Elevated levels of organotins in Lake Geneva: bivalves as sentinel organism.
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Biomedical subjects
Publications and source records attributed to K Becker.
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We report the case of a patient with renal insufficiency who was admitted for the evaluation of splenomegaly. He had received a kidney allograft 6 1/2 years ago. Treatment with azathioprine and prednisolone for immunosuppression had been discontinued 1 year before admission. The underlying cause of the splenomegaly appeared to be an idiopathic portal hypertension. Until now, this disease has been described in only 13 kidney transplant patients receiving long-term immunosuppressive therapy with azathioprine. For the first time we demonstrate that azathioprine can cause this chronic liver disease even if the drug has been withdrawn some time before. Therefore, the indication for azathioprine must be considered very carefully.
We investigated immunohistologically 160 teeth and dental germs in various stages of tooth development taken from human individuals (13th week of pregnancy to the 24th year of life) to study the osteonectin expression in dental hard tissue. In the course of dentinogenesis, the predentin, the odontoblasts, and their cell processes show a positive osteonectin staining reaction. During cementogenesis, osteonectin is synthesized by cement-producing fibroblasts, cementoblasts, and cementocytes. The expression of osteonectin during dentinogenesis and cementogenesis is closely related to the development of the respective calcified tissue. All cells of the inner and outer enamel epithelium, the cells of the stratum reticulare and stratum intermedium, the ameloblasts, and the enamel substance are osteonectin negative, just as dentin and cement are. The results of this study indicate one important physiological role of osteonectin as a protein associated with the formation of collagen containing mineralizing tissues like human bone, as well as human dentin and cement.
1. Four Zebu and four Simmental oxen were submitted to moderate and exhaustive work. Venous blood samples were taken before, immediately after and 30 min after work and assayed for several blood parameters. 2. Draught work led to a decrease in carbon dioxide (pvCO2) and increases in pH, oxygen (pvO2), triglycerides, free fatty acids (FFA) and lactate. 3. Zebu oxen had higher pvCO2 and FFA and lower pH, pvO2 and lactate in response to exercise. 4. Ratios of individual draught power output and values of pvO2 and lactate after work enable the identification of fit and/or weak individuals.
2'-5'-oligoadenylate synthetase, an interferon-induced enzyme and a sensitive indicator of the presence of interferon, was measured in peripheral blood mononuclear cells in children with inflammatory disorders of known and unknown origin in order to assess the value of such a test in patient management. Differences in median 2'-5'-oligoadenylate synthetase values in groups of children with viral or bacterial diseases or healthy children were observed. Considerable overlap of the 2'-5'-oligoadenylate synthetase range in the three groups was observed. All children with acute viral infections had increased levels early in their disease and a low value clearly argued against an acute viral infection. However, as more than one-third of children with bacterial diseases displayed elevated 2'-5'-oligoadenylate synthetase concentrations, distinction between a viral and bacterial cause of disease by measuring this enzyme was difficult. Estimation of 2'-5'-oligoadenylate synthetase concentrations in patients with inflammatory diseases of unknown origin, including juvenile rheumatoid arthritis, systemic lupus erythematosus, idiopathic uveitis and glomerulonephritis did not contribute to establishing a diagnosis or measuring disease activity.
The "discovery" of alpha 2-receptors permits the explanation of the mechanism of xylazine that was hitherto poorly understood. The substance can be classified as an alpha 2-adrenoceptor agonist. In the near future two new alpha 2-adrenoceptor agonists will be available in Germany: medetomidine for small animals and detomidine for large animals. Also a new alpha 2-adrenoceptor antagonist will be introduced: atipamezole. alpha 2-adrenoceptor agonists cause sedation, analgesia and muscle relaxation. Notable side effects are bradycardia, heart block and a dose dependent respiratory depression. A comprehensive survey on the pharmacology of the alpha 2-adrenoceptor agonists is given. The previous literature is summarized and discussed, including own studies and clinical experience. An attempt is made to assess the clinical importance of the new drugs. For certain indications medetomidine alone may not be satisfying and combination with other drugs becomes necessary. If sedation is inadequate, the combination with benzodiazepines or propofol is advised; if analgesia is poor, the combination with ketamine or an opioid is recommended.
