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Biomedical subjects

A Fuchs

Publications and source records attributed to A Fuchs.

At least 145 records · Page 8Linked to original sources

Chemical inducers of differentiation, dimethylsulfoxide, butyric acid, and dimethylthiourea, induce selective ultrastructural patterns in B16 melanoma cells.

The morphology and ultrastructure of B16 melanoma cells was examined after treatment of the cells with the chemical inducers of differentiation dimethylsulfoxide (DMSO), butyric acid, and dimethylthiourea (DMTU). The treated B16 melanoma cells seemed to be enlarged and more flattened, and to possess dendrite-like structures as revealed by scanning electron microscopy. The main ultrastructural features, depicted by transmission electron microscopy in DMSO-treated B16 cells were: a marked increase in melanin granules, migration of the melanin granules to the dendrites, and appearance of melanosome aggregates. Butyric acid did not induce melanin biosynthesis; however, it stimulated rough endoplasmic reticulum (RER) formation all over the cytoplasm. The DMTU-treated cells also showed a well developed RER accompanied by early stages of melanosomes and melanin granules. The increase in the endoplasmic reticulum was also reflected by enhancement of NADPH cytochrome c reductase activity, an enzymatic marker of the endoplasmic reticulum. The mitochondria in the DMTU-treated cells were swollen with disrupted cristae. The results indicate that DMSO, butyric acid, and DMTU induce different ultrastructural patterns in B16 melanoma cells. These findings correlate with the biochemical alterations induced in melanoma cells by these agents.

Animals↗

Altered light/dark activity difference with aging in two rat strains.

The daily activity rhythm of adult and senescent male rats of two different strains (Iva:SDIV and Emd:Wi-AF/Han) was evaluated over several days with a capacitance-induction motility monitor. The Iva:SDIV rats were 6 to 9 or 29 to 32 months old and the Emd:Wi-AF/Han rats were 3 to 5, 16 to 18, or 31 to 39 months old at the time of testing. The rats were maintained in individual cages under a 12:12 hr light/dark regimen prior to and during this experiment. Senescent rats were much less active during the dark phase and somewhat more active during the light phase than same-strain young adult rats. This pattern of results was found for measurement of gross and fine movements combined (high sensitivity setting) and to a lesser extent for gross movements alone (low sensitivity setting). Furthermore, in the senescent rats the absolute magnitude of the light/dark activity difference was found to be positively related to the subsequent survival time.

Aging↗

Long-term treatment of tumor-operated mice with high doses of alpha-difluoromethylornithine.

Mice inoculated subcutaneously with a mammary adenocarcinoma M3cell suspension and submitted 10 to 15 days later to the surgical removal of primary tumors have been chosen in our laboratory as the experimental model to study the effect of several drugs on metastasis spreading. A 90-day treatment of tumor-operated mice with high doses of alpha-difluoromethylornithine showed, in addition to a marked decrease of lung metastases, several side effects including a loss of body weight, a delay of surgical wound healing and a reduced number of megakaryocytes in bone marrow. The measurement of ceruloplasmin in serum has indicated that treated animals contained increased levels of this oxidase activity in spite of the polyamine depletion caused by alpha-difluoromethylornithine. These results rule out a direct correlation between ceruloplasmin activity and polyamine concentration.

Adenocarcinoma↗

Avoidance acquisition in adult and senescent rats.

Male rats aged 6, 19, or 33 months were trained successively in one- and two-way avoidance tasks. The one-way avoidance test consisted of up to 30 trials given in a single session with the conditional stimulus (CS; 14-kHz tone) presented for either 3 s or for 10 s in separate groups. Senescent rats performed poorest, middle-aged rats intermediately, and young adult rats best. Failure of the longer CS to yield better acquisition than the short CS in the senescent group suggested that the age-related deficit probably did not result from slower responding. In subsequent shuttle box training there was no appreciable age difference in achieving the learning criterion. A compound visual-auditory CS was used, and in further evaluation of well-trained rats it was found that the auditory component was much more effective than the visual component in eliciting avoidance. However, this differential effect of the two stimuli was much weaker in the senescent group than in the young adult group. Nonetheless, these same senescent and adult rats readily learned to make avoidance responses using only the auditory CS, demonstrating that this was an effective stimulus for all age groups.

Aging↗

Pharmacodynamic profile of the selective beta 1-adrenoceptor antagonist bisoprolol.

