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Biomedical subjects

M Binder

Publications and source records attributed to M Binder.

At least 37 records · Page 2Linked to original sources
PubMed1997

Embryonic lethality and impairment of haematopoiesis in mice heterozygous for an AML1-ETO fusion gene.

Acute myeloid leukaemia (AML) is a major haematopoietic malignancy characterized by the proliferation of a malignant clone of myeloid progenitor cells. A reciprocal translocation, t(8;21)(q22;q22), observed in the leukaemic cells of approximately 40% of patients with the M2 subtype of AML disrupts both the AML1 (CBFA2) gene on chromosome 21 and the ETO (MTG8) gene on chromosome 8 (refs 3-5). A chimaeric protein is synthesized from one of the derivative chromosomes that contains the N terminus of the AML1 transcription factor, including its DNA-binding domain, fused to most of ETO, a protein of unknown function. We generated mice that mimic human t(8;21) with a "knock-in' strategy. Mice heterozygous for an AML1-ETO allele (AML1-ETO/+) die in midgestation from haemorrhaging in the central nervous system and exhibit a severe block in fetal liver haematopoiesis. This phenotype is very similar to that resulting from homozygous disruption of the AML1 (Cbfa2) or Cbfb genes, indicating that AML1-ETO blocks normal AML1 function. However, yolk sac cells from AML1-ETO/+ mice differentiated into macrophages in haematopoietic colony forming unit (CFU) assays, unlike Cbfa2-/- or Cbfb-/-cells, which form no colonies in vitro. This indicates that AML1-ETO may have other functions besides blocking wild-type AML1, a property that may be important in leukaemogenesis.

Animals↗
PubMed1997

Impact of the renin-angiotensin-aldosterone system on blood pressure response to intravenous enalaprilat in patients with hypertensive crises.

The purpose of the study was to evalute the impact of the renin-angiotensin-aldosterone (RAA) system on blood pressure (BP) response in patients with hypertensive emergencies and urgencies treated with intravenous enalaprilat. Thirty-five patients with a systolic BP (SBP) >210 mm Hg and/or diastolic BP (DBP) >110 mm Hg received 5 mg enalaprilat intravenously. The extent of systolic and DBP reduction was correlated with pretreatment concentrations of angiotensin II (ANGII) (SBP: r = -0.47; P = 0.006; DBP: r = -0.55; P = 0.001) and plasma renin activity (PRA) (SBP: r = -0.49; P = 0.003; DBP: r = 0.48; P = 0.007). Non-responders to enalaprilat exhibited significant lower pretreatment levels of PRA, angiotensin-converting enzyme (ACE) and ANG II compared to responders (PRA: 5.5 +/- 3.7 vs 1.1 +/- 2.2 ng/ml/h, P < 0.001; ACE: 12.8 +/- 3.5 vs 8.2 +/- 4.8 U/l, P = 0.003; ANG 11:8.7 +/- 6.2 vs 5.0 +/- 3.8 pg/ml, P = 0.04). In patients with severe hypotension following application of enalaprilat ANG II concentrations were significantly higher compared to patients with mean arterial BP reduction <25% (12.3 +/- 6.7 vs 5.6 +/- 4.0 pg/ml,P = 0.013). These data indicate that PRA and ANG II are the major determinants for BP response to enalaprilat. This relation between BP response and RAA system activity have important clinical implications for the treatment of patients with severe hypertension. Primary therapeutic failure indicates that the RAA system contributes very little to the hypertensive status of the patient. Thus, repetitive application on an ACE inhibitor in primary responders is clinically unhelpful and may result in an unnecessary delay of an effective BP reduction. In contrast, high ANG II concentrations are associated with a considerable risk for severe hypotension after enolanalaprilat application. Therefore, the status of the RAA system determines the efficacy as well as the safety of ACE inhibitor treatment in patients with severe hypertension.

Adult↗
PubMed1997

Regulation of the yeast SPS19 gene encoding peroxisomal 2,4-dienoyl-CoA reductase by the transcription factors Pip2p and Oaf1p: beta-oxidation is dispensable for Saccharomyces cerevisiae sporulation in acetate medium.

