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Biomedical subjects

R Maier

Publications and source records attributed to R Maier.

At least 55 records · Page 3Linked to original sources
PubMed1998

Local and systemic delivery of low molecular weight heparin following PTCA: acute results and 6-month follow-up of the initial clinical experience with the porous balloon (PILOT-study). Preliminary Investigation of Local Therapy Using Porous PTCA Balloons.

The purpose of this study was to assess safety and feasibility of intracoronary delivery of reviparin using a porous balloon following percutaneous transluminal coronary angioplasty. The 2.7 mm porous balloon used in this study had 35 holes arranged in a spiral pattern. Eighteen patients (male n = 10, female n = 8, age 63 +/- 9 years) undergoing successful PTCA in coronary arteries with a vessel diameter of 2.5 to 3.0 mm determined by online QCA (LAD = 11, RCX = 3, RCA = 4) were included. They received a bolus of 7,000 anti-Xa-IU reviparin followed by local delivery of 1,500 anti-Xa-IU in 4 ml with an injection pressure of 2 atm. The patients received additionally 10500 anti-Xa-units intravenously during the following 24 hours and a daily dose of 7000 anti-Xa-units reviparin subcutaneously for the following 28 days. Angiograms were obtained before and after PTCA, directly after local delivery, at 24 hours postintervention and after 6 months. The primary success rate was 100%. Quantitative coronary angiography showed a minimum luminal diameter of 0.42 +/- 0.14 mm before PTCA, 1.87 +/- 0.45 after PTCA, 1.67 +/- 0.43 after LDD, 1.63 +/- 0.46 after 24 hours, and 1.06 +/- 0.6 after 6 months. Angiographic follow-up was obtained in all patients. No major complications occurred during the 6-month follow-up period. The angiographic restenosis rate was 28% (5/18) at follow-up. This study demonstrates safety and feasibility of local intracoronary delivery of reviparin with a porous balloon following PTCA even in smaller diameter coronary arteries.

Aged↗
PubMed1997

Cloning of P2Y6 cDNAs and identification of a pseudogene: comparison of P2Y receptor subtype expression in bone and brain tissues.

Cellular responses to ATP/UTP and analogs are mediated by G-protein coupled P2Y receptors and have been proposed to play a role in the regulation of bone metabolism. Using a degenerate PCR approach on MG-63 cell cDNA we found PCR fragments coding for human P2Y1 and a new receptor, P2Y6. cDNA cloning of the P2Y6 receptor identified three of cDNA isoforms. Two contained the same contiguous ORFs but differed in their 5 UTRs and may therefore originate by alternative splicing whereas the third represents a pseudogene. Analysis of P2Y receptor subtype expression in human bone and the osteoblastic cell lines OHS-4 and MG-63 by RT-PCR showed that all known human P2Y receptor subtypes (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y7) were expressed. In contrast, analysis of brain-derived cell lines suggests that a selective expression of P2Y receptor subtypes occurs in brain tissue.

Alternative Splicing↗
PubMed1997

Cloning of P2Y6 cDNAs and identification of a pseudogene: comparison of P2Y receptor subtype expression in bone and brain tissues.

Cellular responses to ATP/UTP and analogs are mediated by G-protein coupled P2Y receptors and have been proposed to play a role in the regulation of bone metabolism. Using a degenerate PCR approach on MG-63 cell cDNA we found PCR fragments coding for human P2Y1 and a new receptor, P2Y6. cDNA cloning of the P2Y6 receptor identified three cDNA isoforms. Two contained the same contiguous ORFs but differed in their 5' UTRs and may therefore originate by alternative splicing whereas the third represents a pseudogene. Analysis of P2Y receptor subtype expression in human bone and the osteoblastic cell lines OHS-4 and MG-63 by RT-PCR showed that all known human P2Y receptor subtypes (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y7) were expressed. In contrast, analysis of brain-derived cell lines suggests that a selective expression of P2Y receptor subtypes occurs in brain tissue.

Alternative Splicing↗
PubMed1997

Effects of a novel 2,3-oxidosqualene cyclase inhibitor on cholesterol biosynthesis and lipid metabolism in vivo.

