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Biomedical subjects

K Wagner

Publications and source records attributed to K Wagner.

At least 163 records · Page 9Linked to original sources
PubMed1996

Immunolocalization of type X collagen in normal fetal and adult osteoarthritic cartilage with monoclonal antibodies.

For studies on processing and tissue distribution of type X collagen, monoclonal antibodies were prepared against human recombinant collagen type X (hrCol X) and tested by ELISA, immunoblotting and immunohistology. Forty-two clones were obtained which were grouped into four different subsets based on their reactivity against native and denatured hrCol X, pepsin-treated hrCol X, and the C-terminal NC-1 domain. Here we present results obtained with four monoclonal antibodies: Clone X 53, a representative of group I, binds with high affinity to both native and pepsin-digested hrCol X but with low affinity to the NC-1 dimer; monoclonal antibodies of group II and III recognized native and denatured hrCol X but not NC-1; antibodies of group II, but not III, reacted to some extent with pepsin treated hrCol X; one antibody (X 34) was obtained that reacted strongly with the isolated NC-1 dimer and native hrCol X but not with the NC-1 monomer or pepsin-digested hrCol X (group IV). Antibodies of all groups stained specifically the hypertrophic zone of fetal human epiphyseal cartilage. Mab X 53 stained the peri- and extracellular matrix of hypertrophic chondrocytes in the lower hypertrophic zone and in the calcified cartilage core in endochondral bone trabecules, while clone X 34 stained intracellularly and the pericellular matrix. All other tissues or cells of the epiphysis were negative. Antibody X 53 reacted also with canine, murine and guinea pig hypertrophic cartilage in tissue sections, but not with bovine or porcine type X collagen. In sections of osteoarthritic cartilage, clusters of hypertrophic chondrocytes in the deep zone were stained, confirming previous observations on enhanced chondrocyte hypertrophy and type X collagen expression in osteoarthritic articular cartilage.

Adult↗
PubMed1996

Neuropsychological effects of Interferon Alfa-n3 treatment in asymptomatic human immunodeficiency virus-1-infected individuals.

Eighteen asymptomatic HIV-1-infected (HIV+) individuals were evaluated neuropsychologically before and during Interferon Alfa-n3 treatment. All 18 were evaluated twice, and 9 were evaluated three times. Analyses revealed few significant effects of treatment on cognitive, motor, and affective function. Improvements occurred over visits on measures of attention and appeared to reflect practice effects. Decrements occurred over visits on measures of procedural and supraspan learning. Examination of the data suggested that decrements were due to procedural artifacts and were not medication effects. In contrast to prior studies reporting significant neuropsychiatric side effects of interferon alpha treatment, few such effects occurred when HIV+ individuals were treated with Interferon Alfa-n3 and were evaluated neuropsychologically in a systematic manner.

Adult↗
PubMed1996

Experimental and clinical experience with the use of tacrolimus (FK506) in kidney transplantation.

Tacrolimus is a recently developed immunosuppressive agent, based on a mechanism similar to cyclosporin. A broad variety of trials has provided evidence for its efficacy in human liver transplantation. In these trials, the incidence of acute rejection was markedly reduced. The following article reviews recent knowledge regarding clinical and experimental experience with tacrolimus in kidney transplantation. In summary, clinical trials suggested a marked reduction of acute allograft rejections comparable to those observed in liver transplantation. Its efficacy in steroid-resistant rejections is also well documented, while not critically analyzed in a prospective trial. Its effect is independent of the preceding administration of antilymphocyte antibodies. Thus, its use seems warranted even in the presence of steroid-resistant graft rejection, when treatment with antilymphocyte antibodies is contraindicated. Based on preliminary experience with tacrolimus in previous studies of primary immunosuppressive treatment and on the compelling evidence that the drug is effective in rescue therapy, its use as primary immunosuppressive regimen in immunologic high risk patients should now be considered.

Animals↗
PubMed1996

Initial experience with tacrolimus rescue therapy in OKT3 resistant rejection.

