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Biomedical subjects

S Wagner

Publications and source records attributed to S Wagner.

At least 289 records · Page 16Linked to original sources
PubMed1993

Increased expression of epidermal IL-8 receptor in psoriasis. Down-regulation by FK-506 in vitro.

IL-8 is a chemotactic cytokine with proinflammatory and growth-promoting activities. Recently it has been shown to influence several functions of keratinocytes, including HLA-DR expression, chemotaxis, and proliferation by binding to a specific receptor. Because psoriasis vulgaris is characterized by epidermal hyperproliferation and infiltration of inflammatory cells, we investigated the expression of IL-8 and its receptor in normal and psoriatic epidermis using semiquantitative reverse-transcriptase-polymerase chain reaction. In addition the mRNA levels of the proto-oncogenes c-ras, c-raf, c-myc, and HER-2 were also investigated as potential growth-promoting stimuli in psoriatic epidermis. IL-8 mRNA was only detected in lesional psoriatic epidermis, and IL-8R-specific mRNA was found to be 10 times increased in lesional psoriatic epidermis. There was no significant difference in the protooncogene mRNA levels. In order to test the relevance of the massively increased IL-8R levels in psoriatic epidermis, we investigated the effect of the antipsoriatic drug FK-506 on specific IL-8 and IL-8R mRNA expression. FK-506 dose dependently inhibited IL-8R expression and function. Our data suggest that in psoriatic skin, elevated IL-8 levels and markedly increased IL-8R expression may act in concert to induce the cardinal signs of psoriasis--epidermal hyperproliferation and leukocyte infiltration. IL-8R may prove a molecular target for antipsoriatic drugs such as FK-506.

Adult↗
PubMed1993

Molecular cloning of RhD cDNA derived from a gene present in RhD-positive, but not RhD-negative individuals.

The Rh blood group system plays a major role in immune and nonimmune hemolytic states. Although an Rh cDNA has been previously cloned, there is no information on which Rh antigenic protein it encodes. Using polymerase chain reaction (PCR) amplification, we have identified this original Rh clone, here designated Rh21, and an additional Rh cDNA clone, Rh13, that is 96% nucleotide- and 92% amino acid-identical to Rh21, with the substitutions scattered throughout the sequence. A molecular genetic approach was used to match this Rh clone with an Rh specificity. The mRNA transcript for Rh13 was present in reticulocytes from RhD-positive individuals, but was absent from the reticulocytes of RhD-negative individuals. Using conventional screening of genomic libraries, as well as PCR cloning, partial genomic clones for these two Rh cDNAs were obtained. Based on PCR analysis and Southern blots, the Rh21 gene was present in all individuals, but an intact Rh13 gene was only present in RhD-positive and not RhD-negative individuals. Thus, by correlating the presence of Rh mRNA and gene sequences with individual Rh phenotypes, we were able to establish that the new Rh13 cDNA clone represents the RhD protein.

Amino Acid Sequence↗
PubMed1993

Activating transcription factor-1 can mediate Ca(2+)- and cAMP-inducible transcriptional activation.

Increased intracellular cAMP and Ca2+ levels can activate transcription of a number of eukaryotic genes through a common promoter element, the cAMP/Ca2+ response element. This element is the binding site for activating transcription factor (ATF)/CREB proteins, an extensive transcription factor family. Here we report that one member of this family, ATF-1, can mediate both Ca2+ and cAMP transcriptional responses, but that the responses to the two pathways differ in magnitude. In contrast, another family member, CREB, has been shown to mediate Ca2+ and cAMP responses to similar levels. Taken together, these results suggest a mechanism that allows cells to integrate and differentiate gene regulation by cAMP and Ca2+.

Activating Transcription Factor 1↗
PubMed1993

Persistence of sham feeding after intragastric meals in rats.

