Traumatic diaphragmatic herniation.
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Biomedical subjects
Publications and source records attributed to J D Rose.
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Corticotropin-releasing factor (CRF) administration has been shown to act centrally to enhance locomotion in rats and amphibians. In the present study we used an amphibian, the roughskin newt (Taricha granulosa), to characterize changes in medullary neuronal activity associated with CRF-induced walking and swimming in animals chronically implanted with fine-wire microelectrodes. Neuronal activity was recorded from the raphe and adjacent reticular region of the rostral medulla. Under baseline conditions most of the recorded neurons showed low to moderate amounts of neuronal activity during periods of immobility and pronounced increases in firing that were time-locked with episodes of walking. These neurons sometimes showed further increases in discharge during swimming. Injections of CRF but not saline into the lateral ventricle produced a rapidly appearing increase in walking and pronounced changes (mostly increases) in firing rates of the medullary neurons. CRF produced diverse changes in patterns of firing in different neurons, but for these neurons as a group, the effects of CRF showed a close temporal association with the onset and expression of the peptide's effect on locomotion. In neurons that were active exclusively during movement prior to CRF treatment, the post-CRF increase in firing was evident during episodes of walking; in other neurons that also were spontaneously active during immobility prior to CRF infusion, post-CRF activity changes were evident during immobility as well as during episodes of locomotion. Thus, a principal effect of CRF was to potentiate the level of neuronal firing in a population of medullary neurons with locomotor-related properties. Due to the route of administration CRF may have acted on multiple central nervous system sites to enhance locomotion, but the results are consistent with neurophysiological effects involving medullary locomotion-regulating neurons.
Fighting behavior between male copperheads (Agkistrodon contortrix) occurs during the two mating periods (late summer/fall and spring) to gain priority of access to females. Fights are characterized by prominent vertical challenge displays, swaying, and a high degree of physical contact that does not involve biting. At the moment of subordination, losers retreat quickly from fights and winners respond by chasing. Subsequently, losers do not participate in further challenge displays or fighting for at least 7 days, and also they show behavioral signs of stress, which includes submissive acts and suppression of sexual behavior. The goal of this study was to determine whether or not losers show elevated levels of plasma corticosterone (B) and depressed levels of plasma testosterone (T) relative to winners and controls. Winners and losers were produced in 13 staged trials. Two different controls (N = 26) were run. Males with no recent agonistic experience were (1) tested in the fighting arena in the absence of a competitive male but paired with a single female (N = 13), and (2) tested alone in their cages (N = 13). All trials, including controls, were conducted in spring and late summer. Mean B in losers at 1-hr postfight was significantly greater than in winners and both control groups in both seasons. Mean T was significantly greater in late summer in all groups, as expected, but in each season was not significantly different between the groups. Levels of B and T were not correlated with SVL, mass, or duration of fighting. This study provides further support for the social insensitivity/challenge hypotheses and is the first to document postfight B and T levels in snakes.
