Issues in the management of prisoners infected with HIV-1: the King's College Hospital HIV prison service retrospective cohort study.
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Adult↗
Biomedical subjects
J Buggy
Publications and source records attributed to J Buggy.
AP-1 DNA binding activity induced by hyperosmolality in the rat hypothalamic supraoptic and paraventricular nuclei.
Immediate early gene products (c-fos, c-jun and their cognates) act as transcription factors coupling physiologically relevant stimuli to long-term responses by binding to the AP-1 site in the promoter region of target genes. The induction of c-fos has been identified in the paraventricular (PVN) and supraoptic (SON) hypothalamic magnocellular nuclei after hyperosmotic stimulation by using in situ hybridization and immunocytochemistry. In this study, AP-1 DNA binding activity, an indicator of the functional form of the c-fos transcription factor, was examined in nuclear extracts prepared from these brain regions using an electrophoretic mobility shift assay and a labeled oligonucleotide containing the AP-1 consensus sequence. Two hours after hypertonic saline injection (i.p.), rats were killed and nuclear proteins were extracted from tissue punches of brain regions to assess AP-1 binding activity. Hyperosmolality induced an increase of AP-1 binding activity in nuclear protein from SON and PVN, but not striatum. This binding was competitively displaced by excess unlabeled AP-1 oligonucleotide whereas addition of increasing amounts of unlabeled SP-1 oligonucleotide (promoter site on housekeeping genes for the ubiquitous SP-1 transcription factor) did not decrease the binding. The binding protein was shown to contain c-Fos/Fra and c-Jun since addition of c-Fos/Fra antiserum formed a supershift of the DNA, protein and antibody complex, and c-Jun antibody blocked the protein DNA binding. These data suggest that hyperosmolality leads to a selective and specific increase in AP-1 DNA binding activity which may be responsible for regulating secondary target gene expression in the hypothalamic SON and PVN.
Animals↗
Human glucagon receptor monoclonal antibodies: antagonism of glucagon action and use in receptor characterization.
This paper describes the development and characterization of the first monoclonal antibody specific for the recently cloned human glucagon receptor (hGR), and its use in probing receptor structure and function. We demonstrate specificity of one of the antibodies, CIV395.7A, by immunofluorescence staining and immunoprecipitation analysis. In addition, CIV395.7A specifically competes with glucagon for the hormone binding site on the receptor, indicating that the antibody's specific recognition epitope overlaps with the receptor's hormone binding domain. As a consequence, the mAB antagonizes glucagon-stimulated signal transduction as assayed by in vitro cAMP accumulation. Binding inhibition studies further reveal that the antibody specifically recognizes the human and rat GR, but not mouse. Using hGR/glucagon-like peptide I receptor chimeras, we have localized the recognition epitope of the antibody to the membrane-proximal half of the amino-terminal extension of the receptor, thus defining a domain on the receptor which is involved in glucagon binding.
Animals↗
Exercise- and hypertension-induced collagen changes are related to left ventricular function in rat hearts.
Chronic hypertension, known to affect the collagen profile of the heart, and exercise result in impaired or improved heart function, respectively. Collagen types I [alpha 1(I)2 and alpha 2(I)] and III [alpha 1(III)3] are the predominant interstitial collagens thought to influence cardiac function, and the ratio of type III to I (collagen III/I) is thought to be a significant factor in the altered relaxation observed in hypertrophy. The present study tested the hypothesis that the myocardial structure and function are different in chronically exercise-trained vs. hypertensive rat hearts. Male rats were either chronically exercised (XTr) or submitted to experimental hypertension by coarctation of the abdominal aorta (Hyp) for 10 wks. Heart rate, blood pressure, and maximal rate of fall of the left ventricular pressure (-dp/dt) were recorded during isoproterenol stimulation. Results showed that both Hyp and XTr had higher heart weight and left ventricular weight-to-body weight ratios (P < 0.05). Mean arterial pressure (MAP) was higher in Hyp and lower in XTr (P < 0.05), whereas (-dP/dt)/MAP was diminished in Hyp but enhanced in XTr. Left ventricular collagen was higher in Hyp than XTr, whereas collagen III/I was reduced in Hyp compared with XTr (P < 0.05). Scanning and transmission electron microscopy also supported an accumulation of left ventricular collagen in Hyp compared with XTr. A negative correlation was observed between collagen III/I and (-dP/dt)/ MAP (r = -0.91; P < 0.05). These results suggest an important relationship between adaptations in left ventricular collagen and the changes in diastolic function observed in both chronic hypertension and exercise cardiac stress.
