Biomedical subjects
M Binder
Publications and source records attributed to M Binder.
Epiluminescence microscopy of small pigmented skin lesions: short-term formal training improves the diagnostic performance of dermatologists.
BACKGROUND: Epiluminescence microscopy (ELM) makes subsurface structures of the skin accessible for in vivo examination and provides additional criteria for the clinical diagnosis of pigmented skin lesions (PSLs). We demonstrated that ELM increases diagnostic sensitivity in dermatologists formally trained in the use of this technique but decreases diagnostic ability in dermatologists not formally trained in its application. OBJECTIVE: Our purpose was to determine the effects of short formal ELM training on the diagnostic performance of 11 previously untrained dermatologists. METHODS: One hundred image-pairs of randomly selected histologically proven PSLs, photographed with (ELM) and without oil immersion (surface microscopy), were presented by slide projection to the testees. To evaluate the effects on diagnostic performance before and after short-term training, we used the receiver-operator characteristics technique. RESULTS: Without training the use of ELM did not enhance diagnostic accuracy, but rather decreased it in 8 of 11 testees. In contrast, after 9 hours of formal training in ELM the diagnostic performance of the testees was significantly enhanced with an average gain of 8.4%. CONCLUSION: Our data confirm that formal training is required for the useful application of the ELM technique.
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.
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.
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.
Molecular cloning of histone H1 in Entamoeba histolytica and histone H2B in Entamoeba histolytica and Entamoeba dispar.
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Molecular cloning and biochemical characterization of hexokinases and phosphoglucomutases from Entamoeba histolytica and Entamoeba dispar.
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A new strategy for isolating genes expressing proteins involved in the import of peroxisomal proteins.
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Regulation of malate synthase activity.
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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.
Creatine kinase-mb fraction and cardiac troponin T to diagnose acute myocardial infarction after cardiopulmonary resuscitation.
OBJECTIVES: This study sought to evaluate the diagnostic value of the biochemical markers creatine kinase (CK), creatine kinase-MB fraction (CK-MB) and cardiac troponin T (cTNT) to diagnose acute myocardial infarction (AMI) after cardiopulmonary resuscitation (CPR). BACKGROUND: Elevations of CK and CK-MB after CPR are a frequent finding and might be associated with ischemic myocardial injury, as well as physical trauma to the chest. METHODS: Patients who had cardiac arrest and primary successful resuscitation were included in the study. The diagnosis of AMI was confirmed or ruled out by means of typical electrocardiographic findings, thallium-201 myocardial scintigraphy or autopsy, if death occurred during the hospital period, in 39 primary survivors of sudden cardiac death. In 24 patients (62%) the diagnosis of AMI was established. Serum cTNT, CK and CK-MB were measured, and the CK-MB/CK ratio was calculated on admission and after 12 h. RESULTS: On admission all markers of myocardial injury proved to be weak methods for the diagnosis of AMI. After 12 h cTNT as well as CK-MB exhibited a similar diagnostic performance; CK and the CK-MB/CK ratio proved to be worthless. Sensitivity and specificity for a cTNT cutoff value of 0.6 ng/ml, 12 h after cardiac arrest, were 96% and 80%, respectively. For a CK-MB cutoff value of 26 U/liter, sensitivity was 96% and specificity was 73%. CONCLUSIONS: Cardiac TNT and CK-MB are valuable tools in detecting AMI as the cause of sudden cardiac death. However, there is a considerable lack of sensitivity and specificity. Cardiac injury is probably caused not only by AMI, but also by myocardial damage related to CPR efforts.
103Pd brachytherapy and external beam irradiation for clinically localized, high-risk prostatic carcinoma.
PURPOSE: To summarize biochemical failure rates and morbidity of external beam irradiation (EBRT) combined with palladium (103Pd) boost for clinically localized high-risk prostate carcinoma. METHODS AND MATERIALS: Seventy-three consecutive patients with stage T2a-T3 prostatic carcinoma were treated from 1991 through 1994. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (71 patients), Gleason score 7-10 (40 patients), prostate specific antigen (PSA) > 15 (32 patients), or elevated prostatic acid phosphatase (PAP) (17 patients). Patients received 41 Gy EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose: 80 Gy). Biochemical failure was defined as a PSA greater than 1.0 ng/ml (normal < 4.0 ng/ml). Patients whose PSA was still decreasing at the last follow-up were censored at that time. Patients whose PSA plateaued at a value greater than 1.0 were scored as failures at the time the PSA first plateaued. RESULTS: The overall, actuarial freedom from biochemical failure at 3 years after treatment was 79%. In Cox proportional hazard multivariate analysis, the strongest predictor of failure was elevated acid phosphatase (p = 0.04), followed by PSA (p = 0.17), Stage (p = 0.23), and Gleason score (p = 0.6). Treatment-related morbidity was usually limited to temporary, RTOG Grade 1-2 urinary symptoms. One patient, who had both a transurethral incision of the prostate (TUIP) and a transurethral resection of the prostate (TURP), developed low-volume urinary incontinence. The actuarial potency rate at 3 years after implantation was 77% for 46 patients who were sexually potent prior to implant. CONCLUSION: Biochemical freedom from failure rates following combined EBRT and 103Pd brachytherapy for clinically localized, high-risk prostate cancer compare favorably with that reported after conventional dose EBRT alone. Morbidity has been acceptable.
