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K White

Publications and source records attributed to K White.

At least 199 records · Page 11Linked to original sources

Altered branching of serotonin-containing neurons in Drosophila mutants unable to synthesize serotonin and dopamine.

The anatomy of peripheral serotonin-containing fibers (5-HT fibers) in the gut of wild-type Drosophila larvae was compared to mutants deficient in the gene that encodes the enzyme dopa decarboxylase (DfDdc mutants). The 5-HT fibers, located in the proventriculus and midgut, were visualized immunocytochemically by using a monoclonal antibody against 5-HT. Since DfDdc larvae are devoid of 5-HT and dopamine in the nervous system, the highly selective uptake capability of 5-HT neurons was used to visualize the 5-HT fibers. We found that the absence of 5-HT and dopamine in the nervous system of DfDdc animals does not prevent 5-HT fibers from reaching their appropriate targets. However, these fibers in the mutant show a 2-fold increase in the extent of branching. This effect is specific to 5-HT fibers, since glutamate-like and FMRFamide-like immunoreactive fibers of the proventriculus and midgut remain unaffected in the mutant. Low but detectable levels of dopamine and 5-HT in the CNS are sufficient to prevent the increase in arborization, as indicated by analyses of a temperature-sensitive Ddc allele (Ddcts2), which has very low dopa decarboxylase activity. The abnormally extensive branching of 5-HT fibers also can be partially rescued by feeding DfDdc larvae with dopamine. In contrast, feeding with a 5-HT-containing diet had no effect on the mutant phenotype. Hypotheses that could explain the mutant phenotype are proposed.

Animals↗

Clonazepam in the treatment of obsessive compulsive disorder associated with panic disorder in one patient.

The authors present the case of a 21-year-old man with obsessive compulsive disorder (OCD) complicated by panic disorder, whose OCD and panic symptoms resolved during clonazepam treatment. Prior treatment with an equivalent dose of lorazepam had ameliorated his panic attacks without affecting his obsessions or compulsions. Clonazepam worked with a rapidity and completeness uncharacteristic of more established treatments for OCD.

Adult↗

Acute cardiovascular response to monoamine oxidase inhibitors: a prospective assessment.

Despite the widespread use of monoamine oxidase inhibitors (MAOIs) and the well-known adverse event of hypertensive crisis, few studies have addressed the acute cardiovascular response to an MAOI dose. We prospectively measured pulse and blood pressure changes just before and at 1, 2, 3, and 4 hours after MAOI administration in 18 patients. Significant but asymptomatic increases from baseline in mean systolic and diastolic blood pressure occurred within 2 hours after MAOI administration, with return to near baseline by 4 hours. The mechanism of this reaction is unknown.

Agoraphobia↗

The elav gene product of Drosophila, required in neurons, has three RNP consensus motifs.

A sequence of developmental events transforms neurons from their immature state to their mature, terminally differentiated state. The elav locus is one of the first examples of a gene that is expressed in neurons early during this developmental sequence. This gene has been shown to be required for the proper development of young neurons and for the maintenance of mature neurons. DNA sequence data presented in this report suggest that the elav gene product is an RNA binding protein, based on the presence of RNP (ribonucleoprotein) consensus sequences. This leads to the proposal that this protein is involved in the RNA metabolism of neurons.

Amino Acid Sequence↗

Induction of ferritin subunit synthesis by iron is regulated at both the transcriptional and translational levels.

Synthesis of the iron storage protein ferritin is induced in rat liver by iron administration, the ferritin L subunit being preferentially stimulated over the H subunit. To examine the basis for this differential regulation of the two subunits, the transcription rates of the L and H genes, the total cellular levels of L and H subunit mRNA, and the distribution of the mRNAs between a stored ribonucleoprotein form and the polysomes were examined in rat liver at several times after iron injection. Iron caused a rapid increase in transcription of the L subunit gene, followed by a rise in L mRNA levels, whereas H subunit gene transcription and H mRNA levels did not increase significantly. Differential transcriptional regulation of ferritin L and H mRNA levels by iron contrasted with the coordinate control of the two subunit mRNAs at the translational level. On giving iron, there was a rapid and synchronous shift of both mRNAs from the ribonucleoprotein fraction onto the polysomes, the same proportion of each mRNA being mobilized. Thus, regulation of ferritin subunit synthesis at these two levels allows both a rapid translational response and a specific transcriptional response to increased intracellular iron levels.

Animals↗

Catecholamine-containing neurons in Drosophila melanogaster: distribution and development.

