Transition States Between Pyramids and Domes During Ge/Si Island Growth.

Real-time observations were made of the shape change from pyramids to domes during the growth of germanium-silicon islands on silicon (001). Small islands are pyramidal in shape, whereas larger islands are dome-shaped. During growth, the transition from pyramids to domes occurs through a series of asymmetric transition states with increasing numbers of highly inclined facets.

Expression and regulation of RAB3 proteins in osteoclasts and their precursors.

The ruffled membrane, the resorptive organelle of the osteoclast, is generated by fusion of intracytoplasmic acidifying vesicles with the plasma membrane, an event analogous to regulated exocytosis. While the ruffled membrane is essential to the bone resorptive process, the mechanisms governing its generation are unknown. However, regulated exocytosis is mediated, in part, by isoforms of the Rab3 subset of Rab GTPases.

Multipaint FISH: a rapid and reliable way to define cryptic and complex abnormalities.

We present the use of a multipaint fluorescence in situ hybridisation (FISH) approach for the detection and interpretation of chromosome abnormalities that could not be resolved by conventional cytogenetics alone. In case 1, a de novo add(Xp) was shown to be an unbalanced X;12 translocation; in case 2, a complex rearrangement involving a deletion of 5p was shown to include a previously undetected cryptic 5;6 translocation. In addition, in case 3, this technique defined additional complexities and nine breakpoints in an acquired rearrangement of chromosomes 2, 9, 11, 16 and 22 in a patient with myelodysplasia.

Nucleotide and dinucleotide effects on rates of paroxysmal depolarising bursts in rat hippocampus.

Slices of rat hippocampus can be induces to generate spontaneous interictal-like bursts of action potentials when perfused with a with a medium containing no added magnesium and 4-aminopyridine (4AP). The frequency of these bursts is depressed by adenosine 5'triphosphate (ATP) and this effect can be prevented by cyclopentyltheophylline but not by adenosine deaminase. AMP (50 microM) had a similar action to reduce discharge rate.

Identification of false-positive CBFbeta/MYH11 RT-PCR results.

Persistent problems with false positive results were encountered when carrying out a published RT-PCR method to detect the CBFbeta/MYH11 transcripts associated with the inv(16)(p13q22) cytogenetic abnormality in acute myeloid leukaemia. These were shown to be due to amplification of part of the intronic MYH11 sequence, presumably from very small amounts of contaminating DNA or unspliced primary RNA transcripts, amplified because of partial homology of the CBFbeta3 primer to intronic MYH11 sequence.

Estrogen decreases TNF gene expression by blocking JNK activity and the resulting production of c-Jun and JunD.

Central to the bone-sparing effect of estrogen (E(2)) is its ability to block the monocytic production of the osteoclastogenic cytokine TNF-alpha (TNF). However, the mechanism by which E(2) downregulates TNF production is presently unknown. Transient transfection studies in HeLa cells, an E(2) receptor-negative line, suggest that E(2) inhibits TNF gene expression through an effect mediated by estrogen receptor beta (ERbeta).

1,25 dihydroxyvitamin D3 and dexamethasone induce the cyclooxygenase 1 gene in osteoclast-supporting stromal cells.

Commitment of members of the monocyte/macrophage family to the bone resorptive phenotype, in vitro, requires contact, of these osteoclast precursors, with osteoblasts or related stromal cells. The osteoclast-inductive properties of these stromal cells are typically expressed, however, only in the presence of steroid hormones such as 1,25 dihydroxyvitamin D (1,25D3) and dexamethasone (DEX). To gain insight into the means by which steroid treated accessory cells induce osteoclast differentiation we asked, using differential RNA display (DRD), if gene expression by this stromal cell population differs from that of their untreated, non-osteoclastogenic counterpart.

Fluorescence in situ hybridization analysis of masked (8;21)(q22;q22) translocations.

