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Biomedical subjects

M Stoll

Publications and source records attributed to M Stoll.

At least 37 records · Page 2Linked to original sources

[Helper cells, viral load, genetic factors, co-infections. Prognostic factors in HIV-1 infection].

The ideal time to initiate antiretroviral therapy in asymptomatic patients with chronic HIV infection remains to be defined. The most relevant laboratory parameter is the CD4 cell count. Therapy should be started before the CD4 cells drop below 200/microliter and the immune system becomes compromised. In contrast to past recommendations, viral load should not be used as a single laboratory parameter for initiation of antiretroviral therapy in asymptomatic untreated patients. The determination of genetic factors to assess the prognosis of HIV patients has not yet been incorporated into daily clinical practice. While co-infection with GBV-C is a prognostically favorable factor for the course of the HIV infection, replicative hepatitis C is associated with increased mortality.

AIDS-Related Opportunistic Infections↗

[Cerebrovascular reserve capacity].

Cerebrovascular reserve capacity (CVR) describes how far cerebral perfusion can increase from a baseline value after stimulation. Measurement of cerebral blood flow (CBF) can be done by PET or SPECT. Noninvasive and easily performed transcranial Doppler sonography (TCD) is mostly used as indirect perfusion measurement. Stimulation of cerebral perfusion is often done by CO2 inhalation or acetazolamide injection. Alternative stimuli are breath holding or cerebral activation by hand-gripping. Normal values for these tests are presented. The hemodynamic effect of stenoses of the internal carotid artery (ICA) can be estimated using CVR. The relevance of CVR is discussed controversially, since cerebral infarction due to stenosis of arteries supplying the brain is probably mostly of embolic, not hemodynamic origin. The indication for carotid artery surgery according the NASCET and ECST investigations takes into account only the degree of the stenoses and not the CVR. According to recent studies, the risk of cerebral infarction in these patients is considerably higher with reduced CVR. Therefore, CVR can be used as an additional parameter if the indication for surgery is not defined, especially in asymptomatic carotid artery stenosis. It seems also possible to identify patients who might profit from an extra-intracranial bypass operation and high-risk patients for cerebral ischemia with cerebral microangiopathy. Furthermore, the risk of cerebral infarction during carotid artery surgery and also during heart surgery can be estimated using CVR. More studies with a higher number of patients are needed to confirm the potential predictive diagnostic value of CVR in order to establish CVR measurement as part of a routine diagnostic neuroangiologic program.

Blood Flow Velocity↗

A genomic-systems biology map for cardiovascular function.

With the draft sequence of the human genome available, there is a need to better define gene function in the context of systems biology. We studied 239 cardiovascular and renal phenotypes in 113 male rats derived from an F2 intercross and mapped 81 of these traits onto the genome. Aggregates of traits were identified on chromosomes 1, 2, 7, and 18. Systems biology was assessed by examining patterns of correlations ("physiological profiles") that can be used for gene hunting, mechanism-based physiological studies, and, with comparative genomics, translating these data to the human genome.

Animals↗

Infection with GB virus C and reduced mortality among HIV-infected patients.

BACKGROUND: The flavivirus GB virus C (GBV-C, also designated hepatitis G virus) was identified in a search for hepatitis viruses, but no disease is currently known to be associated with it. We investigated the relation between coinfection with GBV-C and the long-term outcome in patients infected with the human immunodeficiency virus (HIV). METHODS: A total of 197 HIV-positive patients were followed prospectively beginning in 1993 or 1994. Of these patients, 33 (16.8 percent) tested positive for GBV-C RNA, 112 (56.9 percent) had detectable antibodies against the GBV-C envelope protein E2, and 52 (26.4 percent) had no marker of GBV-C infection and were considered unexposed. We assessed the relation between GBV-C infection and the progression of HIV disease. We also tested 169 GBV-C-positive plasma samples with a quantitative branched-chain DNA (bDNA) assay in order to investigate possible correlations between GBV-C viral load and both the CD4+ cell count and the HIV load. RESULTS: Among the patients who tested positive for GBV-C RNA, survival was significantly longer, and there was a slower progression to the acquired immunodeficiency syndrome (AIDS) (P<0.001 for both comparisons). Survival after the development of AIDS was also better among the GBV-C-positive patients. The association of GBV-C viremia with reduced mortality remained significant in analyses stratified according to age and CD4+ cell count. In an analysis restricted to the years after highly active antiretroviral therapy became available, the presence of GBV-C RNA remained predictive of longer survival (P=0.02). The HIV load was lower in the GBV-C-positive patients than in the GBV-C-negative patients. The GBV-C load correlated inversely with the HIV load (r=-0.33, P<0.001) but did not correlate with the CD4+ cell count. CONCLUSIONS: Coinfection with GBV-C is associated with a reduced mortality rate in HIV-infected patients. GBV-C is not known to cause any disease, but it is possible that its presence leads to an inhibition of HIV replication. However, GBV-C infection could also be a marker for the presence of other factors that lead to a favorable HIV response.

Adult↗

Identification of two susceptibility loci for vascular fragility in the Brown Norway rat.

