Genetics and molecular biology of rhythms.
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Animals↗
Biomedical subjects
J C Hall
Publications and source records attributed to J C Hall.
Circadian and ultradian rhythms in period mutants of Drosophila melanogaster.
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Animals↗
Cryptococcal cellulitis with multiple sites of involvement.
Cryptococcal cellulitis is an uncommon cutaneous manifestation of generalized cryptococcal disease. We describe the only reported incidence with multiple sites of cutaneous involvement. In an immunosuppressed patient an apparent cellulitis, even with multiple sites of involvement, that does not respond to appropriate antibiotics should alert one to the possible diagnosis of cryptococcal cellulitis.
Adult↗
Molecular mapping of point mutations in the period gene that stop or speed up biological clocks in Drosophila melanogaster.
The pero1 and the pers mutations in Drosophila melanogaster, which seem to eliminate or speed up, respectively, the clocks underlying biological rhythmicity, were mapped to single nucleotides. Chimeric DNA fragments consisting of well-defined wild-type plus mutant DNA subsegments were constructed, introduced into flies by germ-line transformation, and assayed for biological activity. These experiments localized both pero1 and pers to a 1.7-kilobase DNA fragment that is mostly coding DNA. Sequencing of this subsegment from each mutant showed that pero1 is completely accounted for by a nonsense mutation in the third coding exon of a 4.5-kilobase RNA transcribed from this locus. The pers mutation is also a single nucleotide substitution, in the fourth coding exon, which results in a serine-to-asparagine substitution in the per gene protein product. The functional significance of these changes is discussed with reference to the phenotypes of the two mutations.
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↗
Behavioral and cytogenetic analysis of the cacophony courtship song mutant and interacting genetic variants in Drosophila melanogaster.
The courtship song of a Drosophila melanogaster male consists of tone pulses interspersed with humming sounds. An X chromosomal mutation, cacophony (cac), causes the production of polycyclic pulses readily distinguishable from those in wild type, which are mono- or bicyclic. Yet, courtship hums and flight wing beats are normal in this mutant, suggesting a specific role of the cac gene in the neural program underlying one particular feature of the fly's wing vibrations. A precise cytogenetic localization of cac is presented; this was obtained by uncovering the song abnormality with deletions that are missing all or the distal part of region 11A; the flies tested were diplo-X adults that had been turned into males by the transformer mutation. Duplications including distal 11A covered cac. The possibility of behavioral specificity for cac's effects was examined by screening a variety of sexual and nonsexual behaviors; these experiments included tests of flies in which the mutation was uncovered by a small deletion. We conclude that cac causes only a limited array of well-defined defects: longer and louder tone pulses in the song and depressed locomotor activity. Further complementation tests involving cac and other closely linked genetic variants--the night-blind-A (nbA) visual mutation, l(1)L13 lethal mutations, and a series of X chromosomal breakpoints--suggested complex interactions among these factors: the breakpoints uncover all three types of mutations; cac and nbA appear to be alleles of l(1)L13, whereas the two behavioral mutations complement each other.
Animals↗
Changes in rat sperm membrane glycosidase activities and carbohydrate and protein contents associated with epididymal transit.
Rat spermatozoa were recovered from the caput, corpus, and cauda epididymides and assayed for glycosidase activity, total nonamino (neutral) carbohydrate, and protein content. The activities of beta-glucosidase, beta-galactosidase, beta-N-acetylglucosaminidase, and beta-N-acetylgalactosaminidase were fluorometrically assayed in spermatozoa and membrane-enriched fractions. Except for beta-glucosidase, the activities of the glycosidases based on protein content were greatest in whole sperm and membrane-enriched fractions obtained from the cauda epididymides. Based on sperm concentration, however, glycosidase activities increased proceeding from the caput to the corpus epididymides, then declined from the corpus to the cauda epididymides. Analyses of nonamino carbohydrate and protein content based on sperm number indicated regional trends similar to those of glycosidase activity. Total nonamino carbohydrate and protein content were highest in corpus sperm, and lowest in cauda sperm. These data indicate major quantitative changes in cell surface carbohydrate as spermatozoa traverse the epididymis. A positive correlation for the membrane-enriched fraction between increasing glycosidase activity and decreasing carbohydrate and protein content suggests that glycosidases may play a significant role in modifying the spermatozoon surface during epididymal transit and maturation.
Animals↗
Chronic cutaneous herpes simplex and X-linked hypogammaglobulinemia.