The translocation (8;21)(q22;q22) is associated with acute myeloblastic leukemia (AML M2). The accurate detection of this chromosomal rearrangement is vital due to its association with a favorable prognosis. Variant translocations exist; these may be hidden within an unusual or complex karyotype.

The impact of work related trauma on the psychological health of nursing staff: a cross sectional study.

This study aims to investigate the effects of work-related trauma exposure on the health of nursing staff in hospitals. The survey was conducted using a randomised sample of 314 nurses. Half (52.

Comparative genomic hybridization and histological variation in primitive neuroectodermal tumours.

The objective of this study was to test the hypothesis that chromosomal imbalances in central nervous system primitive neuroectodermal tumours (PNETs) reflect site and histology. We used comparative genomic hybridization to study 37 cases of PNET, of which four were cerebral and 31 were medulloblastomas classified histologically as classic (n = 17) or nodular/desmoplastic (n = 14). Tumour immunophenotype was characterized with antibodies to neuroglial, mesenchymal and epithelial markers.

Practice nurses and the care of patients receiving depot neuroleptic treatment: views on training, confidence and use of structured assessment.

The movement of care into the community for the mentally ill with severe and enduring problems has important implications for primary care services. This paper reports the findings from an interview with practice nurses working in south-west London, United Kingdom, who had participated in a randomised control trial to investigate the effectiveness of training and structured assessment on clinical and social outcomes of patients receiving maintenance medication of depot antipsychotics. The aim of the interview was to explore current practice, attitudes, confidence and priorities for training in relation to these patients.

Differential expression of alphav integrins in K1735 melanoma cells.

Tumor cell adherence to and migration on the extracellular matrix is an important aspect of cancer progression. This interaction with the extracellular matrix is mediated primarily through the integrin class of cell adhesion molecules. We identified a restricted expression of alphavbeta3 in highly metastatic K1735M2 and of alphavbeta5 in poorly metastatic K1735C23 murine melanoma cells.

Randomized controlled trial of teaching practice nurses to carry out structured assessments of patients receiving depot antipsychotic injections.

Background: A third of patients with schizophrenia are out of contact with secondary services. Many of these patients receive maintenance medication as depot antipsychotics from practice nurses, most of whom have negligible training in mental health.

Aim: To examine the impact of a structured assessment on the process of care and clinical status of schizophrenia patients by practice nurses who received a one-day training course.

Tumor necrosis factor-alpha mediates orthopedic implant osteolysis.

Osteolysis complicating arthroplasty reflects progressive generation of implant-derived wear particles, which prompt an inflammatory reaction attended by recruitment of osteoclasts to the prosthesis-bone interface. To identify a soluble mediator of periprosthetic osteolysis we first showed that implant particles induce c-src in murine bone marrow macrophages (BMMs), a protein specifically expressed when these cells commit to the osteoclast phenotype. The fact that tumor necrosis factor-alpha (TNF) is a potent osteoclastogenic agent while at the same time is the only soluble moiety known to be c-src inductive suggests that this cytokine may mediate implant particle-induced osteoclastogenesis.

Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival.

beta3 integrins have been implicated in a wide variety of functions, including platelet aggregation and thrombosis (alphaIIbbeta3) and implantation, placentation, angiogenesis, bone remodeling, and tumor progression (alphavbeta3). The human bleeding disorder Glanzmann thrombasthenia (GT) can result from defects in the genes for either the alphaIIb or the beta3 subunit. In order to develop a mouse model of this disease and to further studies of hemostasis, thrombosis, and other suggested roles of beta3 integrins, we have generated a strain of beta3-null mice.

The integrin alphavbeta5 is expressed on avian osteoclast precursors and regulated by retinoic acid.

Osteoclasts arise by proliferation, differentiation, and subsequent fusion of marrow-derived precursors, all processes requiring attachment to matrix. Integrins are important mediators of cell-matrix recognition and bone is rich in proteins containing the Arg-Gly-Asp motif, recognized primarily by alphav integrins. Thus, we determined if avian osteoclast precursors express integrins capable of mediating initial attachment to matrix proteins.

