PubMed Health⌕ Search

Biomedical subjects

U Fuchs

Publications and source records attributed to U Fuchs.

At least 37 records · Page 2Linked to original sources

Transplantation of fetal liver tissue suspension into the spleens of adult syngenic rats: effects of various mitogens and cytotoxins on cytochrome P450 (P450) isoforms expression and on P450 mediated monooxygenase functions.

Syngenic fetal liver tissue suspensions were transplanted into the spleens of adult male Fisher 344 inbred rats. Four months after surgery, transplant recipients and age matched control rats were treated with various mitogens (fluorene [FEN], fluorenone [FON] and 2-acetylaminofluorene [AAF]) or cytotoxins (allyl alcohol [AAL], bromobenzene [BBZ] and carbon tetrachloride [CCl4]) or the respective solvents 24 or 48 hours before sacrifice. The expression of three cytochrome P450 (P450) isoforms, 1A1, 2B1 and 3A2, within spleens and livers was assessed by immunohistochemistry and P450 mediated monooxygenase functions in spleen and liver 9000 g supernatants by the model reactions ethoxyresorufin O-deethylation (EROD), ethoxycoumarin O-deethylation (ECOD), and ethylmorphine N-demethylation (EMND). The orthotopic livers of both solvent treated transplant recipients and control rats displayed only in few lobules a slight P450 1A1, but in all lobules a moderate P450 2B1 and 3A2 expression, all mainly located in the hepatocytes around the central veins. Correspondingly, regular EROD, ECOD and EMND activities were observed. Each of the three mitogens increased the P450 1A1 expression in the hepatocytes of the perivenous zones of the liver lobules. FON administration caused an additional P450 1A1 immunostaining in the periportal areas, and AAF treatment a P450 1A1 expression in bile duct epithelia. Also the staining for P450 2B1 and 3A2 in the hepatocytes of the perivenous and intermediate zones of the liver lobules was intensified after treatment with any of the mitogens. The three model reactions were significantly increased within the livers after FEN and FON administration, whereas after AAF treatment only ECOD was enhanced, EROD remained unaffected and EMND was decreased. The cytotoxin AAL caused small lesions and fatty degeneration of hepatocytes only in some periportal areas. BBZ only produced a perivenous necrosis of single cells, whereas CCl4 caused complete necrosis of the centrilobular parenchyma. Immunohistochemically, AAL administration led to an increase in the P450 2B1 expression in the perivenous hepatocytes, whereas the staining for P450 1A1 was not affected and that for P450 3A2 was even decreased in the periportal areas. Due to AAL treatment EROD and EMND activities were not affected and ECOD activity was increased. BBZ administration caused a P450 1A1 expression in the periportal hepatocytes but a decrease in this staining of the perivenous cells. The number of hepatocytes positively stained for P450 2B1 and 3A2 in the perivenous and intermediate zones was diminished in comparison to the livers of solvent treated rats. After BBZ treatment, EROD and EMND activities were decreased, ECOD activity was not affected. CCl4 administration caused a strong reduction in the expression of all three P450 isoforms and in the activity of all three model reactions. Spleens of control rats displayed almost no P450 isoforms expression and P450 mediated monooxygenase functions, without as well as after treatment with the mitogens or cytotoxins. Similar to adult liver, the hepatocytes in the transplant containing spleens showed nearly no P450 1A1, but a noticeable P450 2B1 and 3A2 expression. No staining was observed within the bile duct cells of the intrasplenic transplants.

2-Acetylaminofluorene↗

Ribonucleolytic activities in the Escherichia coli in vitro translation system and in its separate components.

mRNA stability is a limiting parameter for the efficiency of in vitro protein biosynthesis. In order to develop strategies to prolong the mRNA half-life, we investigated the ribonuclease activities in the complete Escherichia coli system, in the separate cell fractions 70S ribosomes and S-100 and in the non-cellular fraction. Our results imply that the amount of ribonucleolytic activities and the insensitivity to placental RNase inhibitor in the complete system are due to the 70S ribosome fraction, whereas the generation of small degradation products is due to the S-100 fraction. Remarkably, the human placental RNase inhibitor is able to reduce mRNA degradation in the bacterial S-100 fraction.

