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H J Altermatt

Publications and source records attributed to H J Altermatt.

138 records · Page 8Linked to original sources

[Immunopathology of the inner ear].

Immunologically mediated tissue lesions or functional disturbances can result from immune responses either to foreign antigens or autoantigenic constituents. Before a disease or a functional disorder can be called an (auto)immune disease, it must be established that immunological processes are involved in its etiology and/or pathogenesis. After reviewing the available data on immunology and on research on immunobiology of the inner ear, as well as clinical observations on disorders of the inner ear of possibly immunological origin, an attempt is made to determine whether (auto)immunopathology can be assumed in some patients with sensineural hearing loss. In patients with disorders presently recognized as autoimmune diseases, no hearing loss has been described so far. However, serum antibodies can be found via the indirect immunofluorescence method in some patients having functional disorders of the inner ear. These serum antibodies interact with normal human inner ear tissue. However, as long as immunopathological mechanisms have not been confirmed, these disorders should merely be called "diseases with autoimmune markers." It has been shown in animal experiments that the production of autoantibodies against inner ear components is associated with morphological and functional changes of the inner ear. The human endolymphatic sac releases secretory IgA into the lumen. Its epithelium contains (intraepithelial) lymphocytes, whereas lymphocytes, plasma cells (IgA, IgG) and macrophages occur in the perisaccular region. In this manner, the inner ear has its own immune system, which can possibly react independently of the systemic immune system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Histopathologic findings in the posterior pharyngeal wall 8 years after treatment of velar insufficiency with Teflon injection].

After a teflon injection into the submucosa of the posterior pharyngeal wall in a child, a corrective operative procedure was carried out eight years later because of severe open nasality due to velopharyngeal incompetence. A biopsy was taken from the eight year old teflon depot. The histological examination revealed a marked foreign body reaction with a persistent inflammation and fibrosis. The micromorphological comparison of the sizes of the teflon particles in the used teflon-glycerol paste with those detected in the examined tissue sample indicates the (cellular, lymphogenic) removal of the smaller teflon particles.

Adolescent↗

[Qualitative detection of immunoglobulins in the human endolymphatic sac].

Healthy human temporal bones and samples of the endolymphatic sac taken during surgery or from fresh cadavers were studied with regard to the presence of immunoglobulins. For demonstration of IgG, IgM, IgA and SIgA immunofluorescent methods and the immunoperoxidase-antiperoxidase method were used. Immunoglobulins are exclusively present within the endolymphatic sac whereas other structures of the healthy human inner ear do not show any positive reaction to the methods used for the demonstration of immunoglobulins.SIgA is clearly shown in epithelial cells of the rugosal part, whereas IgG predominantly is located in the flat endothelium--like cells of the extratemporal part. IgA and IgG further are detected within glycoproteins of the sac lumen and in plasma cells beneath the epithelium. Finally all subepithelial lymphatic spaces contain rich amounts of IgG. In one single temporal bone with tympanogenic labyrinthitis IgG and IgM wee present not only in all three layers of the round-window-membrane but also within the perilymphatic exudate. In this case IgM was found in the perisaccular tissue. The presence of free and local bound immunoglobulins exclusively in the region of the endolymphatic sac postulates and immunologic defense mechanism of this organ for the inner ear.

Antibody Formation↗

Determination of 5,10,15,20-tetra-(m-hydroxyphenyl)chlorin in human plasma by high performance liquid chromatography.

A high performance liquid chromatographic method for the determination of the photodynamic chemotherapeutic agent 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (m-THPC) in human plasma following intravenous infusion is described. The procedure involves extraction of the drug in plasma with methanol/dimethyl sulphoxide (4:1 v/v) containing 5,10,15,20-tetra(p-hydroxyphenyl)chlorin as the internal standard and separation on a C18 reversed phase column with acetonitrile:0.1% trifluoroacetic acid (77:23 v/v) as the mobile phase. The drug was detected specifically and sensitively at its absorption maximum of 423 nm with a detection limit of 15 ng/mL (signal-to-noise ratio of 5). The intra- and inter-assay coefficients of variation (CV) on analysis of a plasma spiked with m-THPC (1 micrograms/mL) were 2.3 and 3.4% (n = 6), respectively.

Antineoplastic Agents↗

Determination of 5,10,15,20-tetra-(m-hydroxyphenyl)chlorin in tissues by high performance liquid chromatography.

A procedure for the extraction and high performance liquid chromatographic (HPLC) determination of the photodynamic therapeutic agent 5,10,15,20-tetra(m-hydroxyphenyl)chlorin in human, rat and mouse tissues following intravenous administration of the drug is described. The tissue (tumour, skin, muscle and liver) was homogenized and extracted into a mixture of methanol:dimethyl sulphoxide:water (32:8:1 by vol.) containing, 5,10,15,20-tetra(p-hydroxyphenyl)chlorin as the internal standard. The precipitated proteins were removed by centrifugation and the supernatant was separated by reversed phase HPLC on a Hypersil-ODS column with 77% (v/v) acetonitrile in 0.1% trifluoroacetic acid as the mobile phase. The solute was detected with high sensitivity and specificity by a UV-VIS detector set at 423 nm.

Animals↗

Alterations of cell cycle regulators are less frequent in advanced non-small cell lung cancer than in resectable tumours.

