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Biomedical subjects

K White

Publications and source records attributed to K White.

At least 127 records · Page 7Linked to original sources
PubMed1995

Two distinct temperature-sensitive alleles at the elav locus of Drosophila are suppressed nonsense mutations of the same tryptophan codon.

The Drosophila gene elav encodes a 483-amino-acid-long nuclear RNA binding protein required for normal neuronal differentiation and maintenance. We molecularly analyzed the three known viable alleles of the gene, namely elavts1, elavFliJ1, and elavFliJ2, which manifest temperature-sensitive phenotypes. The modification of the elavFliJ1 allele corresponds to the change of glycine426 (GGA) into a glutamic acid (GAA). Surprisingly, elavts1 and elavFliJ2 were both found to have tryptophan419 (TGG) changed into two different stop codons, TAG and TGA, respectively. Unexpectedly, protein analysis from elavts1 and elavFliJ2 reveals not only the predicted 45-kD truncated ELAV protein due to translational truncation, but also a predominant full-size 50-kD ELAV protein, both at permissive and nonpermissive temperatures. The full-length protein present in elavts1 and elavFliJ2 can a priori be explained by one of several mechanisms leading to functional suppression of the nonsense mutation or by detection of a previously unrecognized ELAV isoform of similar size resulting from alternative splicing and unaffected by the stop codon. Experiments described in this article support the functional suppression of the nonsense mutation as the mechanism responsible for the full-length protein.

Alleles↗
PubMed1995

The pharmacokinetics of phenytoin in gingival crevicular fluid and plasma in relation to gingival overgrowth.

The aim of this study was to determine whether phenytoin (PHT) could be detected in gingival crevicular fluid (GCF), and to relate its concentration to both plasma level and degree of gingival overgrowth. 23 patients medicated with phenytoin for at least 6 months were clinically examined for signs of periodontal disease and gingival overgrowth. 12 patients out of these demonstrated clinically significant overgrowth and their plaque scores and gingival inflammation were greater than for the non-overgrowth group (p < 0.001). Phenytoin concentrations were determined by high performance liquid chromatography, and was detected in GCF. There was a significant correlation between the GCF and plasma phenytoin concentrations (p < 0.05), but it was not related to the extent of gingival overgrowth. Inflammation increased the GCF volume, but was not a determinant of GCF phenytoin concentration. It is concluded that effusion of phenytoin into GCF is regulated by the plasma levels of the drug, but its concentration in GCF is not related to the incidence of gingival overgrowth.

Adult↗
PubMed1995

Professional needs of palliative care nurses in New South Wales.

A survey of 108 palliative care nurses practising in New South Wales, Australia, was undertaken to explore their professional needs and clinical knowledge. Opportunity for improved training was the most frequently nominated professional need. Only 12% of the sample had postgraduate qualifications in palliative care and fewer than 20% were currently undertaking postgraduate training. Sixty-three per cent of nurses indicated that a lack of opportunity for formal study was a problem for them. The results of the knowledge survey revealed a need for additional training. Many nurses did not have the clinical knowledge identified as minimal by an expert committee. Those nurses who had a postgraduate qualification in oncology scored more highly on the knowledge questionnaire than did those whose general nursing training was undertaken outside Australia. The implications of these findings for training and other professional support are discussed.

Adult↗
PubMed1994

Programmed cell death in Drosophila.

During Drosophila development, large numbers of cells undergo natural cell death. Even though the onset of these deaths is controlled by many different signals, most of the dying cells undergo common morphological and biochemical changes that are characteristic of apoptosis in vertebrates. We have surveyed a large fraction of the Drosophila genome for genes that are required for programmed cell death by examining the pattern of apoptosis in embryos homozygous for previously identified chromosomal deletions. A single region on the third chromosome (in position 75C1,2) was found to be essential for all cell deaths that normally occur during Drosophila embryogenesis. We have cloned the corresponding genomic DNA and isolated a gene, reaper, which is capable of restoring apoptosis when reintroduced into cell death defective deletions. The reaper gene is specifically expressed in cells that are doomed to die, and its expression precedes the first morphological signs of apoptosis by 1-2 h. This gene is also rapidly induced upon X-ray irradiation, and reaper deletions offer significant protection against radiation-induced apoptosis. Our results suggest that reaper represents a key regulatory switch for the activation of apoptosis in response to a variety of distinct signals.

Animals↗
PubMed1994

Genetic control of programmed cell death in Drosophila.

A gene, reaper (rpr), that appears to play a central control function for the initiation of programmed cell death (apoptosis) in Drosophila was identified. Virtually all programmed cell death that normally occurs during Drosophila embryogenesis was blocked in embryos homozygous for a small deletion that includes the reaper gene. Mutant embryos contained many extra cells and failed to hatch, but many other aspects of development appeared quite normal. Deletions that include reaper also protected embryos from apoptosis caused by x-irradiation and developmental defects. However, high doses of x-rays induced some apoptosis in mutant embryos, and the resulting corpses were phagocytosed by macrophages. These data suggest that the basic cell death program is intact although it was not activated in mutant embryos. The DNA encompassed by the deletion was cloned and the reaper gene was identified on the basis of the ability of cloned DNA to restore apoptosis to cell death defective embryos in germ line transformation experiments. The reaper gene appears to encode a small peptide that shows no homology to known proteins, and reaper messenger RNA is expressed in cells destined to undergo apoptosis.

