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F Stenbäck

Publications and source records attributed to F Stenbäck.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

[Arctic medicine].

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Arctic Regions↗

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↗

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↗

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↗

Tamoxifen and natural progesterone as supplements to low-dose postmenopausal estrogen therapy.

Postmenopausal women received 1 mg estrone sulfate a day for 3 weeks in 12 sequences separated by a 7-day interval without medication and every second time by a 10-day treatment with natural progesterone, 100 mg 2 times daily (n = 16), or tamoxifen, 10 mg 2 times daily (n = 17). Both treatments alleviated climacteric symptoms, maturated the vaginal epithelium, and decreased follicle-stimulating hormone, luteinizing hormone, and prolactin concentrations while lipid metabolism remained unaltered. In the estrogen-progesterone group 4 women (25%) were persistently amenorrheic, 12 (75%) experienced 1-5 bleedings per year, and 4 women had proliferative endometrium after treatments. In the estrogen-tamoxifen group 11 women (65%) were amenorrheic, 6 (35%) had 1-4 bleedings per year, and 5 had proliferative endometrium. With the present treatment schedules, tamoxifen was more effective than natural progesterone in inhibiting estrogen stimulation of postmenopausal endometrium.

Alanine Transaminase↗

Preventive effect of malotilate on carbon tetrachloride-induced liver damage and collagen accumulation in the rat.

Malotilate is a new drug suggested for use in chronic liver diseases. It is shown here to prevent liver damage caused by CCl4. The concomitant administration of malotilate with CCl4 significantly decreased hydroxyproline accumulation in the liver, liver prolyl 4-hydroxylase and liver and serum galactosylhydroxylysyl glucosyltransferase activities. However, it had no effect on the daily urinary hydroxyproline excretion or the hydroxyproline content of the skin, liver or lungs in normal young growing rats. It also had no specific inhibitory effect on hydroxyproline synthesis or secretion in fibroblast cultures, and did not affect the amount of procollagen-alpha 1(I)-specific mRNAs in these cultures. Thus it seems to have no direct inhibitory effect on collagen metabolism. In addition to inhibition of liver collagen accumulation, malotilate was also able to prevent the development of morphological changes in the liver such as focal necrosis, fatty infiltration and inflammatory changes. It also normalized almost completely the standard liver-function tests. It is possible that malotilate may prevent excessive collagen deposition by inhibiting the inflammation caused by CCl4-induced liver damage.

Animals↗

Hydroxylamine effects on cryptogenic neoplasm development in C3H mice.

The effect of administration of hydroxylamine (HA) to male and female mice was studied because of reports suggesting an anticarcinogenic effect and an enhancement of lifespan. In this study, two C3H sublines were used: the C3H/HeN which carries a germinal provirus of the mouse mammary tumor virus and the C3H/HeJ(+) which also carries the milk-transmitted exogenous virus. Lifetime administration of 10 mM HA in the drinking water resulted in a decrease in mammary neoplasm incidence in female C3H/HeN mice, but not in female C3H/HeJ(+) mice. Ovarian neoplasms and cysts were common in all groups, indicating ovarian dysfunction, but these were not affected by treatment. The incidences of other cryptogenic neoplasms found in controls in significant numbers, i.e. liver carcinomas, lymphomas, lung adenomas and adrenal cortex tumors were only marginally affected by the treatment. However, an increased incidence of vascular neoplasms of the spleen in hydroxylamine-treated female C3H/HeN mice and vascular neoplasms of the lymph nodes in hydroxylamine-treated male C3H/HeJ(+) mice indicated a subline-related action on the reticuloendothelial system. The survival of control mice was 35-58% at 2 years and this was not increased in either subline by hydroxylamine, which is interpreted to indicate that this antiioxidant does not increase lifespan of animals under conditions of maintenance that are adequate for good survival.

Animals↗

Retinyl acetate effects on the life span and the incidence of cryptogenic neoplasms in C3H mice.

The effect of feeding 0.02% retinyl acetate on the development of cryptogenic neoplasms and the life span of C3H/HeJ (+) mice of both sexes was studied. The survival at 105 weeks was 58% in untreated males and 28% in untreated females vs. 39% in treated males and 14% in treated females. The average weight in treated groups was also 10-15% lower. The incidence (percent) of neoplasm-bearing animals and total neoplasms was 87% and 57, respectively, in female controls vs. 93% and 55 in treated females. In male controls, these values were 57% and 39 compared with 50% and 38 in treated males. In treated animals, there was no reduction in the most common neoplasms, that is, neoplasms of the mammary gland and liver. The numbers of ovarian neoplasms and lung adenomas were slightly lower. Therefore, retinyl acetate exerted, at best, only a slight inhibitory effect on development of some types of cryptogenic neoplasms in mice.

