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Biomedical subjects

W Arnold

Publications and source records attributed to W Arnold.

At least 145 records · Page 8Linked to original sources
PubMed1994

Adoptive transfer of an autoimmunological labyrinthitis in the guinea pig; animal model for a sympathetic cochleolabyrinthitis.

Sensorineural hearing loss is a common problem in the otolaryngologist's practice, with autoimmune disease of the inner ear being one possible cause. The restoration of auditory function in some patients following immunosuppressive therapy has created a desire to define and understand this disease better. Because of the lack of a well defined detection method to identify this entity clinically, this study was undertaken in order to provide an animal model for autoimmune disease of the inner ear. Previous studies with guinea pigs have demonstrated that sensitized lymphocytes from the systemic circulation migrate to the labyrinth during an immune response in the inner ear. The aim of this study was to prove the capacity of sensitized lymphocytes to transfer autoimmune inner ear disease, and to describe the resulting morphological and physiological changes. Therefore two groups of sensitized lymphocytes partially labelled with a radioactive marker from inbred guinea pigs with an immune response within the inner ear were injected into the bloodstream of naive recipient animals. Most of the labelled cells were observed in the apical turn of the experimental cochlea, while only few cells were detectable in the control cochleas. In addition, the absence of otoacoustic emissions and the loss of outer hair cells observed by electron microscopy were interpreted as a sign of damage caused by the provoked immunopathologic mechanism. The results are discussed as a possible model for a sympathetic cochleolabyrinthitis.

Animals↗
PubMed1994

Low genetic variability in a natural alpine marmot population (Marmota marmota, Sciuridae) revealed by DNA fingerprinting.

Genetic heterogeneity is usually considered an important factor for the viability of a population, yet there are cases in which populations sustain themselves despite virtual homozygosity. A prior step to studying the effects of such low levels of genetic variability can be the analysis of its causes. We analysed a population of the highly social alpine marmot (Marmota marmota, Sciuridae) by multilocus DNA fingerprinting. The fingerprint patterns revealed a very low degree of polymorphism in our main study population. We show that this lack of hypervariability is caused by a low effective population size, rather than by an unusual low mutation rate of the fingerprint loci studied. However, the current number of breeding pairs was found to be about an order of magnitude larger than the one that would be expected to lead to such a low degree of heterozygosity. We conclude that there must have been bottlenecks in the history of the Berchtesgaden marmot population that have severely affected its genetic heterozygosity.

Animals↗
PubMed1994

[Palliative surgical and endoscopic therapy of malignant bile duct occlusion].

Cholestatic jaundice is the result of a malignancy of the bile duct itself, of the gallbladder, of the ampulla or (as in most cases) of the pancreas. Patients without evidence of metastases or other signs of advanced cancer (e.g. ascites) are candidates for explorative laparotomy. In the vast majority of cases resection of a tumor is not feasible and the surgeon is faced with the objective of providing palliation. To date there exists not only one palliative procedure, and the surgeon has to take into account the following: In patients with pancreatic cancer palliation can be given with biliary bypass with or without gastroenterostomy. This carries an operative mortality of almost 20% and means a survival of only 5-6 months. Nonsurgical procedures as transpapillary stenting play an increasing role in the management of patients with obstructive jaundice due to pancreatic cancer. In some cases however resectable tumors perhaps will be overlooked. The results of controlled studies comparing endoscopic stenting and surgical bypass are encouraging for stenting techniques (lower morbidity and mortality (< 10%), technical success rates exceeding 90%). The availability of different palliative treatment modalities for carcinoma of the bile ducts suggests that no approach is definitely superior. Operative biliary-enteric anastomosis gives a tolerable operative mortality rate in younger patients, less morbidity, than external biliary drainage by better quality of life of the patients. In retrograde placement of prosthetic stents, in patients with high bile duct obstruction difficulties are frequently. In such cases the percutaneous drainage should be reserved for endoscopic failures, in cases the endoscopic and percutaneous approaches can be combined in the 'rendezvous' procedure. In recent years several reports have advocated extensive surgery for biliary neoplasms. Preoperative staging of these patients remains an issue as none of the commonly modalities are accurate in predicting resectability.