Cell-Free System↗

Hepatic retinopathy: morphological features of retinal glial (Müller) cells accompanying hepatic failure.

More than 80 years ago, Alzheimer described changes in the brains of patients who had suffered hepatic failure. Astrocytes are primarily affected; their nuclei become swollen, their intermediate filament protein composition is altered and their cytoplasm becomes vacuolated. Cells with these features are called Alzheimer type II astrocytes and these changes have been attributed to the toxic effects of elevated ammonia levels. The present study investigates whether the dominant glia of another part of the central nervous system, the Müller cells of the retina, undergo similar changes. Retinae of patients who had died with symptoms of hepatic failure were processed for histology, histochemistry, and immunocytochemistry. Cell nuclei were measured from brain astrocytes (insula cortex), Müller cells, and retinal bipolar neurons. Hepatic failure resulted in the enlargement of nuclei in astrocytes and Müller cells, and the enhanced expression in Müller cells of glial fibrillary acidic protein, cathepsin D, and the beta-subunit of prolyl 4-hydroxylase (glial-p55). In some retinae, signs of gliosis were also observed. We conclude that increased levels of serum ammonia resulting from hepatic insufficiency cause changes in Müller cells that are similar to those seen in brain astrocytes. We term this condition hepatic retinopathy.

Adult↗

[Treatment of endometriosis with the GnRH agonist buserelin (Suprecur): a multicenter study].

A phase III multicentre study was carried out with the GnRH agonist buserelin (Suprecur) at five university institutions (Dept. of Obstetrics and Gynaecology of Essen, Kiel, Tübingen, Münster and Erlangen) to evaluate the effect of Buserelin (3 x 300 micrograms daily intranasal) on endometriosis for a period of 6 months. Endometriosis was verified by light microscopy in all cases. The data of 430 patients could be evaluated. The extent of the endometriotic lesions was studied before the start and at the end of therapy. The mean age of the patients was 30 +/- 5 years. For 300 patients (66.4%) sterility was a main problem. Previous treatment for endometriosis consisted of operation in 20.5%, treatment with danazol in 16.8% and treatment with gestagens in 11.6% of the patients. Under treatment FSH changed from 11.0 +/- 31.4 mIU/ml to 7.0 +/- 5.6 mIU/ml at the end of therapy; LH from 11.1 +/- 12.9 mIU/ml to 7.4 +/- 7.3 mIU/ml; estradiol from 113.9 +/- 89.0 to 35.9 +/- 60.3 pg/ml and progesterone from 7.2 +/- 11.2 ng/ml to 0.8 +/- 1.4 ng/ml. The effect on endometriosis was judged according to the revised American Fertility Society score (rAFS 1985). The changes of the rAFS-score stages were as follows (before/after therapy): Stage 0: 0%/42.8%; stage I: 43.5%/38.5%; stage II: 31.1%/11.2%; stage III: 18.1%/2.2%; stage IV: 6.3%/0.2%. The total mean AFS-stage changed from 1.9 to 0.7. The frequency of clinical symptoms improved (before/after therapy): dysmenorrhoea 65.0%/11.2%; pelvic pain 48.2%/14.1%; pain at the time of gynaelogical examination 40.0%/9.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

Isolation, characterization and sequence of a cDNA encoding gamma-tubulin protein from the fern Anemia phyllitidis L. Sw.

A complete cDNA encoding gamma-tubulin protein from Anemia phyllitidis is presented. The deduced amino acid sequence shows an average similarity of 81-86% to known gamma-tubulin genes from insects, mammals and fungi. Northern blots indicate the existence of transcripts of ca. 1.9 kb which are expressed during gametogenesis of A. phyllitidis. The gene described is the first cloned and entirely sequenced gamma-tubulin gene in any plant.

Amino Acid Sequence↗

Lifelong learning of physicians: contributions of different educational phases to practice performance.

