Biomedical subjects
Publications and source records attributed to E Fischer.
Acromegaly with an elevated level of growth hormone causes a high bone turnover the part of resorption of which becomes noticeable in numerous details at the margin of the ungual tufts. The resorption at these margins and the intracortical resorption may have their own courses.
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Oligomerization of band 3 protein has been recently indicated as an early event in senescent or damaged red cell membrane followed by specific deposition of anti-band 3 antibodies and binding of complement C3 fragments. The band 3-anti-band 3-C3b complex is recognized by homologous monocytes, and phagocytosis ensues. This study shows that recognition of the anti-band 3-C3b complex by the monocyte C3b receptor type one (CR1) plays a crucial role in the process of removal of damaged red cells. Indeed, blocking of monocyte CR1 with an anti-CR1 monoclonal antibody abrogated phagocytosis of diamide-treated red cells. Platelet-activating factor (PAF) is a phospholipid mediator involved in inflammatory processes. Nanomolar (R)-PAF enhanced the CR1-dependent phagocytosis of diamide-treated human red cell and of sheep red cells coated with C3b, induced the fast translocation of protein kinase C to monocyte membrane compartment, and stimulated the phosphorylation of monocyte CR1. The biologically inert lyso-PAF and the enantiomer (S)-PAF were inactive. PAF receptor antagonists and inhibitors of protein kinase C blocked the enhancement of phagocytosis induced by PAF. Protein kinase C translocation, phosphorylation of CR1, and stimulation of this receptor to an active state capable of mediating phagocytosis represent a novel pathway by which PAF interferes with red cell homeostasis and possibly modulates inflammatory reactions and host mechanisms against infections.
Over the past two decades patients with acute myocardial infarction have been treated with intravenous streptokinase therapy at the hospital in Geldern. Based on experiences in the first study from 1970 to 1979, the second study emphasized instruction on early thrombolytic therapy. Informations were given to general practitioners and to patients at risk for acute myocardial infarction. In the study from 1980 to 1985 the percentage of patients with acute myocardial infarction being treated with thrombolytic agents within two hours after the acute event was 69%. Patients with a duration of ischemia of less than two hours had a significantly decreased in-hospital mortality compared to patients who received therapy more than two hours after onset of symptoms. We conclude that intensified information and instruction of physicians and of patients at risk for myocardial infarction enables early thrombolytic therapy and results in reduced in-hospital mortality of acute myocardial infarction.
In order to obtain information on the current magnitude of occupational disease in New York State, four data sources were reviewed: Workers' Compensation records, disease registries maintained by the state department of health, data from the Bureau of Labor Statistics (BLS), and data from the California's physician reporting system. A proportionate attributable risk approach is used to develop estimates of mortality due to occupational diseases. The distribution of occupational hazards was assessed using data from the Occupational Safety and Health Administration (OSHA), the National Institute for Occupational Safety and Health (NIOSH), and the New York State Department of Environmental Conservation (NYDEC). Finally, econometric estimates of the direct and indirect costs of occupational illness were developed. The best available data indicate that 5,000 to 7,000 deaths are caused each year in New York State by work-related illnesses, and at least 35,000 new cases of occupational illness develop each year in the State. It is also estimated that between 150,000 and 750,000 workers in New York State are employed in the 50 most hazardous industries. OSHA standards regulating exposure to selected chemicals were found to have been violated frequently. The annual costs of occupational disease in New York State are approximately $600,000,000; only a small fraction is covered by workers' compensation insurance. Of the 52,000 physicians in New York State, only 73 are board-certified in occupational medicine. Most of these are involved in administrative, teaching, and research aspects of occupational medicine. Of the 300 industrial hygenists in New York State, two-thirds are employed by major corporations. Recommendations are described to improve the recognition of occupational disease in New York State and to reduce the burden of this disease. A statewide network of occupational health clinical services is proposed and has been funded by the New York State Legislature. Other recommendations are also given.
Occupational diseases and deaths are costly events. They are responsible for: 1) direct medical costs; 2) indirect costs, resulting from lost production, foregone opportunities, and diminished investment; and 3) non-economic costs, including pain and suffering, disrupted careers, and devastated families. To develop a partial estimate of the total costs of occupational disease in New York State, we have examined four categories of illness: occupational cancer, chronic respiratory disease and the pneumoconioses, cerebrovascular and cardiovascular disease, and end-stage renal failure. We base our partial estimate on the human capital approach to the costs of these illnesses. Using the best measures available, including both incidence and prevalence statistics, mortality records, and a variety of financial data, we employ two cost accounting techniques of the human capital approach, the incidence method, and the prevalence method. Our analysis shows that these four occupational illnesses are costing New York over $600 million per year. This figure is a pragmatic but conservative, lower-bound estimate of the relative magnitude of total economic costs of occupational disease in New York State. The largest proportion of these costs (80%) is due to occupational cancer. The failure of the health care system to recognize the costs of occupational disease precludes recognition of the economic benefits which would result from preventing these illnesses. This study, it is hoped, will stimulate advances in epidemiological and economic approaches to resolve this important measurement problem.
