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Biomedical subjects

S Weiss

Publications and source records attributed to S Weiss.

At least 19 recordsLinked to original sources

[TGF-beta1 as a pathophysiological factor in fracture healing].

AIM: TGF-beta1 is an important local and systemic regulatory molecule during fracture healing. Various authors have shown differences in the systemic levels of TGF-beta1 over the time taken for bone healing in distraction osteogenesis and osteotomies. Previous studies have shown characteristic differences in the physiological levels of growth factors between normal fracture healing and delayed fracture union. The aim of the present study was to evaluate possible differences in sera levels of patients with normal and delayed union fracture healing. METHODS: Patients with long bone shaft fractures were recruited prospectively. Peripheral blood samples were collected over a period of 1 year using a standardized time schedule. At the end of the individual's investigation period, TGF-beta1 levels were determined. To achieve a homogeneous collective of patients, only those with a maximum of two fractures were included in the study. After matching for four criteria, we compared patients with normal fracture healing to patients with delayed unions. The fact of delayed union was accepted in case of failed consolidation 4 months after trauma. RESULTS: During a prospective study period of 1 year, 15 patients with normal fracture healing could be compared to 15 patients suffering from delayed union. By determining the absolute sera levels we found a typical increase of TGF-beta1 up to 2 weeks after fracture in both groups, with a subsequent decrease up to the sixth week after fracture. However, a decline in serum concentration occurred earlier in patients with delayed union, causing significantly lower TGF-beta1 levels in the non-union group 4 weeks after trauma (P=0.00006). CONCLUSION: Even with a relatively small number of patients, we could show a significant difference in serum concentrations of TGF-beta1 between the investigated groups. If these results can be verified within a larger collective, TGF-beta1 could be used as a predictive cytokine for delayed fracture healing.

Adult↗

[Improving the diagnosis of septic arthritis by use of a pediatric blood culture system].

BACKGROUND: Prognosis and outcome of bacterial joint infections are dependent on the fast and reliable identification of pathogens in the synovial fluid. Previous studies have suggested the possible advantage of using a blood culture system in contrast to conventional culture methods. PATIENTS AND METHODS: A total of 101 synovial specimens from patients presenting with symptoms suggesting septic arthritis were taken by aspiration with a sterile syringe. We compared the diagnostic results of automated analysis in a blood culture system against conventional culture on solid agar plates. RESULTS: Some 67 specimens (66.3%) were found to be negative in both preparations, while samples from 21 patients (20.8%) yielded the same microorganisms. In 13 cases (12.9%), the isolation of a pathogen was possible only with the blood culture method, whereas the conventional method never yielded a positive result when the blood culture was negative. Thus, the diagnostic yield was significantly improved by use of the blood culture system (P <0.001). CONCLUSION: The use of a commonly available blood culture system offers a fast, reliable and cost-effective approach for the diagnosis of septic arthritis and should therefore be considered as an useful alternative to conventional culture methods.

Adolescent↗

Risk factors for venous thromboembolic events in cancer patients.

BACKGROUND: Cancer patients of the Department of Internal Medicine (Cancer Research) of the Essen University Medical School (Tumor Clinics), Germany, were examined and questioned with the aim of identifying those who run a high risk of deep vein thrombosis (DVT). PATIENTS AND METHODS: Between September 2002 and April 2003, cancer therapy and DVT risk factors of 507 cancer patients (53% males, 47% females, mean age 56+/-12 years) were documented. During a mean follow-up of 8+/-5 months, 60 patients (12%) suffered from new venous thromboembolic events (VTE): 28 at the lower limb, 25 at the upper limb and 13 pulmonary embolisms. RESULTS: The following factors were considered as predictive for an increased VTE risk: inpatient treatment (P<0.0001), prior DVT in medical history (P=0.0275), DVT in family (P=0.0598), chemotherapy (P=0.0080), fever (P=0.0093) and CRP (P<0.001). After combining factors in one variable (number of factors) the predicted VTE risk increased with the number of factors in both outpatients (OR 1.85, 95% CI 1.18-2.88, P=0.0071) and inpatients (OR 2.34, 95% CI 1.63-3.36, P<or=0.0001). In the absence of all these factors the predicted VTE risk was 2.3%, increasing to 72% if all were present. CONCLUSIONS: In cancer patients the risk of VTE steadily increases with the number of risk factors, and identification of patients at high risk is possible.