Animals↗
Isolation and structural analysis of the 5' flanking region of the gene encoding the human glucagon receptor.
The gene encoding the human glucagon receptor, including several kb of upstream sequence, was isolated from a bacteriophage lambda FIX II library constructed from human placental DNA. We report here the novel sequence of the 5' flanking region of the gene, the identification of a previously unreported intron of 5 kb, and the identification of the transcription start point of the glucagon receptor-specific transcript, which estimates the length of the first exon to be 300 bp.
Base Sequence↗
Cloning and characterization of senC, a gene involved in both aerobic respiration and photosynthesis gene expression in Rhodobacter capsulatus.
The purple nonsulfur photosynthetic eubacterium Rhodobacter capsulatus is a versatile organism that can obtain cellular energy by several means, including the capture of light energy for photosynthesis as well as the use of light-independent respiration, in which molecular oxygen serves as a terminal electron acceptor. In this study, we have identified and characterized a novel gene, senC, mutations in which affect respiration as well as the induction of photosynthesis gene expression. The protein coded by senC exhibits 33% sequence identity to the yeast nucleus-encoded protein SCO1, which is thought to be a mitochondrion-associated cytochrome c oxidase assembly factor. Like yeast SCO1, SenC is required for optimal cytochrome c oxidase activity in aerobically grown R. capsulatus cells. We further show that senC is required for maximal induction from the puf and puh operons, which encode the structural polypeptides of the light-harvesting and reaction center complexes.
Amino Acid Sequence↗
Proto-oncogene c-fos and the regulation of vasopressin gene expression during dehydration.
Secretion of the antidiuretic hormone (ADH) vasopressin is increased when body fluid homeostasis is disturbed by dehydration. Associated with this increased secretion is an elevation of vasopressin mRNA in magnocellular hypothalamic neurons projecting to the posterior pituitary. The proto-oncogene c-fos codes for a nuclear phospho-protein Fos which binds to specific DNA elements and acts as a transcriptional regulator coupling short-term extracellular stimuli to long-term responses by altering secondary target gene expression. This study in rats examined the time courses of dehydration induced c-fos expression and the change of vasopressin gene expression in the magnocellular neurons of the hypothalamus. Immunocytochemical and in situ hybridization study demonstrated that c-fos was induced by acute intracellular dehydration in the hypothalamic magnocellular nuclei of paraventricular (PVN), supraoptic (SON), and accessory groups such as nucleus circularis. Double-label immunocytochemical study co-localized Fos and vasopressin-neurophysin immunoreactivity in the same magnocellular neurons in the SON and PVN. In situ hybridization analysis after acute dehydration revealed a rapid and transient c-fos induction followed by a persistent increase in vasopressin mRNA for up to 2 days even after rehydration. Furthermore, prevention of c-fos translation by pretreatment with protein synthesis inhibitor cycloheximide attenuated this dehydration induced increase in vasopressin mRNA. This study demonstrated that an increase in vasopressin transcription after acute dehydration is dependent on an early phase of protein synthesis.
Animals↗
Control of photosystem genes in Rhodobacter capsulatus.
Two environmental factors, oxygen and high light intensity, are known to repress synthesis of the Rhodobacter capsulatus photosystem. One level of regulation is the control of light harvesting and reaction centre gene expression at the point of transcription initiation. This has recently been shown to involve transcriptional activators which exhibit sequence similarity to members of the 'two-component' class of prokaryotic regulators. An additional level of regulation involves the formation of 'superoperons' that transcriptionally link pigment biosynthesis operons with operons that code for the light harvesting and reaction centre structural genes. A final level of regulation involves the selective degradation of reaction centre mRNA transcripts which influence the stoichiometric synthesis of the light harvesting and reaction centre complexes.
Anaerobiosis↗
Effects of intracranial self-stimulation on selected physiological variables in rats.
