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Biomedical subjects

J D Rose

Publications and source records attributed to J D Rose.

At least 19 recordsLinked to original sources

Investigation of familiar and novel chemosensory stimuli by golden hamsters: effects of castration and testosterone replacement.

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.

Animals

Changes in limbic neuronal function during hormonal induction of lordosis in behaving hamsters.

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.

Animals

The management of variceal bleeding.

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.

Catheterization

Changes in hypothalamic neuronal function related to hormonal induction of lordosis in behaving hamsters.

The hypothalamus is known to be critical for the neuroendocrine control of sexual behavior, but the neural effects of gonadal hormones on behavior-related activity of hypothalamic neurons has received little investigation. The present study examined the effects on single hypothalamic neurons of lordosis-inducing estrogen and progesterone administration to behaving golden hamsters. The lordosis-inducing action of the hormones was associated with rapidly emerging, cumulative changes in the activity level and somatosensory responsiveness of neurons throughout the hypothalamus, as well as the appearance in most neurons of lordosis-correlated firing. This functional reconfiguration of hypothalamic neuronal properties resembled, in time course and other aspects, effects of estrogen and progesterone previously observed in hamster midbrain neurons. Although the firing rates of the hypothalamic neurons were typically low, the lordosis-related activity of these neurons was compatible with a role in the control of individual episodes of lordosis as well as a state-related tendency to exhibit the lordosis response.

Animals

Identity of genes A2 and A3 of bacteriophage BF23.

The polypeptide coded by gene A3 of bacteriophage BF23 has been purified and its N-terminal amino acid sequence determined. This sequence is identical to the N-terminal sequence of the polypeptide coded by gene A2. The two gene products have identical molecular weight. We conclude that these two gene products are identical, and are coded by one and the same gene, namely gene A2-A3, which was previously thought to be two genes, A2 and A3.

Coliphages

Forebrain influences on brainstem and spinal mechanisms of copulatory behavior: a current perspective on Frank Beach's contribution.

In a 1967 Physiological Reviews paper, Frank Beach put forth four propositions regarding forebrain and hormonal control of brainstem-spinal mechanisms of copulatory behavior. Simply stated, he proposed that: 1) the forebrain exerted an inhibitory control over species-typical copulatory reflexes through descending effects on brainstem-spinal mechanisms and 2) gonadal hormones influence these reflexes largely by actions on forebrain control processes rather than by direct effects on the brainstem or spinal cord. This theoretical scheme was of great heuristic significance during the subsequent two decades of research, which has largely supported and delineated in greater mechanistic detail the processes Beach hypothesized to exist. This subsequent research has also shown the central nervous system actions of gonadal hormones to be more widespread and complex than Beach proposed. Some of these recent research findings are presented, with emphasis on neurophysiological studies which have identified hormone-induced functional changes in forebrain and brainstem neurons. It is proposed that these functional changes may represent a mechanism for the behavior-controlling actions of hormones that were hypothesized by Beach.

Animals

Possible role of histamine in the regulation of secretion of luteinizing hormone in the ewe.

Concentrations of histamine were quantified by an enzymatic isotopic assay in different regions of the brain and pituitary gland of gonadal-intact and chronically ovariectomized ewes during the anestrous season. Sera concentrations of LH were confirmed to be elevated in ovariectomized compared with intact animals immediately before tissues were obtained. Areas of the brain that were examined included cerebral cortex, thalamus, pineal gland, hypothalamus (rostral, medial basal, median eminence), midbrain, cerebellum and brain stem. Concentrations of histamine were greatest within the thalamus, pineal gland, medial basal hypothalamus and median eminence. Histamine within the medial basal hypothalamus was greater (P less than .05) in ovariectomized than in ovarian-intact animals. Further experiments were designed to determine the effect of antihistaminic drugs on secretion of LH. Ovariectomized ewes were treated every 6 h (i.m.) for 24 h with diphenhydramine (an antagonist of the H1-receptor for histamine), cimetidine (an H2-receptor antagonist), a combination of the drugs, or vehicle. Twelve hours after initiation of treatments, animals were injected with estradiol. Diphenhydramine depressed (P less than .01) basal serum concentrations of LH and the positive feedback effect of estradiol on serum concentrations of LH. Cimetidine did not influence the pattern of secretion of LH. Diphenhydramine did not alter LHRH-induced release of LH in ovariectomized ewes or basal serum concentrations of LH in ovarian-intact anestrous ewes. We suggest that histamine acts at the level of the central nervous system through an H1-receptor mechanism to control secretion of LH in female sheep.

