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Biomedical subjects

M Schaub

Publications and source records attributed to M Schaub.

At least 19 recordsLinked to original sources

Risk assessments for forest trees: the performance of the ozone flux versus the AOT concepts.

Published ozone exposure-response relationships from experimental studies with young trees performed at different sites across Europe were re-analysed in order to test the performance of ozone exposure indices based on AOTX (Accumulated exposure Over a Threshold of X nmol mol(-1)) and AF(st)Y (Accumulated Stomatal Flux above a threshold of Y nmol m(-2) s(-1)). AF(st)1.6 was superior, as compared to AOT40, for explaining biomass reductions, when ozone sensitive species with differing leaf morphology were included in the analysis, while this was not the case for less sensitive species. A re-analysis of data with young black cherry trees, subject to different irrigation regimes, indicated that leaf visible injuries were more strongly related to the estimated stomatal ozone uptake, as compared to the ozone concentration in the air. Experimental data with different clones of silver birch indicated that leaf thickness was also an important factor influencing the development of ozone induced leaf visible injury.

Betula↗

Comparison of different stomatal conductance algorithms for ozone flux modelling.

A multiplicative and a semi-mechanistic, BWB-type [Ball, J.T., Woodrow, I.E., Berry, J.A., 1987. A model predicting stomatal conductance and its contribution to the control of photosynthesis under different environmental conditions. In: Biggens, J. (Ed.), Progress in Photosynthesis Research, vol. IV. Martinus Nijhoff, Dordrecht, pp. 221-224.] algorithm for calculating stomatal conductance (g(s)) at the leaf level have been parameterised for two crop and two tree species to test their use in regional scale ozone deposition modelling. The algorithms were tested against measured, site-specific data for durum wheat, grapevine, beech and birch of different European provenances. A direct comparison of both algorithms showed a similar performance in predicting hourly means and daily time-courses of g(s), whereas the multiplicative algorithm outperformed the BWB-type algorithm in modelling seasonal time-courses due to the inclusion of a phenology function. The re-parameterisation of the algorithms for local conditions in order to validate ozone deposition modelling on a European scale reveals the higher input requirements of the BWB-type algorithm as compared to the multiplicative algorithm because of the need of the former to model net photosynthesis (A(n)).

Algorithms↗

Effect of pre-treatment with catecholamines on cold preservation and ischemia/reperfusion-injury in rats.

Treatment of organ donors with catecholamines reduces acute rejection episodes and improves long-term graft survival after renal transplantation. The aim of this study was to investigate the effect of catecholamine pre-treatment on ischemia/reperfusion (I/R)- and cold preservation injury in rat kidneys. I/R-injury was induced by clamping the left kidney vessels for 60 min along with a contralateral nephrectomy. Cold preservation injury was induced by storage of the kidneys for 24 h at +4 degrees Celsius in University of Wisconsin solution, followed by syngeneic transplantation. Rats were pre-treated with either dopamine (DA), dobutamine (DB), or norepinephrine (2, 5, and 10 microg/kg/min, each group) intravenously via an osmotic minipump for 24 h before I/R- and cold preservation injury. Pre-treatment with DA (2 or 5 microg/kg/min) and DB (5 microg/kg/min) improved recovery of renal function after I/R-injury and dose dependently reduced mononuclear and major histocompatibility complex class II-positive cells infiltrating the kidney after I/R-injury. One day after I/R-injury, upregulation of transforming growth factor (TGF)-beta 1 and 2 and phosphorylation of p42/p44 mitogen-activated protein kinases was observed in kidneys of animals treated with DA or DB. DA (5 microg/kg/min) and DB (5 microg/kg/min) pre-treatment reduced endothelial cell damage after 24 h of cold preservation. Only DA pre-treatment improved renal function and reduced renal inflammation after 24 h of cold preservation and syngeneic transplantation. Our results demonstrate a protective effect of pre-treatment with catecholamines on renal inflammation and function after I/R- or cold preservation injury. This could help to explain the potent organoprotective effects of catecholamine pre-treatment observed in human kidney transplantation.

Animals↗

Physiological and foliar symptom response in the crowns of Prunus serotina, Fraxinus americana and Acer rubrum canopy trees to ambient ozone under forest conditions.

