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Biomedical subjects

B Mohr

Publications and source records attributed to B Mohr.

At least 37 records · Page 2Linked to original sources
PubMed2001

Constraint-induced therapy of chronic aphasia after stroke.

Patients with chronic aphasia were assigned randomly to a group to receive either conventional aphasia therapy or constraint-induced (CI) aphasia therapy, a new therapeutic technique requiring intense practice over a relatively short period of consecutive days. CI aphasia therapy is realized in a communicative therapeutic environment constraining patients to practice systematically speech acts with which they have difficulty. Patients in both groups received the same amount of treatment (30 to 35 hours) as 10 days of massed-practice language exercises for the CI aphasia therapy group (3 hours per day minimum; 10 patients) or over a longer period of approximately 4 weeks for the conventional therapy group (7 patients). CI aphasia therapy led to significant and pronounced improvements on several standard clinical tests, on self-ratings, and on blinded-observer ratings of the patients' communicative effectiveness in everyday life. Patients who received the control intervention failed to achieve comparable improvements. Data suggest that the language skills of patients with chronic aphasia can be improved in a short period by use of an appropriate massed-practice technique that focuses on the patients' communicative needs.

Adult↗
PubMed2001

The prognostic value of Bcl-XL gene expression for remission induction is influenced by cytogenetics in adult acute myeloid leukemia.

BACKGROUND AND OBJECTIVES: There is growing evidence that altered expression of genes belonging to the BcL-2 family of apoptosis regulators might influence chemotherapy-induced apoptosis in malignant cells and therefore could confer multidrug resistance. So far expression studies of apoptosis-regulating genes on acute myeloid leukemia (AML) have mainly focused on Bcl-2 itself and most of them have not included other factors involved in drug resistance or apoptosis as parameters determining response to chemotherapy, disease progression and survival. DESIGN AND METHODS: We therefore examined Bcl-2, Bcl-XL and Bax gene expression in 235 adult patients with de novo or secondary myeloid leukemia. The expression levels were correlated with established prognostic factors such as age, cytogentic aberrations, mdr1 gene expression and clinical outcome in a multivariate analysis. RESULTS: Bcl-2 and Bcl-XL positive patients had a much lower white blood cell count than negative patients (p<0.001 and p=0.003, respectively). Bcl-2 expression correlated with FAB subtype M0 (p=0.03), Bax with M5b (p=0.02) and Bcl-XL with M6 (p=0.005). Mdr1 expression was more frequently seen in Bcl-2 and Bcl-XL positive patients (p=0.03 and p=0.02, respectively). Remarkably Bax was significantly less frequently expressed in de novo AML patients with high risk cytogenetics (p=0.007). No difference in expression was recognized for Bcl-2 or Bcl-XL when statistical analyses were done for cytogenetic risk groups. However, in the multivariate analysis regarding the group of de novo AML patients < or =60 years with intermediate risk cytogenetics, Bcl-XL expression was found to be an independent negative prognostic factor for response to induction therapy (p=0.04). In contrast, no prognostic impact of Bcl-XL expression on treatment response was seen within the group of patients with high risk cytogenetic findings. Neither Bcl-2 nor Bax nor Bcl-XL expression had a significant influence on overall or disease-free survival. INTERPRETATION AND CONCLUSIONS: These data indicate that the prognostic value of Bcl-XL gene expression for treatment response in AML patients < or =60 years is dependent on cytogenetics.

Acute Disease↗
PubMed2001

Acceleration of recovery after injury to the peripheral nervous system using ultrasound and other therapeutic modalities.