Amino Acid Sequence↗
PubMed1994

Stem cell factor and basic fibroblast growth factor are synergistic in augmenting committed myeloid progenitor cell growth.

Stem cell factor (SCF) and basic fibroblast growth factor (bFGF) are hematopoietic cytokines produced by bone marrow stromal cells. It is known that, although SCF and bFGF have limited clonogenic activity on their own, they can augment colony-stimulating factor (CSF)-mediated progenitor cell growth. Because these factors are both sequestered by stromal cells, we examined their interaction on progenitor cell growth in conjunction with granulocyte-macrophage-CSF (GM-CSF). In this study, we show that clonogenic growth derived from low-density bone marrow cells stimulated by GM-CSF is significantly augmented (P < .001) in the presence of maximal (100 ng/mL) concentrations of SCF in combination with 100 ng/mL of bFGF. When CD34+ cells are used, the synergistic effect of bFGF and SCF for GM-CSF-mediated progenitor cell growth is further increased, resulting in as much as a sevenfold increase in detectable colony-forming units granulocyte-macrophage (P < .001). These data suggest that the synergistic activity of bFGF and SCF is mediated directly on hematopoietic precursors. These observations suggest that bFGF and SCF, concentrated locally on stromal cell surfaces, might interact in concert with other hematopoietic cytokines to regulate stem cell proliferation and differentiation in hematopoietic niches in the bone marrow.

Antigens, CD↗
PubMed1994

Chronopharmacological study of moclobemide effect on the rat pineal melatonin biosynthesis.

The chronopharmacological hypothesis of the mechanism of the antidepressant effect of MAO-A inhibitors predicts that clinical efficacy depends upon the time of the day at which the drugs are administered. In the present study moclobemide (10 mg/kg, s.c.) injected at the end of the light phase advanced the onset of the nighttime increase of the rat pineal melatonin biosynthesis while the same dose of drug injected at the end of the dark phase delayed the daytime decrease of melatonin biosynthesis. The results obtained suggest that the timing of MAO-A inhibitor administration should be considered in clinical practice.

Animals↗
PubMed1994

Chronic effect of the irreversible and reversible selective MAO-A inhibitors on rat pineal melatonin biosynthesis.

Acute administration of the irreversible MAO-A inhibitor, clorgyline (2.0 mg/kg, s.c.) and the reversible MAO-A inhibitor, moclobemide (10 mg/kg, s.c.), increased rat pineal melatonin and related indoles content (HPLC-fluorimetric method). Chronic (21 days) administration of clorgyline attenuated the acute effect of clorgyline on pineal melatonin biosynthesis. The acute effect of moclobemide on melatonin biosynthesis was not affected by chronic moclobemide administration. The observed difference in the chronic effects of irreversible and reversible selective MAO-A inhibitors on melatonin biosynthesis could have clinical implications.

Animals↗
PubMed1994

Neural specificity of elav expression: defining a Drosophila promoter for directing expression to the nervous system.

The Drosophila melanogaster vital gene, embryonic lethal abnormal visual system (elav), is required for the postdeterminative development of the nervous system. Its gene product encodes an RNA binding protein that was found to be expressed in all neurons right after their birth. This specific, ubiquitous, and continuous pattern of neural expression has led to the increasingly popular use of ELAV protein as a neural-specific marker. To understand the molecular basis of this neural-specific expression, we have defined and analyzed the structure of the elav promoter. Cis-acting sequences important for conferring the neural specificity of elav expression were identified by analyzing the reporter gene expression in transformants carrying different elav-beta-galactosidase fusion genes. This analysis delimits a 333-bp region (-92 to +241) that is necessary for specifying the elav pattern of nervous system expression. A 3.5-kb promoter fragment encompassing this region was designed for targeting gene expression specifically to the nervous system and would be a useful tool for the analysis of nervous system function.

Animals↗
PubMed1994

The role of previous radiographs and reports in the interpretation of current radiographs.