BIBB 515 (1-(4-chlorobenzoyl)-4-((4-(2-oxazolin-2-yl) benzylidene))piperidine) is a potent and selective inhibitor of 2,3-oxidosqualene cyclase (OSC) [EC 5.4.99.7]. In rats and mice BIBB 515 inhibited OSC in vivo in a dose-dependent manner after 1, 3, and 5 h with ED50 values from 0.2 to 0.5 mg/kg (1 to 5 h) in rats and 0.36 (1 h) to 15.5 (3 h) and 33.3 (5 h) mg/kg in mice. Inhibition of [14C]acetate incorporation into sterols was found to parallel the effects on OSC when measured after 1 h (mice) or 3 h (rats). ED50 calculated were 0.9 mg/kg (mice) and 0.1 mg/kg (rats). Dose-dependent lipid-lowering activity was seen in normolipemic hamsters after 11 days treatment (-19% for total cholesterol and -32% for VLDL + LDL cholesterol at 55 mg/kg BIBB 515 per day) and in hyperlipemic hamsters after 25 days (-25% for total cholesterol and -59% for LDL-cholesterol at 148 mg/kg BIBB 515 per day). Calculation of kinetic parameters revealed no relevant differences between control and treatment groups in LDL clearance or fractional catabolic rates, but significant reductions of LDL production rates (-30% to -54%). Liver LDL receptor mRNA of the treated animals was not or only slightly increased. Liver VLDL secretion as measured by the Triton WR1339 method was reduced after BIBB 515 in rats and hamsters. It is concluded that the lipid-lowering effect of BIBB 515 is mainly the result of an inhibition of LDL production rather than due to an increase in LDL catabolism. OSC inhibitors may offer a novel approach for lipid-lowering therapy.

Animals↗
PubMed1996

[The Schnitzler syndrome as a cause of recurrent fever of unknown origin].

HISTORY AND CLINICAL FINDINGS: For 4 years a 56-year-old woman had been suffering from chronic urticaria. In the past two years she had developed recurrent fever, each 1-3 days in duration. In the last 6 to 8 months she also had severe aching in the legs. There were no significant findings on physical examination other than non-itching urticarial rash over trunk and limbs. INVESTIGATIONS: Blood sedimentation rate was increased (maximum 88/110 mm), as were WBC count (16,200/microliter, 83% neutrophils) and the activity of alkaline leucocyte phosphatase (225 U/l). Monoclonal IgM gammopathy type kappa and circulating IgM immune complex (15.4 mg/dl) were demonstrated in serum. Skin biopsy of a new urticarial lesion revealed vasculitis. Iliac crest biopsy was unremarkable and showed no lymphoid cell infiltration. Bone scintigraphy revealed bilaterally increased storage in femur and tibia. Magnetic resonance imaging demonstrated marrow infiltration without space-occupying features in the affected femur and tibia. TREATMENT AND COURSE: Conjunction of fever, generalised urticaria, joint/bone pain and monoclonal gammopathy of kappa type having established the diagnosis of Schnitzler's syndrome, treatment with ibuprofen was started (initially 1,200 mg daily by mouth, followed by reduction to 600 mg daily). All symptoms rapidly improved and the bone changes regressed, but not the monoclonal gammopathy. But when the ibuprofen dosage had been decreased to 600 mg daily, the urticaria recurred, though in milder form. CONCLUSION: This case demonstrates the efficacy of ibuprofen in the treatment of the Schnitzler's syndrome. Furthermore reversibility of scintigraphic bone lesions could be demonstrated under ibuprofen treatment.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Evidence for the presence of NK1 and NK3 receptors on cholinergic neurones in the guinea-pig ileum.

In a guinea-pig ileum longitudinal muscle preparation, substance P (SP) (> or = 6 nM) caused an initial contraction followed by a sustained plateau contraction of about 20-50% of the initial response. This plateau contraction is caused by the SP-induced activation of cholinergic motoneurones which contract the smooth muscles by the released acetylcholine (ACh). We investigated the contribution of neurokinin NK1 and NK3 receptors during this 'plateau phase' of contraction. The plateau contraction induced by SP (60 nM) was significantly reduced by the NK1 receptor antagonist CP-96,345 (200 nM) added 5 min after SP, but was not affected by its inactive enantiomer CP-96,344 (200 nM). The NK1 receptor antagonist CP-99,994 (100 nM) significantly reduced the plateau contraction induced by SP (60 nM and 600 nM) and that induced by the NK1 receptor agonist substance P-O-methylester (SPOMe; 100 nM). CP-99,994 (100 nM), however did not affect the plateau contraction induced by the NK3 receptor agonist [Asp5,6, MePhe8]-SP(5-11) (100 nM). The plateau contraction induced by SP (600 nM) was not affected by the NK3 receptor antagonist SR-142,801 (100 nM), added 5 min after SP. Pre-incubation of the ileum with SR-142,801 (100 nM) 30 min prior to the addition of SP (600 nM) also had no significant effect on the plateau contraction. However, it significantly reduced the ileal contraction in the first minutes after the initial spasmogenic contraction. We suggest that SP induces the plateau contraction of the guinea-pig ileum longitudinal muscle mainly by the activation of NK1 receptors on cholinergic neurones.