The crowns of five canopy dominant black cherry (Prunus serotina Ehrh.), five white ash (Fraxinus americana L.), and six red maple (Acer rubrum L.) trees on naturally differing environmental conditions were accessed with scaffold towers within a mixed hardwood forest stand in central Pennsylvania. Ambient ozone concentrations, meteorological parameters, leaf gas exchange and leaf water potential were measured at the sites during the growing seasons of 1998 and 1999. Visible ozone-induced foliar injury was assessed on leaves within the upper and lower crown branches of each tree. Ambient ozone exposures were sufficient to induce typical symptoms on cherry (0-5% total affected leaf area, LAA), whereas foliar injury was not observed on ash or maple. There was a positive correlation between increasing cumulative ozone uptake (U) and increasing percent of LAA for cherry grown under drier site conditions. The lower crown leaves of cherry showed more severe foliar injury than the upper crown leaves. No significant differences in predawn leaf water potential (psi(L)) were detected for all three species indicating no differing soil moisture conditions across the sites. Significant variation in stomatal conductance for water vapor (g(wv)) was found among species, soil moisture, time of day and sample date. When comparing cumulative ozone uptake and decreased photosynthetic activity (P(n)), red maple was the only species to show higher gas exchange under mesic vs. drier soil conditions (P < 0.05). The inconsistent differences in gas exchange response within the same crowns of ash and the uncoupling relationship between g(wv) and P(n) demonstrate the strong influence of heterogeneous environmental conditions within forest canopies.

Acer↗

Seasonal trends in reduced leaf gas exchange and ozone-induced foliar injury in three ozone sensitive woody plant species.

Seasonal trends in leaf gas exchange and ozone-induced visible foliar injury were investigated for three ozone sensitive woody plant species. Seedlings of Populus nigra L., Viburnum lantana L., and Fraxinus excelsior L. were grown in charcoal-filtered chambers, non-filtered chambers and open plots. Injury assessments and leaf gas exchange measurements were conducted from June to October during 2002. All species developed typical ozone-induced foliar injury. For plants exposed to non-filtered air as compared to the charcoal-filtered air, mean net photosynthesis was reduced by 25%, 21%, and 18% and mean stomatal conductance was reduced by 25%, 16%, and 8% for P. nigra, V. lantana, and F. excelsior, respectively. The timing and severity of the reductions in leaf gas exchange were species specific and corresponded to the onset of visible foliar injury.

Air Pollutants↗

[Cannabis and psychosis--a review].

The present review focuses on articles dealing with clinical or epidemiological studies on the association between cannabis use and psychoses. Included are all articles published since 1990 that were located by a Medline or Psyclit data-base research and those earlier articles that are needed for a correct understanding of studies published during the index episode. The three main topics found are 1) is there evidence for a so called cannabis psychosis 2) do cannabis users exhibit a higher risk of developing a psychotic disorder or 3) does its use worsen the course in established schizophrenia spectrum disorders. The review concludes that very high doses of cannabis can induce a brief psychosis but that this condition is extremely rare. Therefore, such a diagnosis should only be made after careful exclusion of other etiologies. The actual evidence regarding the impact of cannabis use on persons vulnerable to psychosis is not conclusive. Cannabis use seems to worsen the course of schizophrenia spectrum disorders. Adolescents run a higher risk from using cannabis than older people. They should be strongly advised not to indulge in such behaviour.

Cannabinoids↗

Impact of donor dopamine on immediate graft function after kidney transplantation.

Optimizing medical donor management may have a considerable impact on transplantation outcome. This study investigated the effect of donor dopamine on initial graft function in renal allograft recipients, involving 254 consecutive recipients of a cadaver kidney, aged 18-74 years, transplanted between 1990 and 2003. Immunosuppression was based on cyclosporine. Patients were grouped according to donor use of dopamine during intensive care. Delayed graft function (DGF), and serial creatinine concentrations were compared between the groups. Dopamine-treated and -untreated donors were very similar regarding hemodynamics and renal function. Delayed graft function occurred in 47/158 treated and 48/96 untreated kidneys (p = 0.001). Donor dopamine was associated with a more rapid decrease of s-creatinine, which became obvious on the first postoperative day. Of patients in the treated and untreated group, respectively, 81.9% and 65.8% reached a s-creatinine level less than 2 mg/dL during the first month (p = 0.005). Donor dopamine remained predictive of a normalized s-creatinine level [HR 1.71; 95% CI 1.22-2.41] after controlling for confounding factors by multivariate Cox regression. Donor dopamine is associated with improvements of initial graft function after kidney transplantation. The beneficial effect of dopamine is achievable without side-effects for the recipients, and correlates with superior long-term graft survival.

