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Biomedical subjects

K Wagner

Publications and source records attributed to K Wagner.

At least 235 records · Page 13Linked to original sources
PubMed1990

Molecular and cytogenetic analysis in two patients with microdeletions of 7p and Greig syndrome: hemizygosity for PGAM2 and TCRG genes.

Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder that has been mapped to 7p13. We have investigated two patients with GCPS and a cytogenetically visible microdeletion of the short arm of chromosome 7 with gene probes that have been assigned close to the proposed Greig locus. Deletion breakpoints were determined from high-resolution G- and R-banded chromosomes. In patient BC with a de novo deletion (7p12.3-7p14.2) we have found a loss of the genomic region containing the T-cell receptor gamma (TCRG) gene cluster, whereas the other patient IR with a deletion (7p11.2-7p13) due to a de novo translocation was apparently normal for this region. Gene dosage analysis revealed a loss of the phosphoglycerate mutase muscular form (PGAM2) gene locus in both patients. Hox 1.4 and interferon-beta 2 (IFNB2) showed a normal gene dosage. Our investigations revealed the following ordering and assignments of the studied genes: PGAM2 and GCPS in 7p12.3-13; TCRG in the distal part of 7p13-7p14.2; Hox 1.4 and IFNB2 distal to 7p14.2. Our results suggest a location of the TCRG gene more proximal than that reported previously. Furthermore, we were able to exclude the Hox 1.4 gene from involvement in the pathogenesis of GCPS.

Bisphosphoglycerate Mutase↗
PubMed1990

Medial (hamate) facet of the lunate.

One hundred sixty-five cadaveric wrists were dissected to assess the incidence of a medial (hamate) facet on the lunate and any associated pathologic conditions. Forty-seven of these specimens and 137 clinical patients' radiographs were reviewed to attempt to recognize and further assess the incidence of a medial (hamate) facet on the lunate. Two types of lunate were identified. Type I, in which there was no medial facet, was evident in 34.5% of the dissected specimens and type II, in which there was a medial facet, was evident in 65.5% of the dissected specimens. The medial facets in the type II lunates ranged from a shallow 1 mm facet to a deep 6 mm facet. Significant cartilage erosion with exposed subchondral bone at the proximal pole of the hamate, which was not identifiable by radiograph, was evident at dissection in 44.4% of the type II lunates, while none (0%) of the type I lunates had such associated hamate pathologic conditions. This type II lunate, with the high incidence of associated hamate pathology, may be an unidentified cause of wrist pain on the ulnar side.

Adolescent↗
PubMed1990

Amelioration of postischaemic acute renal failure in conscious dogs by human atrial natriuretic peptide.

We studied the effect of human ANP (alpha-hANP)-99-126 on the course of postischaemic acute renal failure in unilaterally nephrectomised, conscious dogs subjected to 120 min of renal ischaemia. In contrast to a control group A (n = 7), the investigational group B (n = 9) received an intra-aortic bolus injection of 100 micrograms/kg alpha-hANP and an additional continuous infusion of 0.3 micrograms/kg per min x 180 min immediately after ischaemia. On days 1 and 2 after ischaemia, only the bolus injection was repeated. Administration of hANP resulted in a marked restoration of GFR (29 +/- 2 vs 18 +/- 4 ml/min, P less than or equal to 0.01), diuresis (0.8 +/- 0.1 vs 0.5 +/- 0.1 ml/min, P less than or equal to 0.05), and natriuresis (44 +/- 7 vs 25 +/- 4 mumol/min, P less than or equal to 0.05) on the first postischaemic day, which was mirrored by a reduction in nitrogen retention (Purea: 8 +/- 1 vs 12 +/- 2 mmol/l P less than or equal to 0.05, Pcrea: 137 +/- 20 vs 204 +/- 37 mumol/l). Renal perfusion, however, was only slightly improved on day 1 after ischaemia (198 +/- 20 vs 163 +/- 27 ml/min, N.S.). Our data clearly demonstrate that repeated bolus applications of hANP ameliorate postischaemic acute renal failure in conscious dogs. We assume that the observed beneficial effect on GFR might be the consequence of an increase in glomerular capillary pressure rather than an improvement of renal perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1990

In vitro activities of tosufloxacin, temafloxacin, and A-56620 against pathogens of diarrhea.

Tosufloxacin (A-60969 HCl), a new quinolone with broad activity against gram-positive and anaerobic organisms, was compared in vitro with other quinolones against bacterial pathogens of diarrhea. Tosufloxacin was the most active agent against Salmonella spp., Shigella spp., Campylobacter spp., Aeromonas hydrophila, and Vibrio spp. Temafloxacin (A-62254) also demonstrated good activity against these organisms.

Anti-Bacterial Agents↗
PubMed1990

Folate nephropathy occurring during cytotoxic chemotherapy with high-dose folinic acid and 5-fluorouracil.

