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Biomedical subjects

G Schmid

Publications and source records attributed to G Schmid.

At least 55 records · Page 3Linked to original sources
PubMed2000

Strategies for the anchoring of metal complexes, clusters, and colloids inside nanoporous alumina membranes.

Two complementary strategies are presented for the anchoring of molecular palladium complexes, of cobalt or platinum clusters or of gold colloids inside the nanopores of alumina membranes. The first consists in the one step condensation of an alkoxysilyl functional group carried by the metal complex with the hydroxy groups covering the surface of the membrane pores. Thus, using the short-bite alkoxysilyl-functionalized diphosphane ligands (Ph2P)2N(CH2)3Si(OMe)3 (1) and (Ph2P)2N(CH2)4SiMe2(OMe)] (2) derived from (Ph2P)2NH (dppa) (dppa bis(diphenylphosphanyl)amine), the palladium complexes [Pd(dmba)(kappa2-P,P-(Ph2P)2N(CH2)3Si(OMe)3)] Cl (3) and [Pd(dmba)[kappa2-P,P-(Ph2P)2N(CH2)4SiMe2(OMe)]]Cl (4) (dmba-H = dimethylbenzylamine). respectively, were tethered to the pore walls. After controlled thermal treatment. confined and highly dispersed palladium nanoparticles were formed and characterized by transmission electron microscopy (TEM). This method could not be applied to the cobalt cluster [Co4(CO)8(mu-dppa)[mu-P,P-(Ph2P)2N(CH2)4SiMe2(OMe)]] (7) owing to its too limited solubility. However, its anchoring was achieved by using the second method which consisted of first derivatizing the pore walls with 1 or 2. The covalent attachment of the diphosphane ligands provides a molecular anchor that allows subsequent reaction with the cluster [Co4(CO)10(mu-dppa)] 6 to generate anchored 7 and this step was monitored by UV/Vis spectroscopy. In addition, the presence of carbonyl ligands in the cluster provides for the first time a very sensitive spectroscopic probe in the IR region which confirms both cluster incorporation and the retaining of its molecular nature inside the membrane. The presence of the bridging dppa ligand in 6 provides additional stabilization and accounts for the selectivity of the procedure. Using this method, platinum clusters (diameter ca. 2 nm) and gold colloids (diameter ca. 13 nm) were immobilized after passing their solution through the functionalized membrane pores. The resulting membranes were characterized by TEM which demonstrated the efficiency of the complexation and showed the high dispersion of the metal loading. The successful application of these methods has demonstrated that nanoporous alumina membranes are not only unique supports to incorporate metal complexes, clusters, or colloids but can also be regarded as functional matrices or microreactors, thus opening new fields for applications.

Journal Article↗
PubMed2000

Homophilic interaction of junctional adhesion molecule.

Junctional adhesion molecule (JAM) is an integral membrane protein that belongs to the immunoglobulin superfamily, localizes at tight junctions, and regulates both paracellular permeability and leukocyte transmigration. To investigate molecular determinants of JAM function, the extracellular domain of murine JAM was produced as a recombinant soluble protein (rsJAM) in insect cells. rsJAM consisted in large part of noncovalent homodimers, as assessed by analytical ultracentrifugation. JAM dimers were also detected at the surface of Chinese hamster ovary cells transfected with murine JAM, as evaluated by cross-linking and immunoprecipitation. Furthermore, fluid-phase rsJAM bound dose-dependently solid-phase rsJAM, and such homophilic binding was inhibited by anti-JAM Fab BV11, but not by Fab BV12. Interestingly, Fab BV11 exclusively bound rsJAM dimers (but not monomers) in solution, whereas Fab BV12 bound both dimers and monomers. Finally, we mapped the BV11 and BV12 epitopes to a largely overlapping sequence in proximity of the extracellular amino terminus of JAM. We hypothesize that rsJAM dimerization induces a BV11-positive conformation which in turn is critical for rsJAM homophilic interactions. Dimerization and homophilic binding may contribute to both adhesive function and junctional organization of JAM.

Animals↗
PubMed2000

Overexpressed poly(ADP-ribose) polymerase delays the release of rat cells from p53-mediated G(1) checkpoint.