Adolescent↗

Physiological and foliar injury responses of Prunus serotina, Fraxinus americana, and Acer rubrum seedlings to varying soil moisture and ozone.

Sixteen black cherry (Prunus serotina, Ehrh.), 10 white ash (Fraxinus americana, L.) and 10 red maple (Acer rubrum, L.) 1-year old seedlings were planted per plot in 1997 on a former nursery bed within 12 open-top chambers and six open plots. Seedlings were exposed to three different ozone scenarios (ambient air: 100% O3; non-filtered air: 98% ambient O3; charcoal-filtered air: 50% ambient O3) within each of two different water regimes (nine plots irrigated, nine plots non-irrigated) during three growing seasons. During the 1998 and 1999 growing season, leaf gas exchange, plant water relations, and foliar injury were measured. Climatic data,ambient- and chamber-ozone-concentrations were monitored. We found that seedlings grown under irrigated conditions had similar (in 1998) but significantly higher gas exchange rates (in 1999) than seedlings grown within non-irrigated plots among similar ozone exposures. Cherry and ash had similar ozone uptake but cherry developed more ozone-induced injury (< 34% affected leaf area, LAA) than ash (<5% LAA), while maple rarely showed foliar injury, indicating the species differed in ozone sensitivity. Significantly more severe injury on seedlings grown under irrigated conditions than seedlings grown under non-irrigated conditions demonstrated that soil moisture altered seedling responses to ambient ozone exposures.

Acer↗

Assessment of ozone visible symptoms in the field: perspectives of quality control.

The second UN/ECE ICP-Forests Intercalibration Course on the Assessment of Ozone Injury on European Tree Species was carried out in August 2001 at Lattecaldo (Canton Ticino, CH) and Moggio (Lombardy, I). Forty-eight experts from several European countries participated in the exercises and assessed visible symptoms of ozone injury both in open-top chambers (OTC) (Lattecaldo) and under open field (Moggio) conditions. Evaluation of the results indicated a large variability among the teams and call for adequate training of the observers prior to symptom assessment for quality assurance purposes. Highest variability was found for the species developing unclear symptoms which could be confused with senescence processes; such species should not be used in the field. The authors provide suggestions to improve the reliability of the ozone injury assessment on forest plant species.

Air Pollutants↗

Long-term cisapride treatment improves diabetic gastroparesis but not glycaemic control.

BACKGROUND: In patients with diabetic gastroparesis, delayed food delivery to the intestine may become a major obstacle to post-prandial glycaemic control. AIM: To investigate whether cisapride accelerates gastric emptying in the long term or improves diabetes control in patients with diabetic gastroparesis. METHODS: Eighty-five patients with long-standing insulin-dependent diabetes mellitus (glycosylated haemoglobin (HbA1c) > 7.0%), dyspepsia and diabetic neuropathy were tested for impaired gastric emptying of solids by the 13C-octanoate breath test. Nineteen of these patients with severe diabetic gastroparesis (i.e. t1/2 > 170 min) were randomly treated with 10 mg cisapride t.d.s. (n=9) or placebo (n=10) for 12 months. Thereafter, the breath test, dyspeptic symptoms and HbA1c values were reassessed. RESULTS: Half emptying times in nine patients with diabetic gastroparesis were significantly shortened by cisapride (175 +/- 46 min vs. 227 +/- 40 min; P < 0.03). Half emptying times in the 10 patients taking placebo did not change (205 +/- 37 min vs. 211 +/- 36 min, P=0.54). Cisapride significantly reduced dyspepsia (score: 4.1 +/- 1.6 vs. 2.0 +/- 0.5, P=0.002). HbA1c values after 12 months of treatment were not different (cisapride: 7.7 +/- 0.4% vs. 7.6 +/- 0.9%, P=0.76; placebo: 7.5 +/- 0.6% vs. 7.6 +/- 1.5%, P=0.89). CONCLUSIONS: Prokinetic treatment with cisapride accelerates gastric emptying of solids and improves dyspeptic symptoms in diabetic gastroparesis. Glycaemic control, however, is not affected by cisapride.