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Umbilical hides from 536 dairy cattle in Minnesota were tested for the microfilarial stage of Onchocerca species to determine the distribution of onchocerciasis in the state. The infection was widespread as microfilariae were obtained from 214 (40%) of the animals, representing nearly all areas of the state. Adult Onchocerca parasites were collected primarily from nodules associated with tibial bones but also were found to a lesser extent within the gastrosplenic ligament. Specific identity of these organisms is unclear as they exhibit certain morphological features previously described as being characteristic of either Onchocerca gutturosa, Onchocerca lienalis, or Onchocerca stilesi.
Iodo-doxorubicin (I-DOX) is a new doxorubicin (DOX) analog presently in phase II clinical trials in Europe. This drug is similar to DOX in its metabolism but differs in its pharmacokinetics. We describe correlations between pharmacokinetic parameters and toxicity. There is a linear relationship between the dose in mg/m2 and the nadirs of the reduction in white blood cells (WBC), neutrophils (PMN), platelets (PLT), and hemoglobin (HB). Furthermore, a linear correlation exists between the dose in mg/m2 and the area under the curve (AUC) of I-DOX. The relationship between the AUC of I-DOX and the reduction of PMNs plotted on a logarithmic scale shows a sigmoidal curve, whereas no such correlation was found between I-doxorubicinol, the major cytostatic metabolite, and the reduction in PNMs. The variation in the AUC for I-DOX correlated with the relative amount of metabolism of I-DOX. A correlation existed between the relative amount of metabolism of I-DOX and the reduction in PNMs. These results may have an impact on the evaluation of I-DOX in phase II trials, since a sound understanding of the pharmacokinetic/pharmacodynamic relationships can yield important information for minimizing unacceptable toxicity during phase II, as well as phase III, trials.
To elucidate the early events of cancer development in the columnar cell-lined lower esophagus, 13 esophagectomy specimens with early adenocarcinoma (T1) were histopathologically studied and the morphometry of the lesion was performed on a histologic map. Eleven (84.6%) of the 13 early Barrett's carcinomas were contiguous to both the distinctive specialized-type Barrett's mucosa and squamous epithelium. Furthermore, ten (76.9%) of the 13 tumors had residual squamous islands on the surface. These data suggest that carcinomas in Barrett's esophagus mostly develop at a place very close to the squamocolumnar epithelial border. The distance from the tumor center to the nearest squamous epithelium, including squamous islands, was 2 cm or less in all cases but one. Therefore, the authors conclude that the primary site of cancer development in Barrett's esophagus is the metaplastic columnar-lined area, particularly of specialized type, within 2 cm from the squamocolumnar epithelial border.
The course of disease in 119 HIV-infected patients (117 men, 2 women; median age 38.5 years) with malignant tumours other than Kaposi's sarcoma was analyzed in a multi-centre retrospective study. This was conducted to obtain initial information concerning the incidence, clinical features and results of therapy in HIV-associated neoplasms, especially malignant lymphomas. The most frequent tumour was malignant non-Hodgkin's lymphoma (98 patients, 82.5%), seven patients had Hodgkin's disease, five had solid tumours, four a polyclonal lymphoproliferative syndrome, three an acute lymphocytic leukaemia, and two had other lymphoproliferative diseases. 58% of the non-Hodgkin's lymphomas occurred in patients with marked immunodeficiency, 85% were high grade malignancies and 47% had primary extranodal disease. 56% of primary nodal lymphomas also had visceral spread (Stage IV). Lymphoblastic non-Hodgkin's lymphoma was more common in patients with favourable immunological status, presented less frequently with primary extranodal disease, was diagnosed earlier than other non-Hodgkin's lymphomas, and appeared to carry a better prognosis. 78 out of the 98 patients with non-Hodgkin's lymphoma had been treated, 66 with cytotoxics. The median survival time was 6 months. Longer remission periods, of at least 12 months, were seen in ten of the 78 patients (13%). Despite the overall poor prognosis and the pre-existing immune defect, palliative (chemo-)therapeutic measures are both justified and promising, and may also result in life-prolonging remissions.
