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Biomedical subjects

A Richter

Publications and source records attributed to A Richter.

At least 217 records · Page 12Linked to original sources
PubMed1996

Behavioral and neurochemical dysfunction in the circling (ci) rat: a novel genetic animal model of a movement disorder.

One of the crucial breakthroughs in research on parkinsonism was the observation of circling behaviour in rodents after unilateral intranigral injection of 6-hydroxydopamine. This Ungerstedt model remains one of the basic animal models of Parkinson's disease. We report here the first mutant rat strain with abnormal circling behaviour and several other features reminiscent of the Ungerstedt Parkinson model. The neurological disorder in the novel mutant rat strain is determined monogenetically by a recessive autosomal gene termed circling (ci). Mutant rats of both genders exhibit an intense asymmetric circling in an open-field or rotometer, which is enhanced by treatment with amphetamine. Neurochemical determinations show that mutants of both genders have significantly lower concentrations of dopamine and dopamine metabolites in the striatum ipsilateral to the preferred direction of rotation. Furthermore, in a forelimb-reaching test for assessing the skilled motor capacities of rats, ci rats show a marked deficit on the side contralateral to the preferred direction of turning, which is analogous to motor deficits previously described for rats subjected to unilateral 6-hydroxydopamine lesions. The new mutant rat strain thus exhibits remarkable similarities to the Ungerstedt model and could be used to study the endogenous processes, particularly the genetic components, that might eventually lead to progressive motor dysfunctions.

Amphetamine↗
PubMed1996

[Confocal in vivo microscopy after 15 mm sclerocorneoplasty à chaud in necrotizing keratitis].

BACKGROUND: Confocal microscopy allows an in-vivo visualization of corneal structures in frontal optical sections. By means of this method we show morphological changes in a corneal transplant after sclerocorneoplasty à chaud because of a necortizing keratitis. CASE REPORT AND METHOD: We report on a patient who had to undergo a 15 mm diameter sclerocorneoplasty à chaud because of a necrotizing keratitis of his right functionally last eye in October 1993. Five months after transplantation there was a circular vascularization of the scleral rim and a progressive crystalline deposition in the periphery of the cornea. The main part of the donor cornea remained clear with a vision of 0.6. After one year the patient had developed a mature complicated cataract and got a phacoemulsification with a tunnel in the transplanted cornea and an implantation of a posterior chamber lens. In May 1995 the visual acuity was 0.9. We examined the epithelium, stroma and endothelium of the graft by means of in-vivo confocal slit scanning microscopy. RESULTS: All layers of the cornea are demonstrated. There were crystalline needle-like structures in the peripheral stroma and round cystic bodies in the deep stroma. Nerves were visible one year after transplantation. The endothelial cells showed a mild polymorphism and still a density of 2200 cells/mm2. CONCLUSIONS: Confocal microscopy is a useful non invasive technique for routine examinations after keratoplasty. Microscopical changes in the tissue are also visible in case of absent postoperative complications. With growing knowledge the confocal microscopy will give more insight into processes of wound healing.

Aged↗
PubMed1996

[Geriatric tumor surgery--change in the patient sample].

The comparison of our surgical tumor patients over 65 years of age treated in 1973-1974 or 1993-1994 showed the following results: increased average age and more patients with a greater unfavorable preoperative risk profile, an increase in colorectal tumors, a decrease in gastric carcinomas, no changes in tumor stages, more frequent sphincter-preserving operations for rectal tumors, an increase in the curative resection rate, lower mortality and shorter hospital stays. A curative resection of a malignant tumor is justified in the majority of elderly patients and should be performed considering the post-operative quality of life.

Aged↗
PubMed1996

[Surgical therapy of pancreatic carcinoma in elderly patients over 70].

Between October 1972 and December 1994, 519 pancreatic resections were performed at the Chirurgische Universitätsklinik Mannheim, 372 for pancreatic carcinoma. Of 328 patients who underwent a partial duodenopancreatectomy for cancer, 45 patients were older than 70 years: only in one case a partial duodenopancreatectomy was performed for chronic pancreatitis. In comparison to all patients the perioperative morbidity increased to 39.1% (21.5% vs. 39.1%). The perioperative mortality of all patients was 1.9%, the mortality of patients older than 70 years was 4.3%. The mean survival time of 28 patients who died subsequently was 30.6 (5-96) months. Despite increased perioperative morbidity and mortality, the patient's age is not considered to be a limiting factor to an attempt at curative resection of pancreatic or periampullary cancer.