Chronic mucocutaneous or cutaneous herpes simplex is a rare syndrome associated with immunosuppression. We report the first case associated with X-linked hypogammaglobulinemia and illustrate the effectiveness of oral acyclovir in this potentially serious illness.
Acyclovir↗
The cardiovascular actions of dopexamine hydrochloride, an agonist at dopamine receptors and beta 2-adrenoceptors in the dog.
The receptor pharmacology of the cardiovascular effects of dopexamine hydrochloride in the anaesthetized dog (given by i.v. infusion of 3 X 10(-9)-10(-7) mol kg-1 min-1) has been analysed by the use of selective receptor antagonists and of ganglionic blockade. The increases in cardiac output, contractility, and rate were antagonized by the beta 2-adrenoceptor antagonist, ICI 118551. Renal blood flow rose secondary to reduction in renal vascular resistance and this was antagonized by SCH 23390, a highly selective DA1-receptor antagonist. Peripheral vasodilation and reduction of blood pressure were mediated by a combination of DA1- and DA2-receptor and beta 2-adrenoceptor stimulation. In a separate group of dogs, the cardiac stimulant effects of dopexamine HCl were partially reflex and were reduced by ganglion block, revealing responses due to stimulation of cardiac beta 2-adrenoceptors. Thus the beta 2-adrenoceptor agonist action of dopexamine HCl is not only partly responsible for afterload reduction but also leads to direct cardiac stimulation. From its cardiovascular profile, dopexamine HCl is likely to be of use in acute treatment of heart failure.
Adrenergic Agonists↗
Lack of inotropic selectivity of phosphodiesterase enzyme inhibitors in-vitro.
Phosphodiesterase enzyme (PDE) inhibitors form a diverse category of chemical structures which display positive inotropic activity, but it is unclear as to how force/rate selective these are on the heart. In this study several recently developed PDE inhibitors, almost all of which are selective for the cardiac PDE III isoenzyme, were compared with the xanthine PDE inhibitor IBMX and with ouabain and the direct and indirect adenylate cyclase activators, forskolin and isoprenaline, respectively. These compounds were active in increasing paced guinea-pig left atrial force, the order of potency being: isoprenaline greater than ouabain greater than forskolin greater than pimobendan greater than IBMX greater than sulmazole greater than buquineran greater than carbazeran greater than milrinone greater than piroximone greater than amrinone. Ro 13-6438 and enoximone were however, both inactive. With the exception of buquineran and carbazeran, which produced bradycardia and were therefore force specific, all of the recently discovered PDE inhibitors increased the rate of contraction of the right atria and they were rate selective to the same extent as IBMX, isoprenaline and forskolin. Sulmazole, the only force selective PDE inhibitor of the compounds studied, was intermediate between IBMX and ouabain in force/rate selectivity and pimobendan showed no selectivity. Since both these agents also possess other actions, then these results suggest that in general, PDE III inhibitors do not show advantageous force selectivity in guinea-pig atria.
Animals↗
Genetic and molecular analysis of biological rhythms.
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Animals↗
Immunohistochemical localization of choline acetyltransferase during development and in Chats mutants of Drosophila melanogaster.
The distribution of choline acetyltransferase (CAT) in the nervous system of Drosophila melanogaster was determined by indirect immunohistochemical procedures using a monoclonal antibody specific to the enzyme. Immunoreactivity was first detected in the nervous system of 16 hr embryos, and increased considerably by the end of embryogenesis. Neuropil was preferentially stained, though cell bodies could also be observed. Staining was prominent in the CNS of all 3 larval instars but decreased substantially during the mid-pupal stage. Prior to eclosion, the level of immunoreactivity increased and the adult staining pattern became discernible. In the adult brain, staining was extensive, with numerous structures, such as the optic lobes and mushroom bodies, staining strongly. The adult thoracic ganglia were also moderately immunoreactive. These results imply a wide distribution of cholinergic neurons in the CNS of Drosophila. Immunoreactivity was also determined for 2 temperature-sensitive CAT mutants, Chats1 and Chats2. These files exhibit reduced CAT activity at permissive temperature, 18 degrees C, which eventually falls to undetectable levels after incubation at nonpermissive temperature, 30 degrees C. Chats2 mutants, after incubation at either 18 or 30 degrees C displayed virtually no staining. This result indicated that the immunoreactivity observed in wild-type flies was specifically associated with the enzyme encoded by the Cha gene. The intensity of staining in Chats1 mutants incubated at 18 degrees C appeared greater than in control flies, even though CAT enzyme activity in Chats1 is lower. This suggests that the enzyme molecule itself is structurally altered in Chats1 mutants. After incubation at 30 degrees C, staining in Chats1 flies decreased but did not disappear.
