Regional localization of two MRX genes to Xq28 (MRX28) and to Xp11.4-Xp22.12 (MRX33).

Two genes responsible for a nonspecific form of X-linked mental retardation (MRX28 and MRX33) were localized by linkage analysis with 40 highly polymorphic DNA markers situated along the entire the X chromosome. In family 1, the gene could be mapped within a 14-cM interval at Xq28, distal to the recombining marker DXS1113 (MRX28). The maximum LOD score was 2.

Magnetic resonance imaging and neurological evaluation after treatment with high-dose methotrexate for acute lymphocytic leukaemia in young children.

This study evaluates the occurrence of permanent cerebral white matter changes and neurological abnormalities in children treated at a young age for acute lymphocytic leukaemia. Our pilot treatment protocol did not include central nervous system irradiation, but intrathecal methotrexate and high-dose methotrexate infusions followed by very intensive folinic acid rescue. We examined 12 children in complete remission and off therapy 18 months to 9.

[Public health fairs on "environment and human health"--participants, topics, attitudes].

19 meetings dealing with environment and human health, including 7 public hearings related to the planning of an incineration plant and 5 training courses for asthmatic patients, were analysed with regard to participation, persons participating in the discussions, topics covered by the remarks and also emotional involvement and standard of information. There was a total of 835 participants; 1471 "units of statements" were assessed. In the open meetings 18-33% of the participants took part in the discussion, in the closed training sessions the number was 66%.

STAT protein complexes activated by interferon-gamma and gp130 signaling molecules differ in their sequence preferences and transcriptional induction properties.

Activation of members of the STAT (signal transducers and activators of transcription) family of latent transcription factors is an early event following the binding of many cytokines to their cognate receptors. Although the patterns of STATs activated by different cytokines are well described, the consequences of differential STAT activation are less well studied. We show by mutational analysis that STAT binding elements (SBEs) exist that discriminate between STAT complexes containing STAT1 alpha, STAT3 or both, and that these elements show altered cytokine responsiveness.

Triosephosphate isomerase deficiency: biochemical and molecular genetic analysis for prenatal diagnosis.

Inherited deficiency of the glycolytic enzyme triosephosphate isomerase leads to a multisystem disorder characterized by progressive neuromuscular dysfunction, chronic nonspherocytic hemolytic anemia and increased susceptibility to severe infections. Most patients die within the first 6 years. We examined a family with severe triosephosphate isomerase deficiency.

Spacing of palindromic half sites as a determinant of selective STAT (signal transducers and activators of transcription) DNA binding and transcriptional activity.

Signal transducers and activators of transcription (STAT proteins) bind to palindromic sequence elements related to interferon gamma (IFN-gamma) activation sites, which were first identified in the promoters of IFN-gamma-inducible genes. Although the sequences of the natural palindromic STAT-binding elements vary considerably, they conform to the general structure TT(N)5AA. We have systematically examined the effects of the spacing between the TT and AA core half sites on the binding of the STAT complexes activated by IFN-gamma, interleukin (IL) 6, granulocyte-macrophage colony-stimulating factor, and IL-4.

DiGeorge syndrome and partial monosomy 10p: case report and review.

DiGeorge syndrome (DGS) is predominantly caused by partial monosomy 22q11, but a subset of patients with DGS show deletions of 10p or other chromosomal abnormalities. The authors describe a 20 months old girl with DGS and a monosomy 10p bringing the number of DGS patients with this chromosomal abnormality to nine. She has a monosomy 10p13-pter and a trisomy 10q26-qter due to a meiotic recombination of a maternal inversion (10) (p13q26).

Rapid activation of the interferon-gamma signal transduction pathway by inhibitors of tyrosine phosphatases.

Induction of gene expression by interferon-gamma involves the activation of a latent cytoplasmic transcription factor, p91, by phosphorylation on a single tyrosyl residue. This phosphorylation triggers dimerization, nuclear translocation, and the binding of p91 to interferon-gamma response elements present in the promoters of induced genes. Phosphorylation of p91 requires the activation of two tyrosine kinases, JAK1 and JAK2, that themselves become phosphorylated on tyrosyl residues shortly after interferon-gamma binds to its receptor.

Rapid activation of the STAT3 transcription factor by granulocyte colony-stimulating factor.

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that stimulates proliferation and differentiation of progenitor cells of neutrophils by signaling through its receptor (G-CSFR). Although the G-CSFR belongs to the cytokine receptor superfamily, which lacks an intracellular kinase domain, G-CSF-induced tyrosine phosphorylation of cellular proteins is critical for its biologic activities. We report here that JAK1 and JAK2 tyrosine kinases are tyrosine phosphorylated in response to G-CSF induction.

Medical education change: a detailed study of six medical schools.

This article reports a comparative case study of six selected USA medical schools, undertaken to identify factors that facilitate or obstruct innovation in medical education. The findings suggest that the culture of each medical school results from a combination of intra-institutional and external factors. Together these forces influence substantially the fate of educational innovations.

