Analysis of Jak2 signaling reveals resistance of mouse embryonic hematopoietic stem cells to myeloproliferative disease mutation.

The regulation of hematopoietic stem cell (HSC) emergence during development provides important information about the basic mechanisms of blood stem cell generation, expansion, and migration. We set out to investigate the role that cytokine signaling pathways play in these early processes and show here that the 2 cytokines interleukin 3 and thrombopoietin have the ability to expand hematopoietic stem and progenitor numbers by regulating their survival and proliferation. For this, they differentially use the Janus kinase (Jak2) and phosphatidylinositol 3-kinase (Pi3k) signaling pathways, with Jak2 mainly relaying the proproliferation signaling, whereas Pi3k mediates the survival signal.

Signaling from the sympathetic nervous system regulates hematopoietic stem cell emergence during embryogenesis.

The first adult-repopulating hematopoietic stem cells (HSCs) emerge in the aorta-gonads-mesonephros (AGM) region of the embryo. We have recently identified the transcription factor Gata3 as being upregulated in this tissue specifically at the time of HSC emergence. We now demonstrate that the production of functional and phenotypic HSCs in the AGM is impaired in the absence of Gata3.

Zebrafish based assays for the assessment of cardiac, visual and gut function--potential safety screens for early drug discovery.

Introduction: Safety pharmacology is integral to the non-clinical safety assessment of new chemical entities prior to first administration to humans. The zebrafish is a well established model organism that has been shown to be relevant to the study of human diseases. The potential role of zebrafish in safety pharmacology was evaluated using reference compounds in three models assessing cardiac, visual and intestinal function.

Validation of the use of zebrafish larvae in visual safety assessment.

Introduction: The use of zebrafish (Danio rerio) larvae was investigated to predict adverse visual effects and to establish the potential application of this organism in early drug safety assessment.

Methods: Following a comparison of the effects of 4 compounds in TL and WIK strains of zebrafish larvae, a blinded validation set of 27 compounds was tested on WIK strain of larval zebrafish in the optomotor response (OMR) assay. Selected compounds were also tested in the optokinetic response (OKR) and locomotor assays.

Repetitive DNA variation and pivotal-differential evolution of wild wheats.

Several polyploid species in the genus Triticum contain a U genome derived from the diploid T. umbellulatum. In these species, the U genome is considered to be unmodified from the diploid based on chromosome pairing analysis, and it is referred to as pivotal.

Developments in the meiotic analysis of hybrids. I. Review of theory and optimization in triploids.

The theory, construction and optimization of a model of chromosome pairing in triploid hybrids are re-examined and the model reconstructed. A new approach to optimization is described that removes a bias in the estimation of x, the measure of relative affinity, by weighting the observed and calculated meiotic figure frequencies by the number of chromosomes in each figure type. The amended analysis is compared with its antecedent and with other models.

Developments in the meiotic analysis of hybrids. II. Amended models for tetraploids.

Amended models of meiotic behaviour in tetraploid species' hybrids have been constructed which better reflect the theory and assumptions about chromosome pairing necessary to conduct such analyses. In particular they correct problems concerning the distribution of chiasmata among and within chromosome configurations inherent in the earlier models of Kimber & Alonso (1981). In general these analyses give similar interpretations to the earlier models but in some cases call the previous conclusions into question.

Production and meiotic analysis of autotriploid Triticum speltoides and T. bicorne.

Autotriploid Triticum speltoides and T. bicorne (2n=3x=21) were produced by pollinating autotetraploids with pollen from their respective diploids. The autotriploid plants were vigorous, male sterile, and morphologically resembled their diploid parents.

Genomic analysis of diploid plants.

The numerical analysis of meiosis in the triploid hybrid between an induced autotetraploid and a related diploid provides the basis for investigations of the genomic relationships of diploid species based on chromosome pairing. It is also possible to make legitimate comparisons between different triploid hybrids of this type so that the genomic relationships can be converted into measures of phylogenetic distance for taxa where only diploids are known.

Headache and blood pressure: evidence of a close relationship.

Although headache is sometimes regarded as a symptom of severe hypertension, its relationship to blood pressure is not clear. In 11,710 patients with mild to moderate essential hypertension we have found that headache was common and may be reduced by treatment. We found a clear relationship between the frequency of reports of headache and both systolic and diastolic blood pressure irrespective of treatment or the type of drug used to treat hypertension.

Analysis of pivotal-differential evolutionary patterns.

The numerical analysis of meiosis in hybrids between a wild allotetraploid and an autotetraploid of one of its putative diploid progenitors allows the identification of which genomes are pairing and also the verification of pivotal-differential evolution. This type of analysis should be applicable to all genera in which allopolyploid series exist.

Post-marketing surveillance of enalapril: experience in 11,710 hypertensive patients in general practice.