We have previously reported that in cells ectopically expressing temperature-sensitive p53(135val) mutant, p53 formed tight complexes with poly(ADP-ribose) polymerase (PARP). At elevated temperatures, p53(135val) protein, adopting the mutant phenotype, was localized in the cytoplasm and sequestered the endogenous PARP. To prove whether an excess of p53(135val) protein led to this unusual intracellular distribution of PARP, we have established cell lines overexpressing p53(135val) + c-Ha-ras alone or in combination with PARP. Interestingly, immunostaining revealed that PARP is sequestered in the cytoplasm by mutant p53 in cells overexpressing both proteins. Simultaneous overexpression of PARP had no effect on temperature-dependent cell proliferation and only negligibly affected the kinetics of p53-mediated G(1) arrest. However, if the cells were completely growth arrested at 32 degrees C and then shifted up to 37 degrees C, coexpressed PARP dramatically delayed the reentry of transformed cells into the cell cycle. Even after 72 h at 37 degrees C the proportion of S-phase cells was reduced to 20% compared to those expressing only p53(135val) + c-Ha-ras. The coexpressed PARP stabilized wt p53 protein and its enzymatic activity was necessary for stabilization.

Animals↗
PubMed2000

Characterization of distinct consecutive phases in non-genotoxic p53-induced apoptosis of Ewing tumor cells and the rate-limiting role of caspase 8.

To dissect the p53-dependent apoptotic pathway, events following induction of temperature sensitive (ts) p53val138 were studied in a Ewing tumor cell line. Transcriptional deregulation of p53 targets first observable after 1 h at 32 degrees C preceded activation of caspases and the break-down of mitochondrial respiratory activity. Activation of caspases was first observed 4 h after p53 induction. Using peptide inhibitors we identified activation of caspase 8 upstream of caspases-9 and -3. Although the caspase 8 specific inhibitor z-IETD.fmk did not affect translocation of BAX to the mitochondrial membrane and cytochrome C release it almost completely blocked cleavage of the prototype caspase substrate PARP and DNA fragmentation while enforcing mitochondrial depolarization and production of reactive oxygene species (ROS). Activation of caspase 8 did not involve death-domain receptor signaling. Expression of BCL2 only partially suppressed caspase activation but blocked apoptosis. Replacement of the N-terminus of p53val138 by the related VP16 transactivation domain created a ts p53 with a tanscriptional activity indistinguishable from p53val138 until the time of caspase activation. However, the VP16 - p53 fusion failed to trigger caspases and subsequent induction of the ROS producing gene pig3 paralleled by complete loss of apoptotic activity. These results indicate that p53-dependent transcriptional deregulation, triggering of the caspase cascade and the mitochondrial break-down occur in a timely ordered sequence coordinated by the genuine p53 amino terminus and suggest caspase 8 and PIG3 as key regulatory elements in this process. Oncogene (2000) 19, 4096 - 4107

Apoptosis↗
PubMed2000

Naked Au55 clusters: dramatic effect of a thiol-terminated dendrimer

Reaction of the thiol-terminated fourth-generation dendrimer 2-G4 (96 SH groups) with the gold cluster compound Au55(PPh3)12Cl6 in a 3:1 molar ratio in dichloromethane results in the formation of bare Au55 clusters. The cuboctahedrally shaped Au55 particles coalesce to well-formed microcrystals (Au55) infinity. The role of the dendrimer is not only to remove the phosphine and chlorine ligands but also to act as an ideal matrix for perfect crystal growth. Transmission electron microscopy (TEM), small- and wide-angle X-ray diffraction (SAXRD and WAXRD) measurements indicate a structure where rows of edge-linked Au55 building blocks form a distorted cubic lattice. The X-ray data fit best if a 5% reduction of the Au-Au bond length in the Au55 clusters is assumed, in agreement with previous extended X-ray absorption fine structure (EXAFS) measurements. Energy-dispersive X-ray spectroscopy (EDX) analyses and IR investigations show the absence of PPh3 and Cl in the microcrystals.

Journal Article↗
PubMed2000

Characterization of a human angiotensinogen cleaved in its reactive center loop by a proteolytic activity from Chinese hamster ovary cells.

Angiotensinogen, the renin (E.C. 3.4.23.15) substrate, belongs to the serpins superfamily and has been classified as a noninhibitory serpin. Using mass spectroscopy, angiotensinogen purified from Chinese hamster ovary cell supernatant shows a broad spectrum. The absence of protease inhibitors throughout the purification leads to an angiotensinogen cleaved within the reactive center loop. This cleavage does not affect the Ang I generation because kinetic parameters are similar to the values of the full-length angiotensinogen. Although cleavage is complete, the cleaved angiotensinogen migrates after deglycosylation on SDS-polyacrylamide gel electrophoresis as a doublet differing by 4 kDa. To test whether the circulating angiotensinogen is cleaved in the reactive center loop, it was purified from a pool of human plasma and was shown to be uncleaved. Its migration was obviously slower than of cleaved angiotensinogen but also consisted of two bands pointing to a so far unexplained residual heterogeneity. We then compared the heat-induced polymerization of full-length- and reactive center loop-cleaved angiotensinogens. Both monomers were able to aggregate, revealing a particular behavior of angiotensinogen distinct from that of reactive center loop-cleaved serpins. Lacking the three-dimensional structure of angiotensinogen, we propose and discuss a structural model of the serpin fold within the renin substrate.

