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Biomedical subjects

M Schweiger

Publications and source records attributed to M Schweiger.

At least 19 recordsLinked to original sources
PubMed2006

Non-neuronal acetylcholine and choline acetyltransferase in oviductal epithelial cells of cyclic and pregnant pigs.

Certain female reproductive tissues are known to express the non-neuronal cholinergic system. Using different experimental approaches, we tested the hypothesis that acetylcholine (ACh) in the porcine oviduct may also be derived from non-neuronal structures. Immunohistochemistry was performed to detect acetylcholine synthesizing enzyme choline acetyltransferase (ChAT) in different segments of the oviduct of cyclic and pregnant sows. Immunohistochemical experiments revealed strong immunoexpression of ChAT in the entire oviductal epithelium at metoestrus. Thereby, a particular pronounced staining was found in the supranuclear region of almost all epithelial cells. Immunostaining of ChAT decreased markedly during dioestrus and prooestrus stages, respectively. At prooestrus, ChAT immunoreactivity was confined to ciliated cells. Furthermore, we found elevated level of staining intensity of ChAT in the pregnant oviduct at day 13. Using the same ChAT antibody for Western blot analyses, we detected immunoreactive bands of MW 69,000 and 46,000 mainly in ampulla, while MW 58,000 and 30,000 forms were present mainly in infundibulum and isthmus. Furthermore ACh was detected by HPLC and fluorimetric methods in oviductal epithelium. In conclusion, we show expression of ChAT in oviductal epithelial cells at different stages of the oestrus cycle and pregnancy, indicating that these cells can synthesize ACh in a cycle-dependent manner. These results suggest as yet unexplored roles of epithelial ACh in the oviduct.

Acetylcholine↗
PubMed2006

Reconstructing absorption and diffusion shape profiles in optical tomography by a level set technique.

A shape reconstruction algorithm for optical tomography is introduced that uses a level-set formulation for the shapes. Evolution laws based on gradient directions for a cost functional are derived for two different level-set functions, one describing the absorption and one the diffusion parameter, as well as for the parameter values inside these shapes. Numerical experiments are presented in 2D that show that the new method is able to simultaneously recover shapes and contrast values of absorbing and scattering objects embedded in a moderately heterogeneous background medium from simulated noisy data.

Absorption↗
PubMed2005

Three-dimensional whole-head optical tomography of passive motor evoked responses in the neonate.

Optical tomography has been used to reconstruct three-dimensional images of the entire neonatal head during motor evoked responses. Data were successfully acquired during passive movement of each arm on four out of six infants examined, from which eight sets of bilateral images of hemodynamic parameters were reconstructed. Six out of the eight images showed the largest change in total hemoglobin in the region of the contralateral motor cortex. The mean distance between the peak response in the image and the estimated position of the contralateral motor cortex was 10.8 mm. These results suggest that optical tomography may provide an appropriate technique for non-invasive cot-side imaging of brain function.

Algorithms↗
PubMed2005

The normal cellular prion protein (PrPc) is strongly expressed in bovine endocrine pancreas.

Expression of the cellular prion protein (PrP(c)) has been shown to be crucial for the development of transmissible spongiform encephalopathies and for the accumulation of the disease-associated conformer (PrP(sc)) in the brain and other tissues. One of the emerging hypotheses is that the conversion phenomenon could take place at the site where the infectious agent meets PrP(c). In this work we have studied whether PrP(c), a protein found predominantly in neurons, could also exist in pancreatic endocrine cells since neuroectoderm-derived cells and pancreatic islet cells share a large number of similarities. For this purpose we have examined the expression of PrP(c) in a series of fetal and postnatal bovine pancreatic tissue by immunohistochemistry and RT-PCR. Using immunostained serial sections and specific antibodies against bovine PrP(c), insulin, glucagon, somatostatin, chromogranin A and chromogranin B we found that PrP(c) is highly expressed in all endocrine cells of fetal and adult pancreatic islets with a particular strong expression in A-cells. Moreover it became evident that the PrP(c) gene-neighbour chromogranin B as well as chromogranin A are coexpressed together with PrP(c). The selective expression of PrP(c) in the bovine endocrine pancreas is of particular importance regarding possible iatrogenic transmission routes and demonstrates also that bovine pancreatic islet cells could represent an interesting model to study the control of PrP-gene expression.

Animals↗
PubMed2005

Late acute cardiac allograft rejection: new therapeutic options?

