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Biomedical subjects

E Voss

Publications and source records attributed to E Voss.

At least 19 recordsLinked to original sources
PubMed2004

[Changes in needs for assistance and care after hip fractures in the elderly].

For the prevention and rehabilitation of fall-related fractures, not only functional status is important. It is necessary to describe the level of help and care needed at the time the fracture happened and its changes after a certain period. Investigations of the changes in the need of help and care after a fall-related fracture hardly exist for the Federal Republic of Germany. The first step in the present investigation was to analyze the changes in the need of help and care. In a second step, different developments of changes in the need of help and care after a fall-related hip fracture should be identified. Data for the present analysis were taken from a prospective 12-month observational survey (Fractures in late life). A total of 332 people aged 65 and over were assessed at two timepoints (T1-within the first 4 days post-fracture and T2-six months later by phone call). The assessed aspects were formal and informal support, financial support, ability to walk, cognition (only at T1) and form of housing. After the fall-related fracture the strain of formal and informal support increases. The strain of financial support and institutional care also increases. 20% of the patients achieved for the first time the criteria for the lowest level in the legal care system of Germany which indicates a higher level of need of care. 5% of the patients achieved post-fracture a higher level in the legal care system. Six different groups of patients could be identified by cluster analyses. They show differences in the changes in the ability to walk, form of housing, mortality and level of care and help. The different health status before and after the fall-related fracture leads to different developments post-fracture. In prevention and rehabilitation of patients with fall-related fractures, the individual needs of the subgroups should be taken into consideration.

Activities of Daily Living↗
PubMed2003

A protein interaction map of Drosophila melanogaster.

Drosophila melanogaster is a proven model system for many aspects of human biology. Here we present a two-hybrid-based protein-interaction map of the fly proteome. A total of 10,623 predicted transcripts were isolated and screened against standard and normalized complementary DNA libraries to produce a draft map of 7048 proteins and 20,405 interactions. A computational method of rating two-hybrid interaction confidence was developed to refine this draft map to a higher confidence map of 4679 proteins and 4780 interactions. Statistical modeling of the network showed two levels of organization: a short-range organization, presumably corresponding to multiprotein complexes, and a more global organization, presumably corresponding to intercomplex connections. The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components. This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans.

Animals↗
PubMed2003

[Case management and functional outcome in persons aged 65 years and over with hip fracture].

The goal of the investigation was to study case management and functional outcome in older patients with hip fracture. A prospective observational survey was performed, including all patients aged 65 years and over presenting with hip fracture in Heidelberg, from 1 July 1999 to 30 June 2000. All patients were reassessed by telephone calls 6 months post-fracture. A total of 331 patients were included (mean age 81.5 years, 81% female,23.8% nursing home residents). Hip fracture incidence per 1,000 was 7.8/year, and nursing home residents had a six times higher incidence rate than those living at home. Prior to the fracture, half of the patients were dependent in ambulation and a third needed support in basic activities. With substantial comorbidity (42% cognitive impairment), complications were common. Geriatric care was needed for 82% of the survivors. In-hospital treatment costs were about 10,000 Euro per fracture. Mortality at 6 months was 19.9%. The majority of survivors showed loss of competence and mobility. Functional outcome in older patients with hip fracture is disappointing. As the majority of the patients are frail, clinical treatment is complicated by "geriatric" problems. Thus, improved interdisciplinary care, with close cooperation between geriatricians and surgeons might result in a better functional outcome.

Age Factors↗
PubMed2000

Clathrin plays a novel role in the regulation of cell polarity, pseudopod formation, uropod stability and motility in Dictyostelium.

Although the traditional role of clathrin has been in vesicle trafficking and the internalization of receptors, a novel role in cytokinesis was recently revealed in an analysis of a clathrin-minus Dictyostelium mutant (chc(-)). chc(-) cells grown in suspension were demonstrated to be defective in assembling myosin II into a normal contractile ring. To test whether this defect reflected a more general one of cytoskeletal dysfunction, chc(-) cells were analyzed for cell polarity, pseudopod formation, uropod stability, cell locomotion, chemotaxis, cytoskeletal organization and vesicle movement. chc(-) cells crawled, chemotaxed, localized F-actin in pseudopods, organized their microtubule cytoskeleton in a relatively normal fashion and exhibited normal vesicle dynamics. Although chc(-) cells extended pseudopods from the anterior half of the cell with the same frequency as normal chc(+) cells, they extended pseudopods at twice the normal frequency from the posterior half of the cell. The uropods of chc(-) cells also exhibited spatial instability. These defects resulted in an increase in roundness, a reduction in polarity, a reduction in velocity, a dramatic increase in turning, a high frequency of 180 degrees direction reversals and a decrease in the efficiency of chemotaxis. All defects were reversed in a rescued strain. These results are the first to suggest a novel role for clathrin in cell polarity, pseudopod formation, uropod stability and locomotion. It is hypothesized that clathrin functions to suppress pseudopod formation and to stabilize the uropod in the posterior half of a crawling cell, two behavioral characteristics that are essential for the maintenance of cellular polarity, efficient locomotion and efficient chemotaxis.