In rats on a stringent deprivation schedule and at reduced body weight, an intragastric load of liquid diet that equals or exceeds normal meal size has no effect at all on subsequent sham feeding of milk diet or of glucose. Removing the acute deprivation period and reversing, or preventing, severe weight reduction has no effect on this "persistence" of sham feeding: a full intragastric meal may leave sham feeding quite unaffected, even if that meal follows the previous meal at a physiological interval, in rats at normal weight. These data contrast with graded, dose-dependent effects of other manipulations by other investigators. Perhaps such effects depend on conditioned or anticipatory controls of feeding, whereas our findings apply to unconditioned controls.

Animals↗
PubMed1993

Pharmacokinetics and pharmacodynamics of famotidine in patients with reflux oesophagitis.

The pharmacokinetics, pharmacodynamic effect and clinical efficacy of famotidine were studied in 10 patients with reflux oesophagitis Grades I and II. For the pharmacokinetic studies the patients received 20 mg famotidine i.v. The half-life of famotidine was 3.8 h, the total plasma clearance was 297 ml.min-1, and a steady state volume of distribution of 1.2 l.kg-1 was found. For pharmacodynamic assessment, intraoesophageal pH-metry was performed without and after acute treatment with famotidine 20 mg i.v. and following 3 weeks of oral famotidine 80 mg b.d. The resultant percentage total acid exposure time (pH < 4 within 24 h) were 23.9%, 19.0% and 19.2% (median), respectively (NS). At the end of 6 weeks of oral therapy, symptomatic and endoscopic improvement had occurred in 9 and 5 patients, respectively. Our study shows that the pharmacokinetics of famotidine in patients with reflux oesophagitis is comparable to that in healthy volunteers and peptic ulcer patients. The clinical response to the treatment appeared comparable to that found after other H2-receptor antagonists.

Adult↗
PubMed1993

High incidence of carpal tunnel syndrome in diabetic patients after combined pancreas and kidney transplantation.

Fifty-eight patients with long-standing type 1 (insulin-dependent) diabetes were studied prospectively after combined pancreas and kidney transplantation for a mean observation period of 47.9 months (range 17-116 months). Thirty-three per cent of these patients (19/58) developed carpal tunnel syndrome after a mean interval of 1.7 years (range 3 months-5 years). This rate is about twice that in type 1 diabetic patients. The manifestation of carpal tunnel syndrome was not significantly associated with worsening of diabetic polyneuropathy or with deterioration of kidney or pancreas function. In all but one patient symptoms improved without surgical intervention. This study suggests that patients after combined pancreas and kidney transplantation have an increased risk of carpal tunnel syndrome for which the etiology and pathophysiology are unknown. In most patients no surgical intervention is necessary.

Adult↗
PubMed1993

Fibre type specific expression of Leu19-antigen and N-CAM in skeletal muscle in various stages after experimental denervation.

Leu-19 antigen, which seems to be identical with neural cell adhesion molecule (N-CAM), plays a major role in the innervation of muscle cells, and in adult muscle appears after denervation and during regeneration of muscle fibres, where it acts as part of a signalling system increasing the probability of re-innervation. This combined enzyme-histochemical and immunohistochemical study examined whether this signalling process was regulated in a uniform or differential pattern for type 1 and type 2 muscle fibres. The subscapular nerve of 18 rabbits was transsected with subsequent complete denervation of the supraspinatus muscle. Leu-19 and N-CAM immunohistochemistry was performed 2 to 64 days after surgery. Whereas in normal muscle there are virtually no Leu-19/N-CAM positive muscle fibres; from day 2 after denervation an increasing proportion of fibres expressed Leu-19/N-CAM, prior to any neurogenic atrophy. In the early stage of denervation Leu19/N-CAM expression was confined to type 1 fibres. After 11 days nearly all fibres were Leu19/N-CAM positive irrespective of their fibre type. Sixty-four days after denervation type 1 fibres became Leu19/N-CAM negative, while atrophic type 2 fibres showed intensive staining. Thus, expression of Leu-19 antigenicity is differently regulated in both fibre types.

