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Biomedical subjects

A Schubert

Publications and source records attributed to A Schubert.

At least 19 recordsLinked to original sources
PubMed2005

Hemodynamic effects of spontaneous breathing in the post-operative period.

BACKGROUND: During mechanical ventilatory support, spontaneous breathing has been linked to improved hemodynamics. These findings may be explained by a decrease in intrathoracic pressure which may improve venous return to the heart. Such a mechanism should result in a dose-response relation between the amount of spontaneous breathing and an increase in the global end-diastolic volume (GEDV) and cardiac output (Q(t)). METHODS: To test this hypothesis, 15 patients were studied after major elective surgery during weaning from mechanical ventilation using bilevel positive airway pressure (BIPAP). BIPAP allows unrestricted spontaneous breathing during every phase of the respiratory cycle. Thus, ventilatory support was modified by changing the mechanical respiratory rate only, whereas inspiratory airway pressure and PEEP were kept constant. GEDV and Q(t) were measured by transpulmonary thermodilution. RESULTS: GEDV (P = 0.055), stroke volume (P = 0.027) and subsequently also Q(t) (P < 0.001) increased when spontaneous breathing increased. In contrast, no difference was observed for central venous pressure (P = 0.19). CONCLUSION: The beneficial hemodynamic effects of spontaneous breathing during mechanical ventilatory support can partially be explained by improved venous return to the heart which increases stroke volume and Q(t).

Adult↗
PubMed2004

Age associated changes of AGE-receptor expression: RAGE upregulation is associated with human heart dysfunction.

The binding of advanced glycation endproducts (AGEs) to their receptors is known to cause changes in cell function during normal ageing and is implicated in the pathogenesis of cardiovascular disease. In this study, expression of the AGE-receptor 3 (AGE-R3) and the receptor for AGEs (RAGE) was compared on the mRNA and protein level in the ageing human heart. Western blot and RT-PCR analysis of the AGE receptors from the cardiac auricles in senescent and adult patients was performed and compared with young controls. Whereas the expressions of AGE-R3 as well as RAGE protein were significantly upregulated in the senescent population, only the upregulation of RAGE is associated with reduced heart function. Therefore, our results support a pathophysiological function for RAGE in the ageing human heart.

Adult↗
PubMed2004

Early experiences with cervical disc prostheses.

UNLABELLED: The standard cervical disc surgery includes removal of the disc and fusion using an anterior approach. The loss of motion associated with fusion has prompted a search for other options. Early experiences and results after implantation of disc prostheses allowing for biomechanical motion of healthy discs are evaluated in this study. PATIENTS AND METHODS: 51 prostheses were implanted in 50 patients using an anterior approach. Follow-up ranged from one month to 14 months. RESULTS: The only significant complications were haemorrhages in two cases requiring surgical removal but otherwise all patients had an uneventful recovery. No infection or dislocation of the implants or formation of new spondylophytes have been noted yet. Resolution of pain and neurological disorders were excellent with a back-to-work rate of 80 % at three months after surgery. CONCLUSION: As the implantation of cervical disc prostheses carries no obvious risk higher than the risk of conventional anterior fusion, further analysis of its practicability and long-term outcome is recommended.

Adult↗
PubMed2002

Type I IgE receptor, interleukin 4 receptor and interleukin 13 polymorphisms in children with nephrotic syndrome.

Polymorphisms in the genes encoding the high-affinity IgE receptor, the interleukin 4 (IL4) receptor and IL13 can be associated with the development of asthma and allergy. Although several studies have described an association between atopy and idiopathic childhood nephrotic syndrome (NS), it is not clear whether this association is of a causal nature. Furthermore, it is not known whether these polymorphisms are associated with the clinical course of NS. A total of 84 children (52 male and 32 female; mean age 12.1 years) with NS were included in the present study. Of these, 78 could be classified as either atopic or non-atopic. Atopy was defined by elevated IgE levels (>100 k-units/l) and/or a positive history of atopy (33 of 78 patients). DNA was extracted from blood collected in EDTA tubes, and polymorphisms at positions 50 and 551 of the IL4 receptor, position 110 of IL13 and position 181 of the high-affinity IgE receptor were investigated by sequence-specific PCR or direct sequencing. Although we noted a strong tendency towards a higher allele frequency of polymorphisms in children with atopy and NS compared with children with NS but without atopy (IL4 50, 30% compared with 18%; IL4 551, 39% compared with 31%; IL13 110, 45% compared with 33%; IgE 181, 12% compared with 13%), these differences did not reach statistical significance. There were no differences in the frequency of polymorphisms between the different clinical courses of NS (frequent relapsers, steroid-dependent or steroid-resistant NS). We conclude that polymorphisms in the IL4 receptor, the high-affinity IgE receptor and IL13 do not seem to predict the clinical course of NS, despite the fact that serum IgE elevations are more frequent in patients with NS than in normal control subjects. The investigated polymorphisms may contribute to the IgE switch in patients with NS.

