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Biomedical subjects

K Schmid

Publications and source records attributed to K Schmid.

At least 55 records · Page 3Linked to original sources

Active unfolding of precursor proteins during mitochondrial protein import.

Precursor proteins made in the cytoplasm must be in an unfolded conformation during import into mitochondria. Some precursor proteins have tightly folded domains but are imported faster than they unfold spontaneously, implying that mitochondria can unfold proteins. We measured the import rates of artificial precursors containing presequences of varying length fused to either mouse dihydrofolate reductase or bacterial barnase, and found that unfolding of a precursor at the mitochondrial surface is dramatically accelerated when its presequence is long enough to span both membranes and to interact with mhsp70 in the mitochondrial matrix. If the presequence is too short, import is slow but can be strongly accelerated by urea-induced unfolding, suggesting that import of these 'short' precursors is limited by spontaneous unfolding at the mitochondrial surface. With precursors that have sufficiently long presequences, unfolding by the inner membrane import machinery can be orders of magnitude faster than spontaneous unfolding, suggesting that mhsp70 can act as an ATP-driven force-generating motor during protein import.

Bacterial Proteins↗

Field evaluation of a fenbendazole slow release bolus in the control of nematode infections in first-season cattle.

The efficacy of a fenbendazole slow release bolus in controlling nematode infections of first-season cattle was evaluated in a field study in northern Germany. Two groups, each of 11 male calves, were set-stocked on separate pastures from May until October 1989 (157 days). The animals of one group were given the bolus at turnout and the animals of the control group were treated with fenbendazole (7.5 mg/kg bodyweight) eight weeks after turnout. Clinical inspections and measurements of faecal egg and larval counts, herbage trichostrongyle larval counts, plasma pepsinogen concentrations and bodyweight were made throughout the study. All the animals were slaughtered for worm counts and the evaluation of carcase quality two weeks after housing. The pasture grazed by the control group showed a marked increase in trichostrongyle larvae from late August onwards and, as a result, the control calves had increasing faecal egg counts and increased plasma pepsinogen concentrations in the latter part of the grazing season, although no clinical signs of parasitic gastroenteritis were apparent. The fenbendazole slow release bolus suppressed the trichostrongyle infections during the grazing season, and larval counts on the pasture grazed by the bolus-treated group remained low throughout the study. Postmortem examination showed that the bolus-treated calves harboured significantly (P < 0.01) fewer trichostrongyle worms, including inhibited stages, than the controls. Because of an inadequate lungworm challenge during the grazing season it was not possible to evaluate the efficacy of the fenbendazole slow release bolus in preventing parasitic bronchitis. At slaughter, the bolus-treated animals weighed more than the controls and tended to have a better carcase quality.

Animals↗

[Cardiovascular diseases caused by unemployment? An analysis from the viewpoint of social medicine].

Unemployment has become a sociopolitical problem of great importance in the Western industrialised countries. Although negative effects on social life and psyche resulting from unemployment are regarded as scientifically accepted today, a possible causal relationship between job loss and somatic illnesses is still a matter of controversy. A possible target organ is the cardiovascular system. The aim of this study was, therefore, to check by means of extensive literature analysis to what extent unemployment can be seen to influence cardiovascular morbidity. Particular attention was paid to the method used and the clinical relevance of the results. Person-related epidemiological studies published since 1980 which investigated changes in cardiovascular risk factors associated with unemployment or prevalence rates of manifest disease influenced by unemployment, were included in the final evaluation. In some cases statistically significant associations were found between unemployment and the increase in cholesterol levels or systolic/diastolic blood pressure, but the clinical relevance of such slight changes is questionable. To consider unemployment as an independent, social, cardiovascular risk factor is at present unwarranted. An increase in the prevalence rates of coronary heart disease or arterial hypertonia causally linked in some studies with unemployment is scientifically questionable due to severe methodological shortcomings. On the basis of the currently available methodologically acceptable studies, the question of a qualitative contribution of unemployment to cardiovascular disease cannot be answered conclusively.

Adult↗

Natural and imposed astigmatism and their relation to emmetropization in the chick.

