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Biomedical subjects

S Wagner

Publications and source records attributed to S Wagner.

At least 307 records · Page 17Linked to original sources

Combined ultrasonographic and neurographic examination: a new technique to evaluate phrenic nerve function.

In this report a new technique for simultaneous assessment of the electrical and mechanical properties of the diaphragm is presented. The phrenic nerve of 9 healthy persons was stimulated at the neck using magnetic stimulation. Electrical activity was recorded using chest surface electrodes. The mechanical function of the diaphragm was evaluated by performing combined B- and M-mode ultrasonographic examination. The data show that this method helps to distinguish the diaphragm muscle compound action potential from electrical activity derived from neighboring muscles activated by the brachial plexus. Furthermore, it provides a non-invasive tool which can easily be used in clinical practice to study the mechanical properties of the diaphragm.

Action Potentials↗

[Psoriasis arthropathica].

BACKGROUND: Five to seven percent of patients with psoriasis suffer additionally from accompanying arthritis. AIM OF THE STUDY: In this article, we review the current knowledge on clinical, diagnostic and therapeutic aspects of the disease. PATIENTS AND RESULTS: Data are presented on the treatment of six patients with the immunosuppressant ciclosporin. Therapeutic results with this drug are superior to agents traditionally used for management of psoriatic arthritis. CONCLUSION: The therapeutic options have been enlarged by the introduction of new immunosuppressive drugs, particularly ciclosporin.

Adolescent↗

MR lymphography using iron oxide particles. Detection of lymph node metastases in the VX2 rabbit tumor model.

MR images of the iliac lymph nodes of 25 VX2 carcinoma-bearing rabbits and of 5 tumor-free rabbits were obtained at 1.5 T before and after endolymphatic administration of superparamagnetic iron oxide particles (SPIO) at a dose of 1 mumol Fe per extremity. Imaging results were correlated with histology. In unenhanced images intranodal metastases were not detectable with any of the pulse sequences used and the signal intensities of tumor-free and metastatic lymph nodes did not differ significantly. After administration of the contrast medium, a significant signal loss (p < or = 0.05) occurred in the healthy lymph node tissue, whereas the signal intensity of lymph node metastases remained unchanged. In SPIO enhanced images, the threshold size for detection of lymph node metastases was 2 mm. Metastatic involvement was detected in 28 of the 30 tumorous lymph nodes with the SE 2000/15 sequence but in a smaller number of lymph nodes with the sequences SE 500/22 (n = 27) and 2000/65 (n = 21).

Animals↗

Elevated lipoprotein(a) is lowered by a cholesterol synthesis inhibitor in a normocholesterolaemic patient with premature myocardial infarction.

We have identified a 37-year-old patient suffering from two myocardial infarctions, with a markedly elevated lipoprotein(a) [Lp(a)] level and normal levels of cholesterol and triglycerides. Clinically this patient presented with xanthelasma and arcus lipoides corneae. After treatment with a cholesterol synthesis inhibitor (Pravastatin), the Lp(a) concentration in this patient was reduced significantly. This case report supports the hypothesis that elevated Lp(a) is an independent risk factor for coronary artery disease. The effect of the cholesterol synthesis inhibitor on Lp(a) may be due to the upregulation of the LDL-receptor, suggesting a role for LDL receptor in Lp(a) catabolism.

Adult↗

Retinoblastoma gene product activates expression of the human TGF-beta 2 gene through transcription factor ATF-2.

The retinoblastoma susceptibility gene product (pRb) plays an important role in constraining cellular proliferation and in regulating the cell cycle. The pRb inhibits transcription of genes involved in growth control (reviewed in ref. 3) and can regulate transforming growth factor beta 1 (TGF-beta 1) gene expression. TGF-beta isoforms also down-regulate cellular proliferation. To determine whether pRb also regulates expression of other TGF-beta isoforms, we examined the effect of pRb on the expression of the human TGF-beta 2 gene. The human TGF-beta 2 promoter contains multiple elements including an ATF site, which is essential for basal promoter activity. Here we report that pRb activates transcription of the human TGF-beta 2 gene. The promoter element responsible for pRb-mediated transcriptional regulation is a binding site for ATF proteins, an extensive transcription factor family. We provide evidence that implicates ATF-2 in pRb-responsiveness. First, the ATF promoter element in the TGF-beta 2 gene is a high-affinity ATF-2-binding site. Second, a GAL4-ATF2 fusion protein can support pRb-mediated transcriptional activation of a promoter containing GAL4-binding sites. Third, ATF-2 in nuclear extracts can interact with pRb. Our results reveal a new mechanism by which pRb constrains cellular proliferation: by activating expression of the inhibitory growth factor, TGF-beta 2.

