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Biomedical subjects

S Winkler

Publications and source records attributed to S Winkler.

At least 91 records · Page 5Linked to original sources

Molecular, serological and population studies of the alleles and products of HLA-B*41.

The HLA-B41 specificity was first identified over 25 years ago and, although both serological and biochemical studies have suggested its subdivision, it is only recently that two HLA-B*41 alleles (B*4101 and B*4102) have been identified and sequenced. We designed three oligonucleotide primers, combined in two mixtures to define these alleles by PCR using sequence-specific primers (PCR-SSP) in a random normal population of 9,464 HLA-A, B, DR, DQ typed Northern European Caucasoid donors from the Welsh Bone Marrow Donor Registry. The HLA-B41 phenotype frequency was 0.835%, and of the 79 HLA-B41 subjects 22 (27.85%) were B*4101 and 57 (72.15%) were B*4102. The phenotype frequencies of B*4101 and B*4102 were 0.232 and 0.602%, respectively, and the gene frequencies were 0.00116 and 0.00301, respectively. Formal two-locus linkage disequilibrium (LD) analysis demonstrated significant associations between B*4101 and A30 and DR11, and between B*4102 and A66 and DR13. LD analysis of three loci showed significant associations between B*4101, DR7, DQ2 and B*4101, DR11, DQ7 (DQB1*0301/0304) and between HLA-A3, B*4102, DR13; A66, B*4102, DR7; A66, B*4102, DR13; B*4102, DR13, DQ6 and B*4102, DR13, DQ7. Examination of the HLA phenotypes (including HLA-C) of the B*41 subjects, together with the LD analysis findings, suggested four different HLA haplotypes bearing B*4101 and five B*4102 haplotypes. The most frequent B*4101 haplotype was: HLA- A30 or other A allele, Cw*1701, B*4101, DRB1*1102, DQB1*0301 and the most freqent B*4102 haplotype was: A*6601 or A3 or other A allele, Cw*1701, B*4102, DRB1*1303, DQB1*0301. In addition, the well-known association of A66 with B41 was between A*6601 and B*4102, and although both B*41 alleles were commonly in association with Cw*1701, B*4101 was found with Cw*07. One-dimensional isoelectric focusing (1D-IEF) analysis of HLA-B proteins from 2 B*4101 and 2 B*4102 subjects clearly showed that the B41.1 and B41.2 1D-IEF variants, identified in the 10th International Histocompatibility Workshop, corresponded to B*4101 and B*4102 products, respectively. Serological titration studies, with 59 lymphocytotoxic pregnancy antisera, containing an HLA-B41 component and stimulated by up to five different HLA-B specificities, were unable to differentiate the two groups of B*41 subjects. This suggests that partition of the HLA-B41 specificity will not normally be achieved by classical serological methods. It is suggested that the previous alleged serological subdivision of HLA-B41 was founded on the unwitting use of antisera detecting the HLA-Cw*17 products.

Alleles↗

Depressed taste and smell in geriatric patients.

BACKGROUND: Geriatric patients have a number of dental care problems that younger patients do not encounter. The oral changes associated with aging can have a significant effect on the efficacy of dental treatment. TYPES OF STUDIES REVIEWED: The authors reviewed studies dealing with the causes of depressed sense of taste and smell; the causes included aging, disease, medications and dental problems. Based on their findings, the authors described the location and anatomy of taste buds and receptor cells for smell and explored appetite, saliva, food seasonings, nutrition and dietary recommendations. They also discussed the relationship of smoking and tongue cleaning to taste sensations. RESULTS: The authors found that considerable differences exist between elderly people and young people in regards to sensory perception and pleasantness of food flavors. Salt and bitter taste acuity declines with age, but sweet and sour perceptivity does not. Olfactory acuity also declines with age. The authors found that most of the studies reviewed suggested that the sense of smell is more impaired by aging compared with the sense of taste. Smoking diminishes the taste of food and makes flavorful foods taste flat, while tongue brushing can increase taste sensation for geriatric patients. CLINICAL IMPLICATIONS: Food can become tasteless and unappetizing for geriatric patients as the result of declining taste and smell perception. Geriatric patients should be encouraged to add seasonings to their food instead of relying on excessive consumption of salt and sugar to give their food flavor. Adequate nutrition, tongue cleaning and smoking cessation are recommended for geriatric dental patients.