Aged↗

Treatment of chronic renal allograft rejection in rats with a low-molecular-weight heparin (reviparin).

BACKGROUND: Low-molecular-weight heparin (LMWH) has been shown to prolong survival of rat cardiac allografts independently from immunosuppressive treatment. Furthermore, long-term treatment reduces the development of chronic graft vascular disease after experimental heart transplantation. The aim of the present study was to determine whether treatment with the LMWH reviparin has a beneficial effect on chronic rejection in a rat renal allograft model. METHODS: Kidneys of Fisher (F344) rats were transplanted into unilaterally nephrectomized Lewis (LEW) recipients. LEW-->LEW isografts served as controls. Animals were treated with cyclosporine (5 mg/kg/d) for the first 10 days. Nephrectomy of the remaining kidney was performed after 10 days. Allografted animals were treated either with reviparin (2 mg/kg/d subcutaneously) for 24 weeks (Allo-24), from week 12 to 24 (Allo-12), or with vehicle for 24 weeks. Proteinuria was determined at regular intervals. Kidneys were harvested after 24 weeks for histomorphological and immunohistochemical evaluation. RESULTS: No major bleeding complications were observed in reviparin-treated animals. Proteinuria was significantly reduced in allografted animals both by early as well as by late-onset treatment with reviparin. Transplant glomerulopathy was diminished in Allo-24 and in Allo-12 groups compared to vehicle-treated animals, whereas tubulointerstitial inflammation was influenced only in animals immediately treated with reviparin. Immunohistochemical studies demonstrated a marked reduction of renal monocyte and T-cell infiltration as well as expression of MHC II by treatment with reviparin. CONCLUSIONS: Treatment with the LMWH reviparin significantly improved chronic renal allograft rejection in the F344-to-LEW rat model, both after early and late start of therapy. Although the exact mechanisms of this beneficial effect remain unclear, our data offer a potential new therapeutical approach for prevention of chronic allograft nephropathy.

Animals↗

Structural organization of Staf-DNA complexes.

The transactivator Staf, which contains seven contiguous zinc fingers of the C(2)-H(2)type, exerts its effects on gene expression by binding to specific targets in vertebrate small nuclear RNA (snRNA) and snRNA-type gene promoters. Here, we have investigated the interaction of the Staf zinc finger domain with the optimal Xenopus selenocysteine tRNA (xtRNA(Sec)) and human U6 snRNA (hU6) Staf motifs. Generation of a series of polypeptides containing increasing numbers of Staf zinc fingers tested in binding assays, by interference techniques and by binding site selection served to elucidate the mode of interaction between the zinc fingers and the Staf motifs. Our results provide strong evidence that zinc fingers 3-6 represent the minimal zinc finger region for high affinity binding to Staf motifs. Furthermore, we show that the binding of Staf is achieved through a broad spectrum of close contacts between zinc fingers 1-6 and xtRNA(Sec)or optimal sites or between zinc fingers 3-6 and the hU6 site. Extensive DNA major groove contacts contribute to the interaction with Staf that associates more closely with the non-template than with the template strand. Based on these findings and the structural information provided by the solved structures of other zinc finger-DNA complexes, we propose a model for the interaction between Staf zinc fingers and the xtRNA(Sec), optimal and hU6 sites.

Amino Acid Sequence↗

Intrathymic immunomodulation in sensitized rat recipients of cardiac allografts: requirements for allorecognition pathways.