This pilot study was designed to find out where and when in their education physicians thought they had acquired the competencies they used in their daily practices five years after completion of their formal training. Specifically, the study sought physicians' views about the relative contributions of seven major phases of medical education (i.e., preclinical, clinical, "practice phases 1 and 2," specialty training, formal continuing education, and independent learning) to their practice performances. In 1991, the authors distributed a questionnaire to 330 physicians participating in a continuing medical education course in Germany, asking them about the relative contributions of these educational phases to their practice performances. A total of 141 (43%) returned questionnaires, of which 114 were suitable for evaluation. Specialty education was believed to have contributed most to the physicians' daily practices, with a median contribution of 20%. Practice-based independent learning, in which 38% participated in groups, contributed, with a median of 18%, and was superior to formal continuing education, with a median of 5%, and to university education, 15%. The frequency distribution of the percentages allotted to the seven phases showed great variation. Thirty-four respondents stated that they had not gained appreciably from preclinical education or formal continuing education but that the other five phases had contributed 50% to 90% of the knowledge and skills they used in their practices.

Clinical Competence↗

[DNA flow cytometry of malignant melanoma of the choroid].

Thirty-five choroidal melanomas were analyzed by flow cytometry. DNA euploidy, aneuploidy and polyploidy were found in approximately 54, approximately 46, and approximately 20% of the tumors, respectively. No correlation between histological type and ploidy was found. The synthesis phase was irregular in approximately 25 and approximately 38% of the spindle and the mixed cell melanomas, respectively. The G2M peak was broadened in approximately 50% and in approximately 23% of the spindle and the mixed cell melanomas. About 20% of the malignant melanomas were highly proliferative. In 25% of the melanomas chemotherapy seemed to be useful.

Brachytherapy↗

The effect of relaxin and ubiquitin on sperm motility.

Ubiquitin and relaxin--2 low molecular weight substances--have different effects on sperm motility. These two compounds are not separable by chromatographic procedures. Ubiquitin in different concentrations had no effect on 4 parameters of sperm motility, as evaluated by the Lazymot analyser. However, relaxin at a concentration of 1.99 pmol inhibited all 4 parameters of sperm motility compared with saline, Taumild or ubiquitin.

Animals↗

Cytoskeleton in neuroectodermally derived epithelial and muscle cells of the human iris and ciliary body.

The cytoskeleton of epithelial and muscle cells of the human iris and ciliary body was analyzed by immunohistochemistry in three morphologically normal formalin-fixed, paraffin-embedded eyes and in 34 eyes containing a uveal melanoma. Both layers of the iris epithelium reacted with monoclonal antibodies (MAb) V9 and Vim 3B4 to vimentin, whereas the ciliary epithelia additionally reacted with MAb CAM 5.2, CK5, KS-B17.2, and CY-90, recognizing cytokeratins 8 and 18. The same cytokeratin MAb labeled the retinal pigment epithelium, which lacked vimentin. The muscle portion of the anterior iris epithelium, which forms the dilator muscle, as well as the sphincter and ciliary muscles, reacted with MAb DE-U-10 to desmin and 1A4 to alpha-smooth muscle actin. The dilator and ciliary muscles also reacted with V9 and Vim 3B4 to vimentin, and some dilator fibers were weakly immunopositive for cytokeratin 8 and 18 with CY-90 and CAM 5.2. The antigenic profile of iris and ciliary epithelia infiltrated by melanoma cells remained unchanged. The intraocular epithelia, which are developmentally related but differ in function, and the intraocular muscles, which differ in origin but are functionally related, have distinct cytoskeletal profiles and may provide insights into the functional significance of intermediate filament expression.

Adult↗

An immunohistochemical and prognostic analysis of cytokeratin expression in malignant uveal melanoma.

