Search PubMed⌕ Search

Biomedical subjects

G Fuhrmann

Publications and source records attributed to G Fuhrmann.

At least 37 records · Page 2Linked to original sources
PubMed1996

Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells.

The totipotent stem cells of the pregastrulation mouse embryo which give rise to all embryonic somatic tissues and germ cells express Oct-4. The expression is downregulated during gastrulation and is thereafter only maintained in the germline lineage. Oct-4/lacZ transgenes were used to determine how this pattern of expression was achieved, and resulted in the identification of two separate regulatory elements. The distal element drives Oct-4 expression in preimplantation embryos, in migratory and postmigratory primordial germ cells but is inactive in cells of the epiblast. In cell lines this element is specifically active in embryonic stem and embryonic germ cells. The proximal element directs the epiblast-specific expression pattern, including downregulation during gastrulation; in cell lines its activity is restricted to epiblast-derived cells. Thus, Oct-4 expression in the germline is regulated separately from epiblast expression. This provides the first marker for the identification of totipotent cells in the embryo, and suggests that expression of Oct-4 in the totipotent cycle is dependent on a set of factors unique to the germline.

Animals↗
PubMed1995

The role of exogenous/endogenous basic fibroblast growth factor (FGF2) and transforming growth factor beta (TGF beta-1) on human corneal endothelial cells proliferation in vitro.

Adult human corneal endothelial cells (HCEC) have extremely low turnover rates but undergo rapid division in vitro when stimulated with soluble growth factors. We have investigated the role played by FGF2 and TGF beta-1 in the regulation of HCEC growth stimulation. HCEC from donors who were over 30 years old were cultured and experiments performed on cultures between the 2nd and the 6th passage in the presence of 5% NCS. Cell counts revealed a maximal stimulation of 2.1x for FGF2 and 1.9x for TGF beta-1 compared to control cultures. When both factors were added, a synergistic effect was noticed with a maximal stimulation of the proliferation rate of 4.5x over controls. In addition, endogenous FGF2 produced by HCEC was quantitated in a sensitive EIA assay. After 5 days in culture, 10(6) cells contained 150 ng FGF2 and 35 ng was extracted from trypsin-digested ECM. Two molar NaCl washes of ECM released 15.6 ng FGF2, which induced a slight mitogenic activity (1.5x over control) in HCEC cultures, which was partially inhibited by an anti-FGF2 antibody. Northern blot analysis of HCEC extracts revealed the presence of FGF receptors R1 and R2 mRNA. The bioactive FGFRs were demonstrated by the toxic effect of a mitotoxin FGF2-SAP. These results suggest that FGF2 could participate in the autocrine regulation of HCEC proliferation and survival. The synergy between exogenously added FGF2 and TGF beta demonstrates that a combination of different growth factors may be important to stimulate proliferation of these cells in vivo.

Adult↗
PubMed1995

[Experimental studies of the load capacity of DHS osteosyntheses after various kinds of osteotomy in the area of the femoral trochanter].

Standardized osteotomies were performed to mimic fractures classified as (a) stable, (b) partly unstable and (c) complete unstable (according to Evans) in 32 postmortem femoral bones. The stability of all preparations was examined after the performance of an osteosynthesis with a dynamic hip screw. Cycled loadings were increased stepwise every 500 N to the maximum loading capacity (load of fracture). In addition, the distortion at 2000 N was measured. There were no statistically significant differences between the three groups (a), (b), and (c). The average maximum load capacity was significantly lower in group (c) than in groups (a) and (b). Nevertheless, the lowest value (2275 N) recorded for the maximum loading capacity in our study means that in a normal weight person full weight-bearing can be allowed postoperatively.

Aged↗
PubMed1995

Titanium intervertebral disc and instrumentation for fusion in anterior cervical discectomy. Technical note.

A new titanium intervertebral disc for fusion in anterior cervical discectomy is described. The advantages of the device, apart from avoidance of graft explanation, include biocompatibility, simple instrumentation, availability of different forms and sizes, and restoration of physiologic lordosis. Following extensive biochemical testing and implantation in animals, first long-term experience in 15 patients with an average follow-up of three years (28-73 month) are described. Infections, anterior angulation deformities, and graft extrusions were not observed in this series.

Adult↗
PubMed1994

Spatial and temporal expression patterns of FGF receptor genes type 1 and type 2 in the developing chick retina.

