Biomedical subjects

Birgitt Wiese

Publications and source records attributed to Birgitt Wiese.

17 recordsLinked to original sources

PubMed2006

The suppressor of cytokine signalling-1 (SOCS-1) gene is overexpressed in Philadelphia chromosome negative chronic myeloproliferative disorders.

The suppressor of cytokine signalling-1 (SOCS-1) is a negative regulator of signal transduction mediated by cytoplasmic tyrosine kinases such as the Janus kinases (JAKs). We investigated SOCS-1 expression in bone marrow cells from Philadelphia chromosome negative chronic myeloproliferative disorders (Ph(-) CMPD) and normal haematopoiesis (n=121), and additionally in peripheral blood samples (n=18). Except for chronic idiopathic myelofibrosis harbouring wild-type JAK2, other Ph(-) CMPD expressed significantly higher SOCS-1 levels of up to 14-fold compared to the control group (p<0.001) independent of the JAK2 status. The mononuclear cell fraction but not granulocytes in patients with Polycythaemia vera also significantly overexpressed SOCS-1. We conclude that up-regulation of the SOCS-1 gene might reflect a compensatory feedback mechanism with different emphasis among Ph(-) CMPD subtypes independent of an underlying JAK2 (V617F) mutation.

Adult↗

PubMed2006

Transcription factor Fli-1 expression by bone marrow cells in chronic myeloproliferative disorders is independent of an underlying JAK2 (V617F) mutation.

OBJECTIVES: Friend leukemia integration-1 (Fli-1), a member of the Ets gene family of transcription factors, has been demonstrated to be a target of a leukaemia inducing virus in mice, and is known to be part of a fusion gene in Ewings' sarcoma in humans. Wild-type Fli-1 is involved in lineage commitment of megakaryocytes and myeloid progenitors through induction of Janus kinases (JAKs) following ligand binding to cytokine and growth factor receptors. Proliferation of atypical megakaryocytes is a predominant histopathological feature in Philadelphia chromosome negative chronic myeloproliferative disorders (Ph(-) CMPD) and a potential aberrant expression of Fli-1 has not been investigated so far. METHODS: Fli-1 expression was investigated by real-time RT-PCR and immunohistochemistry in bone marrow cells derived from Ph(-) CMPD (n = 80) and non-neoplastic haematopoiesis (n = 21) following determination of the JAK2 status. RESULTS: Fli-1 mRNA expression was significantly higher in Essential thrombocythaemia (ET) with JAK2 (V617F) compared with other Ph(-) CMPD and control (P < 0.001). By immunohistochemistry, Fli-1 protein could be detected in nuclei of atypical megakaryocytes in Ph(-) CMPD and, less accentuated, in non-neoplastic megakaryocytes. Fli-1 protein expression by myeloid progenitors was considerably heterogenous in Ph(-) CMPD independent of an underlying JAK2 (V617F) mutation and without notable differences to non-neoplastic haematopoiesis. CONCLUSION: Fli-1 is rather constitutively expressed by bone marrow cells in Ph(-) CMPD independent of the underlying JAK2 status. The overall stronger labelling for Fli-1 in megakaryocytes in Ph(-) CMPD most likely reflects the degree of polyploidisation but aberrant activation of nuclear target genes can not be excluded.

Adult↗

PubMed2006

Aberrant collagenase expression in chronic idiopathic myelofibrosis is related to the stage of disease but not to the JAK2 mutation status.

Bone marrow fibrosis in chronic idiopathic myelofibrosis (cIMF) most likely represents an imbalance between synthesis and turnover of collagen fibers. Because the JAK-STAT signaling pathway is involved in the regulation of genes encoding matrix metalloproteinases (MMPs), we examined the expression of MMPs, their tissue inhibitors (TIMPs), and collagen types in relation to the JAK2 status (V617F mutation versus wild-type) in cIMF (n = 64). Whereas no correlation was found between the JAK2 status and MMP gene products, there was an evident association with the stage of disease. Membrane type 1-MMP (MMP-14) was overexpressed by up to 80-fold in advanced stages that progressed to fibrosis (P < 0.001), and megakaryocytes and endothelial cells were unmasked as the major cellular source. By contrast, a significantly higher expression of neutrophil collagenase (MMP-8) was encountered in the prefibrotic stages of cIMF (P < 0.001). Altogether, the stepwise progress of myelofibrosis in cIMF was associated with expression of a defined subset of target genes as shown in sequential trephine biopsies of cIMF patients. We conclude that the expression of matrix-modeling genes in cIMF is not influenced by the JAK2 mutation status but is predominantly related to the stage of disease.