Anastomosis, Surgical↗
PubMed1993

Analysis of the Rhizobium meliloti exoH/exoK/exoL fragment: ExoK shows homology to excreted endo-beta-1,3-1,4-glucanases and ExoH resembles membrane proteins.

Nucleotide sequencing of a 4.15 kb DNA fragment from megaplasmid 2 of Rhizobium meliloti 2011 revealed the location of the genes exoH, exoK and exoL. The putative proteins encoded by these genes have molecular weights of 41, 30, and 44 kDa, respectively. The hydrophobicity profile of the ExoH amino acid sequence resembles that of transmembrane proteins. The predicted exoL gene product does not contain hydrophobic regions, indicating a cytoplasmic localization. The exoK gene product is characterized by a putative signal peptide and exhibits significant homology to endo-beta-1,3-1,4-glucanases of bacilli and Clostridium thermocellum. R. meliloti exoK mutants induced pink nodules and synthesized a reduced amount of exopolysaccharide (EPS). Colonies of this mutant showed a delay in the appearance of the Calcofluor white fluorescence. In addition, the formation of the characteristic halo was strongly delayed. R. meliloti exoL and exoH mutants induced pseudonodules. The exoH, but not the exoL mutant, synthesized an EPS that could be precipitated by cetyl pyridinium chloride (CPC) and also by ethanol. Plasmid integration mutagenesis revealed promoter regions preceding exoH, exoK and exoL.

Amino Acid Sequence↗
PubMed1993

Identification and analysis of the Rhizobium meliloti exoAMONP genes involved in exopolysaccharide biosynthesis and mapping of promoters located on the exoHKLAMONP fragment.

Sequence analysis of a 7.494 kb DNA fragment from megaplasmid 2 of Rhizobium meliloti 2011 involved in exopolysaccharide I (EPS I) biosynthesis revealed the presence of five exo genes designated exoA, exoM, exoN, exoO, and exoP. ExoN was found to show strong homology to a UDP-glucose pyrophosphorylase from Acetobacter xylinum, whereas ExoO displayed weak homologies to the NodC proteins from R. meliloti and R. loti. Surprisingly, different mutations in exoP resulted in divergent phenotypes. One exoP mutant was able to establish an effective symbiosis with alfalfa, although no EPS I polymer could be detected. In contrast, other exoP mutations prevented the formation of an effective symbiosis. The transcriptional organization of the exoA-exoP gene region has been analysed in conjunction with the exoH, exoK and exoL genes. Using exo-lacZ transcription fusions in association with plasmid integration mutagenesis a strong promoter was identified upstream of exoH, which is able to direct transcription of the whole exoHKLAMONP gene cluster. A much weaker promoter upstream of exoL was found to be involved in the transcription of the exoLAMONP genes. In addition, weak promoters were identified upstream of exoK, exoA, exoN and exoP.

Amino Acid Sequence↗
PubMed1993

The Ca2+-release channel/ryanodine receptor is localized in junctional and corbular sarcoplasmic reticulum in cardiac muscle.