Fibroblast growth factors are known to influence the growth and differentiation of cultured cells derived from the chick retina. The fibroblast growth factors can interact with a family of at least four closely related receptor kinases. To find a correlation between the presence of fibroblast growth factor receptors and eye development, the patterns of expression of transcripts encoding the type 1 (FGF-R1) and type 2 (FGF-R2) receptors in the developing chick retina have been studied. Northern blot analysis of RNA of the whole retina was used to observe that FGF-R1 transcripts are abundant at embryonic day 4 and then decrease until day 11. After this stage, the level of expression of FGF-R1 increases and its peak of expression at embryonic day 18 is concomitant with the detection of the opsin transcript. FGF-R2 transcript is also detected by Northern blots of RNA of the whole retina until embryonic day 6. However, the re-expression after embryonic day 11 of FGF-R2 could only be demonstrated by PCR studies. The same pattern of expression is observed with in situ hybridization of sagittal sections. The two genes are coexpressed in the pigmented epithelium and in the neural retina during embryonic development. The expression follows the retinal layering according to a gradient from the vitreous humor to the choroid. Quantification of the in situ hybridization signals demonstrates that the pattern of expression of both receptors diverges after embryonic day 6 between the pigmented epithelium and the neuronal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Fibroblast growth factor receptor deficiency in dystrophic retinal pigmented epithelium.

The retinal pigmented epithelium (RPE) is known to be the site of the primary lesion in inherited retinal dystrophy in the Royal College of Surgeons (RCS) rat, a model for retinitis pigmentosa. Although the only functional defect so far detected in these cells is their failure to efficiently phagocytose shed photoreceptor outer segment debris, the actual cause of photoreceptor cell death is still unknown. Recently the possibility of "trophic factors" important in photoreceptor survival produced by normal RPE but not by dystrophic RPE has been suggested. Hence we decided to investigate the presence and abundance of two candidate diffusible factors, the acidic and basic fibroblast growth factors (aFGF and bFGF, respectively), as well as their high affinity cell surface receptors (FGF-R). mRNA was isolated from primary cultures of purified normal and dystrophic RPE and analyzed by PCR amplification using specific oligonucleotide primers for aFGF and bFGF: the size and abundance of amplified fragments was similar for both cell types. Also, aFGF protein, detected by immunocytochemistry using specific antisera, appeared to be present in approximately equal amounts and distributed in a similar pattern. However, scatchard analysis of radio-labelled bFGF binding to primary cultures of normal and dystrophic rat RPE revealed that dystrophic RPE possess only 29% the number of surface receptors compared to congenic normal cells. Furthermore, the level of expression of FGF-R2 mRNA, but not that of FGF-R1, was significantly different. Other parameters measured (receptor affinity, profile of ligand internalization and degradation, receptor molecular weight and mitogenic activity) did not show any significant differences between normal and dystrophic RPE. The precise role of FGF-R deficiency in the etiology of the disease hence remains to be determined, but it indicates the importance of trophic factors in the normal functioning of the retina.

Animals↗
PubMed1993

Dose-dependent heart rate reducing effect of nizatidine, a histamine H2-receptor antagonist.

1. Twelve healthy subjects were treated in a randomised placebo-controlled crossover study with placebo, 150 mg, 300 mg, and 600 mg nizatidine, 100 mg pirenzepine, and 300 mg nizatidine plus 100 mg pirenzepine for 1 week each. 2. On the seventh treatment day, heart rate, blood pressure, systolic time intervals, impedance cardiographic and Doppler ultrasound variables were measured. 3. Stroke volume and blood pressure were not altered by nizatidine and/or pirenzepine. By contrast, heart rate and cardiac output significantly (P < 0.05) decreased in a dose-dependent manner 1.5 and 3 h after administration of 300 and 600 mg nizatidine. Treatment with 150 mg nizatidine led to similar though non-significant trends. 4. While a slightly insignificant rise in heart rate was detected with pirenzepine alone, heart rate and cardiac output remained unchanged upon combined nizatidine and pirenzepine treatment as compared with placebo and baseline values. 5. In conclusion, nizatidine reduced heart rate and cardiac output in a dose-dependent manner, whereas this negative chronotropic effect was counteracted by concurrent administration of the anti-cholinergic drug pirenzepine.

Adult↗
PubMed1993

aFGF binding to low and high affinity receptors induces both aFGF and aFGF receptors dimerization.