Adult↗

PubMed2005

Effects of different subanesthetic doses of (S)-ketamine on neuropsychology, psychopathology, and state of consciousness in man.

This is the first neuropsychological study using the S-enantiomer of the noncompetitive N-methyl-D-aspartate antagonist ketamine. In 2 randomized placebo-controlled trials we studied effects of two different doses of (S)-ketamine (low dose/high dose) on neuropsychological functions and psychopathology in 12 healthy male volunteers. Impairment was measured via standardized neuropsychological tests. Results indicate that both subanaesthetic doses produce only nonsignificant impairment in most of the tasks. Tasks involving divided and sustained attention as well as scores for objective and subjective psychopathology show significant impairment in a dose-dependent manner. Implications of these findings for the neuropsychology of attention and schizophrenia are discussed.

Adult↗

PubMed2005

Follow-up investigations of tau protein and S-100B levels in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

BACKGROUND: S-100B and tau protein have a high differential diagnostic potential for the diagnosis of Creutzfeldt-Jakob disease (CJD). So far there has been only limited information available about the dynamics of these parameters in the cerebrospinal fluid (CSF). However, there is a special interest in finding biochemical markers to monitor disease progression for differential diagnosis and treatment. PATIENTS AND METHODS: We analyzed CSF of 45 patients with CJD and of 45 patients with other neurological diseases for tau protein and S-100B in a follow-up setting. All diagnoses of CJD were later neuropathologically verified. A ratio between tau protein differences and the time between lumbar puncture was calculated. The same was done for S-100B. RESULTS: Tau protein levels of 34 cases were above the cut-off level for CJD (>1,300 pg/ml) in the first CSF sample. In 7 of 11 patients with lower tau levels in the first CSF sample, tau levels rose. The above-mentioned ratio was significantly higher in the CJD group than in the group with other neurological diseases. Similar results were obtained for S-100B. CONCLUSION: We conclude that follow-up investigations and calculation of ratios is a useful tool in the differential diagnosis of CJD. Variations in this pattern were observed in single cases.

Adult↗

PubMed2005

Osteosclerosis in advanced chronic idiopathic myelofibrosis is associated with endothelial overexpression of osteoprotegerin.

Advanced chronic idiopathic myelofibrosis (IMF) with osteosclerosis and increase and thickening of bone trabeculae is typically contrasted by the absence or sparse presence of osteoclasts. Because osteoclast formation can be inhibited by osteoprotegerin (OPG) we investigated OPG expression in IMF with severe fibrosis and osteosclerosis, which expressed significantly higher (up to 71-fold) OPG mRNA levels when compared with prefibrotic cellular IMF and control cases. The receptor activator of nuclear factor kappaB ligand (RANKL), a positive regulator of osteoclast differentiation and putative antagonist of OPG was overexpressed by up to 34-fold exclusively in advanced IMF. Case-specific calculation of the RANKL/OPG ratio in advanced IMF showed a wide range without significant differences when compared with the prefibrotic IMF and non-neoplastic haematopoiesis. Immunohistochemical detection of OPG protein revealed strong labelling of endothelial cells within proliferating vessels in fibrotic IMF and heterogeneously labelled megakaryocytes, and fibroblasts. Osteosclerosis and impaired osteoclast function in IMF appears to be associated with upregulated endothelial OPG expression but concomitant reduction of the antagonist RANKL could not be demonstrated. We conclude that osteosclerosis in IMF is associated with increased endothelial OPG expression without concomitant RANKL downregulation.

Adult↗

PubMed2005

Inhibitory effect of sodium fluoride and chlorhexidine on the growth of oral lactobacilli.

