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Biomedical subjects

K White

Publications and source records attributed to K White.

At least 181 records · Page 10Linked to original sources
PubMed1990

The costs and benefits of providing early intervention to very young, severely hearing-impaired children in the United States: the conceptual outline of a longitudinal research study and some preliminary findings.

This paper presents the conceptual framework for a newly instituted longitudinal research study into the costs and benefits of providing early intervention to very young, severely hearing-impaired children in the USA and the results of one of the studies after 2 years of intervention. The research design employs randomised procedures, blind assessment and treatment verification. The overall project is part of a 20 experiment national study that addresses specific questions about the effects of early intervention on the psychological development of hearing-impaired children. Those questions regard age-at-start, treatment intensity and programme variation. Two of the three experiments with hearing-impaired children are still in developmental stages, whilst the third, a communication methods comparison, has been started. The preliminary findings of the third experiment (which include 2 years of intervention effects) are presented. Two groups of young, severely hearing-impaired children between the ages of 18 months and 5 years (one an oral-aural group and one called an English sign language group) have received 20 months of intervention in one or other of the groups. Their developmental progress has been measured using the Battelle Developmental Inventory, several specific English language measures and two family measures. Whilst both groups showed significant progress over intervention time on all measures, the performance differences between the two groups were not statistically significant in any of the psychological domains tested.

Child Health Services↗
PubMed1990

What next? A review of pharmacologic strategies for treatment resistant depression.

When an antidepressant fails to help a depressed patient, clinicians are faced with the daunting task of choosing the next treatment. Several pharmacologic and nonpharmacologic strategies exist, but the evidence available to help clinicians decide which treatment will be most effective is limited. To help clinicians evaluate the literature on treatment resistant depression (TRD), we critically review several selected pharmacologic strategies.

Depression↗
PubMed1990

Role of circumsporozoite protein-specific T-cells in protective immunity against Plasmodium berghei.

The Plasmodium berghei circumsporozoite (CS) protein-specific T-cell repertoire was analysed in C57Bl/6 (H-2b), Balb/c (H-2d), and C3H/HeN (H-2k) mice immunized with irradiated sporozoites and the proliferative responses were correlated with the protective status of each strain. Splenic lymphocytes responded to the priming antigen, but the responses varied according to both murine strain and immunization schedule. Analysis of cytolytic T lymphocyte (CTL) responses in mice immunized with irradiated P. berghei sporozoites or with a Salmonella-recombinant CS protein construct revealed that each immunization induces CTLs recognizing different epitopes on the target cells. The variations in immune reactivities among different murine strains to the CS protein antigens and the variations in the responses to the authentic versus recombinantly expressed CS protein suggest that distinct immune mechanisms may be involved in rendering immune protection. Furthermore, the molecular context of the immunizing antigen may influence the outcome of the fine specificity of T cells involved in immune protection.

Animals↗
PubMed1990

Fluvoxamine in the treatment of tricyclic-resistant depression.

Following an initial double-blind, randomized, parallel treatment group comparison of fluvoxamine, desipramine, and placebo in 89 outpatients with major depression at two centers, double-blind crossover to fluvoxamine was offered to 13 of 22 desipramine-treated completers of the initial phase who were considered failures on desipramine. Twelve elected to cross over to blinded fluvoxamine, and eleven continued on fluvoxamine for at least eight weeks. Nine of these eleven improved, and overall there was a statistically significant decrease in average Hamilton Depression Scores, from 24 to 13, for these fluvoxamine-treated desipramine-resistant patients.

Adult↗
PubMed1990

Identification, secretion, and neural expression of APPL, a Drosophila protein similar to human amyloid protein precursor.