Anticoagulants↗

Systemic regulation of angiogenesis and matrix degradation in bone regeneration--distraction osteogenesis compared to rigid fracture healing.

Aim of this study was the investigation of systemic biochemical regulation mechanisms of bone regeneration by angiogenic and matrix-degrading enzymes during distraction osteogenesis compared to rigid osteotomy bone healing. Serum samples of 10 otherwise healthy patients with callus distraction for lower limb-lengthening and 10 osteotomy patients undergoing elective axis correction have been collected prospectively in a standardized time schedule before and up to 6 months after the procedure. At the end of the individual investigation period, concentrations of metalloproteinases (MMP-9, -13), tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and the angiogenic factors angiogenin and VEGF have been detected by use of commercially available enzyme immunoassays. Results have been compared to our preliminary study on proMMP-1-3. In distraction osteogenesis, significantly elevated serum concentrations compared to baseline could be detected postoperatively for proMMP-1, MMP-9, TIMP-1, angiogenin and VEGF but not for proMMP-2, proMMP-3 or TIMP-2. In patients with rigid osteotomy healing, MMP-9, TIMP-1, TIMP-2, angiogenin and VEGF were significantly increased respectively. Comparison of both patient collectives revealed significantly higher increases of serum proMMP-1, VEGF and TIMP-1 in distraction patients during the lengthening period and significantly higher serum concentrations of TIMP-2 in late fracture healing period in osteotomy patients. Serum levels of MMP-13 were below the lowest standards, and therefore quantitative analysis was not possible. Bone regeneration in distraction osteogenesis and rigid osteotomy healing is accompanied by systemic increase of matrix-degrading and angiogenic factors in a certain time course and quantity. This might reflect biochemical regulation of local bone healing in the circulation. ProMMP-1, VEGF and TIMP-1 seem to be key regulatory factors during distraction osteogenesis.

Adult↗

Relationship of taurine and other amino acids in plasma and in neutrophils of septic trauma patients.

Recently, an interdependency of plasma taurine and other amino acids as well as metabolic and clinical variables implicating therapeutic options was reported. This result may be an indication that plasma taurine levels are directly related to intracellular levels. Therefore, the aim of this study was to analyse the possible relationship between taurine levels in plasma and in neutrophils, the relationship to other amino acids, and variables quantifying metabolic impairment and severity of sepsis in multiple trauma patients developing sepsis. After multiple trauma taurine decreased significantly in plasma in thirty-two patients as well as within the neutrophil and does not recover in sepsis. Lower individual levels in the neutrophil did not follow lower individual levels in plasma and no correlation of taurine in plasma and in the neutrophils could be observed. In sepsis, only plasma showed an interdependency of taurine, aspartate, and glutamate. No association between taurine plasma or intracellular levels and SOFA score as indicator for severity of sepsis or metabolic variables was observed. After multiple trauma and in sepsis, taurine uptake in cells (which is regulated in different ways), and intracellular taurine (which serves e.g. as an osmolyte) can be influenced. Therefore a prediction of the neutrophil taurine pool seems not fully possible from taurine plasma levels. Intracellular taurine has some unique properties explaining the missing interdependency despite some similarities in osmoregulation and metabolic interactions to other amino acids. The association of taurine, aspartate, and glutamate in plasma cannot be simply transferred to the neutrophils intracellular level. The clinical meaning of the plasma correlation remains unclear. A dependency of plasma and neutrophil taurine to severity of sepsis and to metabolic variables seems not possible because of the multifactorial pathophysiology of sepsis.

Adult↗

TGF-beta1 as a marker of delayed fracture healing.