The accumulation of microorganisms in dental plaque is related to the etiology of caries and periodontal disease, with a high prevalence worldwide. The prophylactic measures include the use of chemical agents as NaF and chlorhexidine. Lactic acid bacteria are members of the normal microbiota of the oral cavity being discussed with regard to their beneficial or detrimental effect in this environment. The present study was performed to determine the growth of some species of Lactobacillus at different concentrations of NaF and chlorhexidine. The strains were isolated from both caries-free and caries patients. Their growth parameters were evaluated by the application of the Gompertz model to the experimental data of optical density as a measurement of growth. The degree of inhibition of the growth of all of the lactobacilli studied was different, depending on each particular strain. NaF at 1 mmol x L(-1) inhibited between 5% and 46%, at 5 mmol x L(-1) between 13% and 65%, and at 20 mmol x L(-1) between 57% and 84%. CHX at higher concentrations (197 and 98 mmol x L(-1) showed a complete inhibition of some of the strains. The significance of the results was evaluated by the application of a multivariate analysis and also compared with the inhibition of pathogenic Streptococcus mutans and with lactobacilli strains from collection cultures.

Chlorhexidine↗

PubMed2004

Analysis of risk factors of the evolution of myelofibrosis in pre-fibrotic chronic idiopathic myelofibrosis: a retrospective study based on follow up biopsies of 70 patients by using the RECPAM method.

The advanced, fibrotic phase of chronic idiopathic myelofibrosis (CIMF) is preceded by a pre-fibrotic stage. However, the factors which may influence or predict the development of myelofibrosis are not well established. Thus we investigated follow up biopsies of 70 patients with CIMF, diagnosed in stages of no or only scant fiber increase, for the development of myelofibrosis. The influence of histopathological (megakaryocytes, initial fiber content), clinical (age, gender, splenomegaly, chemotherapy) and hematological (Hb, leukocyte- and platelet count) parameters on the development of myelofibrosis was evaluated by using the univariate Log Rank method and the multivariate recursive partition and amalgamation (RECPAM) analysis. Surveying a mean observation period of 47 months we found a development of significant myelofibrosis in 30 of the 70 patients. In the univariate analysis, the development of myelofibrosis was associated with increased megakaryocytes, initial fiber content and age of the patient. In the RECPAM analysis, the patients with a high megakaryocytic count and older age showed the highest risk of developing myelofibrosis (mean 58.3 and 60.1 months). The group with the best prognosis comprised the patients under 60 years which have a low content of megakaryocytes (mean 137 months). We found that the development of myelofibrosis in CIMF was best predicted by an increase of megakaryocytes within the bone marrow, possibly reflecting the release of growth factors by these cells. The next important risk factor was the age of the patients.

Adult↗

PubMed2003

Effects of acute alcohol withdrawal on memory performance in alcohol-dependent patients: a pilot study.

Studies on the neuropsychological performance in detoxified alcoholic patients often begin by acknowledging that there is a cognitive impairment to be found. Only little attention has been paid to date to the question as to how acute alcohol withdrawal might affect cognitive functions. Twenty-nine alcohol-dependent inpatients, nine in moderate alcohol withdrawal, treated with carbamazepine (group 1), 10 in mild alcohol withdrawal without pharmacological treatment (group 2), 10 in mild alcohol withdrawal with carbamazepine treatment (group 3) and 31 healthy subjects as controls (group 4) underwent repeated investigations using memory tests. The tests were performed on the first, third, seventh and fourteenth days of withdrawal. Immediate free recall of a word-list was impaired in the three patient groups in comparison with the control group on the 1st day. Thereafter no significant differences could be revealed between patients and controls. In a word-list recognition test the memory functions were not impaired in group 1 and group 2 in comparison with the control subjects. However, patients in group 3 showed impairment in this recognition test in comparison with the healthy subjects on the first and third days. The present study suggests that acute alcohol withdrawal impairs memory functions, especially free recall. This should be considered in treatment interventions in the early days of withdrawal.

Adult↗

PubMed2003

Growth and lactic acid production by vaginal Lactobacillus acidophilus CRL 1259, and inhibition of uropathogenic Escherichia coli.

Lactic acid-producing lactobacilli were selected from 134 human vaginal isolates by testing their capability to inhibit the growth of different pathogenic micro-organisms. Lactobacillus acidophilus CRL 1259 (from the CERELA Culture Collection) was selected to study the effects of temperature, pH and culture medium on growth and lactic acid production. Growth parameters were estimated by using the model of Gompertz. Kinetics of inhibition of uropathogenic Escherichia coli were evaluated in mixed cultures of the pathogen and L. acidophilus. Optimal conditions for growth and lactic acid production by L. acidophilus were pH 6.5 or 8.0 and 37 degrees C. Under these conditions, growth was higher in LAPTg (yeast extract/peptone/tryptone/Tween 80/glucose) broth than in MRS (De Man-Rogosa-Sharpe) broth. However, lactic acid production was more efficient in MRS broth. Under optimal conditions for lactic acid production, L. acidophilus inhibited the growth of E. coli. These results suggest that inclusion of L. acidophilus CRL 1259 in probiotic products for vaginal application would be beneficial.

