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Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 397 records · Page 22Linked to original sources

Aneurysms and vacuolar degeneration of cerebral arteries in late-onset acid maltase deficiency.

We present a case of late-onset acid maltase deficiency (AMD) with pronounced involvement of the liver and skeletal muscles. In addition, and in contrast to other adult cases of AMD, the case presented here shows CNS pathology with hypodense and hyperintense white matter areas on CT and MRI scans, and myelin changes ranging from focal areas of demyelination to necrosis. Neuropathologic changes seem to be related to unusual vascular pathology consisting of vacuolar degeneration of small and large arterial blood vessels. Vacuoles of varying size, partly filled with granular PAS-positive material, were found in pericytes and smooth muscle cells of arterial vessel walls. Electron microscopy revealed lysosomal and cytoplasmic free glycogen in smooth muscle cells in the intima of large cerebral arteries as well as in pericytes of arterioles and capillaries. Accumulation of glycogen locally was associated with severe cellular damage and necrosis. The formation of a great number of small aneurysms of intracerebral arteries is thought to be the result of cell damage in the vessel walls.

Adult↗

Antiasthmatic effects of onions: inhibition of 5-lipoxygenase and cyclooxygenase in vitro by thiosulfinates and "Cepaenes".

Nine thiosulfinates (TS) and four "Cepaenes" (CS) isolated from onions and/or synthetized by us showed dose dependent (0.25 to 100 microM) marked inhibitory effects on both cyclooxygenase (CA, tested on sheep seminal vesicle microsomes) and 5-lipoxygenase activity (LO, tested on porcine leukocytes). The following rank order of activity was observed: saturated aliphatic TS less than aromatic TS approximately alpha, beta-unsaturated TS less than CS. CS inhibited both CA and LO by more than 75% at 10 and 1 microM concentrations respectively. Most likely, these in vitro effects are responsible for antiinflammatory and antiasthmatic properties of onion extracts observed in vivo, at least in part.

Allium↗

New biologically active triterpene-saponins from Randia dumetorum.

Two new triterpene-saponins, 3-O-[O-beta-D-glucopyranosyl-(1----4)-O-beta-D-glucopyranosyl-(1----3)-( beta- D-glucuronopyranosyl)]oleanolic acid (1), 3-O-[O-beta-D-glucopyranosyl-(1----6)-O-beta-D-glucopyranosyl- (1----3)-(beta-D-glucuronopyranosyl)]oleanolic acid (2) together with five known saponins (3-7) were isolated from the methanolic extract of the fruits of Randia dumetorum (Retz) Lam. (Rubiaceae). Their structures were established on the basis of chemical and spectral data. The compounds 1, 3, 4, 5 were found to enhance significantly the proliferation of human lymphocytes in vitro. The crude saponin fraction showed haemolytic, molluscicidal, and immunostimulating activities.

Animals↗

Primary central nervous system lymphoma in patients with and without the acquired immune deficiency syndrome. A retrospective analysis and review of the literature.

Twenty-two cases of PCL were reviewed, in which 9 patients had AIDS and 13 did not. A review of the literature identified 247 cases of AIDS-related PCL. Differences between patients with AIDS and immunocompetent PCL were noted in our series. AIDS-related PCL when compared to non-AIDS PCL in our series has the following notable clinical features: 1) significantly younger age at presentation, median age 34 versus 59 years; 2) significantly higher incidence of B symptoms, 44% versus 8%; 3) worse median performance status at presentation, 3 versus 1; and, 4) shorter median survival, 3 versus 10 months. Differences in performance status and survival, however, were not significant. AIDS-related PCL is further characterized by frequent (44%) ring-enhancing mass lesions on head CT scan, a finding that makes it clinically difficult to distinguish from toxoplasmosis. Median survival appears to be improved in the absence of opportunistic infection at time of diagnosis of PCL, 6 versus 2 months. The therapeutic approach to patients with PCL, with and without AIDS, is variable. Combined modality therapy may improve the survival in patients with non-AIDS PCL. Therapy for patients with AIDS-related PCL is tailored to the status of the individual and it is, therefore, difficult to make comparisons to non-AIDS PCL patients. AIDS patients are often too ill to tolerate aggressive surgery or systemic treatment and in this instance, radiotherapy alone may be an acceptable alternative. Nonetheless, overall survival for patients with AIDS-related and non-AIDS PCL remains poor.