The development of catecholamine-containing neurons (CA neurons) in the fruit fly Drosophila melanogaster was studied. Glyoxylic-acid-induced histofluorescence and antibodies against dopamine and tyrosine hydroxylase were used to describe catecholamine distribution in the larval central nervous system (CNS). The three techniques gave rise to a similar pattern of distribution of putative CA neurons. At all developmental stages CA neurons were distributed widely throughout the CNS but represented only a small fraction of all CNS neurons. Catecholamine-containing processes were confined to the CNS. The CA neurons are first discerned at about 18 hours of embryonic development. We suggest that these larval CA neurons are maintained throughout the ontogeny of the fly and that the adult CA pattern is composed of embryonic neurons and neurons that differentiate during metamorphosis.

Animals↗

Serotonin-containing neurons in Drosophila melanogaster: development and distribution.

Antibodies made against serotonin (5HT) were used to identify the serotonin neuronal system in the developing and adult nervous system of Drosophila melanogaster. The 5HT neuronal pattern is composed of a small number of neurons, 84 in larvae and 106 in adults, distributed in clusters composed of one to five neurons in the CNS; 5HT immunoreactive (5HT-IR) neurons appear to be predominantly intrasegmental interneurons; however, intersegmental 5HT-IR fibers are observed and at least some neurons send peripheral fibers. Acquisition of 5HT immunoreactivity in the CNS occurs late in embryogenesis, by 16-18 hours, and most if not all the 5HT neurons appear to persist into adulthood. During early metamorphosis, the intensity of 5HT-IR neuropil transiently decreases. Other changes in the CNS during this period are reflected in the appearance of two new 5HT clusters and 5HT-IR neuropil in the developing optic lobes. Comparison of the 5HT-IR pattern with other transmitter systems in Drosophila as well as comparison of the 5HT-IR pattern within different insect species is presented.

Animals↗

Primary carcinoma of the gallbladder: TNM staging and prognosis.

In order to investigate the lethality of carcinoma of the gallbladder and several of the coexisting features, a retrospective analysis of 53 patients with this disease was undertaken. Abdominal pain, obstructive jaundice, and a right upper quandrant mass were present in approximately one-half of the patients. Laboratory and radiological data were frequently nonspecific and did little to identify the diagnosis. The most common preoperative diagnoses were cholelithiasis or chronic cholecystitis. Cholecystectomy was the most frequently performed procedure. Fifteen wedge liver resections were performed. No radical or extended liver resections were done. Eighty-one percent of the patients had sufficient data for staging. Five patients (11.6%) had stage I lesions, three patients (7.0%) had stage II lesions, while 17 (39.5%) and 18 (41.9%) patients had stage III and IV lesions, respectively. Mean survival was 6.4 months for the entire group. Three patients are still alive (two longer than 5 years and one at 2 years) for an overall survival of 5.7%. Both staging and grading of the tumor correlated well with patient survival. Those patients with stage I lesions survived significantly longer (23 months vs. 3 months) than those with stage IV tumors. Also, those with more favorably graded (well-differentiated) neoplasms lived an average of 13 months longer than patients with poorly differentiated lesions.

Adenocarcinoma↗

The locus elav of Drosophila melanogaster is expressed in neurons at all developmental stages.

The locus elav (ella-vee) of Drosophila melanogaster, which is necessary for the proper development of the embryonic and adult nervous systems, has been characterized both genetically and molecularly. This locus has been shown to be transcribed exclusively within, and ubiquitously throughout, the developing nervous system during Hours 6 to 12 of embryogenesis. We present in situ RNA localization data which demonstrate that elav is expressed in the central nervous system as well as the peripheral nervous system of embryos, larvae, pupae, and adults. We also demonstrate that elav is not transcribed in embryonic or larval neuroblasts (the neuronal progenitor cells), or in at least one type of glial cell. These data provide evidence that the requirement for elav function is not limited to the 6- to 12-hr embryonic nervous system and the adult eye and developing optic lobe, but that its function is required for the development and continued maintenance of all neurons of the organism.

Animals↗

Isolation and characterization of cDNAs coding for the beta subunit of the high-affinity receptor for immunoglobulin E.

Among receptors that bind the Fc region of immunoglobulins ("Fc receptors"), only the one with high affinity for immunoglobulin E (IgE) is known to consist of more than a single polypeptide. In addition to the IgE-binding alpha chain, the receptor contains a single beta chain and two, disulfide-linked, gamma chains. From a cDNA library of a rat mucosal mast cell tumor, from which we recently cloned cDNAs coding for the alpha chain, we have now isolated cDNAs coding for the beta subunit. In vitro transcription-translation of the cDNA directed the synthesis of a polypeptide reactive with two distinctive anti-beta monoclonal antibodies and whose molecular weight was identical to that of authentic beta chains. Polyclonal antibodies to beta peptides expressed in Escherichia coli reacted with intact receptors and isolated beta chains. The gene encodes a protein of 243 residues with no leader sequence. A hydropathicity plot suggests that the polypeptide crosses the plasma membrane four times. The epitope recognized by one of the monoclonal antibodies was localized to the NH2 terminus; that by the other was localized to the COOH terminus. Since those antibodies react with membranes and not with intact cells, we suggest that both ends of the beta subunit are cytoplasmic. RNA transfer blots at high stringency failed to reveal mRNA for beta chains in a variety of cells (in particular, monocytes) that do not contain the high-affinity receptor for IgE.

