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Biomedical subjects

J C Hall

Publications and source records attributed to J C Hall.

At least 163 records · Page 9Linked to original sources

An ultrashort clock mutation at the period locus of Drosophila melanogaster that reveals some new features of the fly's circadian system.

A rhythm mutant of Drosophila melanogaster was induced by chemical mutagenesis and isolated by testing for locomotor activity rhythms, which in the new variant had periods of approximately 16 hr. The sex-linked mutation responsible for this ultrashort period causes 20-hr rhythms when heterozygous with a normal X. This semidominance notwithstanding, the new mutation was revealed to be an allele of the period (per) gene by noncomplementation with per-null variants, in the sense that females heterozygous for perT (as the ultrafast-clock allele is called) and per- exhibited periods that were much shorter than in the case of perT/+. These tests also revealed in a clearer manner than in previous cases that two "doses" of a fast-clock per mutation lead to appreciably shorter periods than those exhibited by one-dose females whose other per allele is a loss-of-function variant. In light-dark cycles (LD 12:12), flies carrying perT in a genotypic condition leading to free-running periods that are 8 hr faster than normal nevertheless entrained, by phase-shifting that large number of hours each day; the evening peak of locomotor activity was, however, many hours earlier than normal. The use of a newly developed device for monitoring Drosophila eclosion automatically showed that perT exhibits a very marginal emergence rhythm at 25 degrees C, but periodicity of ca. 17-18 hr at 19 degrees. Staining of the per-encoded protein (PER) in sections of perT versus normal pharate adults revealed for the first time that the immunohistochemically detected signal cycles in its intensity in wild-type, in a manner that is similar to the PER rhythm previously demonstrated in adults. The staining cycle in pharate adults expressing perT differed from that of wild-type. Temperature compensation of the adult activity rhythm of perT was found to be faulty, in that periods became appreciably shorter as the flies were heated. However, the mutant exhibited a normal degree of period lengthening when its locomotor activity was monitored in the presence of heavy water. The perT mutation interacted with the long-period Andante allele of the dusky locus in a manner that was anomalous (in comparison to dyAnd interactions with per+ or another short-period per mutation). This and other unique features of perT are discussed from the standpoint of the new mutation's heuristic value, including that which may stimulate a deeper understanding of the period gene's action at the molecular level.

Activity Cycles↗

Educational interventions and the use of parenteral nutrition.

The Georgetown Total Parenteral Nutrition Forum generated consensus statements about the need for nutrition support. The main concern is that the excessive use of parenteral nutritional is both dangerous and expensive. We performed confidential audits using these criteria before and after educational interventions. The incidence of doubtful usage decreased from 29% (8/28) in mid-1991 to 3% (1/30) in mid-1992 (Fisher Exact Probability = 0.01): A post-audit review one year later in mid-1993 revealed an incidence of doubtful usage of 0% (0/19). It is concluded that the consensus document from the Georgetown Parenteral Nutrition Forum is a useful tool for deriving usage guidelines, educating staff and performing criterion audits. In this way, it is possible to generate cost savings and improve the quality of care.

Australia↗

Signet-ring cell variant of invasive lobular carcinoma of the breast. A clinicopathologic study of 11 cases.

In signet-ring cell carcinoma of the breast, which was recognized in 1976 as a distinct clinicopathologic variant of lobular carcinoma, more than 20% of the malignant cells appear as signet rings formed by mucin-positive intracytoplasmic vacuoles. Several recent studies have demonstrated that the neoplasm behaves aggressively and is associated with a poor prognosis. However, the literature lacks information concerning steroid hormone receptor assays and DNA ploidy profiles, especially regarding how these tests affect a patient's prognosis. During a 5-year period (1985 to 1990), 11 (8.7%) of 126 cases of invasive lobular carcinoma met the criteria for signet-ring cell carcinoma. Ten of 11 cases were positive for estrogen and progesterone receptors; six cases showed type I and five showed type III DNA histograms. The high incidence of positive hormone receptors is significant: patients with receptor positive tumors, even those with type III DNA histograms, who were treated with tamoxifen citrate therapy after surgery had a significant increase in disease-free survival (30 months). Both the pathologist and the clinician should be aware of the prognostic influence of hormone receptor studies in the management of signet-ring cell carcinoma of the breast.

Adult↗

Transfer of dye among salivary gland cells is not affected by genetic variations of the period clock gene in Drosophila melanogaster.