Taken together, these studies show the promise of various therapeutic modalities for the noninvasive treatment of peripheral nerve injury. Further progress on these promising methods requires determining the biologic mechanisms responsible for the ability of these modalities to enhance peripheral nerve recovery. Necessary investigations include validation or refutation of the hypothesis that these therapies act on various aspects of the natural healing process. Examples include cellular and molecular processes involved in promoting Wallerian degeneration and the rate and specificity of axonal regeneration and remyelination and muscle reinnervation, processes that are distributed between the regenerating nerve itself, the pathway of the regenerating axon, and the target of the regenerating nerve. An increased understanding of the biologic mechanisms underlying the enhancement of peripheral nerve recovery after injury would lend greater insight into the cellular and molecular mechanisms involved in successful nerve regeneration and muscle reinnervation. This increased understanding may also result in clinically beneficial treatments for peripheral nerve disorders.

Animals↗
PubMed2000

Interhemispheric cooperation during word processing: evidence for callosal transfer dysfunction in schizophrenic patients.

Functional lateralization and interhemispheric interaction during word processing were investigated in schizophrenic patients (n=12) and matched healthy controls (n=18). Words and phonologically regular pseudowords were presented tachistoscopically either in the left or right visual field (unilateral conditions), or simultaneously in both visual hemifields (bilateral condition). Consistent with earlier findings, healthy controls showed a right visual field advantage (RVFA), indicating left-hemispheric dominance for language. The patients showed a RVFA similar to that of controls, consistent with normal left-hemispheric language dominance. Importantly, controls performed much better on words presented in the bilateral condition, when two copies of the same word appeared twice, compared to stimulation in only one of the visual hemifields. This bilateral advantage, which has been interpreted as evidence for cooperation between the hemispheres, was absent in schizophrenics. These data show that schizophrenic patients can exhibit similar lateralization patterns as healthy controls. Their specific functional deficit may be a lack of cooperation between the hemispheres.

Adult↗
PubMed2000

Shift of aberrant antigen expression at relapse or at treatment failure in acute leukemia.

The flow cytometric detection of aberrant antigen expression is one method proposed for the quantification of minimal residual disease (MRD) in acute leukemias. The present study was designed to investigate the stability of the aberrant antigen expression at relapse or at treatment failure of initial chemotherapy. For this purpose, multiparameter immunophenotyping with a panel of 15 monoclonal antibodies was used at diagnosis as well as at relapse (43 patients with overall 65 aberrations) and at treatment failure (35 patients with overall 66 aberrations). There was a significant decrease in the percentage of the initially described aberrant antigen expression on leukemia blasts at relapse (P = 0.001; n = 65) as well as at treatment failure (P = 0.0001; n = 66) considering all aberrations in the whole leukemia population. Concerning only patients with acute myelogenous leukemia (AML), significant decreases in the aberrant expression could be detected at relapse (P = 0.031; n = 42) and at treatment failure (P = 0.0001; n = 52). The changes in patients with acute lymphoblastic leukemia (ALL) were significant only at relapse (P = 0.006; n = 23). Initially, the most informative aberration was not detectable in four patients at relapse and in seven patients at treatment failure. A decrease of under 50% of the initial value was observed in another 8 patients at relapse and in 10 patients at treatment failure. In further studies assessing the detection of aberrant antigen expression for MRD, quantification of the relapses should be explicitly analyzed regarding the persistence of the initially described aberrant antigen expression.

Adult↗
PubMed2000

[Congenital pachyonychia type II (Jackson-Lawler syndrome)].

Pachyonychia congenita (PC) is a rare ectodermal dysplasia with variable expression. The condition is usually inherited as an autosomal dominant trait. Several classifications of PC have been proposed. Feinstein and colleagues suggested four clinical types of PC. Type II, the Jackson-Lawler-Syndrome, is characterized by multiple epidermal cysts, palmoplantar bullae and hyperhidrosis as well as natal teeth in addition to the main findings of pachyonychia, palmoplantar hyperkeratosis and follicular keratosis. We report two patients (father and son) with Jackson-Lawler-Syndrome and describe in detail pathogenesis, diagnostic criteria and treatment approaches as well as the different classifications of pachyonychia congenita.

Adolescent↗
PubMed2000

Operant conditioning of left-hemispheric slow cortical potentials and its effect on word processing.

