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Biomedical subjects

W Arnold

Publications and source records attributed to W Arnold.

607 records · Page 34Linked to original sources

Ultrastructural histopathology in a case of human ototoxicity due to loop diuretics.

The temporal bones of a patient who suffered sudden deafness and ataxia after administration of both furosemide and ethacrynic acid, were prepared for light and electron microscopy. There was no loss of hair or supporting cells. However, some hair cells, in both the vestibular neuroepithelium and the organ of Corti, particularly in the basal turn, were more densely staining and more granular than normal. Membrane whorls also were common within mitochondria of such cells. The endoplasmic reticulum of some spiral ganglion cells was dilated. The major cytologic changes were found in the stria vascularis of the cochlea and dark cell areas of the vestibular system. There was marked dilatation of the intercellular fluid spaces, consistent with the biochemical observation that loop diuretics interfere first with enzyme systems responsible for fluid transport within the inner ear.

Cochlea↗

Morphological evidence of viruses in nasopharyngeal carcinoma?

Human tumor tissue from patients with nasopharyngeal carcinoma was investigated electron microscopically before and after transplantation to nude mice. Although we were unable to find distinct herpes type-C particles in human tissue, these particles could be seen following tissue transplantation to nude mice in two cases. The findings are discussed as to whether those particles are either endogenous in nude mice or expressed by the tumor tissue as a consequence of transplantation.

Animals↗

Evidence of serum antibodies against inner ear tissues in the blood of patients with certain sensorineural hearing disorders.

In healthy human temporal bones, immunoglobulins (IgG, IgA) and the secretory component are demonstrated by two immunohistochemical methods in epithelial cells and in the lumen of the endolymphatic sac. The normal human inner ear does not otherwise show any localization of immunoglobulins. By means of indirect immunofluorescence, antibodies against healthy inner ear tissue were found in the serum of 15 out of 21 patients with double-sided progressive or fluctuating sensorineural hearing loss of undefined etiology. In 2 cases of Cogan's syndrome, it was also possible to demonstrate serum antibodies against epithelial structures of the cornea. The lymphocyte mitogen stimulation test performed with the fresh blood of 5 patients with positive detection of serum antibodies against healthy inner ear tissue was negative.

Autoantibodies↗

Immunohistochemical investigation of the human inner ear. Limitations and prospects.

The application of highly sensitive and specific immunohistochemical methods in routine light microscopy has been rewarded by a great many new observations. The essential underlying antigen-antibody reaction has allowed the recognition and identification of some unknown or unidentified components of the cell. Successful results are best achieved by means of reliable fixation and the use of frozen sections. Frozen sections of the human cochlea are, however, impaired by unavoidable damage to the tissues to be studied. The temporal bone has to be decalcified, resulting in a reduction of the range of suitable methods and an interference with a reliable interpretation of the results. The preservation of the specific antigenicity of the tissues is of paramount importance, allowing the detection of the investigated antigen by the antibody applied. The investigation of different fixatives and various methods of decalcification in tissues possessing some familiar and readily identifiable antigens has confirmed the immunohistochemical suitability of properly fixed and adequately decalcified human temporal bones. The present demonstration deals with some of the principal technical procedures and includes examples of their application for the study of the human inner ear. The goal of our research is the development of reliable immunohistochemical methods of fixation and decalcification to be employed in the study of specimens from patients with Ménière's disease, sudden deafness, progressive loss of hearing, genetic sensorineural syndromes, etc. This will lead to the extension of our knowledge of some unrecognized causes of sensorineural hearing loss.

Ear, Inner↗

Outer hair cells as fast and slow cochlear amplifiers with a bidirectional transduction cycle.

Cochlear hair cells fulfil the key function in hearing. However, possible differences in functions of inner and outer hair cells are the subject of a current scientific discussion. In the present paper, we present steps of the sensory transduction in living mammalian hair cells. The transduction is a mechano-electrical process based upon ionic channels in the outer cell membrane. These mechanisms are suggested to be similar in inner and outer hair cells, allowing inner hair cells the actual sound perception. By contrast, the outer hair cells seem to control actively the micromechanics of the inner ear on the basis of fast and slow motor properties. Our results revealed that in these cells, electro-mechanical mechanisms can induce fast and slow motile events. Together with the above-mentioned mechano-electrical transduction, the electro-mechanical mechanisms are assumed to establish a bidirectional transduction cycle in outer hair cells. These active motor properties of outer hair cells are obviously disturbed in acute attacks of Meniére's disease or in aminoglycoside intoxication, and may thus partly explain the resulting deafness.

Animals↗

Structurally based new functional interpretations of the subsurface cisternal network in human outer hair cells.