Activating Transcription Factor 2↗

Production and analysis of specific monoclonal antibodies against the cell wall of Mycobacterium avium.

Monoclonal antibodies (mAbs) against Mycobacterium avium were produced which specifically reacted with cell walls of M. avium. The binding pattern was not limited to one subtype. The three most specific mAbs showed binding to the outer surface of M. avium but not to other mycobacterial or bacterial cell surfaces. The combined results of enzyme-linked immunosorbent assay, immunoblot and dot blot showed that mAb 4A006 bound to an epitope located in the cell wall and on the cell surface and mAb 4A010 to an epitope exposed on the cell surface and the cytoplasm. The mAb 4A009-binding epitope was only detectable on the cell surface but not in the cell wall or cytoplasmic fractions of M. avium. In the immunoblot technic a protein antigen with a molecular mass of 27-29 kDa was identified by the mAbs. The mAb 4A006 reacted with 142 out of 143 M. avium subtypes 1, 4 and 8 obtained from AIDS patients. These mAbs seem to be applicable for the identification of M. avium complex after culture.

Animals↗

Inhibition of cyclooxygenase attenuates baroreceptor function and increases the pressor response to norepinephrine in man.

The possible influence of prostaglandins on baroreceptor function in man has been investigated. Baroreceptor reflex was activated by intravenous infusion of norepinephrine and the pressor response was measured, both before and after administration of indomethacin. Resting blood pressure remained unchanged after indomethacin while resting heart rate was significantly decreased as compared to placebo and the norepinephrine-induced rise in mean arterial blood pressure was significantly more pronounced. The baroreceptor-mediated decrease in heart rate tended to be smaller. Baroreceptor sensitivity (delta heart rate/delta blood pressure) was significantly reduced by indomethacin to about half of the control value. In addition to attenuation of sensitivity, the findings represent resetting of the baroreceptor setpoint and a more pronounced pressor response to norepinephrine after cyclooxygenase inhibition. Thus, eicosanoids originating via the cyclooxygenase pathway of arachidonate metabolism may modulate the vascular response to adrenergic stimulation and may participate in the regulation of baroreceptor reflex setpoint and sensitivity.

Adult↗

Macrophages in normal human bone marrow and in chronic myeloproliferative disorders: an immunohistochemical and morphometric study by a new monoclonal antibody (PG-M1) on trephine biopsies.

An immunohistochemical and morphometric study was performed on routinely processed trephine biopsies of the bone marrow in 30 normal individuals and in 90 patients with various subtypes of chronic myeloproliferative disorder. Using a new monoclonal antibody (PG-M1) directed against a formalin-resistant epitope on macrophages and by employment of the Prussian blue reaction, quantitation of this cell population was feasible. Morphometric analysis revealed that the number of iron-laden macrophages represented only a fraction of the total number of histiocytic reticular cells. As could be expected, in polycythaemia rubra vera, no haemosiderin deposits were detectable, but the content of macrophages slightly exceeded that of the normal bone marrow. In chronic myeloid leukaemia 9 of 30 patients showed a significant increase in PG-M1-positive reticular cell elements. These were consistent with pseudo-Gaucher cells, sea-blue histiocytes and intermediate cell types. Primary (idiopathic) myelofibrosis-osteomyelosclerosis was characterized by a significant increase in macrophages (25 of 30 patients). Involvement of macrophages in the complex mechanisms generating bone marrow fibrosis and angiogenesis and in bone remodelling (osteosclerosis) may be responsible for this finding.

Adipose Tissue↗

Evaluation of a monoclonal antibody for detection of Helicobacter pylori in a direct immunofluorescence test.

A monoclonal antibody was developed for detection of Helicobacter pylori in gastric tissue sections in a direct immunofluorescence test. On a comparison of the immunofluorescence test with standard methods for detection of Helicobacter pylori, i.e. culture, the urease activity test and histological examination of tissue sections, using 158 biopsy specimens, 30 specimens were positive in all methods and 64 negative. In the remaining cases comparison was not possible because either immunofluorescence (29 specimens) or the standard methods (16 specimens) gave ambiguous results. The direct immunofluorescence test may have potential as an alternative to standard methods, but further testing in a defined patient population is necessary.

Adolescent↗

Solitary true cyst of the pancreas in an adult.

