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Biomedical subjects

W Hoffmann

Publications and source records attributed to W Hoffmann.

At least 127 records · Page 7Linked to original sources

Ambulatory blood pressure monitoring in healthy schoolchildren.

Ambulatory blood pressure monitoring (ABPM) was performed in 564 healthy schoolchildren during normal circadian activities. The data of two cohorts (155 boys and 139 girls aged 9-13 years and 184 boys and 168 girls with a body height between 120 and 155 cm) are presented. From the age of 9 to 13 years the mean 24-h systolic/diastolic blood pressure (SBP/DBP) increases from 107 +/- 9/66 +/- 7 mmHg to 115 +/- 13/68 +/- 9 mmHg in boys and from 104 +/- 5/64 +/- 6 mmHg to 109 +/- 8/65 +/- 9 mmHg in girls. When related to body height the values rise from 105 +/- 6/64 +/- 6 mmHg at 120 cm to 113 +/- 8/67 +/- 7 mmHg at 155 cm in boys and from 100 +/- 7/65 +/- 7 mmHg to 112 +/- 9/66 +/- 9 mmHg in girls. In comparison with the causal blood pressure data obtained from European studies, the presented ABPM values (daytime BP) are higher throughout, which may be explained by the increased activity during daytime with ABPM. There is a mean difference of 4.4 mmHg in boys and of 3.0 mmHg in girls for SBP and of 10.8 mmHg in boys and of 9.0 mmHg in girls for DBP when related to age. In relation to body height, there is a mean difference of 4.4 mmHg in boys and of 3.5 mmHg in girls for SBP and of 10.9 mmHg in boys and of 10.5 mmHg in girls for DBP. We conclude that standards derived from causal blood pressure measurements should not be used for the evaluation of ABPM data.

Adolescent↗

LLC-PK1 epithelia as a model for in vitro assessment of proximal tubular nephrotoxicity.

LLC-PK1 cells, an established epithelial cell line derived from pig kidney, were used as a model system for assessment of nephrotoxic side effects of three cephalosporin antibiotics: cephaloridine, ceftazidime, and cefotaxime. Toxic effects of these xenobiotics were monitored on confluent monolayers by light and electron microscopy and by the release of cellular marker enzyme activities into the culture medium. In addition, LLC-PK1 cells were grown on microporous supports, and cephalosporin-induced alteration of epithelial functional integrity was monitored by a novel electrophysiologic approach. For this purpose, an Ussing chamberlike experimental setup was used. The dose-dependent effects on transepithelial ionic permselectivity were monitored under conditions in which defined fractions of the apical culture medium NaCl contents were replaced iso-osmotically by mannitol. This method of determining the functional intactness of the epithelial barrier by measuring dilution potentials was found to be far more sensitive than monitoring cell injury by means of morphology or measurement of enzyme release. As expected from animal experimental data, a dose-dependent disruption of monolayer integrity was detected with all three methodologies applied. Cephaloridine was found the most toxic compound followed by ceftazidime, where a 3-fold, and cefotaxime, where a 10-fold dose of that of cephaloridine was needed to produce cell injury. Measurement of transepithelial dilution potentials was more sensitive as compared to the release of the apical plasma membrane marker enzyme activities alkaline phosphatase and gamma-glutamyltranspeptidase, the cytosolic lactate dehydrogenase, or the mitochondrial glutamate dehydrogenase. The data were compared to the effects of the aminoglycoside antibiotic gentamicin, which at least with respect to its effects on LLC-PK1 morphology and enzyme release, but not transepithelial electrical properties, was already investigated.

Acetylglucosaminidase↗

Molecular and cellular analysis of rP1.B in the rat hypothalamus: in situ hybridization and immunohistochemistry of a new P-domain neuropeptide.

P-domain peptides, a new family of secretory polypeptides, have been identified mainly in the gastroenteropancreatic tract of humans, rodents, and amphibians as well as in amphibian skin. In the present study, with PCR and RNA analysis a transcript has been discovered in rat brain termed rP1.B. The deduced polypeptide consists of a single P-domain and its amino acid sequence matches that of rat intestinal trefoil factor (rITF). Thus far, rP1.B is the only P-domain peptide expressed in neuronal cells of the CNS. Immunostained magnocellular perikarya were visible in the paraventricular, supraoptic and periventricular nuclei. Parvocellular rP1.B neurons were found in the arcuate nucleus. Additionally, specific hybridization signals with radiolabeled transcripts were observed in the same regions. rP1.B in the rat hypothalamus may be involved in the control of hypothalamo-hypophysial functions.