The regimen conferring competence for uptake of transforming DNA is shown to render Escherichia coli osmolabile. Three different K-12 strains were exposed to the standard procedure of competence induction, i.e. incubation in the presence of 0.1 M Ca2+ or Mg2+ for 50 min at 0 degrees C, interrupted by a heat shock for 5 min at 37 degrees C. Upon osmotic challenge of competent cells formation of protoplasts was observed in approximately 2% of the treated cells. Incubation of competent cells of strain W1485 in phosphate-buffered saline for 1, 2, and 3 h reduced the viable counts to 67, 58, and 41%, respectively. Competence induction with divalent cations altered the affinity of penicillin-binding proteins (PBPs) for [125I]ampicillin. In isolated cell envelopes the presence of Ca2+ and Mg2+ stimulated the binding of [125I]ampicillin to PBPs 1, 3, 4, 5, and 6, whereas the binding to PBP 2 remained unchanged. The binding to PBP 1 C was inhibited by 0.23 M Ca2+. In living cells the binding to PBPs 1, 3, and 4 was enhanced, while the binding to PBP 8 was inhibited. Newly [125I]ampicillin-labelled proteins of Mr 55,000 and 45,000 were apparent, especially after competence induction with Ca2+. Interaction of divalent cations with PBPs is suggested to contribute to osmolability of competent cells. Disintegration of the cell wall may be necessary for uptake of transforming DNA.
In addition to the low risk of agranulocytosis, several more frequent side effects are associated with clozapine therapy. We tried to estimate the incidence of these side effects. We analysed 391 treatments in 315 inpatients, who received clozapine alone or combined with other neuroleptic and antidepressant drugs. Two thirds were combined treatments, one third were treatments with clozapine alone (i.e., no other neuroleptic, antidepressant or anticonvulsive drugs were allowed). The numbers in brackets show the incidence based on the analysis of the treatments with clozapine alone. In 49% (61%) of the treatments a rise in the liver enzyme values was observed. However, counting only the cases in which a two-fold increase over the normal values was observed, the incidence was reduced to 20% (31%). Increase in temperature was observed in 4% (6%) and leukopenia (leukocyte count under 3500/microliters) was recorded in 2% (2%). Hypotensive dysregulation (systolic blood pressure under 90 mm Hg) was observed in 25% of all treatments and pharmacogenic delirium in 8%. No cases of agranulocytosis were observed. Mean treatment duration was 56 days, mean daily dosage 257 mg. The mean age of the patients was 34 years. In the overall evaluation 71% of the treatments were classified as successful; clozapine therapy was continued after discharge in 68% of the treatments. Adverse reactions (delirium, rise in temperature, hypotension, fatigue, rise in liver enzymes) necessitated a change of medication in 17% of the treatments. Changeover to another neuroleptic drug due to ineffectiveness of clozapine was necessary in 7% of the treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
In a field investigation (1983-1985) comprising eight places of the most important viticultural regions in the Federal Republic of Germany, the contents of the radionuclides tritium (3H), carbon-14 (14C), strontium-90 (90Sr), and cesium-137 (137Cs) in air, soils, leaves of the vine, grapes and wine were measured and site-specific transfer factors were calculated. Data concerning soil parameters, climatic conditions, cultivation and vinification were collected. The tritium content of all samples was 10 Bq/l water of combustion, independent of location and year. The specific activity of 14C in the atmosphere and in biological material was 0.22 Bq/g carbon, independent of site and year. 90Sr contents of soils fluctuated between 0.7 and 3.5 Bq/kg dry matter. The mean content of leaves was 2 Bq/kg fresh material, of grapes 0.035 Bq/kg and of wine 0.008 Bq/l. 137Cs content of soils fluctuated between 1.3 and 7.9 Bq/kg dry matter. The mean content of leaves was 0.098 Bq/kg fresh material, of grapes 0.021 Bq/kg and of wine 0.0085 Bq/l. A relation between transfer of radionuclides and soil parameters and between the contents of grapes and wine was not recognizable. While cultivar-specific differences were not observed in grapes, red wines contained somewhat more 137Cs than white wines. Transfer factors soil grapes were 0.027 for 90Sr and 0.0057 for 137Cs. Site-specific influences such as soil parameters, climate, cultivation, vinification and differences between years led to a relatively small fluctuation of values. An influence of the nuclear power station Neckarwestheim has not been found in any of the radionuclides.