A 35-yr-old woman was presented to the hospital because of nausea 20-30 min after eating, associated with weight loss. A CT scan revealed a cystic lesion in the neck of the pancreas. At operation, a 3-cm diameter cyst was excised from the pancreas. Endoscopic retrograde pancreatography (ERP) was used intraoperatively to identify the transected pancreatic duct, after which a Roux-Y pancreaticojejunostomy was performed. Histologically, the cyst proved to be unilocular and was lined with cuboidal epithelium. The natural history of this lesion is unknown as only four previous case reports of unilocular true cysts in adults have been reported in the English literature. These are reviewed.

Adult↗

Expression of protease nexin-II in human dorsal root ganglia. A correlative immunocytochemical and in situ hybridization study.

Protease nexin-II (PN-II) is a potent chymotrypsin inhibitor that forms SDS-stable inhibitory complexes with epidermal growth factor binding protein, the gamma-subunit of nerve growth factor, and trypsin, and represents the secreted form of the amyloid beta-protein precursor (APP) that contains the Kunitz-type protease inhibitor domain. To determine the expression of PN-II within the peripheral nervous system, human dorsal root ganglia were processed for immunocytochemistry using well-characterized monoclonal antibodies against PN-II and for in situ hybridization studies using 35S-RNA PN-II probes for both APP751 and APP770. Highly specific immunoperoxidase staining of PN-II was demonstrated within the cytoplasm of dorsal root ganglia neurons and their processes in cryostat (fresh frozen) and vibratome (paraformaldehyde-fixed) sections. In situ hybridization using an anti-sense 35S-RNA PN-II probe demonstrated the presence of intense neuronal labeling. Labeling was not observed when the corresponding sense 35S-RNA PN-II probe was used. Although the precise functional role of PN-II/APP is not clear, the accumulation of amyloid beta-protein within the neuropil appears to be one of the earliest events in the pathogenesis of Alzheimer's disease (AD). Thus knowledge of the cell populations expressing the PN-II/APP gene would certainly be helpful for studies of the molecular mechanisms leading to the morphological and functional changes of AD. The results of this study clearly establish the expression of PN-II and its mRNA within the dorsal root ganglia neurons and their processes, and provide another point of departure for studies of the molecular mechanisms underlying the deposition of amyloid beta-protein and its relationships to the formation of neuritic plaques and neurofibrillary tangles.

Amyloid beta-Protein Precursor↗

Effect of body weight manipulations on sham feeding in the rat.

Rats with chronic esophageal fistulas were permitted to sham-feed a carbohydrate solution (a simplified model food) for a 40-min session each day. Body weight was elevated, then reduced again, by varying the caloric density of the liquid diet by which the rats were maintained. With 1M glucose as tastant, induction of mild obesity caused an abrupt reduction in sham meal size. Sucrose concentration-intake functions were lowered at all concentrations by mild obesity, but without change in slope. Both changes were reversed by weight reduction to around normal body weight; further weight reduction produced no further change. Therefore, some correlate of body weight biases the oral control of bout size. The bias seems to change rather abruptly between one value and another at a weight level slightly above normal.

Animals↗

Macrophages (phagocytic-histiocytic reticular cells) in reactive-inflammatory lesions of the bone marrow and in myelodysplastic syndromes (MDS). An immunohistochemical and morphometric study by use of a new monoclonal antibody (PG-M1).

An immunohistochemical and morphometric study was performed on trephine biopsies of the bone marrow in 52 patients (28 males/24 females; age 68 years) with various subtypes of myelodysplastic syndromes (MDS) to determine the number of macrophages (phagocytic-histiocytic reticular cells). Quantifications included the haemosiderin-storing subpopulation (Prussian-blue reaction) of this lineage as well as the iron-free compartment. The latter was identified by a new monoclonal antibody (PG-M1) which is specifically directed against histiocytic reticular cells. Bone marrow specimens of individuals without haematological disorders and those showing reactive lesions served as controls. In comparison with the normal bone marrow and inflammatory changes (i.e. rheumatoid arthritis) 23 of the 52 patients with MDS revealed a significant increase in macrophages. This increase encompassed not only the iron-laden subpopulation but also the total number of phagocytic reticular cells. Accumulation of macrophages in MDS was speculated to be due to a premature and enforced degradation of dysplastic cell elements leading to phagocytosis of haemosiderin and debris material. Moreover, cells of the monocyte-macrophage system could be involved in the complex pathomechanism of fibrillogenesis, since in a considerable percentage of patients with MDS, an increase in reticulin (argyrophilic) fibres was noticeable. Our finding of an expansion of the macrophage compartment in about half of the patients with MDS is in keeping with results of cell culture studies on colony formation of granulocyte-macrophage precursors (CFU-GM).

