Search PubMed⌕ Search

Biomedical subjects

G Schmidt

Publications and source records attributed to G Schmidt.

At least 73 records · Page 4Linked to original sources
PubMed2000

Effects of abciximab and tirofiban on vitronectin receptors in human endothelial and smooth muscle cells.

human umbilical venous endothelial cells. 7E3 binding correlated with alphavbeta3-expression in all cell types. Integrin-mediated cell functions were analysed with adhesion and spreading assays on vitronectin. In human umbilical venous endothelial cells, these functions were mediated by alphavbeta3 and in human iliac arterial smooth muscle cells by alphavbeta5. In human umbilical venous smooth muscle cells, both vitronectin receptors were involved. Abciximab potently inhibited alphavbeta3-mediated cell adhesion and spreading. With tirofiban, no significant inhibition of vascular cell functions was observed. The present data demonstrate that vitronectin-cell interactions in vascular cells are mediated via two distinct integrin-receptors, alphavbeta3 and alphavbeta5. Abciximab, which solely inhibits alphavbeta3-mediated cell functions, may be particularly effective in human endothelium and in beta3-integrin expressing vascular smooth muscle cells.

Abciximab↗
PubMed2000

Expression pattern of XIRG, a marker for non-neural ectoderm.

XIRG (for Xenopus IRG) was cloned by screening a cDNA library of UV-ventralized stage 13 Xenopus laevis embryos for specifically ventrally expressed mRNAs. Embryonic XIRG mRNA expression is restricted to non-neural ectoderm at the gastrula and neurula stages. In adult X. laevis, XIRG mRNA can be detected in skin and kidney. Extensive searches in nucleic acid and protein databases revealed homologous sequences in mouse, human and zebrafish. Mouse IRG1 mRNA is expressed in cultured macrophages as a response to bacterial lipopolysaccharide treatment.

Amino Acid Sequence↗
PubMed2000

Biomechanical analysis of sit-to-stand transfer in healthy and paraplegic subjects.

OBJECTIVE: An experimental study of the sit-to-stand transfer in healthy adults with/without arm-support and in paraplegic patients with/without electrical stimulation of the quadriceps muscles was performed. The study was aimed to compare the joint torques, momentum transfer hypothesis, and stability of the sit-to-stand transfer in the healthy and paraplegic subjects. METHODS: A planar 3-linkage rigid body model was used to compute the body-segmental linear momentum and the reaction forces and torques at the joints from measured data. RESULTS: In healthy subjects the arm-support enlarged the support base of the body and thus, increased the postural stability. Strong arm-assistance reduced the maximum hip and knee joint torques by more than 50%. It was observed that the healthy participants rising with arm-support used momentum transfer to facilitate the transition from sitting to standing. The paraplegic participants did not apply the momentum transfer strategy and the sit-to-stand transfer was accomplished in a quasi-static manner. Stimulating the quadriceps, the legs could participate partly in the movement dynamics. CONCLUSION: Our results indicate that some significant differences exist between the maneuver applied by the paraplegic patients to stand up and the strategies used by the healthy adults rising with arm-support. RELEVANCE: Analysis of the biomechanical factors underlying the sit-to-stand activity is essential in the design of competent closed-loop neuroprosthesis controllers which assist paraplegic patients during rising.

Adult↗
PubMed2000

Sex ratio of transsexuals in Germany: the development over three decades.

OBJECTIVE: The higher incidence of man-to-woman transsexuals compared to woman-to-man transsexuals varies markedly from country to country. This is the first survey of the sex ratio to be made in Germany. METHOD: It covers 1785 patients who between 1964 and 1998 were diagnosed as transsexual at the four largest German centres offering treatment. RESULTS: From 1970 to 1994 the sex ratio remained constant at 2:1 in favour of man-to-woman transsexuals. Over the past 4 years, however, it has altered considerably and reached 1.2:1. CONCLUSION: Up to 1994 our results do not support the assumption that transsexualism is gradually becoming equally prevalent in both sexes. The drop in the sex ratio after 1994 can be explained either as a reduction of an overhang of male-to-female transsexuals or as an artificial phenomenon caused by recent developments in therapy and by the views of transsexuals' groups on the treatment they are offered.

Adolescent↗
PubMed2000

The paradox of low body mass index and high body fat percentage among Chinese, Malays and Indians in Singapore.