Acidic Fibroblast Growth Factor (aFGF) binds on two classes of fibroblast growth factor receptors, the high affinity receptors (HAR) a family of four known transmembrane tyrosine kinases and the low affinity receptors (LAR), related to cell surface heparan sulfate proteoglycan (HSPG). We analysed the relationship between the binding of aFGF on the HAR and on the LAR in bovine lens epithelial (BEL) cells in the presence of heparin or suramin. Through Northern blotting analysis we demonstrated that the three immunoglobulin-like transcript of FGF receptor type 1 (FGF-R1) is the major expressed high affinity receptor in BEL cells. On the contrary, HAR-aFGF complexes are present in two forms (150 kDa and 135 kDa) revealed by cross-linking experiments with 125I aFGF. Moreover 125I aFGF binding to BEL cell surface induces the spontaneous formation of a 125I aFGF dimer (31 kDa) which is then internalized and degraded in the cells as the 15.5 kDa aFGF native form is. It has been observed that heparin at 10 micrograms/ml (1) in cross-linking experiments, reduces by half the total number of HAR complexes by preventing the formation of the 150 kDa complex but does not affect the 135 kDa complex, (2) in binding experiments, suppress the spontaneous formation of the 125I aFGF dimer bound to LAR, and then its internalization and degradation in the cells. Moreover, we demonstrate that (1) only HAR contributes specifically and directly to the aFGF internalization process, (2) HAR internalization is ligand concentration and time saturable, (3) there is no desensitization of aFGF internalization induced by ligand binding to HAR, (4) a FGF dimerization process is highly dependent on the apparent affinity of FGF for heparin, since aFGF mutant with a reduced affinity for heparin does not promote the dimerization. These data strongly suggest that a heteroreceptor-aFGF complex (150 kDa) is formed by one molecule of HAR (FGF-R1) associated to one molecule of LAR through their respective interactions with a very stable aFGF homodimer. Such a three component receptor induced by FGF dimerization may be a process involved in the mechanism of action of FGFs which could explain the diversity of the biological response of FGF depending on the presence of the HSPG on the extra cellular matrix. In addition prebinding of unlabelled aFGF to the cells induces a 4 fold increase in the affinity of HAR to 125IaFGF concomitant with its down regulation by 80% and initiates the formation of the HAR homodimer.(ABSTRACT TRUNCATED AT 400 WORDS)

Allosteric Regulation↗
PubMed1993

[Titanium implant as an alternative possibility in fusion of the cervical vertebrae--initial clinical experiences].

We report on our experience with the use of titanium for disc replacement in the cervical spine. In 52 patients a total of 55 titanium grafts were implanted. Follow-up examinations were available in 48 patients with an observation time of 14 month on average. Results of clinical-neurological examinations were excellent or good in 37 patients (77%), moderate in 9 cases (19%), while two patients (4%) showed poor outcome. Radiological follow-up examinations showed a correct position in 47 of the 48 patients. Incorrect position as observed in 1 case made operative revision necessary. According to our results, titanium grafts seem to be a useful alternative method as compared to conventional techniques of fusion. Essential advantages are simple handling, biocompatibility of the material as well as the solid bond achieved by the special qualities of the graft with respect to surface and form. Availability of different graft sizes allows tailored fusion.

Adult↗
PubMed1992

Interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis and demonstration of FGF receptor expression in megakaryocytes and megakaryocytic-like cells.

We have investigated the interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis. Acidic FGF (aFGF) stimulated the proliferation of murine megakaryocytes and human erythroleukemia (HEL) cells in a concentration-dependent manner. The concentrations of aFGF required to elicit half-maximum and maximum effects were similar for HEL and megakaryocytic colony formation. The effect of aFGF was comparable to that of basic FGF (bFGF) in both cell types. The effect of both FGFs was found to be synergistic with interleukin-3 (IL-3), and was abrogated by a monoclonal anti-IL-6 antibody. A specific cell surface receptor complex of approximately 120 Kd was detected for FGF by crosslinking experiments on HEL cells and total bone marrow (BM) cells. Single-cell autoradiography of megakaryocytes in BM smears and BM cultures showed binding sites for 125I-aFGF. Northern blot analysis of messenger RNA (mRNA) from total BM and HEL cells showed a 4.4-kb mRNA specific for FGF receptors type 1 (flg) and type 2 (bek). This was confirmed by polymerase chain reaction, which also showed the presence of FGF receptor mRNA in megakaryocytic-like cells, normal megakaryocytes, and platelets. Together, these results indicate that FGF is involved in megakaryocytopoiesis and suggest that this interaction may be mediated via FGF receptor type 1 and type 2 located on the megakaryocytic lineage or on accessory cells responsible for the release of megakaryocytic growth-promoting activities.

