PubMed Health⌕ Search

Biomedical subjects

M Kurz

Publications and source records attributed to M Kurz.

At least 55 records · Page 3Linked to original sources
PubMed1998

3874 H1 and H3, novel antifungal heptaene antibiotics produced by Streptomyces sp. HAG 003874.

New antifungal antibiotics, designated as 3874 H1 and H3, were discovered in the fermentation broth of the strain Streptomyces sp. HAG 003874. The compounds were obtained as yellow powders after sequential purification by chromatography on MCI Gel CHP20P, Fractogel HW-40 and ODS reversed phase chromatography. On the basis of the results of spectroscopic analysis, it was found that 3874 H1, C58H86N2O18, MW 1098, belongs to the p-aminoacetophenone containing family of heptaene antibiotics, while 3874 H3, C57H87NO18, MW 1073, is a non-aromatic heptaene. In addition to these, a minor component, 3874 H2, C59H88N2O18, MW 1112, a N-methyl derivative of 3874 H1 has been detected. The structures were elucidated through mass spectral analyses and 1-D and 2-D homonuclear and heteronuclear NMR data. The outstanding physico-chemical feature of 3874 H3 is its improved solubility. The new heptaenes are potent antifungal compounds with broad activity spectra, encompassing dermatophytes, yeasts and filamentous fungi.

Anti-Bacterial Agents↗
PubMed1997

The effect of opioids on thermoregulatory responses in humans and the special antishivering action of meperidine.

In summary, both mu-receptor and combined mu/kappa-receptor opioids impair thermoregulatory control. Alfentanil, a pure mu-receptor agonist slightly increased the thresholds for sweating and markedly decreased the thresholds for vasoconstriction and shivering. However, the vasoconstriction-to-shivering range remained normal during alfentanil administration as it does during general anesthesia. Meperidine, a combined mu- and kappa-receptor agonist, also slightly increased the threshold for sweating and reduced the thresholds for vasoconstriction. However, meperidine reduced the shivering threshold twice as much as the vasoconstriction threshold, thus significantly increasing the vasoconstriction-to-shivering range. Furthermore, shivering during meperidine administration, once triggered, was of low intensity suggesting that the drug also decreased the gain of shivering. The special antishivering action of meperidine appears to result, at least in part, from its kappa-receptor activity.

Alfentanil↗
PubMed1997

Nuclear transport of H1 histones meets the criteria of a nuclear localization signal-mediated process.

We have studied the nuclear transport of H1 histones using the digitonin permeabilization assay system in order to establish the transport requirements for H1 translocation to the nucleus. Using HeLa cells and fluorescence-labeled calf thymus H1, we show that the H1 nuclear transport in permeabilized cells requires the addition of cytoplasmic extract. Furthermore, it can be blocked by energy depletion and by chilling or by addition of wheat germ agglutinin or by nonhydrolyzable GTP analogs. Thus, the import of H1 histones follows the criteria established for nuclear import mediated by nuclear localization signals (NLS). The distribution of basic amino acids in average H1 sequences, however, does not allow the assignment of a specific element as a classical NLS.

Biological Transport↗
PubMed1997

Fluconazole versus nystatin in the prevention of candida infections in children and adolescents undergoing remission induction or consolidation chemotherapy for cancer.

An open, prospective, randomized pilot study was performed to assess the efficacy and safety of oral fluconazole 3 mg/kg once daily compared with oral nystatin 50,000 units/kg/day in four divided doses in preventing candida infections in 50 children undergoing remission induction or consolidation therapy for cancer. In 21 of 25 fluconazole-treated and 20 of 25 nystatin-treated patients the overall outcome of prophylaxis was clearly successful. Mild and transient oropharyngeal candidosis was observed in two and three patients in the fluconazole and nystatin groups respectively. One patient randomized to fluconazole and two patients randomized to nystatin required empirical treatment with amphotericin B and one patient assigned to fluconazole developed tissue-proven candida colitis. Initially non-colonized patients remained yeast-free throughout treatment with no differences between the two study arms. Initially colonized patients stayed colonized throughout treatment although at the end of the study, more patients randomized to nystatin were still harbouring yeasts (P = 0.05). Almost exclusively, Candida albicans (95%) was isolated. A change in species was observed in one patient in each arm of the study. Candida krusei or Candida glabrata were not encountered. Transient elevations of hepatic transaminases were more common in the fluconazole group, although not statistically significant (28% vs 12%, P = 0.15). Reversible grade I gastrointestinal and skin symptoms were observed in four patients randomized to fluconazole (16 vs 0%, P < 0.05). Fluconazole was as safe and effective as nystatin in controlling yeast colonization and in preventing superficial and invasive candida infections and the empirical use of amphotericin B in children and adolescents undergoing intensive chemotherapy for cancer.