A group of 52 patients with malignant uveal melanoma treated by primary enucleation in 1977-1979 was studied to determine the frequency of immunoreactivity for cytokeratins (CK) in primary and metastatic melanoma, the CK types present, and the prognostic significance of CK expression. By immunohistochemistry, monoclonal antibody (MAb) V9 to vimentin reacted with all 52 formalin-fixed, paraffin-embedded primary tumors and all 31 metastases from 11 patients. MAb CAM 5.2 to CK 8 and 18 reacted with 20 and MAb CY-90 to CK 18 with 25 primary melanomas, whereas MAb KS-B17.2 and MAb CK5 to CK 18 labeled 8 and 6 tumors, respectively. Antibodies to CK 13 and CK 19 each labeled single cells in one specimen, and other CK types were not detected. In 6 primary melanomas, only a few tumor cells were immunopositive for CK 8 and 18, but in 17 cases up to one quarter, and in 2 tumors more than one quarter, of them were labeled. The positive cells were spindle, epithelioid, or intermediate in shape, and tended to be more frequent in mixed than in spindle cell melanomas. MAbs CAM 5.2 and CY-90 did not react with any of the 16 liver metastases, but labeled 7 of 15 other metastases. Metastases were somewhat more common when the primary tumor was immunoreactive for CK 8 and 18, apparently because CKs were more frequent in mixed cell melanomas. Although CK expression is of diagnostic significance and can denote low levels of epithelioid differentiation, it is not an independent prognostic factor in malignant uveal melanoma.

Adolescent↗

Histopathology studies in human malignant melanomas of the choroid after unsuccessful treatment with 106Ru/106Rh ophthalmic applicators.

Choroidal malignant melanomas were examined after unsuccessful brachytherapy with 106Ru/106Rh ophthalmic plaques. The histologic findings were compared with those obtained in non-irradiated melanomas similar in size and location. Both groups revealed no significant clinical difference apart from the lower average age of the irradiated patients. Some of the histologic features (scar formation, changes in the distribution of cell types, rate of mitosis) represented reactions to irradiation. No single histologic feature was strongly correlated to the irradiated group. The phenomenon of radioinsensitivity observed in some malignant melanomas cannot be fully elucidated using conventional histologic methods.

Brachytherapy↗

[Androgens and other hormones in buserelin therapy].

23 women of reproductive age were treated with Buserelin nose-spray for endometriosis, which had been diagnosed by laparoscopic and bioptic methods. The treatment period was 6 months. Various hormones in serum were determined after 2, 4, 8, 12, 16, 20 and 24 weeks during treatment. LH, E2, prolactin, progesterone, and testosterone concentrations were significantly decreased under Buserelin therapy, whereas there was only a slight decrease in FSH, free testosterone and androstendion. No changes were observed in the concentrations of DHEAS and SHEBG. Buserelin had no androgenic effect. There was a significant decrease of endometriosis as judged by the implantation score.

Administration, Intranasal↗

Cytoskeleton in normal and reactive human retinal pigment epithelial cells.

The cytoskeleton of normal and reactive retinal pigment epithelium (RPE) was analyzed immunohistochemically in five light microscopically normal formalin-fixed, paraffin-embedded human eyes enucleated because of orbital tumor and in 44 eyes with a uveal melanoma. In 26 eyes, the RPE overlying the tumor was morphologically normal or atrophic; in 18 eyes, hyperplastic changes were present. Normal RPE cells lacked vimentin, but it was present in 35 of 44 eyes with uveal melanoma. Antibodies that recognize cytokeratins CK8 and CK18 labeled normal and reactive RPE cells in all specimens. Although CAM 5.2 and CY-90 detected RPE cells strongly and quantitatively, clones CK5, KS-B17.2, and pancytokeratin antibody lu-5 reacted weakly and did not label some specimens. Immunoblotting supported the presence of CK8 and CK18 in human RPE. Normal RPE cells did not express other simple epithelial cytokeratins, but both atrophic and hyperplastic reactive RPE cells were labeled with antibodies to CK7 or CK19 in 24 of the 44 eyes. Hyperplastic proliferating RPE cells that formed subretinal membranes reacted positively for alpha-smooth muscle actin in 13 of 18 eyes. Antibodies to CK8 and CK18 are valuable markers of normal and reactive human RPE cells, but a panel of reagents is necessary to document reactive changes in the cytoskeleton. Acquisition of alpha-smooth muscle actin by human RPE cells may be related to their ability to form periretinal membranes and contribute to intraocular proliferative diseases.