OBJECTIVE: To study the relationship between body fat percentage and body mass index (BMI) in three different ethnic groups in Singapore (Chinese, Malays and Indians) in order to evaluate the validity of the BMI cut-off points for obesity. DESIGN: Cross-sectional study. SUBJECTS: Two-hundred and ninety-one subjects, purposively selected to ensure adequate representation of range of age and BMI of the general adult population, with almost equal numbers from each ethnic and gender group. MEASUREMENTS: Body weight, body height, sitting height, wrist and femoral widths, skinfold thicknesses, total body water by deuterium oxide dilution, densitometry with Bodpod(R) and bone mineral content with Hologic(R) QDR-4500. Body fat percentage was calculated using a four-compartment model. RESULTS: Compared with body fat percentage (BF%) obtained using the reference method, BF% for the Singaporean Chinese, Malays and Indians were under-predicted by BMI, sex and age when an equation developed in a Caucasian population was used. The mean prediction error ranged from 2.7% to 5.6% body fat. The BMI/BF% relationship was also different among the three Singaporean groups, with Indians having the highest BF% and Chinese the lowest for the same BMI. These differences could be ascribed to differences in body build. It was also found that for the same amount of body fat as Caucasians who have a body mass index (BMI) of 30 kg/m2 (cut-off for obesity as defined by WHO), the BMI cut-off points for obesity would have to be about 27 kg/m2 for Chinese and Malays and 26 kg/m2 for Indians. CONCLUSIONS: The results show that the relationship between BF% and BMI is different between Singaporeans and Caucasians and also among the three ethnic groups in Singapore. If obesity is regarded as an excess of body fat and not as an excess of weight (increased BMI), the cut-off points for obesity in Singapore based on the BMI would need to be lowered. This would have immense public health implications in terms of policy related to obesity prevention and management.

Absorptiometry, Photon↗
PubMed2000

GAP activity of the Yersinia YopE cytotoxin specifically targets the Rho pathway: a mechanism for disruption of actin microfilament structure.

The YopE cytotoxin of Yersinia pseudotuberculosis is an essential virulence determinant that is injected into the eukaryotic target cell via a plasmid-encoded type III secretion system. Injection of YopE into eukaryotic cells induces depolymerization of actin stress fibres. Here, we show that YopE exhibits a GTPase-activating protein (GAP) activity and that the presence of YopE stimulates downregulation of Rho, Rac and Cdc42 activity. YopE has an arginine finger motif showing homology with those found in other GAP proteins. Exchange of arginine 144 with alanine, located in this arginine finger motif, results in an inactive form of YopE that can no longer stimulate GTP hydrolysis by the GTPase. Furthermore, a yopE(R144A) mutant is unable to induce cytotoxicity on cultured HeLa cells in contrast to the corresponding wild-type strain. Expression of wild-type YopE in cells of Saccharomyces cerevisiae inhibits growth, while in contrast, expression of the inactive form of YopE, YopE(R144A), does not affect the yeast cells. Co-expression of proteins belonging to the Rho1 pathway of yeast, Rho1, Rom2p, Bck1 and Ste20, suppressed the growth phenotype of YopE in yeast cells. These results provide evidence that YopE exhibits a GAP activity to inactivate RhoGTPases, leading to depolymerization of the actin stress fibres in eukaryotic cells and growth inhibition in yeast.

Actin Cytoskeleton↗
PubMed2000

Intermittent chaos in electron scattering

The motion of an electron in a uniform magnetic field and positive point charge is not integrable. Phase space is often divided between regular regions farther from the positive charge and chaotic regions nearby. As the electron transits the chaotic region, intermittent chaotic behavior ensues. An analytic method to estimate the location of the transit parameters is also developed.

Journal Article↗
PubMed2000

Pseudomonas aeruginosa ExoT is a Rho GTPase-activating protein.

Transient intracellular expression of ExoT in CHO cells stimulated cell rounding and actin reorganization. Biochemical studies showed that ExoT was a GTPase-activating protein for RhoA, Rac1, and Cdc42. Together, these data show that ExoT interferes with Rho signal transduction pathways, which regulate actin organization, exocytosis, cell cycle progression, and phagocytosis.

Actins↗
PubMed2000

A Comparison between Composition and Density of the Fat-Free Mass of Young Adult Singaporean Chinese and Dutch Caucasians.