Adolescent↗
PubMed1997

Hepatotoxicity of clozapine.

Two hundred thirty-eight patients treated with either haloperidol or clozapine were investigated to shed more light on the incidence and severity of antipsychotic-induced liver enzyme increase. Serum glutamic-pyruvic transaminase (SGPT) increase was most frequently seen in both treatment groups. When analyzing the incidence rates for patients with increased liver enzyme values (serum glutamic-oxaloacetic transaminase, SGPT, gamma-glutamyl transpeptidase) that were higher than twice the upper limit of the normal range, clozapine-treated patients showed an SGPT increase (37.3%) significantly more frequently than patients treated with haloperidol (16.6%). Both patients with higher clozapine plasma levels and male patients were at a higher risk for an SGPT increase. At least 60% of the increase of the different enzymes remitted within the first 13 weeks of treatment. In general, the authors conclude that clozapine-induced liver enzyme elevation seems to be a common and mostly transient phenomenon.

Adult↗
PubMed1997

Activation of the CD95 system increases with disease progression in human immunodeficiency virus type 1-infected children and adolescents.

BACKGROUND: Increased apoptosis in infected as well as noninfected cells has been invoked in CD4+ T helper cell depletion during HIV-1 infection. A strong increase in the expression of CD95 (APO-1/Fas) and CD95 ligand, key regulators of apoptosis in normal T cells, has previously been described in freshly isolated T cells from HIV-1-positive children when compared with healthy age-matched controls. We also found an increase in spontaneous as well as specific CD95-mediated apoptosis in CD4+ and CD8+ T cells from these patients. However, the relationship of these findings to disease progression in children with HIV infection is not known. MEASUREMENTS AND SUBJECTS: We studied expression of CD95 and CD95 ligand as well as sensitivity towards spontaneous and anti-CD95-triggered apoptosis of T cells in 33 HIV-1-positive children and adolescents in different disease stages. RESULTS: Loss of CD4+ T cells in vivo was paralleled by an increase in the percentage of CD95 high T cells and an increase in anti-CD95-induced apoptosis of CD4+ T cells. CD95L mRNA was constantly up-regulated in T cells from patients in intermediate disease stages whereas patients with normal CD4 counts and patients with advanced T cell loss showed CD95 ligand-mRNA levels in or slightly above the range of normal controls. CONCLUSIONS: Disturbed regulation of the CD95 system may play an important role in the development of immunodeficiency during the course of HIV infection in children.

Acquired Immunodeficiency Syndrome↗
PubMed1996

3D structure of ramoplanin: a potent inhibitor of bacterial cell wall synthesis.

The 3D structure of ramoplanin was studied by NMR spectroscopy in aqueous solution. A total of 320 interproton distances were determined from a NOESY spectrum and were used as restraints in distance geometry calculations. A structural refinement was carried out by molecular dynamics calculations in a solvent box. The structure of ramoplanin is characterized by two antiparallel beta-strands which are formed by the residues 2-7 and 10-14, respectively. The beta-strands are connected by six intramolecular hydrogen bonds and a reverse beta-turn which is formed by Thr8 and Phe9 (in positions i+1 and i+2, respectively). Residues 2 and 14 are connected by a loop consisting of Leu15, Ala16, Chp17, and the side chain of Asn2. Although residues 14-17 show the formation of a beta-turn, only the N-terminal end of the turn is directly connected to one of the beta-strands (Gly14), whereas the C-terminal end (Chp17) is linked via the side chain of Asn2. The 3D conformation of ramoplanin is also stabilized by a hydrophobic cluster of the aromatic sidechains of the residues 3, 9, and 17. This hydrophobic collapse leads to a U-shaped topology of the beta-shee: with the beta-turn at one end and the loop at the other end. The structure found for ramoplanin differs corsiderably from the published structure of ramoplanose which might be due to a smaller number of NOE distance restraints used in the previous study.