Adolescent↗
PubMed2001

Specific DNA binding and transactivation potential of recombinant, purified Stat5.

The signal transducers and activators of transcriptions (Stats) are central mediators of cytokine responses especially in hematopoietic cells. The detailed molecular mechanisms of Stat activation, particularly the role of post-translational modifications and co-operation with cellular transcription factors are subject to intense investigation. The phosphorylation of a tyrosine residue in the carboxyl terminal domain is a common characteristic for the biologically active state of all known Stats. We studied the biological potential of purified recombinant murine Stat5a and Stat5b. These proteins were expressed in Sf9 insect cells upon infection with Stat5 encoding baculoviruses. We also obtained the tyrosine phosphorylated, activated forms of the Stat5 proteins by expressing the tyrosine kinase Janus kinase2 (Jak) in the same cells through co-infection with a kinase encoding virus. After purification, only the tyrosine phosphorylated form was able to bind specifically in vitro to the Stat5 DNA response element. This activated form of Stat5 is also able to support specific cell free in vitro transcription of a gene with a Stat5 response element in its promoter region. The recombinant purified Stat5 proteins were treated with the tyrosine specific protein phosphatase or with potato acidic phosphatase, which removes phosphate groups from serine and tyrosine residues. Phosphatase treatment resulted in the loss of specific DNA binding ability. This property could be restored by an in vitro reaction with recombinant, purified EGF or PDGF receptor kinases. Tyrosine rephosphorylation in vitro also restored the transactivation potential of Stat5. This modification is, therefore, a sufficient prerequisite for transcriptional induction by Stat5.

Animals↗
PubMed2001

Regression of left ventricular hypertrophy after surgical therapy for aortic stenosis is associated with changes in extracellular matrix gene expression.

BACKGROUND: Regression of left ventricular hypertrophy (LVH) after surgical correction for aortic stenosis is not fully understood on the molecular level. The aim of this study was to examine whether there is an association between LVH regression and extracellular matrix (ECM) gene expression. METHODS AND RESULTS: A standard model of controlled LVH induction by supracoronary banding (A=baseline) was applied in 44 growing sheep (age, 6 to 8 months). Surgical correction to release the pressure gradient was performed 8.3+/-1 months later (B). The animals were killed after another 10.1+/-2 months (C). At all time points, hemodynamic evaluations and quantitative analysis of mRNA and protein expression for matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) was performed. Left ventricular mass index was 82+/-21 (A) versus 150+/-33 (B), P<0.01, and 78+/-18 g/m(2) (C), P<0.01. Left ventricular function and cardiac index remained stable. Myocardial fiber diameter index was 9.1+/-1.2 (A) versus 12.3+/-1.4 (B), P<0.01, and 8.4+/-1.3 micrometer/m(2) (C), P<0.01. In parallel to the development of LVH at B, gene expression was increased significantly for MMP-1, MMP-2, MMP-3, and MMP-9 and for TIMP-1 and TIMP-2 and decreased significantly for TIMP-3. After surgical correction (C), there was a complete regression of gene expression to baseline measures. CONCLUSIONS: Controlled induction of compensated LVH leads to significant increase in ECM gene expression. The regression of LVH after surgical therapy is associated with complete regression of ECM gene expression. However, no cause-and-effect relation could be demonstrated.