BACKGROUND: Late acute cellular rejection is associated with decreased survival and the development of CAV. Among new immunosuppressive drugs introduced into clinical practice, everolimus, has been shown to be safe in cardiac transplantation. We report our experience with everolimus in heart transplant recipients who developed late acute cellular cardiac rejection. METHODS: Patients with a history of previous rejection episodes who experienced cardiac rejection were switched to an everolimus, cyclosporine, and steroid immunosuppressive regimen. All patients had already received statins and antihypertensive medications. Everolimus, cyclosporine trough levels, and laboratory values were controlled monthly. Drug administration was adapted to an everolimus trough level between 3 and 8 ng/mL, mean maintenance dosage was 0.25 to 1.5 mg twice a day. Death, safety, side effects, biopsy-proven acute rejection episodes, laboratory values, and blood levels were evaluated retrospectively. RESULTS: Four cardiac allograft recipients (two male, two female), at a median of 1473.25 days post-orthotopic heart transplantation (oHTx) (range = 65 to 3045), received 1 to 1.5 mg everolimus per day. Over a follow-up period of at least 2 month (range = 2 to 10) the mortality was 0%. The drug was well tolerated; no acute cellular rejection greater than grade 1a (ISHLT grading) was observed after 2 months. In one patient increased cholesterol values and in two others, elevated triglyceride levels were seen, but were controlled with increased statin therapy. No obvious increased creatinine values were seen with everolimus. CONCLUSION: In conclusion, conversion to an everolimus-based immunosuppressive regimen after late cardiac rejection is safe and effective; no major side effects were observed.

Acute Disease↗
PubMed2004

Improving the rate of organ donation.

BACKGROUND: Organ shortage is a major problem in transplantation. Many potential donors are still lost due to a lack of information and communication. Many transplantation centers report a major donor increase after introducing new donor policies. The aim of this study was to evaluate in retrospective fashion a new donor policy in our region. METHODS: For the past 10 years all reported donors from intensive care units (ICUs) in our region were evaluated. Our new policy had 2 main steps: accepting more marginal grafts and using a transplantation representative. The goal was the improved communication with ICUs to support physicians involved in donor care. A public information program was also implemented. RESULTS: In the first year, numbers of donors obviously improved (+60.5%) and remained stable the following year. The mean donor age increased to 41.56 years. The donor pool showed mainly an improved kidney-donation rate (+53%) with also an increase in multiorgan donation (+37%). One year posttransplantation survival was not negatively influenced by this donor pool. As expected, transplantation activities increased notably, particularly liver transplantation (+31.11%) but also kidney transplantation (+26.73%). DISCUSSION: Many donors are lost because physicians in charge of brain dead patients are not fully informed about modified donation criteria. The reason for this is a lack of information and communication by transplantation units. Improved surgical techniques and better preoperative, intraoperative, and postoperative treatment have yielded better results with marginal grafts. Immediate graft function in recipients of suboptimal grafts may be delayed, but without a significantly negative impact on patient and graft survival. Because the age of organ recipients is steadily increasing with fewer contraindications for transplants, more organs will be needed.

Brain Death↗
PubMed2004

Nontuberculous mycobacteria in non-HIV patients: epidemiology, treatment and response.

Recent international guidelines published in 1997 and 1999 have proposed diagnostic and treatment criteria for disease caused by nontuberculous mycobacteria (NTM). In this paper, the epidemiological data, diagnostic criteria, treatment regimens and outcomes from 117 HIV-negative patients who had a positive culture for NTM between 1995-1999 are reviewed. The authors wished to identify factors associated with improved outcome in these patients. A total of 71 patients were believed to have a clinical disease caused by NTM, as defined by international criteria. A total of 72% patients were found to have had pulmonary disease. There was a rise in infections between 1995-1999, with a peak in infections in 1997. The most striking rise was in Mycobacterium avium intracellulare complex infections (1995: 33% infections; 1996: 36% infections; 1997: 41% infections; 1998: 61% infections; 1999: 57% infections). There was a link between deprivation and number of positive NTM isolates (34.4% isolates occurred in the areas of lowest Carstairs deprivation index versus 20.6% isolates from areas of least deprivation). There was a significant association between appropriate therapy, defined by American Thoracic Society and British Thoracic Society guidelines, and successful outcome (74%) in contrast to those who received inappropriate treatment prior to the publication of these guidelines. Nontuberculous mycobacteria infections remain a significant problem in non-HIV patients. Adherence to published guidelines may improve patient outcomes.

Adult↗
PubMed2003

A method for generating patient-specific finite element meshes for head modelling.

Finite element modelling of fields within the body, whether electrical or optical, requires knowledge of the geometry of the object being examined. It can be clinically impractical to obtain accurate surface information for individual patients, although a limited set of measurements such as the locations of sensors attached to the body, can be acquired more readily. In this paper, we describe how a generic surface taken from an adult head is warped to fit points measured on a neonatal head surface to provide a new, individual surface from which a finite element mesh was generated. Simulations show that data generated from this mesh and from the original neonatal head surface are similar to within experimental errors. However, data generated from a mesh of the best fit sphere were significantly different from data generated from the original neonatal head surface.