Aged↗
PubMed1996

[Is diagnostic laparoscopy a reliable addition to preoperative staging of pancreatic carcinoma?].

Over the last decade several authors proposed adopting diagnostic laparoscopy as an early diagnostic routine method in the staging of pancreatic carcinoma to prevent exploratory laparotomy. In our hospital only 11.6% of all patients who underwent explorative laparotomy would have benefitted from diagnostic laparoscopy. Therefore, we do not recommend diagnostic laparoscopy as a routine method to assess resectability of pancreatic carcinoma?

Angiography↗
PubMed1996

Corneal reinnervation following penetrating keratoplasty--correlation of esthesiometry and confocal microscopy.

Thus far assessment of corneal reinnervation after penetrating keratoplasty has been possible only by esthesiometry techniques. Since the introduction of confocal microscopy, we have been capable of performing structural corneal in vivo examinations. The purpose of our study was to correlate esthesiometry results with confocal microscopy findings. We used a Cochet-Bonnet esthesiometer and a Microphthal confocal microscope to investigate corneal grafts in vivo. A total of 46 eyes were examined preoperatively and for up to 3 years after penetrating keratoplasty. At 8 weeks after keratoplasty the first stromal nerves were detected in the periphery of the graft. The first nerves in the middle and superficial stroma of the graft center were observed at 7 months after surgery. Reinnervation of the central basal epithelium was found at 2 years after keratoplasty. The highest level of sensitivity was detected in young patients with reinnervation of the basal epithelium. Confocal microscopy enables us to correlate morphologically and functionally corneal reinnervation after surgery. The present study shows that corneal reinnervation is influenced by the amount of time elapsing after surgery, the patient's age, and the preoperative diagnosis. In none of our patients was normal nerve morphology or sensitivity observed during the follow-up period. Comparison of the morphology of nerves seen in eyes after nonsurgical trauma with that observed in corneal grafts indicates that surgically induced scar formation may limit nerve regeneration in grafts.

Adolescent↗
PubMed1996

Confocal in vivo microscopy and confocal laser-scanning fluorescence microscopy in keratoconus.

The purpose of this study was the determination of morphological changes in the corneal epithelium and the keratocyte network in keratoconus. In all, 33 eyes of 19 patients were examined in vivo using the confocal slit-scanning microscope Microphthal. After penetrating keratoplasty, recipients' trephanates were stained with the Live/Dead kit and examined using the confocal laser-scanning fluorescence microscope Diaphot 300/Odyssey. The fluorescence images were reconstructed three-dimensionally. All findings were compared with data from healthy corneas. Morphological alterations were found only in the area of the corneal apex; obviously elongated superficial epithelial cells arranged in a whorl-like fashion were found. Near Bowman's membrane, highly reflective changes and fold-like structures were visible. The anterior stroma also showed an increased reflectivity. In the posterior stroma, typical findings were Vogt's striae and keratocytes with extremely long processes arranged nearly in parallel. In scarred stroma the keratocytes were spindle-shaped and arranged irregularly. The spatial organization of the living keratocyte network could be demonstrated through three-dimensional reconstructions.

Adult↗
PubMed1996

Assessment of corneal alterations following laser in situ keratomileusis by confocal slit scanning microscopy.

This investigation was done to evaluate in vivo changes in corneal micromorphology occurring after laser in situ keratomileusis. By means of confocal microscopy, nine eyes of eight patients showing uncomplicated wound healing at 2-16 weeks after surgery and one eye of one patient at 30 weeks after initial surgery who had to undergo two retreatments because of a central island were examined. Video recording was used to register the data. The distribution of scattered light in the treated corneae was registered with the z-scan of the microscope. Slit-lamp findings obtained several weeks postoperatively showed only minor corneal alterations. Confocal microscopy revealed morphological changes as a result of the surgery, especially in the epithelium and in the anterior stroma. With the z-scan an additional peak determined by higher reflectivity in the anterior stroma was found. The retreated patient showed marked folds in the area of the interface and flap. Confocal in vivo microscopy is suitable for the noninvasive detection of micromorphological alterations following refractive corneal surgery and for observation of the postsurgical wound-healing phase, including nerve regeneration.

