Biomedical subjects
Publications and source records attributed to A Wagner.
The findings at plain radiography, myelography, CT, and MR imaging in 3 cases of fracture of the lumbar vertebral ring apophysis are presented. Familiarity with this entity is important in evaluating low back pain in children and young adults. Conventional radiographs and/or MR imaging may suggest ring apophysis fracture; CT will confirm and classify the diagnosis.
Transcription of the Saccharomyces cerevisiae CTT1 gene encoding the cytosolic catalase T has been previously shown to be derepressed by nutrient stress. To investigate whether expression of this gene is also affected by other types of stress, the influence of heat shock on CTT1 expression was studied. The results obtained show that expression of the gene is low at 23 degrees C and is induced rapidly at 37 degrees C. By deletion analysis, a promoter element necessary for high level induction by heat shock was located between base pairs -340 and -364 upstream of the translation start codon. This region was demonstrated to be sufficient for heat shock control by placing it upstream of a S. cerevisiae LEU2-lacZ fusion gene. Mutagenesis of the region showed that the response to heat shock is not mediated by a sequence similar to canonical heat shock elements, but by DNA elements also involved in nutrient control of transcription. Catalase T appears to have a function in protecting yeast cells against oxidative damage under stress conditions. Catalase T-containing strains are less sensitive to exposure to 50 degrees C ("lethal heat shock") than isogenic catalase T-deficient mutants, and catalase T-containing strains pretreated by incubation at 37 degrees C are less sensitive to H2O2 than pretreated catalase-deficient mutants.
To ascertain whether autopsies still provide important information in the face of modern diagnostic procedures, the findings in 780 autopsies (543 men and 237 women: mean age 58 [1-94] years), performed between 1977 and 1990, were compared with the clinical diagnoses. Autopsy confirmed the clinical diagnosis in 74.9% of cases, a clinically not diagnosed basic disease was demonstrated in 13.6%, and a not recognized final complication in 11.5%. In 9.7% of autopsies previously unrecognized but clinically important additional diseases were found. There was no decrease in the proportion of unrecognized basic diseases in the course of the observation period. It was unrelated to the duration of hospital stay, but increased with increasing age of the patients. These observations indicate that even nowadays, in the age of highly technical medicine, autopsies point to any limitations of diagnosis and are thus of importance for clinical quality control.
Transcription of the CTT1 (catalase T) gene of Saccharomyces cerevisiae is controlled by oxygen via heme, by nutrients via cAMP and by heat shock. Nitrogen limitation triggers a rapid, cycloheximide-insensitive derepression of the gene. Residual derepression in a cAMP-nonresponsive mutant with attenuated protein kinase activity (bcy1 tpk1w tpk2 tpk3) demonstrates the existence of an alternative, cAMP-independent nutrient signaling mechanism. Deletion analysis using CTT1-lacZ fusion genes revealed the contribution of multiple control elements to derepression, not all of which respond to the cAMP signal. A positive promoter element responding to negative control by cAMP was inactivated by deletion of a DNA region between base pairs -340 and -364. Upstream fragments including this element confer negative cAMP control to a LEU2-lacZ fusion gene. Northern analysis of CTT1 expression in the presence or absence of heme, in RAS2+ (high cAMP) and ras2 mutant (low cAMP) strains and in cells grown at low temperature (23 degrees C) and in heat-shocked cells (37 degrees C) shows that CTT1 is only induced to an appreciable extent when at least two of the three factors contributing to its expression (oxidative stress signaled by heme, nutrient starvation (low cAMP) and heat stress) activate the CTT1 promoter.
Natural (tritium, 14C, 40K, 226Ra) and man-made radionuclides (90Sr, 134Cs, 137Cs) were determined in soil (top 30 cm), vine leaves, grapes and wine in eight locations of the most important viticultural regions in the Federal Republic of Germany. The results obtained in 1983-1985 have been published previously. Part II of this study presents results obtained in 1986 and 1987, i.e. after the reactor accident at Chernobyl in the Soviet Union. The mean content of 137Cs before (after) Chernobyl was 4 (9) Bq/kg dry matter in soil, 0.07 (3) Bq/kg fresh matter in leaves, 0.02 (0.4) Bq/kg in grapes, and 0.008 (0.9) Bq/L in wine. As compared with 1986, distinctly lower levels were found in leaves, grapes and wine in 1987. In 1986 the content of 134Cs was about half that of 137Cs. Owing to its shorter half-life, 134Cs was below the detection limit in many of the 1987 samples. Transfer factors such as from soil to leaves and from soil to grapes for caesium agreed well in 1983-1985 and 1987, but showed considerable deviations in 1986, due to the ubiquitous contamination of the environment. Results of 90Sr determinations confirmed other reports showing this radionuclide to be a very minor contributor to the total radioactivity released at Chernobyl. No effect of the reactor accident on levels of the other radionuclides was detected.