Adult↗
PubMed2003

Colocalization of chromogranin A and inositol 1,4,5-trisphosphate receptor in ciliated cells of the bovine oviduct.

Previous investigations of the expression of chromogranin A (CgA) have been performed primarily in neuroendocrine tissues containing amine and peptide secretory vesicles. More recently it has been shown that CgA, as a high capacity Ca2+ storage protein, interacts with the inositol 1,4,5-trisphosphate receptor/Ca2+ channel (InsP3R) which has been found to be selectively localized in oviductal cells of the mouse. To examine a possible role of this coupling in the Ca2+-dependent ciliary movement, we investigated the topographical and cellular distribution of cells positive for CgA and inositol 1,4,5-trisphosphate receptor type 2 (InsP3R2) in the bovine oviduct at different stages of the oestrous cycle. Using immunohistochemical techniques on paraffin-embedded tissue we have successfully shown that CgA is selectively expressed in ciliated cells of the bovine oviduct. The labelled cells show intense positive staining in the apical surface area in close vicinity to the ciliary apparatus. CgA-positive ciliated cells are most frequently observed at dioestrous while a lower number appears at oestrous. Additionally, secretory and intraepithelial neuroendocrine cells consistently do not stain with the CgA-antiserum. We then investigated whether the reported expression of the InsP3R in oviductal cells of the mouse corresponds to the expression of the InsP3R in bovine oviductal cells. Using a polyclonal antibody to the type 2 InsP3R, we found that the receptor is also selectively expressed in a similar matter to CgA in the apical cytoplasm of ciliated cells. This is the first morphological demonstration of the colocalization of CgA and InsP3R in epithelial ciliated cells of the bovine oviduct. Our results suggest that CgA and InsP3R could be involved in controlling the ciliary activity of oviductal epithelial cells.

Adrenal Glands↗
PubMed2001

Accelerated telomere shortening in Fanconi anemia fibroblasts--a longitudinal study.

Fanconi anemia (FA) is a fatal inherited disease displaying chromosomal instability, disturbances in oxygen metabolism and a high burden of intracellular radical oxygen species. Oxygen radicals can damage DNA including telomeric regions. Insufficient repair results in single strand breaks that can induce accelerated telomere shortening. In a longitudinal study we demonstrate that telomeric DNA is continuously lost at a higher rate in FA fibroblasts compared to healthy controls. Furthermore, we show that this loss is caused rather by an increased shortening per cell division in regularly replicating cells than by apoptosis.

Adolescent↗
PubMed2001

Three-dimensional time-resolved optical tomography of a conical breast phantom.

A 32-channel time-resolved imaging device for medical optical tomography has been employed to evaluate a scheme for imaging the human female breast. The fully automated instrument and the reconstruction procedure have been tested on a conical phantom with tissue-equivalent optical properties. The imaging protocol has been designed to obviate compression of the breast and the need for coupling fluids. Images are generated from experimental data with an iterative reconstruction algorithm that employs a three-dimensional (3D) finite-element diffusion-based forward model. Embedded regions with twice the background optical properties are revealed in separate 3D absorption and scattering images of the phantom. The implications for 3D time-resolved optical tomography of the breast are discussed.

Journal Article↗
PubMed2001

Regulation of glutamate dehydrogenase by reversible ADP-ribosylation in mitochondria.

Mitochondrial ADP-ribosylation leads to modification of two proteins of approximately 26 and 53 kDA: The nature of these proteins and, hence, the physiological consequences of their modification have remained unknown. Here, a 55 kDa protein, glutamate dehydrogenase (GDH), was established as a specific acceptor for enzymatic, cysteine-specific ADP-ribosylation in mitochondria. The modified protein was isolated from the mitochondrial preparation and identified as GDH by N-terminal sequencing and mass spectrometric analyses of tryptic digests. Incubation of human hepatoma cells with [14C]adenine demonstrated the occurrence of the modification in vivo. Purified GDH was ADP-ribosylated in a cysteine residue in the presence of the mitochondrial activity that transferred the ADP-ribose from NAD+ onto the acceptor site. ADP- ribosylation of GDH led to substantial inhibition of its catalytic activity. The stoichiometry between incorporated ADP-ribose and GDH subunits suggests that modification of one subunit per catalytically active homohexamer causes the inactivation of the enzyme. Isolated, ADP-ribosylated GDH was reactivated by an Mg2+-dependent mitochondrial ADP-ribosylcysteine hydrolase. GDH, a highly regulated enzyme, is the first mitochondrial protein identified whose activity may be modulated by ADP-ribosylation.

Adenosine Diphosphate↗
PubMed2001

Characterization of recombinant human nicotinamide mononucleotide adenylyl transferase (NMNAT), a nuclear enzyme essential for NAD synthesis.