The pharmacodynamic activity of (+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropylamino-2- propranol- hemifumarate (bisoprolol, EMD 33 512) has been investigated under in vitro and in vivo conditions. Bisoprolol was found to be an effective beta-adrenoceptor antagonist, the pA2 values determined against isoprenaline in guinea pig atria and tracheal muscle being 7.45 and 6.41, respectively. Thus, the selectivity ratio of bisoprolol in favour of beta 1-adrenoceptors is 11. Inhibition of the isoprenaline-induced tachycardia in guinea pigs indicated a long duration of action for bisoprolol. The compound was devoid of intrinsic sympathomimetic activity as shown by the lack of effect on heart rate in anaesthetized and reserpine pretreated rats. Studies in rabbits and guinea pigs revealed a local anaesthetic activity of bisoprolol at high concentrations. Bisoprolol protected the hearts of anaesthetized dogs against the sequelae of intermittent coronary occlusions, as judged by the reduction of the ST-segment elevation in the epicardial ECG. Bisoprolol exerted a blood pressure lowering effect in conscious renal hypertensive dogs after oral administration of 30 micrograms/kg. There was no indication of any action on the CNS in monkeys following an oral dose of up to 8 mg/kg.

Adrenergic beta-Antagonists↗

Drug induced hypothermia in adult and senescent rats.

Temperature regulation was evaluated in senescent (34-40 month old) and adult (8-9 month old) female Iva:WIWU and Emd:Wi-AF/Han rats. Injection of 1.5 mg/kg BW apomorphine HCl or 1.0 mg/kg BW oxotremorine sesquifumarate produced comparable maximal hypothermic responses in adult and senescent rats. However, the latency to reach maximal hypothermia after oxotremorine (but not apomorphine) was longer in senescent than in adult rats of both strains.

Aging↗

Drinking by senescent and adult rats in response to regulatory challenges.

The regulation of water and electrolyte balance was elevated in senescent (greater than 31 months) and adult (5-10 months) rats of several strains. Weekly food and water intake, drinking induced by 24-hr water deprivation and drinking induced by injection of hypertonic saline were roughly the same in old and adult rats. However, senescent rats drank less after injection of the beta-adrenergic agonist isoprenaline than adult rats. There were no appreciable strain differences in drinking in response to these regulatory challenges although baselines sometimes differed between strains.

Aging↗

Location of the angiogenic activity in the pregnant human uterus.

Angiogenic activity was known to be intensely dynamic during pregnancy with a geometric orientation towards the site of implantation. Therefore this study was designed to test whether the uterine lining of pregnancy, the decidua, induces angiogenic activity on the chorioallantoic membrane (CAM). Twenty-three decidual specimens obtained during legally induced abortions were implanted into the 9-day-old chick CAM. All decidual specimens showed strong angiogenic activity as measured by 9-fold increase in radial blood vessels, with a geometrical formation of 'spokewheel' pattern extending over a range of 1.2 cm within 48 h.

Adult↗

High-performance size exclusion chromatography as a rapid method for the separation of steroid hormone receptors.

High-performance size exclusion chromatography ( HPSEC ) on TSK 3000SW molecular sieve columns was used to separate estrogen, progestin, and androgen receptors from several target tissues within 50 min on the basis of size and shape (Stokes radius). Moreover, this system provided for the detection of heterogeneity of receptor species (isoforms) in a manner superior to that observed with sucrose density gradient centrifugation. HPSEC separated various estrogen receptor isoforms having Stokes radii of greater than 61 A, approximately 48 A and 29-32 A. Agents such as potassium chloride and sodium molybdate which alter the distribution of estrogen receptor species on sucrose density gradient centrifugation, promote similar alterations in receptor profiles when HPSEC was employed. Our investigations suggest the use of [125I]iodoestradiol-17 beta and HPSEC allows the sequential analysis of estrogen receptor species providing new insights into receptor composition and structure. It is concluded that HPSEC has a broad application in the field of steroid hormone receptors. This method should be useful in studies ranging from measurements of molecular and kinetic properties to their mode of cellular interaction and regulation.

Animals↗

The dynamics of the stress stage of osmotic haemolysis.

A simple physical model for the dynamics of the stress stage of osmotic haemolysis is presented. An 'elastic restitutive coefficient' for the red cell membrane is defined to relate the increase of internal pressure to the volume change during the stress stage, and it is estimated on the basis of the work of Evans et al. (1976, 1977). It is shown that the time elapsed between complete swelling and the start of haemoglobin leakage can be a substantial part of the total haemolysis time, in accordance with experimental results reported in the literature.

Biomechanical Phenomena↗

[Estrogen and progesterone receptors in malignant ovarian neoplasms].

Estrogen receptors (ER) and progesterone receptors (PR) were evaluated in 173 primary ovarian cancers and in 6 ovarian metastases. In epithelial ovarian carcinomas 63% had ER and 46% PR. Almost all granulosa cell tumours were receptor-positive, while sarcomas, dysgerminomas, and teratomas lacked ER and PR. Both receptors were found less often in tumours of the histological grade I than in those of grade II and III. During the development of metastases and during chemotherapy there was a loss of PR in 27% and 53% of the cases, respectively, while the amount of ER remained more or less constant. In addition to ovarian cancers ER and PR were present in carcinomas of the fallopian tube as well. ER-negative and especially PR-negative tumours seemed to respond better to chemotherapy than receptor-positive carcinomas. The possible significance of ER and PR with regard to the success of an endocrine treatment is discussed.

Carcinoma↗