BACKGROUND: Intrathymic injection of alloantigen in the form of donor cells, soluble major histocompatibility complex (MHC) molecules, or MHC allopeptides induces donor-specific tolerance in a variety of acute allograft rejection models. We have previously shown that a single intrathymic injection of donor spleen cells into pre-sensitized rats abrogates accelerated (circa 24-hour) rejection and prolongs the survival of cardiac allografts to about 7 days. The present study was designed to investigate the mechanisms by which intrathymic administration of donor cells modifies the course of accelerated rejection. METHODS: Lewis RT1(1) (LEW) rats sensitized by transplantation with Wistar-Furth RT1(u) (WF) skin grafts received WF cardiac allografts 7 days later-a classic model of accelerated rejection. At the time of skin challenge, however, certain animals received intrathymic cell suspensions (either allogeneic or syngeneic) or donor-derived class I and/or class II MHC peptides. RESULTS: Control animals (sensitized by skin grafts but receiving no other treatment) rejected cardiac allografts within 24 hours. Intrathymic injection of WF splenocytes at the time of skin transplantation abrogated rejection at 24 hours and prolonged cardiac allograft survival to 6.6+/-0.6 days (p<0.001), whereas intrathymic administration of syngeneic (LEW) or allogeneic third party Brown Norway RT1(n) cells was ineffective in this regard. Intrathymic injection of gamma-irradiated donor cells marginally extended cardiac allograft survival to 3.0+/-0.9 days (p< 0.001), but the grafts were still rejected in an accelerated fashion. Intrathymic injection of donor-derived class I and/or class II MHC allopeptides at the same time period also failed to prolong cardiac allograft survival beyond 3 days. In the group receiving unmodified donor cells, elevated immunoglobulin M (IgM) and immunoglobulin G (IgG) allo-antibodies were found at the time of cardiac transplantation; this pattern was not observed with any other treatment. CONCLUSION: The superiority of non-modified donor spleen cells over gamma-irradiated donor cells or donor specific allopeptides in modifying the course of accelerated cardiac rejection suggests that direct allorecognition is the dominant pathway initiating rejection in sensitized transplant recipients. Marked alterations in the antidonor IgM and IgG responses are associated with successful abrogation of accelerated rejection by thymic immunomodulatory mechanisms.

Animals↗

Treatment with a combined endothelin A/B-receptor antagonist does not prevent chronic renal allograft rejection in rats.

A markedly increased expression of endothelin (ET)-1 has been observed in renal allografts with chronic rejection, one of the most common causes of kidney graft loss. In this study we investigated the effect of treatment with a combined ET-A/B-receptor antagonist on the course of chronic renal allograft rejection. Experiments were performed in the Fisher-to-Lewis rat model of chronic rejection. Lewis-to-Lewis isografts and uninephrectomized Lewis rats served as controls. Animals were treated with either the oral combined ET-A/B-receptor antagonist LU224332 (20 mg/kg/day) or vehicle. Animal survival, blood pressure, creatinine clearance, proteinuria, and urinary ET excretion were investigated for 24 weeks. Kidneys were removed for light-microscopic evaluation and immunohistochemical assessment of cell-surface markers. Treatment with LU224332 did not improve survival after 24 weeks (0.47 vs. 0.38; p > 0.05 by log-rank test), nor did it have an influence on blood pressure, creatinine clearance, or proteinuria. Combined ET-A/B-receptor blockade was associated with a reduction of expression of cell-surface markers for macrophages (EDI), T-cells (R73), and major histocompatibility complex (MHC) II (F17-23-2), but did not lead to an improvement of histologic changes of chronic allograft rejection. Our data show that blocking both ET-A- and -B receptors, in opposition to a previously published beneficial effect of selective ET-A blockade, does not prevent the progression of chronic renal allograft rejection and does not prolong survival in this model. Functional integrity of the ET-B receptor therefore seems to play an important role in the nephroprotection provided by selective ET-A-receptor antagonists in chronic renal allograft nephropathy.

Animals↗

The renoprotective potential of endothelin receptor antagonists.

The endothelin system has been identified as having a substantial role in renal failure, both acute and chronic. Beside its well characterised haemodynamic effects, its mitogenic and pro-fibrotic properties have gained increased interest in the pathophysiology of chronic renal failure. This review outlines the role of endothelin in the pathogenesis of various renal diseases with a special focus on the potential of blocking this system with endothelin receptor antagonists. So far, most data were derived from animal models, but they provide strong evidence that endothelin receptor antagonists may represent a powerful therapeutic strategy in ameliorating the course of acute and chronic renal failure.

Animals↗

Prevention of chronic renal allograft rejection in rats with an oral endothelin A receptor antagonist.