Animals↗
PubMed1996

TSG-6 expression in human articular chondrocytes. Possible implications in joint inflammation and cartilage degradation.

OBJECTIVE: The hyaluronan-binding protein TSG-6 (tumor necrosis factor-stimulated gene 6) forms a stable complex with the serine protease inhibitor, inter-alpha-inhibitor, potentiates the inhibition of plasmin activity, and has antiinflammatory effects in vivo. This study examines the expression of TSG-6 in human articular chondrocytes and cartilage. METHODS: Human articular chondrocytes and cartilage explants were stimulated with cytokines, growth factors, and other agents. TSG-6 expression was analyzed by imaging-assisted Northern and Western blotting. RESULT: TSG-6 messenger RNA (mRNA) expression was upregulated by cytokines and growth factors, predominantly interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), platelet-derived growth factor AA (PDGF-AA), and transforming growth factor beta 1 (TGF beta 1). TSG-6 mRNA induction by TGF beta 1 was delayed as compared with IL-1beta. Treatment of the cells with the glucocorticoid dexamethasone neither induced TSG-6 mRNA nor did it affect IL-1 beta-induced transcript levels. TSG-6 mRNA induction may involve several signal transduction pathways. The strong transcriptional stimulation by phorbol myristate acetate suggests protein kinase C (PKC)-mediated signaling. In contrast, PKA- and Ca- dependent signals are only marginally involved as messengers leading to increased TSG-6 levels after IL-1beta and TNF alpha treatment. In chondrocyte and cartilage organ cultures, both free TSG-6 (35 kd) and the complex with inter-alpha-inhibitor (120 kd) were present and upregulated by IL-1 beta, TNF alpha, or TGF beta 1. CONCLUSION: Chondrocytes are a source of TSG-6 which may play a role in cartilage remodeling and joint inflammation.

Cartilage, Articular↗
PubMed1996

Motorcycle helmet use and injury outcome and hospitalization costs from crashes in Washington State.

OBJECTIVES: The incidence, type, severity, and costs of crash-related injuries requiring hospitalization or resulting in death were compared for helmeted and unhelmeted motorcyclists. METHODS: This was a retrospective cohort study of injured motorcyclists in Washington State in 1989. Motorcycle crash data were linked to statewide hospitalization and death data. RESULTS: The 2090 crashes included in this study resulted in 409 hospitalizations (20%) and 59 fatalities (28%). Although unhelmeted motorcyclists were only slightly more likely to be hospitalized overall, they were more severely injured, nearly three times more likely to have been head injured, and nearly four times more likely to have been severely or critically head injured than helmeted riders. Unhelmeted riders were also more likely to be readmitted to a hospital for follow-up treatment and to die from their injuries. The average hospital stay for unhelmeted motorcyclists was longer, and cost more per case; the cost of hospitalization for unhelmeted motorcyclists was 60% more overall ($3.5 vs $2.2 million). CONCLUSIONS: Helmet use is strongly associated with reduced probability and severity of injury, reduced economic impact, and a reduction in motorcyclist deaths.

Accidents, Traffic↗
PubMed1996

Effects of a novel 2,3-oxidosqualene cyclase inhibitor on the regulation of cholesterol biosynthesis in HepG2 cells.