Animals↗
The assessment of nutritional status in surgical patients.
OBJECTIVE: To determine the reliability of clinical assessments of nutritional status in surgical patients. METHOD: Prospective observer assessment. RESULTS: In this study, clinical estimates of nutritional well-being have been compared with objective markers of nutritional status. Clinicians tended to under-diagnose the extent of nutritional depletion.
Adult↗
The use of nasogastric tubes after abdominal surgery--a criteria audit.
OBJECTIVE: To evaluate the use of nasogastric tubes after gastrointestinal surgery. METHOD: Prospective criteria audit. RESULTS: In this study, 32.5% of patients (65/200) undergoing laparotomy had a nasogastric tube inserted during the perioperative period. Of these patients, 20% vomited whilst the tube was in situ and there was a poor correlation between the volumes of fluid aspirated and the timing of tube removal. These results suggest that nasogastric tubes were inserted too often and then left in situ for too long.
Abdomen↗
The CHILD syndrome. Histologic and ultrastructural studies.
A 4 1/2-month-old female infant had cutaneous and musculoskeletal changes consistent with the diagnosis of congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome. This syndrome encompasses abnormalities of several organ systems, and its origins and pathogenesis are poorly understood. This report describes an additional patient with this uncommon syndrome and includes light and electron microscopic studies of her skin lesions. Our patient's clinical features of meningocele, Shone's syndrome, and the electron microscopic findings have not previously been described in the American literature (to our knowledge) in association with this syndrome.
Abnormalities, Multiple↗
Interspecific genetic control of courtship song production and reception in Drosophila.
The genetic control of courtship song differences between Drosophila melanogaster and Drosophila simulans males was investigated by producing hybrids from reciprocal crosses. The song rhythm difference between the parental species appears to be due to sex-linked genes, whereas the basic interpulse-interval difference is autosomally inherited. Hybrid females show selective preferences for artificially generated songs carrying intermediate "hybrid" characteristics.
Animal Communication↗
Strategies of hemopoietic stress adaptation within the medullary cavity.
Gravimetric determination of total bone water space was used as an index of available bone marrow space in mice following various specific stressors, i.e., splenectomy, hypoxia, bone fracture, and estrone-induced osteosclerosis. Data was corrected for bone weight and was reported as specific bone marrow volume (total bone water space/mg dry bone X 100). A direct relationship was observed between specific bone marrow volume and medullary hemopoietic activity induced by stress. Absolute and/or relative marrow space increased following splenectomy, hypoxia, and fracture. Osteosclerotic animals shift most hemopoietic activity from marrow to spleen, and splenectomized osteosclerotic animals become anemic. Both intact and splenectomized hypoxic animals develop increased specific bone marrow volume and successfully compensate for hypoxia with enhanced erythropoiesis. Animals sustaining a fracture callus increase both specific bone marrow volume and hemopoietic activity at the callus without an increase in hemopoietic demand. Increased specific bone marrow volume extends the marrow bone interface, where primitive stem cells accumulate, while expanding marrow stromal space, where stem cells lodge, proliferate and differentiate. Therefore, it would appear that availability of competent marrow space may play an integral part in passively permitting hematopoiesis and in determining hemopoietic reserve capacity. Stem cell migration increases during intensified hemopoietic demand, which also may be related to available marrow space. Mice have a low medullary hemopoietic reserve capacity; subsequently, when available medullary hematopoietic stroma becomes occupied, stem cells are more likely to migrate from the marrow to extra-medullary sites where they mature before entering the circulating pool.
Adaptation, Physiological↗
Is operative cholangiography always necessary?
To determine whether operative cholangiography could be performed on a selective basis, 272 consecutive patients undergoing cholecystectomy and routine operative cholangiography were studied prospectively. Appropriate clinical, biochemical and operative data were recorded and the surgeon was asked to estimate the likelihood of common bile duct stones. These factors were correlated with the subsequent cholangiographic and operative findings. From this information, four criteria were selected as indications for performing an operative cholangiogram: an abnormal common bile duct, a wide cystic duct, or elevated levels of alkaline phosphatase or bilirubin documented in the previous six months. Operative cholangiograms would have been indicated by the presence of one or more of these criteria in only 139 of the 272 patients in the study (51 per cent). Only one unsuspected stone would have been missed. It is concluded that a policy of selective cholangiography could have been safely adopted in this series of patients.
Adolescent↗