Acquired Immunodeficiency Syndrome↗

Immunomodulation by intravenous immunoglobulin.

In 1980, it was observed in a child with idiopathic thrombocytopenic purpura (ITP) that intravenous administration of pooled human immunoglobulin-G (IVIG) was followed by a rapid increase of the platelet count. Prompted by this finding, a pilot study and two prospective multicenter studies on children with ITP were organized. Efficacy of this new treatment for ITP was soon confirmed worldwide. In addition to the immediate effect, long-term observations following administration of IVIG suggested the occurrence of modulation of the immune response. Also, concomitant with studies on the mechanism of action of IVIG, the use of IVIG in the treatment of patients with other immune-related disorders was explored.

Adjuvants, Immunologic↗

Immunity to mycobacteria: possible role of alpha/beta and gamma/delta T lymphocytes.

Immunity to pathogenic mycobacteria is mediated by T lymphocytes. The possible contribution of CD4 alpha/beta T cells, CD8 alpha/beta T cells and gamma/delta T cells as well as the possible role of interleukin-mediated macrophage activation and target cell lysis through direct cell contact is discussed. Furthermore, attempts to define mycobacterial antigens for T lymphocytes with particular emphasis on heat shock proteins are described. The data currently available suggest complex interactions between different T-cell types in immunity to mycobacteria.

Antigens, Bacterial↗

Anti-inflammatory effects of onions: inhibition of chemotaxis of human polymorphonuclear leukocytes by thiosulfinates and cepaenes.

Seven different synthetic thiosulfinates, and cepaene- and/or thiosulfinate-rich onion extracts were found to inhibit in vitro the chemotaxis of human granulocytes induced by formyl-methionine-leucine-phenylalanine in a dose-dependent manner and at a concentration range of 0.1-100 microM. Diphenylthiosulfinate showed the highest activity and was found to be more active than prednisolone. The anti-inflammatory properties of onion extracts are related, at least in part, to the inhibition of inflammatory cell influx by thiosulfinates and cepaenes.

Adult↗

Aromatase inhibition with 4-hydroxyandrostenedione in the treatment of postmenopausal patients with advanced breast cancer: a phase II study.

Estrogen deprivation by aromatase inhibition is an effective treatment in breast cancer. Between October 1986 and March 1988, 91 postmenopausal patients with advanced breast cancer entered a phase II study performed jointly in three center to investigate the new aromatase inhibitor 4-hydroxyandrostenedione. Patients received 500 mg 4-hydroxyandrostenedione intramuscularly (IM) every 2 weeks for 6 weeks, and 250 mg every 2 weeks thereafter. There were two complete (CRs) and 19 partial remissions (PRs) (response rate, 23%). Disease stabilization (no change; NC) was seen in 26 patients, and in 44 patients (48%), disease progression occurred. Duration of the CRs is 20+ months, median durations of PR and NC are 13+ and 8 months, respectively. Receptor status, relapse-free interval, and sites of metastatic lesions did not appear to influence treatment results. However, efficacy of previous tamoxifen treatment favorably predicted response to 4-hydroxyandrostenedione. Serum estradiol levels decreased significantly in patients after 2 weeks of treatment. Side effects were mostly nonspecific and of low degree, requiring discontinuation of treatment in only 3% of the patients. We conclude that aromatase inhibition with 4-hydroxyandrostenedione is efficacious in the treatment of postmenopausal breast cancer.

Adult↗

[Birdshot retinochoroidopathy. Case report].