Animals↗

Hepatic drug metabolism and the activities of NADPH generating enzymes and glucose-6-phosphatase in phenobarbital treated genetically obese (ob/ob) mice.

We aim to evaluate the effects of phenobarbital (PB) on the liver drug metabolism, NADPH production capacity and terminal gluconeogenic enzyme, glucose-6-phosphatase (G6Pase) activity in the diabetic state associated with genetic obesity in mice. The results showed that PB treatment increased the amount of liver total cytochrome P450 (cytP450), a drug metabolizing monooxygenase enzyme in genetically obese, hyperglycemic (ob/ob) mice 6-fold and the total activities of other monooxygenase enzymes NADPH cytP450 reductase and 7-ethoxyresorufin O-deethylase (ERDE) 2- and 6.5-fold, respectively. In addition, the regimen increased the liver total activities of two NADPH generating enzymes, 6-phosphogluconate dehydrogenase (6PGDH) and malic enzyme (ME) in obese mice suggesting that the regimen enhanced liver NADPH production capacity in the animals. The data further showed that PB treatment decreased the high hepatic G6Pase activity in obese mice. Both enhanced NADPH generating enzyme activities and lowered G6Pase activity may suppress hepatic glucose output. Since NADPH is required for drug oxidation reactions as a reducing cofactor, high NADPH generating capacity may facilitate liver drug metabolism in vivo. Although the diabetic state in obese mice differs somewhat from that seen in non-insulin dependent diabetic subjects (NIDDs), these findings provide some knowledge about the possible biochemical mechanisms whereby PB treatment normalizes drug metabolism and glycemic control in NIDDs, as has been noted in previous studies.

Animals↗

Hepatic mixed function oxidase system and enzymatic glucose metabolism in rats.

Therapy with enzyme inducing drugs may improve glycemic control in patients with non-insulin-dependent diabetes mellitus. We evaluated the role of a mixed function oxidase system on glucose metabolism with an animal model. Rats were treated with an inducer (phenobarbital), an inhibitor (cimetidine) and a hepatotoxin (carbon tetrachloride) for a week to cause alterations in the liver. The mixed function oxidase system was assayed by determination of the cytochrome P-450 content and NADPH cytochrome c reductase in liver. Carbohydrate metabolism was evaluated by determining blood glucose, enzymes associated with glucose phosphorylation in the liver (glucokinase, hexokinase), glucose storage as glycogen and enzymatic delivery, glucose-6-phosphatase, and peripheral tissue by determining phosphorylating enzyme (hexokinase) and a key glycolytic enzyme (pyruvate kinase) and glycogen content in muscles. The therapy with the inducer enhanced glucose utilization in liver and storage in muscles. The inhibitor decreased the mixed function oxidase system, reduced glucose phosphorylating, but not gluconeogenetic enzymes, in the liver and increased glycolysis in muscles. Carbon tetrachloride, a hepatotoxin, impaired mixed function oxidase, glucose phosphorylating and delivering enzyme activity in liver, reduced blood glucose and caused glycogen accumulation in muscles. The function of liver microsomal enzyme system seems to be closely related to enzymatic glucose metabolism in the liver and muscles.

Animals↗

The carcinogenic properties of topical PUVA. A lifelong study in mice.

The tumorigenic properties of topical methoxsalen (8-MOP) and trioxsalen (TMP) plus ultraviolet light A (UVA) were studied in NMRI female mice. The animals were treated three times weekly for 9 months, and followed up for 18 months. Acetonic solutions of TMP (0.1 mg in 0.2 ml) and 8-MOP (0.6 mg in 0.2 ml) were applied to the shaved back skin of the mice and irradiated with UVA. The doses needed to elicit equivalent phototoxic effects were 0.29 J/cm2 in the TMP group and 1.09 J/cm2 in the 8-MOP group. Papillomas, keratoacanthomas, and squamous cell carcinomas developed in the 8-MOP group only, and the first tumor was seen at 10 months after the beginning of the study. The results suggest that the carcinogenicity of these two modes of photochemotherapy may differ.

Animals↗