Animals

Platelet number and size in relation to serum orosomucoid concentration in Crohn's disease.

The relationship between platelet size and platelet count was investigated in 41 patients with Crohn's disease. A high platelet count was associated with a decrease in platelet size, but an overall increase in the platelet crit. There was also a significant correlation between the patient's platelet count and serum orosomucoids, which have traditionally been used to assess disease activity.

Adolescent

Cardiff Crohn's disease jubilee: the incidence over 50 years.

The incidence of Crohn's disease in Cardiff between 1931 and 1985 has been examined using hospital diagnostic indices supplemented in recent years by records from clinicians, and the departments of pathology and radiology. Four hundred and seven new patients were confirmed after all notes had been reviewed. There has been a large increase from 0.18 cases/10(5) of the population per year in the 1930s to current values of 8.3/10(5)/year. The incidence continues to rise and shows an increasing proportion of patients with colorectal disease. Peak age specific incidences occur in the third and eighth decades of life.

Age Factors

Estrogen-dependent and estrogen-independent effects of progesterone on the electrophysiological excitability of dorsal midbrain neurons in golden hamsters.

During the induction of lordosis responses in golden hamsters, the joint actions of estradiol (E) and progesterone (P) have been found to produce major changes in the activity levels, sensory responsiveness and movement-related firing of neurons in the dorsal midbrain, a region vital for lordosis in this species. The present study investigated the possibility that these effects of E and P on dorsal midbrain neurons might arise through changes in transsynaptic excitability or spike-generating processes. Single dorsal midbrain neurons were orthodromically or antidromically activated by ventromedial midbrain tegmental stimulation in ovariectomized, urethane-anesthetized hamsters before and after subcutaneous injection of P in propylene glycol vehicle. P injection produced two neurophysiological effects: (1) a strong depression of transsynaptic activation, and (2) in antidromically invaded neurons, a change in the amplitude (either an increase or decrease) of the soma-dendritic spike component. Both of these effects appeared rapidly (i.e. within 10-20 min) after P injection. The P effect on orthodromic neuronal excitability was contingent upon E priming of the hamsters, but, in contrast, the P effect on antidromic spike amplitude was not. Several features of these neurophysiological effects of P imply that the hormone may have been acting through nongenomic mechanisms, possibly involving receptors in neuronal membranes.

Animals

Synthesis of potential anticancer agents: imidazo[4,5-c]pyridines and imidazo[4,5-b]pyridines.

The 1,2-dihydropyrido[3,4-b]pyrazines (1) are mitotic inhibitors with significant antitumor activity in mice. Also, the active imidazo[4,5-b]pyridine 3 was shown to cause the accumulation of cells at mitosis. Routes were developed for the synthesis of congeners of 3 by cyclization of 4-(substituted amino)-5,6-diaminopyridines with ethyl orthoformate. Oxidative cyclization of either 4,5- or 5,6-diaminopyridines with aryl aldehydes produced the [4,5-c] and [4,5-b] imidazopyridine ring systems, respectively. The latter reaction with 6-(substituted amino)-4,5-diaminopyridines gave imidazo[4,5-c]pyridine ring analogues of 1. Biological studies indicated that the target compounds were less active than 1 and 3.

Animals

Functional reconfiguration of midbrain neurons by ovarian steroids in behaving hamsters.

Previous studies have demonstrated the importance of the midbrain, especially the tectum, in the sensorimotor control of the sexually-receptive posture, lordosis, in female golden hamsters. In the present study, midbrain single unit activity was recorded during hormonal induction of lordosis, to identify neuronal activity mediating the sensorimotor control of the response and to observe functional changes in these neurons associated with the hormones' behavioral effect. Progesterone administration to estrogen-primed hamsters initiated pronounced changes in neuronal activity levels, somatosensory responsiveness and movement-related firing. These changes began in some neurons within 10 min of subcutaneous hormone injection and affected progressively more neurons until lordosis was elicitable 2-4 hr later. The pattern of these changes, including increased neuronal responsiveness to lumbosacral stimuli, appearance of lordosis-related firing (especially in the tectum) and reduced incidence of firing associated with lordosis-incompatible behaviors, constituted a transformation, or reconfiguration of midbrain sensorimotor function. It is proposed that this reconfiguration enables the elicitation and maintenance of lordosis by lumbosacral stimuli. Neural effects of comparable magnitude didn't result from control progesterone injections which failed to induce lordosis.