This study investigated the ocular response of young chicks to astigmatic errors imposed by spectacle lenses and as a related issue, we examined the nature and prevalence of astigmatism in young chicks, and its relation to corneal development and natural emmetropization. Normal hatchling chicks exhibited significant against-the-rule refractive astigmatism (approx. 8 D) of which 60-90% was corneal. Both types of astigmatism decreased in magnitude with normal corneal development as part of emmetropization. The apparent association with corneal growth is consistent with two further observations: (1) that smaller corneas, induced by constant light rearing, had higher than normal astigmatism (1.5 D greater at 15 days), (ii) that enlarged corneas, due to form deprivation, had reduced astigmatism (2.4 D less). When astigmatism was artificially imposed with (+/-10 DC spectacle lenses), altered ocular growth patterns were observed, although the changes were not consistent with the chicks having emmetropized to the imposed astigmatism. Irrespective of the axis setting used in positioning the lenses (45 degrees, 90 degrees, 180 degrees), eyes became hyperopic with +10 DC lenses (+8.8 +/- 1.3 D), and became slightly myopic with 10 DC lenses (-1.8 +/- 1.9 D). These refractive changes are consistent with the chicks having emmetropized to the more myopic meridian rather than the equivalent mean spherical error imposed (responses of control groups to +5 D and -5 D spherical lenses were +5.2 +/- 1.0 D and -5.1 +/- 0.8 D resp.). The same was true for chicks first prevented from accommodating by prior ciliary nerve section, except for one group wearing the 10 DC lens at 45 degrees axis where astigmatic changes consistent with partial compensation were seen, although this may represent an artefact of the surgery. These results argue against 'astigmatic emmetropization' as a normal phenomenon. Also consistent with this finding was the lack of significant astigmatic changes with accommodation-stimulating and inhibiting drugs (nicotine and vercuronium resp.), for normal chicks. These results imply that accommodation, while the most likely mechanism for astigmatic emmetropization, has little capacity to compensate for imposed astigmatic focussing errors.

Accommodation, Ocular↗

Internal exposure to hazardous substances of persons from various continents: investigations on exposure to different organochlorine compounds.

UNLABELLED: The aim of the study was to investigate the concentration of organochlorine compounds of environmental-medical relevance in biological materials from refugees with regard to their countries of origin and to compare these concentrations with the internal exposure of the German general population. METHODS: During medical examination after entry to Germany specimens could be taken from the refugees to determine the following parameters of biological monitoring: 1,1-dichloro-2,2-bis(-chlorophenyl)-ethylene (DDE-P), polychlorinated biphenyls (PCB-P), pentachlorophenol (PCP-P) and the beta- and gamma-hexachlorocyclohexanes (beta-HCH-P, gamma-HCH-P) in plasma and the excretion of chlorophenols (4-MCP-U, 2,4-DCP-U, 2,5-DCP-U, 2,4,5-TCP-U, 2,4,6-TCP-U, 2,3,4,5-TeCP-U, 2,3,5,6-TeCP-U) in urine. One hundred and three men (13 from former Yugoslavia, 29 from the former USSR, 33 Africans and 28 Asians) ranging from 16 to 53 years of age (median 27 years) were investigated. Thirty four male Germans without occupational exposure to these substances and a similar age structure (age 25-36 years; median 26 years) served as a control group. RESULTS: A much higher level of internal exposure was found for the DDT metabolite, DDE, for those persons from Asia, the former USSR and Africa compared with the German controls (medians: 16.9 micrograms/l, 11.9 micrograms/l and 10.9 micrograms/l) and 1.1 micrograms/l). The levels of PCB in plasma were below the detection limit in the majority of refugees. In the control group, however, the PCB levels were higher (sigma PCB; median: 2.1 micrograms/l, maximum: 13.3 micrograms/l). The highest beta-HCH concentrations, up to a maximum of 15.5 micrograms/l, were detected in the persons from the former USSR and Asia. The five groups do not differ with regard to internal exposure to PCP and gamma-HCH. Renal excretion of 4-MCP, 2,4-DCP and TeCP did not differ between the five groups. The concentrations of 2,5-DCP in urine, however, were significantly lower in the Germans than the refugees from the four regions investigated. The median for the Germans was 3.0 micrograms/l and for the refugees between 10.8 and 14.7 micrograms/l. Also the levels of 2,4,5-TCP and 2,4,6-TCP in urine were lower in the German controls than in the men from the former USSR, Africa and Asia. CONCLUSIONS: Organochlorine compounds exist worldwide due to their extensive use. There are, however, regional differences for the various substance groups, which during biological monitoring are seen in the different background exposures of the general population. Particularly characteristic are markedly higher levels of DDE in plasma from the refugees compared with the German population.

Adolescent↗

[Sports-induced acute epicondylitis of the elbow and conservative therapy].

