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Biomedical subjects

G Schmidt

Publications and source records attributed to G Schmidt.

At least 55 records · Page 3Linked to original sources
PubMed2001

Rac and phosphatidylinositol 3-kinase regulate the protein kinase B in Fc epsilon RI signaling in RBL 2H3 mast cells.

FcepsilonRI signaling in rat basophilic leukemia cells depends on phosphatidylinositol 3-kinase (PI3-kinase) and the small GTPase Rac. Here, we studied the functional relationship among PI3-kinase, its effector protein kinase B (PKB), and Rac using inhibitors of PI3-kinase and toxins inhibiting Rac. Wortmannin, an inhibitor of PI3-kinase, blocked FcepsilonRI-mediated tyrosine phosphorylation of phospholipase Cgamma, inositol phosphate formation, calcium mobilization, and secretion of hexosaminidase. Similarly, Clostridium difficile toxin B, which inactivates all Rho GTPases including Rho, Rac and Cdc42, and Clostridium sordellii lethal toxin, which inhibits Rac (possibly Cdc42) but not Rho, blocked these responses. Stimulation of the FcepsilonRI receptor induced a rapid increase in the GTP-bound form of Rac. Whereas toxin B inhibited the Rac activation, PI3-kinase inhibitors (wortmannin and LY294002) had no effect on activation of Rac. In line with this, wortmannin had no effect on tyrosine phosphorylation of the guanine nucleotide exchange factor Vav. Wortmannin, toxin B, and lethal toxin inhibited phosphorylation of PKB on Ser(473). Similarly, translocation of the pleckstrin homology domain of PKB tagged with the green fluorescent protein to the membrane, which was induced by activation of the FcepsilonRI receptor, was blocked by inhibitors of PI3-kinase and Rac inactivation. Our results indicate that in rat basophilic leukemia cells Rac and PI3-kinase regulate PKB and suggest that Rac is functionally located upstream and/or parallel of PI3-kinase/PKB in FcepsilonRI signaling.

Animals↗
PubMed2001

Results of flexor tendon repair of the hand by the motion-stable wire suture by Towfigh.

We compared the motion-stable wire suture by Towfigh (MSWST) with a modified Kessler suture (MKS) by following up flexor tendon repairs (MSWST, n = 21/39 digits; MKS, n = 20/31 digits). For MSWST we found 31 (79.5%) "excellent", 3 (7.7%) "good", and 5 (12.8%) "fair" results, when using the scoring system of Buck-Gramcko. In 3 (14.3%) patients the MSWST had to be removed owing to local irritation. In a further 3 (14.3%) patients, this was done when secondary tenolysis was necessary. The latter was also performed in 4 (20.0%) patients in whom the MKS was used. Here we found 23 (74.2%) excellent, 7 (22.6%) good, and 1 (3.2%) fair result. The statistical evaluation of the data concerning the patients' age, sex, the involved zone, the side, and the functional outcome did not reveal a significant difference (P < 0.05) between both groups and the chosen type of repair. The results of MSWST and MKS are similar, but MSWST allows early motion therapy without a splint or rubber-band protection.

Adolescent↗
PubMed2001

Body fat measurement among Singaporean Chinese, Malays and Indians: a comparative study using a four-compartment model and different two-compartment models.