The subcellular distribution of the Ca(2+)-release channel/ryanodine receptor in adult rat papillary myofibers has been determined by immunofluorescence and immunoelectron microscopical studies using affinity purified antibodies against the ryanodine receptor. The receptor is confined to the sarcoplasmic reticulum (SR) where it is localized to interior and peripheral junctional SR and the corbular SR, but it is absent from the network SR where the SR-Ca(2+)-ATPase and phospholamban are densely distributed. Immunofluorescence labeling of sheep Purkinje fibers show that the ryanodine receptor is confined to discrete foci while the SR-Ca(2+)-ATPase is distributed in a continuous network-like structure present at the periphery as well as throughout interior regions of these myofibers. Because Purkinje fibers lack T-tubules, these results indicate that the ryanodine receptor is localized not only to the peripheral junctional SR but also to corbular SR densely distributed in interfibrillar spaces of the I-band regions. We have previously identified both corbular SR and junctional SR in cardiac muscle as potential Ca(2+)-storage/Ca(2+)-release sites by demonstrating that the Ca2+ binding protein calsequestrin and calcium are very densely distributed in these two specialized domains of cardiac SR in situ. The results presented here provide strong evidence in support of the hypothesis that corbular SR is indeed a site of Ca(2+)-induced Ca2+ release via the ryanodine receptor during excitation contraction coupling in cardiac muscle. Furthermore, these results indicate that the function of the cardiac Ca(2+)-release channel/ryanodine receptor is not confined to junctional complexes between SR and the sarcolemma.

Animals↗
PubMed1993

Dystrophin-glycoprotein complex and laminin colocalize to the sarcolemma and transverse tubules of cardiac muscle.

The expression and subcellular distribution of the dystrophin-glycoprotein complex and laminin were examined in cardiac muscle by immunoblot and immunofluorescence analysis of rabbit and sheep papillary muscle. The five dystrophin-associated proteins (DAPs), 156-DAG, 59-DAP, 50-DAG, 43-DAG, and 35-DAG, were identified in rabbit ventricular muscle and found to codistribute with dystrophin in both papillary myofibers and Purkinje fibers. The DAPs and dystrophin codistributed not only in the free surface sarcolemma but also in interior regions of the myofibers where T tubules are present. Neither the DAPs nor dystrophin were detected in intercalated discs, a specialized region of cardiac sarcolemma where neighboring myocardial cells are physically joined by cell-cell junctions. Similarly, in bundles of Purkinje fibers, which lack T tubules, DAPs and dystrophin were also found to codistribute at the free surface sarcolemma but were not detected either in the region of surface sarcolemma closely apposed to a neighboring Purkinje fiber or in interior regions of these myofibers. Comparison between the distribution of the dystrophin-glycoprotein complex and laminin showed that laminin codistributes with the components of this complex in both papillary myofibers and Purkinje fibers. These results are consistent with previous findings demonstrating that the extracellularly exposed 156-DAG (dystroglycan) of the skeletal muscle dystrophin-glycoprotein complex binds laminin, a component of the basement membrane. Although we demonstrate that DAPs, dystrophin, and laminin colocalize to the sarcolemma in rabbit and sheep papillary myofibers as they do in skeletal myofibers, the most striking difference between the subcellular distribution of these proteins in cardiac and skeletal muscle is that the dystrophin-glycoprotein complex and laminin also localize to regions of the fibers where T tubules are distributed in cardiac but not in skeletal muscle. These results imply that the protein composition and thus possibly some functions of T tubules in cardiac muscle are distinct from those of skeletal muscle.

Animals↗
PubMed1993

Protein patterns in human vestibular ganglion cells and hair cells, with functional interpretations.

Cytoskeletal organization was analysed in the vestibular ganglion cells and in the sensory epithelia of all five vestibular organs of the adult human temporal bone. A pancellular rigidity of the upper surfaces of the vestibular organs, evidenced by large quantities of intermediate filaments and actin, seems of importance for the mechanoelectrical transduction by opposing the motion of the cupulae and statoconial layers. Immunostaining for the calcium-binding protein synaptophysin in the sensory hair bundles and in the area close to the cuticular plates--the first of its kind to be demonstrated in human vestibular organs--indicates the presence of calcium-dependent ionic channels. The hypothesis is presented that the calyx might be involved in a short-loop feed back control of type I hair cells, i.e. of the mechanoelectrical transduction itself. Subpopulations of vestibular ganglion cells were identified by the staining pattern of cytoskeletal proteins, but not by ordinary ultrastructural analysis.

Actins↗
PubMed1993

Comparative DNA image cytometry in imprint-, cytospin- and tissue section preparations of breast carcinoma.