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Hybridomas producing monoclonal antibodies of different isotypes were isolated from BALB/c antibody responses to the capsid protein VP1 of the foot-and-mouth disease virus (FMDV) strain O1. According to antigen binding measured by ELISA a weak-binding (81D10, IgM) and a strong-binding antibody (113C12, IgG2a) were selected. As RNA sequencing of productive immunoglobulin VH and VK genes turned out, both chains of the weak-binding antibody (81D10) are encoded by germline (i.e. not mutated) genes whereas the gene encoding the strong-binding antibody (113C12) k chain is mutated at several sites. Therefore, rearranged VH and VK genes of 81D10 were cloned, expressed in immunoglobulin non-producing plasmacytoma cells, and mice transgenic for the 81D10 k gene were produced. These mice provide a first step in the development of a transgenic mouse model for genetical investigations in the affinity maturation of anti-viral immunoglobulin variable genes.
Theophylline (p less than 0.05) and ketotifen (p greater than 0.05) markedly reduced, but the lipoxygenase inhibitors and PAF receptor antagonists were without any influence on the endothelin-1 (ET-1 1 nmol/kg i.v.) induced increase of pulmonary inflation pressure of anaesthetised and ventilated guinea-pigs. The ET-1 induced increase in mean arterial blood pressure as well as the secondary TXB2 release into bronchoalveolar lavage fluid or plasma was not decreased. TXB2 release cannot be the only mechanism of bronchopulmonary ET-1 effects in guinea-pigs in vivo.
With vital yeast cells, a hybrid protein consisting of the amino-terminal third of the precursor to cytochrome b2 and of the entire dihydrofolate reductase was arrested on the import pathway into mitochondria. Accumulation of the protein in the mitochondrial membranes was achieved by inducing a stable tertiary structure of the dihydrofolate reductase domain. Thereby, three salient features of mitochondrial protein uptake in vivo were demonstrated: its posttranslational character; the requirement for unfolding of precursors; and import through translocation contact sites. The permanent occupation of translocation sites by the fusion protein inhibited the import of other precursors; it did, however, not lead to leakage of mitochondrial ions, implying the existence of a channel that is sealed around the membrane spanning polypeptide segment.
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Rabbits and mice were infected by Toxoplasma gondii (RH and HanR) and Hammondia hammondi. An enzyme immunoassay with monoclonal antibodies was used to reveal circulating Toxoplasma antigens. They were found only in mice and rabbits that had been infected by the cyst-forming strain Toxoplasma HanR. In mice infected by Hammondia hammondi low antibodies titres were found that showed a cross-reaction with Toxoplasma. The enzyme immunoassay for evidence of Toxoplasma antigens demonstrated a negative reaction in these animals.
The incidence of capillary sclerosis in the mucosa of the upper urinary tract was beyond expectation, according to a multicenter study conducted at 11 pathological institutes in all regions of the former GDR from which the following more specific findings were obtained: Capillary sclerosis was recorded primarily from women (1.4:1) in 3.6% of 3,929 autopsy cases (minimum age being 40 years). This result has close to the outcome of a study conducted in Basle, Switzerland, though highest severity (0.33%) and the complete morphological picture of analgesic nephropathy (0.54%) were clearly less frequent, as compared to the above Swiss findings. No reliable conclusion can as yet be drawn regarding the infrequent case of renal pelvis carcinoma. Epidemiological and clinical studies are likely to suggest that an increase in findings might be expected in this part of Germany and might be aetiologically attributable to abuse of analgesics.