This cross-sectional study compared body fat percentage (BF%) obtained from a four-compartment (4C) model with BF% from hydrometry (using 2H2O), dual-energy X-ray absorptiometry (DXA) and densitometry among the three main ethnic groups (Chinese, Malays and Indians) in Singapore, and determined the suitability of two-compartment (2C) models as surrogate methods for assessing BF% among different ethnic groups. A total of 291 subjects (108 Chinese, seventy-six Malays, 107 Indians) were selected to ensure an adequate representation of age range (18-75 years) and BMI range (16-40 kg/m2) of the general adult population, with almost equal numbers from each gender group. Body weight was measured, together with body height, total body water by 2H2O dilution, densitometry with Bodpod and bone mineral content with Hologic QDR-4500. BF% measurements with a 4C model for the subgroups were: Chinese females 33.5 (sd 7.5), Chinese males 24.4 (sd 6.1), Malay females 37.8 (sd 6.3), Malay males 26.0 (sd 7.6), Indian females 38.2 (sd 7.0), Indian males 28.1 (sd 5.5). Differences between BF% measured by the 4C and 2C models (hydrometry, DXA and densitometry) were found, with underestimation of BF% in all the ethnic-gender groups by DXA of 2.1-4.2 BF% and by densitometry of 0.5-3.2 BF%). On a group level, the differences in BF% between the 4C model and 2H2O were the lowest (0.0-1.4 BF% in the different groups), while differences between the 4C model and DXA were the highest. Differences between the 4C model and 2H2O and between the 4C model and DXA were positively correlated with the 4C model, water fraction (f(water)) of fat-free mass (FFM) and the mineral fraction (f(mineral)) of FFM, and negatively correlated with density of the FFM (D(FFM)), while the difference between 4C model and densitometry correlated with these variables negatively and positively respectively (i.e. the correlations were opposite). The largest contributors to the observed differences were f(water) and D(FFM). When validated against the reference 4C model, 2C models were found to be unsuitable for accurate measurements of BF% at the individual level, owing to the high errors and violation of assumptions of constant hydration of FFM and D(FFM) among the ethnic groups. On a group level, the best 2C model for measuring BF% among Singaporeans was found to be 2H2O.

Absorptiometry, Photon↗
PubMed2001

Who works in addictions treatment services? Some results from an Ontario survey.

This paper summarizes results from a survey of staff of specialized addiction treatment agencies in Ontario and includes information on demographic characteristics, education and related issues for those working in different types of agencies. Across all agencies 80% of staff had some sort of post secondary academic qualification and the majority reported taking professional development courses in the previous 12 months. However, only 20% of all respondents were "certified" as either an addictions counsellor or as another type of human service provider. There were differences within and between different agencies, and between respondents with and without administrative/supervisory responsibilities, with respect to education and certification status. Discussion concerns professionalization of the addiction treatment field, preparatory training for work in addictions treatment, and the generalizability of results.

Certification↗
PubMed2001

Small plants, large plants: the importance of plant size for the physiological ecology of vascular epiphytes.

Recently, a number of publications have reported that many physiological properties of vascular epiphytes are a function of plant size. This short review will summarize what is known to date about this phenomenon, describe the possible mechanism and will discuss the consequences for the present understanding of epiphyte biology. Size-related changes are also known from other plant groups and it is argued that close attention should be paid to the size of the organisms under study in order to understand the performance and survival of a species in the field. In the light of these findings, the results of many earlier studies on epiphyte ecophysiology are now difficult to interpret because essential information on the size of the specimens used is missing.

Adaptation, Physiological↗
PubMed2001

Transcriptional regulation of 3,4-dihydroxy-2-butanone 4-phosphate synthase.

The filamentous hemiascomycete Ashbya gossypii is a strong riboflavin overproducer. A striking but as yet uninvestigated phenomenon is the fact that the overproduction of this vitamin starts when growth rate declines, which means that most of the riboflavin is produced in the stationary phase, the so-called production phase. The specific activity of 3,4-dihydroxy-2-butanone 4-phosphate (DHBP) synthase, the first enzyme in the biosynthetic pathway for riboflavin, was determined during cultivation and an increase during the production phase was found. Furthermore, an increase of RIB3 mRNA, encoding DHBP synthase, was observed by competitive RT-PCR in the production phase. The mRNAs of two housekeeping genes, ACT1 (encoding actin) and TEF (encoding translation elongation factor-1 alpha), served as standards in the RT-PCR. Reporter studies with a RIB3 promoter-lacZ fusion showed an increase of beta-galactosidase specific activity in the production phase. This investigation verified that the increase of RIB3 mRNA in the production phase is caused by an induction of promoter activity. These data suggest that the time course of riboflavin overproduction of A. gossypii is correlated with a transcriptional regulation of the DHBP synthase.