BACKGROUND: The body composition was measured in 30 female Singapore Chinese and 34 female Dutch Caucasians aged (mean +/- SD) 22.7 +/- 3.6 years and in 39 male Singapore Chinese and 39 male Dutch Caucasians aged 23.3 +/- 3.2 years. METHODS: The body fat percentage (BF%) was measured using densitometry and deuterium oxide dilution as well as a chemical four-compartment model, including fat mass, water, mineral, and protein. The chemical composition of the fat-free mass (FFM) and its density were calculated. RESULTS: Mean body mass index (kg/m(2)) and BF% based on the four-compartment model in the four subgroups were 20.3 +/- 1.5 and 29.7 +/- 5.3 for the Singapore Chinese females, 22.1 +/- 1.2 and 28.9 +/- 5.2 for the Dutch females, 21.5 +/- 2.5 and 19.4 +/- 6.1 for the Singapore males, and 22.2 +/- 1.8 and 15.8 +/- 4.9 for the Dutch males. The contributions to the FFM of water, protein, and mineral were, respectively, 72.8 +/- 1.5, 19.2 +/- 1.8, and 7.9 +/- 0.8% for the Singaporean females and 74.2 +/- 1.4, 18.3 +/- 1.5, and 7.6 +/- 0.5% for the Dutch females. In males these figures were 73.2 +/- 1.7, 19.6 +/- 1.7, and 7.3 +/- 0.5% for the Singaporeans and 72.9 +/- 1.4, 20.5 +/- 1.4, and 6.6 +/- 0.5% for the Dutch. In females, these figures were for all components significantly different between the ethnic groups; in males the differences were significant for protein and mineral only. The calculated densities (kg/l) of the FFM were 1.1074 +/- 0.0057, 1.1012 +/- 0.0051, 1.1027 +/- 0.0065, and 1.1004 +/- 0.0055 for the Chinese females, Caucasian females, Chinese males, and Caucasian males, respectively. CONCLUSIONS: Although it cannot be excluded that the differences in density and composition of the FFM are due to methodological differences between the study sites, the findings may have consequences for the validity of single (reference) methods due to violation of normally used assumptions. The findings explain the observed underestimation of BF% from density using Siri's formula in the Chinese subjects, especially in females. The use of deuterium oxide as a single method to determine the BF% resulted in a smaller bias than densitometry (overall 1.6 +/- 2.0% for densitometry, 0.3 +/- 1.7% for deuterium dilution), suggesting that the deuterium oxide method may be more suitable as a single method in comparative body composition studies.

Adipose Tissue↗
PubMed2000

Angiotensin II and PDGF-BB stimulate beta(1)-integrin-mediated adhesion and spreading in human VSMCs.

beta(1)-Integrins play an important role for adhesion and spreading of human smooth muscle cells. In the present study we examined the influence of angiotensin II and platelet-derived growth factor (PDGF)-BB on beta(1)-integrin-dependent functions of human smooth muscle cells obtained from iliac arteries. Treatment of these cells with PDGF-BB (20 ng/mL) and Angiotensin II (1 micromol/L) did not change beta(1)-integrin expression up to 48 hours as analyzed by flow cytometry and reverse transcription polymerase chain reaction. beta(1)-integrins predominantly mediated adhesion of human smooth muscle cells to collagen I (79.7+/-4.4%, P<0.01) and fibronectin (66. 6+/-2.4%, P<0.01). Treatment of smooth muscle cells with Angiotensin II (1 micromol/L) and PDGF-BB (20 ng/mL) significantly increased the adhesion to collagen I by 56.5% and 44.3%, respectively, and to fibronectin by 49.6% and 36.4%, respectively (all P<0.05). Angiotensin II-induced effects were mediated by the AT(1) receptor. The PDGF-BB mediated increase of adhesion was inhibited in the presence of genestein, a tyrosine-kinase inhibitor and by protein kinase C downregulation with phorbol 12-myristate 13-acetate. Spreading of smooth muscle cells also was beta(1)-integrin dependent on collagen I and alpha(5)beta(1)-integrin dependent on fibronectin. Angiotensin II and PDGF-BB increased cell spreading on fibronectin up to 276% and 318%, respectively, and on collagen I up to 133% and 138% (all P<0.05). These increases were significantly inhibited by blocking antibodies against beta(1)-integrin, alpha(5)-integrin on fibronectin, the AT(1) receptor blocker irbesartan, and genestein. The present data demonstrate that angiotensin II and as well PDGF-BB enhance beta(1)-integrin-dependent adhesion and spreading of human vascular smooth muscle cells. Furthermore, the experiments with PDGF suggest an involvement of protein kinase C activation leading to these enhanced effects.

Angiotensin II↗
PubMed2000

Barriers to recovery in a First Nations community.

The practice of psychiatric rehabilitation is a concept and method that developed in urban-based settings. It has become a widely used guiding principle in mental health practice. This research examines how psychiatric rehabilitation fits within a remote First Nations community. Ten people--service providers, consumers, and family members--were interviewed to gather information about their perceptions of and experiences within the mental health system. The interview material was examined using content analysis. The results suggest that geographic and economic factors create serious barriers to application of the psychiatric rehabilitation method in a remote First Nations community.