The yeast SPS19 gene encoding the peroxisomally targeted 2,4-dienoyl-CoA reductase shares its promoter region (291 bp) with the sporulation-specific gene SPS18. SPS19 is induced during sporulation in diploids but to a lesser extent than SPS18; under oleate induction conditions, SPS19, but not SPS18, is transcribed via an oleate response element (ORE) independently of ploidy or sporulation. The SPS19 ORE is the binding target of the Pip2p and Oaf1p transcription factors, and an SPS19-lacZ reporter gene, which is highly expressed in oleate-induced cells, is not activated in haploids devoid of either protein. We examined the expression of CYC1-lacZ reporter constructs carrying the SPS19 and CTA1 OREs in diploids propagated under sporulation conditions and have shown that OREs are not sufficient for heterologous expression during yeast development. In addition, diploids deleted at either PIP2 or OAF1 demonstrated abundant ascosporogenesis, indicating that these genes are not essential for sporulation. A deltapex6 strain lacking peroxisomal structures and one devoid of fatty acyl-CoA oxidase (deltapox1), the first step in fungal beta-oxidation, were both proficient for sporulation and, hence, beta-oxidation and the peroxisomal compartment containing it are dispensable for meiotic development.

Acetates↗
PubMed1997

Noninvasive assessment of cardiac output in critically ill patients by analysis of the finger blood pressure waveform.

OBJECTIVE: To assess whether the measurement of cardiac output by computer-assisted analysis of the finger blood pressure waveform can substitute for the thermodilution method in critically ill patients. DESIGN: Prospective data collection. SETTING: Emergency department in a 2000-bed inner city hospital PATIENTS: Forty-six critically ill patients requiring invasive monitoring for clinical management were prospectively studied. INTERVENTIONS: Under local anesthesia a 7-Fr pulmonary artery catheter was inserted via the central subclavian or jugular vein. Cardiac output was determined by the use of a cardiac output computer and injections of 10 mL ice-cold glucose 5%. Noninvasive cardiac output was calculated from the finger blood pressure waveform by the use of the test software program. MEASUREMENTS AND MAIN RESULTS: Three hundred twenty-three pairs of invasive and noninvasive hemodynamic measurements were collected in intervals of 30 mins from 46 patients (mean age 61.9 +/- 12.4 yrs; 35 male, 11 female). The average cardiac index during the study period was 2.83 L/min/m2 (range 0.97 to 5.56). The overall discrepancy between both measurements was 0.14 L/min/m2 (95% confidence interval: 0.10-.018, p < .001). Seventy-five (23.2%) measurements had an absolute discrepancy > +/- 0.50 L/min/m2. Noninvasive and invasive comparisons of mean differential cardiac output were out of phase for 9.7% of all readings. CONCLUSION: Computer-assisted analysis of finger blood pressure waveform to assess cardiac output is not a substitute for the thermodilution method due to a high percentage (23.2%) of inaccurate readings; however, it may be a useful tool for the detection of relative hemodynamic trends in critically ill patients.

Adult↗
PubMed1997

Blood glucose concentration after cardiopulmonary resuscitation influences functional neurological recovery in human cardiac arrest survivors.

Experimental data suggest that postischemic blood glucose concentration plays an important role in modulating both ischemic cerebral infarction and selective neuronal necrosis. This study investigated the association between functional neurological recovery and blood glucose concentrations in human cardiac arrest survivors. A group of 145 nondiabetic patients were evaluated after witnessed ventricular fibrillation cardiac arrest. Data regarding cardiac arrest were collected according to an internationally accepted protocol immediately after arrival. Blood glucose was measured on admission and 6, 12, and 24 h thereafter. To control for duration of cardiac arrest and cardiogenic shock, both known to influence outcome as well as blood glucose, levels, Spearman rank partial correlation was used. In this multivariate analysis, a high admission blood glucose level tended to be associated with poor neurological outcome (rs = -0.16, n = 142, p = 0.06). The association between high median blood glucose levels over 24 h and poor neurological outcome was strong and statistically significant (rs = -0.2, n = 145, p = 0.015). High blood glucose concentrations occurring over the first 24 h after cardiac arrest have deleterious effects on functional neurological recovery. Whether cardiac arrest survivors might benefit from reduction of blood glucose levels needs further investigation.

Adult↗
PubMed1997

A simple and reliable reverse-phase high-performance liquid chromatographic procedure for determination of paclitaxel (taxol) in human serum.