Amino Acid Sequence↗
PubMed1996

Does eosinophilia predict clozapine induced neutropenia?

The atypical antipsychotic clozapine carries a high risk of inducing agranulocytosis. We attempted to investigate whether eosinophilia during clozapine treatment has predictive value for subsequent neutropenia/agranulocytosis. One hundred and seventy-seven patients were studied in a prospective naturalistic design using haloperidol as the reference compound. Clozapine was found to differ from haloperidol in respect to their influence on neutrophil granulocytes. In the clozapine group patients with eosinophilia showed a decrease in neutrophil count (less than 2000/mm3 neutrophil granulocytes) significantly more often than patients without eosinophilia.

Adolescent↗
PubMed1996

Lack of DNA synthesis among CD34+ cells in cord blood and in cytokine-mobilized blood.

Flow cytometric DNA analysis was performed in combination with three-colour immunological staining of cell surface antigens on density-separated mononuclear cells (MNC) obtained from peripheral blood (PB) before, during and after cytokine stimulation of healthy adults. The aim of the study was to determine the cell-cycling status of haemopoietic progenitor cells mobilized into the blood of healthy volunteers during a 5 d treatment period with 5/micrograms per kg body weight of either granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-simulating factor (GM-CSF). Despite considerably increasing numbers of CD34+ PB MNC, the latter were not found to be in S/G2M phase, whereas, among the CD34- MNC, the proportion of cells in S/G2M phase increased from < 0.1% to 0.75 +/- 0.4% (GM-CSF) and to 1.34 +/- 0.75% (G-CSF) and dropped again after discontinuation of the cytokine stimulation. These cells expressed CD33 but were negative for CD45RA, CD3, CD19 and CD14 and were thus considered granulopoietic cells. Analogous results were obtained from analyses of cord blood (CB). In contrast, CD34+ cells from bone marrow (BM) were partially (between 9% and 15%) found to be in S/G2M phase. The non-cycling status of PB and progenitor cells was confirmed by the analysis of CD34+ cells enriched from the two cells sources. However, in vitro stimulation of these progenitor cells using IL3, GM-CSF, erythropoietin and steel factor (SF) revealed that, after 48 h in suspension culture, up to 30% of the CD34+ cells were in S/G2m phase. The fact that cycling CD34+ cells are only detectable in BM but not in PB or CB may suggest different adhesive properties of migrating/mobilized 'stem cells' which may require the BM micro-environment for adequate proliferation in vivo.

Adult↗
PubMed1996

Graft failure after donor leucocyte infusion in relapsed chronic myeloid leukaemia: successful treatment with cyclophosphamide and antithymocyte globulin followed by peripheral blood stem cell infusion.

We report a patient with chronic myeloid leukaemia who underwent allogeneic marrow transplantation (BMT) but had a molecular relapse 5 months and haematological relapse 15 months after BMT. Since therapy with alpha-interferon had been ineffective he received leucocyte infusions from his sibling donor. He developed acute graft-versus-host disease and became aplastic 6 weeks later. Despite donor marrow infusion and cytokine stimulation marrow aplasia persisted for 13 weeks. Then, donors' peripheral blood stem cells were given after conditioning with cyclophosphamide and antithymocyte globulin resulting in trilineage engraftment of donor haemopoiesis. Since then, the patient has been in continuous molecular remission for 11 months.

Antilymphocyte Serum↗
PubMed1996

Specificities of anti-platelet antibodies in multitransfused patients with haemato-oncological disorders.

The clinical condition and the formation of platelet-reactive antibodies influence the post-transfusion platelet increment. We analysed the specificities of platelet-reactive antibodies in 81 multitransfused patients with haemato-oncological diseases refractory to platelet transfusions, or prior to a scheduled stem cell transplantation. In 17 additional patients we prospectively determined the development of platelet-reactive antibodies at the time of chemotherapy in weekly intervals. Sera were tested by the monoclonal antibody-specific immobilization of platelet antigens (MAIPA)-technique for antiplatelet antibodies against HLA class I antigens, the human platelet-specific alloantigens (HPA)-1, -2, -3, -5, and the platelet membrane glycoproteins (GP) Ia/IIa, Ib/IX, IIb/IIIa (panreactive). Platelet reactive antibodies were found in 54% of blood samples. They were frequent in patients with a history of possible previous immunization, particularly if patients were refractory to platelet transfusions. Platelet-reactive HLA antibodies were the most common antibodies. Even patients without a known risk of primary immunization who received exclusively leucocyte-depleted blood products formed antibodies. By the MAIPA technique, even LCT-negative sera were found to contain platelet-reactive antibodies.