This study investigated whether language-related cognitive processes can be modified by learned modulation of cortical activity. Study participants received feedback of slow cortical potentials (SCPs) recorded above left-hemispheric language cortices and were reinforced for producing negative and positive shifts upon two different discriminative stimuli. In all subjects who achieved reliable control of left-hemispheric brain responses, substantial modification of word processing was observed. Behavioral modification could be documented in two experiments in which word probes were presented following discriminative stimuli. When negative shifts of the EEG were required, lexical decisions on words were substantially speeded, while they were slowed during positivity conditions. There was no indication for any performance difference between conditions in control subjects who failed to achieve control over SCPs after feedback training. This result was replicated in an experiment using lateralized-tachistoscopic stimulus presentation. Comparisons of word and pseudoword responses in both experiments indicated that behavioral modification was most pronounced for word responses. It was also not seen in a simple reaction time task not involving language materials. This argues against a global effect related to perception, visuo-spatial attention, or motor processes. We conclude that linguistic processes can be influenced by modification of cortical activity due to operant conditioning. In closing, tentative explanations of the present results based on theories of language and attention processes are being discussed.

Adult↗
PubMed2000

Comparison of spectral karyotyping and conventional cytogenetics in 39 patients with acute myeloid leukemia and myelodysplastic syndrome.

Spectral karyotyping (SKY) was performed in patients with acute myeloid leukemia (AML; n = 25), secondary AML (s-AML; n = 7), myelodysplastic syndrome (MDS; n = 6) and s-MDS (n = 1) to complement conventional cytogenetic investigations. According to the results of conventional cytogenetics the patients were subdivided into three groups: group 1, normal karyotype, n = 19 cases, median age = 64 years; group 2, patients displaying either one or two single aberrations, n = 10 cases, median age = 54 years; group 3, patients with > or =3 independent aberrations, n = 10 cases, median age = 61.5 years. SKY identified no abnormal metaphases in group 1. In one patient of group 2 a hidden translocation t(7;14)(q3?1;q2?2) could be revealed with SKY. Conventional cytogenetics had only shown trisomy 8. A similar t(7;14) was also detected in one patient of group 3. SKY was helpful for the delineation of marker chromosomes and additional material. Furthermore, SKY could distinguish between partial and total monosomies or real existing and apparent deletions. The combination of G-banding, FISH and SKY was found very useful for the precise delineation of the karyotype. As a result of our study we recommend SKY investigation as an important additional tool for accurate chromosome analysis. The detected t(7;14) might represent a novel recurrent translocation in acute myeloid leukemias.

Acute Disease↗
PubMed2000

Plasma endotoxin concentrations during cardiac surgery may be related to atherosclerosis.

Systemic endotoxemia develops during cardiopulmonary bypass, probably due to intestinal ischaemia. Differences in endotoxaemia among various cardiac operations and the relationship between endotoxemia and postoperative complications were studied in high-risk patients. Blood samples were obtained at termination of bypass in 136 adults undergoing elective cardiac surgery. Postoperative complications were registered prospectively. Plasma endotoxin was quantified by a kinetic limulus amebocyte lysate assay. Mean endotoxin concentrations were significantly lower in patients undergoing isolated valve replacement (89 ng/l) than in patients undergoing coronary artery bypass grafting alone (234 ng/l), or combined with valve replacement (278 ng/l) or carotid artery surgery (321 ng/l) (p < 0.05). In multivariate linear regression, only the number of grafts (0, 1-3, 4-5) was significantly correlated to endotoxin concentrations (p < 0.0005). Endotoxin concentrations were related to development of gastrointestinal dysfunction (p = 0.03), but not to mortality (p = 0.24) or other complications (p = 0.62).

Aged↗
PubMed2000

Cytokine-driven differentiation of blasts from patients with acute myelogenous and lymphoblastic leukemia into dendritic cells.