Three cases of fracture of the lumbar ring apophysis representing type I, II, and III are described in detail and the natural history of these fractures is discussed. The symptoms of apophyseal fractures are usually low back pain, sciatica, tension signs, and neurological deficits, thus imitating the symptoms of lumbar disc herniation. Plain radiography and magnetic resonance are often inconclusive and computed tomography is essential for the true diagnosis. An explanation of the different types of fractures, based on the osteogenesis of the human vertebra, is proposed. Recognition of these fractures is essential for proper planing of surgery, and apophyseal ring fractures must be suspected when children and young adults show signs of lumbar disc herniation.
In vitro activation of human granulocytes leads to altered expression of distinct surface antigens. Compared with the changes observed with classic activating reagents such as the phorbol ester PMA similar, but less pronounced alterations of surface antigen expression were observed upon granulocyte activation with human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF). In particular, stimulation with hrGM-CSF is followed by an enhanced expression of the complement receptors CD35 (CR1) and CD11b (CR3) while the low affinity Fc-gamma receptor CD16 (FcRIII) is downregulated. In order to investigate whether there are similar effects under in vivo conditions, we studied the granulocytes from patients undergoing rhGM-CSF therapy before, during, and after treatment. We found a marked increase in CD35 (CR1) and CD11b (CR3) expression and a substantial decrease or even loss of CD16 (FcRIII) on these granulocytes. These changes correlated well with our in vitro data and occurred extremely rapidly after therapy onset. Furthermore, therapy monitoring using ratios calculated by the mean fluorescence channel numbers of CR and FcRIII stainings may combine the advantage of high sensitivity with high reproducibility as a result of the contrasting change in CR and FcRIII expression during granulocyte activation. Being nonparametric values, such ratios are not influenced by individual flow cytometry standardization. Taken together, these activation-associated changes of surface receptor expression and especially of CR over FcRIII ratios are useful parameters for monitoring the in vivo effects of rhGM-CSF.
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Utilizing a double-blind, placebo design, the effects of a high (0.8 mg/kg) and a low (0.4 mg/kg) dose of methylphenidate alone and in combination with behavioral parent training plus child self-control instruction were evaluated with 96 attention deficit hyperactivity disorder children. No evidence of the superiority of the combined conditions relative to medication alone was found. Some limited support was found for the hypothesis that the effects of a high dose of psychostimulant medication could be achieved by combining the low dose with a behavioral intervention. The importance of the latter finding is highlighted by the fact that both the benefits and untoward effects of the psychostimulants appear to increase with the dose.
Five out of 430 patients (1.16%) undergoing kidney transplantation developed an atypical clinical picture of herpetic dendritic keratitis within four weeks after surgery. It was manifested by multiple dendrites, located mainly in the corneal periphery or the limbus, developing in relatively uninflamed eyes. The response to acyclovir therapy was prolonged and took at least three weeks. Additionally, subepithelial infiltrates with ultimate scarring developed in all patients. Disciform keratopathy was not found. This clinical course is ascribed to the patients' immunosuppressed state.
Harvesting of peripheral blood stem cells (PBSC) by cytapheresis was performed in 57 patients, who underwent chemotherapy. The best yields were obtained when the leukocyte count was above 1 x 10(9)/l and the platelet count was raised above 80 x 10(9)/l. Using a Haemonetics V-50 or a Baxter CS-3000, 374 PBSC-aphereses were performed with a median of six aphereses per patient. The median number of PBSC (CFU-GM) retransfused in 22 patients who received PBSC for hematological reconstitution only was 3.26 x 10(4)/kg. For 22 patients who received autologous bone marrow plus BPSC, the median number of retransfused PBSC was 2.14 x 10(4)/kg. Myeloid engraftment was achieved in all patients, but megakaryopoiesis was delayed when the number of PBSC was less than 5.0 x 10(4)/kg. The results demonstrate that harvesting of a sufficient number of PBSC after chemotherapy is feasible but further measures like the use of rh GM-CSF will be necessary to reduce apheresis procedures and to obtain high yields to ensure rapid and complete engraftment.
The transfusion service (TS) plays an important role in bone marrow transplantation (BMT). Many of the techniques and methods employed are also used in the daily work of a TS like tissue typing, apheresis techniques, handling of blood and its components under sterile conditions. In the pretransplantation phase the TS is responsible for the typing of recipient and presumptive donors, harvesting of autologous blood and selection of appropriate blood components. During BMT the TS can perform bone marrow harvesting, depletion of red cells in case of ABO-incompatibility and bone marrow manipulation when T-cell depletion or purging procedures are considered. Peripheral stem cell harvest by apheresis is also best performed by the TS experienced in such techniques. Storage of hematopoietic cells in liquid nitrogen and thawing are also techniques already used in most of the transfusion services. Post BMT, the support with blood components, irradiated and almost free of white cells to avoid TA-GVH and CMV-infection, is a major job of the TS. These facts demonstrate that a well organized transfusion service is a 'conditio sine qua non' for successful BMT.