Follow-up of 9 renal transplant recipients who were converted from cyclosporin A to tacrolimus (FK506) as recue therapy for intractable rejection is described. All patients initially received a cyclosporin A based immunosuppression. They developed biopsy proven acute rejections 22 +/- 11 days after transplantation which did not resolve by i.v. steroids and subsequent OKT3. Fifty-three +/- 11 days post transplantation the patients were converted from cyclosporin A to tacrolimus. After conversion to tacrolimus 6 patients developed a stabile transplant function. One transplant recipient who initially responded to tacrolimus lost his graft due to a chronic rejection 9 months following conversion. Two patients with never functioning kidneys remained on dialysis despite tacrolimus therapy. After conversion no serious adverse events occurred and only a slightly increased infection rate and hyperglycemia were noted as major side effects of tacrolimus. Tacrolimus rescue therapy was effective in treating acute renal allograft rejection unresponsive to steroids and OKT3. Tacrolimus rescue therapy was not accompanied by a substantial rise in complications. Patients with never functioning kidneys did not seem to benefit from tacrolimus rescue therapy.

Adult↗
PubMed1996

[Charcot-Marie-Tooth syndrome. Clinico-genetic correlation in an affected family].

Hereditary motor and sensory neuropathy (HMSN) is one of the most frequently inherited causes of peripheral neurological disability. To date, the classification has been based on clinical, histological and genetic grounds. Due to increased genetic knowledge at the molecular level in recent years, diagnosis of the different subtypes has been considerably improved and their relationship clarified. We describe three generations of a family with HMSN IA (Charcot-Marie-Tooth disease IA = CMT 1A) with a genetic defect mapped to chromosome 17 and show the importance of genetic testing. Even in benign and clinically non-manifested causes of the disease, an early and non-invasive diagnosis should be made by genetic testing to identify affected persons; thus, nerve biopsy can be abandoned. Operations of pes cavus, which are not indicated and are often complicated by delayed healing, may be avoided. Instead, patients should undergo early physiotherapy and be counselled about their professional careers and family planning.

Adult↗
PubMed1995

[Tuberous sclerosis: typical complications of a hereditary disease and therapeutic options].

BACKGROUND: Tuberous sclerosis is an autosomal-dominant hereditary disease (incidence and prevalence 1:10,000) which is characterized by hamartomas in various organs. PATIENTS AND METHODS: We demonstrate three patients with different and partly atypical manifestations: All had facial angiofibroma. No patient was mentally retarded and epilepsy was observed only intermittently. In all cases periventricular calcifications were noted and renal angiomyolipomas were found. Two patients requested dialysis after nephrectomy. One patient suffered from severe complications of the rare pulmonary lymphangioleiomyomatosis. RESULTS: Therapy of this multiorgan disease is only symptomatic. Operations should be considered as second line treatment. In one case, successful renal transplantation is described. CONCLUSIONS: Genetic counselling is warranted in this disease with high penetrance, particularly the broad spectrum of manifestations should be taken into account.

Adult↗
PubMed1995

Interleukin-4 and interleukin-5 are rarely co-expressed by human T cells.

Interleukin (IL)-4 and IL-5 are two cytokines which synergize in the induction of several biological effector functions. They are produced by mouse and human T helper 2 (Th2) and T helper 0 (Th0) cells. Little is known about the regulation of the two cytokines at the single-cell level. Here we show, using a flow cytometric intracellular staining technique, that IL-4 and IL-5 are predominantly produced by different human peripheral CD4+ and CD8+ T cells, whereas interferon (IFN)-gamma and IL-2 are produced by the same cells. In contrast, cloned human Th0 and Th2 cells were able to produce IL-4 and IL-5 simultaneously. The segregation of IL-4 and IL-5 in activated peripheral T cells was found within 72 h of activation upon anti-CD3 or phorbol ester + ionomycin stimulation. The kinetics of IL-4 and IL-5 production were different at the mRNA and the intra- and extracellular protein level, indicating that the cytokines are regulated differently. T cells from three patients with hyper-IgE syndrome did not display a substantial proportion of IL-4/IL-5 double-positive cells. However, simultaneous production could be induced in normal human T cells after prolonged stimulation with a minimum of two restimulation cycles. We conclude that the simultaneous production of IL-4 and IL-5 is a feature of repetitively activated human T cells.

Base Sequence↗
PubMed1995

FK 506 versus cyclosporin in the prevention of renal allograft rejection--European pilot study: six-week results.

