Complex three-way translocation involving MLL, ELL, RREB1, and CMAHP genes in an infant with acute myeloid leukemia and t(6;19;11)(p22.2;p13.1;q23.3).

Rearrangements affecting the MLL gene in hematological malignancies are associated with poor prognosis. Most often they are reciprocal translocations and more rarely complex forms involving at least 3 chromosomes. We describe an unusual case with cutaneous leukemic infiltrates that waxed and waned until progression to acute myeloid leukemia, AML-M5. The leukemic cells harbored a novel apparent 3-way translocation t(6;19;11)(p22.2;p13.1;q23.3). We utilized advanced molecular cytogenetic methods including 24-color karyotyping, high-resolution array comparative genomic hybridization (aCGH) and DNA sequencing to characterize the genomic complement in the leukemic cells from aspirated bone marrow cells at AML diagnosis. Karyotyping showed 47,XY,t(6;19;11)(p22;p13;q23),+der(6)t(6;11)(p22;q23)[17]/48,sl,+8[3]/48,sl,+8,der(12)t(1;12)(q11;p13)[3]/ 48,sdl,der(Y)t(Y;1)(q12;q11),+8[7] conferring MLL-ELL fusion. Oligo-aCGH analysis confirmed gains of 6p22qter and 11q23.3qter involving the CMAHP and MLL genes, respectively. DNA sequencing disclosed an additional breakpoint at 6p24.3 (at RREB1 gene). Retrospective fluorescence in situ hybridization revealed presence of the MLL-involving rearrangement in the initial stages of disease before clear morphological signs of bone marrow involvement. The patient responded well to therapy and remains in remission>6 years from diagnosis. This apparent 3-way translocation is remarkable because of its rarity and presentation with myeloid sarcoma, and may, as more cases are characterized, further our understanding onto how such complex translocations contribute to promote leukemogenesis and respond to therapy.

[Treatment situation of long-term unemployed with psychological disorders]. / Versorgungssituation von Langzeitarbeitslosen mit psychischen Störungen.

BACKGROUND: Untreated psychiatric disorders of long-term unemployed persons represent a medical problem and a placement barrier to the labor market that can be eliminated. The objective of the study was to assess the spectrum of diagnoses and the treatment rates in a group of unemployed persons (≥ 50 years) referred by the employment exchange of the job center in Munich to a center for psychosocial coaching. METHODS: Out of 105 participants 44 (42%) showing signs of psychiatric disorders according to the patient health questionnaire (PHQ) screening were included in the evaluation. The psychiatric diagnoses were assessed by means of a fully structured diagnostic interview, the Munich composite international diagnostic interview (M-CIDI). A semi-structured interview was conducted to investigate the treatment rates and treatment compliance with guidelines. RESULTS: Affective disorders (70%) were in the foreground followed by anxiety disorders (55%, specific phobias, other and unspecified phobic anxiety disorders were excluded) and disorders due to abuse of alcohol (32%). Of the participants 61 % received no disorder-specific treatment or no treatment at all and treatment compliant with guidelines was received by 9%. CONCLUSIONS: Untreated psychiatric disorders (especially depression) or those that are not treated in compliance with guidelines represent a medical problem and a placement barrier to the labor market that can be eliminated.

A case of childhood acute myeloid leukemia associated with inversion (7)(p21q31).

We describe a case of acute myeloid leukemia in a 2 1/2-year-old boy presenting with a mediastinal tumor causing respiratory distress, and lymph node enlargement in the cervical and inguinal regions. Apart from myeloid markers CD13 and CD33, blast cells also expressed stem cell marker CD34 and megakaryocytic marker CD61. Cytogenetically, inv(7)(p21q31) was found in 9/25 and 15/25 analyzed metaphases from short-term cultures of lymph node and bone marrow cells, respectively. The patient is in continued complete remission 26 months post diagnosis. The case demonstrates that chromosome aberrations other than inv(16), t(8;21), and t(9;11) may be associated with extramedullary disease, and that not all chromosome 7 aberrations are prognostic adverse findings.