Gene Expression Regulation, Fungal↗
PubMed2001

Recombinant Yersinia YopT leads to uncoupling of RhoA-effector interaction.

Yersinia enterocolitica, Yersinia pseudotuberculosis, and Yersinia pestis deliver different Yop (Yersinia outer proteins) effector proteins into mammalian cells by a type III secretion mechanism. Recently, it was shown that Yersinia producing YopT leads to disruption of the actin cytoskeleton of HeLa cells (M. Iriarte and G. R. Cornelis, Mol. Microbiol. 29:915-929, 1998). To analyze the molecular mechanism of YopT, we cloned and expressed YopT as a glutathione S-transferase fusion protein. Recombinant YopT caused rounding up of embryonic bovine lung cells and redistribution of the actin cytoskeleton rapidly after microinjection. The Escherichia coli cytotoxic necrotizing factor (CNF1), which constitutively activates Rho proteins, was not able to inhibit or revert YopT-induced cell rounding. YopT caused release of RhoA from embryonic bovine lung membranes and released recombinant isoprenylated RhoA from artificial PE or PE/PIP2 vesicles. Incubation of lysate or cytosol with YopT caused inhibition of the RhoA-rhotekin interaction but led to increased RhoA-RhoGDI interaction. It is suggested that inhibition of the interaction between RhoA and effectors is the underlying mechanism of the YopT action on the cytoskeleton.

Amino Acid Sequence↗
PubMed2001

Lysine and polyamines are substrates for transglutamination of Rho by the Bordetella dermonecrotic toxin.

Bordetella dermonecrotic toxin (DNT) catalyzes the transglutamination of glutamine-63/61 of Rho GTPases, thereby constitutively activating Rho proteins. Here we identified second substrates for transglutamination of RhoA by DNT. The enzymatically active fragment of DNT (residues 1136 to 1451, DeltaDNT) induced the incorporation of L-[(14)C]lysine in RhoA in a concentration-dependent manner. Also, Rac and Cdc42, but not Ras, were transglutaminated with lysine by DeltaDNT. Transglutamination of the GTPase with L-lysine inhibited intrinsic and Rho-GAP-stimulated GTP hydrolysis of RhoA. In contrast to lysine, treatment of RhoA with alanine, arginine, and glutamine were not able to substitute for lysine in the transglutamination reaction. DNT increased the incorporation of L-[(14)C]lysine into embryonic bovine lung cells. Microinjection of GST-RhoA together with the enzymatically active DNT fragment into Xenopus oocytes, subsequent affinity purification of modified GST-RhoA, and mass spectrometry identified attachment of putrescine or spermidine at glutamine-63 of RhoA. A comparison of putrescine, spermidine, and lysine as substrates for DNT-induced transglutamination of RhoA revealed that lysine is a preferred second substrate at least in vitro.

Animals↗
PubMed2001

Development of a multi-modal virtual human knee joint for education and training in orthopaedics.

Due to limited simultaneous access to a greater pool of patients an effective training of medical students or young orthopedic physicians is difficult. A knee joint simulator that comprises the properties of a healthy or pathological knee can support medical education and training. In this paper a mechatronic system is presented that provides visual, acoustic, and haptic (force) feedback so that it allows a user to touch and move a virtual shank, bones or muscles within the leg, and simultaneously observe the generated movement, feel the contact force, and hear sounds. These and further features enable the user to study and assess the properties of the knee, e.g. by testing the joint laxity and end-point stiffness in six degrees-of-motion (DOF) and by grasping and pulling at muscles, rupturing ligaments or changing muscle/ligament paths. Such a tool can support training of physical knee evaluation required for diagnosis and therapeutic planning, since any kind of pathology of any subject type can be tested at any time. Furthermore, it can provide a better understanding of functional anatomy, e.g. for the education of medical students.

Computer Simulation↗
PubMed2001

[Screening for violence against women. Validation and feasibility studies of a French screening tool].