Animals↗
PubMed2001

Differentially expressed genes in L6 rat skeletal muscle myoblasts after incubation with inflammatory cytokines.

OBJECTIVE: The mechanism underlying exercise intolerance in chronic heart failure is still unclear. An increased concentration of inflammatory cytokines could be detected in the serum of patients with chronic heart failure (CHF) exhibiting a correlation with the severity of the disease. The variety of molecular alterations triggered by these cytokines in the skeletal muscle is almost unknown. The study was designed to analyze the differential gene expression in skeletal muscle myoblasts after stimulation with inflammatory cytokines. METHODS: L6 rat skeletal muscle myoblasts were incubated for 24 h with a combination of IL-1beta/IFN-gamma and the differential gene expression profile was determined by a PCR-based subtractive hybridization method. RESULTS: Out of 173 picked clones 141 different sequences could be identified. By comparison with Genebank, the identity of 73 genes (51.7%) could be confirmed, whereas the rest did not show a homology to any known gene. Some of the identified genes are known to be altered in patients with CHF. CONCLUSION: In summary, the results of this study provide information about changes in gene expression after exposure of skeletal muscle cells to inflammatory cytokines. This information may yield a new gene pool, worthwhile to be analyzed in skeletal muscle of patients with chronic heart failure.

Animals↗
PubMed2001

The roles of MHC class II, CD40, and B7 costimulation in CTL induction by plasmid DNA.

DNA-based vaccines generate potent CTL responses. The mechanism of T cell stimulation has been attributed to plasmid-transfected dendritic cells. These cells have also been shown to express plasmid-encoded proteins and to become activated by surface marker up-regulation. However, the increased surface expression of CD40 and B7 on these dendritic cells is insufficient to overcome the need for MHC class II-restricted CD4(+) T cell help in the priming of a CTL response. In this study, MHC class II(-/-) mice were unable to generate a CTL response following DNA immunization. This deficit in CTL stimulation by MHC class II-deficient mice was only modestly restored with CD40-activating Ab, suggesting that there were other elements provided by MHC class II-restricted T cell help for CTL induction. CTL activity was also augmented by coinjection with a vector encoding the costimulatory ligand B7.1, but not B7.2. These data indicate that dendritic cells in plasmid DNA-injected mice require conditioning signals from MHC class II-restricted T cells that are both CD40 dependent and independent and that there are different roles for costimulatory molecules that may be involved in inducing optimal CTL activity.

Adjuvants, Immunologic↗
PubMed2001

Extracellular matrix gene expression correlates to left ventricular mass index after surgical induction of left ventricular hypertrophy.

The cardiac extracellular matrix (ECM) is a dynamic entity maintaining the structural and functional properties of the myocardium. Little is known about alterations in ECM regulation during controlled induction of compensated left ventricular hypertrophy (LVH) using experimental aortic stenosis. Fifteen growing sheep received supra-coronary banding at an age of 7 +/- 1 months whereas 10 age-matched sheep served as the control group (C). Explantation of the hearts was performed 8.3 +/- 1 months after banding. Gene sequences for sheep matrix metalloproteinase (MMP)-1,-2,-3,-9 and tissue inhibitors (TIMP)-1,-2,-3 were isolated and cloned. Then mRNA and protein gene expression analyses were performed. Concentric LVH with no evidence of heart failure was diagnosed at explantation. Left ventricular mass index (LVMI) was 150 +/- 33 g/m2 (LVH) versus 88 +/- 23 (C) and 82 +/- 21 (baseline) (p < 0.01 versus LVH). Parallel to LVH there was a significant increase in mRNA and protein expression for MMP-1,-2,-3, -9 and for TIMP-1,-2 whereas there was a significant decrease in TIMP-3 gene expression. A close correlation between changes in LVMI and ECM gene expression was found. Compensated LVH goes along with a significant modification of MMP and TIMP gene expression. Alterations in ECM gene expression may be part of the adaptive process during left ventricular remodeling.

Animals↗
PubMed2001

Single molecule spectroscopy on the light-harvesting complex II of higher plants.