Estimation of disc compression during transient whole-body vibration.

This study was performed to examine health effects of transient whole-body vibrations on the lumbar spine. The aim was to detect extremes in the time course of compressive load acting on the disc L3-4 in order to estimate the health risk which depends on the amplitude of peak values of compression. Five healthy males were repeatedly exposed to various transient displacements with nearly sinusoidal or half-sinusoidal waveforms, different durations, and peak accelerations between about 1.

Interaction of inhibitors with phosphoenolpyruvate mutase: implications for the reaction mechanism and the nature of the active site.

The active site and mechanism of action of the enzyme phosphoenolpyruvate mutase have been probed using substrate and intermediate analogues as inhibitors of the mutase-catalyzed reaction. Smaller anions (e.g.

Control of positioning the cervical spine and its application to measuring extensor strength.

The great variability of the flexion of the cervical spine renders an exact description of the control of various positions difficult. A method was developed enabling a precise control of positioning the cervical spine and head in the sagittal plane. In three repeated measurements the mean values of the position of external anatomical landmarks and distances between them exhibited a good reproducibility.

[Familial akinesia-hypokinesia sequence (Pena-Shokier phenotype)].

The Pena Shokeir phenotype (PSP) is characterised by multiple ankyloses, camptodactyly, facial dysmorphisms and lung hypoplasia with hydramnios. The basic neuromuscular defect leads, through a fetal hypokinesia-akinesia, to the development of this nonspecific phenotype and a respiratory insufficiency with early postnatal mortality. Severe central nervous anomalies are described in one-third of the reported cases.

Rapid activation of proteins that interact with the interferon gamma activation site in response to multiple cytokines.

Many cytokines and growth factors trigger rapid changes in gene expression upon binding to their receptors. In many cases, the mechanism by which these changes are affected is unknown. In this report, we show that interleukin-2 (IL-2), IL-3, IL-4, IL-6, leukemia inhibitory factor (LIF), erythropoietin (Epo), and granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment of cells causes rapid activation of DNA-binding activities that recognize a DNA sequence element previously implicated in regulation of gene expression by interferon gamma (IFN gamma).

Evaluation of serious adverse events in patients treated with protocols including methotrexate infusions.

During the period 1979 to 1992 we treated 141 children for various malignant diseases with protocols including methotrexate (MTX) infusions in doses ranging from 0.5 to 33.6 g/m2.

The relationship between the electromyogram-amplitude and isometric extension torques of neck muscles at different positions of the cervical spine.

A group of 12 healthy men volunteered for the experiment. Electromyograms (EMG) were obtained from semispinalis capitis, splenius capitis, levator scapulae, and trapezius muscles. The flexion angle of the cervical spine was precisely adjusted to 0 degrees, 10 degrees, 20 degrees, and 30 degrees relative to the horizontal, with a constant angle of the atlanto-occipital joint.

Early effects of benzene exposure in mice. Hematological versus genotoxic effects.

Female BDF1 mice were exposed to 100, 300 and 900 ppm benzene 6 h/day, 5 days/week, up to 8 weeks. Hematological studies included peripheral blood data, T4 and T8 lymphocyte counts in the blood and the spleen, hemopoietic stem and progenitor cell assays in the marrow (CFU-S, CFU-C, BFU-E, CFU-E). The single cell gel assay ("comet assay") was applied in parallel with cells from the peripheral blood, bone marrow, spleen and liver.

Reduction of benzene toxicity by toluene.

BDF1 mice were exposed in inhalation chambers to benzene (900 ppm, 300 ppm) and/or toluene (500 ppm, 250 ppm) 6 hr per day, 5 days per week, for up to 8 weeks. Benzene alone induced a slight anemia after 4 and 8 weeks and a reduction of BFU-E and CFU-E numbers in the marrow. The coexposure to toluene reduced the degree of anemia.

Selective non-nucleoside HIV-1 reverse transcriptase inhibitors. New 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones and related compounds with anti-HIV-1 activity.

A series of substituted 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones and related compounds 1-73 were synthesized and evaluated for their ability to inhibit reverse transcriptase (RT) of the human immune deficiency virus 1 (HIV-1) and replication of HIV-1 in MT2 cells. The antiviral activity of these compounds depends on the stereoselective configuration of the substituent in position 9b. Structure-activity studies were done within these series of compounds to determine the optimum substituents for antiviral activity.

Selected health risks caused by long-term, whole-body vibration.

The problem of a "vibration disease" caused by low-frequency whole-body vibration (wbv) is critically discussed. Disorders of the nervous, circulatory, and digestive systems are interpreted not to be predominantly wbv-specific, but to be related to the totality of working conditions. Long-term wbv exposure can probably contribute to the pathogenesis of disorders of female reproductive organs (menstrual disturbances, anomalies of position) and disturbances of pregnancy (abortions, stillbirths).