Actins↗
PubMed1999

Pathogenic and vaccine significance of toxin-coregulated pili of Vibrio cholerae E1 Tor.

Vibrio cholerae O1 strains are classified into one of two biotypes, classical and E1 Tor, the latter being primarily responsible for cholera cases worldwide since 1961. Recent studies in our laboratory have focused upon the pathogenic and vaccine significance of the toxin-coregulated pili (TCP) produced by strains of E1 Tor biotype. Mutants in which the tcpA gene (encoding the pilin subunit protein) has been inactivated are dramatically attenuated in the infant mouse cholera model, showing markedly reduced colonisation potential in mixed-infection competition experiments. Significantly, in the vaccine context, antibodies to TCP are sufficient to prevent experimental infection, although our data suggest that this protective effect might be limited to strains of homologous biotype. Since we have shown that tcpA sequences are conserved within a biotype but differ between biotypes, this latter observation suggests that the biotype-restricted pilin epitopes might have greater vaccine significance. Similar studies indicate that TCP also play a critical role in colonisation by strains of the recently-recognised O139 serogroup, which is thought to have evolved from an O1 E1 Tor strain. In contrast to the effect of introducing mutations in the tcpA gene, strains carrying inactivated mshA genes (encoding the subunit of the mannose-sensitive haemagglutinin pilus) show unaltered in vivo behaviour. Consistent with this finding is our inability to demonstrate any protective effect associated with antibodies to MSHA. Ongoing approaches to vaccine development are variously aimed at improving the immunogenicity of the current inactivated whole-cell vaccine, or assessing the field efficacy of a promising live attenuated strain. The possible implications of our findings are discussed in relation to both of these options.

Animals↗
PubMed1999

Aminoguanidine inhibits albuminuria, but not the formation of advanced glycation end-products in skin collagen of diabetic rats.

Aminoguanidine, an inhibitor of advanced glycation reactions in vitro, inhibits the development of diabetic complications in animal models of diabetes, suggesting that it acts by inhibition of advanced glycation reactions in vivo. However, effects of aminoguanidine on the formation of specific advanced glycation end-products (AGEs) in vivo have not been rigorously examined. Therefore, we studied the effects of aminoguanidine on the formation of pentosidine and N(epsilon)-(carboxymethyl)lysine (CML), measured by analytical chemical methods, in collagen of streptozotocin-diabetic Lewis rats at doses which ameliorated urinary albumin excretion, an index of diabetic nephropathy. At 12 weeks, diabetic animals had fivefold higher blood glucose, threefold higher glycated hemoglobin and fivefold higher collagen glycation, compared to metabolically healthy controls; pentosidine and CML in skin collagen were increased by approximately 30 and 150%, respectively. Administration of aminoguanidine, 50 mg/kg by daily intraperitoneal injection, significantly inhibited the development of albuminuria (approximately 60%, P < 0.01) in diabetic rats, without an effect on blood glucose or glycation of hemoglobin or collagen. Surprisingly, aminoguanidine failed to inhibit the increase in pentosidine and CML in diabetic rat skin collagen. Similar results were obtained in an independent experiment in which aminoguanidine was administered in drinking water at a dose of 0.5 g/l. We conclude that the therapeutic benefits of aminoguanidine on albuminuria may not be the result of inhibition of AGE formation.

Albuminuria↗
PubMed1999

Pregnancy and laparoscopic surgery.