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Research on a wide variety of vertebrates, from fish to mammals, reveals that corticosteroid hormones and vasotocin-like neuropeptides can potently modulate reproductive behaviors. But, it is not clear how the behavioral effects of these chemical messengers relate to functional properties of behavior-controlling neurons. This problem was investigated in the roughskin newt, Taricha granulosa, an amphibian in which the administration of arginine vasotocin (AVT) facilitates and corticosterone (CORT) inhibits courtship clasping of females by males. In waking, immobilized male newts, neurophysiological effects of AVT and CORT were studied in neurons in the rostral medulla due to the probable role of these neurons in the control of clasping. Topical medullary application of a clasp-facilitating dose of AVT produced a rapid increase in neuronal responsiveness to pressure on the cloaca, a trigger stimulus for clasping responses. Neuronal responses to noncloacal somatic stimuli and to moving visual stimuli were also enhanced. Systemic CORT administration, which has previously been shown to depress newt medullary neuronal sensory responsiveness, reversed the action of AVT such that the peptide depressed sensory responsiveness when applied 30 min after CORT. When AVT application preceded CORT injection by 10-17 min, however, the usual suppressive CORT effect was reversed and this treatment resulted in a rapidly appearing potentiation of neuronal activity and enhanced somatic sensory responsiveness. If the interval between AVT and CORT was increased to 30 min, the steroid caused a rapid depression of firing and a diminished somatic sensory responsiveness in most neurons, similar to what occurs in newts treated with CORT alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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Investigations into the neuroendocrine regulation of reproductive behaviors in an amphibian (Taricha granulosa) reveal the same basic repertoire of chemical messengers as regulators of male behaviors in other vertebrates. These studies have identified seasonal neural interactions between gonadal steroids and neuropeptides that facilitate male courtship behavior. In addition, this species has served to elucidate how stress-induced suppression of courtship is mediated by corticosterone action through a neuronal membrane receptor and subsequent, rapid neurophysiological effects. These findings indicate that a principal mechanism by which steroids and neuropeptides control male reproductive behavior is the modulation of neural processing of specific sensory stimuli.
X-ray crystallography and computer-assisted molecular modeling (CAMM) studies aided in the design of a potent series of mammalian purine nucleoside phosphorylase (PNP) inhibitors. Enhanced potency was achieved by designing substituted 9-(arylmethyl)-9-deazaguanine analogs that interact favorably with all three of the binding subsites of the PNP active site, namely the purine binding site, the hydrophobic pocket, and the phosphate binding site. The most potent PNP inhibitor prepared during our investigation, (S)-9-[1-(3-chlorophenyl)-2-carboxyethyl]-9-deazaguanine (18b), was shown to have an IC50 of 6 nM, whereas the corresponding (R)-isomer was 30-fold less potent.
Alicyclic and heteroalicyclic derivatives of 9-deazaguanine (2-amino-1,5-dihydro-4H-pyrrolo[3,2-d] [pyrimidin-4-one) are, with one exception, potent inhibitors of purine nucleoside phosphorylase (PNP) equaling the corresponding 9-arylmethyl derivatives previously investigated. The mode of binding of these compounds to PNP was determined by X-ray crystallography.
Purine nucleoside phosphorylase (PNP, EC 2.4.2.1) is a salvage enzyme important to the T-cell-mediated part of the immune system and as such is an important therapeutic target. This paper describes the design, synthesis, and enzymatic evaluation of potent, competitive inhibitors of PNP. Potential inhibitors were designed using the three-dimensional structure of the enzyme in an iterative process that involved interactive computer graphics to model the native enzyme and complexes of it with the inhibitors, Monte Carlo-based conformational searching, and energy minimization. Studies of the enzyme/inhibitor complexes were used to determine priorities of the synthetic efforts. The resulting compounds were then evaluated by determination of their IC50 values and by X-ray diffraction analysis using difference Fourier maps. In this manner, we have developed a series of 9-(arylmethyl)-9-deazapurines (2-amino-7-(arylmethyl)-4H-pyrrolo[3,2-d]-pyrimidin-4-ones) that are potent, membrane-permeable inhibitors of the enzyme. The IC50 values of these compounds range from 17 to 270 nM (in 1 mM phosphate), with 9-(3,4-dichlorobenzyl)-9-deazaguanine being the most potent inhibitor. X-ray analysis explained the role of the aryl groups and revealed the rearrangement of hydrogen bonds in the binding of the 9-deazaguanines in the active site of PNP relative to the binding of the 8-aminoguanines that results in more potent inhibition of the enzyme.