A Drosophila gene [amyloid protein precursor-like (Appl)] has recently been identified whose predicted amino acid sequence (APPL) shares extensive homology with the beta-amyloid protein precursor (APP) associated with Alzheimer's disease. Characterization of proteins encoded by the Appl gene was initiated with the expectation that this simple model system might help elucidate the basic function provided by APPL and APP proteins. In this report, we identify 2 forms of the APPL protein in embryonic extracts, primary cultures, and transfected cells. APPL is synthesized as a 145-kDa membrane-associated precursor that is converted to a 130-kDa secreted form that lacks the cytoplasmic domain. Both forms are N-glycosylated. Pulse-chase and subcellular localization studies suggest that the conversion is very rapid. The similarities of biogenesis between APP and APPL provide further evidence that APPL and APP might be functionally homologous, and that the secretion event is of physiological significance. Immunocytochemical studies show that the APPL proteins are first detected in developing neurons concomitant with axonogenesis and remain associated with differentiated neurons. APPL immunoreactivity was observed in neuronal cell bodies, axonal tracts, and neuropil regions. In the embryo, APPL proteins are expressed exclusively in the CNS and PNS neurons, consistent with the Appl transcript localization. The expression pattern of APPL proteins suggests an ancestral function for this protein in the nervous system.

Amyloid beta-Peptides↗
PubMed1990

Serotonin synthesis and distribution in Drosophila dopa decarboxylase genetic mosaics.

In Drosophila, the enzyme dopa decarboxylase (DDC) catalyzes the last step in the biosynthesis of serotonin (5HT) and dopamine. In the present study, the distribution of DDC and one of its biosynthetic products (5HT) was determined in CNSs that were genetic mosaics, composed of neurons that have DDC activity and neurons that lack DDC activity. Phenotypic mosaicism, that is, immunoreactive (IR) and non-IR neurons within the same nervous system, was observed for both DDC and 5HT immunoreactivity. DDC-IR neurons were always 5HT-IR, but some 5HT-IR neurons devoid of DDC immunoreactivity were also observed. 5HT-IR neurons devoid of DDC immunoreactivity were always in close apposition to other DDC-IR neurons. We suggest that in vivo uptake mechanisms are responsible for 5HT accumulation in neurons devoid of DDC immunoreactivity.

Animals↗
PubMed1990

Results of a double-blind placebo controlled trial of a new serotonin uptake inhibitor, sertraline, in the treatment of obsessive-compulsive disorder.

Eighty-seven patients with a DSM-III diagnosis of obsessive-compulsive disorder (OCD) without depression were entered into a double-blind, placebo-controlled study of the efficacy of sertraline, a new serotonin uptake inhibitor. After a 1-week washout period, patients were randomly assigned to receive either placebo or sertraline. After a 2-week titration period in which the once-daily sertraline dose was increased from 50 mg/day to a maximum of 200 mg/day, dosage was maintained until the end of the eighth week, then patients were titrated off medication over the next 2 weeks. Efficacy was measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), NIMH General Obsessive-Compulsive Scale, Maudsley Obsessive Compulsive (MOC) Inventory, and Clinical Global Impressions (CGI) Severity and Improvement scales. Results on the MOC Inventory showed trends in favor of active drug that were not statistically significant compared with placebo. Results of the Y-BOCS total score, the NIMH score, and the global severity and improvement scores demonstrated a statistically significant superiority of sertraline compared with placebo.

1-Naphthylamine↗
PubMed1989

Complete structure and expression in transfected cells of high affinity IgE receptor.

The high-affinity receptor for immunoglobulin E, Fc epsilon RI, is found exclusively on mast cells and basophils. When multivalent allergens bind to the receptor-bound IgE, the consequent aggregation of the receptors leads to the release of mediators responsible for allergic symptoms. In rodents Fc epsilon RI is a tetrameric complex of non-covalently attached subunits: one IgE-binding alpha subunit, one beta subunit and a dimer of disulphide-linked gamma subunits. Complementary DNA encoding the alpha and the beta subunits has recently been isolated, but expression of IgE-binding by transfected cells has not yet been achieved. Here we report the cloning of cDNA for the gamma subunit, and propose a model for the alpha beta gamma 2 tetramer which accounts for many of the structural features of the receptor. The rodent receptor on the surface of COS 7 cells was expressed only when the cDNAs for all three subunits were cotransfected. Successful expression of human IgE receptors should now be possible, eventually to permit the detailed analysis of the human IgE-receptor interaction and assist the search for therapeutically effective inhibitors.