The purpose of this investigation was to characterize selected metabolic, cardiovascular, and hormonal responses to reinforcing intracranial self-stimulation (ICSS) of the ventral tegmental area (VTA) in rats. Twenty male Sprague-Dawley rats were stereotaxically implanted with bipolar electrodes aimed at the VTA of the brain. Rats were trained to lever-press for ICSS for 1 wk. While they adapted to the experimental environment by sitting in a metabolic operant chamber, they were connected to the electrode cable but did not lever-press. All animals were instrumented with arterial catheters. Rats receiving contingent stimulation (C-St; n = 10) performed 30 min of lever pressing in the metabolic operant chamber for reinforcing brain stimulation. Oxygen consumption (VO2), heart rate (HR), mean arterial pressure (MAP), and rectal temperature (Trec) increased with the onset and continuation of contingent brain stimulation over 30 min (P < 0.05). In addition, plasma norepinephrine (NE), epinephrine (Epi), and corticosterone increased significantly above resting values in C-St rats (P < 0.05). Five animals received investigator-delivered reinforcing brain stimulation (noncontingent stimulation; NC-St), with MAP, HR, VO2, NE, and Epi increasing significantly above resting values (P < 0.05). Trec and corticosterone were not responsive to noncontingent brain stimulation. With the exception of HR, nonstimulated controls (n = 5) did not experience increases above resting values in any of the variables measured. The responses suggest that contingent brain stimulation reward elicits heightened sympathetic arousal.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Exercise training alters cardiovascular and hormonal responses to intracranial self-stimulation.
Both reinforcing intracranial self-stimulation (ICSS) and physical exercise result in heightened cardiovascular and endocrine responses. This study compared the cardiovascular and endocrine responses to ICSS in rats after either chronic ICSS or treadmill running. Male rats (n = 35) were implanted with bipolar electrodes aimed at the ventral tegmental area of the brain, and those that performed vigorous lever pressing for ICSS (> 50 presses/min; n = 30) were counter balanced into three groups: chronic ICSS (PRESS), chronic run training (RUN), or sedentary controls (CONT). PRESS, RUN, and CONT rats performed ICSS, ran on a motorized treadmill, or sat quietly in cages for 30 min/day, 5 day/wk, for 12 wk, respectively. All animals then performed 30 min of lever pressing for ICSS and were immediately killed. Oxygen consumption, heart rate, blood pressure, rectal temperature, and plasma norepinephrine, epinephrine, and corticosterone increased (P < 0.05) for all groups during lever pressing. PRESS rats did not differ from CONT rats for any variable studied. However, heart rate was lower and oxygen consumption, norepinephrine, and corticosterone were higher in RUN than in CONT rats. Heart and ventricle weights were higher in PRESS and RUN than in CONT rats; body weights were not different. These data suggest that chronic treadmill running results in adaptations that influence cardiovascular and hormonal responses to ICSS.
Animals↗
Application of confocal laser scanning microscopy to the deep pineal gland and other neural tissues.
The study of the deep pineal gland of the Mongolian gerbil and other neuronal tissue from the rat by means of confocal laser scanning microscopy (CLSM) is described. Opical serial sectioning was performed on thick (100-200 microns) sections of the deep pineal gland of the Mongolian gerbil stained immunohistochemically using antisera to S-antigen and tyrosine hydroxylase (TH). Both dual-stained and single-stained material was examined using the fluorochromes fluorescein isothiocyanate (FITC) and Texas Red. High resolution images were obtained showing that pinealocytes have 1-3 processes that extend primarily to other pinealocytes or presumptive pinealocytes. Pinealocytes are located within the deep pineal gland as well as adjacent to the posterior aspect of the medial habenular nuclei. Pinealocyte processes were not seen extending into the habenular nuclei, but rather ended within the deep pineal gland a significant distance from their perikarya. The TH-immunopositive fibers were distributed throughout the deep pineal gland, often forming "baskets" of fibers around pinealocytes rather than being associated primarily with blood vessels. Other uses of the confocal microscope are demonstrated on rat neural tissue reacted with peroxidase/diaminobenzidine (DAB) immunohistochemistry and FITC fluorescence immunohistochemistry (paraventricular nucleus) as well as Golgi-stained neuronal tissue (cerebral cortex). The HRP/DAB and Golgi-stained images were visualized using the reflected image mode of the confocal system.(ABSTRACT TRUNCATED AT 250 WORDS)
3,3'-Diaminobenzidine↗
Intracranial self-stimulation motivates treadmill running in rats.