Pip2p: a transcriptional regulator of peroxisome proliferation in the yeast Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, peroxisomes are the exclusive site for the degradation of fatty acids. Upon growth with the fatty acid oleic acid as sole carbon source, not only are the enzymes of beta-oxidation and catalase A induced, but also the peroxisomal compartment as a whole increases in volume and the number of organelles per cell rises. We previously identified a cis-acting DNA sequence [oleate response element (ORE)] involved in induction of genes encoding peroxisomal proteins. The aim of our investigation was to test whether a single mechanism acting via the ORE coordinates the events necessary for the proliferation of an entire organelle. Here we report the cloning and characterization of the oleate-specific transcriptional activator protein Pip2p (pip: peroxisome induction pathway). Pip2p contains a typical Zn(2)-Cys(6) cluster domain and binds to OREs. A pip2 deletion strain is impaired in growth on oleate as sole carbon source and the induction of beta-oxidation enzymes is abolished. Moreover, only a few, small peroxisomes per cell can be detected. These results indicate that fatty acids activate Pip2p, which in turn activates the transcription of genes encoding beta-oxidation components and acts as the crucial activator of peroxisomes.
Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis.
The CBFA2 (AML1) gene encodes a DNA-binding subunit of the heterodimeric core-binding factor. The CBFA2 gene is disrupted by the (8;21), (3;21), and (12;21) chromosomal translocations associated with leukemias and myelodysplasias in humans. Mice lacking a CBF alpha 2 protein capable of binding DNA die between embryonic days 11.5 and 12.5 due to hemorrhaging in the central nervous system (CNS), at the nerve/CNS interfaces of cranial and spinal nerves, and in somitic/intersomitic regions along the presumptive spinal cord. Hemorrhaging is preceded by symmetric, bilateral necrosis in these regions. Definitive erythropoiesis and myelopoiesis do not occur in Cbfa2-deficient embryos, and disruption of one copy of the Cbfa2 gene significantly reduces the number of progenitors for erythroid and myeloid cells.
Creatine kinase and creatine kinase-MB release after nontraumatic cardiac arrest.
The aim of the study was to describe the course of serum creatine kinase (CK) and its MB fraction (CK-MB) in patients surviving cardiac arrest, and to identify factors influencing CK and CK-MB release. The study was set in the community of Vienna, Austria. Data concerning cardiopulmonary resuscitation, collected within a period of 33 months, were evaluated retrospectively and compared with laboratory blood investigations collected prospectively (on admission and after 6, 12, and 24 hours) in 107 adult patients surviving a witnessed cardiac arrest for 24 hours. CK and CK-MB were elevated in >75% of the patients within 24 hours. Release of CK and CK-MB was mainly associated with electrocardiographic evidence of acute myocardial infarction (AMI) cumulative energy administered during defibrillation, and duration of chest trauma by compression. The CK-MB/CK ratio was elevated in 32% of the patients. Of patients with electrocardiographic evidence of AMI, only 49% had an elevated CK-MB/CK ratio. In conclusion, the elevation in serum CK and CK-MB fraction in patients after nontraumatic cardiac arrest is a frequent finding, and is associated with ischemic myocardial injury, as well as physical trauma to the chest. This should be considered when interpreting the course of CK and CK-MB fraction for the diagnosis of AMI.
Impaired hemorheology in patients with postmastectomy lymphedema.
Lymphedema of the arm is one of the most disabling and serious complications of breast cancer. Apart from tumor infiltration or fibrosis of lymphatic pathways, little is known about factors favoring the development of lymphedema. In the present study, we investigated the impact of rheologic parameters, e.g. red cell aggregation (EA) and plasma viscosity (PV), and of capillary morphology and capillary flow in patients with breast cancer with (n = 18) and without (n = 18) lymphedema. Patients with lymphedema showed a significant increase of red cell aggregation (p < 0.001) that indicates a systemic component of lymphedema and might offer a possibility of prevention and therapy of this condition. A hitherto unclassified protein factor favoring red cell aggregation and lymphedema might be postulated.
Immunogold labeling of yeast cells: an efficient tool for the study of protein targeting and morphological alterations due to overexpression and inactivation of genes.
Immunogold labeling on Lowicryl HM20 resin sections is a valuable complement to biochemical methods as well as methods of molecular biology in the study of basic mechanisms in the yeast system. This contribution presents an overview of the state of the art. Emphasis is put on the explanation of caveats and pitfalls rather than on detailed bench protocols. In the Applications section the morphological aspect of genetic manipulation is accentuated and links to human pathology are indicated. The morphological consequences of genetic manipulations may gain importance in view of the efforts made to establish gene therapies. In particular, the contribution of immunoelectron microscopy to the elucidation of peroxisomal targeting signals and to the detection and identification of morphological alteration due to overexpressed, mutated or deleted genes in the context of peroxisome biogenesis is described.
Hemodynamic effects of active compression-decompression after prolonged CPR.
BACKGROUND: This study was designed to test the effects of active compression-decompression (ACD) versus standard (STD) cardiopulmonary resuscitation (CPR) on hemodynamics after prolonged cardiac arrest (CA). METHODS AND RESULTS: After nontraumatic prehospital CA, 21 patients were resuscitated in a prospective nonblinded setting sequentially with STD and ACD CPR at the emergency department, if it had not been possible to achieve restoration of spontaneous circulation (ROSC) before admission. The compression rate was 80/min with a 50% duty cycle, and 1 mg epinephrine was given every 5th min. Invasive arterial, central venous pressure and end tidal CO2 (ETCO2) were monitored. Comparing coronary perfusion pressure (CoPP) and ETCO2, no significant differences between STD and ACD CPR were found. In 3 cases ROSC could be achieved for a short time. CONCLUSIONS: In our study, a comparison of STD and ACD CPR revealed no significant differences in coronary perfusion pressures and ETCO2. We conclude that after prolonged CA, ACD CPR does not provide an apparent hemodynamic advantage over STD CPR.