Search PubMed⌕ Search

Biomedical subjects

J C Hall

Publications and source records attributed to J C Hall.

At least 37 records · Page 2Linked to original sources

A meta-analysis of peritoneal lavage for acute pancreatitis.

BACKGROUND AND AIM: It has been postulated that continuous irrigation of the peritoneal cavity with crystalloid solutions in patients with acute pancreatitis can improve mortality and morbidity. The aim of the study is to perform a meta-analysis of available randomized prospective clinical trials, to evaluate whether lavage influences mortality and morbidity in patients with acute pancreatitis. METHODS: We performed a computer search of Medline for all available literature on the use of lavage in patients with acute pancreatitis. A meta-analysis was conducted on eight randomized, prospective, clinical trials (a total of 333 patients) evaluating continuous peritoneal lavage in patients with acute pancreatitis. The end-points were mortality and morbidity (i.e. pancreatic necrosis, peripancreatic fluid collections, intra-abdominal abscess formation, septicemia, organ system failure). RESULTS: Continuous lavage did not improve either mortality (weighted mean difference 1.6%, 95% CI -6.7% to 9.9%, not significant (n.s.)) or morbidity (weighted mean difference 6.2%, 95% CI -3.2% to 15.6%, n.s.) when compared with control patients. CONCLUSIONS: The use of continuous peritoneal lavage in patients with acute pancreatitis has not been found to be associated with any significant improvement in mortality or morbidity.

Acute Disease↗

The prevention of wound infection in patients undergoing colorectal surgery.

Colorectal operations are, at best, clean-contaminated procedures, and at times there is gross contamination of both the peritoneal cavity and the surfaces of the surgical wound. In addition, the diseases of the large bowel that require surgery tend to afflict elderly patients. Collectively, the combination of an unclean environment, major surgery and debilitated patients creates a situation that is associated with a very high incidence of wound infection. This review documents the considerable support from clinical trials and meta-analyses that exists for the prophylactic use of a single dose of a suitable parenteral antimicrobial agent. In addition, although the evidence is less clear cut, it does not appear that the use of mechanical bowel preparations reduces the incidence of wound infections after colorectal surgery.

Age Factors↗

The nonA gene in Drosophila conveys species-specific behavioral characteristics.

The molecular basis of species-specific differences in courtship behavior, a critical factor in preserving species boundaries, is poorly understood. Genetic analysis of all but the most closely related species is usually impossible, given the inviability of hybrids. We have therefore applied interspecific transformation of a single candidate behavioral locus, no-on-transient A (nonA), between Drosophila virilis and D. melanogaster, to investigate whether nonA, like the period gene, might encode species-specific behavioral information. Mutations in nonA can disrupt both visual behavior and the courtship song in D. melanogaster. The lovesong of nonA(diss) mutant males superficially resembles that of D. virilis, a species that diverged from D. melanogaster 40-60 mya. Transformation of the cloned D. virilis nonA gene into D. melanogaster hosts carrying a synthetic deletion of the nonA locus restored normal visual function (the phenotype most sensitive to nonA mutation). However, the courtship song of transformant males showed several features characteristic of the corresponding D. virilis signal, indicating that nonA can act as a reservoir for species-specific information. This candidate gene approach, together with interspecific transformation, can therefore provide a direct avenue to explore potential speciation genes in genetically and molecularly tractable organisms such as Drosophila.

Animals↗

Molecular genetic dissection of the sex-specific and vital functions of the Drosophila melanogaster sex determination gene fruitless.

A multibranched hierarchy of regulatory genes controls all aspects of somatic sexual development in Drosophila melanogaster. One branch of this hierarchy is headed by the fruitless (fru) gene and functions in the central nervous system, where it is necessary for male courtship behavior as well as the differentiation of a male-specific abdominal structure, the muscle of Lawrence (MOL). A preliminary investigation of several of the mutations described here showed that the fru gene also has a sex-nonspecific vital function. The fru gene produces a complex set of transcripts through the use of four promoters and alternative splicing. Only the primary transcripts produced from the most distal (P1) promoter are sex-specifically spliced under direction of the sex-determination hierarchy. We have analyzed eight new fru mutations, created by X-ray mutagenesis and P-element excision, to try to gain insight into the relationship of specific transcript classes to specific fru functions. Males that lack the P1-derived fru transcripts show a complete absence of sexual behavior, but no other defects besides the loss of the MOL. Both males and females that have reduced levels of transcripts from the P3 promoter develop into adults but frequently die after failing to eclose. Analysis of the morphology and behavior of adult escapers showed that P3-encoded functions are required for the proper differentiation and eversion of imaginal discs. Furthermore, the reduction in the size of the neuromuscular junctions on abdominal muscles in these animals suggests that one of fru's sex-nonspecific functions involves general aspects of neuronal differentiation. In mutants that lack all fru transcripts as well as a small number of adjacent genes, animals die at an early pupal stage, indicating that fru's function is required only during late development. Thus, fru functions both in the sex-determination regulatory hierarchy to control male sexual behavior through sex-specific transcripts and sex-nonspecifically to control the development of imaginal discs and motorneuronal synapses during adult development through sex-nonspecific transcript classes.