We reviewed the English literature regarding laparoscopic surgery during pregnancy and found that of 518 reported procedures, the most common was cholecystectomy (45%), followed by adnexal surgery (34%), appendectomy (15%), and other operations (6%). We add six cases to this list; three cholecystectomies, an adnexal procedure, and two for abdominal pain. Thirty-three percent were performed in the first trimester, 56% in the second, and 11% in the third trimester. This review demonstrates a definite trend, indicating that laparoscopy in pregnancy appears to be safe when performed by experienced practitioners. (J Am Assoc Gynecol Laparosc 6(3):347-351, 1999)

Abdominal Pain↗
PubMed1998

A computer-assisted system for reconstructing and interpreting the dynamic three-dimensional relationships of the outer surface, nucleus and pseudopods of crawling cells.

Newly developed software additions to the three-dimensional dynamic image analysis system, 3D-DIAS, are described for simultaneously reconstructing and motion analyzing in three dimensions the outer surface, nucleus and pseudopods of living, crawling cells. This new system is then used to describe for the first time a nuclear behavior cycle in translocating Dictyostelium discoideum amoebae and to investigate the role of pseudopod extension in this process. The nuclear behavior cycle is tuned to the two phases of the general cell behavior cycle [Wessels et al., 1994], and includes nuclear migration both in the z- and in the x,y-axes from the proximal border of the prior anterior pseudopod to the proximal border of a newly expanding anterior pseudopod. Nuclear migration is cued by pseudopod-substratum contact, achieves velocities in excess of 50 microm/min, and is accompanied by characteristic changes in nuclear shape. The rules and characteristics of nuclear behavior are demonstrated to be intact in two mutants affecting pseudopod formation, a myosin IB null mutant (myoB-) and a myosin II heavy chain phosphorylation mutant (3XALA). The rules and characteristics of nuclear migration, however, are disrupted upon dissolution of microtubules by colcemid. Together the above results demonstrate that the newly developed 3D-DIAS system can be used to gain new insights into the dynamic changes in the intracellular 3D architecture associated with cellular translocation.

Animals↗
PubMed1998

Antibodies to lipopolysaccharide block adherence of Shiga toxin-producing Escherichia coli to human intestinal epithelial (Henle 407) cells.

Shiga toxin-producing Escherichia coli (STEC) are a diverse group of organisms known to cause diarrhoea, haemorrhagic colitis and haemolytic uraemic syndrome (HUS) in humans. During the early stage of infection, numbers of STEC in the gut may be very high (of the order of 10(9)/g faeces), but as disease progresses, the numbers may drop rapidly such that STEC are undetectable within a week. Convalescent sera from patients recovering from HUS frequently contain high levels of antibody to E. coli lipopolysaccharide (LPS) of the infecting serotype, and it is possible that a local immune response to LPS contributes to elimination of the organism from the gut. We have recently demonstrated that STEC strains isolated from HUS cases have enhanced adherence to a human intestinal epithelial cell line (Henle 407) compared with STEC strains from non-human sources. In this study, we examined the capacity of STEC strains belonging to O-antigen types O111 and O157 to adhere to human intestinal epithelial (Henle 407) cells in the presence or absence of anti-LPS. Adherence was inhibited by up to 95% by anti-LPS of the homologous, but not heterologous serotype. This effect was not an artefact of serum bactericidal or agglutinating activity. Preincubation with purified homologous or heterologous LPS did not prevent adherence, suggesting that LPS was not acting as an adhesin per se. Nevertheless, these findings raise the possibility that oral administration of preparations containing anti-LPS may interfere with colonization of the human gut by STEC, and therefore could be of potential therapeutic value if administered early in the course of infection.

Antibodies, Bacterial↗
PubMed1998

Molecular analysis of Shiga toxigenic Escherichia coli O111:H- proteins which react with sera from patients with hemolytic-uremic syndrome.

