Search PubMed⌕ Search

Biomedical subjects

K White

Publications and source records attributed to K White.

At least 145 records · Page 8Linked to original sources
PubMed1993

Basic fibroblast growth factor counteracts the suppressive effect of transforming growth factor-beta 1 on human myeloid progenitor cells.

We have previously shown that basic fibroblast growth factor (bFGF) is mitogenic for human bone marrow stromal cells and enhances myelopoiesis in human long-term bone marrow culture. In the present study, we examined the mechanism by which bFGF enhances granulopoiesis. We observed that bFGF significantly abrogated the inhibitory effect of transforming growth factor-beta 1 (TGF-beta 1) on granulocyte-macrophage colony-stimulating factor (GM-CSF)-supported progenitor cell growth (P = .009). The partial reversal of TGF-beta 1-mediated suppression was dependent on the dose of bFGF used. In addition, we noted that the inclusion of neutralizing antibody to TGF-beta 1 significantly augmented the clonogenic response to GM-CSF. We have also shown that 10 ng/mL or 100 ng/mL of bFGF resulted in a 30% to 100% increase in GM-CSF-mediated progenitor cell growth (P = .0001). These data suggest that bFGF may enhance myelopoiesis by modulating the inhibitory response to TGF-beta 1.

Antibodies↗
PubMed1993

Plasmodium berghei-specific T cells respond to non-processed sporozoites presented by B cells.

The mechanism of malaria protective immunity induced by immunization with radiation-attenuated Plasmodium sporozoites (SPZ) is only partially understood. For example, B and T cell responses specific for the circumsporozoite (CS) protein, a 46 kDa SPZ surface protein, have been characterized; however, events leading to SPZ-specific T cell activation, i.e., processing and presentation of SPZ by antigen-presenting cells have not been investigated. In the present study we describe the in vitro analysis of requirements for accessory cell function in the presentation of SPZ to SPZ-immune T cells. The results establish that SPZ-induced proliferative T cells are reactive to non-processed SPZ presented by activated B cells and, thus, imply that the non-processed form of the SPZ-associated CS protein restricts the induction of the potential CS protein T cell repertoire.

Animals↗
PubMed1993

Gene elav of Drosophila melanogaster: a prototype for neuronal-specific RNA binding protein gene family that is conserved in flies and humans.

Regulated gene activity is crucial to the formation and function of the nervous system. It is well known that gene regulation can occur at the transcriptional, post-transcriptional, translational, and post-translational levels. In this review our focus has been on the post-transcriptional regulation in neurons and on neural-specific RNA binding proteins that may be involved in post-transcriptional modulation of gene activity. We have taken advantage of this opportunity to review our work on the elav gene of Drosophila melanogaster which encodes a neural-specific RNA binding protein and relate it to other members of this elav-like gene family. We report new data that suggests that elav is post-transcriptionally regulated and we demonstrate that below-threshold levels of ELAV protein severely affects neuronal differentiation.

Animals↗
PubMed1993

Comorbidity of panic and major depressive disorder.

The objective of this report is to determine whether those patients with panic disorder who have current major depression disorder (MDD) differ from those who do not in terms of demographics, comorbid disorders, severity of illness, nature of symptoms of panic attacks and psychosocial functioning. The sample consisted of 182 patients with current or history of panic disorder measured by standardized interview techniques. For analysis these patients were then divided by presence or absence of current MDD. The two groups were not different in age, sex, or marital status, age of onset, or symptom characteristics of panic attacks. However, patients with MDD were more likely to have Social Phobia and Generalized Anxiety Disorder, been hospitalized, made suicide attempts or gestures, have poorer psychosocial functioning, and currently be experiencing panic with more severe symptoms. These findings are discussed in terms of previous literature in the area.

Adult↗
PubMed1993

Induction of cytolytic and antibody responses using Plasmodium falciparum repeatless circumsporozoite protein encapsulated in liposomes.