Previous research has indicated that chronically decerebrate adult female rats are incapable of exhibiting lordosis in response to lumbosacral somatic stimuli, suggesting a dependency of this response on forebrain influence. Since vaginocervical stimulation facilitates lordosis to lumbosacral stimuli in rats, the present study investigated the possibility that chronically decerebrate rats could show lordosis in response to flank palpation if vaginocervical pressure was applied concurrently. Six of nine ovariectomized, decerebrate rats exhibited a coordinated display of lordosis-like responses to flank palpation if this stimulus was accompanied by vaginocervical stimulation, but not in response to flank and perineal pressure alone. Estradiol-progesterone treatment increased the magnitude of the response in five of six animals. As in intact rats, cervix pressure in the decerebrates also produced immobilization and blocked responses to nociceptive stimuli. Thus, the caudal neuraxis can mediate expression of essential components of the lordosis response in the absence of forebrain influence.
Histamine has been implicated as a neuromodulator of secretion of gonadotropins in several species. Concentrations of histamine were analyzed within discrete brain regions and endocrine tissues to help determine whether this amine has the potential to exert a similar function in ewes expected to have dramatically different serum concentrations of LH. Following collection of blood samples at 12-min intervals for 4-hr, ovariectomized (OVX) and OVX-estradiol treated (OVX-E) ewes were slaughtered during the breeding and anestrous seasons (five animals/group). Concentrations of LH were depressed by treatment with estradiol (E; P < .01), but to a greater extent (P < .05) during the anestrous season compared to the breeding season. Concentrations of histamine in tissues (ng/mg) differed (P < .01) between the breeding and anestrous seasons, in the medial thalamus (39.2 +/- 14.1 vs 109.9 +/- 13.0), posterior pituitary gland (247.6 +/- 50.7 vs 23.0 +/- 9.1) and midbrain tegmentum (10.4 +/- 5.6 vs 50.7 +/- 3.9). Estradiol containing implants decreased (P < .05) concentrations of histamine in the midbrain tegmentum (20.3 +/- 7.1 vs 37.7 +/- 7.8) and posterior pituitary gland (87.3 +/- 24.0 vs 258.2 +2- 67.5) compared to non-estradiol treated controls. Histamine concentrations in the pineal and anterior pituitary glands and brain regions; stalk-median eminence, medial basal hypothalamus, preoptic area, cerebellum, parietal neocortex, were not (P > .05) affected solely by either season or E. An interaction between effects of season and estradiol on concentrations of histamine occurred (P < .05) in the posterior pituitary gland and the preoptic area.(ABSTRACT TRUNCATED AT 250 WORDS)
A case of enteropathy associated T cell lymphoma (EATCL) is described, which was diagnosed by biopsy of a lymphomatous pleural mass. Retrospective radiological review showed that this lesion had been present when an initial diagnosis of coeliac disease had been made 12 months previously and a detailed description of the natural history of the lymphoma during this period was thus available. The findings show that EATCL may behave in an indolent fashion and masquerade as coeliac disease, delaying the correct diagnosis. The relation of this disorder with coeliac disease and lymphocytic gastritis is discussed with reference to recent published works.
Courtship clasping of females by male roughskin newts (Taricha granulosa) is rapidly blocked by exposure to corticosterone (CORT). This behavioral effect appears to result from CORT binding to a receptor in neuronal membranes. The present study investigated effects of intraperitoneal CORT administration on neurophysiological properties of extracellularly recorded single medullary neurons in acutely prepared newts. CORT produced multiple neurophysiological effects that emerged within 3 min of injection and increased in magnitude during the next 20-30 min. Spontaneously active and sensory-responsive neurons showed a decline or cessation of firing concomitant with a loss of sensory responsiveness, especially to cloacal pressure, a clasp-facilitating stimulus in behaving newts. After CORT administration, reticulospinal neurons that were backfired (antidromically activated) by spinal cord stimulation, exhibited reduced antidromic action potential amplitude, slowed rates of spike generation and other indications of reduced excitability. Comparable effects of CORT were also evident in newts with a premedullary brainstem transection, indicating a direct hormone action on the caudal neuraxis. Dexamethasone (DEX), a glucocorticoid that binds poorly to the CORT membrane receptor and has little effect on clasping, had little or no direct neurophysiological effect, but DEX injection 30 min before CORT interfered with the neurophysiological action of CORT. The rapidity, time course and specificity to CORT of these neurophysiological effects are consistent with mediation through the CORT membrane receptor. In addition, the pattern and dose sensitivity of these neurophysiological actions plus their occurrence in the medulla, suggest that they could underlie the CORT effect on courtship clasping.