Interaction between the mRNA of the 55-kDa tumor necrosis factor receptor and cellular proteins. Possible involvement in post-transcriptional regulation of receptor expression.

Numerous effects of tumor necrosis factor are signaled by its 55-kDa receptors. Studying their expression we found that the level of receptor mRNA was decreased during the phorbol ester-induced differentiation of myelomonocytic cell lines. While only minor changes in transcription were noted, the half-life of receptor mRNA in the differentiated cells was markedly decreased, indicating the involvement of post-transcriptional regulation. In an electrophoretic mobility shift assay, formation of complexes between radiolabeled receptor mRNA and cellular proteins was observed. The decrease in receptor mRNA levels during phorbol ester-induced differentiation was paralleled by a change in the pattern of those complexes. Protein-RNA interaction was selective, as it was not competed by unrelated RNAs. Yet, certain mRNAs that contain AU-rich sequences, known to be involved in the control of their stability, did compete with the receptor mRNA, although the latter is devoid of such sequences. A region of 18 nucleotides within its coding region was found to contain an element essential for the formation of all complexes and sufficient for the formation of those with lower molecular mass. Adjacent bases were required in addition for the formation of the complexes with higher molecular mass. The results suggest that proteins interacting with this region of the 55-kDa tumor necrosis factor receptor mRNA contribute to the regulation of its expression.

UVAL-MED a universal visual associative language for medicine.

We describe UVAL-MED, a Universal visual associative language for medicine, and propose its use in combination with diagnostic reasoning and decision support systems. When fully developed, our system will automatically translate SNOMED terms to UVAL-MED terms. Grammar and syntax for UVAL-MED are defined and its features as a language-independent tool are discussed. The perceived advantages of our graphical language for rapid integration of knowledge and the assessment of developing situations could thus facilitate decision making.

An intelligent interactive simulator of clinical reasoning in general surgery.

We introduce an interactive computer environment for teaching in general surgery and for diagnostic assistance. The environment consists of a knowledge-based system coupled with an intelligent interface that allows users to acquire conceptual knowledge and clinical reasoning techniques. Knowledge is represented internally within a probabilistic framework and externally through a interface inspired by Concept Graphics. Given a set of symptoms, the internal knowledge framework computes the most probable set of diseases as well as best alternatives. The interface displays CGs illustrating the results and prompting essential facts of a medical situation or a process. The system is then ready to receive additional information or to suggest further investigation. Based on the new information, the system will narrow the solutions with increased belief coefficients.

Graphic summaries of expert knowledge for the medical curriculum: an experiment in second-year nephrology.

This study was conducted to test the effects of Concept Graphics on learning in clinical nephrology. Second-year medical students were exposed to summaries of the major renal pathologies presented as text with, or without Concept Graphics for 30 minutes, followed by a quiz. Concept Graphics summarize diagnoses using icons that are metaphors of objects or processes. Of nine quiz questions, five were classified as correlation questions and four as memorization questions. The experimental group (n = 39) performed better than the controls (n = 33) in answering the correlation questions (p = 0.018). The experimental group mentioned more frequently than the controls two pathogonomic criteria of the nephritic syndrome (p = 0.02). Results of an opinion poll of the students, comparing sources used in their studies of nephrology were treated by correspondence analysis; the Concept Graphics ranked closest to the classification "very useful".

Concept graphics: a language for medical knowledge.

This paper makes a case for Concept Graphics, a novel form of medical knowledge representation. Concept Graphics are assemblies of icons each of which has a precise meaning. Individual icons are metaphors of the object or process they represent. Concept Graphics are analogs of pathological situations, their symptoms, signs and other relevant components necessary for a diagnosis. We propose three principal areas of application for Concept Graphics: medical education, medical records management and research based on medical records. Our earlier work in medical education showed a clear advantage in using Concept Graphics in parallel with text of equivalent information content, over text alone. A Concept Graphics based intelligent tutoring systems (ITS) is being developed. In the area of medical records management we are developing a system for the rapid identification of relevant records based on rapid visual screening. The Concept Graphics based system can reveal properties common to specific groups of records. As such the graphics are a research tool.