RATIONALE AND OBJECTIVES: The authors studied radiologists' patterns of using old reports and previous radiographs in the interpretation of current radiographic studies. Supplying information from previous studies is considered necessary for accurate interpretation; however, it is not clear how this information is used. METHODS: Eighteen radiologists interpreted 305 plain-film studies in a general radiologic interpretation area. Radiologists described their perceptions of the use of previous radiographs and reports in film interpretation. RESULTS: Overall, old films were used for 99% of interpretations and previous reports were used for 65%. Prior information increased confidence in 89% of cases, influenced diagnosis in 56% of cases, and assisted in detecting new pathology in 6% of interpretations. Old radiographs were judged most valuable in documenting the progression, regression, or stability of disease in 89% of cases. Previous reports were principally used to obtain patient history (43%). In no cases did the radiologist perceive that the old reports assisted in locating new pathology. CONCLUSIONS: Old films are judged more valuable than reports for documenting disease progress, and radiologists are unlikely to accept written reports as a substitute. Previous reports are used principally to improve clinical histories, a function that might be eliminated if adequate clinical data could be captured by other means.

Attitude of Health Personnel↗
PubMed1994

Remission and relapse in subjects with panic disorder and panic with agoraphobia: a prospective short-interval naturalistic follow-up.

This article reports on the course of uncomplicated panic disorder and panic with agoraphobia on 309 patients participating in the Harvard/Brown Anxiety Research Project, a prospective longitudinal study of patients with DSM-III-R-defined anxiety disorders. At 1 year, there was a .39 probability of full remission for uncomplicated panic disorder and a .17 probability of full remission for panic disorder with agoraphobia Similar differences in time to remission for these syndromes were still found when criteria for remission were made less stringent. However, even requiring less improvement for remission left a large percentage of subjects in an episode, and for those that remitted, relapse occurred quickly, indicating a chronic and recurrent course of illness. This is the first longitudinal, prospective, naturalistic study on a large cohort of subjects with anxiety disorders to have regular, structured, short-interval follow-up. Our results are consistent with the view that panic disorder has a chronic course with high rates of relapse after remission and longer episodes when agoraphobia is a part of the constellation of symptoms.

Adult↗
PubMed1994

Prevalence of medical illness in patients with anxiety disorders.

OBJECTIVE: This investigation examines the prevalence and characteristics of medical illness in 711 patients enrolled in the Harvard/Brown Anxiety Disorders Research Program (HARP), a multi-center, longitudinal study of anxiety disorders. METHOD: Eligible subjects were those with present or past index anxiety disorders: panic disorder without agoraphobia, panic disorder with agoraphobia, agoraphobia without panic disorder, social phobia, or generalized anxiety disorder. They were assessed by trained raters using structured diagnostic interviews and the Medical History Form II. RESULTS: Patients with panic disorder and co-morbid major depressive disorder had significantly higher rates of reported medical illness than anxiety disorder patients without depression. When the rates of medical illness for all subjects were compared with those from the Rand Health Insurance Experiment, we found the prevalence of several medical problems to be disproportionately increased. CONCLUSIONS: Although our results are preliminary, it appears that patients with panic disorder have more reported medical problems than the public at large, in particular, more ulcer disease, angina, and thyroid disease. Somatic complaints in patients with panic disorder, therefore, need to be carefully considered.

Adult↗
PubMed1994

Osteogenic protein-1 (OP-1) expression and processing in Chinese hamster ovary cells: isolation of a soluble complex containing the mature and pro-domains of OP-1.

We have characterized the expression and processing of Osteogenic Protein-1 (hOP-1), a bone morphogenic protein of the TGF-beta family, in Chinese hamster ovary cells. The hOP-1 is initially synthesized as a monomeric 50 kDa pro-protein that is dimerized, glycosylated, and then proteolytically cleaved at the Arg-Xaa-Xaa-Arg maturation site in an acidic cellular compartment before secretion into the medium. Of the four potential N-linked glycosylation sites two are used, one in the mature domain and one in the pro-domain. Gel permeation chromatography of secreted hOP-1 in physiological buffers yields an apparent molecular weight of 110-120 k, indicating that after proteolytic processing the two pro-domains remain non-covalently associated with the disulfide linked mature dimer in a complex termed soluble hOP-1. Purified soluble hOP-1 is significantly more soluble in physiological buffers than the purified mature OP-1.

Amino Acid Sequence↗
PubMed1994

Patient violence toward a nurse: predictable and preventable?

1. It is estimated that half of all health care professionals will be assaulted at some point in their careers. 2. Prediction of violence depends not only on obvious factors, such as threats made by the patient, but also on more subtle violations of boundaries, such as patient contact with the clinician outside the clinical setting by telephone or in-person encounters in the clinician's home. A specific factor associated with danger seems to be the patient's perception of an unrealistic, "special" relationship with the person targeted. 3. Health care professionals should avoid creating a sense of guilt and shame in clinicians about such issues as countertransference. Staff members should be able to discuss issues without laying blame and possibly prevent dangerous situations.

Adult↗
PubMed1994

Clinical approaches to low back pain. Part 1. Epidemiology, diagnosis, and prevention.

The epidemiology and difficulties in diagnosing low back pain are discussed. Clinical investigations should be limited to those tests that will provide useful information for effective management. Prevention is the best strategy for avoiding low back pain but is realistically hard to practise because the disorder has many environmental and intrinsic risk factors.

Acute Disease↗