British Columbia↗
PubMed2000

Is respite care available for chronically ill seniors?

OBJECTIVE: To determine family physicians' perceptions of how available respite care is and how easy it is to refer chronically ill older people to it, and to examine their opinions of respite care. DESIGN: Mailed survey to family physicians on the Thames Valley Family Practice Research Unit's mailing list. SETTING: London, Ont, and surrounding area. PARTICIPANTS: Of the 448 surveys mailed to eligible physicians, 288 were completed and returned for a response rate of 64.3%. MAIN OUTCOME MEASURES: Respondents' perceptions of how available respite care is and how easy it is to refer chronically ill older people to it and their opinions on the effectiveness of respite care. RESULTS: More than half the respondents reported that outpatient respite care is always available, but how available depended on practice location. Inpatient respite care was reported as less available. More than half the respondents found referral to respite care difficult. Respondents were very positive about the role of respite services in long-term care and in lowering caregiver stress. Respondents' perceptions varied according to where they had attended medical school. Their perceptions of respite care's role in long-term care and in helping patients remain at home were influenced by whether they thought respite care was available. CONCLUSION: Family physicians need education in the value of respite services for their chronically ill older patients and their families. Physicians also need information on the respite services available and strategies for accessing them. Our findings suggest a need for greater attention to regional discrepancies in availability of services.

Aged↗
PubMed2000

Application of the Woman Abuse Screening Tool (WAST) and WAST-short in the family practice setting.

BACKGROUND: Our study objectives were to assess the validity and reliability of the Woman Abuse Screening Tool (WAST) in the general population within the family practice setting; to determine the comfort levels of family physicians administering the WAST, their perceptions of its ability to help them identify abused women, and their willingness to continue using it in practice; and to determine the self-reported comfort of patients being asked the WAST questions by their family physicians. METHODS: We included a stratified random sample of 20 physicians practicing in both urban and rural settings drawn from 400 family physicians in London, Ontario, Canada, and the surrounding area. These physicians administered the WAST to 10 to 15 eligible and consenting patients during the course of regular care. Following the physician-patient encounter, patients were asked to complete both a measure about their comfort in being asked each of the WAST questions and the Abuse Risk Inventory (ARI). RESULTS: Scores on the WAST correlated well with those on the ARI. The reliability of the WAST among this sample was demonstrated by a coefficient alpha of 0.75. With the WAST-Short (the first 2 questions of the WAST), 26 of the 307 patients screened (8.5%) were identified as experiencing abuse. The physicians were comfortable administering the WAST to their women patients, and 91% of the patients reported being comfortable or very comfortable when asked the WAST questions by their family physician. CONCLUSIONS: The WAST was found to be a reliable and valid measure of abuse in the family practice setting, with both patients and family physicians reporting comfort with it being part of the clinical encounter.

Adolescent↗
PubMed1999

The N-terminal domain of Pseudomonas aeruginosa exoenzyme S is a GTPase-activating protein for Rho GTPases.

Pseudomonas aeruginosa exoenzyme S (ExoS) is a bifunctional cytotoxin. The ADP-ribosyltransferase domain is located within the C terminus part of ExoS. Recent studies showed that the N terminus part of ExoS (amino acid residues 1-234, ExoS(1-234)), which does not possess ADP-ribosyltransferase activity, stimulates cell rounding when transfected or microinjected into eukaryotic cells. Here we studied the effects of ExoS(1-234) on nucleotide binding and hydrolysis by Rho GTPases. ExoS(1-234) (100-500 nM) did not influence nucleotide exchange of Rho, Rac, and Cdc42 but increased GTP hydrolysis. A similar increase in GTPase activity was stimulated by full-length ExoS. Half-maximal stimulation of GTP hydrolysis by Rho, Rac, and Cdc42 was observed at 10-11 nM ExoS(1-234), respectively. We identified arginine 146 of ExoS to be essential for the stimulation of GTPase activity of Rho proteins. These data identify ExoS as a GTPase-activating protein for Rho GTPases.

ADP Ribose Transferases↗
PubMed1999

Identification of the C-terminal part of Bordetella dermonecrotic toxin as a transglutaminase for rho GTPases.