Adult↗

PubMed2003

Effects of different subanaesthetic doses of (S)-ketamine on psychopathology and binocular depth inversion in man.

The role of the N-methyl-D-aspartate (NMDA) neurotransmitter system in relation to psychoses is not completely understood, but represent a challenge in neurobiological research. The psychotic states induced by NMDA antagonists such as phencyclidine and ketamine have been described as being most similar to schizophrenia and the NMDA system has been implicated in the pathogenesis of schizophrenia. Binocular depth inversion, an illusion of visual perception, has been shown to be impaired in psychotic and psychotomimetic states in healthy and schizophrenic subjects. In this study, pictures of natural and artificial objects were presented stereoscopically to 12 healthy male volunteers and depth perception assessed using an operationalized method. The effects of the psychotomimetic S-enantiomer of the anaesthetic ketamine in two different subanaesthetic doses were compared with those of a placebo. In spite of dose dependence and grave subjective and significant objective psychopathology, no significant impairment of binocular depth perception was found with (S)-ketamine. Implications related to memory function, perceptogenesis and 'bottom-up' processing in ketamine model psychosis and schizophrenia are discussed.

Adult↗

PubMed2002

Inter-laboratory and inter-observer reproducibility of immunohistochemical assessment of the Ki-67 labelling index in a large multi-centre trial.

Proliferative activity of tumour cells, as assessed by the Ki-67 labelling index, has been suggested as a potential prognostic indicator in many neoplastic diseases. Meaningful application of the immunohistochemically determined tumour cell growth fraction in clinical decision-making requires information about its inter-laboratory reproducibility. To assess the reproducibility of Ki-67 determined growth fraction, a multi-centre immunohistochemical trial was performed with 172 participating laboratories, each testing 30 different tissue samples. Evaluating 5160 Ki-67 labelling indices with a newly developed tissue microarray, good inter-observer reproducibility but high inter-laboratory variability was found. Reassessment of all stainings revealed considerable inter-laboratory differences in the intensity and frequency of labelled nuclei, suggesting that antigen retrieval or staining techniques are predominantly responsible for the inter-laboratory variability found in this trial. Consequently, cut-off levels for Ki-67, suggested to distinguish prognostic subgroups in tumours, appear to have limited reproducibility in a multi-centre approach. It is concluded that there is a need to standardize the immunohistochemical determination of the Ki-67 labelling index when it is used as a prognostic indicator in surgical pathology.

Biomarkers, Tumor↗

PubMed2002

Increase in detrusor wall thickness indicates bladder outlet obstruction (BOO) in men.

Detrusor wall thickness decreases continuously while the bladder fills to 50% of its capacity and then remains constant until 100%. Therefore, detrusor wall measurements were performed in patients when the bladder was filled to maximum capacity only. Mean detrusor wall thickness for unobstructed (n = 14), equivocal (n=23) and obstructed patients (n=33) were 1.33, 1.62 and 2.4 mm, respectively (P <0.001). With increasing CHESS letters and CHESS numbers, the thickness of the detrusor wall increased as well (P< 0.001). The positive predictive value of detrusor wall measurement (95.5% for a cut-off value greater than or equal to 2 mm) was superior to all other predictors investigated. The thickness of the detrusor wall increases depending on the extent of BOO. Both constrictive and compressive BOO lead to an increase in detrusor wall thickness. BOO is found in 95.5% of men with a detrusor wall thickness greater than or equal to 2 mm. Measuring the thickness of the detrusor wall can be used as a screening test to detect BOO.

Adolescent↗

PubMed2002

Acupuncture has no immediate treatment effect on the neutrophil respiratory burst: a randomized single-blinded two-period crossover study.