Western blot analysis was used to assess the reactivity of convalescent-phase sera from patients who were associated with an outbreak of hemolytic-uremic syndrome (HUS) caused by fermented sausage contaminated with Shiga toxin-producing Escherichia coli (STEC). The predominant STEC isolated from HUS patients belonged to serotype O111:H-, and reactivity to O111:H- whole-cell lysates, treated or untreated with proteinase K, was examined. As expected, all five serum samples demonstrated a marked anti-lipopolysaccharide response, but several protein bands were also immunoreactive, particularly one with an apparent size of 94 kDa. One convalescent-phase serum sample was subsequently used to screen an O111:H- cosmid bank and 2 of 900 cosmid clones were found to be positive, both of which contained a similar DNA insert. Western blot analysis of one of these clones identified three major immunoreactive protein bands of approximately 94, 70, and 50 kDa. An immune response to the three proteins was detectable with all five convalescent-phase serum samples but not with healthy human serum. Immunoreactive 94- and 50-kDa species were produced by a deletion derivative of the cosmid containing a 7-kb STEC DNA insert. Sequence analysis of this region indicated that it is part of the locus for enterocyte effacement, including the eaeA gene which encodes intimin. The deduced amino acid sequence of the O111:H- intimin was 88.6% identical to intimin from O157:H7 STEC, and the most divergent region was the 200 residues at the carboxyl terminus, which were only 75% identical. Such variation may be antigenically significant as serum from a HUS patient infected only with the O111:H- STEC reacted with intimin from an enteropathogenic E. coli O111 strain, as well as several other eaeA-positive STEC isolates, but not with an eaeA-positive STEC belonging to serotype O157:H-. Sera from two of the other HUS patients also failed to react with intimin from this latter strain. However, intimin from O157:H- STEC did react with serum from a patient infected with both O111:H- and O157:H- STEC.

Adhesins, Bacterial↗
PubMed1997

Prognostic value of serum cardiac troponin I and T in chronic dialysis patients: a 1-year outcomes analysis.

To determine the incidence and prognostic value of increased serum cardiac troponin I and T concentrations over 12 months in chronic hemodialysis patients, we performed a retrospective chart review in 16 patients undergoing chronic renal hemodialysis randomly selected from the Regional Kidney Disease Program without prior knowledge of their cardiac status. Serum markers of myocardial injury (cardiac troponin I [cTnI], cardiac troponin T [cTnT], and creatine kinase MB [CK-MB]) were measured and clinical outcomes were assessed. At the beginning of the study, 12 of 16 (75%) patients had increased serum enzyme-linked immunosorbent assay (ELISA) cTnT concentrations greater than 0.20 micrograms/L, eight (50%) had increased serum CK-MB greater than 5.0 micrograms/L, and three (19%) had an increased cTnI greater than 0.8 micrograms/L. Over the 1-year study period, the cardiac event rate (n = 4 with fatal myocardial infarction) was correlated to the patients who displayed the higher elevations of cTnT, CK-MB, and cTnI. In the remaining 12 patients studied at the end of 1 year, seven (58%) had increased ELISA cTnT levels and five (42%) had increased CK-MB levels; no patients had elevated cTnI levels. Reanalysis of ELISA cTnT values with a newly formulated Enzymun cTnT assay showed no significant differences. Our data suggest that whereas substantial increases in cardiac markers tended to have a poor prognostic outcome, there was a high incidence of increased cTnT and CK-MB concentrations without evidence of myocardial injury in chronic hemodialysis patients. The lack of absolute cardiospecificity of cTnT and CK-MB may prove cTnI to be the desired serum marker for the detection of myocardial injury in patients with chronic renal disease.

Adult↗
PubMed1997

Shiga toxin-producing Escherichia coli isolates from cases of human disease show enhanced adherence to intestinal epithelial (Henle 407) cells.

Shiga toxin-producing Escherichia coli (STEC) strains are a diverse group of organisms which are known to cause diarrhea and hemorrhagic colitis in humans. We have recently described a large food-borne outbreak of STEC disease caused by contaminated semidry fermented sausage (A. W. Paton, R. Ratcliff, R. M. Doyle, J. Seymour-Murray, D. Davos, J. A. Lanser, and J. C. Paton, J. Clin. Microbiol. 34:1622-1627, 1996). STEC strains belonging to several O serotypes were isolated from the contaminated food source, but of these, only a subset were isolated from patients with diarrhea or hemolytic-uremic syndrome (HUS). In the present study, we characterized these STEC isolates with respect to the presence of putative virulence-associated genes and the capacity to adhere to a human intestinal epithelial cell line (Henle 407). The O111:H- STEC strain 95NR1 (isolated from one of the outbreak HUS patients) was shown to adhere to Henle 407 cells in a dose-dependent, mannose-resistant fashion. Microscopic examination revealed a diffuse pattern of adherence for this as well as several other STEC strains. Interestingly, the adherence of STEC strains from HUS cases (both outbreak related and sporadic) was significantly greater than that of STEC strains found in the contaminated food source but not found in any patients. These studies support the hypothesis that an enhanced capacity to adhere to intestinal cells is one of the factors which distinguishes human-virulent STEC strains from those of lesser clinical significance.