Amino Acid Sequence↗
PubMed2000

Flexible tantalum stents for the treatment of renovascular hypertension: a 10-year experience.

The aim of this study was to determine long-term success of flexible tantalum stents for the treatment of ostial and truncal renal artery stenosis. Since 1989, flexible tantalum stents (type Strecker) were implanted in 34 patients (36 arteries, 25 ostial lesions, 11 truncal lesions) with uncontrollable renovascular hypertension, 9 of them in association with renal insufficiency. Stents were placed unilaterally in 32 patients, and bilaterally in 2 patients for the treatment of renal artery stenosis. Thirty-five of 36 lesions were atherosclerotic, including 5 recurrencies after previous percutaneous transluminal renal angioplasty (PTRA). One patient had Takayasu arteritis. Stents were implanted after unsuccessful PTRA of 11 truncal and 23 ostial lesions, and as a primary procedure in 2 ostial lesions. Follow-up examinations included blood pressure measurement, determination of serum creatinine level, color duplex sonography, or angiography. The technical success rate was 92%. Technical failure included incorrect stent placement (1 of 36 lesions, 2.8 % ), and stent dislocation (2 of 36 lesions, 5.6 %), and two stents were retrieved percutaneously. In one case of Takayasu arteritis, residual stenosis of 40% was observed. After technically successful stent placement, 77% of patients became normotensive with or without medication. In the remaining patients there was partial improvement with blood pressure between 140 and 180 mmHg. Renal function improved in 76% of patients (completely in 3 of 8, 38%; and partially in 3 of 8, 38%). Primary patency rate including all stented lesions and initial technical failures was 82.4% +/- 6.8 (1 year) and 82.4% +/- 9.2 (3 years). After technically successful stent placement, patency rates were 89.9 +/- 5.6% (1 year), and 89.9 +/- 7.6% (3 years). For ostial lesions, primary patency rate was 87.9 +/- 6.7% (1 year) and 87.9 +/- 9.2% (3 years). Placement of flexible tantalum stents in renal arteries is technically demanding, especially in ostial lesions. Once placed successfully stent patency rate is excellent.

Aged↗
PubMed2000

NK3 receptor blockade prevents hyperalgesia and the associated spinal cord substance P release in monoarthritic rats.

Previous studies in vitro have shown that NK3 receptors exist on primary afferent terminals in rat spinal cord and mediate potentiation of the depolarisation-evoked substance P (SP) release. In the present study we have investigated the role of the NK3 receptor-mediated SP release system in a model of inflammatory pain. Monoarthritis was induced in rats by unilateral injection of complete Freund's adjuvant (CFA); withdrawal latencies to a thermal stimulus were subsequently measured at various times following CFA. The CFA-treated paw displayed hyperalgesia as early as 4 h after CFA injection and hyperalgesia was maintained until day 4 but had disappeared by day 21. The thermal hyperalgesia was associated with an increase in basal SP release from spinal cord synaptosomes. The possible involvement of endogenous neurokinin B acting at NK3 receptors was tested by using SB 223412-A [(S)-(-)-N-(alpha-ethylbenzyl)-3-hydroxy-2-phenylquinoline-4-carbo xamide hydrochloride], a novel, potent (Ki=30 nM) and selective (Ki>10,000 nM for NK1 and NK2 receptors), non-peptidic NK3 receptor antagonist. In vitro SB 223412-A antagonised the potentiation of SP release produced by senktide in spinal cord synaptosomes. Administered systemically to monoarthritic rats (50 mg/kg, p.o., b.i.d., for 4 days), the NK3 receptor antagonist SB 223412-A significantly reduced thermal hyperalgesia and normalised the basal release of SP from spinal cord synaptosomes. The data suggest that neurokinin B acting at NK3 receptors that mediate SP release within the spinal cord play a role in inflammation. These NK3 receptors may represent, therefore, appropriate targets in the therapy of inflammatory pain.