Within the cholesterol biosynthesis cascade, the enzyme 2,3-oxidosqualene cyclase [EC 5.4.99.7] is of special interest due to its dual function: cyclization of 2,3-monoepoxysqualene to lanosterol and 2,3;22,23-diepoxysqualene to oxylanosterol. Further determination of the significance of this enzyme for the intracellular cholesterol homeostasis was done with BIBX 79, a new potent, specific inhibitor of this enzyme. In HepG2 cells the effects of BIBX 79 on cholesterol biosynthesis, 2,3-oxidosqualene cyclase as well as HMG-CoA reductase activities were studied. BIBX 79 is a potent inhibitor of sterol biosynthesis in HepG2 cells (IC50 4 x 10(-9) M). No other enzyme within the cholesterol biosynthesis cascade was significantly inhibited as was evidenced by a radio HPLC detection system. In contrast to simvastatin, no direct interaction with HMG-CoA reductase was observed. When incubating HepG2 cells for 16 h with the HMG-CoA reductase inhibitor simvastatin (10(-6)-10(-10) M) HMG-CoA reductase activity was increased up to 180%. BIBX 79 did also affect HMG-CoA reductase activity under these conditions: in concentrations of BIBX 79 "> or =" 10(-9) "< or =" 10(-7) M, where a partial inhibition of 2,3-oxidosqualene cyclase is observed, HMG-CoA reductase activity was decreased. However, higher concentrations of BIBX 79 that totally blocked 2,3-oxidosqualene cyclase led to an increase in HMG-CoA reductase activity. This effect of BIBX 79 on HMG-CoA reductase is thought to be mainly mediated by oxysterols that are formed by the cyclization of 2,3;22,23-diepoxysqualene. 2,3;22,23-Diepoxysqualene is preferentially cyclized by the 2,3-oxidosqualene cyclase and, consequently, only high inhibitor concentrations will also block 2,3;22,23-diepoxysqualene cyclization. Thus, by partial blockade of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.

Benzamides↗
PubMed1996

[Smoking behavior and views on the smoking topic in the Styrian population--results of a survey at the Graz autumn convention].

Cigarette smoking has been identified as a major risk factor for cardiovascular diseases apart from hypercholesterolemia and arterial hypertension. Diseases of the respiratory system and several neoplasms as well as complications of pregnancy are considered to be "smoking-related", too. In order to survey the smoking habits and views on smoking in the Styrian population, a questionnaire was issued to 1034 visitors of the Graz Autumn Fair 1992. Pleasure proved to be the main motivation for smoking both in men and in women, habit, addiction, stress and boredom being further motivations. Not only non-smokers, but also smokers were assessed to be aware of smoking being a health hazard. Prohibition of tobacco advertising was accepted most widely as a mean of anti-smoking campaign. About half the non-smokers are exposed to environmental tobacco smoke, at place of work more frequently than at home. Percentage of smokers differs with age and job classes, however, no geographical variations were found. Further anti-smoking measures should be considered. Smoking restrictions at place of work and in public could prevent passive smoking. Ban on advertising seems to be the most effective anti-smoking campaign.

Adolescent↗
PubMed1995

Sequence constraints and recognition by CTL of an HLA-B27-restricted HIV-1 gag epitope.

Previous studies on the variation of an immunodominant HLA-B27-restricted HIV-1 gag p24 epitope (KRWIIL GLNK, amino acids 263-272) have demonstrated the persistence of variants recognized by CTL. Sequence comparisons of HIV isolates showed that this region is relatively conserved and as a consequence might restrict antigenic variation. To evaluate the possibility of HIV-1 to yield infectious mutants of this epitope that lack the ability to bind to HLA-B27 or escape HLA-B27-restricted CTL recognition, single-point mutations were constructed in the infectious molecular clone of HIV-1 Lai. Changes of arginine 264, the anchor amino acid for HLA-B27, to lysine or glycine resulted in infectious HIV-1 variants. The respective synthetic peptides showed reduced ability to sensitize target cells for CTL recognition and a corresponding loss of binding affinity to HLA-B27. In contrast, mutation of glycine 269 to lysine or glutamate abrogated HIV-1 infectivity. The corresponding peptides were able to bind to HLA-B27 but were not recognized by CTL. These data show that HIV-1 tolerates some genetic variation of the HLA-B27-restricted CTL epitope in gag p24 and that single-point mutations can alter quantitatively the immunologic properties. Further, it demonstrates that the mere nonrecognition of peptides derived from quasispecies analysis of small regions might simply correspond to nonviable virus variants and cannot be taken as evidence for CTL escape mutants. Together with the previously published data on the persistence of CTL epitopes, these results suggest that CTL do not play a major role in driving HIV-1 evolution in vivo.

Amino Acid Sequence↗
PubMed1995

Tyrosine kinases are involved with the expression of inducible nitric oxide synthase in human articular chondrocytes.