The clinical findings and results of perfusion-pressure videoangiography (PVA) are described in a 50-year old patient suffering from birdshot retinochoroidopathy. PVA according to Ulrich and Ulrich makes it possible to observe the gradual filling of the retinal and choroidal vessels relative to ocular perfusion pressure. The patient's PVA reveals that the fluorescein penetrates the vessel wall in the interstitial tissue in the region of the large choroidal arterioles close to the entry of the short posterior ciliary arteries in the eye. This occurs long before the blood flow has reached the choriocapillaries, i.e., at distinctly lower perfusion pressures than are necessary for filling the leaking choroidal capillaries. The leakage of fluoresceine from the large choroidal arterioles explains the typical birdshot pattern of the fundus.

Blood Pressure↗

[Joint-preserving osteotomy in segmental femur head necrosis].

Joint-preserving osteotomies for segmental necrosis of the femoral head are clinically important, as necrosis often occurs in relatively young people in whom one is hesitant to perform femoral head replacement. The principle in all joint-preserving osteotomies is to remove the necrotic area from the zone subject to load, thereby guarding against indentation of the joint surface. The most universal and most frequently indicated osteotomy is intertrochanteric valgus flexion osteotomy with ventral capsule resection. The result of the operation depends mainly on the extent of the necrosis. If the angle of the necrosis is under 200 degrees, the hip joint can be preserved with great precision and in a good enough state to allow joint replacement to be postponed for many years.

Adult↗

[Pelvic tilt and leg length correction].

Pelvic tilt is often the consequence of a discrepancy in leg length and can be corrected either with orthotic devices or by operative equalization of the leg length. However, pelvic tilt can also occur independently of the leg length in cases of asymmetry of the pelvis, malposition of the hip joint or contracted scoliotic deviation of the spine. In such cases with complex deformities correction of the pelvic tilt should aim a balanced body posture rather than necessarily a symmetric level of the iliac crests.

Adolescent↗

Application of free flow electrophoresis to the preparative purification of basic proteins from an E. coli cell extract.

The application of free flow electrophoresis (FFE) to the purification of a basic protein from a complex protein mixture was investigated. For this purpose lysozyme (E.C.3.2.1.17) from hen egg white, serving as a model for a basic protein, was added to a crude E. coli cell extract and reisolated. For three techniques of FFE (zone electrophoresis, isoelectric focusing and field step electrophoresis), suitable electrolyte systems were developed. The purity, purification factor, recovery and throughput were determined for the optimized experiments. A combination of field step electrophoresis and zone electrophoresis gave the best purification factor (9.5) and the highest recovery (95%). The purification factors achieved in zone electrophoresis and isoelectric focusing were comparable to each other and ranged from 3.5 to 4.75. In isoelectric focusing, 94% of the enzyme activity was recovered. Zone electrophoresis gave recoveries of 82% and 87%, respectively. Purities of more than 95% were achieved with all the techniques described. With the exception of zone electrophoresis, all the techniques effected a concentration of the enzyme during the separation. Zone electrophoresis and field step electrophoresis were very simple in application.

Bacterial Proteins↗

Enhancement of acute ethanol hepatotoxicity under conditions of low oxygen supply and ischemia/reperfusion. The role of oxygen radicals.

