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J Winkler

Publications and source records attributed to J Winkler.

At least 91 records · Page 5Linked to original sources
PubMed1998

[New nerve cells for the adult brain. Adult neurogenesis and stem cell concepts in neurologic research].

A growing branch of neuroscience is investigating conditions that permit neurogenesis in the adult brain. Partially, this aims at using the neuroectodermal stem or precursor cells that persist in the adult brain to induce neuroregenerative processes in the treatment for neurologic disorders. In ex vivo approaches, isolated precursor cells are implanted into the host brain, while in vivo concepts favor a stimulation of precursor cells in situ.

Adult↗
PubMed1998

An alpha-actinin-profilin chimaera with two alternatively operating actin-binding sites.

Studying the mode of interaction between actin and actin-binding proteins, we constructed a chimaeric protein consisting of the sequence for bovine profilin I (P), to which the sequence for the actin-binding domain of Dictyostelium discoideum alpha-actinin (alphaA1-2) was fused N-terminally. The resulting hybrid clone was expressed in Escherichia coli, and the chimaeric protein, alphaA1-2P, purified by affinity chromatography on poly-(L-proline) (PLP) columns and identified using specific antibodies. High resolution electron microscopy demonstrated that this protein consists of two discrete subdomains. In biochemical, viscometric and electron microscopic analyses, we showed that both modules in this molecule are biologically active. The chimaera binds to poly-(L-proline) and inhibits the polymerization of G-actin in KCl, which is consistent with the assumption that the profilin part is intact. Inhibition of actin polymerization in KCl was stronger than that of the parental profilin, and the Kd value of its interaction with rabbit skeletal muscle actin, as determined by falling ball viscometry, was smaller (mean value 0.5 x 10(-6) M, as compared to 1.9 x 10(-6) M for bovine profilin). In 2mM MgCl2, the actin polymerized rapidly, consistent with the interpretation that under these conditions the chimaera, like profilin, is less efficient as an actin-sequestering agent. In the presence of alphaA1-2P, the resulting filaments were decorated with particles projecting from the filament axis. We conclude that under these conditions the alphaA1-2 domain of alphaA1-2P is preferentially active, attaching the chimaeric particles laterally to the filaments. Hence, the parental modules combined in alphaA1-2P permit this molecule to switch from a G-actin- to an F-actin-binding form.

Actinin↗
PubMed1998

Rhinocerebral zygomycosis following bone marrow transplantation in chronic myelogenous leukaemia. Report of a case and review of the literature.

We report on a man suffering from chronic myelogenous leukaemia treated by allogeneic bone marrow transplantation who, in the late post-transplantation phase, developed a hyperacute fatal invasive rhinocerebral zygomycosis. The origin of the ascending infection was the sinus sphenoidalis from which fungal hyphae spread to the central nervous system via the skull and the dura mater. The first symptoms of this severe infection were cerebral convulsions and a bilateral total amaurosis. The isolation of the pathogen from post mortem tissue was not successful. The present case is compared with previous reports of zygomycoses after bone marrow transplantation.

Adult↗
PubMed1998

Analysis of breast milk to assess exposure to chlorinated contaminants in Kazakstan: high levels of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) in agricultural villages of southern Kazakstan.

To assess levels of chlorinated contaminants in breast milk, we measured organochlorine pesticides, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) in breast milk samples collected in 1994 according to the World Health Organization protocol from 92 donors that were representative of regional populations in southern Kazakstan. High levels (10-120 pg/g fat) of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic of the PCDD/PCDF congeners, were found in breast milk samples from an agricultural region. TCDD was the major contributor (75%) to the international toxicity equivalents of these samples. The same distinctive PCDD/PCDF congener pattern was found in 15 breast milk samples and 4 serum samples collected in 1996 in a follow-up study, and has now been confirmed by three analytical laboratories.

Adolescent↗
PubMed1998

[Successful therapy of pulmonary aspergillosis in a patient with non-Hodgkin lymphoma].