Aged↗

Contact angle measurement on dental implant biomaterials.

Wettability may be one of the surface factors to be considered when selecting dental implant biomaterials. Contact angles of dental implant surface preparations influence wettability and tissue adhesion. The contact angles of eight implant surface preparations were determined in this study. Contact angles were measured by a tele-microscope equipped with a protractor eyepiece. Groups 1 to 6 had a Ti6Al4V substrate. Group 1 was metallurgically polished, group 2 was blasted with 180 microns Al2O3, group 3 was blasted with 710 microns Al2O3, group 4 was hydroxyapatite (HA) blasted (125 microns), group 5 had a Calcitite HA plasma-sprayed coating, and group 6 was coated with plasma-sprayed MP-1 HA. Group 7 was metallurgically polished commercially pure (CP) titanium (grade 1), and group 8 was etched CP titanium (grade 1). Contact angles were measured 30 times for each group with distilled water and glycerol, and the determinations were statistically analyzed. Mean contact angles for groups 1 to 8 were 65.5, 65.3, 62.5, 67.9, 46.6, 81.7, 58.5, and 69.0, respectively, when tested with distilled water, and 70.7, 68.3, 81.6, 75.4, 67.1, 70.7, 62.3, and 82.5, respectively, when tested with glycerol. Analysis of variance and Tukey's Honestly Significant Difference test (p = 0.05) demonstrated significant differences between group 5 and all other groups when groups were tested with distilled water and demonstrated no significant differences between groups 5 and 7 when groups were tested with glycerol. Surface preparation of implant biomaterials affects wettability. In this study, Ti6Al4V coated with Calcitite HA had the lowest contact angles and the best wettability.

Alloys↗

Increased frequency of Th2-type cytokine-producing T cells in microfilaremic loiasis.

The frequency of cytokine-producing peripheral blood mononuclear cells was assessed in 28 subjects with microfilaremic loiasis and in 14 amicrofilaremic individuals. In addition, a subgroup of seven microfilaremic individuals coinfected with Plasmodium malariae was evaluated. By using flow cytometry for the intracellular detection of cytokines, a more pronounced T helper (Th)2 cell-type response with the expansion of interleukin (IL)-4, IL-10, and IL-13 expressing CD4+ cells in the microfilaremic compared with the amicrofilaremic group was noted. Expression of IL-5 was equivalent in both groups as was the frequency of Th2-type cytokines expressing CD8+ cells and of Th1-type cytokines (interferon [IFN]-gamma, IL-2, IFN-gamma/IL-2) producing CD4+ and CD8+ cells. Th0-type cytokine-expressing cells, represented by IL-4/IFN-gamma, IL-10/IFN-gamma, and IL-13/IFN-gamma, were equally distributed within groups. Coinfection of P. malariae did not significantly alter the cytokine expression compared with microfilaremic individuals without P. malariae infections. By identifying a large panel of cytokine-producing T cell subpopulations, a Th2-driven immune response in microfilaremic Loa loa patients was noted.

Adult↗

Frequency of cytokine-producing CD4-CD8- peripheral blood mononuclear cells in patients with Plasmodium falciparum malaria.