Extracts from myelinated and unmyelinated nerves, prepared using Nonidet P-40, contained receptors for C3b/C4b (CR1). Extracts from myelinated nerves inhibited EAC3b rosette formation with peripheral blood leucocytes and agglutinated EAC3b, whereas extract from unmyelinated nerves did not. Rosette formation with EAC3bi or EAC3d was not affected. CR1 in extracts from myelinated nerves also expressed decay-accelerating activity of the alternative pathway C3 convertase and cofactor activity in factor I-mediated cleavage of C3b, whereas CR1 in extract from unmyelinated nerves did not. Monoclonal anti-CR1 antibodies, but not monoclonal anti-CR2 (C3d receptors) or anti-CR3 (C3bi receptors) antibodies inhibited the functional activities. Accordingly, CR1 are the only C3 receptor present in the extracts and only CR1 in myelinated nerve extracts are functionally active. CR1 in both myelinated and unmyelinated nerve extracts had a molecular weight of approximately 190 kDa. The electrophoretic mobility did not change after reduction and the 190 kDa band was stained by concanavalin A, indicating that the CR1 are single-chained glycoproteins. Binding to lentil lectin-Sepharose 4B further sustained the glycoprotein nature of the CR1. Periodic acid abolished functional activities of CR1, whereas trypsin and heat did not, indicating the functional significance of the carbohydrate moiety. That CR1 are functionally active in myelinated nerves, but not in unmyelinated nerves, may therefore be due to differences in the carbohydrate moiety. The cofactor and decay-accelerating activities of CR1 may be of significance in the pathogenesis of demyelinating polyneuropathies by limiting complement activation.
Stool specimens from 766 hospitalized children, 418 with diarrhoea and 348 controls, were investigated for C. difficile. In both groups the rate of isolation was highest (about 30%) during the first year of life, dropping to nearly 5% in older children. There was no significant difference in the frequency of C. difficile in children with diarrhoea and the controls nor was there a significant influence of previous antibiotic therapy on the rate of isolation. 111/135 strains (82.2%) produced toxin B and 58/135 strains (43%) produced toxin A measured by Y-1- cell culture (toxin B) and rabbit ileal loop test (toxin A). We did not find any significant difference in the toxin production between strains isolated from diarrhoeal children and from the controls. A total of 285 stool specimens was investigated for toxin B production in vivo. There was no significant difference of toxin B in the stool specimens of both groups.
A prospective study of 52 patients with various focal liver lesions was carried out using a multislice-gradient echo sequence and this was compared with spin-echo sequences. The multislice-gradient echo sequence provides the possibility of obtaining heavily T1-weighted images of the entire liver during one examination, thereby reducing the time of the examination. Contrast is significantly better than that of a T1-weighted spin-echo sequence (p greater than 0.05). The multislice-gradient echo sequence examination, taking 5.4 minutes, provides good and diagnostically useful image quality.
The ungual tuft of the digits corresponds to an enthesis at which usually numerous reactions take place especially in adults. These reactions are to be classified into formation and reduction of bone. The formation of bone is the dominant reaction and causes diagnostic problems only in irregular shapes. On the contrary, the usual reduction of bone after the preceding formation causes more diagnostic problems because the borderline to pathology is a flowing one. Reductions of bone demand a meticulous observation of possible further osseous changes to record systemic enthesopathic or high-bone turnover situations in their early or minimal stages.
The exb locus in Escherichia coli consists of two genes, termed exbB and exbD. Exb functions are related to TonB function in that most TonB-dependent processes are enhanced by Exb. Like tonB mutants, exb mutants were resistant to colicin M and albomycin but, in contrast to tonB mutants, showed only reduced sensitivity to colicins B and D. Overexpressed tonB on the multicopy vector pACYC177 largely restored the sensitivity of exb mutants to colicins B, D, and M but only marginally increased sensitivity to albomycin. Suppression of the btuB451 mutation in the structural gene for the vitamin B12 outer membrane receptor protein by a mutation in tonB occurred only in an exb+ strain. Degradation of the unstable overproduced TonB protein was prevented by overproduced ExbB protein. The ExbB protein also stabilized the ExbD protein. Pulse-chase experiments with radiolabeled ferrichrome revealed release of ferrichrome from exbB, tonB, and fhuC mutants, showing that ferrichrome had not crossed the cytoplasmic membrane. It is concluded that the ExbB and ExbD proteins contribute to the activity of TonB and, like TonB, are involved in receptor-dependent transport processes across the outer membrane.