Alleles↗

Pretreatment with glycine reduces the severity of warm intestinal ischemic-reperfusion injury in the rat.

Free jejunal flaps may experience adverse effects immediately after revascularization because of ischemic-reperfusion injury. In this study the authors evaluated the ability of glycine to protect the small intestine against the effects of a warm ischemic-reperfusion injury. Male Wistar rats (N = 30) were randomized to either a baseline group (no intervention), a control group (local arterial infusion with normal saline), or a glycine group (local arterial infusion with 20% glycine). Pretreatment with 20% glycine increased significantly (p < 0.05) mucosal protein and deoxyribonucleic acid content, reduced intestinal myeloperoxidase activity, and maintained mucosal glutaminase activity. These results indicate that some of the indicators of ischemic-reperfusion injury are improved by pretreatment with a 20% glycine solution.

Animals↗

Decompression, fusion, and instrumentation surgery for complex lumbar spinal stenosis.

Between 1990 and 1993, 54 consecutive patients were treated with decompression, fusion and instrumentation surgery for complex lumbar spinal stenosis. The mean age of the patients was 60 years. The average followup was 39 months. Clinically, there was one deep wound infection, and three mechanical failures. There were two staged operations. There were three revision surgeries performed for mechanical reasons. Of the 47 patients who completed the questionnaire, 96% of patients were very satisfied or somewhat satisfied with the operation, 98% were satisfied with relief of pain, 94% were satisfied with their ability to walk, 89% were satisfied with their strength, and 94% were satisfied with balance. Survivorship analysis (failure endpoint was revision surgery) revealed that at the end of 4 years, the patient had a 92% chance of not undergoing revision surgery for any reason (mechanical and infectious), and a 94% chance of not undergoing revision surgery for mechanical reasons. Lumbar decompression, fusion, and instrumentation surgery seems to be efficacious in patients with complex lumbar spinal stenosis (associated previous lumbar spine operations with evidence of radiographic instability, radiographic evidence of junctional stenosis after surgery, radiographic evidence of instability, degenerative spondylolisthesis greater than Grade I with instability, if present, and degenerative scoliosis with a curve greater than 20 degrees).

Decompression, Surgical↗

The effects of competition and competitiveness on cardiovascular activity.

Cardiovascular activity was measured at resting baseline and in response to a car racing game, undertaken in competition or in cooperation with an experimenter, or individually. Competitiveness and win and goal orientations were assessed by questionnaire. Competition provoked increases in blood pressure and heart rate, and a significant shortening of the preejection period, an index of enhanced beta-adrenergic influences on the heart. The cooperation task was largely without effect, and although the solo task affected cardiovascular activity, it did so to a lesser extent and much less consistently than did the competition task. The three task conditions, then, were largely distinguishable by their capacity to activate beta-adrenergic processes. Participants high in competitiveness and desire to win showed higher blood pressure reactions and greater shortening of the preejection period to competition than those low in these characteristics.

Adult↗

Two novel doubletime mutants alter circadian properties and eliminate the delay between RNA and protein in Drosophila.

Phosphorylation is an important feature of pacemaker organization in Drosophila. Genetic and biochemical evidence suggests involvement of the casein kinase I homolog doubletime (dbt) in the Drosophila circadian pacemaker. We have characterized two novel dbt mutants. Both cause a lengthening of behavioral period and profoundly alter period (per) and timeless (tim) transcript and protein profiles. The PER profile shows a major difference from the wild-type program only during the morning hours, consistent with a prominent role for DBT during the PER monomer degradation phase. The transcript profiles are delayed, but there is little effect on the protein accumulation profiles, resulting in the elimination of the characteristic lag between the mRNA and protein profiles. These results and others indicate that light and post-transcriptional regulation play major roles in defining the temporal properties of the protein curves and suggest that this lag is unnecessary for the feedback regulation of per and tim protein on per and tim transcription.

Alleles↗

Neuroanatomy of cells expressing clock genes in Drosophila: transgenic manipulation of the period and timeless genes to mark the perikarya of circadian pacemaker neurons and their projections.