UNLABELLED: ANAMNESIS AND CLINICAL PICTURE: A 65-year old male with non-Hodgkin lymphoma developed severe invasive pulmonary aspergillosis during a state of leucopenia after chemotherapy. INVESTIGATION: The initial manifestation was an infiltration in the right upper lobe of the lung, identified by lung scintigraphy as a peripheral wedge-shaped loss of perfusion. Both serum and bronchoalveolar lavage extreme high titre of Aspergillus antigen were seen as a laboratory indication of an invasive aspergillosis. The mould Aspergillus fumigatus was repeatedly isolated from bronchoalveolar lavage and bronchial secretion. THERAPY AND CLINICAL COURSE: Treatment was started with amphotericin B plus 5-flucytosine together with repeatedly bronchoscopic instillation of miconazole followed by thoracosurgical intervention with resection of the right upper lobe of the lung. Despite prophylaxis by itraconazole, a relapse of invasive aspergillosis occurred three months later probably due to persistence of aspergillus fungal elements in the left lung. The aspergillosis relapse was treated at first with liposomal amphotericin B. After eighteen days of treatment this was changed to a combination of 5-flucytosine with oral application of itraconazole, and cure was achieved.

Aged↗
PubMed1997

A Study of the Mechanism of Bleaching Cotton Using Peracids and Hydrogen Peroxide as Model Systems

The mechanism of bleaching cotton dyed with the reactive dye 5-(4,6-dichlorotriazinyl)aminofluorescein has been investigated using hydrogen peroxide as a model system. A general strategy for the study of the mechanism and kinetics of bleaching is presented followed by the relevant theory to enable a discriminatory assessment of the experimental data obtained. A brief extension to the industrially relevant class of peracid bleaches is given. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1997

Flexibility and fine structure of smooth-muscle alpha-actinin.

The microfilament protein alpha-actinin exists as a dimer. The N-terminal regions of both polypeptides, arranged in antiparallel orientation, comprise the actin-binding regions, while the C-terminal, larger parts consist of four spectrin-like repeats that interact to form a rod-like structure. To elucidate the fine structure of smooth-muscle alpha-actinin, we used energy-filtered transmission electron microscopy in conjunction with negative staining. Survey pictures of the protein purified from chicken gizzard revealed discrete, elongated particles whose length and width varied with the ionic strength of the buffer. It was determined to to 29.3 nm x 4.8 nm in 0.05 M KCl and 32.6 nm x 4.4 nm in 0.15 M KCl. Both ends of the molecule displayed hook-like structures consisting of globular domains, which were highly variable in their orientation with respect to the long axis of the molecule. Their location at the ends of the molecule, and the finding that these hooks were missing from particles obtained by thermolysin digestion indicated that they probably correspond to the N-terminal actin-binding regions. The rod-like center of the molecule revealed discrete globular masses which probably comprise the spectrin-like repeats. Their arrangement was compatible with the interpretation that three spectrin repeats of each polypeptide chain can form pairs with the respective sequences of the other chain. The rod-like 53-kDa fragment obtained after thermolysin digestion largely retained this structural organization but appeared wider (22.5 nm x 5.9 nm). Our results help to clarify previous discrepancies on the quatenary organization of alpha-actinin and suggest that effective actin-binding and cross-linking of alpha-actinin is based on the high flexibility of the terminal hooks.

Actinin↗
PubMed1997

Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain.

Neurons and glia are generated throughout adulthood from proliferating cells in two regions of the rat brain, the subventricular zone (SVZ) and the hippocampus. This study shows that exogenous basic fibroblast growth factor (FGF-2) and epidermal growth factor (EGF) have differential and site-specific effects on progenitor cells in vivo. Both growth factors expanded the SVZ progenitor population after 2 weeks of intracerebroventricular administration, but only FGF-2 induced an increase in the number of newborn cells, most prominently neurons, in the olfactory bulb, the normal destination for neuronal progenitors migrating from the SVZ. EGF, on the other hand, reduced the total number of newborn neurons reaching the olfactory bulb and substantially enhanced the generation of astrocytes in the olfactory bulb. Moreover, EGF increased the number of newborn cells in the striatum either by migration of SVZ cells or by stimulation of local progenitor cells. No evidence of neuronal differentiation of newborn striatal cells was found by three-dimensional confocal analysis, although many of these newborn cells were associated closely with striatal neurons. The proliferation of hippocampal progenitors was not affected by either growth factor. However, EGF increased the number of newborn glia and reduced the number of newborn neurons, similar to the effects seen in the olfactory bulb. These findings may be useful for elucidating the in vivo role of growth factors in neurogenesis in the adult CNS and may aid development of neuronal replacement strategies after brain damage.