Larval salivary gland cells of Drosophila melanogaster were injected with a fluorescent dye to assess strengths of intercellular communication among such cells, as influenced by mutations at the period locus and by a per transgene. This clock gene had been reported to increase the extent of dye transfer when mutated such that it shortens the period of biological rhythms; the previous study also showed that a per-null mutant decreased the strength of transfer among salivary gland cells. Our re-examination of this feature of larval physiology--in observer-blind analyses, using the pers and per0 mutants as well as two per-normal strains--revealed no appreciable differences in extents of dye transfer among these four genotypes. These results are discussed in the context of emerging findings which suggest that the period gene's product controls pacemaker functioning as an intracellularly acting entity.

Animals↗

Antibiotic prophylaxis in cardiac operations.

This clinical trial, which was composed of 1,031 adults undergoing cardiac operations, compared the efficacy of a single dose of 1 g of ceftriaxone with a 48-our regimen consisting of flucloxacillin and gentamicin. There was no significant difference (p = 0.89) in the overall incidence of major infections: 30 of 515 patients (5.8%; 95% confidence interval, 5.4% to 6.2%) taking ceftriaxone and 29 of 516 patients (5.6%; 95% confidence interval, 5.2% to 6.0%) taking flucloxacillin and gentamicin. Subgroup analyses, with a lower statistical power, failed to show a significant difference between patients who received ceftriaxone and those who received flucloxacillin/gentamicin: major sternal wound infections arose in 2.7% of the patients taking ceftriaxone versus 1.6% in those on the 48-hour regimen (p = 0.20) and major limb wound infections arose in 4.2% and 5.4%, respectively (p = 0.44). Single-dose prophylaxis was associated with fewer intravenous administrations (864 doses versus 9,570 doses) and cost less (A$17,248 versus A$78,510). Although the regimen that included gentamicin was associated with the greatest biochemical impairment of renal function, the overall toxicity for both groups was low. We conclude that a single dose of ceftriaxone provided cost-efficient prophylaxis for adults undergoing cardiac operations when compared with a 48-hour regimen of gentamicin and flucloxacillin. The general principle revealed by our data is that the short-term administration of an appropriate antibiotic regimen represents optimal prophylaxis for patients undergoing cardiac procedures.

Adolescent↗

Enzyme immunoassay based survey of precipitation and surface water for the presence of atrazine, metolachlor and 2,4-D.

The suitability of enzyme immunoassay (EIA) as a method of analysis for 2,4-D, atrazine and metolachlor contamination in water samples was determined by comparing EIA results to gas chromatography (GC) results. The comparison of EIA and GC results yielded a correlation coefficient of 0.92, 0.98 and 0.92 for 2,4-D, atrazine and metolachlor, respectively. EIA was used to monitor seasonal trends in the concentrations of 2,4-D, atrazine and metolachlor in surface water and precipitation throughout the province of Ontario, Canada. 2,4-D was detected in excess of 4 micrograms/L in urban creeks during the period of application. Concentrations of 43 and 9 micrograms/L of atrazine and metolachlor, respectively, were detected during the field application period in surface water samples from the Kintore Creek watershed. The levels of 2,4-D, atrazine and metolachlor detected exceeded the Canadian Water Quality Guidelines for the protection of fresh water aquatic life. Concentrations as high as 445 and 322 ng/L of atrazine and metolachlor, respectively, were detected in precipitation samples collected from 17 locations in Ontario during the herbicide application period. The EIA was shown to be qualitatively and quantitatively comparable to GC analysis.

2,4-Dichlorophenoxyacetic Acid↗

The influence of age on endocrine responses to ultraendurance stress.

BACKGROUND: Aging produces significant changes in the human endocrine system. This study was designed to determine if elderly and younger individuals differ in various endocrine measures before and after ultraendurance stress. METHODS: Sixteen young and 19 older subjects competing in a world championship triathlon had blood samples acquired for 13 hormones before, immediately after the event, and 18 hours into recovery. RESULTS: Following the triathlon, almost every hormone level increased. Significantly higher basal circulating levels of dihydroepiandrosterone sulfate (DHEA-S) and thyroid stimulating hormone (TSH) were found in 20-year-old individuals, whereas higher levels of norepinephrine (NEPI) and sex hormone binding globulin (SHBG) were found in the 50- to 74-year-old group. Older subjects had lower postexercise levels of EPI, DHEA-S, GH, and PRL and higher postexercise levels of estradiol than younger individuals. Similarity in pre- and postrace weights as well as Hgb and Hct levels suggested that dehydration, while present, did not significantly contribute to the endocrine changes. CONCLUSIONS: Ultraendurance stress produced dramatic increases in all but one of the hormones evaluated. Whether frequent exercise can alter the endocrine changes that occur with aging cannot be answered by this study. It is clear, however, that when comparisons are made with young active individuals, frequent exercise does not eliminate the differences in basal concentrations of TSH, DHEA-S, SHBG, and NEPI or exercise-induced release of estradiol, GH, and PRL that occur with aging.