Afferent Pathways↗
PubMed2000

[Measurement of eye length and eye shape by optical low coherence reflectometry].

BACKGROUND: The precise and rapid measurement of eye length and eye shape are essential for investigating eye growth regulation and myopia. For this purpose, we developed an optical low coherence reflectometer and obtained preliminary measurements in volunteers. METHODS: The instrument includes a rotating glass cube to produce longitudinal scans at a velocity of 0.42 m/s and a repetition rate of approximately 13 scans/s. Heterodyne detection of light reflected from the anterior cornea and the posterior retina permits to measure axial eye length and eye shape (off-axis eye length). Each measurement consists of five consecutive scans. Reproducibility and precision were determined in one volunteer by measuring axial eye length five consecutive times, each time repositioning the eye. Eye shapes were determined in right eyes of four volunteers by measuring eye length every 3.3 degrees from 10 degrees nasally to 10 degrees temporally. RESULTS: Axial eye length measured repeatedly in one volunteer did not differ between or within the measurements (one-factor ANOVA). The average standard deviation was 11 microns. Eye shapes a) varied substantially among subjects and b) differed considerably from the corresponding shapes of spherical model eyes with identical axial eye lengths. CONCLUSION: The newly developed reflectometer permits the precise and rapid measurement of eye length and eye shape. Such measurements, especially in children, may provide important information about mechanisms of eye growth regulation and the development of myopia.

Eye↗
PubMed2000

Occupational risks for lung cancer among nonsmokers.

We conducted a case-control study in 12 European study centers to evaluate the role of occupational risk factors among nonsmokers. We obtained detailed occupational histories from 650 nonsmoking cases (509 females/141 males) and 1,542 nonsmoking controls (1,011 females/531 males). On the basis of an a priori definition of occupations and industries that are known (list A) or suspected (list B) to be associated with lung carcinogenesis, we calculated odds ratios (ORs) for these occupations, using unconditional logistic regression models and adjusting for sex, age, and center effects. Among nonsmoking men, an excess relative risk was observed among those who had worked in list-A occupations [OR = 1.52; 95% confidence interval (C) = 0.78-2.97] but not in list-B occupations (OR = 1.05; 95%), CI = 0.60-1.83). Among nonsmoking women, there was an elevation of risk for list-A occupations (OR = 1.50; 95% CI = 0.49-4.53), although this estimate was imprecise, given that less than 1% of cases and controls were exposed. Exposure to list-B occupations was associated with an increase in relative risk (OR = 1.69; 95% CI = 1.09-2.63) in females, but not in males. Women who had been laundry workers or dry cleaners had an OR of 1.83 (95% CI = 0.98-3.40). Our findings confirm that certain occupational exposures are associated with an increased risk for lung cancer among both female and male nonsmokers; however, knowledge on occupational lung carcinogens is biased toward agents to which mainly men are exposed.

Adult↗
PubMed2000

Reliability and validity of the German version of the European Addiction Severity Index (EuropASI).

OBJECTIVE: This study provides data on the psychometric characteristics of the German version of the European Addiction Severity Index (EuropASI). The ASI is a frequently used clinical and research instrument that measures problem severity among people with substance dependence. METHOD: The German ASI was used in a sample of 112 consecutively admitted male psychiatric inpatients seeking treatment for severe alcohol problems. The conceptual structure of the German ASI subscales was investigated by analyzing the intercorrelations of the severity ratings and composite scores. Internal consistency, interrater reliability and concurrent validity in terms of correlations with other assessment instruments were evaluated. RESULTS: The German ASI subscales proved to be independent or moderately correlated (-0.17 < r < 0.34). Each correlation coefficient between corresponding severity ratings and composite scores was significant (p < .0005), ranging from r = 0.47 to r = 0.93. Reliability measures indicated moderate to good internal consistency (Cronbach's alpha: 0.69-0.92) and moderate to excellent interrater reliability (intraclass correlation coefficient: 0.62-0.99). Validity was supported by significantly higher ratings in the alcohol section in alcohol dependent patients compared to patients without dependence (t = 2.99, 108 df, p = .004). Significant correlations (p < .001) were found between the alcohol use section and the Michigan Alcoholism Screening Test (r = 0.34 composite score and r = 0.44 severity rating) and between psychiatric status and the Symptom Checklist-90-revised (r = 0.55/0.51), supporting concurrent validity. CONCLUSIONS: The German version presented evidence of acceptable psychometric properties and its applicability in German-speaking countries could be confirmed.

Adult↗
PubMed2000

Ordered Two-Dimensional Monolayers of Au(55) Clusters.