OBJECTIVE: To replicate, in a Francophone community, our prior work determining the reliability and validity of the full Woman Abuse Screening Tool (WAST) and a two-item version (WAST-Short). DESIGN: Questionnaires completed by abused and nonabused women. SETTING: Two women's shelters in Francophone communities in Ontario and Quebec and participants' homes or workplaces. PARTICIPANTS: A convenience sample of 25 abused women currently residing in two women's shelters and a convenience sample of 21 women who reported they were not abused. MAIN OUTCOME MEASURES: Women's responses to French versions of the WAST, the Abuse Risk Inventory (ARI), and comfort in answering the questions were compared. Also, the reliability and validity of French versions of WAST and WAST-Short were assessed. RESULTS: Abused (n = 23) and not abused (n = 21) women were demographically similar. A strong single-factor structure that accounted for 81% of total variance in the French WAST items was identified. The French WAST was found to be highly reliable with a coefficient alpha of .95 and demonstrated construct and discriminant validity. The WAST-Short correctly classified all the nonabused women and 78.7% of the abused women. The abused women reported feeling less comfortable responding to the WAST questions than the nonabused women. CONCLUSION: The French version of the WAST demonstrated good reliability and validity and discriminated between known samples of abused and nonabused women. Even though the French WAST-Short did not perform as well as the English version, results of this study support further evaluation of the WAST for screening women in Francophone or bilingual family practice settings.

Adult↗
PubMed2001

Linker length in podophyllotoxin-acridine conjugates determines potency in vivo and in vitro as well as specificity against MDR cell lines.

We have synthesized two podophyllotoxin-acridine conjugates-pACR6 and pACR8. In these compounds an 9-acridinyl moiety is beta linked to the C4 carbon of the four ring system in 4'-demethylepipodophyllotoxin (epiDPT) via eighter an N-6-aminohexanylamide linker (pACR6) or via an N-8-aminooctanylamide linker containing two more carbon atoms (pACR8). The acridine-linker moiety occupies the position where different glucoside moieties, dispensable for activity, are normally linked to epiDPT in the well known epipodophyllotoxins VP-16 and VM-26. As with VP-16 and VM-26, pACR6 and pACR8 show evidence of being topoisomerase II poisons as they stimulate topoisomerase II mediated DNA cleavage in vitro and induce DNA damage in vivo. This in vivo DNA damage, as well as pACR6/pACR8 mediated cytotoxicity, is antagonized by the catalytic topoisomerase II inhibitors ICRF-187 and aclarubicin, demonstrating that topoisomerase II is a functional biological target for these drugs. Despite their structural similarities, pACR6 was more potent than pACR8 in stimulating topoisomerase II mediated DNA cleavage in vitro as well as DNA damage in vivo and pACR6 was accordingly more cytotoxic towards various human and murine cell lines than pACR8. Further, marked cross-resistance to pACR6 was seen among a panel of multidrug-resistant (MDR) cell lines over-expressing the MDR1 (multidrug resistance protein 1) ABC drug transporter, while these cell lines remained sensitive towards pACR8. pACR8 was also capable of circumventing drug resistance among at-MDR (altered topoisomerase II MDR) cell lines not over-expressing drug transporters, while pACR6 was not. Two resistant cell lines, OC-NYH/pACR6 and OC-NYH/pACR8, were developed by exposure of small cell lung cancer (SCLC) OC-NYH cells to gradually increasing concentrations of pACR6 and pACR8, respectively. Here, OC-NYH/pACR6 cells were found to over-express MDR1 and, accordingly, displayed active transport of 3H-labeled vincristine, while OC-NYH/pACR8 cells did not, further suggesting that pACR6, but not pACR8, is a substrate for MDR1. Our results show that the spatial orientation of podophyllotoxin and acridine moieties in hybrid molecules determine target interaction as well as substrate specificity in active drug transport.

Aclarubicin↗
PubMed2000

First observation of self-amplified spontaneous emission in a free-electron laser at 109 nm wavelength

We present the first observation of self-amplified spontaneous emission (SASE) in a free-electron laser (FEL) in the vacuum ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approximately 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width, and intensity fluctuations, are all consistent with the present models for SASE FELs.