Adolescent↗
PubMed1996

Immunophenotyping of human bone marrow-derived macrophages.

In vitro cultured cells derived from human bone marrow stimulated with macrophage-colony stimulating factor (M-CSF) or granulocyte-macrophage-colony stimulating factor (GM-CSF) were investigated for their immunophenotypic surface characteristics by flow cytometry. Approximately 80-90% of the cells showed morphological and histochemical features of macrophages and bore CD11a, CD11b, CD11c, CD14, CD29, CD32, CD33, CD44, CD45, CD54, CD64, CD71, HLA-DR antigen. The expression of CD4, CD25 and CD45RO were detected only in low density. Bone marrow-derived macrophages were negative for CD8, CD45RA, CD16 and CD23. Functionally, macrophages were able to phagocytose opsonized Escherichia coli, but no oxidative bursts were induced either by fmlp or by opsonized bacteria. Cell surface phenotyping revealed a CD pattern very similar to monocyte-derived phagocytes, and was partially distinct from resident stromal macrophages.

Adult↗
PubMed1996

The composition of CD34 subpopulations differs between bone marrow, blood and cord blood.

Our previous data obtained by flow cytometry and by clonogenic assay had consistently shown a lower cloning efficiency of hematopoietic progenitor cells in bone marrow (BM) compared to those in blood (PB) or in cord blood (CB). Also, recent clinical reports have described more rapid reconstitution after PB than after BM transplantation. We have applied two- or three-color flow cytometric analysis using monoclonal antibodies directed against the stem- and progenitor cell antigen CD34, in combination with other cell surface markers. We report significant differences in the composition of progenitor cells contained in BM (238 specimens from 53 healthy donors and from patients in remission), PB (301 samples from 92 patients with or without cytokine support) and CB (n = 37). Leukapheresis products (Pher, n = 69) were included in the study as well as positively selected CD34+ cells obtained from BM (BMsel, n = 2), PB (PBsel, n = 28) and CB (CBsel, n = 5). We used monoclonal antibodies directed against CD7, CD19, CD34, CD38, CD45RA and glycophorin A. The highest proportion of CD34+ cells (in % of the MNC) was found in BM (mean 5.37% +/- 4.5). In the other sources, the mean values were 1.79% +/- 2.46 (PB), 1.48% +/- 1.81 (Pher) and 1.1% +/- 1.69 (CB). However, BM was the only source in which a considerable proportion of the CD34+ cells coexpressed the B cell antigen CD19 (mean 30.1%, median 28, range 0 to 84%). The amount of earlier myeloid progenitors as determined by their non-expression of the CD45RA antigen was lowest among BM CD34+ cells (26.7% +/- 16.6). In the other sources, the respective values were 57.5% +/- 17.9 (PB), 63.6% +/- 13.9 (Pher) and 70.4% +/- 16.1 (CB). These results were confirmed by subtype analyses of the CD34+ cells positively selected from the three sources. Enrichment showed minor CD34+ subpopulations to be identified. The mean proportions of B cell progenitors were 0.11% +/- 0.24 (PBsel) and 1.3% +/- 1.42 (CBsel) of the CD34+ cells. The CD34+ cells from all cell sources coexpressed GPA (median 0.15%, range 0 to 1.8%) and CD7 (median 0.25%, range 0 to 1.2%). The proportion of CD38- cells ranged from 0.7 to 4% of the CD34+ MNC. Thus, despite higher CD34 counts in BM, the relative proportions of myeloid progenitors are higher in PB and in CB. This suggests that, if timely reconstitution depends on the number of CD34+ cells transplanted, the mean number of "stem cells' (SC) required is 1.4-fold (for myeloid cells) or 2.2-fold (for earlier myeloid cells) higher for BM than for PB.