48 patients with an acute lateral and/or medial epicondylitis of the elbow, induced by sporting activities, were treated in a prospective, controlled, double-blind, and randomised clinical study over a period of one to two weeks in a standard manner, either with taping and the oral NSAID proglumetacine b.i.d. (26 patients: 8 women, 18 men; mean age of 37.8 years) or with taping and an oral placebo b.i.d. (22 patients: 11 women, 11 men; mean age of 40.0 years). The course of complaints was followed on the basis of a functional index (created according to Lequesne). Taking into account the prior definition of efficacy, at the end of the 1st week of all 22 NSAID group patients, enrolled and treated according to the protocol, there were already 21 responders and of all 19 corresponding placebo group patients, there were 12 responders. The difference is statistically significant (p = 0.0157). The rate of efficacy was 95.5% in the verum (plus taping) group and 63.2% in the placebo (plus taping) group with a further amelioration in both groups at the end of the study. Safety was comparably good in both the verum as well as the placebo group.

Acute Disease↗

Identification of a new porin, RafY, encoded by raffinose plasmid pRSD2 of Escherichia coli.

The conjugative plasmid pRSD2 carries a raf operon that encodes a peripheral raffinose metabolic pathway in enterobacteria. In addition to the previously known raf genes, we identified another gene, rafY, which in Escherichia coli codes for an outer membrane protein (molecular mass, 53 kDa) similar in function to the known glycoporins LamB (maltoporin) and ScrY (sucrose porin). Sequence comparisons with LamB and ScrY revealed no significant similarities; however, both lamB and scrY mutants are functionally complemented by RafY. Expressed from the tac promoter, RafY significantly increases the uptake rates for maltose, sucrose, and raffinose at low substrate concentrations; in particular it shifts the apparent K(m) for raffinose transport from 2 mM to 130 microM. Moreover, RafY permits diffusion of the tetrasaccharide stachyose and of maltodextrins up to maltoheptaose through the outer membrane of E. coli. A comparison of all three glycoporins in regard to their substrate selectivity revealed that both ScrY and RafY have a broad substrate range which includes alpha-galactosides while LamB seems to be restricted to malto-oligosaccharides. It supports growth only on maltodextrins but not, like the others, on raffinose and stachyose.

Amino Acid Sequence↗

Substrate recognition domains as revealed by active hybrids between the D-arabinitol and ribitol transporters from Klebsiella pneumoniae.

Two new genes, dalT and rbtT, have been cloned from the dal operon for D-arabinitol and the rbt operon for ribitol uptake and degradation, respectively, in Klebsiella pneumoniae 1033-5P14, derivative KAY2026. Each gene codes for a specific transporter which, based on sequence data, belongs to a large family of carbohydrate transporters which constitutes 12 transmembrane helices. DalT and RbtT show an unusually high similarity (86.2% identical residues for totals of 425 and 427 amino acids, respectively). This allowed the construction of DalT'-Rbt"T and RbtT'-Dal'T crossover hybrids by using a natural restriction site overlapping Met202. This site is located within the large cytoplasmic loop which connects the putative helices 6 and 7 and in particular the amino- and the carboxy-terminal halves of the transporters. Both hybrids have close to normal transport activities but essentially the substrate specificities and kinetic properties of the amino-terminal half. This result localizes essential substrate binding and recognition sites to the amino-terminal halves of the proteins in this important class of carbohydrate transporters.

Amino Acid Sequence↗

CTnscr94, a conjugative transposon found in enterobacteria.

Conjugational transposons are important for horizontal gene transfer in gram-positive and gram-negative bacteria, but have not been reported yet for enteric bacteria. Salmonella senftenberg 5494-57 has previously been shown to transfer by conjugation genes for a sucrose fermentation pathway which were located on a DNA element called scr-94. We report here that the corresponding scr genes for a phosphoenolpyruvate-dependent sucrose:phosphotransferase system and a sucrose metabolic pathway are located on a large (ca. 100 kb) conjugative transposon renamed CTnscr94. The self-transmissible element integrates at two specific attachment sites in a RecA-independent way into the chromosome of Escherichia coli K-12 strains. One site was identified within pheV, the structural gene for a tRNA(Phe). Sequencing of both ends of CTnscr94 revealed the presence of the 3' part of pheV on one end such that after integration of the element, a complete pheV gene is retained. CTnscr94 represents, to our knowledge, the first conjugational transposon found in enteric bacteria.