High-dose folinic acid with 5-fluorouracil (5-FU) is a novel combination chemotherapy used in the treatment of metastatic gastrointestinal cancer. One of the mechanisms of action of 5-FU is its conversion into fluorodeoxyuridylate (FdUMP), which inhibits thymidilate synthetase (TS). The rate of inhibition of TS is augmented by increasing concentrations of folinic acid. On the other hand, it is well known that treatment of animals with high doses of folinic acid results in acute renal failure due to tubular obstruction. In order to find out whether there are similar findings in the clinical setting, we investigated 8 patients (pts.) with metastatic gastrointestinal cancer who were treated with this chemotherapy. We used the following parameters: 1. excretion of four urinary enzymes (LDH, LAP, GGT, NAG); 2. creatinine clearance on days 1 and 5. Therapy consisted of folinic acid 200 mg/m2 i.v. on days 1-5 and 5-fluorouracil 400 mg/m2 on days 1-5. Each treatment cycle was repeated on day 28. We found a constant decrease in the excretion of all 4 enzymes from normal to subnormal values which was statistically significant (p less than .05) during the two treatment cycles. Creatinine clearance decreased about 50% in three patients from normal initial values. In conclusion, during therapy with high-dose folinic acid and 5-fluorouracil we found signs of tubular damage which are similar to those found in folate nephropathy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Hepatitis. The forgotten disease.

Hepatitis is a significant disease process for health care professionals. Because of the large number of procedures performed by podiatrists in the course of patient care, they are at particular risk. The variants of hepatitis are reviewed, and the modes of transmission are discussed. Recommendations are made on protective measures to reduce contraction of this disease.

Environmental Exposure↗
PubMed1990

The synthetic prostaglandin E1 analogue rioprostil reduces the nephrotoxic potential of cyclosporine A.

Acute CyA nephrotoxicity involves alteration in the proximal tubule and leads to glomerular lesions. Administration of a vasodilatator agent such as the prostaglandin E1 analogue Rioprostil (Bayer AG, BAY 06893) might prevent preglomerular vasoconstriction and hence reduce cyclosporin nephrotoxicity. As an increased excretion of urinary enzymes as a consequence of CyA-nephrotoxicity is well known we investigated in 40 male Wistar rats the excretion of three urinary enzymes: the brush border enzyme gamma-glutamyltransferase (GGT), the leucine aminopeptidase (LAP), and the lysosomal enzyme N-acetyl-beta-glucosaminidase (NAG). Additionally we determined s-creatinine and CyA plasma level. The kidneys were studied histologically at the end of the study. Wistar rats receiving 20 or 50 mg CyA/kg/d showed a marked deterioration in renal function and an increase of all urinary enzymes determined. In the rats receiving 20 mg CyA/kg/d and Rioprostil (150 micrograms/d) renal function and the enzymes determined remained in the normal range. There was no change in the enzyme excretion and only a minor improvement of renal function in rats receiving 50 mg CyA/kg/d and Rioprostil. Histological findings showed prevention of CyA nephrotoxicity in the 20 mg/kg/d group and diminished renal damage in the 50 mg/kg/d group.

Acetylglucosaminidase↗
PubMed1990

Frequency of the delta Phe508 mutation and correlation with XV.2c/KM-19 haplotypes in an American population of cystic fibrosis patients: results of a collaborative study.

The cystic fibrosis (CF) gene has been recently cloned, and a deletion of 3 basepairs (bp) of DNA was found on most of the CF chromosomes. This deletion leads to the synthesis of a protein that lacks a phenylalanine residue at position 508. Using two polymerase chain reaction protocols to study the frequency of this mutation in a series of 192 CF patients, we found the mutation on 72% of affected chromosomes. We then used this value to calculate the predictive value of a negative test result in a population-based screening program for CF carrier status. Haplotype analysis with the polymorphic markers XV.2c and KM-19 on 239 CF chromosomes revealed that 90.7% of CF chromosomes with the deletion had a single haplotype. This haplotype was also associated with 60.4% of CF chromosomes with unknown mutations. These values can be used to calculate the probability of whether an individual from the general population is a carrier of any CF mutation.

Base Sequence↗
PubMed1989

Generation of a recombinant mouse-human chimaeric monoclonal antibody directed against human carcinoembryonic antigen.

A procedure was devised for the identification and specific cloning of functionally rearranged variable region immunoglobulin (Ig) gene segments from genomic DNA of a murine hybridoma cell line which produces a high-affinity monoclonal antibody (MAb) directed against human carcinoembryonic antigen (CEA). The cloned, functionally-rearranged murine Ig H-chain and L-chain variable region gene segments were incorporated into plasmid vectors capable of directing the expression of a chimaeric mouse-human antibody molecule with human (gamma 4, kappa) constant region sequences. Expression plasmids were transfected into a mouse myeloma cell line by electroporation and transfectomas secreting functional chimaeric antibody selected. Chimaeric antibody generated by transfectomas was analysed and shown to compete effectively with its murine counterpart for binding to the CEA epitope, and to have an equivalent antigen-binding affinity. This anti-CEA recombinant antibody should find application in in vivo diagnosis by immunoscintigraphy of human colonic carcinoma, and possibly also in therapy of the disease, overcoming some of the difficulties associated with the repeated use of non-human immunoglobulins in human patients.