The human complement system is comprised of 19 plasma components and regulatory proteins and of at least 9 distinct cellular receptors for these proteins or their activation fragments. The important role of complement in host defense against infection is related to its capacity to opsonize microorganisms, lyze target cells, and induce the release of inflammatory mediators from leukocytes. Complement participates in the processing and clearance of immune complexes and in regulation of the immune response. Most of the biologic effects derived from complement activation depend on ligand-receptor interactions between complement proteins or their cleavage fragments and specific receptors on cells. Two types of ligands are generated during complement activation: soluble low-molecular-weight ligands, such as the anaphylatoxins C3a and C5a, and so-called bifunctional ligands that attach both to the target of complement activation (opsonins) and to the appropriate receptor on effector cells. The most abundant complement protein in plasma is C3. Activation of the classic and alternative complement pathways generates C3 convertases that cleave C3 into an anaphylatoxic fragment, C3a, and a major fragment, C3b, which is capable of forming a covalent linkage with the targets of complement activation. Surface-bound C3b is the preferential ligand for the C3b receptor, CR1 (CD 35), which is expressed on most peripheral blood cells. The receptor plays an important role in the processing of immune complexes, the phagocytosis of C3b-bearing microorganisms, and regulation of the immune response. The cellular expression of the molecule is decreased in patients with systemic lupus erythematosus (SLE) and in patients infected with the human immunodeficiency virus (HIV).
Staphylococcus aureus cells, strain Cowan 1, were coated with an anti-Clostridium difficile serum, produced in rabbits. This reagents were used in the coagglutination (coa-test) for detection of Clostridium difficile. A total of 275 bacterial cultures of different species were tested for detection of Clostridium difficile by coa-test and bacterial culture. Of 183 strains positive by isolation of the organism, 181 were positive by coa-test. The sensitivity and specificity of the coa-test relative to bacterial culture was 98.9% and 90.2%. A total of 206 stool specimens of children were tested also for detection of Clostridium difficile with both methods. From 16 specimens which were positive in bacterial culture 12 were positive in coa-test. The total number of samples which were positive with the coa-test was 46. The sensitivity and specificity of the coa-test in stool specimens relative to the isolation of the organism were 75.0% and 75.8%, respectively. The high predictive value for a negative result of the coa-test relative to the culture from 97.6% (bacterial cultures) and 97.3% (stool specimens) suggest that the coa-test will be a useful, rapid and simple screening test for Clostridium difficile. Specimens positive by the coa-test must be confirmed by the bacterial culture. Of some other Clostridium spp. tested, strains of Clostridium bifermentans and Clostridium sordelli also gave a positive result.
Twenty-six sites of muscle and ligament attachment around the wrist were evaluated for enthesopathic proliferative bone changes in psoriatic arthritis (PA), rheumatoid arthritis (RA), and diffuse idiopathic skeletal hyperostosis (DISH). Proliferations were found to be most frequent, most irregular, and largest in PA, followed in declining order by RA and DISH. In PA only, the bony proliferations and the underlying bone often had the appearance of mineralized woven bone, though smooth proliferations with a regular bone structure do occur in PA as well as in RA. The entheses of the trapezium, scaphoid and the radial styloid process are most frequently affected, followed by the bases of the first and fifth metacarpals and the pisiform. It is exceptional for huge bony proliferations to be observed at the entheses in DISH.
The effect of ligand interactions with the C3d/C3dg complement receptor (CR2) on proliferation of human B lymphoblastoid cells was investigated by using cell cultures performed at low density (1 to 1.5 x 10(3) cells/ml) in a serum-free defined medium to which only transferrin had been added. This medium does not allow proliferation of Raji cells which die within 48 hr with formation of polykaryons. Addition of purified human C3 to the cultures resulted in a dose-dependent proliferation of the cells. A steady growth of Raji cells with a doubling time of 36 hr was observed in cultures containing 10 micrograms/ml of C3. A growth rate similar to that observed in the presence of native C3 was found in the presence of equimolar concentrations of purified C3dg but not of C3c. F(ab')2 anti-C3d but not F(ab')2 anti-C3c antibodies inhibited the mitogenic effect of C3. Preincubation of Raji cells with monoclonal antibody OKB7 which directly inhibits the binding of C3dg to CR2, totally suppressed C3-induced growth of the cells. C3 did not enhance growth of the T lymphoma-derived cell line JM and monocytic cell line U937 which do not express CR2. These results provide direct evidence that the interaction between CR2 and C3 fragments stimulates proliferation of human cells of the B lineage. Because CR2 also acts as a receptor for Epstein-Barr virus on B cells, our results may pertain to the B cell mitogenic properties of the virus.