Amino Acid Sequence↗

Treatment of esophagorespiratory fistulas with silicone-coated self-expanding metal stents.

Nine self-expanding silicone-coated modified Gianturco metal stents were inserted in 8 patients (mean age, 58.2 years) for palliation of malignant esophagorespiratory fistulas caused by esophageal (n = 5) or bronchial (n = 3) carcinoma. One patient with a fistula above a 12-cm-long malignant stenosis received two overlapping stents. The implantation procedure was well tolerated by all patients under intravenous sedation and analgesia. After release, the stents expanded to their full diameter, leading to complete occlusion of the fistulas and bridging of the concomitant stenoses. Two patients with lung cancer received an additional tracheobronchial stent before esophageal stent insertion. Failure to maintain complete contact between the proximal stent margin and the esophageal wall led to insufficient sealing of the fistula of 1 patient and recurrent aspiration, manifested 6 days after stent implantation (overall success, 87.5%). The other patients could swallow semi-solid food until death. Seven patients died of advanced metastatic disease after 21 to 121 days (mean, 54 days) and 1 patient of massive hemoptysis 10 days after stent placement, which could be regarded as a complication (procedure-related mortality rate, 12.5%). These preliminary results suggest that peroral insertion of the modified silicone-coated Gianturco stent is a rapid, reasonably safe, and effective procedure for palliation of malignant esophagorespiratory fistulas.

Adenocarcinoma↗

[Vitamin A in tumor therapy: significance of clinical and pre-clinical findings for radiologic oncology].

PURPOSE: Retinoids are a class of compounds structurally related to vitamin A which have been found to be active agents experimentally as well as clinically in the prevention and treatment of tumors. The data available suggest to study whether they might improve treatment results if combined with irradiation. METHODS: The clinical results in the prevention and treatment of cancer with retinoids are reviewed. In the context of experimental studies evaluating the antiproliferative effects of retinoids, cytokines and radiation alone or in combination our own experimental investigations analyzing a combination of all-trans-retinoic acid, interferon-alpha (IFN-alpha) and ionizing radiation in squamous cell carcinoma cell lines are described. RESULTS: There is a solid body of experimental and clinical data to combine retinoids with cytokines (e.g.IFN-alpha). Since it is known that vitamin A alters the radiation response in experimental tumors our analyses further support the combination of retinoids and IFN-alpha with ionizing radiation. CONCLUSIONS: We emphasize further clinical investigations evaluating the combined treatment with retinoids/IFN-alpha and ionizing radiation in squamous cell carcinomas such as head and neck tumors and cervical cancer.

Animals↗

Ependymins and their potential role in neuroplasticity and regeneration: calcium-binding meningeal glycoproteins of the cerebrospinal fluid and extracellular matrix.

1. Ependymins are unique, highly divergent secretory proteins of the fish endomeninx. Thus far, no homologous sequences have been characterized in mammals. 2. Soluble ependymins are the predominant constituents of the cerebrospinal fluid of many teleost fish. A bound form of these glycoproteins is associated with the extracellular matrix probably with collagen fibrils. The latter may be the functional form of ependymins. 3. Ependymins bind Ca2+ via N-linked sialic acid residues leading to a conformational transition. 4. The molecular function of ependymins seems to be related to cell contact phenomena involving the extracellular matrix. For example, adhesive or anti-adhesive interactions may possibly influence ingrowing axons.

Amino Acid Sequence↗

[The value of the supine chest x-ray with digital luminescence radiography in relation to the experience of the observer. A ROC analysis in CT-validated cases].

The aim of the present study was to evaluate supine chest radiographs obtained by DLR for the diagnosis of pleural and parenchymatous changes and to compare the accuracy of observers in relation to their experience. 50 examinations, which had been checked by CT, were chosen. The images were examined by 7 doctors (2 non-radiologists, 5 radiologists). Our experience indicates that DLR has high specificity but low sensitivity for the diagnosis of a pneumothorax but relatively high sensitivity and low specificity for other changes (pleural effusions, atelectases and other intrapulmonary opacities). The area under the ROC curve averaged over the 7 rater was similar for these 4 entities. There were marked differences between the observers; the radiologists were considerably better than the non-radiologists. Altogether, the diagnostic value of single DLR examinations was relatively low. In indeterminate cases, additional diagnostic methods should, therefore, be used.

Adolescent↗

Molecular anatomy of a skin gland: histochemical and biochemical investigations on the mucous glands of Xenopus laevis.