The present study characterizes mechanisms involved with the induction of nitric oxide (NO) production, nitric oxide synthase (NOS) enzymatic activity and mRNA expression in human articular chondrocytes. Activation of chondrocytes with lipopolysaccharide (LPS) or IL-1 resulted in time- and dose-dependent increases in iNOS mRNA followed by increased NOS enzymatic activity and NO release. The protein tyrosine kinase (PTK) inhibitors herbimycin A or genistein reduced IL-1 or LPS-induced NO release and NOS enzymatic activity. This was associated with inhibition of iNOS mRNA expression as determined by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. In contrast, inhibitors of protein kinase C (PKC) or protein kinase A (PKA) did not affect these responses. These results were confirmed in experiments with second messenger agonists where neither activation of PKC, nor increases in cyclic adenosine monophosphate (cAMP) or increased intracellular calcium levels were associated with the induction of iNOS mRNA or NO release. These results suggest that PKC, PKA and calcium-dependent signals are not required or sufficient for the stimulation of NO production. However, NO production is dependent on tyrosine kinases due to their role in the expression of iNOS mRNA.

Amino Acid Oxidoreductases↗
PubMed1995

[Clinical experiences and results of high-dosage methylprednisolone therapy in spinal cord trauma 1991 to 1993].

Studies in animals and especially the NASCIS II study illustrated the neuroprotective effects of methylprednisolone, but they are disputed. At the University Clinic of Traumatology, Vienna, 31 patients with spinal cord injuries were given methylprednisolone as a bolus of 30 mg/kg body weight followed by a maintenance dose of 5.4 mg/kg body weight/h for another 23 hours. Twenty-seven patients were stabilised within 8 hours, 2 patients were not operated on, because of their low prognosis. Two patients could be treated conservatively, because the spinal fractures were supposed to be stabile. Then follow-up studies of these patients were between 1 and 3.2 years. All patients (100%) with incomplete neurologic deficits (n = 18) showed a significant recovery and even 3 patients (23.1%) with primarily a complete tetraplegia (n = 13) showed a nearly entire recovery. Compared to these results we look back at 113 patients with complete and incomplete neurologic deficits who were treated at the I. University Clinic of Traumatology, Vienna, and would have got methylprednisolone following our current management procedures.

Adolescent↗
PubMed1995

Stereoselective increase of plasma concentrations of the enantiomers of propranolol and atenolol during exercise.

OBJECTIVE: In vitro studies have shown that, like catecholamines, both propranolol and atenolol are taken up by and released from adrenergic cells. We performed this study to investigate whether this may also play a role in humans and whether stereoselective aspects are important. METHODS: This was a randomized, double-blind, placebo-controlled, crossover study of two groups of 12 healthy volunteers. Subjects received single oral doses of 80 mg (R,S)-, 40 mg (R)-, and 40 mg (S)-propranolol; 100 mg (R,S)-, 50 mg (R)-, and 50 mg (S)-atenolol; and placebo at intervals of 1 week. Exercise was performed at 4 and 9 hours after drug intake, and blood samples were taken before and at the end of each exercise period. The plasma concentrations of the (R)- and (S)-enantiomers of propranolol and atenolol, as well as those of epinephrine and norepinephrine, were determined by HPLC. RESULTS: Effects of exercise on the plasma levels of the enantiomers of propranolol and atenolol were similar. When the optically pure enantiomers were administered, exercise caused a marked and significant increase of the plasma concentrations of the (S)- but not of the (R)-enantiomers. When the drugs were administered in the racemic form, the plasma levels of both the (R)- and (S)-enantiomers were elevated to the same extent. The increase of norepinephrine levels during exercise was more pronounced than that of epinephrine and paralleled that of the (S)-enantiomers of the beta-blockers. CONCLUSION: Bearing the in vitro data in mind, we conclude that (S)-propranolol and (S)-atenolol are taken up into and released from adrenergic cells together with norepinephrine during exercise. The reason why the plasma concentrations of (R)-propranolol and (R)-atenolol are increased only during exercise in the presence of the corresponding (S)-enantiomers remains to be determined.

Administration, Oral↗
PubMed1995

A novel transcription factor and two members of the Sp 1 multigene family regulate the activity of the alpha 2 (VI) collagen promoter.

For a better understanding of the processes that lead to the activation or inhibition of type VI collagen synthesis, we have identified and characterized the cis-acting elements of the chicken alpha 2 (VI) collagen promoter. This promoter encompasses four sites, termed S1, S2, X and S3, which interact with nuclear factors. Sites S1, S2 and S3 are each recognized by the same two proteins that belong to the Sp 1 multigene family. Site X appears to interact with a novel transcription factor of 43 kDa. When a fragment containing all four of the elements is placed in front of a reporter gene, the resulting construct is able to induce a high level of transcription in chicken fibroblasts. As soon as a single element is deleted from this construct, the activity decreases drastically. Thus, the four elements are essential for the transcriptional activation of the alpha 2 (VI) collagen gene.

Animals↗