Bordetella dermonecrotic toxin (DNT) causes the deamidation of glutamine 63 of Rho. Here we identified the region of DNT harboring the enzyme activity and compared the toxin with the cytotoxic necrotizing factor 1, which also deamidates Rho. The DNT fragment (DeltaDNT) covering amino acid residues 1136-1451 caused deamidation of RhoA at glutamine 63 as determined by mass spectrometric analysis and by the release of ammonia. In the presence of dansylcadaverine or ethylenediamine, DeltaDNT caused transglutamination of Rho. Deamidase and transglutaminase activities were blocked in the mutant proteins Cys(1292) --> Ala, His(1307) --> Ala, and Lys(1310) --> Ala of DeltaDNT. Deamidation and transglutamination induced by DeltaDNT blocked intrinsic and Rho- GTPase-activating protein-stimulated GTPase activity of RhoA. DeltaDNT deamidated and transglutaminated Rac and Cdc42 in the absence and presence of ethylenediamine, respectively. Modification of Rho proteins by DeltaDNT was nucleotide-dependent and did not occur with GTPgammaS-loaded GTPases. In contrast to cytotoxic necrotizing factor, which caused the same kinetics of ammonia release in the absence and presence of ethylenediamine, ammonia release by DeltaDNT was largely increased in the presence of ethylenediamine, indicating that DeltaDNT acts primarily as a transglutaminase.

Amino Acid Sequence↗
PubMed1999

Identification of the region of rho involved in substrate recognition by Escherichia coli cytotoxic necrotizing factor 1 (CNF1).

The Escherichia coli cytotoxic necrotizing factor 1 (CNF1) and the Bordetella dermonecrotic toxin (DNT) activate Rho GTPases by deamidation of Gln(63) of RhoA (Gln(61) of Cdc42 and Rac). In addition, both toxins possess in vitro transglutaminase activity in the presence of primary amines. Here we characterized the region of Rho essential for substrate recognition by the toxins using Rho/Ras chimeras as protein substrates. The chimeric protein Ras55Rho was deamidated or transglutaminated by CNF1. Rat pheochromocytoma PC12 cells microinjected with Ras55Rho developed formation of neurite-like structures after treatment with the CNF1 holotoxin indicating activation of the Ha-Ras chimera and Ras-like effects in intact cells. The Ras59Rho78Ras chimera protein contained the minimal Rho sequence allowing deamidation or transglutamination by CNF1. A peptide covering mainly the switch II region and consisting of amino acid residues Asp(59) through Asp(78) of RhoA was substrate for CNF1. Changes of amino acid residues Arg(68) or Leu(72) of RhoA into the corresponding residues of Ras (R68ARhoA and L72QRhoA) inhibited deamidation and transglutamination of the mutants by CNF1. In contrast to CNF1, DNT did not modify Rho/Ras chimeras or the switch II peptide (Asp(59) through Asp(78)). Glucosylation of RhoA at Thr(37) blocked deamidation by DNT but not by CNF. The data indicate that CNF1 recognizes Rho GTPases exclusively in the switch II region, whereas the substrate recognition by DNT is characterized by additional structural requirements.

Amino Acid Sequence↗
PubMed1999

Neosynthesis and activation of Rho by Escherichia coli cytotoxic necrotizing factor (CNF1) reverse cytopathic effects of ADP-ribosylated Rho.

Clostridium botulinum exoenzyme C3 inactivates the small GTPase Rho by ADP-ribosylation. We used a C3 fusion toxin (C2IN-C3) with high cell accessibility to study the kinetics of Rho inactivation by ADP-ribosylation. In primary cultures of rat astroglial cells and Chinese hamster ovary cells, C2IN-C3 induced the complete ADP-ribosylation of RhoA and concomitantly the disassembly of stress fibers within 3 h. Removal of C2IN-C3 from the medium caused the recovery of stress fibers and normal cell morphology within 4 h. The regeneration was preceded by the appearance of non-ADP-ribosylated RhoA. Recovery of cell morphology was blocked by the proteasome inhibitor lactacystin and by the translation inhibitors cycloheximide and puromycin, indicating that intracellular degradation of the C3 fusion toxin and the neosynthesis of Rho were required for reversal of cell morphology. Escherichia coli cytotoxic necrotizing factor CNF1, which activates Rho by deamidation of Gln(63), caused reconstitution of stress fibers and cell morphology in C2IN-C3-treated cells within 30-60 min. The effect of CNF1 was independent of RhoA neosynthesis and occurred in the presence of completely ADP-ribosylated RhoA. The data show three novel findings; 1) the cytopathic effects of ADP-ribosylation of Rho are rapidly reversed by neosynthesis of Rho, 2) CNF1-induced deamidation activates ADP-ribosylated Rho, and 3) inhibition of Rho activation but not inhibition of Rho-effector interaction is a major mechanism underlying inhibition of cellular functions of Rho by ADP-ribosylation.

Adenosine Diphosphate Ribose↗