Animals↗
PubMed1997

Energy-filtered electron microscopy reveals that talin is a highly flexible protein composed of a series of globular domains.

Talin is a multidomain cytoskeletal protein containing discrete binding sites for acidic phospholipids, beta-integrin, actin and vinculin. Hence, it is thought to link microfilaments to the cytoplasmic membrane in cell-matrix adhesion sites, and this should critically depend on talin structure. To obtain more information on the latter, we used energy-filtered transmission electron microscopy of negatively stained talin purified from chicken smooth muscle. We show that in buffers of physiological ionic strength, talin adopts an elongated shape (56 +/- 7 nm in length), consisting of a series of globular masses. While these compact elements, arranged like beads on a string, were of rather uniform dimensions (3.8 nm in diameter), their center-to-center spacings varied, indicating the flexibility of the connecting strands. The ends of the elongated molecules frequently formed loops. The images obtained are consistent with the assumption that, under the conditions used, the majority of the talin molecules are monomeric. A minor fraction appeared as dimers, composed of two chains only partially intertwined, thus giving rise to Y-shaped particles. Electron micrographs revealed that the biochemically defined 50-kDa N-terminal talin head domain is composed of two globular subunits, while chemical cross-linking provided evidence that the C-terminal 220-kDa fragment is solely responsible for dimerization. These results imply that in the dimeric molecules, the polypeptide chains are arranged in parallel, in contrast to what has been described for human-platelet talin. In buffers of low ionic strength (0.02 M instead of 0.15 M KCl), the molecules collapsed into a compact shape. By showing the high flexibility and versatility of its morphology, our data favour the concept of talin as an important resilient link in microfilament-plasma-membrane attachment.

Animals↗
PubMed1997

Reversible Schwann cell hyperplasia and sprouting of sensory and sympathetic neurites after intraventricular administration of nerve growth factor.

Substantial dysfunction and loss of cholinergic neurons occur in Alzheimer's disease (AD). Nerve growth factor (NGF) is a potent neurotrophic factor for cholinergic basal forebrain neurons, and the use of NGF to stimulate residual dysfunctional cells in AD is being considered. To define the effects of NGF on other cell populations in the brain, NGF was continuously infused into the lateral ventricle of rats for 7 weeks. At the end of treatment, Schwann cell hyperplasia and abundant sensory and sympathetic neurite sprouting were observed in the subpial region of the medulla oblongata and the spinal cord. Following withdrawal of NGF, the Schwann cell hyperplasia and sprouting of sensory and sympathetic neurites disappeared completely. These findings suggest that better temporal and spatial delivery systems for NGF must be explored to limit potential undesirable side effects while maintaining the survival and function of diseased basal forebrain cholinergic neurons.

Animals↗
PubMed1997

Blood progenitor cell (BPC) mobilization studied in multiple myeloma, solid tumor and non-Hodgkin's lymphoma patients after combination chemotherapy and G-CSF.