FK 506 was compared with cyclosporin in a randomised trial in good-risk cadaveric renal transplant recipients. The objective was to evaluate whether oral FK 506 dosing was viable and whether blood concentrations in the range 10-20 ng/ml would prove to be practical. Thirty-one adult patients were randomised to FK 506 and 16 to cyclosporin. Both groups received an identical regimen of azathioprine and corticosteroids. Serum creatinine concentrations decreased rapidly in both groups with mean values below 200 mumol/l within 2 weeks. One graft in the cyclosporin group was lost due to renal vein thrombosis. During the 6-week study period, 19.4% of patients on FK 506 and 31.3% on cyclosporin experienced acute rejection. One patient in each group experienced corticosteroid-resistant rejection that responded to anti-lymphocyte therapy. Infections were reported in 51.6% of the FK 506 group compared with 37.5% of the cyclosporin group. The spectrum of adverse events was similar in both groups. However, minor neurological disorders were more common in the FK 506 group (54.8% versus 6.3%) whereas hypertension was less common (48.8% versus 75.0%). The results indicate that oral FK 506 rapidly achieves therapeutic blood concentrations and is an effective immunosuppressant for the initial treatment of renal allograft recipients.

Adolescent↗
PubMed1995

Cobalt(III)-ligated peptides as acyl acceptors in peptide synthesis catalyzed by chymotrypsin.

The efficiency of cobalt(III)-ligated peptides as acceptor nucleophiles in acyl transfer reactions catalyzed by alpha-chymotrypsin was examined. A series of metallopeptides with the general formula [H-(Gly)n-OCo(NH3)5]2+ (1 < or = n < or = 4) was tested. The aminolysis rate of acyl-chymotrypsin was measured spectrophotometrically by monitoring the concentration of unreacted nucleophile. The rate of the competing hydrolysis of acyl-chymotrypsin was obtained by automatic titration with base, using a pH-stat. The main result was that the positively charged metallopeptides, in general, were more efficient nucleophiles than the corresponding amides and free peptides that were examined for comparison. A binding model that rationalizes the findings is given.

Amino Acid Sequence↗
PubMed1995

Molecular and clinical findings in Austrian cystic fibrosis patients with mutations in exon 11 of the CFTR gene.

In order to determine the heterogeneity of mutations in exon 11 of the cystic fibrosis transmembrane conductance regular (CFTR) gene in Austrian cystic fibrosis (CF) patients, we analysed 207 non-delta F508 chromosomes by direct sequencing of PCR-amplified genomic DNA. A total of four previously described point mutations present on 14/207 (6.8%) non-delta F508 chromosomes were detected: G542X, G551D, R553X, and R553Q. The second CF mutation was delta F508 in most patients, W1282X (a nonsense mutation in exon 20) in one and a currently unknown non-delta F508 mutation in another case. One patient was documented to be homozygous for G542X. The proportion of non-delta F508 chromosomes among total CF chromosomes is 45% in Austria and 32% in the world population. In our population the mutations G542X, G551D, and R553X were found on 3.9% (1.7%), 1.9% (0.9%) and 0.5% (0.2%) of non-delta F508 chromosomes (of total CF chromosomes), respectively. The average worldwide frequencies of these mutations are higher: 7.1% (2.4%), 4.8% (1.6%), 2.1% (0.7%) of non-delta F508 chromosomes (of total CF chromosomes screened), respectively. A comparison of the allele frequencies in Austria with those detected in neighbouring countries reveals some notable differences. In a subsequent retrospective analysis we found that all nucleotide changes, identified by direct sequencing, can be detected by denaturing gradient gel electrophoresis (DGGE). The lack of any false positive or false negative result suggests that DGGE is a convenient and reliable screening method for point mutations.

Adolescent↗
PubMed1995

Sampling lymph node content of human immunodeficiency virus type 1 nucleic acids and p24 antigen by fine-needle aspiration in early-stage patients.

The potential of lymph node fine-needle aspiration (LNFNA) for sampling viral load was evaluated in excised, peripheral lymph nodes from five patients with early-stage human immunodeficiency virus type 1 HIV-1 disease (asymptomatic, CD4 cells > 300/mm3). The preponderance (> 80%) of viral RNA was within follicular germinal centers as noted by in situ hybridization on lymph node frozen sections (LNFSs) as well as within cohesive groups of 10-20 lymphoid cells (microfragments) in LNFNA preparations. Quantification of cells expressing HIV-1 RNA by in situ hybridization, quantification of HIV-1 gag RNA and gag DNA per 10(5) cells by polymerase chain reaction, and measurement of p24 antigen per 10(5) cells yielded similar values for LNFNA, lymph node mononuclear cells (LNMCs) from tissue homogenates by Ficoll-Hypaque separation, and LNFS. Sampling of lymph node viral load by LNFNA appears to capture viral components associated with both individual expressing cells and follicular germinal centers. Due to the advantages in terms of patients' morbidity, repeatability, and cost, assessment of lymphoid tissue viral load by LNFNA warrants an in vivo feasibility trial as an alternative to lymph node biopsy.

Adult↗