A trait of vascular fragility, characterized by the formation of abrupt defects within the elastic laminae of the abdominal aorta, has been identified in Brown Norway (BN) rats. These lesions are greatly exacerbated in F(1) rats from a BN x New Zealand genetically hypertensive (GH) intercross, implying that the genetic background provided by the GH rat influences lesion severity. The F(2) progeny of the BN x GH intercross were used to identify susceptibility loci for the lesions as well as exacerbating loci. Two major quantitative trait loci (QTLs) for number of internal elastic lamina lesions were identified on rat chromosomes 5 and 10, with the maximum "log of the odds ratio" (LOD) scores at D5Rat119 (LOD 5.0) and at D10Mit2 (LOD 4.5), respectively, together contributing 33.5% to the genetic variance. Further analysis revealed that the chromosome 10 locus exhibits a dominant mode of inheritance, with BN alleles being associated with increased lesion number (P < 0.0002) compared with GH homozygotes. This locus was in epistasis to a modifier locus on rat chromosome 2 at D2Mit14 (LOD score 2.12). A second major locus was identified on chromosome 5, exhibiting a semidominant mode of inheritance, again with the BN allele being significantly associated with increased lesion number (P < 0.0001). Furthermore, a locus influencing lesion severity was identified on chromosome 3 wherein GH alleles associated with increased severity. This is the first study to identify susceptibility loci for vascular elastic tissue fragility.

Animals↗

Angiotensin and its AT2 receptor: new insights into an old system.

The AT2 receptor represents a true receptor, but signals and functions in unexpected ways compared to the respective features of the 'classical' AT1 receptor. Moreover, some of the actions of the AT2 receptor are even directly opposed to those of the AT1 receptor, especially concerning the growth- and differentiation-modulating actions of ANG II. The regulation of the AT2 receptor itself by its agonist, as well as by growth factors during ontogenesis, and its acknowledged effects on the regulation of cell growth, differentiation and apoptosis, points towards a role of a program modulator in embryonic development and regeneration.

Angiotensin II↗

Pulmonary hypersensitivity reaction induced by efavirenz.

HIV-infected patients are at increased risk of developing adverse drug reactions such as a maculopapular rash due to antiretroviral drugs. For example, exanthema induced by non-nucleoside reverse transcriptase inhibitors leads to drug discontinuation in many patients. We present a patient with a severe pulmonary hypersensitivity reaction due to efavirenz.

Adult↗

[The cost of an HIV patient. Lack of funds for optimal treatment?].

Many patients with HIV--a group in urgent need of effective health care measures--are extremely worried by current discussions on budgeting, fearing, as daily practice shows, restrictions on vitally indicated services. The present article describes the results of a recent health economics study of the direct and indirect costs generated by HIV infection.

Anti-HIV Agents↗

[Rehabilitation and pensioning. Social network assimilates the HIV patient poorly].

For HIV patients, the social security net contains considerable gaps; for example, more than one-half of the unemployed patients under 55 receive no pension; in the case of those who go on to develop AIDS, the figure is 30%. Apparently, recognition of inability to work depends on the severity of the disability. Nor does the statutory regulation of rehabilitation measures do justice to those infected with HIV. Despite their higher morbidity, they are under-represented by a factor of 10 in comparison with the average in the general population when it comes to medical rehabilitation. While formerly, the HIV-infected were granted a disablement pension relatively quickly, today the pension insurance carriers appear to be adopting a more restrictive attitude, and often grant a pension for only a limited period. Furthermore, the legislation took effect at the beginning of 2001, has also made early pensioning more difficult.

Disability Evaluation↗

[Fracture of the acromion. Diagnosis--treatment strategy--outcome].

The case of an 22-year-old man is presented, who sustained a dislocated fracture of the left acromion process and a not dislocated fracture of the left scapular body with a large subcutaneous décollement as well as a dammage of nervus axillaris occurring during a traffic accident. After resuming diagnostics by means of CT, a tension banding of the ventral part of the acromion and a plate osteosynthesis of the dorsal part was performed. 7 weeks after injury neurolysis of nervus axillaris has been done. 4 months after accident the patient shows a satisfying functional result in the Constant score. Diagnostic, treatment and functional results after operative treatment of dislocated fractures of the acromion are shown and discussed.

Acromion↗

Genetic rat models of hypertension: relationship to human hypertension.

Experimental models of human disease are frequently used to investigate the pathophysiology of disease as well as the mechanisms of action of therapeutics. However, as long as models have been used there have been debates about the utility of experimental models and their applicability for human disease on the phenotypic and genomic level. The recent advances in molecular genetics and genomics have provided powerful tools to study the genetics of multifactorial diseases, such as hypertension. However, studies of such diseases in humans remain challenging in part due to lack of statistical power and genetic heterogeneity within patient populations. For hypertension, various rat models have been developed and used for the identification of susceptibility loci for genetic hypertension. With the advent of "comparative genomics," the application of genetic studies to both human and animal model systems allows for a new paradigm, where comparative genomics can be used to bridge between model utility and clinical relevance. This review discusses recent approaches in genetics to facilitate gene discovery for polygenic disorders with specific focus on how comparative mapping can be used to select target regions in the human genome for large-scale association studies and linkage disequilibrium testing in clinical populations.