Mitogens of the TGF-beta superfamily have been shown to be crucial local and systemic regulatory molecules involved in fracture healing. However, there exists only little information about systemic regulation of bone regeneration by growth factors and no reports comparing serum levels of bone growth factors between normal and failed fracture healing have been published so far. We hypothesized that quality of fracture healing might be reflected by systemic alterations of key regulatory growth factors involved in bone formation and remodeling. Therefore, the aim of this study was to evaluate possible differences in serum levels of BMP-2, BMP-4, and TGF-beta1 in patients with normal and delayed fracture healing. 103 patients with diaphyseal fractures of long bones were recruited prospectively. Peripheral blood samples were collected over a period of 6 months following a standardized time schedule. At the end of the individual investigation period, growth factor serum levels were measured using commercially available enzyme immunoassays. For the elimination of disturbing influences, patients in both groups were matched by gender, age, fracture type, and localization as well as applied technique of osteosynthesis. During a study period of 1 year, 10 patients with an atrophic type of delayed union could be retrieved and matched to 10 patients with normal fracture healing. The diagnosis of delayed union was assumed in case of failed consolidation 4 months after trauma. We found an increase of TGF-beta1 serum levels up to 2 weeks after fracture in both groups with a following return to the reference value within 6 weeks after trauma. However, decline of serum concentration occurred earlier in patients with delayed fracture healing. At 4 weeks after trauma, serum levels of TGF-beta1 were significantly lower in patients of the delayed union group. Serum levels of BMP-2 and BMP-4 were below detection level in all patients, respectively. These findings support the critical role of TGF-beta1 in fracture healing. Events during the consolidation phase seem to be dependent on sufficient availability of TGF-beta1.

Biomarkers↗

Differential properties of dentate gyrus and CA1 neural precursors.

In the present article we investigated the properties of CA1 and dentate gyrus cell precursors in adult rodents both in vivo and in vitro. Cell proliferation in situ was investigated by rating the number of cells incorporating BrdU after kainate-induced seizures. CA1 precursors displayed a greater proliferation capacity than dentate gyrus precursors. The majority of BrdU-labeled cells in CA1 expressed Nestin and Mash-1, two markers of neural precursors. BrdU-positive cells in the dentate gyrus expressed Nestin, but only a few expressed Mash-1. In animals pretreated with the antimitotic azacytidine, the capacity of kainate to enhance the proliferation was higher in CA1 than in the dentate gyrus. Differences in intrinsic progenitor cell activity could underlie these different expansion capacities. Thus, we compared the renewal- expansion and multipotency of dentate gyrus and CA1 precursors isolated in vitro. We found that the dissected CA1 region, including the periventricular zone, is enriched in neurosphere-forming cells (presumed stem cells), which respond to either EGF or FGF-2. Dentate gyrus contains fewer neurosphere-forming cells and none that respond to FGF-2 alone. Neurospheres generated from CA1 were multipotent and produced neurons, astrocytes, and oligodendrocytes, while dentate gyrus neurospheres mostly produced glial cells. The analysis of the effects of EGF on organotypic cultures of hippocampal slices depicted similar features: BrdU and Nestin immunoreactivities increased after EGF treatment in CA1 but not in the dentate gyrus. These results suggest that CA1 precursors are more stem-cell-like than granule cell precursors, which may represent a more restricted precursor cell.

Analysis of Variance↗

Quantum dots for live cells, in vivo imaging, and diagnostics.

Research on fluorescent semiconductor nanocrystals (also known as quantum dots or qdots) has evolved over the past two decades from electronic materials science to biological applications. We review current approaches to the synthesis, solubilization, and functionalization of qdots and their applications to cell and animal biology. Recent examples of their experimental use include the observation of diffusion of individual glycine receptors in living neurons and the identification of lymph nodes in live animals by near-infrared emission during surgery. The new generations of qdots have far-reaching potential for the study of intracellular processes at the single-molecule level, high-resolution cellular imaging, long-term in vivo observation of cell trafficking, tumor targeting, and diagnostics.

Animals↗

Fetal cord blood: aspects of heightened immune responses.

Neonatal immune responses have been associated with the development of atopy in childhood. We assessed in cord blood mononuclear cells (CBMC) whether increased allergen/mitogen-induced lymphoproliferation (LP) is associated with pro-allergic Th2 cytokine IL-13 or Th1 cytokine IFN-gamma secretion. We determined whether LP to one allergen is related to heightened lymphocyte function to other allergens/mitogen. CBMC from 135 neonates were stimulated with house dust mite (Derf1), cockroach, ovalbumin, or mitogen. LP to one allergen was associated with significantly increased LP to other allergens/mitogen. Increased Derf1-LP was associated with increased Derf1-induced IL-13 secretion (r = 0.21, p = 0.01). After adjusting for neonatal gender, race, and maternal smoking, Derf1-LP remained associated with Derf1-IL-13 (OR 3.08, 95% CI 1.56-6.10). Increased mitogen-induced proliferation was associated with increased mitogen-induced IL-13 secretion (r = 0.37, p < 0.001). For some individuals, a predisposition to a heightened immune response is already evident at birth. Whether this phenotype results in atopy in childhood warrants further investigation.