The frequency of cytokine-producing CD4-/CD8- mononuclear cells was assessed in patients of different age groups (29 infants, aged 1-5 years; 30 schoolchildren, aged 6-14 years, 26 adults, aged > 15 years) with acute Plasmodium falciparum malaria, from Gabon. Fifteen patients were followed up before antimalarial treatment (day 0), during parasite clearance (day 3) and after resolution of parasitemia (day 10). By using flow cytometry for intracellular detection of cytokines, a striking expansion of CD4-/CD8- cells producing the type 1 cytokines interleukin (IL)-2-/interferon (IFN)-gamma+, IL-2+/IFN-gamma+ and IL-2+/IFN-gamma- was observed in adults as compared with children. Type 2 cytokine expression (IL-4+/IFN-gamma-, IL-13+/IFN-gamma-) and type 0 cells (IL-4+/IFN-gamma+, IL-13+/IFN-gamma+) were not significantly different between the three age groups. Patients with severe malaria had a significantly increased frequency of type 2 cytokine-producing CD4-/CD8- cells. Drug-induced clearance of parasitemia was characterized by a decrease of IL-2+/IFN-gamma- and type 2 cytokine expressing CD4-/CD8- cells and by a gradual increase of IL-10+/IFN-gamma- expression. The type 1/type 2 dichotomy observed within the CD4-/CD8- cell population is likely to be of significance in the host response against P. falciparum malaria.

Adolescent↗

Prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis.

The aim of the present study was to evaluate the potential prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis. Twenty-eight patients with gram-positive sepsis were compared to 11 patients with gram-negative sepsis and 15 healthy volunteers. Sepsis was defined by the criteria of Bone et al. (Crit. Care Med. 21, 5447-5463, 1993) and by isolation of at least two positive blood cultures with gram-positive/gram-negative bacteria. Plasma samples for determination of the immunological parameters were collected daily. Analysis of cytokines and adhesion molecules was performed on days 0 (day of sepsis criteria fulfillment), 4, and 7 (or 1 day before death). In the gram-positive group 10 of 28 patients died; in the gram-negative group 4 of 11 died. Only sELAM-1 plasma concentrations were found to be a useful early parameter in predicting patients' outcome in gram-positive sepsis. sELAM-1 concentrations at the onset of the study (day 0) were significantly higher in the nonsurviving patients than those in the survivors. MIP-1 alpha levels were significantly higher only on days 4 and 7. With regard to the measured plasma concentrations we believe that MIP-1 alpha is not a useful parameter for predicting patients' prognosis. The increase of sVCAM-1 might play a role in the pathogenesis of gram-positive sepsis; however, it could not be relied upon as an early prognostic parameter. The potential role of TGF-beta 2 in the development of gram-positive sepsis could not evaluated in the present study, whereas routine measurements of TGF-beta 2 offered no additional prognostic information.

Adult↗

Reciprocal regulation of Th1- and Th2-cytokine-producing T cells during clearance of parasitemia in Plasmodium falciparum malaria.

Flow cytometry for the intracellular detection of T-cell cytokines was performed for 15 Gabonese patients during acute uncomplicated Plasmodium falciparum malaria. A striking expansion of CD4(+) and CD8(+) T cells producing gamma interferon (IFN-gamma) was found during drug-induced clearance of parasitemia, paralleled by a decrease of interleukin-2 (IL-2) production. The frequency of IL-4- and IL-13-producing CD4(+) cells gradually decreased, whereas the frequency of T cells producing IL-2(+)-IFN-gamma+, IL-4(-)-IL-5(+), and IL-4(+)-IL-5(+) cytokines as well as IL-4(+)-IFN-gamma+ and IL-13(+)-IFN-gamma+ cytokines was not significantly altered. The capacity for IL-10 production within the CD4(+) subset increased due to an expansion of both IL-10(+)-IFN-gamma- and IL-10(+)-IFN-gamma+ cytokine-expressing cells. Thus, a more pronounced Th2-driven immune response during acute untreated P. falciparum infection with a shift towards Th1 responsiveness induced by parasite clearance is suggested.

Acute Disease↗

Short report: total serum levels of the nitric oxide derivatives nitrite/nitrate during microfilarial clearance in human filarial disease.