We investigated the ability of both acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) blasts to differentiate into dendritic cells (DC) in vitro. Cytokine-supplemented suspension cultures of leukemic blasts in 98 patients with AML and five patients with ALL (normal karyotype, n = 2; BCR/ABL, n = 3) were performed. Mononuclear cells out of peripheral blood or bone marrow containing between 60% and 90% leukemic blasts were cultured for eight days using different growth factor combinations. The highest yield of CD1a(+)/CD14(-) cells could be obtained with stem cell factor, transforming growth factor-beta, tumor necrosis factor-alpha, GM-CSF, and FLT-3-ligand. In the AML samples the median content of CD1a(+)/CD14(-) cells after eight days of culture was 3.5% (r = 0%-82%). In five informed patients CD1a(+)/CD14(-) cells were sorted by fluorescence-activated cell sorting or immunomagnetic separation. Cytogenetic and polymerase chain reaction analyses showed known primary chromosomal aberrations (monosomy 7 and inversion 16) in the sorted fractions, respectively. Dendritic cells (DC) could be generated out of leukemic blasts in 68% of AML patients. Leukemic DC showed no phagocytosis of latex beads, but stimulated allogeneic naive cord blood-derived T cells more efficiently than did uncultured blasts. In ALL patients the median percentage of CD1a(+)/CD14(-) cells was 1.2% (r = 0.7%-3.8%) after culture. The sorted CD1(+)/CD14(-) fractions were BCR/ABL-negative when analyzed with fluorescence in situ hybridization, indicating their nonleukemic origin. Leukemic DC can be generated out of leukemic progenitors in patients with AML. These cells might become relevant for autologous and allogeneic immunotherapy in selected patients. BCR/ABL-positive lymphoblasts could not be transformed into cells with an early dendritic phenotype with the cytokines used in our experiments.

Adolescent↗
PubMed1999

Semantic or lexico-syntactic factors: what determines word-class specific activity in the human brain?

Words from different classes have been found to activate different brain areas. However, it is unclear whether grammatical word properties, for example their being part of different lexical categories (e.g. nouns vs. verbs) or semantic features of the words (e.g. that they refer to visually perceived entities or to actions) are relevant for eliciting differential brain responses. We tested this by comparing brain potentials elicited by nouns and verbs that varied in their action and visual associations. Naturally spoken word stimuli were from three categories: (1) nouns with strong visual associations; (2) action verbs with strong associations of actions, and (3) nouns with strong action associations. Word-category specific differences became apparent around 500 ms after stimulus onset, approximately 150-200 ms after the average recognition point of the words involved. Brain responses to visual nouns and action verbs differed at central and occipital recording sites. A very similar topographical difference emerged from the comparison of visual vs. action nouns, whereas no significant difference was found between action-related nouns and verbs. These results indicate that grammatical differences alone, e.g. between two lexical classes such as action verbs and action-related nouns, are not sufficient for eliciting differential brain responses. In contrast, semantic differences between items from the same lexical category can be sufficient for changing the topography of cortical processes induced by word stimuli. This is support for associative theories of word processing.

Adult↗
PubMed1999

The HMG-I(Y) A.T-hook peptide motif confers DNA-binding specificity to a structured chimeric protein.

Chromosomal translocations involving genes coding for members of the HMG-I(Y) family of "high mobility group" non-histone chromatin proteins (HMG-I, HMG-Y, and HMG-IC) have been observed in numerous types of human tumors. Many of these gene rearrangements result in the creation of chimeric proteins in which the DNA-binding domains of the HMG-I(Y) proteins, the so-called A.T-hook motifs, have been fused to heterologous peptide sequences. Although little is known about either the structure or biophysical properties of these naturally occurring fusion proteins, the suggestion has been made that such chimeras have probably assumed an altered in vivo DNA-binding specificity due to the presence of the A.T-hook motifs. To investigate this possibility, we performed in vitro "domain-swap" experiments using a model protein fusion system in which a single A. T-hook peptide was exchanged for a corresponding length peptide in the well characterized "B-box" DNA-binding domain of the HMG-1 non-histone chromatin protein. Here we report that chimeric A. T-hook/B-box hybrids exhibit in vitro DNA-binding characteristics resembling those of wild type HMG-I(Y) protein, rather than the HMG-1 protein. These results strongly suggest that the chimeric fusion proteins produced in human tumors as a result of HMG-I(Y) gene chromosomal translocations also retain A.T-hook-imparted DNA-binding properties in vivo.