Because there are a lot of contradictory opinions in the literature we investigated the intra- and extraosseous pathway of the Chorda tympani by dissecting the heads of 6 cadavers. The Chorda nerve leaves the temporal bone in the Fissura sphenopetrosa behind the Spina ossis sphenoidalis. In an angle of 24 degrees-28 degrees the Chorda nerve connects up with the lingual nerve. The extraosseous distance is about 1.3 to 3 time longer then the intraosseous one. The individual variations of the intraosseous distance are greater than those of the extraosseous one. This is behalf the individual variations in the structure of the temporal bone.
The prognostic value of three DNA cytometric parameters--stemline ploidy (STL), stemline shoulder fraction (SSF) and "proliferative" fraction (PRF)--for the prediction of disease transformation and survival was examined for 20 patients with chronic myelogenous leukemia (CML) during the course of their disease and compared with two commonly used hematologic parameters (degree of leukocytosis and percentage of circulating leukemic progenitor cells). With disease progression, STL and SSF increased significantly, whereas PRF showed a steady decrease from diagnosis to blast crisis. The most significant part of these changes took place during the chronic phase, before the clinical onset of disease transformation. Hematologic parameters, in comparison, revealed significant changes later, shortly before blast crisis. The remaining duration of the chronic phase diminished from 25.5 months at the time of diagnosis, when the median STL was 2.0c, to 19.6 months for patients showing an STL of 2.1c, to 15.0 months with an STL of 2.2c and to 1.0 months for those with an STL of greater than or equal to 2.3c. Prognostically relevant limits for SSF and PRF were at 20%. When the SSF passed this limit or the PRF fell below it, the mean remaining chronic phase of these patients amounted to only 14.1 and 10.1 months. Interactive cytometry allows analysis of the DNA cytometric equivalent of changes in leukemic progenitor cells, which are well known from cytogenetic and cell kinetic studies. These three DNA cytometric parameters reflect the "natural history" of CML with the development of a cytogenetically hyperdiploid clone during disease progression in most patients and a simultaneous loss of proliferative potential on the level of myelobasts.(ABSTRACT TRUNCATED AT 250 WORDS)
The interaction of two renin inhibitors, S 86,2033 and S 86,3390, with the uptake system for beta-lactam antibiotics and small peptides in the brush border membrane of enterocytes from rabbit small intestine was investigated using brush border membrane vesicles. Both renin inhibitors inhibited the uptake of the orally active cephalosporin cephalexin into brush border membrane vesicles from rabbit small intestine in a concentration-dependent manner. 1.1 mM of S 86,3390 and 2.5 mM of S 86,2033 led to a half-maximal inhibition of the H(+)-dependent uptake of cephalexin. Both renin inhibitors were stable against peptidases of the brush border membrane. The uptake of cephalexin into brush border membrane vesicles (1 min of incubation) was competitively inhibited by S 86,2033 and S 86,3390 suggesting a direct interaction of these compounds with the intestinal peptide uptake system. The renin inhibitors are transported across the brush border membrane into the intravesicular space as was shown by equilibrium uptake studies dependent upon the medium osmolarity. The uptake of S 86,3390 was stimulated by an inwardly directed H(+)-gradient and occurred with a transient accumulation against a concentration gradient (overshoot phenomenon). The renin inhibitors S 86,2033 and 86,3390 also caused a concentration-dependent inhibition in the extent of photoaffinity labeling of the putative peptide transport protein of apparent Mr 127,000 in the brush border membrane of small intestinal enterocytes. In conclusion, these studies show that renin inhibitors specifically interact with the intestinal uptake system shared by small peptides and beta-lactam antibiotics.
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The residence time distributions of sucrose and taurocholate have been determined from the outflow concentration-time profiles after bolus input into an in situ perfused rat liver preparation. The normalized variance (and the dispersion number) appeared to be independent of perfusate flow rate (10 to 37 ml/min) and perfusate albumin concentration (0.5%). The apparent volume of distribution for sucrose appeared to increase with flow rate but was unaffected by the concentration of albumin (0-5%) present in the perfusate. The changes in taurocholate availability with flow rate were adequately accounted for by the dispersion model, whereas taurocholate availability-protein binding changes required an albumin-mediated transport model to be used in conjunction with the dispersion model.