Adult↗

Phylogenetic analysis of the genus Thymallus (grayling) based on mtDNA control region and ATPase 6 genes, with inferences on control region constraints and broad-scale Eurasian phylogeography.

We present first insights into the molecular phylogeny of the grayling genus Thymallus (Salmonidae) using sequences from the mitochondrial control region and ATPase6 genes. A suite of analytical approaches were applied for each gene separately and for the combined data. The ATPase6 gene is shown to have a mean divergence rate across the genus of 2.46 times faster than the complete control region. Based on the combined data, four major (internal) clades, presumably originating in the Pliocene, were resolved with high support in all analyses and represented two distinct lineages in the Amur basin, one lineage in all remaining Siberian and Mongolian drainages, and one lineage corresponding to European grayling Thymallus thymallus. The resolution of multiple lineages, from both additional internal and terminal clades, within each major drainage basin underscores the complexity and effects that Pleistocene hydrological dynamics have had on the distribution of biodiversity in Siberia.

Animals↗

Lung function and blood levels of copper, selenium, vitamin C and vitamin E in the general population.

BACKGROUND: Increased dietary intake of antioxidants has been associated with higher lung function, but few studies have used biological markers of antioxidant intake. OBJECTIVE: This study aimed to determine if antioxidant status, as measured by blood levels, influences lung function. DESIGN: Using a random subsample of 479 participants, aged 18-65 y old, from a larger cross-sectional observational study, the association of forced expiratory volume in 1 s (FEV1) with plasma copper, vitamin C, vitamin E and serum selenium was assessed. RESULTS: An s.d. increase in blood copper level was associated with a difference in FEV1 of -48 ml (95% confidence intervals: -95, -2 ml, P = 0.04), vitamin C +49 ml (+4, +94, P = 0.03), vitamin E -15 ml (-62, +32, P = 0.53) and selenium +52 ml (+7, +96, P = 0.02). The sizes of association were not appreciably altered in a mutually adjusted model. CONCLUSIONS: Higher levels of serum vitamin C and selenium appear to be associated with higher FEV1. The association between higher serum copper and lower FEV1 requires further study in view of the ubiquitous exposure to this mineral.

Adult↗

Salmonella-mediated oral DNA vaccination using stabilized eukaryotic expression plasmids.

The use of Salmonella for the delivery of plasmid-encoded heterologous antigens to eukaryotic host cells has proven successful in experimental systems, but its general applicability is still hampered by a severe instability of transformants carrying these expression plasmids. To overcome the problem of plasmid instability, new low copy number expression plasmids were constructed using different replicons. Comparative studies between transformants of the high copy number plasmid pCMVbeta and the different low copy number plasmids that contain the pMB1, p15A or pSC101 replicons on the pCMVbeta backbone, revealed a dramatic increase in plasmid stability both in vitro and in vivo. Analysis of the resulting immune responses against antigens encoded by these vectors indicated that the increased stability resulted in a strong and reproducible induction of both antigen-specific CD4(+) and CD8(+) T-cell and antibody responses even after a single application. In addition, protective immunity was induced against Listeria monocytogenes using listeriolysin as antigen, regardless of the copy number of the delivery plasmid employed. Finally, Salmonella expressing two independent antigens on compatible low copy number plasmids elicited robust responses to either antigen that is as effective as Salmonella transformed with each plasmid singly adding further versatility to this delivery system.

Administration, Oral↗

The impact of improved self-efficacy on HIV viral load and distress in culturally diverse women living with AIDS: the SMART/EST Women's Project.