Adult↗

The cost-efficiency of incentive spirometry after abdominal surgery.

This report gives the results of a cost-efficiency analysis of a prospective longitudinal study evaluating two forms of prophylaxis against postoperative pulmonary complications in 876 patients undergoing abdominal surgery. It cost $12.19 per patient for conventional chest physiotherapy, and equivalent costs accrue when incentive spirometers are recycled and used on average 2.3 times (in the Royal Perth Hospital, incentive spirometers are recycled an average of 4.7 times). Maximum cost-containment can be achieved by carefully selecting patients for physical chest care and then instigating a programme of perioperative chest care utilizing recycled incentive spirometers. This approach does not compromise the clinical benefits of prophylactic chest care and allows physiotherapy resources to be directed toward patients with established pulmonary problems.

Abdomen↗

Behavior in light-dark cycles of Drosophila mutants that are arrhythmic, blind, or both.

Certain of the rhythm mutations in Drosophila melanogaster lead to arrhythmic locomotor activity (and aperiodic eclosion) in constant conditions. In light-dark (LD) cycles, however, such mutants exhibit clear fluctuations between high levels of activity when the lights are on and much lower ones when they are off. Our data, in contrast to some previous conclusions, strongly suggest that period0 (per0) adults are, in LD conditions, merely being "forced" into exhibiting periodic behavior. These experiments involved application of 8-, 12-, 16-, and 24-hr LD cycles, in which the arrhythmic mutant could have any of these periodicities imposed upon it, whereas wild-type flies tended to exhibit periods of about 24 hr in cycling conditions whose T values were > 8 hr different from 24. In phase-shift experiments, it was found that Drosophila expressing genotypes associated with rhythmicity achieved a 5-hr advance over a 2-day period following an advanced lights-on; per0 adults altered the phase of their locomotor peaks more rapidly. Against a background of the fact that eyeless or blind flies exhibit normal entrainment, it was hypothesized that double-mutant flies--carrying such visual mutations and per0 as well--should not synchronize to LD cycles, if the forced rhythms seen in the latter single-mutant type are mediated solely by light input through the external photoreceptors. Since an appreciable proportion of the double mutants did synchronize (to LD 12:12), it is thus suggested that the visual cues involved in forcing rhythmicity could be input through the same extraocular photoreceptors that, in general, subserve the fly's rhythm system.

Activity Cycles↗

Circadian oscillations in period gene mRNA levels are transcriptionally regulated.

The period (per) gene is involved in regulating circadian rhythms in Drosophila melanogaster. The per gene is expressed in a circadian manner, where fluctuations in per mRNA abundance are influenced by its own translation product, which also cycles in abundance. Since per gene expression is necessary for circadian rhythmicity, we sought to determine how certain features of this feedback loop operate. The results of this study reveal that fluctuations in per mRNA are primarily controlled by fluctuations in per gene transcription, that per mRNA has a relatively short half-life, and that sequences sufficient to drive per mRNA cycling are present in 1.3 kilobases of 5' flanking sequences. These and other results indicate that the per feedback loop has all of the basic properties necessary to be a component of a circadian oscillator.

Animals↗

Identification of novel RNA-binding proteins that interact in the coding region of protein D sense RNA in vitro.

Ultraviolet (UV)-cross-linking and sodium dodecyl sulfate(SDS) polyacrylamide gel electrophoretic (PAGE) analysis were used to identify proteins of nuclear and cytosolic (S100) origin that specifically bind to an in vitro transcribed mRNA sequence for protein D. The coding region of the protein D cDNA was subcloned, in vitro transcribed to [32P]RNA, and incubated with nuclear and cytosolic extracts of enzymatically dispersed epididymal cells. As revealed by UV-cross-linking and SDS-PAGE analysis, two proteins exhibiting a molecular weight mass of approximately 2.5 and approximately 35 Kd that specifically recognize and bind to the in vitro transcribed mRNA sequence for protein D. Our findings suggest that the regulation of protein D gene expression in the rat epididymis may involve novel RNA-binding proteins.