Animals↗
PubMed1993

Persistence of sham feeding after real-fed gastric loads in rats.

Esophagostomized rats were permitted to "real-feed" a glucose solution (Experiment 1) or milk (Experiment 2), by receiving intragastric (IG) infusions concurrent with sham feeding. This was done for the first part of the feeding session; then the IG infusions were discontinued so that subsequent ingestion was sham. When such infusions stopped after 80% of real-meal volume had been delivered, they had no measurable effect on subsequent oral ingestion: sham feeding persisted as if nothing had been delivered IG. Therefore, the onset of postingestive satiety, at least in experienced sham-feeding rats, is all-or-none or close to it: if the IG loads are even slightly short of what is required to abolish sham feeding, then they do not affect sham feeding at all. This is so even if the postingestive events occur within their normal behavioral context.

Animals↗
PubMed1993

Serial measurements of neuropeptide Y in plasma for monitoring neuroblastoma in children.

Neuropeptide Y (NPY) was studied as a marker for neuroblastoma in 12 children. All but one patient with neuroblastoma had elevated plasma NPY concentrations at diagnosis. During treatment NPY values returned to normal in 9 of 12 children. All three children without normalization of plasma NPY values died; two of them had a relapse and the third died of toxic effects. Plasma NPY appears to be a sensitive marker of neuroblastoma.

Adolescent↗
PubMed1993

Effects of substances inhibiting or uncoupling respiratory-chain phosphorylation of Helicobacter pylori.

The effects of electron transport inhibitors and uncoupling agents as well as of bismuth compounds on the respiratory activity and oxidative phosphorylation of Helicobacter pylori were investigated. Bismuth gallate and bismuth subsalicylate reduced the respiratory chain-dependent phosphorylation. Inhibition was of the same magnitude as that observed with other known inhibitors. It is concluded that bismuth displays an antibacterial effect by inhibiting the respiratory chain of H. pylori.

Anti-Bacterial Agents↗
PubMed1993

Anion exchanger 1 in human kidney and oncocytoma differs from erythroid AE1 in its NH2 terminus.

Acid-secreting intercalated cells of the kidney collecting duct and tumor cells of renal oncocytoma express an anion exchanger that is immunologically related but not identical to the chloride-bicarbonate anion exchanger of erythrocytes (AE1). In this study, we have mapped the binding site of a monoclonal antibody against erythroid AE1 that does not react with either intercalated cells or oncocytoma. The epitope is located close to the NH2 terminus of AE1, indicating that AE1 in intercalated cells and oncocytoma differs in its NH2 terminus from erythroid AE1. This conclusion was supported by an antibody directed against residues 1-14 of erythroid AE1 that does not react with intercalated cells in oncocytoma. Polymerase chain reaction performed with mRNA from a human kidney revealed that the sequence containing the codons for Met-1 and Met-33 in erythroid mRNA is missing in the kidney transcript, whereas the sequence coding for Met-66 is present. DNA sequence data derived from cloning the 5' end of the human kidney AE1 mRNA clearly showed that the 5' untranslated region comprises part of intron 3, the complete exon 4 that is followed by exon 5 containing Met-66 as the site of translation initiation. Altogether, the results indicate that AE1 in the human kidney is an amino-terminally truncated form of erythroid AE1 that is restricted to the basolateral membrane domain of the acid-secreting intercalated cells of the collecting duct and is also expressed in oncocytoma.

Adenoma, Oxyphilic↗
PubMed1993

Interstitial MR lymphography with iron oxide particles: results in tumor-free and VX2 tumor-bearing rabbits.