Animals

Disturbed hypothalamic control of Na,K-ATPase: a cause of somatic symptoms of depression.

Current theories of the causes of somatic symptoms in depression neglect evidence for a general inhibition of Na,K-ATPase. Experimentally, sodium pump inhibition is associated with depolarization of electrically active tissue: the threshold of peripheral nerves is decreased and smooth muscle function altered. Symptoms compatible with these changes are found both in depression and intoxication with digoxin, which inhibits Na,K-ATPase. The hypothalamus contains inhibitors of Na,K-ATPase which are capable of producing depolarization. In depression, changes in hypothalamic activity may increase endogenous inhibition and contribute to the somatic symptoms.

Action Potentials

Lordosis-disrupting tectal lesions alter midbrain unit somatosensory responsiveness in hamsters.

Previous research has shown that bilateral deep tectal lesions in golden hamsters abolish the lordosis response, whereas unilateral lesions selectively impair lordosis elicitation by contralateral flank stimulation. The present study analyzed the neural basis of these lesion effects by assessing the somatosensory responsiveness of midbrain neurons in three groups of urethane-anesthetized hamsters: animals with lordosis-abolishing bilateral tectal lesions, animals with lordosis-impairing unilateral lesions, and intact animals. Animals with bilateral lesions differed from the other groups in three aspects of unit sensory responsiveness by showing: (1) the highest percentage of neurons responsive to somatic stimulation, (2) the highest incidence of unit responsiveness to flank stimulation, and (3) the greatest proportion of responsive neurons in the ventral tegmentum. Hamsters with unilateral lesions showed basically normal unit responsiveness apart from elevated unit response to face stimulation. The results suggest that bilateral tectal lesions may eliminate lordosis by the combined effects of enhanced ventral tegmental somatosensory responsiveness and tectal destruction. Unilateral lesions appear to impair lordosis without changing the somatosensory excitability of remaining midbrain neurons.

Animals

Depression and functional bowel disorders in gastrointestinal outpatients.

Although depression has been linked with both the irritable bowel syndrome and non-organic abdominal pain, which are common in gastrointestinal outpatients, the prevalence of depression in most surveys of outpatient practice has been low. Use of the Beck Depression Inventory to screen new referrals to a general medical and gastrointestinal clinic and to a minor surgical clinic showed that 50 of 100 medical patients were rated as having some degree of depression, compared with 14 of 75 (19%) of the surgical patients in whom abdominal pain and bowel dysfunction were rare (X2 = 9.6, p less than 0.01). In the medical clinic no organic disorder was detected in 64% of the depressed patients, the majority of whom presented with abdominal pain or irritable bowel syndrome. Depression was significantly commoner in this group of patients than in those with other conditions, (X2 = 6.63, p = 0.01). That depression is common in gastrointestinal outpatients is not always appreciated and its symptoms should be sought in all patients with bowel dysfunction and chronic abdominal pain.

Adolescent

Removal of the vomeronasal organ impairs lordosis in female hamsters: effect is reversed by luteinising hormone-releasing hormone.

In female golden hamsters, vomeronasal organ removal disrupts the elicitation of lordosis by lumbosacral tactile stimulation. A similar disruption occurs if the nasopalatine ducts are closed, without removing the vomeronasal organ. Injection of luteinising hormone-releasing hormone reverses the effect of vomeronasal organ removal. These findings suggest that chemosensory signals from the male hamster act via the accessory olfactory system, to facilitate the triggering of lordosis by somatic stimulation.

Animals

Dorsal-ventral differences in the midbrain distribution of single neurons with head movement-correlated and locomotion-correlated firing in the golden hamster.

Movement-correlated firing was studied in 111 midbrain neurons recorded in freely behaving hamsters. For 42% of these cells, most of which lay in the deeper laminae of the superior colliculus, firing occurred principally or exclusively in association with head movements. In 38% of the neurons, most of which were in subtectal regions, activity was greatest during locomotion, but also occurred in correlation with other types of movement.

Animals