Spectroscopic and polarization properties of single light-harvesting complexes of higher plants (LHC-II) were studied at both room temperature and T < 5 K. Monomeric complexes emit roughly linearly polarized fluorescence light thus indicating the existence of only one emitting state. Most probably this observation is explained by efficient triplet quenching restricted to one chlorophyll a (Chl a) molecule or by rather irreversible energy transfer within the pool of Chl a molecules. LHC-II complexes in the trimeric (native) arrangement bleach in a number of steps, suggesting localization of excitations within the monomeric subunits. Interpretation of the fluorescence polarization properties of trimers requires the assumption of transition dipole moments tilted out of the symmetry plane of the complex. Low-temperature fluorescence emission of trimers is characterized by several narrow spectral lines. Even at lowest excitation intensities, we observed considerable spectral diffusion most probably due to low temperature protein dynamics. These results also indicate weak interaction between Chls belonging to different monomeric subunits within the trimer thus leading to a localization of excitations within the monomer. The experimental results demonstrate the feasibility of polarization sensitive studies on single LHC-II complexes and suggest an application for determination of the Chl transition-dipole moment orientations, a key issue in understanding the structure-function relationships.

Fluorescence Polarization↗
PubMed2001

[Remarks to statement from the rate of cause of death due to ischaemic heart diseases].

The rate of cause of death due to IHD ('ischaemic heart diseases') represents a terminal occurrence of the arteriosclerotic basic disease. lts extent is determined by the incidence of cardiovascular diseases, prevalence and duration of sickness. The relative frequency of falling ill as well as the reflection of the risk of falling ill and the extent of the population fallen ill are not known at all or only very insufficiently. Thus the question cannot be answered how the risk to fall ill with the coronary heart disease must be considered in view of the high mortality rate IHD of the population in the total mortality of the population. There are recognizable influences on the rate of cause of death due to IHD, such as the duration of sickness, the increasing average life expectancy and the procedure of coding death certificates and the selection of the basic disease. So the abrupt increase of the infarct mortality after the turn in the new federal states, as well as in Mecklenburg-Western Pomerania is to be attributed to the adoption to the coding procedure. The increasing trend of the mortality rate of IHD up to 1995 in Mecklenburg-Western Pomeranian infers an individual shortening of the sickness of existing coronary heart diseases among the population. After this temporary increase of infarct mortality the decrease of this figure suggests prolongation of the duration of sickness. The rate of cause of death from 'ischaemic heart diseases' also represents a terminal occurrence in life. The development of specific mortality in advanced age leads to the observation that the emphasis within the cause of death structure among those classifications of the elderly at an extremely advanced age, gradually shifts towards mortality caused by ischaemic heart disease. From the accompanying decreasing trend of mortality from acute coronary events in the younger and medium age classes a decrease in the total mortality can be concluded. Even the search for diagnosis during post mortems is reflected in the cause of death statistics, which can be evidenced on the basis of comparisons made between the figures of death from 'ischaemic heart diseases' and from 'senility, other symptoms, and imprecisely described conditions'. The difference between the original federal states and the new federal states of Eastern Germany, as also in the Federal State of Mecklenburg-Western Pomerania is obvious. Summing up, it can therefore be said, that the cause of death rate from 'ischaemic heart diseases' is only of limited significance as regards the hazards from the underlying arteriosclerotic disease of the blood vessels. lt can only be assessed in connection with the age structure of the population and the structure of all causes of death. The validity of the cause of death from 'ischaemic heart diseases' is therefore not very great in reporting practice.

Adult↗
PubMed2001

Hemoglobin and methemoglobin concentrations after large-dose infusions of diaspirin cross-linked hemoglobin.