Adult↗

Preservation of high-energy phosphate reserves in a cat model of post-ischemic myocardial dysfunction.

Brief episodes of myocardial ischemia are known to cause reversible depression of regional myocardial contraction after reperfusion. One of the mechanisms of this persistent regional dysfunction has been proposed to be depletion of high-energy phosphate compounds. Eight cats were prepared with a reversible snare occluder around the left anterior descending artery (LAD); a surface coil sutured to the epicardial surface over the LAD territory for measurement of 31-phosphorus (31P) magnetic resonance spectroscopy (MRS) spectra; and a pair of ultrasonic crystals implanted in the mid-myocardium for measurement of regional segment length shortening. The baseline value of percent segment length shortening (%SS) was 12.8 +/- 1.4%. Increased afterload did not significantly alter high-energy phosphate levels or %SS. All animals exhibited passive systolic bulging during occlusion (-8.4 +/- 3.6% systolic shortening) as well as reduced phosphocreatine (PRc, 30 +/- 3% of control) and increased inorganic phosphorus (Pi) (239 +/- 18%), but there was no change in adenosine triphosphate (ATP). During reflow, %SS did not completely recover (4.0 +/- 2.9%, P less than .05 versus baseline). PCr and Pi returned to control levels during the first 30 minutes of reperfusion. Increased afterload had no significant effect on high-energy phosphates or %SS in stunned hearts. These findings indicate a lack of correlation between recovery of high-energy phosphate stores and regional myocardial contractility in stunned myocardium. High-energy phosphate reserves are preserved in stunned myocardium and are unlikely to be a direct cause of myocardial dysfunction.

Animals↗

Vascular architecture and collagen type IV in primary myelofibrosis and polycythaemia vera: an immunomorphometric study on trephine biopsies of the bone marrow.

Using a monoclonal antibody against collagen type IV, an immunohistochemical and morphometric study was performed on trephine biopsies of the bone marrow to determine the vascular architecture of the myeloid stroma as well as the occurrence of subendothelial collagen type IV deposits. In comparison with a control group (20 patients), we investigated specimens from 20 patients with polycythaemia vera (P. vera) and 40 patients showing primary (idiopathic) osteomyelofibrosis/-sclerosis (OMF). Morphometric analysis disclosed a significant increase in the number of sinusoids and also in the extent of collagen type IV deposits in the latter disorder. Sinusoids of P. vera showed only a dilatation of their lumina corresponding with enlarged areas of sectioned vascular profiles. Contrary to this finding, in OMF sinusoidal distension was accompanied by an excessive deviation from a circular profile and prominent intravascular haematopoiesis. Furthermore, there was a significant formation of basement membrane collagen (collagen type IV). All these features were far less pronounced in early hypercellular stages of OMF than in the late fibro-osteosclerotic subtypes. Our morphometric findings confirm haemodynamic studies on advanced stages of OMF which revealed an increased vascularity. Moreover, these results are in keeping with the assumption that angiogenesis in the evolution of the fibroosteosclerotic marrow process is mediated by certain growth factors. The increase in collagen type IV formation is thought to be generated by the pronounced endothelial cell proliferation in the course of neovascularization.

Aged↗

Bismuth subsalicylate in the treatment of H2 blocker resistant duodenal ulcers: role of Helicobacter pylori.

Fifty nine patients with Helicobacter pylori positive duodenal ulcers that failed to heal after a six week course of treatment with H2 blockers were randomly assigned to one of the following three regimens: (i) bismuth subsalicylate, 600 mg three times daily (n = 19), (ii) ranitidine, 300 mg at night (n = 20), (iii) bismuth subsalicylate plus ranitidine (n = 20). Cumulative ulcer healing rates after four and eight weeks respectively were as follows: bismuth subsalicylate 74% (14/19) and 95% (18/19), ranitidine 40% (8/20) and 65% (13/20), bismuth subsalicylate plus ranitidine 80% (16/20) and 95% (19/20). Bismuth subsalicylate treatment was better than ranitidine at both four and at eight weeks (p less than 0.05). The clearance rates for H pylori after four weeks were: bismuth subsubsalicylate 58%, ranitidine 0%, bismuth subsalicylate plus ranitidine 55%. After stopping bismuth therapy bacterial recrudescence frequently occurred. After bismuth treatment 86% (19/22) of ulcers had healed if H pylori had been cleared, whereas only 65% (11/17) had healed if H pylori persisted (NS). This study shows that bismuth subsalicylate is more effective in the treatment of resistant duodenal ulcers than standard dose ranitidine. It may be that suppression of H pylori by bismuth subsalicylate promotes ulcer healing.

Bismuth↗