Simply dipping polyethyleneimine-modified surfaces into aqueous solutions of acid-functionalized Au(55) clusters generates two-dimensional hexagonal and cubic arrangements of the clusters. The picture shows the transmission electron micrograph of the cubic arrangement; the bar length corrsponds to 10 nm.

Journal Article↗
PubMed2000

Occupational exposure to static, ELF, VF and VLF magnetic fields and immune parameters.

Despite the important role of the immune system in defending the body against infections and cancer, very few investigations have been undertaken to study possible effects of electromagnetic fields on human immunity. The aim of the present study was to examine the effect of occupational exposure on hospital personnel operating magnetic resonance tomographs and on industrial workers at induction heaters. In both categories of workplaces, magnetic flux densities exceeding Austrian exposure standards have been registered. Because of the complexity and high redundancy of the immune system, an extensive range of assay systems was applied: relative and absolute numbers of lymphocytic subsets were counted, the proliferative activity of T and B cells determined, the production of interleukin 2, interferon gamma and tumour necrosis factor alpha analysed, serum immunoglobulins evaluated, as well as non-specific immunity of monocytes and granulocytes measured by their oxidative burst. The number of natural killer cells and oxidative burst in monocytes showed statistically significant differences in workers at induction heaters and controls. The observed effect on oxidative burst was counteracted by a higher number of active cells in the exposed group, indicating normal non-specific immunity. The high number of natural killer cells, observed in some of the study subjects working at induction heaters, was reconfirmed in another investigation and deserves a further follow-up.

Adult↗
PubMed1999

"Scaffold-Hopping" by Topological Pharmacophore Search: A Contribution to Virtual Screening.

A chemically advanced template search (CATS) based on topological pharmacophore models has been developed as a technique for virtual screening. This technique has successfully identified novel potent Ca(2+) antagonists (such as 2) that have a similar activity to 1 (a known T-channel blocking agent) in a library of several hundred thousand compounds on the basis of a correlation vector representation.

Journal Article↗
PubMed1999

Compensatory expression of p73 in PARP-deficient mouse fibroblasts as response to a reduced level of regularly spliced wild-type p53 protein.

We have investigated the effect of PARP gene inactivation on the expression of wild-type (wt) p53 protein. Using immortalized fibroblasts from control and PARP knock-out mice we have found by immunoblotting with the PAb421 antibody a profound decrease of the p53 expression to a barely detectable level in PARP knock-out cells. Surprisingly, longer exposure of immunoblots revealed an immunoreactive band at about 75 kD which was stronger in PARP-deficient cells than in wt cells and was not affected upon doxorubicin treatment. The size of the PAb421 immunoreactive protein and the lack of its inducibility in response to DNA damage resembled those of p73, the first described p53 homologue. Therefore, we examined the reactivity of anti-p53 antibodies with in vitro translated p73 protein. Interestingly, p73 was efficiently immunoprecipitated with distinct antibodies recognizing the carboxy-terminus of p53. In Northern blots we observed p73 signals of comparable intensity in controls and PARP-deficient cells. We conclude that elevated expression of p73 may compensate the reduced level of p53 in PARP-deficient cells.

Animals↗
PubMed1999

[Vertebral destruction with sever pain in the SAPHO syndrome].

HISTORY AND ADMISSION FINDINGS: A 57-year-old man had for the past 18 months complained of recurrent, recently worsening, belt-like backache radiating ventrally. On admission a skin rash consisting of blister and pustules was noted on the palms of both hands. He had pain on pressure over the right upper abdomen, an enlarged prostate and definite pain on percussing the vertebral column with restricted movement of the thoracic vertebral column, but no other physical signs. INVESTIGATIONS: Radiology revealed clearly increased sclerosis of several thoracic vertebrae with osteolytic destruction and a paravertebral soft tissue tumor. Search for a primary tumor was unsuccessful. Bone scintigraphy demonstrated nuclide enrichment of the thoracic vertebrae and of the sternoclavicular joints without increase in the LeukoScan. These findings indicated the diagnosis of SAPHO syndrome (synovitis-acne-pustulosis-hyperostosis-osteomyelitis). TREATMENT AND COURSE: Rapid subjective and objective improvement followed the administration of clindamycin and ibuprofen. CONCLUSION: In case of bone pain of uncertain aetiology, especially when associated with skin rash, the rare SAPHO syndrome should be considered in the differential diagnosis, avoiding lengthy diagnostic steps and allowing early treatment.

Acquired Hyperostosis Syndrome↗