Prognosis of lung cancer is related to stage of disease at time of diagnosis. In this study we examine alterations of pathways governing the cell cycle, in particular pRb-cyclinD1-p16 alpha and p53-p14ARF, in a series of NSCLC (n=92) at different stages at diagnosis. Using immunohistochemistry, we assessed the expression of the retinoblastoma protein (pRb), cyclin D1, p16 alpha, p53 and p14ARF. Tumours in stage I-IIIA (resectable) were more likely to have alterations in the pRb-cyclinD1-p16 alpha pathway than tumours in advanced stage (IIIB-IV) (90% versus 63%, P=0.002). pRb and p14ARF were more frequently downregulated in resectable tumours (P< or =0.03), and cyclin D1, p16 alpha, and p53 were altered at a similar frequency in resectable and advanced tumours. In 12 patients, metastatic sites (5 lymph node, 3 bone, 2 brain and 2 gastrointestinal metastases) were available for comparison with the primary tumour: 19 altered protein expressions were found to be concordant, six additional alterations (in 4 patients) were found in the metastases only, especially in lymph node metastases (3 patients). Compared with normal protein expression, both pathway alterations were associated with a longer survival (P=0.02). In a multivariate analysis (Cox regression) this difference was not maintained after adjustment for age, stage and tumour differentiation. Cyclin D1 was the sole protein with independent prognostic value in resectable tumours: the relative risk of local relapse was 4.7 in tumours without cyclin D1 overexpression (P=0.02, Cox regression analysis). No protein studied had a predictive significance for response after chemotherapy in non-resectable tumours. These results demonstrate a strong correlation between stage and pathway alterations, cell cycle regulators being less likely altered in advanced NSCLC. Tumours with defects in these control pathways tend therefore to remain localised and to metastasize at a later phase in tumour development. This finding might be an explanation for distinct biological behaviour (e.g. chemotherapy response) of resectable versus advanced disease.

Aged↗

Human papillomavirus status in advanced cervical cancer: predictive and prognostic significance for curative radiation treatment.

Human papillomavirus (HPV) infection plays a major role in oncogenesis of squamous cell carcinoma of the cervix. This study was performed to investigate if HPV status and E2 gene integrity are prognostic parameters for clinical outcome and predictive for radiation response. Forty women with locally advanced cervical cancer treated with curative radiotherapy were analyzed for HPV infection and E2 gene integrity by multiplex polymerase chain reaction. Statistical analyses were performed for overall survival, disease-free survival (DFS), local progression-free survival, and treatment response (clinical complete remission). Twenty-eight (70%) of 40 carcinomas were HPV positive. The only significant factor for a better overall survival, DFS, and local progression-free survival was HPV positivity (P < 0.02, P= 0.02, and P < 0.05, log-rank, respectively). HPV-positive tumors had a significantly better clinical complete remission (67% vs 33%, P= 0.04, Fisher's exact test). An intact E2 gene region showed a trend for a better DFS (P= 0.1, log-rank). This study reveals HPV as an independent prognostic parameter for outcome and radiation response. Integration of the virus genome into host cell DNA might be a molecular target to determine the treatment response of HPV-positive cancers.

Adult↗

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↗

Cytomorphology of subependymal giant cell astrocytoma.

The cytomorphology of three subependymal giant cell astrocytomas (SEGA) is described. The tumors occurred in the left lateral ventricle of three males with tuberous sclerosis. The often-polarized spindle and epithelioid tumor cells possessed dense eosinophilic cytoplasm, eccentric nuclei and visible, occasionally prominent nucleoli. In addition, they displayed thick or hairlike processes and had a distinct tendency to form cohesive clusters as well as pseudorosettes. Occasional binucleate and multinucleate cells, as well as "strap" cells and nuclear cytoplasmic inclusions, were further features of this unique tumor. In cytologic terms the principal differential diagnostic considerations include gemistocytic astrocytoma, giant cell glioblastoma and ependymoma. Since, in isolation, SEGA may represent a "forme fruste" of tuberous sclerosis and since patients with tuberous sclerosis may have brain tumors other than SEGA, it is of diagnostic importance to recognize the cytomorphologic features of this essentially benign brain tumor.

Astrocytoma↗

Glucose consumption and lactate production of human placental tissue under different conditions of in vitro incubation.

OBJECTIVE: To assess the glycolytic activity of human placental tissue in the third trimester as measured by glucose consumption and lactate production under different conditions of in vitro incubation. METHOD: An incubation technique was used to study the metabolic activity of the human placenta by comparing large blocks (0.3 cm3, T1) and small fragments (explants, 0.03 cm3, T2). Placentas were obtained from premature (28-33 weeks) and term (39-41 weeks) deliveries. In addition, different experimental conditions were used to investigate the influence of incubation medium (Earle's buffer and cell culture medium NCTC = 135), medium oxygen pressure (PO2) (400 and 30 mmHg), and regional sampling of placental tissue (central, intermediate, and peripheral). All media contained glucose (1 g/L). The tissue (2-3 g/25 mL medium, pH 7.2-7.4) was incubated for 3 hours at 37C. 3H-inulin was used for the determination of the extracellular space. RESULTS: Incubation of both tissue forms yielded a higher metabolic activity as measured by glucose consumption and lactate production when incubated with Earle's buffer compared with incubations with NCTC medium. In general, the metabolic activity was consistently higher for small fragments compared with the large blocks. Extracellular space values found for large fragments (25-31%) were significantly lower than for small pieces (39-46%), indicating that an equilibration of the medium with the extracellular space is inadequate with large fragments. Incubation with small fragments showed that 1) there is a tendency for higher metabolic activity during incubation with lower PO2, 2) the metabolically most active part of the placenta is the intermediate tissue region, and 3) placental metabolic activity was significantly higher at 28-33 weeks (n = 5) than at term (n = 6). These differences were not seen with large fragment incubations. CONCLUSION: The smaller tissue fragments are preferable for the in vitro incubation study of placental glucose metabolism. Apparently, there are differences in the metabolic activity with regard to the placental tissue region and gestational age.

Culture Media↗