Kinetics of inactivation of creatine kinase during modification of its thiol groups.

Kinetics of inactivation and modification of the reactive thiol groups of creatine kinase by 5,5'-dithiobis(2-nitrobenzoic acid) or iodoacetamide have been compared, the former by following the substrate reaction in presence of the inactivator [Wang, Z.-X., & Tsou, C.-L. (1987) J. Theor. Biol. 127, 253]. The microscopic constants for the reaction of the inactivators with the free enzyme and with the enzyme-substrate complexes were determined. From the results obtained it appears that with respect to ATP both inactivators are noncompetitive whereas for creatine iodoacetamide is competitive but DTNB is not. The formation of the ternary complex protects against the inactivation by both DTNB and iodoacetamide. The inactivation kinetics is monophasic with both inactivators, but under similar conditions, the modification reactions in the presence of the transition-state analogue of creatine-ADP-Mg2+-nitrate show biphasic kinetics as also reported by Price and Hunter [Price, N.C., & Hunter, M.G. (1976) Biochim. Biophys. Acta 445, 364]. If the reactive ternary complex and the enzyme complexed with the transition-state analogue react in the same way with these reagents, the modification of one fast-reacting thiol group for each enzyme molecule leads to complete inactivation, indicating that the enzyme has to be in the dimeric state to be active.

A nonuniform detector aperture for CT.

The finite width of the X-ray beam determined by the source and detector aperture limits the resolution of computed tomography (CT) images. Improved resolution can be obtained by reducing the width of the detector, but at a cost in dose utilization efficiency. We show that it is possible to improve the resolution in a CT image with a minimum cost in dose efficiency by varying the sensitivity of (apodizing) the detector response function. Further, we demonstrate how to construct detectors with nonuniform response by changing the reflective coating on the scintillator. Finally, we show improved calculated point response functions for such modified detectors.

Regulation of hamster adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity.

In the adrenal gland of the hamster, the activity of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase [mevalonate:NADP+ oxidoreductase (acylating CoA); EC 1.1.1.34] is mainly located in the postmitochondria fraction. This enzyme exhibits a diurnal rhythm, with a maximum at 1900 h. Peak activity levels are about 1667 pmol/mg protein . min, roughly 8 times the minimum levels. Plasma corticosteroid concentrations closely parallel reductase activity levels. The administration of ACTH or metyrapone (a drug which increases in vivo ACTH secretion) to hamsters enhanced the adrenal reductase activity, whereas aminoglutethimide, an inhibitor of the side chain cleavage of cholesterol, diminished it. The feeding of a 5% cholesterol diet and treatment with 4-aminopyrazolopyrimidine resulted in an increase and a decrease in plasma cholesterol, respectively. Neither treatment significantly altered adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity or the cholesterol content of the gland. Hamster adrenals contain very little free cholesterol (7-11 microgram/mg protein) and even less esterified cholesterol (0.5-2.0 microgram/mg protein). These findings suggest that in the hamster the adrenal gland may be largely autonomous in cholesterol production.

3-Hydroxy-3-methylglutaryl coenzyme A reductase activity in beef adrenal cortex.

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) activity (mevalonate:NADP+ oxidoreductase )CoA-acylating) EC 1.1.1.34) was demonstrated in beef adrenal cortex. Most of the HMG-CoA reductase activity is in the microsomal fraction while a small percentage of the activity is associated with the mitochondria, Mitochondria purified on a linear sucrose gradient are enriched in HMG-CoA reductase and cytochrome c oxidase activities. The reductase present in microsomal preparations from the whole adrenal cortex has an apparent Km of 5.6 X 10(-5) M for (R,S)-HMG-CoA. Reductase activities found in the microsomal fractions from the zona glomerulosa, the zona fasciculata, and the zona reticularis were 1.32, 7.37, and 9.74 nmol mevalonate formed per milligram protein in 30 min respectively.