Histologic sections, imprint preparations and cell preparations by enzymatic lysis from thick sections of cases of breast carcinomas were used to study total nuclear DNA distribution by image cytometry. Histologic sections are a prerequisite to unequivocally identify tumour cells as well as whole connective tissue cells used as a standard. While imprint preparations and lysis preparations are quite comparable with respect to distributional features, only one of them suffices to recognize these features, especially peaks at higher ploidies. Using this two-method approach to breast carcinomas, it was possible to distinguish a distribution separate from previously recognized distributions: a distinct triploid peak appears for predominantly high grade malignant ductal carcinomas.

Breast Neoplasms↗
PubMed1992

The Rhizobium meliloti pmi gene encodes a new type of phosphomannose isomerase.

Interspecific complementation of a Xanthomonas campestris pv. campestris phosphomannose isomerase (PMI) mutant was used to isolate a cosmid from a genomic library of Rhizobium meliloti 2011 carrying the pmi gene of this strain. Subcloning experiments localized the coding region to a 2.0-kb SalI-ClaI fragment. Nucleotide sequence analysis of this fragment indicated the presence of two open reading frames (ORFs), coding for 18- and 43-kDa polypeptides. The analysis of the gene function by gene disruption experiments showed that ORF2 codes for pmi. A comparison of the deduced amino acid sequence with the corresponding sequences of the Pseudomonas aeruginosa and Escherichia coli PMIs revealed no significant homology, indicating that the isolated gene encodes a new type of PMI. The construction of a pmi-deficient mutant of R. meliloti using the sacB-sacR cassette technique showed that the loss of PMI activity does not affect the symbiotic properties of this strain.

Amino Acid Sequence↗
PubMed1992

Investigations of droloxifene and other hormone manipulations on N-nitrosomethylurea-induced rat mammary tumours. 1. Influence on tumour growth.

The effect of droloxifene, a new anti-oestrogenic drug, on N-nitrosomethylurea-induced mammary tumours of Sprague-Dawley rats was investigated and compared with that of tamoxifen. The response of tumour growth to ovariectomy or to treatment with aminoglutethimide or high doses of oestradiol was also studied. Ovariectomy was by far the most effective treatment for mammary-tumour-bearing animals. More than 75% of the tumours in ovariectomized rats did not grow progressively but remained in remission for up to 12 weeks after castration when the experiment was terminated. The inhibitory effects of droloxifene and tamoxifen on mammary tumour growth were similar, but body weight loss of animals treated with tamoxifen was more marked than that of animals treated with droloxifene at the same dose and schedule.

Animals↗
PubMed1992

Investigations of droloxifene and other hormonal manipulations on N-nitrosomethylurea-induced rat mammary tumours. 2. Influence on oestrogen receptor.

In N-nitrosomethylurea-induced rat mammary tumours, tamoxifen is found to compete at the binding sites of the oestradiol receptor if a receptor determination is performed 1 day following the last drug application to animals. Despite a higher binding affinity of droloxifene (3-OH-tamoxifen) to oestradiol receptor, compared to tamoxifen, its influence on the measurable receptor quantity is only very weak or not demonstrable. Therefore, binding affinity is not a valid explanation for the different influences of the two anti-oestrogens on the receptor. These only can be attributed to different behaviour patterns of both substances in relation to their half-lives and metabolism and accumulation in the organism. Owing to the short half-life of droloxifene, even 1 day after the last application too little drug is available to compete for oestradiol binding sites. In the case of both anti-oestrogenic substances, cessation of drug application for 8 weeks abolished any influence on the oestradiol receptor. Furthermore, failure of aminoglutethimide to influence the oestradiol receptor could be observed because this substance does not act via this receptor. The experiments performed confirm literature data regarding the effect of aminoglutethimide therapy on oestradiol receptors in breast tumour tissue of human beings. In summary: receptor investigations of N-nitrosomethylurea-induced rat mammary tumours, used as a model to test therapy regimens with droloxifene or other drugs with a short half-life, may be of limited value only.