Animals↗

A casemix of patients undergoing abdominal surgery.

OBJECTIVE: To construct a casemix for patients undergoing abdominal surgery. DESIGN: A prospective longitudinal study. Wound infection was chosen as the target adverse event. A cluster analysis identified seven risk factors, which were then incorporated into a Boolean cluster (the casemix). SETTING: Royal Perth Hospital. PATIENTS: 1238 adults. MAIN OUTCOME MEASURES: Wound infection, recurrent intraperitoneal sepsis, hospital stay, admission to the intensive care unit, and death. RESULTS: Measures of the severity of illness and the extent of co-morbidity were more important in determining the risk of a poor outcome than was the identity of the diseased organ. CONCLUSIONS: Estimates of severity of illness and extent of co-morbidity should be included in any casemix based system for patients undergoing abdominal surgery.

Abdomen↗

Protein D is differentially expressed and regulated in the rat epididymis.

We report the use of a sensitive and specific enyzme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) to study the expression of protein D, a major androgen-regulated sperm-binding glycoprotein at the protein and mRNA level in different anatomical regions of the rat epididymis. The concentration of protein D in the caput, corpus and cauda region of the epididymis was 10.2 +/- 0.67, 7.3 +/- 0.61 and 22.8 +/- 1.34 ng/micrograms total protein, respectively. The total RNA extracted from the caput, corpus and cauda regions of the rat epididymis was amplified by PCR with oligonucleotide primers specific for the 5' and 3' portion of protein D cDNA. Compared to the caput and cauda region, a significant reduction (greater than 82 +/- 3%) in the expression of protein D mRNA levels was observed for corpus epididymal RNA. This data demonstrates regional differences in the concentration of protein D and suggests that protein D expression may be regulated at the level of mRNA within the corpus epididymidis.

Animals↗

Behavioral and molecular analyses suggest that circadian output is disrupted by disconnected mutants in D. melanogaster.

Mutations in the disconnected (disco) gene act to disrupt neural cell patterning in the Drosophila visual system. These mutations also affect adult locomotor activity rhythms, as disco flies are arrhythmic under conditions of constant darkness (DD). To determine the state of the circadian pacemaker in disco mutants, we constructed with pers double mutants (a short period allele of the period gene) and assayed their behavioral rhythms in light-dark cycles (LD), and their biochemical rhythms of period gene expression under both LD and DD conditions. The results demonstrate that disco flies are rhythmic, indicating that they have an active circadian pacemaker that can be entrained by light. They also suggest that disco mutants block or interfere with elements of the circadian system located between the central pacemaker and its outputs that mediate overt rhythms.

Activity Cycles↗

Evolution of the threonine-glycine repeat region of the period gene in the melanogaster species subgroup of Drosophila.

The Threonine-Glycine (Thr-Gly) region of the period gene (per) in Drosophila was compared in the eight species of the D. melanogaster subgroup. This region can be divided into a diverged variable-length segment which is flanked by more conserved sequences. The number of amino acids encoded in the variable-length region ranges from 40 in D. teissieri to 69 in D. mauritiana. This is similar to the range found within natural populations of D. melanogaster. It was possible to derive a Thr-Gly "allele" of one species from that of another by invoking hypothetical Thr-Gly intermediates. A phylogeny based on the more conserved flanking sequences was produced. The results highlighted some of the problems which are encountered when highly polymorphic genes are used to infer phylogenies of closely related species.

Amino Acid Sequence↗

Artificial neural network classification of Drosophila courtship song mutants.

Courtship songs produced by Drosophila males--wild-type, plus the cacophony and dissonance behavioral mutants--were examined with the aid of newly developed strategies for adaptive acoustic analysis and classification. This system used several techniques involving artificial neural networks (a.k.a. parallel distributed processing), including learned vector quantization of signals and non-linear adaption (back-propagation) of data analysis. "Pulse" song from several individual wild-type and mutant males were first vector-quantized according to their frequency spectra. The accumulated quantized data of this kind, for a given song, were then used to "teach" or adapt a multiple-layered feedforward artificial neural network, which classified that song according to its original genotype. Results are presented on the performance of the final adapted system when faced with novel test data and on acoustic features the system decides upon for predicting the song-mutant genotype in question. The potential applications and extensions of this new system are discussed, including how it could be used to screen for courtship mutants, search novel behavior patterns or cause-and-effect relationships associated with reproduction, compress these kinds of data for digital storage, and analyze Drosophila behavior beyond the case of courtship song.

Algorithms↗