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Biomedical subjects

K White

Publications and source records attributed to K White.

At least 217 records · Page 12Linked to original sources
PubMed1987

Genetic dissection of dopamine and serotonin synthesis in the nervous system of Drosophila melanogaster.

Catecholamine- and serotonin-containing neurons were studied in pale, a Drosophila third-chromosome recessive lethal mutant. Using histofluorescent and immunocytochemical techniques, we show that this mutation only alters catecholamine levels in the CNS. Both the presence of catecholamine-neurons and the expression of serotonin are not affected by the mutation. Furthermore, we show that normal characteristics of catecholamine neurons, such as the presence of the enzyme DOPA decarboxylase and the selective uptake properties are normal in pale mutants. We suggest that pale is either the tyrosine hydroxylase structural gene, or a gene controlling tyrosine hydroxylase activity in Drosophila. The similar genetic location of the putative tyrosine hydroxylase gene and the mutation pale supports the former suggestion.

Animals↗
PubMed1986

Neuropeptide-FMRFamide-like immunoreactivity in Drosophila: development and distribution.

Neuropeptide-FMRFamide-like immunoreactivity was characterized in the fruit fly, Drosophila melanogaster. In the adult central nervous system, a stereotypic pattern of immunoreactive cell bodies and immunoreactive nerve processes and varicosities was observed, indicating a neurochemical role for FMRFamide-like substance(s) in Drosophila. Localization of immunoreactivity in the central nervous system of early larval stage revealed that the majority of the prominent FMRFamide-like immunoreactive neurons were already differentiated. The FMRFamide-like immunoreactive neurons remain immunoreactive throughout postembryonic stage and persist in the adult central nervous system. In the larva, in addition to the central nervous system, FMRFamide-like immunoreactivity was localized in the fibers innervating the ring gland, in the ganglion innervating the gut and in the gastric caeca.

Animals↗
PubMed1986

Development of serotonin-containing neurons in Drosophila mutants unable to synthesize serotonin.

We have initiated a study of the CNS of mutant Drosophila melanogaster larvae carrying a genetic deletion of the gene Ddc that encodes the enzyme dopa decarboxylase (DDC). The two major objectives of this study were (1) to ascertain that the DDC encoded by the gene Ddc was the only decarboxylase utilized in serotonin (5HT)-containing neurons and (2) to determine the effect of DDC deficiency on the development of 5HT-immunoreactive neurons. CNSs of wild-type larvae and of larvae genetically deficient for the gene Ddc were processed for serotonin immunocytochemistry using a monoclonal antibody against 5HT. The pattern of 5HT immunoreactivity in the wild-type and the Ddc-deficient CNS is compared. In contrast to the wild-type, 5HT immunoreactivity is absent in the Ddc-deficient CNSs. The lack of immunocytochemically detectable 5HT in the mutant CNSs is consistent with the idea that the DDC encoded by the gene Ddc is utilized in 5HT-containing neurons. To study the development of neurons committed to the 5HT differentiation pathway in the absence of 5HT, we used a second biochemical property characteristic of 5HT-containing neurons, the ability to take up 5HT. CNSs from mutant animals were incubated in exogenous 5HT and the accumulated 5HT detected immunocytochemically. Neurons capable of selective 5HT uptake were present in the mutant CNSs in the same pattern as the 5HT-immunoreactive neurons in the wild-type CNS. This result suggests that the presumed inability to synthesize 5HT does not preclude differentiation of other normal biochemical properties of 5HT-containing neurons.

Animals↗
PubMed1986

The metabolic consequences of infusing emulsions containing medium chain triglycerides for parenteral nutrition: a comparative study with conventional lipid.

In order to test the hypothesis that medium chain triglycerides (MCT's) are a safe and potentially superior energy source during parenteral nutrition 13 patients were entered into a randomised cross over trial. They received either a long chain triglyceride emulsion (LCT) or a 50% medium chain (MCT)/50% LCT mixture as part of their energy supply. Nitrogen balance was significantly better when MCT/LCT was infused and the greater levels of plasma ketones and lower plasma triglyceride levels suggested that MCT was more readily metabolised in these patients. Routine haematology, biochemistry and liver function tests gave no indication of harmful side effects from MCT.

Adult↗
PubMed1986

Perturbed pattern of catecholamine-containing neurons in mutant Drosophila deficient in the enzyme dopa decarboxylase.