The system of subsurface cisterns (SSC) in human outer hair cells (OHC) was studied by high-resolution transmission electron microscopy (TEM). The SSC consist of only a single layer of cisterns, either flattened or tubular. The subsynaptic cisterns of efferent synapses are an integral part of the SSC. The outer leaflet of the SSC facing the cell membrane is connected to the OHC wall by pillars arranged in a highly regular and geometric pattern. The inner leaflet facing the cytoplasm displays an identical pattern of particles arranged in a star-like configuration so that pores are formed centrally. Pores are also identified at the outer leaflet and at the insertion of the pillars into the cell membrane. It is hypothesized that this highly specific organization of SSC, so far described only in the human OHC wall, is controlled by the efferent acetylcholine-mediated innervation.

Cell Membrane↗

[Changes in area of mucous membrane in otosclerosis].

In 98 samples of middle-ear mucosa, taken from patients during otosclerotic stapes surgery, considerable pathological changes in the organization of the capillaries were found (endothelial hydrops, proliferation of the intima and adventitia, total obliteration of small vessels). They caused pathological reactions of the mesenchymal elements of the submucosa: fibrocytes undergo lysis, collagen fibres show fibolysis and hyalinosis. Free and cellular bound calcium deposits are located in these lytic areas. Even the epithelial stratum reveals uncommon inclusions such as glycogen and acid mucopolysaccharides. The basement membranes of the capillaries as well as of the epithelium show enlargements and solution of their ultrastructure. The changes of the connective tissue and of the epithelium are secondary to the capillary obstructions.

Capillaries↗

[Comparative studies of carcinomas of the human oral mucosa and xenografts in the nude mouse with the aid of computer-supported microscope image analysis].

The complete preservation of the original characteristics of donor tumors after xenografting into nude mice is more and more doubtful. With the aid of traditional biological methods and computer-assisted microscope image analysis the original human tumor tissues, including primary and recurrent tumors and metastases, are compared with nude mouse-grown xenografts. Squamous cell carcinomas of the oral mucosa served as original tumor tissues. Tumor takes were observed in 7 out of 12 cases. 5 transplantable lines could be established. Primaries, recurrent tumors and lymph node metastases are suitable for transplantations into nude mice and yield a comparable success rate. With one exception complete conformity between the original human tumor tissues and nude mouse-grown tumors could be found regarding the degree of differentiation and keratinizing tendency. As to the growth pattern of xenografts characterized by continuous shortening of growth periods, certain variations in the biological properties due to selection processes cannot be excluded. The results of microscope image analysis based on 35 different parameters suggest important differences within the developmental tendency of human tumor tissues and nude mouse-grown xenografts.

Animals↗

Critical evaluation of the immunofluorescence microscopic test for identification of serum antibodies against human inner ear tissue.

One hundred and nineteen serum samples from patients with bilateral sensorineural hearing loss of unknown etiology were investigated for the presence of antibodies against homologous inner ear tissue. 54% of all investigations revealed a binding of serum immunoglobulins even after repeated checks, whereas the investigation of 25 control sera of healthy subjects revealed a false-positive result in only one single case: in this control subject, a manifest rheumatism could be diagnosed later. A correlation between the positive result of the immunofluorescence test and clinical parameters which might indicate a pathoimmune mechanism could not be detected. The question arose as to whether immunologically induced alterations in the region of the human inner ear can be demonstrated at all with the methods of investigation in clinical use today to detect a systemic pathoimmune mechanism.

Autoantibodies↗

Liver-associated toxicity of the HSV-tk/GCV approach and adenoviral vectors.

Intravenous injection of immunodeficient mice with adenoviral vectors carrying the HSV-tk gene led to preferential transduction of liver tissue. Subsequent application of ganciclovir (GCV) resulted in extremely high toxicity with negligible survival rates. This toxicity was only seen when GCV was applied in addition to the adenoviral vector and not if combined with the Ad-beta gal control vector. This indicates a specific Ad-tk/GCV-related toxicity. Low survival rates were seen not only after intravenous administration but also after injection of the vectors into the portal vein, the liver tissue and liver tumors, but not during the treatment of subcutaneous tumors. This, together with extensive signs of liver degeneration occurring as early as one day after the initiation of GCV treatment, strongly suggests a specific liver-associated toxicity. Severe toxicity was observed when animals received GCV treatment as late as 7 weeks after vector administration. Moreover, in vitro survival rates of resting primary hepatocytes treated with Ad-tk and GCV were very low. We therefore suppose a mechanism of toxicity of phosphorylated GCV which is independent from cellular proliferation. Since our results indicate that the Ad-HSV-tk/GCV approach is toxic for the resting liver, additional safety features such as tumor-restricted transgene expression should be included in adenoviral vectors.

Adenoviridae↗