Animals↗
PubMed1996

Comparison of the promoter proximal regions of the toxin-co-regulated tcp gene cluster in classical and El Tor strains of Vibrio cholerae O1.

A physical map has been constructed of the 5-kb XbaI fragment encoding the promoter proximal of region the tcp gene cluster encoding the toxin-coregulated pilus (TCP) of Vibrio cholerae. This fragment contains the major regulatory regions for TCP. Comparison of the nucleotide (nt) sequences from strains of the classical and El Tor biotypes demonstrates that the regions are essentially identical, with several notable exceptions. The intergenic regions, between tcpI and tcpP, and between tcpH and tcpA, show significant sequence divergence which may account for the biotype-related differences in TCP, since this is the location of the major promoter sequences. The C-terminal coding regions of the major pilin subunit, TcpA, also differ. Southern hybridization analyses suggest that the tcpA nt sequence is conserved within a biotype, and Western blot analysis suggests that the two forms of TcpA are antigenically different, but related. Besides tcpA, tcpB, tcpH and tcpI, the genes encoding two additional proteins, TcpP and TcpQ, but not previously defined, were also identified. TcpH and TcpI have been previously suggested to be regulatory proteins but homology data imply that TcpI is a methyl-accepting chemotaxis protein (MCP), as recently reported [Harkey et al., Infect. Immun. 62 (1994) 2669-2678], and TcpH is predicted to be a periplasmic or exported protein. TcpP is thought to be a trans-cytoplasmic membrane (CM) protein which may have a regulatory role.

Amino Acid Sequence↗
PubMed1996

The toxin-coregulated pilus is a colonization factor and protective antigen of Vibrio cholerae El Tor.

We have previously shown that insertional inactivation of tcpA, the gene encoding the major pilin subunit of the toxin-coregulated pilus (TCP), renders Vibrio cholerae O1 strains of El Tor biotype virtually avirulent in the infant mouse cholera model (IMCM). We now report that more refined mutants, bearing an in-frame deletion in tcpA, show a similar dramatic attenuation in vivo. In mixed-infection competition experiments the ratio of wild-type:mutant vibrios increased c. 10(3)-10(5) fold during a period of in vivo growth. An attempt to complement the delta tcpA mutants by providing a functional El Tor tcpA gene in trans was only partially successful. Sera raised against El Tor TcpA were able to passively protect infant mice against challenge with TCP-positive strains of homologous biotype and were also protective against isolates of the novel O139 serovar. These sera failed to protect against challenge with a strain of classical biotype, nor could antibodies to classical TCP confer immunity to El Tor challenge. We conclude that TCP is a critical colonization factor of V. cholerae O1 El Tor and that antibodies to TCP are sufficient to confer protection against such strains in the IMCM. Our data suggest that the biotype-specific epitopes carried by TcpA are of greater vaccine significance than those epitopes common to both proteins.

Animals↗
PubMed1995

Cardiac troponin, CK-MB and myoglobin for the early detection of acute myocardial infarction and monitoring of reperfusion following thrombolytic therapy.

It is important to establish as soon as possible whether patients who present with chest pain are having an acute myocardial infarction (AMI). Ideally, sensitive and specific serum myocardial markers could provide the basis for early detection as well as determine the status of reperfusion following thrombolytic therapy. The present study examined the utility of cardiac troponin I (cTnI), CK-MB, and myoglobin for the sensitive and specific detection of AMI in 98 consecutive patients presenting to the emergency department (ED) with chest pain. In addition, cardiac troponin T (cTnT), CK-MB, and myoglobin samples were measured over a 90 min time period following thrombolytic therapy in nine separate AMI patients to assess reperfusion. In the ED study, CK-MB, myoglobin, and cTnI were equally sensitive (100%) for the detection of AMI in patients who presented 7.4-14 h after onset of chest pain. However, cTnI was the most specific serum marker (specificity 91.9% compared to CK-MB 85.6%, myoglobin 61.4%). Five of the six non-related AMI patients who had an elevated cTnI had clinically documented myocardial involvement. In the reperfusion study, cTnT, CK-MB and myoglobin, relative increases were greater in reperfused compared to non-reperfused patients. Within the reperfused group, the relative increase of cTnT was greater than CK-MB and myoglobin at 90 min following thrombolytic therapy. These findings show the clinical utility of cardiac-specific troponins as markers for the early detection of AMI and monitoring of reperfusion following thrombolytic therapy.

Creatine Kinase↗