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Biomedical subjects

K White

Publications and source records attributed to K White.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Side effects and the "blindability" of clinical drug trials.

A novel, simple approach to retrospective assessment of "blindability" was applied to data on outpatients in a controlled, double-blind clinical comparison of a putative antidepressant, etoperidone, and placebo. A "blind" evaluator proved capable of discriminating between the active drug and placebo on the basis of reported side effects alone, raising questions about the true blindness of the study.

Ambulatory Care↗
PubMed1992

Premenstrual exacerbation of depression: one process or two?

BACKGROUND: Premenstrual symptoms occur in the setting of other psychiatric disorders, particularly affective disorders. The nosologic issue of whether premenstrual syndrome is an entity distinct from other psychiatric disorders is controversial. METHOD: We review the association between depression and premenstrual syndrome and describe symptoms in a small series of patients (N = 5) with premenstrual syndrome both during and after resolution of major depression. RESULTS: The overall symptom severity decreased after antidepressant treatment, but this decrease was only significant for dysphoria. In two subjects, other cyclical symptoms consistent with premenstrual syndrome became more apparent after treatment of major depression, possibly because background symptoms of depression improved. CONCLUSION: Premenstrual symptoms, including dysphoric changes and irritability, can continue despite effective treatment of major depression.

Acute Disease↗
PubMed1992

Pharmacotherapy observed in a large prospective longitudinal study on anxiety disorders.

Data concerning 331 subjects participating in a longitudinal study on anxiety disorders were collected over the first 6 months of the study. Preliminary analyses of somatic treatment according to diagnoses and study site were conducted. The comorbidity of one anxiety disorder with other DSM-III-R diagnoses and other types of anxiety disorders was extensive. Patients with panic disorder received significantly more treatment with a benzodiazepine than patients without panic disorder. Fewer than five percent of the sample were treated with a monoamine oxidase inhibitor. Comorbid depression increased the likelihood of treatment with a newer non-MAOI (non-monoamine oxidase inhibitor), nontricyclic antidepressant. Results suggest a strong effect of treatment site on the pharmacotherapy offered.

Adolescent↗
PubMed1992

Anxiety disorders: an overview.

As a group, anxiety disorders are the most prevalent class of mental disorders. Over the course of a lifetime, 15% of the population experience one or another anxiety disorder.

Agoraphobia↗
PubMed1991

Dual muscarinic and nicotinic action on a motor program in Drosophila.

The effect of cholinergic agonists and antagonists on the central pattern generator of the pharyngeal muscles has been studied in third instar larvae of Drosophila. The pharyngeal muscles are a group of rhythmically active fibers involved in feeding. Bath application of the cholinergic agonists carbachol, muscarine, pilocarpine, and acetylcholine (ACh) to a semiintact preparation including the pharyngeal muscles and the central nervous system (CNS), initiated long-lasting endogenous-like bursting activity in the muscles. The muscarinic antagonists, atropine and scopolamine, blocked these responses as well as endogenous activity. Perfusion with nicotine elicited a short, tonic response that was marginally blocked by mecamylamine but not by curare, alpha-bungarotoxin, hexamethonium, or the muscarinic antagonists. This is the first time that a response to cholinergic drugs has been examined in Drosophila. The pharyngeal muscle preparation may prove to be a valuable system for studying mutations of cholinergic metabolism, receptors, and second messengers.

Acetylcholine↗
PubMed1991

Characterization and spatial distribution of the ELAV protein during Drosophila melanogaster development.

The embryonic lethal abnormal visual system (elav) gene of Drosophila melanogaster is required for the development and maintenance of the nervous system. Transcripts from this locus are distributed ubiquitously throughout the nervous system at all developmental stages. A product of this gene, the ELAV protein, has homology to known RNA binding proteins. The localization of the ELAV protein was studied in all developmental stages using antibodies that were generated against a hybrid protein made in Escherichia coli. In general, these data are consistent with previous results and demonstrate that (1) the ELAV protein is detected in the developing embryonic nervous system at a time coincident with the birth of the first neurons, (2) the ELAV protein is first detected in the majority of neurons of the central and peripheral nervous systems of embryos, larvae, pupae, and adults, (3) the ELAV protein appears to be localized to the nucleus, and (4) the ELAV protein is not detected in neuroblasts or identifiable glia. These data also provide new information concerning elav expression and show that (1) ELAV is not expressed in the ganglion mother cells (GMCs), (2) while the ELAV protein is localized to the nucleus, it is not uniformly distributed throughout this structure, and (3) other Drosophila species do express an ELAV-like antigen. We propose that the elav gene provides a neuronal-housekeeping function that is required for the successful posttranscriptional processing of transcripts from a set of genes the function of which is required for proper neuronal development and maintenance.

Animals↗
PubMed1991

Mutations in a steroid hormone-regulated gene disrupt the metamorphosis of the central nervous system in Drosophila.