Animals↗
PubMed1989

Conformational analysis of cyclic peptides in solution.

The strategy and tactics of conformational analysis of cyclic peptides in solution is demonstrated by the example of cyclo(-D-Pro-Phe-Thr-Phe-Trp-Phe-). Spin-locked experiments like rotating frame nuclear Overhauser enhancement spectroscopy (ROESY), ROTO, and TOCSY are successfully applied to assign all proton signals and to obtain distance information. A crude conformational model was built using the nmr data. This starting model was refined by restrained molecular dynamics (MD) calculations using ROE derived distances and fixed bond angles as determined from homo- and heteronuclear coupling constants. To mimic the solvent and to reduce artifacts in an in vacuo calculation the charges of the solvent-exposed NH protons were gradually reduced according to the temperature gradients. The thus obtained "conformation" (mean of a 40 ps MD trajectory) shows very close similarity to x-ray structures in an orthorhombic and in two monoclinic crystal modifications of the same compound. The main difference is the breaking of an intermolecular hydrogen bond of the threonine hydroxyl group on dissolution of the crystal and forming an intramolecular hydrogen bond in solution.

Models, Molecular↗
PubMed1989

Establishment of a memory in vitro murine IgE response to benzylpenicillin and its resistance to suppression by anti-IL-4 antibody.

Regulation of a memory IgE antibody response may be different from the induction of a primary response and may, therefore, be more relevant to the study of allergic diseases and the therapeutic manipulation of IgE antibody formation. In this paper a murine hapten-specific in vitro memory IgE antibody response to benzylpenicilloyl(BPO)-KLH is described. The response was analyzed by determining the number of antibody-producing cells (APC) in an ELISA spot assay. Of the total number of BPO-specific APC (10,000 APC/10(6) cultured spleen cells), about 1% were IgE-producing cells (100/10(6) cultured cells), as detected on day 6 of culture. The level of the antibody response is antigen dose-dependent, and the detected APC are BPO specific. The memory IgE response is not inhibited by the addition of anti-IL-4 antibody (11B11), even at a high excess. In the presence of the mitogen lipopolysaccharide, it has been shown that switch of B cells to IgE is induced by IL-4, a process which can be inhibited by anti-IL-4 antibody. Because the antigen-induced IgE response cannot be inhibited by anti-IL-4 antibody, in vitro responding cells derived from BPO-KLH-preimmunized mice may, therefore, have already switched in vivo to IgE. On the other hand, B cells switching to IgE in a situation of cognate T-B cell interaction might receive IL-4 in a transsynaptical way from T cells which might not be accessible to inhibition by anti-IL-4 antibody. The identification of the two possibilities in situations of established allergic disorders will be decisive for determining whether pharmacological inhibition of IL-4 (or IL-4-induced switch)--e.g., by putative low molecular weight compounds--will ever be a meaningful approach to suppress allergic diseases.

Animals↗
PubMed1989

The incidence and significance of hemostatic abnormalities in patients with head injuries.

Abnormal coagulation and fibrinolysis is a frequent complication in patients with head injury. This complication can be severe enough to lead to hemorrhage or thrombosis. A study was undertaken to determine if the hemostatic abnormalities are reliable indicators of outcome. Hemostasis in 269 patients with head injuries alone was screened using platelet count (PC), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin clotting time (TCT), fibrinogen assay (FIB), level of fibrin-fibrinogen degradation products (FDP), and disseminated intravascular coagulation (DIC) score in the first 24 hours after injury. Test results were compared with the outcome (discharged or dead) in the entire group and in subgroups divided on the basis of the severity of injury as determined by the Glasgow coma score (GCS). Increased consumptive coagulopathy at admission, as reflected in the DIC score, predicts the outcome of head-injured patients with a high degree of accuracy. The degree of increase of the initial FDP level and prolongation of TCT also correlated positively with the outcome. Prolongation of the APTT correlated strongly with unfavorable outcome in a large group of patients, and in a small group, markedly accelerated APTT also predicted death. Stepwise logistic regression analysis demonstrated that GCS, FDP level, and DIC score predicted outcome. Other tests did not provide additional predictive value. Abnormal hemostasis frequently complicates the course of patients with head injuries. This study demonstrates that hemostasis tests are predictors of outcome in these patients.

Adolescent↗
PubMed1989

[Metabolism of L-thiazolidine-4-carboxylic acid].

L-thiazolidine-(4)-carboxylic acid (TAC) has proven to be a good substrate for long-term parenteral nutrition. In this study the metabolism of TAC in the rat is examined at subcellular level. TAC is oxidized by mitochondrial proline oxidase of liver and kidney to L-thiazoline-(4)-carboxylic acid, which then is hydrolyzed to N-formyl-cysteine (FCYS). FCYS is hydrolyzed to cysteine and formic acid by a cytosolic enzyme.

Animals↗