Most animal running models have traditionally used aversive motivators to induce exercise tasks. This study demonstrates treadmill running motivated by reinforcement of intracranial self-stimulation (ICSS), providing an alternative model with which to study physiological responses to exercise. Twenty-nine male Sprague-Dawley rats were stereotaxically implanted with bipolar electrodes aimed at the ventral tegmental area of the brain. After 7 days of operant lever-press training for ICSS, rats that pressed at least 50 presses/min were randomly divided into three conditions: exercise-reinforcing brain stimulation (Ex-St), exercise-aversive shock (Ex-Sh), and sedentary controls (C). Ex-St and Ex-Sh ran for 30 min at 25 m/min at 5% grade for 2 wk with ICSS and electric shock as the motivator, respectively, while C did not run. At the end of 2 wk, Ex-St and Ex-Sh performed an endurance run. Results show that Ex-St ran longer than Ex-Sh [63 +/- 10 vs. 42 +/- 10 (SD) min; P less than 0.05]. HR was higher in Ex-St than in C (P less than 0.05). Rectal temperature increased similarly in both exercise groups. This model provides a highly effective method to motivate treadmill running in rats and as such can be used to characterize physiological responses to exercise without the potentially confounding influence of stress associated with an aversive shock motivator.
Animals↗
Intracranial self-stimulation motivates weight-lifting exercise in rats.
The purpose of this study was to determine the feasibility of using a positive reinforcement protocol to motivate weight-lifting exercise in rats. Intracranial self-stimulation was used to induce weight-lifting exercise. Bipolar electrodes were implanted in the ventral tegmental area of rats, and the animals were trained to bar press on a continuous reinforcement schedule for electrical brain stimulation. Animals with response rates of 1,200-1,500 presses/h were then trained with a discriminative light stimulus to alternate between a normally positioned bar and an elevated bar that could be reached only by standing on the hindlimbs. The animals were fitted with a weighted jacket at a starting resistance of 5-10% of their body weight. Weight-training sessions were conducted 5 days/wk for 10 wk. Training consisted of 600 presses/session, alternating every 15 presses between the low and high bars. At the beginning of each subsequent week, the resistance was progressively increased, with some animals eventually training at resistances greater than 50% of their body weight. At the end of the training period, the rats were lifting over 550% of the starting weight. Gastrocnemius size and mean fiber diameter were increased in the weight-lifting animals. This model combines exercise with positive incentive and has the advantages of being relatively easy to implement and not producing any apparent physical or mental trauma in the animal.
Animals↗
Circadian rhythmicity after neural transplant to hamster third ventricle: specificity of suprachiasmatic nuclei.
Neural transplants into the third ventricle utilized to quantitatively assess the effectiveness of fetal tissue from selected brain sites in restoring circadian locomotor rhythmicity of adult hamsters rendered arrhythmic by lesions of the suprachiasmatic nuclei (SCN). Circadian function was continuously monitored in recording wheel cages under controlled environmental conditions. Animals which remained arrhythmic for 3-4 weeks after SCN lesions received transplants of neural tissue from 13-14-day-old fetuses: either SCN tissue or non-SCN tissue (cerebral cortex or hypothalamus excluding SCN). Quantitative evaluation of the data indicated partial restoration of circadian rhythmicity in 37% of 19 animals with SCN transplants, but in 0% of the 9 animals with non-SCN neural transplants. The mean time for reappearance of rhythmicity was 20 days after SCN transplantation. Animals were sacrificed 8-10 weeks after transplantation for histological analysis in order to visualize lesion placement and to characterize transplants. The cytoarchitecture and neuropeptide organization of the transplants were consistent with the brain region. Only SCN transplants were characterized by aggregates of small neurons with codistributed immunoreactivity for SCN-characteristic neuropeptides.