Base Sequence↗

[Social medicine evaluation of pre-employment medical screening of civil service candidates].

The findings and resulting number of rejections from 9.043 medical examinations of candidates for posts as civil servants in 1994 in Bavaria and a retrospective evaluation of 500 examinations at two large public health departments in Bavaria were used to discuss the value of such examinations and present possible alternatives. The rate of rejections for medical reasons in the 9.043 examinations of civil servants starting new jobs in Bavaria was 0.57%. The most frequent reason for rejection was obesity. In the retrospective evaluation of 500 medical examinations of candidates starting new jobs there were no cases of final rejection for medical reasons. In 0.4% of cases (n = 2) the candidates were considered suitable for the probationary period before becoming a civil servant, but unsuitable for health reasons for a life-time post in the civil service. In 27% of cases the findings were normal without any diagnosis stated in the examination report. The most frequent diagnoses were refractive ametropia (55.8%) and changes in the locomotor system (22.2%), in particular deviation of the axis are vertebral column (17.6%). The results are comparable with those obtained in studies carried out in Europe, although the procedures and study designs differed. Even with a low number of rejections of around 0.5%, examinations of the candidates economically justified for the employer (the state). In view of the high number of civil servants taking early retirement, the sensitivity and specificity of the medical examinations before starting work are discussed, as well as possible and better alternatives to a single examination. One suggestion is continuous monitoring of all civil servants by a physician specialised in occupational medicine, although in particular for teachers and office workers no standards have been developed for the scope and frequency of occupational-medical health checks and consultation.

Adolescent↗

Inhibitions mediated by glycine and GABAA receptors shape the discharge pattern of bulbar respiratory neurons.

Experiments were performed to identify the glycinergic or GABAergic nature, and the timing of discharge, of the neurons which produce chloride-dependent inhibitions on other bulbar respiratory neurons (RNs) during their silent and active phases. RNs recorded extracellularly in pentobarbital-anesthetized or decerebrate cats, were subjected to iontophoretic applications of glutamate, of the glycine antagonist strychnine, and of the GABAA receptor antagonist bicuculline. Both antagonists induced discharge or increased discharge frequency in restricted parts of the respiratory cycle without affecting the discharge frequency in other parts of the cycle. Strychnine most often elicited activity in late-inspiration and early-expiration, but also in early inspiration and in late expiration. Bicuculline was most often effective throughout the entire discharge period of each neuron with no effect during the silent period, although it also acted selectively during late-inspiration in inspiratory neurons, an effect attributed to GABAA receptor blockade. The convergence of glycinergic afferent inputs during late inspiration and early expiration suggests that glycinergic neurons may play an important role in the inspiratory to expiratory phase transition.

Animals↗

Breed- and gender-dependent differences in eye growth and form deprivation responses in chick.

This study investigated the influences of breed and gender on the response to form deprivation and subsequent changes (recovery) when normal vision was restored. Two breeds of chickens, the White Leghorn and broiler cross, were compared, as well as male and female chicks for the White Leghorn breed. Normal eye growth was faster in the more rapidly growing broiler chicks; gender-differences were not as great as breed-differences although male White Leghorns ultimately became heavier and showed slightly greater normal eye growth than females. While both breeds showed high myopia and axial elongation in response to form deprivation, they differed significantly in the magnitude of their response, with White Leghorns showing more myopia and greater axial elongation and also recovering more slowly. Responses to form deprivation were similar for both genders, with respect to both the amount of myopia and axial elongation produced, although the female chicks recovered faster. Together these observations indicate that, although the overall pattern of response of form deprivation is consistent across both breed and gender, related quantitative differences in responses can be expected and need to be taken into account in experimental design and cross-study comparisons.

Animals↗

[Ring trials in expert assessment--a practicable procedure for quality assurance?].

An intercomparison programme for expert assessment was carried out as part of quality assurance for the public health departments in Bavaria. A file documenting medical diagnoses and reports of a patient was presented to medical doctors in a district of Bavaria and in the Academy for Public Health Services in Munich for assessment. The participation was voluntary and anonymous. The case presented was an obese man who wanted to become a civil servant. The doctors were asked to give an expert assessment of his health. Four criteria were used to evaluate the assessments: the assessment, its conclusiveness, the documentation and the epicrisis. 54 out of 100 doctors asked participated. On average all criteria were adequately fulfilled. This paper discusses the advantages and disadvantages of an intercomparison programme for expert assessments in the field of social medicine. Our results show that an intercomparison programme for expert assessments could form part of quality assurance.