For blood progenitor cell (BPC) mobilization, standard-dose VIP chemotherapy consisting of etoposide, ifosfamide and cisplatin has previously shown effective tumor reduction in solid tumor patients and sufficient progenitor cell mobilization for autologous blood cell transplantation. Mobilization chemotherapy regimens in multiple myeloma (MM) predominantly consist of melphalan or cyclophosphamide that induce marked cytopenia and considerable variability of progenitor cell collection. We studied whether in MM (n = 13), BPCs were efficiently and reproducibly mobilized with etoposide (500 mg/m2) and ifosfamide (1500 mg/m2), followed by daily s.c. G-CSF (5 micrograms/kg). In parallel, patients with solid tumors or non-Hodgkin's lymphomas (n = 28) treated with etoposide (500 mg/m2), ifosfamide (1500 mg/m2) and cisplatin (150 mg/m2) and identical dosing of G-CSF were analyzed. Before chemotherapy (day 0), on day 7 after chemotherapy and on days of leukapheresis (day 9-14), leukocyte numbers, mononuclear cells (MNCs), CD34+ cells and coexpression of lineage markers were analyzed. Median blood leukocyte numbers were 28,100/microliters (range, 19,600-40,400) on day 10 in myeloma patients and progressively declined over the next 4 days. In contrast, in solid tumor and lymphoma patients leukocyte numbers constantly increased from a median of 12,400/microliters (range, 6000-22,000) to 30,000/microliters (range, 16,300-63,300) between day 10 and day 13 after chemotherapy. Similar to leukocyte counts, median MNC numbers decreased in myeloma patients with successive leukaphereses, but steadily increased in solid tumor and lymphoma patients over the same period. CD34+ cell numbers in the blood peaked between day 9 and 11 (median: 40/microliters) in myeloma patients and then declined. In the solid tumor and lymphoma group, median CD34+ counts in the blood peaked on day 12 after mobilization chemotherapy (median: 100/microliters). The median CD34+ yield per leukapheresis in the myeloma group was 2.2 x 10(6)/kg (range, 1.5-4.7) on day 10, and fell steadily to 0.95 x 10(6)/kg on day 12, whereas in solid tumor/NHL patients median CD34+ cell yields remained between 3.5 and 3.7 x 10(6)/kg from day 10 to day 12 after mobilization chemotherapy (P < 0.001). To obtain sufficient cell numbers for engraftment a median of 2 (range, 1-3) mobilization chemotherapy cycles were needed in MM compared to 1 (range, 1-10) in solid tumor or lymphoma patients, with a median of 5 (range, 2-8) leukaphereses in MM compared to 1 (range, 1-10) (P < 0.05). Taken together, we found that for patients with MM, VP16 and ifosfamide efficiently and predictably mobilizes progenitor cells into the PB with > or = 3 x 10(6)/kg CD34+ cells collected after one to two mobilization chemotherapy cycles.

Adult↗
PubMed1997

Circulating aggregated platelets, number of platelets per aggregate and platelet size in chronic dialysis patients.

The accelerated arteriosclerosis of chronic dialysis patients is multifactorial. Both non-uremic patients with atherosclerosis and uremic patients have functional platelet abnormalities. Our aim was to study platelet function in chronic dialysis patients and to correlate the findings with the presence of cardiovascular morbidity. Fifty-three chronic dialysis patients were examined. The presence of risk factors for cardiovascular disease (CVD) was recorded, and the patients were examined for the presence of ischemic heart disease, peripheral vascular disease and cerebrovascular accident. The parameters of platelet function, which were examined with the modified Wu and Hoak method, included platelet number, percentage of totally, reversibly and irreversibly aggregated platelets, average number of platelets per aggregate and percentage of large platelets. Significant differences were found between totally aggregated platelets, reversibly and irreversibly aggregated platelets, the percentage of large platelets (p < 0.0001) and the average number of platelets per aggregate (p < 0.001) in dialysis patients compared with control persons. There was no difference between the 2 groups in platelet count. No differences were found between hemodialysis and peritoneal dialysis groups, and the duration of dialysis treatment had no effect. We conclude that platelet abnormalities evident in chronic dialysis patients are a part of the multifactorial etiology of advanced CVD and may predispose dialysis patients to CVD.

Arteriosclerosis↗
PubMed1997

Analysis of breast milk to assess exposure to chlorinated contaminants in Kazakstan: PCBs and organochlorine pesticides in southern Kazakstan.

Organochlorine pesticides (OC) and polychlorinated biphenyls (PCBs) were measured in samples of breast milk taken from 92 donors representative of regional populations in southern Kazakstan. The World Health Organization protocol for assessing levels of chlorinated contaminants in breast milk was followed. The most prevalent OC residues were beta-hexachlorocyclohexane (beta-HCH), p,p'-DDE, p,p'-DDT, hexachlorobenzene, and alpha-HCH. The measured levels of beta-HCH were among the highest reported in the published literature. Data from Aralsk, near the Aral Sea, indicated continuing DDT exposure. Overall PCB-toxic equivalent levels (22 pg/g fat) were similar to those reported in industrialized European countries. PCBs were highest in Atyrau in the Caspian oilfields.

Adolescent↗