The purpose of the present study was to determine whether changes in self-efficacy over time would be related to changes in disease progression markers (CD4, viral load) in a sample of women with AIDS. A self-efficacy measure was developed and two sub-scales emerged via factor analysis of 391 HIV-positive women: AIDS Self-efficacy and Cognitive Behavioral Skills Self-efficacy. Subsequently, the sub-scales and an additional adherence self-efficacy item were given to 56 HIV-positive women who were measured at two time points three months apart. Half of these women were randomly assigned to a CB intervention and half to a low intensity comparison condition. Increases in AIDS Self-efficacy over the three-month period were significantly related to increases in CD4 and decreases in viral load. Similarly, increases in Cognitive Behavioral Skills Self-efficacy were significantly related to decreases in distress over time. Findings were maintained within the intervention group alone. Interestingly, increases in cognitive behavioral skills self-efficacy and increases in the self-efficacy adherence item were also significantly related to decreases in viral load. Implications of the findings and suggestions for future research are discussed.

Acquired Immunodeficiency Syndrome↗

Individual and combined effects of peroxisome proliferator-activated receptor and {gamma} agonists, fenofibrate and rosiglitazone, on biomarkers of lipid and glucose metabolism in healthy nondiabetic volunteers.

This open-label, randomized, placebo-controlled, incomplete-block, 3-period crossover pilot study investigated the effects of peroxisome proliferator-activated receptor alpha- and gamma-agonists on biomarkers of lipid and glucose metabolism in 12 nondiabetic subjects. Plasma samples were collected before and after each 14-day treatment with placebo, fenofibrate (201 mg/d), rosiglitazone (4 mg twice daily), and combined fenofibrate (201 mg/d) plus rosiglitazone (4 mg twice daily). Except for triglycerides (P < .042) and free fatty acids (P < .074), no significant interaction was demonstrated between fenofibrate and rosiglitazone; thus, the effect due to each drug alone was evaluated (presence/absence of drug). Fenofibrate significantly (P < .050) increased lipoprotein lipase activity (35%) and decreased apolipoproteins B (13%) and C-III (20%). Rosiglitazone significantly (P < .050) decreased fasting glucose (7.3%) and increased apolipoprotein C-III (19%) and adiponectin (137%). Fenofibrate and rosiglitazone also produced effects on triglycerides and free fatty acids, but it was not possible to determine if these effects were synergistic in nature.

Adolescent↗

[The influence of centrifugation on quality and freezability of stallion semen].

The aim of the present study was to investigate the influence of various centrifugation methods on sperm loss and quality of frozen-thawed semen. From at a total of 8 Warmblood stallions of the National Stud Farm in Avenches, 3 ejaculates each were collected and seminal plasma was removed using 3 different centrifugation regimes. In method I (reference method) centrifugation occurred by a speed of 600 x g during 10 minutes. In method II 1000 x g was used during 2 minutes while in method III centrifugation was performed by 2000 x g during 2 minutes. After centrifugation 90%, of the supernatant was removed and sperm loss calculated. After resuspension of the pellet with freezing medium, functional membrane integrity was evaluated by HOS-test and motility determined. In frozen-thawed semen motility, viability as well as functional membrane integrity (HOS-test) and acrosome status using chlortetracyclinassay (CTA) were assessed. Our results demonstrate that mean sperm loss (I, 1.9%; II, 8.7%; III, 3.7%) was significantly (P < 0.05) different between the three centrifugation regimes. Regarding semen quality of frozen-thawed semen, HOS in method III (52.1%) was significantly lower than in methods I (55.5%) and II (55.3%). Evaluation of the acrosome status by CTA showed that more than 70% of sperm cells were capacitated and 25% capacitated and acrosome reacted. From our results we conclude that sperm loss and functional membrane integrity (HOS-test) in frozen-thawed semen were significantly influenced by the centrifugation regime. Therefore, stallion semen should be centrifuged at 600 x g during 10 minutes before freezing in order to obtain low sperm loss and a good quality of frozen-thawed semen.

Acrosome↗

Lipid rafts clustering and signalling by listeriolysin O.

Listeriolysin O, the major virulent determinant of Listeria monocytogenes, is known for forming pores on cholesterol-rich membranes. In the present study, we reveal its other facet, rafts clustering. By immunofluorescence microscopy, we show that the glycosylphosphatidylinositol-anchored proteins CD14 and CD24, which normally exhibit uniform distribution on J774 cells, undergo clustering upon treatment with LLO. The non-raft marker transferrin receptor is unaffected by such treatment. Rafts clustering might explain the induction of tyrosine phosphorylation observed on LLO-treated cells.

Antigens, CD↗