We have initiated a study of catecholamine-containing neurons in Drosophila melanogaster because of the potential, with this organism, to perturb catecholamine metabolism using genetic tools. The major objectives of this study were (1) to define the pattern of catecholamine-containing neurons and (2) to determine the effect of the absence of dopa decarboxylase (DDC) enzyme activity on the catecholamine-containing neurons. We chose to analyze the catecholamine-containing neurons in the ventral ganglion of the larval CNS. To define the catecholamine-containing neurons, CNSs were dissected and reacted with glyoxylic acid. The catecholamine histofluorescence (CF) neuronal pattern (normal-CF neurons) in the wild-type ventral ganglion is stereotypic. In the mutant ventral ganglia, in the absence of DDC enzyme activity, most normal-CF neurons still exhibit CF, probably indicating the presence of accumulated L-dopa. Interestingly, in the mutant CNSs, additional novel neuronal subsets also exhibit CF. Analysis of CNSs from early developmental stages revealed that the novel-CF neurons become fluorogenic earlier than the normal-CF neurons in the mutant CNS. To determine whether neuronal subsets, in addition to the normal-CF, neurons are able to sequester catecholamines, CNSs from wild-type larvae were incubated in exogenous catecholamine (L-dopa or dopamine). Incubations in L-dopa or dopamine revealed normally nonfluorogenic neurons that are able to take up the amine and become fluorogenic. Among the neurons able to sequester L-dopa or dopamine are subsets that are similar to the novel-CF neurons in the mutant CNS. This similarity is best characterized by a major novel-CF neuronal cluster in the subesophageal-thoracic region. These results suggest that in the absence of DDC activity, subsets of normally nonfluorogenic neurons capable of sequestering L-dopa or dopamine accumulate the fluorogenic catecholamine. Hypotheses that might explain the mode of accumulation of the catecholamine within the novel-CF neurons are considered.

Animals↗
PubMed1986

Affective disorders and associated psychopathology: a family history study.

A pedigree in which affective psychosis, obsessive-compulsive phenomena, panic attacks, and eating disorders cluster over three generations is presented. The index proband is a 17-year-old girl with schizoaffective disorder, depressed type, bulimia nervosa, panic attacks, and intraepisode obsessive-compulsive phenomena. She has two male siblings; one has bipolar II disorder and the other has had multiple episodes of major depression. Both have panic attacks and exhibit obsessive-compulsive phenomena while depressed. The phenomenologies of the siblings' illnesses incorporate features from both sides of the family. It is proposed that the association of affective disorders with other forms of psychopathology might best be demonstrated by studying families transgenerationally.

Adolescent↗
PubMed1986

Tranylcypromine: patterns and predictors of response.

Data on 58 patients with major depressive episodes treated with tranylcypromine in the course of two controlled, 4-week trials were examined for clinical predictors of favorable response and patterns of symptom improvement and side effects. Predictors of positive outcome with tranylcypromine were associated with greater initial severity on the Hamilton Rating Scale for Depression (HAM-D) ratings of depressed mood, psychomotor retardation, and weight loss, and with lower initial severity on ratings of middle and late insomnia. Distinct quality of depressed mood predicted poorer response; endogenicity, as defined by Research Diagnostic Criteria or the Nies-Robinson Diagnostic Index, failed to predict outcome. Analysis of improvement on individual symptom items of the HAM-D and Zung Self-Rating Depression Scale indicated a generalized patholysis except in a few areas such as appetite/weight loss and insomnia, which may reflect specific side effects of tranylcypromine.

Adult↗
PubMed1985

Development of learning-disabled and normally achieving children's causal attributions.

The causal attributions of learning-disabled (LD) and normally achieving (NA) children in grades 3 through 8 were compared. Attributions were measured by two scales that asked children to attribute hypothetical academic failure situations to factors that were either within (e.g., insufficient effort) or beyond (e.g., insufficient ability, blaming others) their control. Consistent with a learned helplessness hypothesis. LD girls, regardless of age, were more likely than NA children to attribute their failures to factors beyond their control. In contrast, LD boys' explanations for their failures paralleled those of NA children. That is, with increasing age the LD boys were more likely to attribute their failures to insufficient effort. Explanations and implications of sex differences in developmental patterns of LD children's causal attributions are discussed.

Achievement↗
PubMed1985

The pharmacokinetics of high dose metoclopramide in patients with neoplastic disease.

High dose metoclopramide infusions (10 mg/kg) were administered to nineteen patients with bronchial carcinoma who were receiving intravenous cyclophosphamide as single agent chemotherapy. Considerable interindividual variability in metoclopramide disposition was observed. Mean clearance was 0.33 +/- 0.13 (s.d.) l h-1 kg-1, mean volume of distribution at steady state was 3.8 +/- 1.2 (s.d.) l/kg and mean elimination half-life was 8.3 +/- 4.4 (s.d.) h. These results were significantly different from mean values previously reported for young healthy volunteers given conventional doses (0.70 l h-1 kg-1, 2.2 l/kg and 2.6 h respectively). Significant correlations were found between serum urea, serum creatinine and metoclopramide clearance. The metoclopramide regimens were well tolerated and, with the exception of two patients, were completely effective in the prevention of nausea and vomiting. To achieve and maintain target serum metoclopramide concentrations of 1 microgram/ml, we now administer a loading infusion of 3.61 mg/kg over 30 min followed by a maintenance infusion of 0.36 mg kg-1 h-1 for 10 h. Cyclophosphamide is normally administered concurrently with the second infusion. For patients with evidence of mild renal impairment, the maintenance infusion rate of metoclopramide hydrochloride should be adjusted according to the predicted individual clearance value; CL (l h-1 kg-1) = 0.57 - [0.036 X urea (mmol/l)].