Using isolated hemoglobin-free perfused rat livers we studied the effect of low oxygen supply on ethanol hepatotoxicity in two models. In the first model resembling low blood supply, perfusion rate was lowered from 60 to 10 ml/min after a 30 min-equilibration phase and kept low for 60 min. As a consequence, oxygen consumption fell from 1.76 +/- 0.15 mumol/min/g to 0.51 +/- 0.02 mumol/min/g. In the second model, total ischemia was accomplished by interruption of the perfusion for 30 min and was followed by reperfusion at a perfusion rate of 60 ml/min for a further 30 min. In this model, oxygen consumption returned immediately to normal values upon reperfusion. In both models, low oxygen supply had no toxic effects of its own on livers from fed rats. While ethanol (3 g/l) given under normoxic conditions led to a moderate hepatotoxicity, its application in both models of partial as well as total ischemia and reperfusion resulted in a marked liver damage as evidenced by a strong release of sorbitol dehydrogenase, glutamate-pyruvate-transaminase, lactate dehydrogenase and glutathione, as well as by an increase in hepatic calcium content. Inhibition of ethanol metabolism by 4-methylpyrazol prevented liver damage in both models indicating that metabolism of ethanol is a prerequisite for its toxicity to occur. Also, hepatotoxicity was inhibited partially by catalase and superoxide dismutase and nearly totally by deferrioxamine and allopurinol. Thus, reactive oxygen species which are produced during ethanol metabolism as well as under conditions of low oxygen supply are mediators of hepatic damage in both models employed.

Animals↗

A novel subset of CD2-, CD3/T cell receptor alpha/beta+ human peripheral blood T cells. Phenotypic and functional characterization of interleukin 2-dependent CD2-CD3+ T cell clones.

It is generally believed that CD2 (T11, sheep erythrocyte receptor) is expressed on all human T cells. In the present study we have identified and characterized a minor subset of CD2- CD3/TCR alpha/beta+ T cells in the peripheral blood of healthy individuals. CD2-CD3+ T cells were enriched in PBMC depleted of plastic-adherent macrophages, E-rosetting (i.e., CD2+) T cells and surface Ig+ B cells. CD2-CD3+ T cells accounted for 0.1-0.8% of PBMC in six individuals. IL-2-dependent long-term clones of CD2-CD3+ T cells neither reacted with a panel of anti-CD2 mAbs nor expressed detectable levels of CD2 mRNA by Northern blot analysis. These clones, however, expressed a full-length TCR C beta mRNA and reacted with mAbs against TCR-alpha/beta, CD3, and CD4, and thus were mature T cells. CD2-CD3/TCR+ T cell clones could be triggered into proliferation, IL-2 production, and cytotoxic effector activity by anti-CD3 and anti-TCR mAbs. We conclude that (a) a minor subset of CD2-, CD3/TCR-alpha/beta+ T cells is present in normal peripheral blood; and (b) expression of CD2 at the level of protein and/or mRNA is not required for T cell signaling via the CD3/TCR molecular complex.

Antibodies, Monoclonal↗

Non-C-G recognition sequences of DNA cytosine-5-methyltransferase from rat liver.

The eukaryotic DNA cytosine-5-methyltransferase (E.C.2.1.1.37) is known to methylate cytosine in DNA mainly, but not exclusively in C-G. In the present study the minor, non-C-G recognition sequences of a rat DNA methyltransferase were analyzed by Maxam-Gilbert sequencing of in vitro methylated SV40 DNA. The enzyme methylates C-A and C-T at a 50-fold lower initial rate than C-G. Methylation of C-C at the 5'C was not observed in the piece of DNA sequenced. The methylation of C-A is very low in the trinucleotides ACA and CAC, the other C-A containing trinucleotides in DNA are much better methylacceptors. C-T was found methylated predominantly in the sequences CCTAA, ACTAA, and ACTGT. A comparison of the activity with different substrates is in favour of the enzyme making its recognition in the major groove of the DNA.

Animals↗

Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea.

In this study, acidic arabinogalactan, a highly purified polysaccharide from plant cell cultures of Echinacea purpurea, with a molecular weight of 75,000, was effective in activating macrophages to cytotoxicity against tumor cells and micro-organisms (Leishmania enriettii). Furthermore, this polysaccharide induced macrophages to produce tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1), and interferon-beta 2. Arabinogalactan did not activate B cells and did not induce T cells to produce interleukin-2, interferon-beta 2, or interferon-gamma, but it did induce a slight increase in T-cell proliferation. When injected ip, this agent stimulated macrophages, a finding that may have therapeutic implications in the defense against tumors and infectious diseases.

Animals↗