Animals↗
PubMed1992

[Spontaneous fracture of an implanted anterior chamber lens].

This report deals with an 83-year-old patient who presented with visual deterioration. The patient had had an intracapsulary extraction with anterior chamber lens implantation. The break in the anterior chamber lens happened without any history of traumatic accident and led to dislocation of the lens and corneal decompensation. Scanning electron microscopy of the break area after explantation of the fragments revealed changes in the break zone that were characteristic of alternating tensile and compressive stress. Localization of the break at the transition of the optical part and the haptic where there is the greatest stress in the material points to insufficient strengthening in this critical part of the intraocular lens.

Aged↗
PubMed1989

Tissues at the surface of the new composite material titanium/glass-ceramic for replacement of bone and teeth.

A new composite implant material titanium/glass-ceramic was tested in rabbits using light microscopy, histomorphometry, and biomechanical testing methods. Two rabbit implant models were used. The first premolar tooth was replaced and cylinders inserted into the trabecular bone of the distal femur below the patella sliding plane. There was bone bonding to the glass-ceramic component and additional mechanical interlocking, due to bone ingrowth between the titanium matrix into secondary pores. This was proved by measuring the tensile strength at the interface of the new composite material which was in the same range as compared to pure glass-ceramic implants. In tooth replacement there was a tight attachment of gingival epithelium and stroma to composite titanium/glass-ceramic. These results are of particular clinical interest: physicochemical bone bonding and additional mechanical interlocking result in a resistance of the implant material against shear and tensile loads at the interface. Therefore this new composite material should be suitable for further load-bearing applications.

Animals↗
PubMed1987

Influence of mouse genotype on responses on central neurotransmitters to long-term alcohol exposure in striatum and hippocampus.

A striking strain dependency in response of central neuromediators (dopamine, serotonin, acetylcholine activities and somatostatin) to various periods of alcohol treatment has been noted in striatum and hippocampus in mice. For biogenic amines the C57Bl strain loses tolerance to prolonged alcohol injury earlier than the Balb/c strain. At the opposite the Balb/c strain exhibits a remarkable long lasting tolerance for cholinergic activity. The unequal capacity to adapt, also appears to depend on the nervous structure and the neurotransmitter considered. Such discrepancies may underly differences in behavioral changes observed in alcoholics.

Animals↗
PubMed1986

Effects of hormone therapy on the central cholinergic neurotransmission of the Snell dwarf mouse.

Effects of growth and thyroid hormone therapy on central cholinergic neurotransmission has been followed in the cholinergic-deficient Snell dwarf mouse. Growth hormone and thyroxine can reverse the neurotransmission impairment even in adulthood. Furthermore, it appears that in the dw/dw mouse, hormone deficiency becomes determinant only after the critical period of neurogenesis, in a late postnatal developmental stage. At first sight, these observations show that the disturbed cholinergic neurotransmission of the mutant might be linked to the pituitary and thyroxine deficiency that is characteristic of this mouse. Hormone therapy selectively stimulates cholinergic activity in cholinergic-deficient structures, where it reactivates presynaptic markers. The differential responsiveness of the neuroanatomical and neurochemical targets could be linked to different regulatory hormone effects or to timing in respect to sensitivity to hormones during development.

Acetylcholinesterase↗
PubMed1986

Genotypic differences in age and chronic alcohol exposure effects on somatostatin levels in hippocampus and striatum in mice.

Somatostatin contents of striatum, hippocampus, and pons medulla have been followed in two inbred strains of mice (C57B1/6J and Balb/cJ) with aging and long term alcohol exposure (over a 25 month period of intoxication). Marked strain dependent differences in basic levels of somatostatin and genotypic variations in reactivity of this neuropeptide to aging processes and chronic alcohol exposure were demonstrated. The Balb/c strain exhibits a significant age dependent decrease in striatal and hippocampal somatostatin levels whereas the C57B1 mice remain unchanged until the 27 month. Moreover, only the Balb/c strain reacts to chronic alcohol exposure, showing a significant increase in somatostatin levels in those structures affected by the aging process. Such genotypic differences may be involved in man in specific pathologies in aged individuals and in alcohol induced behavioral alterations in alcoholics.

Aging↗