Adolescent↗

[Morphologic studies of the conductive veins of the leg in superficial varicose veins].

Issuing from the thesis of Fischer and Siebrecht that the epifascial varicosis can be accompanied by an insufficiency of the conducting and muscle veins for the first time morphological investigations on the profound venous system were carried out with the questioning whether the non-thrombotic insufficiency of the profound conducting veins of the leg an adequate morphological correlate is underlying which is to be recognized and proved histologically. On the basis of this first pilot study can be shown that similar forms of reaction take place in the part of the superficial and profound veins which are free from varices. Hitherto it is still unclear which factors are leading for the causes in the pathological mosaic. The insufficiency of the conducting veins, age-conditioned and functional changes and the arteriosclerotic venopathy are discussed. The conception of the insufficiency of the conducting veins also in the field of morphological research proves to be the initiator of exact and further analyses.

Collagen↗

[Adjuvant chemotherapy of breast cancer with the CMFV protocol].

Adjuvant CMFV therapy was administered from 1975 to 1984 at the Department of Gynaecology and Obstetrics of the University of Erlangen in 331 patients from a patient population, who underwent an operation with the intention of curing invasive breast cancer. Six cycles of this therapy were administered to 224 women. Only these patients were considered in the evaluation. 538 patients without axillary lymph node metastases and without adjuvant therapy served as reference population. The significance of adjuvant CMFV therapy in relation to the lymph node and menopausal status was investigated in a retrospective analysis. It was shown, that the five-year actual survivals in the group of premenopausal patients with one to three affected lymph nodes and CMFV therapy (n = 60), did not differ significantly from the group of women with premenopausally negative lymph nodes without adjuvant therapy (n = 198) (87.7% versus 88.2%). On the other hand, in the postmenopausal patients, the five-year actual survivals for the corresponding groups were 65.9% and 83.2%, respectively. The difference was significant. The results indicate, that adjuvant CMFV therapy improves the prognosis in premenopausal women, above all in cases with one to three affected lymph nodes. In the postmenopausal patients, a comparable effect could not be demonstrated in this group of patients.

Adult↗

Stage-dependent depression of melatonin in patients with primary breast cancer. Correlation with prolactin, thyroid stimulating hormone, and steroid receptors.

Serum melatonin was determined over 24 hours in 35 patients with breast cancer with either a fresh primary tumor (n = 23) or a secondary tumor (n = 12) and in 28 patients with untreated benign breast disease (controls) having a fibroadenoma (n = 10), fibrocystic mastopathy (n = 14), or other breast diseases (n = 4). Circadian rhythms existed in all groups with acrophases at 2 a.m. A 50% depression of peak and amplitude occurred in the group of patients with primary breast cancer compared with age-matched controls (P less than 0.001, P less than 0.01). The peak declined with increasing tumor size: 27% at Stage T1, 53% at T2 (P less than 0.001), and 73% at T3 (P less than 0.05). In contrast, patients with secondary breast cancer, particularly those receiving antiestrogen therapy, had a melatonin peak similar to controls. These results demonstrated a transient depression of pineal melatonin secretion in primary breast cancer and indicated a dynamic role of the pineal gland in malignancy. To investigate some endocrine effects of a depressed melatonin peak, the 24-hour rhythms of prolactin (PRL) and thyroid stimulating hormone (TSH) were determined in patients with primary breast cancer and compared with patients with secondary breast cancer. The PRL had significant circadian rhythms in both groups; but acrophases occurred at midnight in patients with secondary breast cancer, and there were unusually high concentrations at noon in patients with primary breast cancer. Circadian rhythms were not seen for TSH, but the 24-hour average secretion was depressed by 45% (P less than 0.01) in patients with primary breast cancer. The abnormal concentrations of PRL and TSH in these patients could be due to a depressed melatonin peak normally serving as a central circadian synchronizer and modulator of the secretion of adenohypophysial hormones. Additionally, a positive correlation existed between the nocturnal melatonin peak and progesterone and androgen receptor concentrations in primary tumors indicating a direct involvement of melatonin in the growth control of breast cancer.

Adult↗