Plasmodium circumsporozoite (CS) protein-induced antibody and T-cell responses are considered to be important in protective immunity. Since the key repeat determinant of the CS protein may actually restrict the recognition of other potential T- and B-cell sites, a modified Plasmodium falciparum CS protein lacking the central repeat region, RLF, was expressed in Escherichia coli. On purification, RLF was encapsulated into liposomes [L(RLF)] and used for the in vivo induction of cytolytic T lymphocytes (CTL) and antibodies. Immunization of B10.Br (H-2k) mice with L(RLF), but not with RLF, induced CD8+ CTL specific for the P. falciparum CS protein CTL epitope, amino acid residues 368-390. Anti-L(RLF) serum reacted with antigens on intact sporozoites and inhibited sporozoite invasion of hepatoma cells. Antibody specificity studies in New Zealand White rabbits revealed new B-cell sites localized in amino acid residues 84-94, 91-99, 97-106 and 367-375. Although the mechanisms by which liposomes enhance cellular and humoral immune responses remain unknown, liposome-formulated vaccines have been well tolerated in humans; hence, their use in vaccines, when efficacy depends on antibody and CTL responses, may be broadly applicable.

Amino Acid Sequence↗
PubMed1993

Euthanasia: a comparison of the lived experience of Chinese and Australian palliative care nurses.

This paper reports on a study which investigated whether nurses from Eastern and Western cultures hold differing definitions of euthanasia and different perspectives of the effect of their attitudes to euthanasia on professional relationships with patients and colleagues. The focus of the study was the lived experience of Chinese and Australian nurses working in palliative care. The results indicate that there were differences between these two groups in their definitions of euthanasia. Lived experience obtained from both groups revealed conflict with patients and colleagues, and a lack of opportunity to discuss the ethical issue of euthanasia in the workplace.

Adult↗
PubMed1993

MacFee incision: a safe approach to the neck.

We reviewed 37 neck dissections done via the MacFee or double horizontal cervical incision to excise neoplasms located in the oral cavity and oropharynx, with draining cervical lymph nodes. One half of the patients had immediate reconstruction with myocutaneous flaps. Approximately 70% of the patients had advanced tumors and many were malnourished at presentation. Three wound complications involving the MacFee incision occurred in patients who were malnourished and required reconstruction. These wound complications were corrected with conservative therapy. Preoperative radiotherapy was a morbid cofactor. None of the patients had carotid artery involvement, wound dehiscence, or deep cervical infections. The MacFee incision can be used in major head and neck resections, with operative morbidity comparable to that of other techniques.

Female↗
PubMed1993

The Drosophila erect wing gene, which is important for both neuronal and muscle development, encodes a protein which is similar to the sea urchin P3A2 DNA binding protein.

The erect wing (ewg) locus of Drosophila melanogaster encodes a vital function important for the development of the nervous system and the indirect flight muscles. In order to understand the ewg function at a molecular level, cDNA clones were isolated. Sequence analysis of cDNAs revealed a single open reading frame (ORF) encoding a protein of 733 residues. The translational start for this ORF is a CTG codon. A 225-amino-acid region of this protein is 71% identical to the DNA binding region of the Strongylocentrotus purpuratus P3A2 DNA binding protein. Additionally, the ORF contains large acidic and basic domains characteristic of those in proteins involved in nuclear regulatory functions. Immunoblot analysis using polyclonal anti-EWG antisera generated against a bacterial fusion protein reveals a single, 116-kDa protein present throughout development, beginning at approximately stage 12 of embryogenesis, which is enriched in adult heads and absent from embryos carrying certain ewg alleles. Additionally, we show that EWG is localized specifically to the nuclei of virtually all embryonic neurons. Finally, a minigene consisting of an ewg cDNA under control of the hsp70 promoter can provide the ewg function in transgenic ewg mutant flies.

Alleles↗
PubMed1993

Programmed cell death during Drosophila embryogenesis.

