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Biomedical subjects

K White

Publications and source records attributed to K White.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

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

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

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

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

Hemispheric dysfunction in schizophrenia: assessment by visual perception tasks.

Before and after a double-blind trial of haloperidol vs. mesoridazine, 24 hospitalized schizophrenics performed visual perception tasks designed to assess function of the cerebral hemispheres. Tasks involved identifying as "same" or "different" two images (either letters, digits, or unfamiliar shapes) projected tachistoscopically to the right or left visual field or to both together. Multivariate analysis of variance related response latency and accuracy to task type, hemisphere stimulated, and pre- vs. posttreatment testing. Both before and after treatment, subjects responded most slowly and least accurately to letter-matching. Bilateral presentation of stimuli resulted in faster and more accurate responses, except on shape-matching. Neuroleptic treatment improved speed and accuracy overall, though not under certain task conditions. Results accorded more with an impairment in verbal processing and interhemispheric coordination than with a specific left-hemispheric deficit in schizophrenia.

Acute Disease

Lithium effects on normal subjects. Relationships to plasma and RBC lithium levels.

15 normal subjects took lithium carbonate for 10 days in dosage sufficient to attain plasma lithium concentrations in the range of 0.7-1.4 mEg/l. Periodic blood specimens were analyzed for both plasma and RBC lithium. Subjects completed Profile of Mood States questionnaires every other day, and listed side effects. Just prior to beginning and ending the lithium trial, 10 subjects completed three tests of psychomotor function. Results indicate that such a course of lithium in normals induces dysphoric mood change and psychomotor slowing, without significant relationship to either plasma or RBC lithium concentrations.

Choice Behavior

Relationship between plasma, RBC, and CSF lithium concentrations in human subjects.

Simultaneous measurement of plasma, RBC, and plasma lithium concentrations took place with 17 inpatients chronically treated with lithium, at various times after the last lithium dose. RBC lithium levels were significantly higher than CSF lithium levels. Specimens drawn 10 or more hours after the last dose showed higher RBC and CSF lithium and lower plasma lithium than specimens drawn 4 or less hours after the last lithium dose. None of the lithium measurements differentiated manic-depressives from schizophrenics or schizoaffectives. Plasma, RBC, and CSF lithium all intercorrelated highly and equally.

Adult