Adult↗

[Internal hazardous substance burden of persons from various regions of origin--studies of lead, mercury, arsenic and cadmium exposure].

AIM OF THE STUDY: The aim of this study was to investigate the concentration of metals of environmental-medical relevance in biological materials in persons seeking asylum with regard to their country of origin. COLLECTIVE AND METHOD: During medical examination after entry into Germany of persons seeking asylum, samples were taken for determination of the following biological monitoring parameters: lead in blood, and arsenic, cadmium and mercury in urine. A total of 103 males were investigated (13 from former Yugoslavia, 29 from the former USSR, 33 Africans and 28 Asians) ranging from 16 to 53 years of age (median 27 years). 34 male Germans without occupational exposure to these substances and a similar age structure (age 25-36 years; median 26 years) served as a control group. RESULTS: The countries of origin had a significant influence on all the biological monitoring parameters investigated. The mean blood lead concentration in the Asians of 75.4 micrograms/L was the highest level found, while the lowest concentration of 38.0 micrograms/L was measured in the German controls. Also the level of arsenic excreted in the urine was on average much higher in the persons seeking asylum than in the German controls. In the Africans a mean level of 9.7 micrograms/g creatinine was reached. The Germans had the lowest arsenic concentrations in urine of 5.3 micrograms/g creatinine. There were, however, considerable interindividual fluctuations, which are probably due to oral uptake of arsenic compounds as a result of eating seafoods. The highest mean concentration of mercury excreted in urine was found in the German controls. Values of 0.9 microgram/g creatinine were determined. The men seeking asylum from former Yugoslavia had significantly higher values than other groups for cadmium excreted in urine. The median of 0.6 microgram/g creatinine was nearly three times as high as found in the Germans. CONCLUSIONS: For all parameters investigated, with the exception of mercury, higher internal exposure was found in the persons seeking asylum than in the German controls. This may be due to individual life style, dietary habits or environmental conditions in the country of origin. For clinical environmental medicine, the 95th percentile, as the upper limit of the reference range, can only be regarded as an orientation aid for classifying the exposure to hazardous substances of an individual compared to other persons from the same environment.

Adolescent↗

Cyclophilin catalyzes protein folding in yeast mitochondria.

Cyclophilins are a family of ubiquitous proteins that are the intracellular target of the immunosuppressant drug cyclosporin A. Although cyclophilins catalyze peptidylprolyl cis-trans isomerization in vitro, it has remained open whether they also perform this function in vivo. Here we show that Cpr3p, a cyclophilin in the matrix of yeast mitochondria, accelerates the refolding of a fusion protein that was synthesized in a reticulocyte lysate and imported into the matrix of isolated yeast mitochondria. The fusion protein consisted of the matrix-targeting sequence of subunit 9 of F1F0-ATPase fused to mouse dihydrofolate reductase. Refolding of the dihydrofolate reductase moiety in the matrix was monitored by acquisition of resistance to proteinase K. The rate of refolding was reduced by a factor of 2-6 by 2.5 microM cyclosporin A. This reduced rate of folding was also observed with mitochondria lacking Cpr3p. In these mitochondria, protein folding was insensitive to cyclosporin A. The rate of protein import was not affected by cyclosporin A or by deletion of Cpr3p.

Amino Acid Isomerases↗

Use of bone mineral content determination by X-ray absorptiometry in the evaluation of osteodystrophy among workers exposed to aluminium powders.

Within the framework of a cross-sectional study, we investigated 61 employees in an aluminium powder factory to see if aluminium had an influence on bone mineral content using the non-invasive method of bone density measurement. Thirty-two workers had been employed for, on average, 151 months in the area of aluminium powder production. Twenty-nine employees in the same factory, who had not been engaged in the production of aluminium powder, served as controls. The groups differed significantly in the concentrations of aluminium in urine and plasma. The bone mineral content, which was determined in the lumbar spine by means of photon absorptiometry showed no significant difference between the groups. The bone density value amounted to 1.00 g/cm2 for those exposed and 1.02 g/cm2 for the control group (median values). No correlation could be determined between the values obtained from the biological monitoring of the plasma or the duration of exposure and the bone density values. To summarise, using osteodensitometry as the method of investigation here, no influence could be detected for an occupational exposure to aluminium powders on the mineral salt content of the skeletal system in the area of the lumbar spine.

Absorptiometry, Photon↗