The deliberate and orderly removal of cells by programmed cell death is a common phenomenon during the development of metazoan animals. We have examined the distribution and ultrastructural appearance of cell deaths that occur during embryogenesis in Drosophila melanogaster. A large number of cells die during embryonic development in Drosophila. These cells display ultrastructural features that resemble apoptosis observed in vertebrate systems, including nuclear condensation, fragmentation and engulfment by macrophages. Programmed cell deaths can be rapidly and reliably visualized in living wild-type and mutant Drosophila embryos using the vital dyes acridine orange or nile blue. Acridine orange appears to selectively stain apoptotic forms of death in these preparations, since cells undergoing necrotic deaths were not significantly labelled. Likewise, toluidine blue staining of fixed tissues resulted in highly specific labelling of apoptotic cells, indicating that apoptosis leads to specific biochemical changes responsible for the selective affinity to these dyes. Cell death begins at stage 11 (approximately 7 hours) of embryogenesis and thereafter becomes widespread, affecting many different tissues and regions of the embryo. Although the distribution of dying cells changes drastically over time, the overall pattern of cell death is highly reproducible for any given developmental stage. Detailed analysis of cell death in the central nervous system of stage 16 embryos (13-16 hours) revealed asymmetries in the exact number and position of dying cells on either side of the midline, suggesting that the decision to die may not be strictly predetermined at this stage. This work provides the basis for further molecular genetic studies on the control and execution of programmed cell death in Drosophila.

Acridine Orange↗
PubMed1993

Drosophila tyrosine hydroxylase is encoded by the pale locus.

We have reintroduced an 8 kb genomic fragment from the Drosophila tyrosine hydroxylase (DTH) locus into the genome of mutant pale (ple) flies. ple was first recovered as a recessive embryonic lethal by Jurgens et al. (1984) and maps to the same chromosomal region as DTH (65A-E). Mutant ple alleles affect pigmentation of the cuticle (L-DOPA, the product of the reaction catalyzed by TH, is an intermediate in the cuticular sclerotization and pigmentation pathways) and catecholamine biosynthesis. In this report we demonstrate that ple does encode the structural gene for TH, since the reintroduced sequences rescue ple flies from lethality to viable adults. Morphological, immunocytochemical, and behavioral characterization of three transformant lines suggests that the reintroduced sequences contain the necessary elements for correct temporal and spatial expression of the gene, but may not contain all the sequences essential for quantitative expression.

Animals↗
PubMed1992

A single locus encodes both phenylalanine hydroxylase and tryptophan hydroxylase activities in Drosophila.

We have used a full-length clone encoding rabbit tryptophan hydroxylase (TRH) to isolate the Drosophila homologue (DTPH). Southern analysis of Drosophila genomic DNA reveals a pattern indicative of a single gene. The single transcript is expressed in adult head and body mRNA but is also detected in mRNA from early embryos. The embryonic transcript is ubiquitously expressed and appears to concentrate in yolk granules. In situ hybridization of TRH-homologous antisense RNA probe to sectioned tissue from third instar larvae demonstrated the presence of this transcript in fat body and cuticular tissue. Developmental immunoblot analysis using antibodies raised against a beta-galactosidase-Drosophila fusion protein revealed a 45-kDa embryonic protein also detected in female abdomens and a 50-kDa protein found in larval and adult stages. Immunocytochemical analysis of the Drosophila protein in the larval central nervous system showed that it appeared to be present in both serotonin- and catecholamine-containing neurons. A nonfusion protein generated in Escherichia coli hydroxylates both tryptophan and phenylalanine. We propose that there are only two aromatic amino acid hydroxylase genes in Drosophila: one encoding tyrosine hydroxylase, DTH, and DTPH, a gene encoding both tryptophan and phenylalanine hydroxylase activities.

Amino Acid Sequence↗
PubMed1992

Regulation of the G1-S transition in postembryonic neuronal precursors by axon ingrowth.