OBJECTIVE: MR lymphography with interstitial injection of superparamagnetic iron oxide particles was optimized in normal rabbits by investigating the pattern of signal reduction in lymph nodes as a function of dose and time after administration. The optimized examination procedure was then used in a rabbit tumor model to study the potential of superparamagnetic iron oxide--enhanced MR lymphography in the detection of metastatic lymph node involvement. MATERIALS AND METHODS: The popliteal and iliac lymph nodes of 18 normal rabbits were imaged to study the dose response and time course of the effect of the contrast agent. For the dose response study, six doses of 2-50 mumol of iron per extremity were administered to three animals per dose, and MR images were obtained before and 12 hr after administration. For the time course study, 20 mumol of iron per extremity was administered to four animals, and images were obtained before and 6 hr to 42 days after administration. VX2 tumor-bearing rabbits were examined 12 hr after administration of 20 mumol (10 animals) and 50 mumol (three animals) of iron per extremity. Superparamagnetic iron oxide was injected into the foot pad of the hind limb. T1-, T2-, and proton density-weighted MR images were obtained with a 1.5-T unit. RESULTS: In normal rabbits, a profound and homogeneous loss of signal intensity was found with doses of 2-5 mumol of iron per extremity in popliteal lymph nodes and with doses of 20-30 mumol in the iliac lymph nodes. Superparamagnetic iron oxide caused maximal loss of signal intensity in both popliteal and iliac lymph nodes 12 hr after administration. In tumor-bearing rabbits, different degrees of metastatic displacement of lymph nodes were discernible, and even small metastases (3 mm in diameter) could be visualized when using the optimized examination protocol and the proton density-weighted spin-echo sequence. CONCLUSION: We conclude that interstitial MR lymphography with superparamagnetic iron oxide enables the detection of lymph node metastases and therefore is a promising technique for improved diagnostic imaging of lymph nodes in the staging of tumors.

Animals↗
PubMed1993

Diabetic neuropathy 3 years after successful pancreas and kidney transplantation.

Twenty-seven patients with successful transplantation and a control group of 14 patients with early rejection of the pancreas graft but functioning kidney graft were examined in a prospective study for 3 yr. Before transplantation, all patients had long-standing type I diabetes with advanced secondary complications, including end-stage diabetic nephropathy. After transplantation in the patients of both groups, kidney function was almost normal. Mean HbA1 levels were normal in the group with pancreas graft survival. In the control group, HbA1 levels were, on average, 1.5% higher compared with the group with pancreas survival (P = 0.00005). After 3 yr, the patients with functioning pancreas graft showed fewer symptoms (mean difference 1.0 in a symptom score ranging from 0 to 16, P = 0.004) compared with the control group. No statistically significant difference between both groups concerning clinical signs of polyneuropathy could be observed. In the pancreas and kidney transplantation group, peroneal and median nerve conduction velocities increased 7.2 m/s (P < 0.01) and 3.5 m/s (P < 0.05), respectively, whereas no increase was registered in the control group. The change of median and sural sensory nerve conduction velocities, peroneal and median compound muscle action potentials, and sural and median sensory action potentials was insignificant. In conclusion, although the improvement of clinical symptoms and neurophysiological signs of polyneuropathy was modest in the pancreas and kidney transplantation group, our data suggest that successful pancreas transplantation is able not only to halt the progression of diabetic polyneuropathy but also to improve it to some extent even at a far advanced stage.

Action Potentials↗
PubMed1993

Skeletal muscle sonography: a correlative study of echogenicity and morphology.

In skeletal muscle sonography high echogenicities have proved to be of diagnostic value. The following study examines whether these echointensities are caused mainly by interstitial fat or fibrosis. Consequently, the echogenicities of 86 muscles, their diameters, and the thickness of subcutaneous fat layers superficial to these muscles were measured and compared for content of fat and connective tissue, which were assessed by morphometry and biochemical testing in the corresponding muscle biopsy samples. The results indicate that fat replacement constitutes the main cause of increased muscle echogenicity, whereas intramuscular fibrosis did not significantly affect the muscles' echogenicity.

Adipose Tissue↗