Amino Acid Sequence↗

Use of a lipid containing medium chain triglycerides in patients receiving TPN: a randomized prospective trial.

Lipid emulsions which contain long chain triglycerides (LCTs) provide a valuable energy source for patients requiring total parenteral nutrition (TPN). We have investigated the use of a new lipid emulsion containing both long and medium chain triglycerides (MCTs) in a randomized prospective trial. Sixty patients received TPN including 500 ml of either 20 per cent Lipofundin S (LCT) or Lipofundin 10 per cent MCT/10 per cent LCT for at least 6 days. Patients with renal or hepatic impairment, or major trauma, were excluded from the study. The MCT/LCT emulsion was found to be as safe and as effective a source of calories as LCT but the differences in metabolic parameters did not differ significantly between the two groups of patients. A lipid emulsion containing MCTs may have important advantages for seriously ill patients, but appears to have no obvious advantages for the majority of patients receiving TPN who are not severely stressed.

Adult↗

Molecular analysis of the locus elav in Drosophila melanogaster: a gene whose embryonic expression is neural specific.

The embryonic lethal abnormal visual system (elav) locus in Drosophila melanogaster, a vital gene mapping within the 1B5-1B9 region of the X-chromosome has been cloned and analysed. Previous developmental analyses have shown that in addition to the embryonic requirement there is a post-embryonic requirement for elav function in the cells of the visual system. A DNA segment containing elav+ function was defined through germ line transformation experiments. This region encodes three embryonic poly(A)+ RNAs and two adult transcripts which are preferentially expressed in the head. In situ hybridization experiments clearly demonstrate that the embryonic expression of elav is restricted to the nervous system.

Animals↗

Conservation of ferritin heavy subunit gene structure: implications for the regulation of ferritin gene expression.

Ferritin stores iron within a protein shell consisting of 24 subunits of two types, heavy (H) and light (L). According to Southern blotting, the rat genome contains four copies homologous to the H-subunit cDNA (H cDNA). To determine whether only one of these is expressed, H cDNAs isolated from rat liver and heart mRNAs were compared and found to share identical nucleotide sequences. Next, genomic clones for three of the four rat H-subunit loci were isolated. Two were classical processed pseudogenes, whereas the third contained an expressed gene. RNase intron mapping of this expressed gene generated the same exon protection pattern when total RNA from rat liver or heart was used, indicating that this gene accounts for most or all of the H-subunit mRNAs (H mRNAs) in these tissues. Comparison of the expressed rat H-subunit gene (H gene) structure with published sequences for other species displays considerable conservation. The coding sequence of the rat H gene predicts 95% similarity to the human amino acid sequence, thus being more highly conserved than the L-subunit sequence of these species. Near the cap region of the 5' untranslated region, the rat H mRNA displays a 28-nucleotide sequence that is almost totally conserved in the corresponding region of the human, bullfrog, and chicken H mRNA and is also faithfully represented in the rat and human L-subunit mRNAs (L mRNAs), thus making this sequence a prime candidate for involvement in the known translational regulation of both subunits by iron. In the 5' flanking region, partially conserved sequences common to H gene and L-subunit gene (L gene) of the rat may be involved in transcriptional regulation by iron, whereas those conserved only in the H gene of man and the rat imply that other factors may independently control H-subunit regulation.

Amino Acid Sequence↗

Construction of an unstable Ring-X chromosome bearing the autosomal dopa decarboxylase gene in Drosophila melanogaster and analysis of Ddc mosaics.

An unstable Ring-X chromosome, Ddc+ -Ring-X carrying a cloned Dopa decarboxylase (Ddc) encoding segment was constructed. The construction involved a double recombination event between the unstable Ring-X, R(1)wvC and a Rod-X chromosome which contained a P-element mediated Ddc+ insert. The resulting Ddc+ -Ring-X chromosome behaves similarly to the parent chromosome with respect to somatic instability. The Ddc+ -Ring-X chromosome was used to generate Ddc mosaics. Analyses of Ddc mosaics revealed that while there was no absolute requirement for the Ddc+ expression in either the epidermis or the nervous system, very large mutant clones did affect the viability of the mosaic.

Animals↗

The importance of considering alternative structural equation models in evaluation research.

The availability of the LISREL computer program and similar software (for example, COSAN, EQS) have made structural equation modeling accessible to researchers interested in program evaluation. An article was published in the December 1985 issue of this journal that used LISREL to investigate the relationship between family medicine residents' moral reasoning and their clinical performance with patients (Sheehan et al., 1985). We present a reanalysis of the data from that study to illustrate the importance of considering alternative structural equation models in evaluation research.

Ethics, Medical↗