Adult↗
PubMed1995

Effects of anthralin and hypericin on growth factor signalling and cell proliferation in vitro.

The effect of the anthranoids, anthralin and hypericin, on epidermal growth factor receptor (EGF-R) activation and their degree of specificity was examined. Hypericin, but not anthralin, was found to inhibit binding of [125I]-labelled epidermal growth factor (EGF) to HN5 squamous carcinoma cells that overexpress EGF-R. This effect was a result of dose- and time-dependent reduction of EGF-R number and affinity. Neither compound directly inhibited EGF-induced tyrosine phosphorylation of the EGF-R in HN5 cells. Although anthralin and hypericin both inhibited the mitogenic effect of EGF in NR6/HER cells (IC50S = 100 nM and 10 microM, respectively), they also had comparable effects on DNA synthesis in response to acidic fibroblast growth factor (aFGF) and platelet-derived growth factor (PDGF). When tested in proliferation assays using cells expressing differing numbers of EGF-R, the growth inhibitory effects of both compounds were independent of EGF-R number. We conclude that, although anthralin and hypericin both inhibit EGF signalling, they do not act specifically on the EGF-R pathway. Moreover, their mechanisms of action do not appear to be comparable.

Anthracenes↗
PubMed1995

Constrained peptide analogues of transforming growth factor-alpha residues cysteine 21-32 are mitogenically active. Use of proline mimetics to enhance biological potency.

Two proline mimetics, the enantiomers of 2-aza-bicyclo[2,2,1]heptane-3-carboxylic acid, have been incorporated in place of Pro30 into synthetic peptides based on the B-loop beta-sheet sequence of human transforming growth factor-alpha (TGF-alpha) (residues Cys21-Cys32). The peptides were further modified by inclusion of an N-terminal phenylalanine and constrained by formation of an intramolecular disulfide bond. While no mitogenic response was observed in the parental NR6 cell line, the peptides stimulated DNA synthesis in NR6/HER cells (NR6 fibroblasts transfected with the human epidermal growth factor receptor). Induction of DNA synthesis was dose dependent, with EC50 values in the range 130-330 microM; in the presence of low doses of TGF-alpha, the mitogenic effect of the peptides was additive, up to the plateau response achieved by maximal doses of TGF-alpha alone. These effects are consistent with the peptides acting via the same mechanism as TGF-alpha. Analysis of the structure of the peptides by NMR indicated that the presence of the mimetics significantly increased the propensity of the peptidyl-proline bond to adopt the cis conformation. These data confirm the role of the beta-sheet in receptor activation, and emphasize the importance of presentation of peptides in an appropriate conformation for recognition.

Amino Acid Sequence↗
PubMed1995

Two newly established cell lines derived from the same colonic adenocarcinoma exhibit differences in EGF-receptor ligand and adhesion molecule expression.

Two morphologically distinct cell lines, GP2d and GP5d, derived from the same adenocarcinoma of the colon, have been established and characterised. Both clones have the same genetic changes, consistent with the usual pattern of tumour progression in colon cancer. The cells also have an inverted duplication of bands 10q11 to 10q21, but Southern blot analysis failed to identify any translocations involving the ret protooncogene, which maps to this region. GP2d grew by spreading from the edges of microcolonies to form a confluent layer of cells. GP5d grew in discrete islands of cells forming multi-layered colonies. These differing patterns of growth correlated with variation in expression or cellular distribution of alpha 2-integrin, desmoplakin and e-cadherin. Only GP2d responded to exogenously added epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha) or insulin with an increase in cell numbers, even though both cell lines possessed similar numbers of EGF receptors. Analysis of EGF receptor ligand expression showed that GP5d cells expressed relatively more TGF alpha mRNA than did GP2d; in contrast, amphiregulin mRNA, which was abundant in GP2d, was virtually undetectable in GP5d. Even though GP5d failed to exhibit a growth response to EGF, it underwent a marked epithelial-mesenchymal transition when treated with EGF, indicating separation of growth and morphological responses to EGF.

Adenocarcinoma↗