A simple, fast, and reliable isocratic (mobile phase: acetonitrile/methanol/water [48/11/41], reverse-phase (C18 column) high-performance liquid chromatography method for the determination of paclitaxel concentration in human serum is presented. The procedure uses a new and convenient one-step sample-purification procedure that requires only 400 microliters of sample and uses N-heptylbenzamide as an internal standard. Paclitaxel is detected by UV absorbance measurement at 227 nm. The method has a broad linear range (0.01 to 10 mg/l, or 0.012 to 11.7 mumol/l; r > 0.999), and the detection limit is 0.01 mg/l (0.012 mumol/l). The deviation from target value is < or = 1.5%, and coefficients of variation are < or = 13.8% within runs and < or = 15.3% between runs. Recovery paclitaxel is > or = 92.6%. No interferences were observed from endogenous compounds or from more than 30 drugs that may be administered with paclitaxel. Docetaxel, which is not concurrently administered, coeluted with paclitaxel. Compared with previously published high-performance liquid chromatography procedures for the determination of paclitaxel, the particular advantage of the method presented here is its simple and rapid single-step sample-purification procedure, which makes a high recovery of paclitaxel from serum samples possible and results in a pure extract, avoiding interferences from endogenous compounds. The method is suitable for pharmacological studies and routine analysis.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Statistical evaluation of epiluminescence microscopy criteria in the differential diagnosis of malignant melanoma and pigmented basal cell carcinoma.

Pigmented basal cell carcinoma (PBCC) is a tumour with distinct clinical features which occasionally may be difficult to differentiate from malignant melanoma (MM). The purpose of this study was to re-examine the epiluminescence microscopy (ELM) criteria for PBCC and to determine their statistical significance in the differential diagnosis of MM. Fifty histologically verified pigmented skin lesions (25 PBCCs and 25 MMs) were investigated using ELM for the presence of ELM criteria; their significance was determined by calculating the odds ratios. We found that individual ELM criteria have different weights of significance in the differential diagnosis of PBCC (leaf-like distribution of diffuse pigmentation, gradual thinning at the periphery and telangiectasia) and MM (pigment network, black and grey pigmentation, radial streaming, pseudopods, brown globules and black dots). Selected patterns of ELM criteria adjusted to the distinct types of pigmented skin lesions are characteristic features for preoperative diagnosis. The prevalence of distinct ELM criteria in PBCC and MM is of critical value in differentiating between the two types of lesions.

Basal Cell Carcinoma↗
PubMed1997

Systemic activation of coagulation and fibrinolysis during varicose vein stripping.

BACKGROUND: Elevation of activation markers of blood coagulation (thrombin-antithrombin complex [TAT], prothrombin fragment 1 + 2 [F1 + 2], D-Dimer] has not only been found in clinically overt thrombosis but also reflects a prethrombotic state. OBJECTIVE: The purpose of our study was to evaluate whether varicose vein stripping, an operative procedure with an extremely low risk of postoperative thromboembolism, induces a prethrombotic state by activation of the hemostatic system. METHODS: In a prospective, observational study we compared the baseline and postoperative values of TAT, F1 + 2, and D-Dimers in 15 patients undergoing varicose vein stripping and in 11 control patients undergoing surgical procedures associated with only minor soft tissue trauma. RESULTS: A highly significant postoperative elevation of TAT (P < 0.001), F1 + 2 (P = 0.006), and D-Dimer (P < 0.001) was observed in the varicose vein stripping group. No significant postoperative change of the respective parameters was detected in the control group. CONCLUSION: We therefore conclude that varicose vein stripping induces a significant hemostatic system activation although postoperative thrombotic events are rare.

Adolescent↗
PubMed1997

Quantification of vascularity in nodular melanoma and Spitz's nevus.

Spitz's nevi are acquired benign melanocytic skin tumors. Usually they are differentiated from nodular melanoma by clinical and histopathological criteria. Since Spitz's nevi are one of the most common simulators of nodular melanomas their bizarre histopathology may cause diagnostic confusion and make it difficult to differentiate these two melanocytic tumors. One of the histologic features shared by Spitz's nevus and nodular melanoma is prominent vascularity. The ability of malignant melanoma to induce angiogenesis is well established whereas benign melanocytic tumors do not have a prominent overall vascularity. The purpose of this study was to find out whether the degree of vascularity of nodular melanomas differs significantly from that of benign Spitz's nevi. In this study the number of microvessels and the vessel area were determined in 23 Spitz's nevi and 16 nodular melanomas. The number of microvessels and the vessel area were determined on Ulex Europaeus agglutinin I-stained sections by computer-assisted image analysis. Two methods of measurement were used, namely systematic and selective sampling. Measurement of the whole tumor specimen (systematic sampling) revealed a vessel count of 10.83/field (SD +/-5.97) for Spitz's nevi whereas nodular melanomas exhibited a significantly lower (p=0.04) vessel count of 6.44/field (SD +/-3.85). This difference was even more pronounced when the vessel area (Spitz's nevi: 17.85x10-4mm2, SD +/-10.32; nodular melanomas: 7.88x10-4mm2, SD +/-5.23) was investigated (p < 0.001). The difference in vessel area and vessel count was insignificant for areas exhibiting the greatest vascularity (selective sampling). Measurement of vessel count and vessel area lead us to conclude that Spitz's nevi have a significantly higher vascularity than do nodular melanomas. Our results thus indicate that angiogenesis in these pigmented lesions is not correlated with malignancy.