Nitric oxide (NO) has recently been shown to be cytotoxic to both microfilariae and adult Brugia malayi in vitro and in a murine model, as well against Onchocerca lienalis microfilariae in vitro. We studied the kinetics of nitrite/nitrate, both stable end products of NO, by high-pressure liquid chromatography during microfilaricidal chemotherapy in four filariasis (three Loa loa, and one Onchocerca volvulus) patients. High serum levels of nitrite/nitrate were released during microfilarial clearance and sustained elevated levels were observed six months after chemotherapy, suggesting a role of NO in the elimination of microfilariae in human filariasis.

Adult↗

Left lateralized P300 amplitude deficit in schizophrenic patients depends on pitch disparity.

The general reduction of P300 amplitude in response to auditory oddball stimuli is one of the most consistently replicated biological observations in schizophrenic patients. Several groups have reported a P300 asymmetry in schizophrenic patients, others have not been able to replicate this finding. In order to clarify this issue, we examined the effect of stimulus discriminability on P300 amplitude distribution in schizophrenic patients and in age-matched normal control subjects, using two different auditory oddball paradigms. The detection of the target tone was either simple or difficult, due to manipulation of pitch disparity. The P300 amplitude was comparatively smaller in the schizophrenic patient group compared to the healthy controls and in the difficult task compared to the simple. The schizophrenic patients showed a specific P300 amplitude reduction over left temporal electrode sites when the simple paradigm was used. The difficult paradigm did not elicit asymmetrical P300 amplitudes in schizophrenic patients.

Adult↗

Molecular typing of Acinetobacter baumannii from ten different intensive care units of a university hospital.

Thirty-one isolates of Acinetobacter baumannii were collected from ten intensive care units of an Austrian university hospital. All isolates were typed by enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR). Two strains colonizing 13 infants in the neonatal intensive care unit were identified by ERIC-PCR. All other Acinetobacter baumannii isolates had highly divergent ERIC-PCR patterns, despite having the same antibiogram. Thus, a hospital-wide clonal distribution, as suggested by identical antibiogram patterns, was excluded by ERIC-PCR.

Acinetobacter↗

[Event-related potentials in semantic speech processing by schizophrenic patients].

Event-related potentials (ERPs) can be used for high-resolution mental chronometry. For about 15 years, this method has been applied to the study of linguistic phenomena. Semantic incongruency produces a negative component at about 400 ms after stimulus onset, the N400. We measured the N400 component in 20 schizophrenic patients and 20 normal control subjects performing a lexical decision task in which semantic distance between prime and target was varied. The results provide evidence of dysfunctional semantic information processing in schizophrenic patients, and reaction time data from previous studies can be interpreted within an electrophysiological framework. The N400 amplitude and latency data support recent spreading activation models of schizophrenic language dysfunction.

Adult↗

Dental implants and the geriatric patient.

Dental care of the aging patient presents a number of problems not encountered in younger patients. Most of these problems result from tissue changes that occur during aging. Dental implants and implant-retained and/or implant-supported prostheses are viable treatment options for older patients. The majority of elderly patients in their younger retirement years are relatively healthy and not limited in activity. The clinician must be aware of the physical, metabolic, and endocrine changes associated with aging and how these changes may affect implant treatment. The elderly deserve the best care the dental profession can offer.

Aged↗

Nutrition and the geriatric implant patient.

The clinician must be cognizant of nutritional factors and deficiencies that can adversely affect implant surgery and subsequent prosthodontic rehabilitation for the geriatric patient. There are many nutrients, vitamins, and minerals that may be useful and even necessary for the geriatric implant patient. Dental implants and implant-retained and/or supported prostheses are viable treatment options for older patients when certain age-related and nutritional factors are considered.

Aged↗

Cytokine profile and correlation to the APACHE III and MPM II scores in patients with sepsis.