Amino Acid Sequence↗
PubMed1999

Heparin-coated cardiopulmonary bypass equipment. I. Biocompatibility markers and development of complications in a high-risk population.

OBJECTIVES: 1. To study possible clinical benefits of heparin-coated cardiopulmonary bypass in patients with a broad range of preoperative risk factors. 2. To evaluate the correlation between the terminal complement complex and clinical outcome. 3. To identify clinical predictors of complement activation and correlates of granulocyte activation during cardiac surgery. METHODS: Blood samples from adults undergoing elective cardiac surgery with Duraflo II heparin-coated (n = 81) or uncoated (n = 75) cardiopulmonary bypass sets (Duraflo coating surface; Baxter International, Inc, Deerfield, Ill) were analyzed for activation of complement (C3 activation products, terminal complement complex), granulocytes (myeloperoxidase, lactoferrin), and platelets (beta-thromboglobulin) by enzyme immunoassays. Preoperative risk was assessed by means of the "Higgins' score." Complications (cardiac, renal, pulmonary, gastrointestinal, and central nervous system dysfunction, infections, death) were registered prospectively. Data were analyzed by analysis of variance, logistic regression, and linear regression. RESULTS AND CONCLUSIONS: Sixty-seven percent of the patients had predefined risk factors. Complications developed in 53 patients (34%), equivalently with and without heparin-coated bypass sets (P =. 44-.82), despite a significant reduction in complement and granulocyte activation by heparin coating. No clear-cut relationship between the terminal complement complex and outcome was found, even if it was significant in the models for renal and central nervous system dysfunction and infections (P =.006). The Higgins' score was significantly related to complement activation (P <.05). Approximately 50% of the variation in granulocyte activation was explained by complement (P </=.01) and platelet activation (P <.05), heparin/protamine dose ratio (P =.02), duration of cardiopulmonary bypass (P <.01), and gender (P <.05). Therefore measures reducing complement activation alone will not necessarily reduce granulocyte activation sufficiently for clinical significance.

Aged↗
PubMed1999

Heparin-coated cardiopulmonary bypass equipment. II. Mechanisms for reduced complement activation in vivo.

OBJECTIVE: Our objective was to study mechanisms for reduced complement activation by heparin coating of cardiopulmonary bypass equipment in clinical heart surgery. METHODS: Adults undergoing elective coronary artery bypass grafting were randomized to cardiopulmonary bypass with Duraflo II heparin-coated (n = 15) or uncoated (n = 14) sets (Duraflo coating surface; Baxter International, Inc, Deerfield, Ill). Blood samples were analyzed with the use of enzyme immunoassays for C1rs-C1 inhibitor complexes and the activation products Bb, C4bc, C3bc, C5a-desArg, and the terminal complement complex. Data were compared by repeated-measures analysis of variance. RESULTS: C1 was activated during bypass, and increases in C1rs-C1 inhibitor complexes were larger with heparin coating (P =.03). C4bc increased after administration of protamine, without intergroup differences (P =.69). Bb (P =.22) and C5a-desArg (P =.13) tended to increase less with heparin coating. Formation of C3bc (P =.03) and the terminal complement complex (P <.01) was significantly reduced with heparin coating. C5a-desArg increased 2-fold during bypass, whereas the terminal complement complex increased 10- to 20-fold. Maximal terminal complement complex concentrations were significantly correlated to maximal Bb and C3bc (R = 0.6, P <.001), but not to C1rs-C1 inhibitor complexes or C4bc (R < 0.05, P >.8). CONCLUSIONS: C1 activation during bypass was increased by heparin coating, but further classical pathway activation was held in check until administration of protamine. Heparin coating significantly inhibited C3bc and terminal complement complex formation. Terminal complement complex concentrations were related to alternative pathway activation and may be useful for evaluation of differences in bypass circuitry. Increases and intergroup differences in terminal complement complex concentrations were much larger than those in C5a-desArg.