UNLABELLED: Diaspirin cross-linked hemoglobin (DCLHb) solution is a purified human hemoglobin product chemically stabilized to deliver oxygen to tissues. We determined the peak plasma hemoglobin concentration and assessed changes in methemoglobin concentration after the infusion of 1 g/kg DCLHb in large blood loss surgical patients. This prospective, randomized study included 26 surgical patients who were either infused with up to three 250-mL units of 10% DCLHb or transfused with up to three units of packed red blood cells during the study infusion period. Serial plasma hemoglobin, plasma methemoglobin, and whole blood methemoglobin levels were measured before and at intervals up to 48 h after the study infusion period. Plasma hemoglobin and blood methemoglobin concentrations increased during the infusion of DCLHb. The plasma hemoglobin values in the DCLHb group continued to increase during each of the infusion periods to reach a peak plasma concentration of 1450 +/- 176 mg/dL. The fraction of whole blood methemoglobin increased from 0.84 +/- 0.77% at baseline to 4.08 +/- 1.36%. With a median DCLHb dose of 936 mg/kg (range 658-1500 mg/kg), the harmonic mean half-life was 10 h, and the increased whole blood methemoglobin reached a range not associated with complications. IMPLICATIONS: The dose of diaspirin cross-linked hemoglobin (DCLHb) (936 +/- 276 mg/kg) used in this study was one of the largest reported in humans to date. The DCLHb mean half-life was 10 h. The half-life observed was 2-4 times that found at smaller doses in previous studies. Whole blood methemoglobin fraction increased during DCLHb infusion but did not reach a range associated with complications.

Aspirin↗
PubMed2001

Identification and molecular analysis of PcsB, a protein required for cell wall separation of group B streptococcus.

Group B streptococcus (GBS) is the leading cause of bacterial sepsis and meningitis in neonates. N-terminal sequencing of major proteins in the culture supernatant of a clinical isolate of GBS identified a protein of about 50 kDa which could be detected in all of 27 clinical isolates tested. The corresponding gene, designated pcsB, was isolated from a GBS cosmid library and subsequently sequenced. The deduced PcsB polypeptide consists of 447 amino acid residues (M(r), 46,754), carries a potential N-terminal signal peptide sequence of 25 amino acids, and shows significant similarity to open reading frames of unknown function from different organisms and to the murein hydrolase P45 from Listeria monocytogenes. Northern blot analysis revealed a monocistronic transcriptional organization for pcsB in GBS. Insertional inactivation of pcsB in the genome of GBS resulted in mutant strain Sep1 exhibiting a drastically reduced growth rate compared to the parental GBS strain and showing an increased susceptibility to osmotic pressure and to various antibiotics. Electron microscopic analysis of GBS mutant Sep1 revealed growth in clumps, cell separation in several planes, and multiple division septa within single cells. These data suggest a pivotal role of PcsB for cell division and antibiotic tolerance of GBS.

Anti-Bacterial Agents↗
PubMed2001

Evidence of a current and lasting national anesthesia personnel shortfall: scope and implications.

OBJECTIVES: To prove the existence of a current anesthesiologist shortage, and to project the balance of labor supply and demand in the future. METHODS: To quantify the current supply we used published health personnel data from federal agencies and the American Medical Association, as well as membership data from the American Society of Anesthesiologists. We estimated anesthesiologist supply in 2001 based on the number of graduating residents and fellows, taking into account the loss of a portion of graduating residents due to temporary visa status. We assumed that neither a shortage nor an oversupply existed in 1994 and that demand for anesthesiologists was approximated by the number of surgical procedures reported by federal agencies. In modeling future supply and demand for anesthesiologists, we assumed that the current health care policy and economic climates will continue. We extrapolated demand using 1.5% to 3% yearly growth rates based on a synthesis of recent and projected procedure growth rates, procedure rates for the elderly, and population aging trends. We estimated the supply for 2001 through 2003 based on the current resident cohort modified by their projected graduation rate. Accounting for attrition during residency and the effect of fellowship training, we assumed that after 2003 the number of American medical graduates will initially increase by 15% annually and that the number of international medical graduates will decrease to a stable level of 500 trained each year. We assumed an average retirement age of 65 years. RESULTS: Our model suggests that there is currently a 3.6% to 10.9% shortage of anesthesiologists nationwide, depending on the assumption of a 2% or 3% increase in annual demand since 1994 and a constant pattern of work distribution by anesthesia providers. This amounts to approximately 1200 to 3800 anesthesiologists. If projected demand continues to increase at the rate of 1.5% to 2% annually, the shortfall will amount to 2.6% to 12.0% of the labor supply by 2005, representing a deficit of 1000 to 4500 anesthesiologists. By 2010, this shortfall is projected to disappear or continue to amount to about 11% of the anesthesiologist supply, depending on the assumptions about the rate of demand for anesthesiologists. Compared with the expected graduating class of 1100 anesthesiology residents in 2001, our model calls for nearly 1600 graduates by 2005 and 2000 by 2010. CONCLUSION: A substantive shortfall of anesthesia personnel exists in 2001 and will continue for years to come, fueled by changing population demographics, population health trends, and accelerating advancements in surgical technology, as well as growth in ambulatory and office-based surgery, pain medicine, and intensive care. In addition to focusing on financing, national health policy needs to address the adequacy of health care personnel resources for an aging population, in particular when they require surgery, are afflicted by painful conditions, or become critically ill.