Nicotinamide mononucleotide adenylyl transferase (NMNAT) is an essential enzyme in all organisms, because it catalyzes a key step of NAD synthesis. However, little is known about the structure and regulation of this enzyme. In this study we established the primary structure of human NMNAT. The human sequence represents the first report of the primary structure of this enzyme for an organism higher than yeast. The enzyme was purified from human placenta and internal peptide sequences determined. Analysis of human DNA sequence data then permitted the cloning of a cDNA encoding this enzyme. Recombinant NMNAT exhibited catalytic properties similar to the originally purified enzyme. Human NMNAT (molecular weight 31932) consists of 279 amino acids and exhibits substantial structural differences to the enzymes from lower organisms. A putative nuclear localization signal was confirmed by immunofluorescence studies. NMNAT strongly inhibited recombinant human poly(ADP-ribose) polymerase 1, however, NMNAT was not modified by poly(ADP-ribose). NMNAT appears to be a substrate of nuclear kinases and contains at least three potential phosphorylation sites. Endogenous and recombinant NMNAT were phosphorylated in nuclear extracts in the presence of [gamma-(32)P]ATP. We propose that NMNAT's activity or interaction with nuclear proteins are likely to be modulated by phosphorylation.

Amino Acid Sequence↗
PubMed2001

Characteristics and clinical relevance of chronic anemia in adult heart transplant recipients.

BACKGROUND: Mild chronic anemia following heart transplantation (HTX), with hemoglobin (Hb) values of 10-14 g/dL in men and 10-12 g/dL in women, is frequent. It has continued to be of uncertain etiology yet clinical relevance. Nonetheless, therapeutic immunosuppression has been regarded as a major cause of chronic anemia in HTX patients. METHODS: Sixty outpatients were observed over a period of 5 yr after HTX. Laboratory values related to anemia such as Hb, erythropoietin (EPO), ferritin, transferrin, iron, and vitamin levels were obtained and analyzed monthly. Patients were divided into two groups retrospectively. Patients with persistent anemia for more than 1 yr were compared with non-anemic patients. RESULTS: Forty-three (72%) of the 60 patients were anemic. Anemia was normochromic, normocytic, and slightly anisocytic. Anemic and non-anemic patients showed EPO levels within the expected range as defined by Erslev (Erythropoietin. N Engl J Med 1991: 324: 1339). Reticulocyte counts were found to be normal in all patients. Iron deficiency and deficiency of vitamin B12 or folic acid were not observed. Patients with persistent anemia showed a significantly shorter survival period than non-anemic patients (p<0.02). CONCLUSIONS: Mild anemia following HTX shows the same characteristics as anemia in chronic diseases. Persisting mild anemia used to be associated with a shorter life expectancy. There is no evidence that standard immunosuppression causes anemia.

Anemia↗
PubMed2001

Abciximab and early adjunctive percutaneous coronary intervention are associated with improved ST-segment resolution after thrombolysis: Observations from the TIMI 14 Trial.

BACKGROUND: Percutaneous coronary intervention (PCI) improves clinical outcomes in selected patients with failed thrombolysis but has not been proven to benefit patients who achieve a patent infarct-related artery. Even after successful epicardial reperfusion, myocardial perfusion may be inadequate. We sought to evaluate whether a strategy that uses a reperfusion regimen containing abciximab and a reduced-dose thrombolytic agent (combination therapy), followed by early adjunctive PCI, would result in improved myocardial perfusion, as assessed by ST-segment resolution. METHODS: ST resolution from 90 to 180 minutes after therapy was calculated for all 410 patients from the TIMI 14 trial who had evaluable electrocardiograms at both time points and who were treated with alteplase or reteplase. Patients were grouped according to whether they were treated with combination therapy or full-dose thrombolytic agent alone and whether they underwent PCI between the 90- and 180-minute electrocardiographic measurements. RESULTS: Among 105 patients who underwent adjunctive PCI between 90 and 180 minutes, mean ST resolution from 90 to 180 minutes was significantly greater in those who had received combination therapy versus those who had received full-dose thrombolytic alone (54% vs 8%; P =.002). Among 241 patients with TIMI grade 3 flow in the infarct-related artery at 90 minutes, adjunctive PCI significantly improved mean ST resolution in patients who had been treated with combination therapy (57% [PCI] vs 24% [no PCI]; P =.006), but PCI did not have this effect in patients who had received thrombolytic therapy alone (1% [PCI] vs 10% [no PCI]; P =.70). In a multivariate model controlling for factors that would be expected to independently influence 90- to 180-minute ST resolution, abciximab treatment remained significantly associated with greater ST resolution (P =.008). CONCLUSIONS: A strategy that uses a combination reperfusion regimen that includes abciximab, followed by early adjunctive PCI, is associated with greater ST-segment resolution, which may reflect enhanced tissue level and microvascular perfusion. Future studies should evaluate prospectively the clinical efficacy of this strategy.

Abciximab↗