The purpose of this study was to investigate the structure and chemical composition of the mucous skin gland of Xenopus laevis by combined morphological and biochemical techniques. Protein backbones of mucins were localized immunohistochemically in the gland with anti-peptide antibodies. Acid mucins were demonstrated by conventional histochemical techniques and their terminal carbohydrate residues were localized by lectin histochemistry. A close correlation between antibody and lectin binding of the same glycoproteins was achieved on Western blots from isolated skin gland mucins, indicating that the lectin-binding sites were due to defined mucin molecules. The cone cell, thought to be a degenerative cell in the past, contained mucin granules with an electron-dense core, strong PAS reactivity, a special lectin-binding pattern, and localization of integumentary mucins FIM-B.1 and FIM-C.1. These results indicate that cone cells are a distinct cell type, elaborating and releasing particular mucins, and that functional heterogeneity of mucus-producing cells exists in the mucous skin glands of X. laevis.

Animals↗

[The clinical picture and therapy of malignant pleural mesothelioma].

BACKGROUND: In the general population malignant pleural mesothelioma is an uncommon tumor with an average annual incidence of 15 cases per million. Its biological behavior is characterized by an infiltrating and aggressive growth. Median survival ranges between 6 and 12 months. There are different therapeutic modalities (surgical treatment, radiotherapy, chemotherapy), which are used alone or in combination to influence the poor outcome of pleural mesothelioma. PATIENTS AND METHODS: We report about 7 of our own cases, treated with surgery and radiotherapy (4) or with a combination of surgery, radiotherapy and chemotherapy (3) and discuss the clinical aspects, diagnosis and the different ways of treatment of malignant pleural mesothelioma and its influence on survival. RESULTS AND CONCLUSION: The extrapleural pleuropneumonectomy should be reserved to patients with stage I disease. Radical operation here offers some prospect of long-term survival. Palliative surgery such as pleurectomy is the treatment of choice for extended disease. Radiotherapy using doses between 45 and 50 Gy is useful in a palliative setting. Anthracyclin or cisplatin based chemotherapy may be helpful in cases with disseminated disease. Prospective trials are necessary to further clarify the role of multimodality treatment programs for malignant pleural mesothelioma.

Aged↗

Calcium binding to sialic acids and its effect on the conformation of ependymins.

Soluble ependymins from the predominant protein constituents in the cerebrospinal fluid from many orders of teleost fish. Furthermore, these glycoproteins also exist in a bound form associated with the extracellular matrix. Ependymins are synthesized in meningeal fibroblasts. In goldfish, their synthesis is increased during the regeneration of the optic nerve and they share several characteristics with molecules involved in cell contact phenomena. In this study, we show by a calcium overlay technique that ependymins from goldfish and rainbow trout are able to bind 45Ca2+. However, nearly all of this Ca(2+)-binding capacity is lost after digestion with sialidase. Furthermore, circular-dichroism spectra from FPLC-purified rainbow trout ependymins have been recorded in the presence and absence of Ca2+. Below 250 nm, the CD spectrum showed a characteristic minimum of ellipticity at 217 nm typical of beta structures. This signal is independent of the Ca2+ concentration. In contrast, the complex signal at 250-310 nm mainly decreased with increasing Ca2+ concentration indicating changes in the environment of aromatic side chains.

Animals↗

hP1.B, a human P-domain peptide homologous with rat intestinal trefoil factor, is expressed also in the ulcer-associated cell lineage and the uterus.

The six-cysteine P-domain motif forms the basic repeat unit of a growing family of mucin-associated peptides. A precursor for a human secretory polypeptide has been discovered by molecular cloning and deduced to have a single P-domain, termed hP1.B. The pre-pro-peptide has 67% amino acid identity with rat intestinal trefoil factor. We find, using the techniques of RNA analysis and in situ hybridization, that this P-domain peptide is expressed in the human gastrointestinal tract, where a number of pathological conditions affect its expression, and surprisingly find it is expressed in the uterus also. In the intestine, hP1.B is expressed by goblet cells, but in Crohn disease this peptide is synthesized and secreted additionally by the ulcer-associated cell lineage that is known to secrete two other trefoil peptides, pS2 and spasmolytic polypeptide (hSP). In the stomach, hP1.B mRNA is relatively scarce but is more abundant in foci of intestinal metaplasia and near to ulceration. Mucin-rich epithelial cells in hyperplastic polyps of the colon also express this peptide. The discovery of this P-domain peptide and its expression in association with mucins support the hypothesis that P-domains with mucins may subserve related functions in the maintenance and repair of mucosal function.

Amino Acid Sequence↗