Aminoglutethimide↗
PubMed1992

Immunohistochemical characterization of the human endolymphatic sac and its associated cell populations.

The use of monoclonal and polyclonal antibodies as specific markers for the localization of tissue constituents in situ allows the characterization of cells according to their state of differentiation and the detection of cellular antigens related to the function of cells and tissues. Our studies focus on the immunohistochemical characterization of the human endolymphatic sac (ES) and its associated cell populations. A panel of 37 monoclonal and polyclonal antibodies were used on frozen sections and fixed material from 64 ES of 32 persons without any clinically known inner ear disorders. The ES were removed at the time of autopsy; case histories were available. The results of our studies on the extraosseous part of the human ES support the assumption that the epithelium is metabolically active and capable of both secretion and absorption. The reactivity of the epithelial cells with antibodies against neuron specific enolase, chromogranin and somatostatin, respectively, implies a paracrine activity of the ES. Further results obtained with antibodies specific for cells of the immune system indicate a possible role of the human ES in the inner ear immune defence and a functional relationship of the ES to the common mucosa-associated immune system.

Adolescent↗
PubMed1992

Genetics of xanthan production in Xanthomonas campestris: the xanA and xanB genes are involved in UDP-glucose and GDP-mannose biosynthesis.

The nucleotide sequence of a 3.4-kb EcoRI-PstI DNA fragment of Xanthomonas campestris pv. campestris revealed two open reading frames, which were designated xanA and xanB. The genes xanA and xanB encode proteins of 448 amino acids (molecular weight of 48,919) and 466 amino acids (molecular weight of 50,873), respectively. These genes were identified by analyzing insertion mutants which were known to be involved in xanthan production. Specific tests for the activities of enzymes involved in the biosynthesis of UDP-glucose and GDP-mannose indicated that the xanA gene product was involved in the biosynthesis of both glucose 1-phosphate and mannose 1-phosphate. The deduced amino acid sequence of xanB showed a significant degree of homology (59%) to the phosphomannose isomerase of Pseudomonas aeruginosa, a key enzyme in the biosynthesis of alginate. Moreover, biochemical analysis and complementation experiments with the Escherichia coli manA fragment revealed that xanB encoded a bifunctional enzyme, phosphomannose isomerase-GDP-mannose pyrophosphorylase.

Amino Acid Sequence↗
PubMed1992

Functional morphology of the human endolymphatic sac. A review.

Modern immunohistochemical methods allow a functional characterization of the human endolymphatic sac (ES) and its associated cell populations. The currently available immunohistochemical data on the extraosseous part of the human ES support the assumption that the epithelium is metabolically active and capable of both secretion and absorption. The reactivity of some epithelial cells with antibodies against neuroendocrine antigens implies a paracrine activity of the human ES. Further results provide evidence for a possible role of the human ES in inner ear immune defense and indicate a putative functional relationship of the human ES to the common mucosa-associated immune system.

Endolymphatic Sac↗
PubMed1992

Case report: top hearing performances of a postlingually deaf cochlear implant user.

On the occasion of the Cochlear Implant Symposium in Geneva in October 1991, top hearing results attained by a young postlingually deaf woman with cochlear implant systems were presented in video recordings. These data are centered on demanding hearing performances in test situations and in a telephone conversation. For various reasons, two reimplantations were necessary in this deaf patient. Initially, she was provided with a single-channel extra-cochlear electrode of the Vienna type, which she found to improve her lipreading substantially, and she attained an unexpectedly good understanding of speech on a purely auditory basis. Today, this postlingually deaf women uses a multichannel intracochlear electrode of the Nucleus type. The excellent results with the first extracochlear system are clearly surpassed with the intracochlear system. Not least because of her above-average speech competence, the cochlear implant user attains a high degree of open speech understanding. Her verbal hearing efficiency is comparable to that of a person with mild to moderately severe hearing loss.

Adolescent↗