In 35 patients fulfilling the criteria of systemic inflammatory response syndrome (SIRS) of infectious origin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), tumor necrosis factor-soluble receptor (TNF-sR), and interleukin-12 (IL-12), C-reactive protein (CRP) levels and the Acute Physiology, and Chronic Health Evaluation III score (APACHE III) were determined on days 1 to 7, 14, 21, and 28. The Mortality Probability Models (MPM) II sepsis score was assessed at the time of admission into the study. The MPM II sepsis score correlated with IL-6 plasma levels on day 1. The APACHE III scores correlated with plasma levels of TNF-sR on days 2-7, with IL-6 levels on days 3-7, and with CRP levels on days 4-7 (p < 0.01). The MPM II sepsis score, the APACHE III score, and the IL-6, TNF-sR, and CRP levels were significantly different between survivors and nonsurvivors and between patients with and without shock (p < 0.05). A significant decrease of the APACHE III scores, IL-6, and CRP levels was observed over the study period in the survivor group only (p < 0.05), while neither the dynamics of TNF-alpha nor IL-12 plasma levels contributed to the risk estimation of mortality.

APACHE↗

Expression in Escherichia coli, purification and characterization of heparinase I from Flavobacterium heparinum.

The use of heparin for extracorporeal therapies has been problematical due to haemorrhagic complications; as a consequence, heparinase I from Flavobacterium heparinum is used for the determination of plasma heparin and for elimination of heparin from circulation. Here we report the expression of recombinant heparinase I in Escherichia coli, purification to homogeneity and characterization of the purified enzyme. Heparinase I was expressed with an N-terminal histidine tag. The enzyme was insoluble and inactive, but could be refolded, and was purified to homogeneity by nickel-chelate chromatography. The cumulative yield was 43%, and the recovery of purified heparinase I was 14.4 mg/l of culture. The N-terminal sequence and the molecular mass as analysed by matrix-assisted laser desorption MS were consistent with predictions from the heparinase I gene structure. The reverse-phase HPLC profile of the tryptic digest, the Michaelis-Menten constant Km (47 micrograms/ml) and the specific activity (117 units/mg) of purified recombinant heparinase I were similar to those of the native enzyme. Degradation of heparin by heparinase I results in a characteristic product distribution, which is different from those obtained by degradation with heparinase II or III from F. heparinum. We developed a rapid anion-exchange HPLC method to separate the products of enzymic heparin degradation, using POROS perfusion chromatography media. Separation of characteristic di-, tetra- and hexa-saccharide products is performed in 10 min. These methods for the expression, purification and analysis of recombinant heparinase I may facilitate further development of heparinase I-based medical therapies as well as further investigation of the structures of heparin and heparan sulphate and their role in the extracellular matrix.

Amino Acid Sequence↗

Increased serum concentration of soluble CD14 is a prognostic marker in gram-positive sepsis.

Increased serum sCD14 concentrations are associated with poor outcome in Gram-negative sepsis and trauma patients. In the present study serum sCD14 concentrations were measured in patients with Gram-positive sepsis and compared with Gram-negative septic and nonseptic intensive care unit patients. Furthermore, serum sCD14 concentration was correlated with patient's outcome. Serum samples of 28 Gram-positive (8 nonsurvivors/20 survivors) and 10 Gram-negative bacteriemic patients (3 nonsurvivors/7 survivors) were obtained at the day they met the sepsis criteria defined by Bone et al. (Day 0) and at Days 4 and 7 and compared with 10 nonseptic ICU patients and 10 healthy volunteers. Serum concentrations of sCD14 were measured by ELISA. Significantly higher sCD14 serum concentrations were found on Days 4 and 7 in Gram-positive nonsurvivors than in Gram-positive survivors (Day 4: 5.85 +/- 0.48 vs 4.07 +/- 0.43 microgram/ml, P < 0.05; Day 7: 6.12 +/- 0.46 vs 3.53 +/- 0.33 microgram/ml, P < 0.01). In addition, sCD14 concentrations of Gram-positive nonsurvivors were significantly higher than those of nonseptic ICU patients and healthy volunteers at any time of observation. However, no significant difference was calculated between Gram-positive and Gram-negative patients. Summarizing our results, the serum level of sCD14 could be proven to be a good prognostic marker in the course of Gram-positive sepsis. Increased levels are associated with a high mortality.

Adult↗