Journal Article↗
PubMed2000

Bacterial protein toxins targeting rho GTPases.

Several bacterial protein toxins target eukaryotic cells by modulating the functions of Rho GTPases that are involved in various signal processes and in the regulation of the actin cytoskeleton. The toxins inhibit Rho functions by ADP-ribosylation or glucosylation and activate them by deamidation and transglutamination. New findings indicate that the GTPases are also targeted by various 'injected' toxins which are introduced into the eukaryotic cells by the type-III secretion system. The injected toxins do not covalently modify Rho GTPases, but manipulate their regulatory GTPase cycle by acting as GTPase-activating proteins or guanine nucleotide exchange factors.

Bacteria↗
PubMed2000

Extent of cardiac sympathetic neuronal damage is determined by the area of ischemia in patients with acute coronary syndromes.

BACKGROUND: Prior studies have demonstrated that acute ischemic injury causes sympathetic neuronal damage exceeding the area of necrosis. The aim of this study was to test the hypothesis that sympathetic neuronal damage measured by (123)I-metaiodobenzylguanidine (MIBG) imaging would be determined by the area of ischemia as reflected by area at risk in patients undergoing reperfusion therapy for acute coronary syndromes. METHODS AND RESULTS: In 12 patients, the myocardium at risk was assessed by (99m)Tc-sestamibi SPECT before reperfusion, and infarct size was measured by follow-up (99m)Tc-sestamibi SPECT 1 week later. All patients also underwent (123)I-MIBG SPECT within a mean of 11 days after onset. The SPECT image analysis was based on a semiquantitative polar map approach. Defect size on the (123)I-MIBG or (99m)Tc-sestamibi SPECT was measured for the left ventricle (LV) with the use of a threshold of -2.5 SD from the mean value of a normal database and was expressed as %LV. The (123)I-MIBG defect size (47+/-18%LV) was larger than the infarct size (27+/-23%LV, P<0. 001) but was similar to the risk area (49+/-18%LV, P=NS). Furthermore, the (123)I-MIBG defect size was closely correlated with the risk area (r=0.905, P<0.001). CONCLUSIONS: Sympathetic neuronal damage measured by (123)I-MIBG SPECT is larger than infarct size and is closely related to risk area, suggesting high sensitivity of neuronal structures to ischemia compared with myocardial cells.

Adult↗
PubMed2000

Priming of PC12 cells for semiquantitative microinjection studies involving Ras.

Nerve growth factor and activated Ras can induce differentiation of rat pheochromocytoma cells (PC12 cells) [Greene and Tischler (1976) Proc. Natl. Acad. Sci. USA 73, 2424-2428] from a chromaffin cell-like morphology into one that resembles sympathetic neurones. We developed a special treatment of PC12 cells which apparently synchronizes these cells such that they are more useful for semi-quantitative microinjection studies for signal transduction pathways. This treatment leads to a faster and more reproducible differentiation which faithfully reproduces the involvement of Ras in the process and allows a comparison of the biological activity of different Ras mutants. It shows that G12V and Q61L oncogenic mutants are not equally potent in inducing differentiation. Partial loss-of-function mutations T35S, E37G and Y40C are inactive and even a triple combination of these does not restore full biological activity.

Amino Acid Substitution↗
PubMed2000

Basic features of the stress response in three species of bifidobacteria: B. longum, B. adolescentis, and B. breve.

The presence of the dnaK heat shock gene could be demonstrated for B. longum NCC481, B. longum NCC490, B. longum NCC585, B. adolescentis NCC251, and B. breve NCC298. Induction of dnaK on the transcriptional level was shown for NCC251 and NCC481 by increasing temperatures. NCC251 showed an additional chaperone-induction after salt or bile-salt treatment. In both strains preconditioning with bile-salts protected against otherwise lethal concentrations thereof. NCC251 when subjected to a heat stress was able to survive an otherwise lethal temperature (55 degrees C). Cross-protection was demonstrated for NCC251 since salt pretreatment resulted in increased tolerance after freeze-thawing cycles or lethal heat stress.

Bifidobacterium↗