epithelial islets and in stroma of undifferentiated epithelial carcinomas. The PIIIP-positive stromal meshwork surrounded individual cells in thecomas, while it was virtually absent in diffuse granulosa cell tumors and distinctly developed in malignant stromal neoplasms, being seen mainly around epithelial islets in mixed mesodermal tumors.

Collagen↗
PubMed1989

Viral agents in two-stage cervical carcinogenesis: an experimental study in mice.

The role of chemical and viral agents in the development of cervical cancer in mice was studied by repeated carcinogen applications, repeated intravaginal instillations of HSV type II virus, and single carcinogen application as initiating agent followed by repeated instillations of virus as promoter. In all the animals studied, repeated applications of 9,10-dimethylbenzanthracene (DMBA) induced dysplastic conditions of the cervix and vagina, mild, moderate, and severe, as well as a large number of invasive squamous cell carcinomas. DMBA alone as initiating agent did not induce tumors or marked dysplasia; when followed by repeated applications of HSV2 virus only mild dysplastic lesions occurred. Repeated applications of HSV2 alone produced inflammatory changes of the cervix and vagina. It is concluded that repeated intravaginal instillation of HSV2 virus as done in this study does not induce cervical cancer or its precursors, and in a two-stage system is only weakly a promoter of carcinogen-induced latent tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Collagen type III formation and distribution in the uterus: effects of hormones and neoplasm development.

The amount and location of interstitial collagen in the endometrial stroma and the uterine wall as well as the effects of hormonal stimulation and neoplastic transformation were studied by light and electron microscopy and immunohistochemical methods using specific antibodies to aminoterminal propeptide type III procollagen (PIIIP). The results showed collagen deposition in atrophic mucosae and in the proliferative endometrium with a decrease in the secretory endometrium. In cystic glandular hyperplasia and adenomatous hyperplasia, PIIIP deposits were abundant. In well-differentiated endometrial adenocarcinoma, dense collagen type III aggregates were found in subepithelial positions, disintegrating with advancing malignancy and decreasing in hormonal-treated morphologically well-differentiated neoplasms. The even distribution of PIIIP around muscle cells and bundles in leiomyomas was disturbed and partly absent in leiomyosarcomas, and surrounded epithelial islets in mixed mesodermal tumors.

Adenocarcinoma↗
PubMed1989

Reversibility of rat liver cirrhosis by medroxyprogesterone acetate.

The possible effects of a synthetic progesterone, medroxyprogesterone acetate (MPA), on carbon tetrachloride/phenobarbital (CCl4/PB)-induced rat liver injury were studied by morphological methods. CCl4/PB-treated rats showed extensive liver fibrosis consisting of procollagen type III aminoterminal propeptide-positive strands and fibres with concomitant extensive basement membrane deposits and fibronectin synthesis. MPA treatment after CCl4/PB-induced liver damage reduced alterations in cytoplasmic organelles, inflammation and hemorrhages and reversed the fibrosis, mostly around individual liver cells, possibly due to the normalization of cellular structure and function with a decrease in fibronectin deposits.

Animals↗
PubMed1989

Morphological, immunohistochemical and ultrastructural changes in dimethylnitrosamine [correction of dimenthylnitrosamine] induced liver injury. Effect of malotilate.

Dimethylnitrosamine (DMN) induced liver injury in rats with cell necrosis, inflammation, hemorrhages, increased collagen type III synthesis and basement membrane component laminin and collagen IV localization in perisinusoidal sites. Malotilate ingestion during DMN treatment abolished inflammation and decreased interstitial collagen deposits and vascularization. It affected clearly less DMN-caused hemorrhage. When malotilate treatment was started subsequently to development of DMN-injury, it also caused decrease in inflammation, though less, as well as in collagen III, BM and fibronectin deposits. We suggest that the mode of the malotilate effect on reducing the DMN-induced fibrosis of the liver is via inhibiting the inflammation, decreased fibronectin deposition possibly also playing a role.

Animals↗
PubMed1989

[Arctic medicine].

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Arctic Regions↗
PubMed1989

Preventive effect of malotilate on dimethylnitrosamine-induced liver fibrosis in the rat.

Dimethylnitrosamine-induced liver damage, which leads to hepatic failure and death of the animal, was prevented by treatment with malotilate. The accumulation of collagen and the morphologic changes caused by dimethylnitrosamine, such as inflammatory cell accumulation and fibrosis, were also prevented by this drug. Malotilate drastically reduced the increases in the amount of type I procollagen alpha 2-chain mRNA and activities of the enzymes prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase, which are early events in liver fibrosis preceding the deposition of collagen. Even when started 14 days after dimethylnitrosamine induction, malotilate treatment was able to reduce liver damage. We suggest that the effect of malotilate is a result of the inhibition of inflammation.

Animals↗
PubMed1988

Effect of lifetime administration of dimethylaminoethanol on longevity, aging changes, and cryptogenic neoplasms in C3H mice.

The effects of lifetime treatment with dimethylaminoethanol on longevity and cryptogenic neoplasm formation were studied in females of two mouse sub-lines, the C3H/HeN which carries a germinal mammary tumor provirus and the C3H/HeJ(+) which also carries the exogenous mammary tumor virus. Administration in the drinking water of 10 mM dimethylaminoethanol to the C3H/HeN mice or 15 mM to the C3H/HeJ(+) mice did not result in significant differences between treated and untreated groups in average survival. No changes in age-related organ structure or morphology were observed with dimethylaminoethanol treatment, except for an apparent decrease in the amount of lipofuscin in the liver judged in histological sections. Among untreated C3H/HeJ(+) females, 89% developed neoplasms of the mammary gland, ovary, liver, lung and reticuloendothelial system, while the incidence was 88% in the treated mice. In C3H/HeN females, neoplasms of the mammary gland, ovary, liver, lung and lymphatic system occurred in 57% and in 60% of treated mice. Also, there was no statistically significant difference between control and treated animals in the age of onset or the type of specific neoplasms. Dimethylaminoethanol did not induce any neoplasms.

Aging↗
PubMed1988

Serum basement membrane and type III procollagen-related antigens in primary biliary cirrhosis.

A characteristic histological lesion in early primary biliary cirrhosis (PBC) is disruption of the basement membrane around small bile ducts, which at later stages of the disease is followed by fibrosis. To assess the significance of serum basement membrane- and type III procollagen-related antigens in reflecting such processes, we have measured radioimmunologically the concentrations of serum laminin, type IV collagen and the aminoterminal propeptide of type III procollagen in 22 patients with PBC, classified into four stages according to liver histology. The mean laminin concentration in PBC patients was twice that of the healthy control subjects. Increased concentrations were observed in all patients with stage III or IV of the disease and also in 60% (6/10) of the patients, with early stages (I or II). Elevated serum type IV collagen concentrations were found only in four patients, all in the late, fibrotic stages of the disease. The basement membrane protein changes in serum were in accordance with immunohistochemical findings obtained with the antibodies against these proteins. Neither of these serum parameters emerged, however, as a significant predictive factor for survival. The changes in serum aminoterminal propeptide of type III procollagen resembled those in laminin P1. Moreover, the propeptide was also significant as a predictive factor for survival.

Adult↗