Adolescent↗
PubMed1996

[Quality of the location as a principle in psychiatric health care planning].

The goal of reasonable accessibility of specialised care to all those who need it must be kept in mind when planning to establish mental health service in the community. For methodological purposes, an attempt is made to quantify and thus render measurable the accessibility factor, also to be called "quality of location", based on "spatial" as well as "non-spatial" indicators. In many areas of community life involving planning and political decision making, the importance of such an approach cannot be underestimated. On the basis of the 1989 case register in the Austrian State of Tyrol, we investigated the relationship between administrative prevalence and the distance between the patient's home and the nearest hospital providing in-patient care, this distance being measured in terms of the time it takes to get to the hospital by public transportation. Our investigation confirmed the phenomenon described for the first time in 1852 by E. Jarvis, that there is an inverse relationship between the frequency of hospital admission and the geographical distance patients had to travel. This observation was validated, first of all, by excluding the possibility of selective migration influencing the inverse relationship between utilisation of available facilities by patients and the distance from their homes, and, secondly, by making suitable adjustments for the influence of "non-spatial" indicators such as rural/urban differences, socio-demographic variables and economic factors as indicated by the census figures. In the health service region we investigated, comprising of small town/rural areas, it was found that the Jarvis effect was slightly weakened; this observation, however, could not be explained solely in terms of the "non-spatial" indicators. What is new in the present investigation is the use of time as a dimension in the description of quality of location, as well as the approach combining the two sets of indicators, the "spatial" and the "non-spatial", which have hitherto been considered isolated from each other. Using the temporal dimension, it was possible to determine the time limit, i.e. the "sensitivity to distance" which can be looked upon as defining reasonable accessibility to in-patient care. This turned out to be about 30 to 45 minutes of travel by public transportation, this being shorter than the figure given by the German Mental Health Service survey. In summary, our investigation shows that the temporal dimension-the distance between home and hospital measured in terms of the time it takes to get to the hospital-is the most significant determinant of the quality of location; socio-demographic and economic factors play merely a secondary role.

Adolescent↗
PubMed1995

Characterization of hematopoietic stem cells.

On the basis of density-separated mononuclear cells isolated from bone marrow, peripheral blood, and cord blood, we have repeatedly shown good correlation between two-color flow cytometric (FACS) CD34 analysis and colony formation in the clonogenic assay. We have analyzed the distributions of CD34 subpopulations in these three stem cell sources using patients' and donors' bone marrow biopsies (n = 196), cord blood samples from full-term deliveries (n = 14), and peripheral blood from patients mobilized by chemotherapy and/or cytokine treatment (n = 258). Irrespective of absolute cell counts, the mean (+/- SD) proportions of CD34+ cells were clearly higher in bone marrow (5.6 +/- 4.6% of mononuclear cells) than in peripheral blood (1.9 +/- 2.6) and cord blood (1.7 +/- 2.6). However, two-color FACS analyses revealed significant differences among these cell sources with regard to their distribution of CD34 subpopulations: B-cell progenitors coexpressing CD34 and CD19, at considerable concentrations of > 0.5%, were only found in bone marrow (mean 30 +/- 24.3% of CD34+ mononuclear cells, median 28.7%, minimum 0%, maximum 83.3%). In addition, CD34+ cells in S/G2M phase were never detected in peripheral blood or cord blood, but only in bone marrow at a concentration of 10-15% of CD34+ mononuclear cells. On the other hand, the proportions of relatively immature myeloid progenitors, as characterized by not expressing CD45RA and by higher clonogenic capacity, were significantly higher in cord blood (76.7 +/- 17.2) and peripheral blood (58.2 +/- 17.5) than in bone marrow (26.4 +/- 16.7). These data were confirmed by analysis of apheresis products and of progenitors positively selected from different cell sources, and they may explain why, in autologous transplantations of analogous amounts of CD34+ cells, peripheral blood is superior to bone marrow. We conclude from our results that if successful transplantation and timely recovery depend on the number of CD34+ cells transplanted, the mean amount of stem cells required is 1.4- (for myeloid cells) or 2.2-fold (for early myeloid cells) higher for bone marrow than for peripheral blood.

Antibodies, Monoclonal↗