Amino Acid Sequence↗
PubMed1989

Comparison of medium and long chain triglyceride metabolism in intensive care patients on parenteral nutrition.

The metabolic effects of an intravenous lipid emulsion containing medium chain triglycerides (MCTs) were studied in eleven critically ill, ventilated patients receiving parenteral nutrition. The effects were compared in a cross-over study with those of a conventional emulsion containing only long chain triglycerides (LCTs). The lipid was well tolerated, but there were differences in the metabolic effects with a significantly greater increase in the plasma concentrations of glycerol and ketones during MCT/LCT infusion compared to LCT. The plasma concentration of non esterified fatty acids was also higher. This fell rapidly post infusion. Since non esterified fatty acids and ketones are readily available energy sources for tissues lipid emulsions containing MCT may prove valuable for catabolic, critically ill patients.

Adult↗
PubMed1989

Phase I trial of combined therapy with bleomycin and the calmodulin antagonist, trifluoperazine.

Calmodulin antagonists, such as trifluoperazine, can enhance the cytotoxic effects of bleomycin both in tissue culture and in vivo. Therefore, we evaluated the effects of combination treatment with these drugs in a phase I clinical trial. Patients with objectively measurable or evaluable cancer refractory to conventional treatment who had an acceptable performance status (ECOG 0-2) and acceptable laboratory studies were eligible. All patients gave written informed consent. A cycle of therapy consisted of three weekly treatments with trifluoperazine (days 1-4) and 30 IU bleomycin (day 3). After three patients completed a cycle of therapy without experiencing dose-limiting toxicity, new patients were entered in the study and received a higher dose of trifluoperazine. The dose of bleomycin remained constant. Evaluable patients received at least 2 weeks of treatment and survived for 6 weeks; of 19 patients, 2 were unevaluable. The major toxicities were neurological and pulmonary and included one case of fatal pneumonia with interstitial pulmonary fibrosis. There was no hematologic toxicity. Two patients underwent partial responses (PRs) and two had complete responses (CRs). We conclude that trifluoperazine can safely be given with bleomycin and that further study of the potential efficacy of this treatment is indicated.

Adult↗
PubMed1989

Sensory preconditioning and UCS inflation in human 'fear' conditioning.

This study describes a human electrodermal conditioning experiment involving processes of sensory preconditioning and UCS inflation. In stage 1 of the experiment Ss received six presentations of a CS+ paired with an innocuous 65 dB tone (UCS) and six presentations of an unpaired CS-. In stage 2, Ss in the experimental group had the aversiveness of the UCS inflated as the intensity of the 65 dB tone was increased to 115 dB. In stage 3, Ss were given test presentations of CS+ and CS-. A differential CR to CS+ was found only in stage 3 of the experiment and only in Ss who had experienced the UCS inflation procedure. These results suggest that (i) sensory preconditioning had occurred in stage 1 despite the failure to observe a differential CR in this stage, and (ii) the differential CR observed in stage 3 was mediated by an internal representation of the UCS whose aversiveness had been inflated in stage 2. As well as confirming that processes of sensory preconditioning and UCS inflation can be observed in human as well as animal Ss, these findings have important implications for contemporary conditioning models of clinical fears. In particular, they suggest that a contemporary conditioning model of acquired fears is not bound by the need to discover contiguous stimulus-trauma experiences in the histories of clinical phobias since, in humans at least, processes of stimulus association and UCS revaluation appear to be relatively independent.

Adolescent↗
PubMed1989

Metabolic effects of intravenous medium- and long-chain triacylglycerols in critically ill patients.