Subsets of brain neurons expressing the clock genes period (per) and timeless (tim) are involved in the generation of circadian behavioral rhythms. However, current knowledge of projection patterns of these neurons is limited to those immunoreactive to an antibody against a crustacean neuropeptide. The GAL4-expression system was utilized to visualize neuronal processes from all per and tim-expressing neurons in the central nervous system. Each of two types of GAL4-driver fusion genes, per-gal4 or tim-gal4, was combined in transgenic flies with marker genes-lacZ, and sequences encoding green fluorescent protein or TAU protein-under the control of the GAL4-responsive element UAS. This allowed visualization of the cytoplasm of GAL4-expressing cells. Thus, neurites of clock neurons in the adult brain as well as those of larvae and pupae were revealed. Among the anatomical patterns revealed by per-gal4- or tim-gal4-driven marker expression were a previously unknown, dorsally located neuronal cluster, along with the projections of these cells and of other dorsal neurons characterized in earlier studies only by the location of their perikarya. The similarity of projections from PER- or TIM-containing neurons during development to those in the adult implies that these features of mature clock neurons are established by the larval stages. Neurons that have never been identified as PER- or TIM-immunoreactive were also visualized in this assay system, indicating promoter activity of the clock genes in these cells and suggesting that their products cannot accumulate to detectable levels in certain neurons.

Animals↗

Spatial, temporal, and sexually dimorphic expression patterns of the fruitless gene in the Drosophila central nervous system.

The fruitless (fru) gene of Drosophila produces both sex-specifically and non-sex-specifically spliced transcripts. Male-specific fru products are believed to regulate male courtship. To further an understanding of this gene's behavioral role, we examined the central nervous system (CNS) for temporal, spatial, and sexually dimorphic expression patterns of sex-specific fru products by in situ hybridization and immunohistochemistry. For the latter, antibodies were designed to detect only male-specific forms of the protein (FRU(M)) or amino acid sequences that are in common among all translated products (FRU(COM)). Sex-specific mRNAs and male-specific proteins were first observed in mature larvae and peaked in their apparent abundances during the first half of the pupal period. At later stages and in adults, faint mRNA signals were seen in only a few neural clusters; in contrast, relatively strong FRU(M) signals persisted into adulthood. Twenty neuronal groups composed of 1700 fru-expressing neurons were identified in the midpupal CNS. These groups overlap most of the neural sites known to be involved in male courtship. Anti-FRU(COM) led to widespread labeling of neural and nonneural tissues in both sexes, but in the female CNS, only in developing ganglia in a pattern different from that of the male's FRU(M) cells. Expression of sex-specific fru mRNAs in the CNS of males analyzed from the earliest pupal stages indicated that sex-specific alternative splicing is not the exclusive mechanism regulating expression of fruitless transcripts.

Animals↗

Disruption of synaptic transmission or clock-gene-product oscillations in circadian pacemaker cells of Drosophila cause abnormal behavioral rhythms.

To study the function of clock-gene-expressing neurons, the tetanus-toxin light chain (TeTxLC), which blocks chemical synaptic transmission, was expressed under the control of promoters of the clock genes period (per) and timeless (tim), each fused to GAL4-encoding sequences. Although TeTxLC did not affect cycling of a clock-gene product at the gross level, it disrupted the rhythmic behavior of adult Drosophila. In constant darkness, the proportion of rhythmic flies was reduced in flies expressing active TeTxLC compared to controls, including those expressing inactive toxin. The behavior of TeTxLC-expressing flies was less synchronized to light:dark cycles than that of controls. To determine which neurons are responsible for these effects on behavior, the toxin was also expressed in restricted subsets of per/tim-expressing, laterally located pacemaker neurons by expressing TeTxLC under the control of a driver in which GAL4-encoding sequences are fused to the promoter of the pigment dispersing factor (pdf) gene. pdf-gal4-driven TeTxLC expression had relatively little effect on behavioral rhythms, implying that per/tim neurons other than pdf-expressing lateral neurons participate in the generation of rhythmic behavior. In another set of experiments, period gene products were expressed under the control of per-gal4 or tim-gal4. This resulted in an increased level of PER protein in many brain cells and reduction of bioluminescence cycling reported by a per-luciferase transgene, especially in the case of per expression affected by tim-gal4. This indicates a disruption of the transcriptional feedback loop that is a part of the oscillatory mechanism underlying Drosophila's circadian rhythms. Consistent with this molecular defect, the proportion of rhythmic individuals in constant darkness was subnormal in flies expressing PER under the control of tim-gal4, and their behavior in light:dark cycles was abnormal.

Animals↗

Glutamine-enriched parenteral nutrition regulates the activity and expression of intestinal glutaminase.