Anesthesiology↗
PubMed2000

Shear stress-dependent regulation of the human beta-tubulin folding cofactor D gene.

The flowing blood generates shear stress at the endothelial cell surface. The endothelial cells modify their phenotype by alterations in gene expression in response to different levels of fluid shear stress. To identify genes involved in this process, human umbilical vein endothelial cells were exposed to laminar shear stress (venous or arterial levels) in a cone-and-plate apparatus for 24 hours. Using the method of RNA arbitrarily primed polymerase chain reaction, we cloned a polymerase chain reaction fragment representing an mRNA species downregulated by arterial compared with venous shear stress (shear stress downregulated gene-1, SSD-1). According to Northern blot analysis, corresponding SSD-1 cDNA clones revealed a similar, time-dependent downregulation after 24 hours of arterial shear stress compared with venous shear stress or static controls. Three SSD-1 mRNA species of 2.8, 4.1, and 4.6 kb were expressed in a tissue-specific manner. The encoded amino acid sequence of the human endothelial SSD-1 isoform (4.1-kb mRNA species) revealed 80.4% identity and 90.9% homology to the bovine ss-tubulin folding cofactor D (tfcD) gene. Downregulation of tfcD mRNA expression by shear stress was defined at the level of transcription by nuclear run-on assays. The tfcD protein was downregulated by arterial shear stress. The shear stress-dependent downregulation of tfcD mRNA and protein was attenuated by the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester. Furthermore, the NO donor DETA-NO downregulated tfcD mRNA. Because tfcD was shown to be a microtubule-destabilizing protein, our data suggest a shear stress-dependent regulation of the microtubular dynamics in human endothelial cells.

Arteries↗
PubMed2000

Regulation of the endothelin system by shear stress in human endothelial cells.

In this study, the effect of shear stress on the expression of genes of the human endothelin-1 system was examined. Primary cultures of human umbilical vein endothelial cells (HUVEC) were exposed to laminar shear stress of 1, 15 or 30 dyn cm-2 (i.e. 0.1, 1.5 or 3 N m-2) (venous and two different arterial levels of shear stress) in a cone-and-plate viscometer. Laminar shear stress transiently upregulates preproendothelin-1 (ppET-1) mRNA, reaching its maximum after 30 min (approx 1.7-fold increase). In contrast, long-term application of shear stress (24 h) causes downregulation of ppET-1 mRNA in a dose-dependent manner. Arterial levels of shear stress result in downregulation of endothelin-converting enzyme-1 isoform ECE-1a (predominating in HUVEC) to 36.2 +/- 8.5 %, and isoform ECE-1b mRNA to 72.3 +/- 1.9 % of static control level. The endothelin-1 (ET-1) release is downregulated by laminar shear stress in a dose-dependent manner. This downregulation of ppET-1 mRNA and ET-1 release is not affected by inhibition of protein kinase C (PKC), or tyrosine kinase. Inhibition of endothelial NO synthase (L-NAME, 500 microm) prevents downregulation of ppET-1 mRNA by shear stress. In contrast, increasing degrees of long-term shear stress upregulate endothelin receptor type B (ETB) mRNA by a NO- and PKC-, but not tyrosine kinase-dependent mechanism. In conclusion, our data suggest the downregulation of human endothelin synthesis, and an upregulation of the ETB receptor by long-term arterial laminar shear stress. These effects might contribute to the vasoprotective and anti-arteriosclerotic potential of arterial laminar shear stress.

Aspartic Acid Endopeptidases↗