Cloning of the murine beta5 integrin subunit promoter. Identification of a novel sequence mediating granulocyte-macrophage colony-stimulating factor-dependent repression of beta5 integrin gene transcription.

We previously noted that the initial receptor by which murine osteoclast precursors bind matrix is the integrin alphav beta5 and that granulocyte-macrophage colony-stimulating factor (GM-CSF) decreases expression of this heterodimer by suppressing transcription of the beta5 gene. We herein report cloning of the beta5 integrin gene promoter and identification of a GM-CSF-responsive sequence. A 13-kilobase (kb) genomic fragment containing part of the beta5 gene was isolated by screening a mouse genomic library with a probe derived from the most 5'-end of a murine beta5 cDNA.

Granulocyte macrophage-colony stimulating factor reciprocally regulates alphav-associated integrins on murine osteoclast precursors.

The integrins alphavbeta3 and alphavbeta3 are expressed reciprocally during murine osteoclastogenesis in vitro. Specifically, immature osteoclast precursors, in the form of bone marrow macrophages, contain exclusively alphavbeta5, surface expression of which declines with commitment to the osteoclast phenotype, while levels of alphavbeta3 increase concomitantly. The distinct functional significance of alphavbeta5 is underscored by the integrin's capacity, unlike alphavbeta3, to mediate both attachment and spreading on ligand, of marrow macrophages, suggesting alphavbeta3 negotiates initial recognition, by osteoclast precursors, of bone matrix.

Ostwald Ripening of Self-Assembled Germanium Islands on Silicon(100).

: We describe here real-time, in situ observations of the formation of nanosize germanium (Ge) islands on silicon (Si). The deposition of Ge onto electron-transparent Si(100) takes place in a UHV transmission electron microscope that has been modified to allow chemical vapor deposition to be carried out in the polepiece. We recorded the growth process at video rate and were therefore able to follow the evolution of individual islands.

Estrogen blocks M-CSF gene expression and osteoclast formation by regulating phosphorylation of Egr-1 and its interaction with Sp-1.

Central to the pathogenesis of osteoporosis is the ability of estrogen deficiency to increase osteoclast formation by enhancing stromal cell production of the osteoclastogenic cytokine macrophage colony-stimulating factor (M-CSF). We report that stromal cells from ovariectomized mice exhibit increased casein kinase II-dependent phosphorylation of the nuclear protein Egr-1. Phosphorylated Egr-1 binds less avidly to the transcriptional activator Sp-1 and the resulting higher levels of free Sp-1 stimulate transactivation of the M-CSF gene.

Tumor necrosis factor-alpha activation of nuclear transcription factor-kappaB in marrow macrophages is mediated by c-Src tyrosine phosphorylation of Ikappa Balpha.

Tumor necrosis factor-alpha (TNF) exerts its transcriptional effects via activation of nuclear transcription factor-kappa B (NF-kappaB). NF-kappaB is sequestered in the cytosol by Ikappa Balpha and, in most cells, released upon serine phosphorylation of this inhibitory protein which then undergoes rapid, ubiquitin-dependent degradation. In contrast, we find TNF induction of NF-kappaB in murine bone marrow macrophages (BMMs), is mediated, by c-Src, in a cell, and cytokine specific manner.

In situ transmission electron microscopy observations of the formation of self-assembled Ge islands on Si.

The in situ transmission electron microscope allows us to visualise processes occurring at surfaces and interfaces in real time and is therefore capable of providing detailed, quantitative information about reaction mechanisms. We have used a UHV TEM equipped with in situ growth capabilities to study the process of chemical vapour deposition of Ge on Si(100), with particular emphasis on the formation of self-assembled, nanosize Ge islands. Video-rate image acquisition enables us to track the development of individual islands from nucleation onwards and to observe the introduction of dislocations as the strained islands relax.