BACKGROUND: Chronic rejection is the most common cause of graft loss in renal transplantation. The pathomechanisms underlying chronic rejection are poorly understood, and no treatment has yet successfully been established. We hypothesized that, in analogy to models of reduced renal mass, the administration of a selective endothelin (ET) A receptor antagonist could improve the course of chronic rejection in renal allografts. METHODS: Experiments were performed in the Fisher-to-Lewis rat model of chronic rejection. Lewis-->Lewis isografts served as controls. Animals were treated with either the oral selective ET-A receptor antagonist LU135252 (50 mg/kg/day) or vehicle. Animal survival, blood pressure, creatinine clearance, proteinuria, and urinary ET excretion were investigated for 24 weeks. Kidneys were removed for light microscopical evaluation, determination of ET mRNA expression and tissue protein concentration, and immunohistochemical assessment of cell surface markers. RESULTS: Rats with chronic rejection showed an increase in renal ET mRNA synthesis and ET protein content. Treatment with LU135252 resulted in a significant improvement in survival after 24 weeks (0.92 vs. 0.38, P<0.01 by log-rank test). Creatinine clearance was higher in animals treated with the selective ET-A receptor antagonist (P<0.05). LU135252 had no influence on blood pressure and proteinuria. Selective ET-A blockade was associated with significantly less morphological changes and a significant reduction of expression of cell surface markers for macrophages (ED1), T cells (R73), and MHC II (F17-23-2). CONCLUSION: The renal ET-A system plays an important role in the pathomechanisms underlying chronic renal allograft rejection, because the treatment with a selective ET-A receptor antagonist dramatically improves the course of chronic renal failure after allograft transplantation. These results offer a novel therapeutical option for treatment of chronic renal allograft rejection, for which so far no therapy is known.

Administration, Oral↗

Maximization of selenocysteine tRNA and U6 small nuclear RNA transcriptional activation achieved by flexible utilization of a Staf zinc finger.

Transcriptional activators Staf and Oct-1 play critical roles in the activation of small nuclear RNA (snRNA) and snRNA-type gene transcription. Recently, we established that Staf binding to the human U6 snRNA (hU6) and Xenopus selenocysteine tRNA (xtRNA(Sec)) genes requires different sets of the seven C2-H2 zinc fingers. In this work, using a combination of oocyte microinjection, electrophoretic mobility shift assays, and missing nucleoside experiments with wild-type and mutant promoters, we demonstrate that the hU6 gene requires zinc fingers 2-7 for Staf binding and Oct-1 for maximal transcriptional activity. In contrast, the xtRNA(Sec) gene needs the binding of the seven Staf zinc fingers, but not Oct-1, for optimal transcriptional capacity. Mutation in the binding site for Staf zinc finger 1 in the tRNA(Sec) promoter reduced both Staf binding and transcriptional activity. Conversely, introduction of a zinc finger 1 binding site in the hU6 promoter increased Staf binding but interfered with the simultaneous Staf and Oct-1 binding, thus reducing transcriptional activity. Collectively, these results show that the differential utilization of Staf zinc finger 1 represents a new, critical determinant of the transcriptional activation mechanism for the Xenopus tRNA(Sec) and human U6 snRNA genes.

Amino Acid Sequence↗

Flexible zinc finger requirement for binding of the transcriptional activator staf to U6 small nuclear RNA and tRNA(Sec) promoters.

The transactivator Staf, which contains seven zinc finger motifs, exerts its effect on gene expression by binding to specific targets in small nuclear RNA (snRNA) and snRNA-type gene promoters. In this work, binding site selection allowed us to identify the 21-base pair ATTACCCATAATGCATYGCGG sequence as the high affinity consensus binding site for Staf. It shows a high sequence divergence with Staf-responsive elements in the Xenopus selenocysteine tRNA (tRNA(Sec)) and human U6 snRNA promoters. By using a combination of approaches, we analyzed the interaction of wild-type and truncated Staf zinc finger domains with the consensus, Xenopus tRNA(Sec), and human U6 sites. Two main conclusions emerged from our data. First, the data clearly indicate that zinc finger 7 does not establish base-specific contacts in Staf-DNA complexes. The second conclusion concerns zinc finger 1, which is required for the binding to the Xenopus tRNA(Sec) site but is dispensable in the case of the human U6 site. Taking into account the sequence differences in the two sites, these findings demonstrate that Staf utilizes zinc finger 1 in a rather flexible manner, illustrating how a protein can interact with DNAs containing targets of different sequences.

Amino Acid Sequence↗