The aim of this study was to examine the effect of glutamine-enriched parenteral nutrition on the activity, expression and distribution of glutaminase mRNA within the small intestine of rats. Central venous lines were inserted into 30 male Wistar rats before they were fed for 6 days with either: (a) conventional parenteral nutrition, (b) 2.5% glutamine-enriched parenteral nutrition, or (c) rat food ad libitum. Jejunal glutaminase activity per milligram of dry matter was greatest in the animals fed rat food (0.94+/-0.29), intermediate in the glutamine supplemented rats (0.69+/-0.19) and least in the rats nourished with conventional parenteral nutrition (0.55+/-0.24) (P<0.05). The data for glutaminase expression exhibited a similar trend (P<0.05). In situ hybridisation analysis confirmed that glutaminase is expressed in the mucosa along the whole length of the small intestine. It was concluded that provision of glutamine alters the activity and expression of glutaminase in intestinal enterocytes. The results suggest that glutamine increases glutaminase activity by promoting the accumulation of intestinal glutaminase mRNA.

Animals↗

Differential regulation of circadian pacemaker output by separate clock genes in Drosophila.

Regulation of the Drosophila pigment-dispersing factor (pdf) gene products was analyzed in wild-type and clock mutants. Mutations in the transcription factors CLOCK and CYCLE severely diminish pdf RNA and neuropeptide (PDF) levels in a single cluster of clock-gene-expressing brain cells, called small ventrolateral neurons (s-LN(v)s). This clock-gene regulation of specific cells does not operate through an E-box found within pdf regulatory sequences. PDF immunoreactivity exhibits daily cycling, but only within terminals of axons projecting from the s-LN(v)s. This posttranslational rhythm is eliminated by period or timeless null mutations, which do not affect PDF staining in cell bodies or pdf mRNA levels. Therefore, within these chronobiologically important neurons, separate elements of the central pacemaking machinery regulate pdf or its product in novel and different ways. Coupled with contemporary results showing a pdf-null mutant to be severely defective in its behavioral rhythmicity, the present results reveal PDF as an important circadian mediator whose expression and function are downstream of the clockworks.

Animals↗

Transplanted Drosophila excretory tubules maintain circadian clock cycling out of phase with the host.

Circadian rhythms in behaviors and physiological processes are driven by conserved molecular mechanisms involving the rhythmic expression of clock genes in the brains of animals [1]. The persistence of similar molecular rhythms in peripheral tissues in vitro [2] [3] suggests that these tissues contain self-sustained circadian clocks that may be linked to rhythmic physiological functions. It is not known how brain and peripheral clocks are organized into a synchronized timing system; however, it has been assumed that peripheral clocks submit to a master clock in the brain. To address this matter we examined the expression of two clock genes, period (per) and timeless (tim), in host and transplanted abdominal organs of Drosophila. We found that excretory organs in tissue culture display free-running, light-sensitive oscillations in per and tim gene activity indicating that they house self-sustained circadian clocks. To test for humoral factors, we monitored cycling of the TIM protein in excretory tubules transplanted into host flies entrained to an opposite light-dark cycle. We show that the clock protein in the donor tubules cycled out of phase with that in the host tubules, indicating that different organs may cycle independently, despite sharing the same hormonal milieu. We suggest that one way to achieve circadian coordination of physiological sub-systems in higher animals may be through the direct entrainment of light-sensitive clocks by environmental signals.

Animals↗

Drosophila CRY is a deep brain circadian photoreceptor.

cry (cryptochrome) is an important clock gene, and recent data indicate that it encodes a critical circadian photoreceptor in Drosophila. A mutant allele, cry(b), inhibits circadian photoresponses. Restricting CRY expression to specific fly tissues shows that CRY expression is needed in a cell-autonomous fashion for oscillators present in different locations. CRY overexpression in brain pacemaker cells increases behavioral photosensitivity, and this restricted CRY expression also rescues all circadian defects of cry(b) behavior. As wild-type pacemaker neurons express CRY, the results indicate that they make a striking contribution to all aspects of behavioral circadian rhythms and are directly light responsive. These brain neurons therefore contain an identified deep brain photoreceptor, as well as the other circadian elements: a central pace-maker and a behavioral output system.

Animals↗

Cryptochromes: sensory reception, transduction, and clock functions subserving circadian systems.

Cryptochromes (CRYs) are blue-light-absorbing proteins involved in a variety of biological phenomena. In animals, CRYs exhibit a certain versatility with regard to these organisms' circadian rhythms, as has been revealed by the effects of mutations and molecular manipulations. The rhythm system of Drosophila uses one gene's worth of CRY protein to transmit light into a circadian clock within the brain, which controls the fly's sleep-wake cycles. In fact, the relevant pacemaking neurons are themselves circadian photoreceptive structures. In peripheral tissues and others located posterior to the brain, Drosophila CRY may be a photoreceptive molecule and also part of the pacemaker mechanism. Mice have two CRY-encoding genes. They are expressed in many tissues, including the retina and a clock structure within the brain. In the former location, mouse CRY may play a circadian-photoreceptive role, along with that mediated by rhodopsins found elsewhere in the retina. In the latter tissue, the hypothalamic suprachiasmatic nucleus, mouse CRYs are closely connected to the multimolecule murine clock mechanism.

Animals↗