Estrous hamsters secrete an odorous vaginal discharge that intact male hamsters investigate vigorously during copulatory behavior. Castrated animals are not attracted to this vaginal discharge. In this study we observed that repeated exposure of intact and castrated hamsters to this vaginal discharge reliably produced habituation of investigatory behavior. Presentation of the odor from a novel female to a habituated male caused an increase in investigation (dishabituation). Castration produced a decrease in investigation within 1 week of surgery. However, the surgery did not produce a decrease in dishabituation until 3 months afterward. Testosterone treatment increased chemosensory investigation in castrated animals. It seems likely that the dishabituation observed in this study may represent a sensory component of the Coolidge Effect.
Several limbic structures influence copulatory behavior and contain receptors for estradiol and progesterone. In the present study, single neuron activity was recorded from septal, amygdaloid, and other limbic regions during the hormonal induction of lordosis in behaving golden hamsters. Limbic neurons had low firing rates and a small number showed firing associated with orienting, sniffing, and rearing. Progesterone administration to estradiol-primed hamsters produced the following neuronal effects: a reduction in the number of active neurons and narrowing of dynamic activity range; enhanced neuronal responsiveness to face stimulation; and lordosis-correlated firing, consisting of depressed activity during lordosis and increased firing at response onset or offset. Unlike previously studied midbrain and hypothalamic neurons, control progesterone injections that didn't produce lordosis were about as effective in altering limbic neuronal activity levels and sensory responsiveness as behaviorally effective injections. The progesterone effects on limbic neurons are consistent with previous evidence suggesting that these neurons tend to suppress lordosis. The significance of these results to hormone influences on epilepsy is discussed.
Variceal bleeding has a high mortality, as the majority of patients have cirrhosis, with hepatic coma, renal failure, ascites and clotting deficiencies as complicating factors. Bleeding varices must therefore be treated as an emergency. Resuscitation, endoscopic diagnosis and haemostasis are the cornerstones of treatment. Once bleeding varices have been identified, attempts to stop the bleeding must be made at once as this will lessen the chances of hepatic failure developing. Endoscopic sclerotherapy at the time of diagnosis is the best available treatment at present, although profusely bleeding varices can be difficult to see and inject. In these circumstances the passage of a Sengstaken tube should stop the bleeding, allowing later sclerotherapy to be successful. If rebleeding recurs and cannot be controlled, oesophageal transection with a stapling gun may be life-saving, although the varices may later recur and long-term endoscopic follow-up will be necessary. Portacaval shunting and the distal splenorenal shunt involve arduous surgery and are followed by a significant incidence of hepatic encephalopathy; they should be reserved for those few cases when simpler measures have failed, although shunts do lead to permanent decompression of the portal system. The acute variceal bleed may also be dealt with pharmacologically. Vasopressin, used in combination with nitroglycerin to lessen the harmful side-effects, is cheaper and as effective as terlipressin or somatostatin and its synthetic analogue octreotide. Several courses of injection sclerotherapy will be required to eliminate oesophageal varices. Thereafter, long-term follow-up will be necessary to deal with any recurrence. The place of non-selective beta-blockers is still contentious, but they do reduce portal pressure and may lessen the chance of rebleeding. There is also a growing role for hepatic transplantation, which not only eliminates the varices but also restores liver function to normal and greatly reduces the risk of subsequent hepatoma development.