Aged↗
PubMed1985

Mutant alleles at the locus elav in Drosophila melanogaster lead to nervous system defects. A developmental-genetic analysis.

We report a developmental and genetic analysis of the X-linked vital locus l(1)EC7 in Drosophila melanogaster. The locus maps in the salivary band region 1B4-5 to 1B8-9, a part of the X chromosome previously shown to be essential for normal neural development. Certain mutant alleles at the locus can cause embryonic lethality, indicating that the function provided by the gene is essential during embryogenesis. A developmental analysis of gynandromorphic genetic mosaics shows that: (1) the gene function is autonomously essential in the eye; (2) the gene function is essential for normal development of the optic lobes; and (3) the gene function is not necessary in most major imaginal-disc cell derivatives with the exception of the eye disc. Conclusions from the developmental analysis of a temperature sensitive allele are consistent with those from the mosaic analysis. The embryonic lethality caused by the mutant alleles and abnormalities observed in the genetic mosaics have led us to rename the locus l(1)EC7 to elav (embryonic lethal, abnormal visual system).

Alleles↗
PubMed1984

Tranylcypromine vs nortriptyline vs placebo in depressed outpatients: a controlled trial.

This study was designed to compare the therapeutic and adverse effects of tranylcypromine (a monoamine oxidase inhibitor), nortriptyline (a tricyclic antidepressant), and placebo. A total of 122 depressed outpatients randomly assigned to double-blind treatment with one of these agents completed the 4-week protocol. Treatment groups were balanced for proportions of endogenous versus nonendogenous depressions, defined according to the Research Diagnostic Criteria; however, nonendogenous depressions outnumbered endogenous depressions by such a large proportion (4:1) that meaningful statistical comparisons were limited to the nonendogenous group. In this group, both active drugs proved more effective than placebo, with little differences between the two active drugs except in the areas of side effects and of differential sensitivity of the outcome scales to a given drug. It was concluded that tranylcypromine, a drug which has received relatively little use and study in recent years, represents an effective and reasonably safe treatment for nonendogenous depression, although significant advantages over tricyclics with this disorder remain to be demonstrated.

Adolescent↗
PubMed1984

The combined use of MAOIs and tricyclics.

Combined MAOI-tricyclic treatment remains a plausible approach to depressions refractory to single drugs. Adherence to published guidelines should minimize special risks of the combined treatment. However, such risks do exist, and should be borne in mind. Most severe reactions - characterized by hyperthermia, delirium, convulsions, and sometimes fatal outcome - have occurred after a tricyclic was added to established MAOI treatment. Combined treatment may be associated with a lower risk of hypertensive crisis than treatment with MAOI alone. There are no data from double-blind, control-group studies to demonstrate an advantage for the MAOI-tricyclic combination in refractory depression. However, almost no such data exist to establish the advantage of any other treatment in this clinical situation. Clinical experience provides the primary basis for continued consideration of this approach when usual treatments have failed.

Aged↗
PubMed1984

Unstable diabetes and unstable families: a psychosocial evaluation of diabetic children with recurrent ketoacidosis.

To investigate the physical and psychological factors associated with labile diabetic control, 30 children and adolescents with recurrent diabetic ketoacidosis were included in a retrospective longitudinal review covering an 8-year period. The details of the ketoacidosis episodes and the psychosocial characteristics of the patient and his family were summarized from the medical record. Only a minority of the ketoacidosis episodes were overtly and solely related to intercurrent illness or poor compliance. A majority of the subjects studied lived in families with substantial psychosocial dysfunction, including chronic unresolved interpersonal conflict, inadequate parenting, father not in home, financial stress, and lack of family involvement with the diabetes. Many of the children displayed behavioral and personality problems. In most of these 30 cases, there was evidence that these dysfunctions existed prior to the onset of diabetes. These psychosocial problems were not immediately apparent in many instances, thus requiring more comprehensive psychosocial assessment and involvement by a social worker and/or a psychologist. Ongoing emotional support and counseling were instrumental in reversing the pattern of recurrent ketoacidosis, in coordination with care by all members of the diabetes team. The findings from this experience suggest that recurrent ketoacidosis warrants prompt evaluation from a psychosocial as well as a physical perspective.

Adolescent↗