1. The metabolic effects of an intravenous lipid emulsion containing medium-chain triacylglycerols (MCT) and long-chain triacylglycerols (LCT) were studied in 16 critically ill, ventilated patients. The effects were compared in a cross-over study with those of a conventional emulsion containing only LCT. 2. The lipid was well tolerated but the metabolic effects of the MCT/LCT infusion differed from those of the LCT infusion. 3. The major differences were a 60% higher insulin concentration and a significantly greater increase in the plasma concentrations of non-esterified fatty acids during MCT/LCT infusion than during LCT infusion. The mean rise in plasma ketone concentration was also higher during MTC/LCT infusion, although this did not reach statistical significance.

Adult↗
PubMed1989

A Drosophila gene encoding a protein resembling the human beta-amyloid protein precursor.

We have isolated genomic and cDNA clones for a Drosophila gene resembling the human beta-amyloid precursor protein (APP). This gene produces a nervous system-enriched 6.5-kilobase transcript. Sequencing of cDNAs derived from the 6.5-kilobase transcript predicts an 886-amino acid polypeptide. This polypeptide contains a putative transmembrane domain and exhibits strong sequence similarity to cytoplasmic and extracellular regions of the human beta-amyloid precursor protein. There is a high probability that this Drosophila gene corresponds to the essential Drosophila locus vnd, a gene required for embryonic nervous system development.

Amino Acid Sequence↗
PubMed1989

Molecular isolation and analysis of the erect wing locus in Drosophila melanogaster.

The molecular study of the erect wing (ewg) locus was initiated by isolating DNA in the 1A8-1B1 interval of the X chromosome. Previous developmental genetic analyses of the mutant alleles at the ewg locus have demonstrated that the wild-type ewg product is essential during embryogenesis and is required postembryonically at least for the development of the indirect flight muscle. To define the ewg-encoding DNA, chromosomal breakpoints that genetically flank the ewg locus were used. P-element-mediated transformation followed by subsequent rescue of the ewg-lethal alleles has defined a 11.5-kilobase genomic fragment as encoding the ewg locus. Northern blot analysis of transcription from this DNA has revealed a complex pattern of transcription with respect to both size and developmental profile. Tissue distribution of putative ewg transcription was examined by in situ hybridization to 6- to 14-h-old embryonic sections. These sections revealed that the expression of putative ewg messages is limited to the central nervous system-derived structures and not observed within the mesoderm during this developmental stage.

Animals↗
PubMed1989

Emerging picture of the receptor with high affinity for IgE.

The cDNAs for two of the subunits of the receptor with high affinity for IgE have been isolated and sequenced. That for the IgE-binding alpha subunit predicts a polypeptide with a single transmembrane segment. The predicted extracellular amino terminal portion, comprised of 180 residues, is homologous to the corresponding region of Fc gamma receptors and contains two truncated immunoglobulin-like domains. The cDNA for beta predicts a peptide with four transmembrane segments, but its sequence is unrelated to known proteins. Experiments to isolate the cDNA for the gamma subunit have begun; when completed, cotransfection of the three genes will be attempted to get expression, a process that has not so far been successful for the individual subunits. Such expression will permit further analysis of the receptor's function and ultimately may provide information on how best to intervene clinically in the activation of mast cells and basophils.

Animals↗
PubMed1989

Prevalence of spondylolisthesis, transitional anomalies and low intercrestal line in a chiropractic patient population.

Five hundred and thirty radiographs were screened for the presence of certain lumbosacral anomalies. The prevalence of spondylolisthesis was found to be 5.1%, lumbarization 6.0%, sacralization 5.5% and low intercrestal line 56.9%. There was no greater prevalence in patients suffering from low back pain when compared against those who did not. There was a propensity for a low intercrestal line among females. Contrary to previous claims that lumbarization is more common in men, we found a moderate predilection for this finding among women. No difference between the two sexes was found in the prevalence of sacralization, contradicting previous claims that is more common in females, nor was spondylolisthesis found more frequently in men, contrary to our expectations.

Age Factors↗