In the newly cellularized Drosophila embryo, progress through the cell cycle is regulated at the G2-M transition. We have examined cell-cycle regulation later in Drosophila development, in a group of postembryonic neuronal precursors. The S-phase precursor cells, which generate photoreceptor target neurons (lamina neurons) in the central nervous system, are not present in the absence of photoreceptor innervation. Here we report that axons selectively approach G1-phase precursors. Without axon ingrowth, lamina precursors do not enter their final S phase and by several criteria, arrest in the preceding G1 phase. These findings provide evidence that at this stage in development the control of cell division can occur at the G1-S transition.

Animals↗
PubMed1992

Age-related regional differences in cerebellar vermis observed in vivo.

We investigated age-related differences in the cerebellar vermis. The areas of five vermal regions of interest were estimated from digitized midsagittal magnetic resonance imaging scans of 29 healthy volunteers and 30 neurologically intact patients (aged 18 to 78 years) who were free of vestibular symptoms, seizures, psychosis, or alcoholism. The five regions of interest included the following: (1) lingula and centralis, (2) culmen, (3) declive, folium, and tuber, (4) pyramis, and (5) uvula and nodulus. The ventral pons was used as a control region. After covarying skull size, we found a significant age-related reduction in the total area of the cerebellar vermis. The area of the dorsal regions declined with age, whereas the ventral segments of the vermis--lingula-centralis and uvula-nodulus--showed no significant age-related shrinkage. Notably, the area of the most dorsomedial portion, the declive-folium-tuber, tended to be more strongly associated with age than other segments. The pontine area was unaffected by age. No sex differences were found in the area of the vermis or its subdivisions, but the ventral pontine area was larger in male subjects than in female subjects, even after adjustment for skull size. The mechanisms underlying the observed differences are unclear. It appears, however, that phylogenetically more recent vermal regions, which are late to mature and are endowed with more extensive cortical connections, are the most vulnerable to the effects of aging.

Adolescent↗
PubMed1992

Qualitative and quantitative experimental models to aid in risk assessment for immunotoxicology.

We have previously reported on the design and content of a screening battery using a "tier" approach for detecting potential immunosuppressive compounds in mice [1]. This battery was composed of various immune function, immunopathology and host resistance tests, the results of which could help establish the potential of chemical and biological agents to cause immunosuppression. The data from these studies, which now encompass over 50 compounds, have been analyzed in an attempt to improve future testing strategies and provide information to aid in the risk assessment process. Specifically, the following two issues will be addressed; what are the likelihood(s) for each of the individual tests and testing configurations to accurately identify immunotoxic compounds? and what are the quantitative and qualitative relationships between the immune tests and host resistance assays?

Animals↗
PubMed1992

Human amyloid precursor protein ameliorates behavioral deficit of flies deleted for Appl gene.

Drosophila amyloid precursor protein-like (Appl) gene encodes a protein product (APPL) similar to beta-amyloid precursor protein (APP) associated with Alzheimer's disease. To understand the in vivo function of APPL protein, we have generated flies deleted for the Appl gene. These flies are viable, fertile, and morphologically normal, yet they exhibit subtle behavioral deficits. We show that a fast phototaxis defect in Appl- flies is partially rescued by transgenes expressing the wild-type, but not a mutant, APPL protein. We further demonstrate a functional homology between APPL and APP, since transgenes expressing human APP show a similar level of rescue as transgenes expressing fly APPL.

Amyloid beta-Protein Precursor↗
PubMed1992

Cognitive bias in the articulated thoughts of depressed and nondepressed psychiatric patients.

Beck's cognitive theory of depression postulates several types of cognitive bias among depressed patients. Empirical studies supporting this hypothesis have usually used questionnaire "endorsement" measures of cognition, which may suggest responses to subjects. We used the articulated thoughts during simulated situations (ATSS) method of cognitive assessment in comparing cognitive processes of 15 outpatients with major depression with those of 15 nondepressed psychiatric outpatients in three simulated situations. Depressed patients exceeded nondepressed patients in cognitive bias only in the negative (not the neutral or positive) simulated situation. Discussion centered on the possible utility of ATSS for research on cognition in stressful situations.

Cognition↗