The actions of steroid hormones on vertebrate and invertebrate nervous systems include alterations in neuronal architecture, regulation of neuronal differentiation, and programmed cell death. In particular, central nervous system (CNS) metamorphosis in insects requires a precise pattern of exposure to the steroid molting hormone 20-hydroxyecdysone (ecdysterone). To test whether the effects of steroid hormones on the insect nervous system are due to changes in patterns of gene expression, we examined Drosophila mutants of the ecdysterone-regulated locus, the Broad Complex (BR-C). This report documents aspects of CNS reorganization which are dependent on BR-C function. During wild-type metamorphosis, CNS components undergo dramatic morphogenetic movements relative to each other and to the body wall. These movements, in particular, the separation of the subesophageal ganglion from the thoracic ganglion, the positioning of the developing visual system, and the fusion of right and left brain hemispheres, are deranged in BR-C mutants. In addition, a subset of mutants shows disorganization of optic lobe neuropil, both within and among optic lobe ganglia. Optic lobe disorganization is found in mutants of the br and l(1)2Bc complementation groups, but not in those of the rbp complementation group. This suggests that the three complementation groups of this complex locus represent distinct but overlapping functions necessary for normal CNS reorganization. This study demonstrates that ecdysterone-regulated gene expression is essential for CNS metamorphosis, illustrating the utility of Drosophila as a model system for investigating the genetic basis of steroid hormone action on the nervous system.

Animals↗
PubMed1991

Organizational analysis of elav gene and functional analysis of ELAV protein of Drosophila melanogaster and Drosophila virilis.

Drosophila virilis genomic DNA corresponding to the D. melanogaster embryonic lethal abnormal visual system (elav) locus was cloned. DNA sequence analysis of a 3.8-kb genomic piece allowed identification of (i) an open reading frame (ORF) with striking homology to the previously identified D. melanogaster ORF and (ii) conserved sequence elements of possible regulatory relevance within and flanking the second intron. Conceptual translation of the D. virilis ORF predicts a 519-amino-acid-long ribonucleoprotein consensus sequence-type protein. Similar to D. melanogaster ELAV protein, it contains three tandem RNA-binding domains and an alanine/glutamine-rich amino-terminal region. The sequence throughout the RNA-binding domains, comprising the carboxy-terminal 346 amino acids, shows an extraordinary 100% identity at the amino acid level, indicating a strong structural constraint for this functional domain. The amino-terminal region is 36 amino acids longer in D. virilis, and the conservation is 66%. In in vivo functional tests, the D. virilis ORF was indistinguishable from the D. melanogaster ORF. Furthermore, a D. melanogaster ORF encoding an ELAV protein with a 40-amino-acid deletion within the alanine/glutamine-rich region was also able to supply elav function in vivo. Thus, the divergence of the amino-terminal region of the ELAV protein reflects lowered functional constraint rather than species-specific functional specification.

Amino Acid Sequence↗
PubMed1991

Effects of a resistive training program on lipoprotein--lipid levels in obese women.

The purpose of this study was to determine the effects of a resistive training program on the time course of changes in strength, body mass index, lipids, lipoproteins, and apolipoproteins in sedentary obese women. Sixteen sedentary obese women strength trained 3 times . wk-1 for 12 wk performing three sets of six to eight repetitions per set with sets 1 and 2 at 60-70% of one-repetition maximum. During set 3, the subjects used the greatest weight possible so that failure occurred between six to eight repetitions. Six sedentary obese women served as controls. Blood samples for serum total cholesterol (TC), high-density lipoproteins (HDL-C), low-density lipoproteins (LDL-C), triglycerides (TG), TC/HDL-C ratio, apolipoprotein A-I (apo A-I), and apolipoprotein B-100 (apo B-100) were obtained pre, and after 4, 8, and 12 wk of training and approximately 3-4 d following the last training session. A 3-d dietary record was obtained on all subjects pre and post, and subjects were instructed not to alter their diet. The 12 wk of resistive training did not result in a significant change in body weight, BMI, or total kilocalories consumed per day but did show a mean improvement of 58% in muscular strength (P less than 0.05). The training program did not significantly alter the TC, HDL-C, LDL-C, TG, TC/HDL-C ratio, apo A-I, or apo B-100 levels, which suggests that this increase in strength owing to resistive training in the absence of body weight loss did not alter the lipid profiles in these sedentary obese women.

Adult↗
PubMed1990

Stimulation of the antigen and interleukin-2 receptors on T lymphocytes activates distinct tyrosine protein kinases.

The T cell antigen receptor complex (TCR) and the interleukin 2 (IL-2) receptor are responsible for signal transduction that results in T lymphocyte activation and proliferation. Stimulation of either the TCR or the IL-2 receptor induces an increase in tyrosine phosphorylation of several cellular proteins indicating that signal transduction by both of these receptors involves the activation of a tyrosine protein kinase. Although the tyrosine protein kinases activated by these receptors have not yet been characterized the receptors themselves are known not to contain a tyrosine protein kinase domain. To determine if these receptors are coupled to the activation of similar or distinct tyrosine protein kinases we examined the patterns and kinetics of tyrosine phosphorylation induced by stimulation of these receptors on a cloned cell line. Hut 78.3 cells co-express the TCR and the p75 IL-2 receptor. These cells were stimulated with either OKT3 antibodies, specific for the TCR, or with IL-2. Signal transduction by these receptors was found to increase the tyrosine phosphorylation of a set of proteins unique to each stimulus. The kinetics of the tyrosine phosphorylation induced by OKT3 antibodies also differed from that induced by IL-2. The OKT3-dependent tyrosine phosphorylation reached maximal levels within 2.5 min and began to decline by 5 min after stimulation. In contrast, the IL-2-induced tyrosine phosphorylation did not achieve maximal levels until 15 min after the addition of IL-2 and the proteins remained phosphorylated even after 60 min of incubation. In addition the tyrosine phosphorylations induced by OKT3 and IL-2 were not affected by prior stimulation with the other agent. These results demonstrate that the TCR and IL-2 receptor are coupled to different signal transduction pathways responsible for the independent activation of distinct tyrosine protein kinases.

Antibodies, Monoclonal↗