Anticoagulants↗
PubMed1999

Rapid quantification of mixed chimerism using multiplex amplification of short tandem repeat markers and fluorescence detection.

Monitoring the engraftment of donor cells after allogeneic blood stem cell transplantation (BSCT) may be important for the early diagnosis of graft failure or relapse of disease. Several techniques have been reported for this purpose. PCR-based assays analyzing polymorphic short tandem repeat (STR) markers are attractive because they are sensitive and can be performed rapidly. The intent of the present study was to test a novel approach for the quantification of mixed chimerism using a commercial multiplex STR assay with fluorescence-based detection for forensic purposes. The feasibility of this assay and the accuracy of quantitative results was tested using serial cell mixtures of unrelated individuals. Sample preparation was optimized to obtain information from minute amounts of starting material, eg from patients with aplasia or from sorted cell populations. Using the STR-PCR, discrimination between donor and recipient was possible in all patients analyzed (n = 25). Cell dilution experiments showed a linear correlation between the cell numbers added and the proportions found, with the limit of detection for a minor cell population being 5%. Comparison of values obtained with standard FISH analysis in patients transplanted from sex-mismatched donors showed an excellent correlation with the STR-PCR results. Taken together, this procedure allows the rapid, versatile and accurate quantification of mixed chimerism, even with minuscule numbers of cells.

Amelogenin↗
PubMed1999

Detection of cytogenetic aberrations both in CD90 (Thy-1)-positive and (Thy-1)-negative stem cell (CD34) subfractions of patients with acute and chronic myeloid leukemias.

Acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) are thought to arise from malignant hematopoietic progenitor cells representing early and undifferentiated stem cell clones. In CML there is evidence for a progenitor cell subset free of leukemic clones, depending on the course of the disease. Additionally, it has been suggested that in AML, the early stem cell compartment (CD34+/90+) does not harbor the malignant clone. We analyzed white blood cells from leukemia patients for the presence of aberrant cells in stem cell subfractions. Sixteen patients with CML, six patients with AML, two patients with acute lymphatic leukemia (ALL) and one with chronic myelomonocytic leukemia (CMMOL), all with known cytogenetic abnormalities, were evaluated according to their CD90 (Thy-1)-positive or -negative phenotype. Subsets were sorted on to slides and further characterized by FISH and/or standard cytogenetic testing. The bcr-abl translocation or gross chromosomal abnormalities could be detected in equally high amounts of 92.2% and 89.2% in both stem cell subsets. We conclude, that in progressed AML and CML cells characterized by specific genetic aberrations implicated in the malignant state can be found in the CD34+/CD90+ and CD90- population, thus making CD90 an inappropriate marker to distinguish benign from malignant cells in these leukemias.

Acute Disease↗
PubMed1998

Learned changes of brain states alter cognitive processing in humans.

Humans can learn to intentionally control their brain states based on information about their own electrocortical activity. Using an operant conditioning technique, twelve healthy volunteers were trained to shift their slow cortical potentials recorded from left-hemispheric language cortices in the positive versus negative direction. After training, six subjects who achieved reliable control of left-hemispheric brain responses showed substantial modification of word processing. During conditioned negative shifts of cortical potentials (activation condition), responses to words were substantially speeded, whereas lexical decisions were slower during positive shifts of slow cortical potentials (inhibition condition). No comparable difference was seen in trained participants who failed to achieve control over slow cortical potentials. Additional data suggest that the effect was not related to perception, attention, or motor processes. Thus, operant conditioning can produce focal cortical activity dynamics and thereby modify specific higher cortical processes such as access to words. This finding may open new perspectives on neuropsychological rehabilitation based on operant conditioning of brain responses.

Adult↗