Little is known about the influence of acupuncture treatment on the immune system. The respiratory burst (RB) of polymorphonuclear leukocytes (PMN) is a recognized measure of their cytotoxicity, an important component of the immune system. The present trial was therefore performed to examine whether a single-acupuncture treatment has an immediate effect on the RB of neutrophil PMNs. Sixteen volunteers were enrolled in the study. After randomization, eight volunteers were treated bilaterally with standard needles at acupoint LI11 and eight volunteers with placebo needles at the same acupoint, each for 30 min. The RB was determined before and 30 min after treatment. After two weeks, each group received the alternative treatment. There was a drop-out of two volunteers. No period or carryover effects were found in the remaining fourteen volunteers. No effect of acupuncture on the neutrophil RB was observed.

Acupuncture↗

PubMed2002

Acupuncture in the treatment of alcohol withdrawal symptoms: a randomized, placebo-controlled inpatient study.

Thirty-four alcoholics were treated with acupuncture to the ear and the body in a randomized single-blind placebo-controlled design over 14 days. Orthodox points and placebo needles to orthodox points were used daily for a total of 10 treatments starting on the first day of admission as add-on therapy to standard medication with carbamazepine. The primary outcome was the Clinical Institute Withdrawal Assessment (CIWA-Ar-scale) assessed on days 1-6, 9 and 14. No initial differences were found regarding sociodemographic data, drinking history and alcohol-related data, indicating successful randomization. Longitudinal analysis of the Clinical Institute Withdrawal Assessment (CIWA-Ar-scale) data showed that patients assigned to acupuncture had a general tendency towards better outcome results and significantly fewer withdrawal symptoms on day 14 (Wilcoxon-W=177.500, Z=-2.009, p = 0.045). No significant differences were found in the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI X1 and X2) and Eigenschaftswoerterliste (EWL S60). We conclude that acupuncture as an adjunctive treatment to carbamazepine medication shows promise for the treatment of alcohol withdrawal symptoms. Further investigation of this treatment modality appears to be warranted.

Acupuncture Therapy↗

PubMed2002

Tissue array technology for testing interlaboratory and interobserver reproducibility of immunohistochemical estrogen receptor analysis in a large multicenter trial.

Semiquantitative immunohistochemical assessment of estrogen receptor (ER) is used to predict the likelihood of response to antiestrogen therapy in breast carcinoma. If semiquantitative immunohistochemical analysis leads to therapeutic decisions, the importance of standardization and quality control increases. ER assessment reproducibility was studied among 172 laboratories using tissue microarray slides with 20 tissue spots negative and 10 tissue spots expressing ER at low, medium, or high levels. More than 80% of the laboratories demonstrated ER positivity in the medium- and high-expressing tissue spots, but only about 43% succeeded with tissue spots with low expression. Poor interlaboratory agreement was based on insufficient retrieval efficacy as shown by additional tests using autoclave pretreatment. The immunohistochemical scores used to quantify therapeutic target molecules remain inconclusive as long as progress toward standardized immunohistochemical procedures and evaluation is not achieved. Tissue microarray technology has proved its suitability for large-scale immunohistochemical trials, giving rise to new dimensions in control assessment.

Female↗

PubMedDate not supplied

Flares in patients with systemic lupus erythematosus are associated with daily psychological stress.

BACKGROUND: The aetiology of systemic lupus erythematosus (SLE) remains unclear. Clinical observations and a small number of studies performed so far suggest an association between psychological stress and self-reported symptoms of SLE patients. This longitudinal study was designed to investigate whether daily psychological stress is associated with flares in SLE patients, measured by clinical and laboratory parameters. METHODS: Female SLE patients (n = 41) were followed over a period of six months. Daily stress was monitored by a hand-held PC diary programmed with 44 items based on standardized measures and clinical experience. Once every four weeks patients visited the outpatient clinic for medical evaluation. Disease activity was evaluated using the European Consensus Lupus Activity Measurement (ECLAM), laboratory parameters, and intake of steroids. RESULTS: Classification and regression tree (CART) patient-wise analyses revealed that SLE patients with vs. without flares using complement and ECLAM as activity measures show greater negative self-ratings in mood, and social duties (p < 0.01). In addition, mixed model analysis of variance showed that daily hassles with social relationships were significantly associated with flares in SLE measured by an increase in steroid medication >5mg/d (p < 0.01). CONCLUSIONS: These results suggest that psychological stress is associated with flares in SLE. Particularly daily stress with social relationships and social duties may be factors to be related to the course of disease activity in SLE.

Adult↗