Animals↗

Differential regulation of thrombospondin-1 and fibronectin by angiotensin II receptor subtypes in cultured endothelial cells.

OBJECTIVES: Angiotensin II (ANG II) can modulate cellular proliferation in various cell types via AT(1) and AT(2) receptors. In the present study, we investigated the effect of the angiotensin AT(1) and AT(2) receptors on DNA-synthesis as well as on the expression of the extracellular matrix (ECM) components, thrombospondin-1 (TSP-1) and fibronectin (FN) in endothelial cells (EC). METHODS: The experiments were performed in microvascular EC derived from rat heart (CEC) and macrovascular EC derived from bovine aorta (BAEC). The experiments were performed in cells of the second and third passage and the expression of AT(1) and AT(2) receptors was verified by binding studies, Northern analysis or RT-PCR. Quiescent rat CEC and BAEC were stimulated to proliferate by the addition of 25 ng/ml bFGF, while ANG II (10(-7) M) and the selective ANG II receptor antagonists, Losartan (10(-5) M) and PD123177 (10(-6) M) or the AT(2) agonist, CGP42112A (10(-7) M) were added 16 h later. RESULTS: ANG II induced a dose-dependent decrease of DNA-synthesis in BAEC measured by [3H]-thymidine incorporation. This inhibitory effect of ANG II was prevented by the addition of the AT(2) receptor antagonist PD123177 (10(-6) M), demonstrating, that the inhibition of DNA synthesis is mediated by the AT(2) receptor. In the presence of Losartan, stimulation of both, CEC and BAEC, with ANG II resulted in a marked increase of TSP-1 mRNA levels, which was maximal between 3 and 6 h in rat CEC and after 9 h in BAEC. In addition, TSP-1 was clearly induced by the AT(2) agonist CGP42112A. In contrast, blockade of the AT(2) receptor by the selective AT(2) antagonist, PD123177 (10(-6) M), resulted in a pronounced down regulation of FN mRNA 9 h after the stimulation. CONCLUSIONS: The present results suggest that the ANG II receptor subtype AT(2) mediates growth inhibition in macrovascular EC similar to what has been shown before in microvascular rat EC and that AT(2) receptors mediates remodeling of the endothelial ECM by upregulation of TSP-1 expression in both macro- and micro-vascular endothelial cells.

Angiotensin II↗

Effects of flue gas composition on the catalytic destruction of chlorinated aromatic compounds with a V-oxide catalyst.

When using catalytic flue gas cleaning, several flue gas compounds may influence oxidation reactions of hazardous volatile organic compounds, possibly leading to lower reaction rates and, thus, to an incomplete destruction. Experimental investigations were performed with regard to the influence of selected flue gas compounds, like hydrogen chloride, sulfur dioxide, oxygen, and water vapour, on the catalytic destruction behavior of chlorobenzenes under flue gas cleaning conditions of an incineration plant. For this purpose, a metal oxide catalyst was operated at different temperatures at a space velocity of 3600 h-1 in a laboratory-scale fixed bed reactor with model flue gases, and with real flue gases generated from the TAMARA waste incineration plant. The results obtained from the studies with model flue gas were analyzed with respect to reaction kinetics. These kinetics were applied for comparison with the experimental data gained in the real flue gas.

Catalysis↗

Automated construction of high-density comparative maps between rat, human, and mouse.

Animal models have been used primarily as surrogates for humans, having similar disease-based phenotypes. Genomic organization also tends to be conserved between species, leading to the generation of comparative genome maps. The emergence of radiation hybrid (RH) maps, coupled with the large numbers of available Expressed Sequence Tags (ESTs), has revolutionized the way comparative maps can be built. We used publicly available rat, mouse, and human data to identify genes and ESTs with interspecies sequence identity (homology), identified their UniGene relationships, and incorporated their RH map positions to build integrated comparative maps with >2100 homologous UniGenes mapped in more than one species (approximately 6% of all mammalian genes). The generation of these maps is iterative and labor intensive; therefore, we developed a series of computer tools (not described here) based on our algorithm that identifies anchors between species and produces printable and on-line clickable comparative maps that link to a wide variety of useful tools and databases. The maps were constructed using sequence-based comparisons, thus creating "hooks" for further sequence-based annotation of human, mouse, and rat sequences. Currently, this map enables investigators to link the physiology of the rat with the genetics of the mouse and the clinical significance of the human.

Algorithms↗

Determination of the bond length and binding energy of the helium dimer by diffraction from a transmission grating

A molecular beam consisting of small helium clusters is diffracted from a 100 nm period transmission grating. The relative dimer intensities have been measured out to the 7th order and are used to determine the reduction of the effective slit width resulting from the finite size of the dimer. From a theoretical analysis of the data which also takes into account the van der Waals interaction with the grating bars, the bond length (mean internuclear distance) and the binding energy are found to be = 52+/-4 A and |E(b)| = 1. 1+0.3/-0.2 mK.

Journal Article↗