Post-marketing surveillance in general practice represents an important part of the monitoring of adverse events associated with newly introduced drugs. Such a study of the angiotensin-converting enzyme inhibitor enalapril maleate has been undertaken in 11 710 patients with essential hypertension. Serious adverse events occurred in 1.

Influence of age on blood pressure response to enalapril.

Based on prevailing hypotheses about the role of renin in essential hypertension, both Laragh and Buhler independently predicted that angiotensin-converting enzyme (ACE) inhibitors would become less effective with increasing age, as elderly hypertensive patients tend to have low plasma renin activity. We have investigated this situation in a large postmarketing surveillance study with enalapril. Following a 2-week no-treatment period, a total of 11,710 patients with essential hypertension received 10-20 mg of enalapril once daily for 6 weeks.

The theory of the pairing of telocentric chromosomes in triploids and trisomics.

The possible pairing patterns of telocentric chromosomes in triploids and trisomics are considered and expressions are derived allowing the prediction of expected meiotic, chromosomal, and cellular pairing patterns. The calculation of the relative affinity of the homoeologous chromosomes involved in the pairing patterns with the telocentrics is discussed.

New hybrids with d genome wheat relatives.

The cytology of nine new D genome hybrids involving Triticum syriacum, Triticum ventricosum, Triticum cyclindricum, Triticum juvenale, Triticum crassum, Triticum tauschii and Triticum aestivum is described. The calculation of numerical values of the relative affinity and the patterns of chromosome pairing indicate that the D genome in T. syriacum and T.

A comparative bioavailability study of Molipaxin capsules and a trazodone liquid formulation in normal volunteers.

The pharmacokinetic parameters of Molipaxin capsules and a trazodone liquid formulation have been compared in healthy volunteers. The mean area under the plasma concentration/time curve was 10.07 micrograms h ml-1 and 10.

A computer simulation of the behavior of reciprocal translocations in autotetraploids.

Reciprocal translocations in autotetraploids create extremely complex cytological and genetic situations. Along with three types of heterozygotes with one, two or three pairs of translocated chromosomes, a large array of aneuploid and unbalanced genotypes can be expected in the F2 and advanced generations. These types arise from gametes formed by adjacent and anomalous disjunctions of multivalents and by numerical non-disjunction of non-cooriented multivalents.

Mathematics of chromosome pairing.

Analysis of frequencies of chromosome configurations in wheat-related species hybrids is extended to include cases involving homoeologous groups of size six. Further, the expected frequencies of the various configurations emanating from homologous and homoeologous pairing events have been determined for groups consisting of two and three homoeologous pairs of homologous chromosomes. Analysis of configuration frequencies of nullisomic 5B of wheat, in which both homologous and homoeologous pairing occurs, led to estimation of the relative frequencies of homologous and homoeologous pairing events as 17.

Comparison of the metabolic response to a glucose tolerance test and a standardized test meal and the response to serial test meals in normal healthy subjects.

The plasma glucose and insulin response to a standardized meal test breakfast was compared with the time-honored glucose tolerance test in the same normal healthy subjects. The amplitude of glycemic excursion and between-subject variation was less with the more physiologic standardized test meal than with that seen with the glucose tolerance test. The glucose tolerance test's prime function is to amplify any glucose intolerance, thus aiding diagnosis, whereas a standardized meal gives a more clinically relevant metabolic status.

Uses of wheat aneuploids.

There is available in wheat a unique series of aneuploids ranging from all 21 possible monosomics to complex types that are simultaneously deficient for one chromosome and duplicate for another. Furthermore, lines with chromosomes from related alien species either added to or substituted for wheat chromosomes are in common cytological use. This contribution condiders the use of this range of material in studies designed to elucidate the evolutionary relationships of the species, in investigations of the genetics of a polyploid with cytological diploidization, and in potential breeding manipulations.

The use of aneuploids in studies of genetics, breeding, and evolution in wheat.

In wheat a unique series of aneuploids is available, ranging from all 21 possible monosomics to complex types which are simultaneously deficient for one chromosome and duplicate for another. Furthermore, lines with chromosomes from related, alien species either added to or substituted for wheat chromosomes are in common cytological use. This contribution considers the use of this range of material in studies designed to elucidate the evolutionary relationships of the species, investigations of the genetics of a polyploid with cytological diploidization, and in potential breeding manipulations.

Giemsa C-banding and the evolution of wheat.

The somatic chromosomes of common wheat, Triticum aestivum L. (2n = 6x = 42), and those of two of its diploid progenitors and T. speltoides, have been individually identified by a Giemsa staining technique.

A reassessment of the origin of the polyploid wheats.

The diploid species that donated the A and D genomes to the polyploid wheats have been recognized for some time. New evidence indicates that Triticum speltoides cannot be the B genome donor to T. turgidum or T.