Humans↗
PubMed1997

Obsessive-compulsive disorder with and without tics in an epidemiological sample of adolescents.

OBJECTIVE: This study was undertaken to discriminate subtypes of obsessive-compulsive disorder in adolescents. METHOD: Forty individuals with obsessive-compulsive spectrum disorders were ascertained from an epidemiological sample of 861 adolescents. Interviews were conducted by child psychiatrists using semistructured diagnostic interviews, including a clinician-rated Yale-Brown Obsessive Compulsive Scale. Discriminant analysis was performed to compare the scores on the Yale-Brown scale of groups with and without comorbid tics and to compare boys and girls. RESULTS: Adolescents with tics were more prone to aggressive and sexual images and obsessions than were adolescents without tics; these differences could not be wholly attributed to sex differences. CONCLUSIONS: The subtypes among unreferred adolescents are similar to those of adult patients with obsessive-compulsive disorder with and without Gilles de la Tourette syndrome. Subtypes evident in adulthood may be established relatively early in the natural course of obsessive-compulsive disorder.

Adolescent↗
PubMed1997

Double-blind trial of botulinum A toxin for the treatment of focal hyperhidrosis of the palms.

We performed a randomized double-blind study within-group comparison in 11 patients to study the effect of subcutaneous injections of botulinum A toxin in focal hyperhidrosis of the palms. A total dose of 120 mU (mouse units) of botulinum A toxin (Dysport) was injected into six different sites on one palm, whereas the other was injected with sterile saline. Objective quantification of sweat production was performed using digitized ninhydrin-stained sheets. Three weeks after treatment, the mean reduction of sweat production in the botulinum A toxin-treated palms was 26% (P < 0.001), after 8 weeks 26% (P = 0.002) and after 13 weeks 31% (P < 0.001). Subjective assessment of sweat production by the patients using a visual analogue scale showed a 38% improvement in the botulinum A toxin-treated palms at 3 weeks (P = 0.002), 40% at 8 weeks (P = 0.002) and 38% at 13 weeks (P = 0.002). Neither the objective measurement nor the subjective rating showed a statistically significant reduction of sweating in the placebo-treated palms. Three patients reported reversible minor weakness of powerful handgrip after injection at the toxin-treated site, lasting between 2 and 5 weeks.

Adult↗
PubMed1997

Arg506 to Gln mutation in the factor V gene causes poor fibrinolytic response in children after venous occlusion.

To determine to what extent the Arg506 to Gln mutation in the factor V gene influences the fibrinolytic response after 20 min venous occlusion (VO) we investigated a population of APC resistant children (n = 60) and a group of age-matched healthy controls (n = 25). After 20 min VO, symptomatic (n = 30) carriers of the common factor V mutation showed significantly reduced t-PA activities compared with asymptomatic (n = 30) carriers (p <0.0001) and healthy controls (p <0.0001). In contrast, PAI 1 activity was significantly (p <0.0001) higher before and after VO in children with the factor V mutation compared with healthy children. No difference was found between symptomatic and asymptomatic probands. A significantly lower PAI 1 antigen decrease along with a lower t-PA antigen release was found in the APC resistant children compared with the controls. No significant difference was seen between individuals with and without previous vascular insults. As the lack of t-PA activity after VO in symptomatic carriers is the most conspicuous result, we suggest that the factor V gene mutation itself might induce the fibrinolytic impairment by increasing the thrombin levels and thus increasing the recently described thrombin-activable fibrinolysis inhibitor (TAFI).

Arginine↗
PubMed1996

The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo.

The CBFbeta subunit is the non-DNA-binding subunit of the heterodimeric core-binding factor (CBF). CBFbeta associates with DNA-binding CBFalpha subunits and increases their affinity for DNA. Genes encoding the CBFbeta subunit (CBFB) and one of the CBFalpha subunits (CBFA2, otherwise known as AML1) are the most frequent targets of chromosomal translocations in acute leukemias in humans. We and others previously demonstrated that homozygous disruption of the mouse Cbfa2 (AML1) gene results in embryonic lethality at midgestation due to hemorrhaging in the central nervous system and blocks fetal liver hematopoiesis. Here we demonstrate that homozygous mutation of the Cbfb gene results in the same phenotype. Our results demonstrate that the CBFbeta subunit is required for CBFalpha2 function in vivo.

Alleles↗