Cerebral Ventricles↗
Angiotensin-estrogen central interaction: localization and mechanism.
Intracerebroventricular (ICVT) administration of estradiol benzoate (EB) to ovariectomized female rats decreased drinking and pressor responses to central injections of angiotensin II (AII). Estrogen treatment does not have this effect in male rats. As EB given ICVT reaches many brain areas, the site of action of EB was localized using crystalline implants of EB in the medial preoptic area or the ventromedial nucleus of the hypothalamus. These areas were chosen as they have a high density of estrogen receptors. Only medial preoptic area application of estrogen decreased angiotensin II-induced drinking. Angiotensin receptor binding was examined in homogenates from different brain regions to determine if the mechanism through which estrogen decreases central responses to AII involves altered receptor function. Systemic EB did not affect AII receptor binding in several brain regions but binding was decreased in homogenates from the preoptic area and septum-thalamus blocks which encompassed structures (median preoptic nucleus, organum vasculosum, and subfornical organ) implicated in central actions of AII. The sex specificity of the effect of estrogen was dependent on sexual differentiation of the brain. Manipulation of the neonatal hormone environment, which alters this brain differentiation, also altered the characteristic responses of the two sexes to estrogen. Neonatal androgenization of females, which causes masculinization and defeminization, resulted in animals which as adults no longer responded to EB with decreased drinking. On the other hand, preventing the development of a male brain by neonatal castration produced animals which as adults tended to decrease their drinking following estrogen. In summary, this study found that EB acts in the preoptic area to depress AII-induced responses by a site specific modulation of central AII receptors. Alteration of early brain development changed the responses of the two sexes to estrogen, perhaps by altering sexual differentiation of the preoptic area.
Angiotensin II↗
Cardiovascular investigations of an endogenous digoxin-like factor.
A circulating factor with digoxin immunoreactivity has been demonstrated. Elevated levels of this substance appear to be present after volume expansion and salt loading, and in some forms of hypertension. The potentially causative role for this factor in hypertension can be demonstrated by the normalization of blood pressure after antidigoxin antibody infusions in low-renin and sodium-dependent hypertension. The possibility that renal excretory defects may be the initiating event to elevate endogenous digoxin is suggested by studies with normotensive humans and monkeys with renal disease. In the latter case cardiovascular deficits were noted that were analogous to those detected in renal hypertensive monkeys with elevated endogenous digoxin. Considered together, these results suggest the existence of a natriuretic and hypertensive substance that plays a role in body fluid homeostasis and blood pressure regulation.
Animals↗
Muscarinic cholinergic receptors in the rat deep cerebellar nuclei: a quantitative autoradiographic study.
The distribution of muscarinic cholinergic receptors within the rat deep cerebellar nuclei was analyzed using in vitro receptor binding of [3H]quinuclidinylbenzilate (QNB) in conjunction with autoradiography. The highest density of QNB binding sites occurred in the lateral cerebellar (dentate) nucleus. Interpositus nuclei displayed an intermediate density of muscarinic cholinergic binding sites with the posterior interpositus nucleus demonstrating higher binding than the anterior nucleus. The fastigial (medial) cerebellar nucleus exhibited the lowest levels of QNB binding among the four cerebellar nuclei. These results indicate that muscarinic cholinergic receptors are present in the deep cerebellar nuclei and that differences in receptor density occur among the four nuclear groups.
Animals↗
Sodium appetite decreased by central angiotensin blockade.
Disturbances in body water and electrolytes that trigger sodium appetite, such as sodium depletion or hypovolemia, are potent activators of the renin-angiotensin system. In the absence of an actual deficit in body fluids, angiotensin injections are adequate to stimulate increased sodium ingestion. To assess whether angiotensin is a significant mediator of sodium appetite induced by acute alterations in body fluids, sodium intake was examined in rats during central or peripheral angiotensin blockade. Central blockade of angiotensin receptors by intracerebroventricular (ICVT) injection of the analogue antagonist saralasin decreased (but did not eliminate) sodium intake after polethylene glycol-induced hypovolemia or sodium depletion resulting from dialysis against glucose. Conversely, peripheral blockade of angiotensin converting enzyme with orally active captopril potentiated rather than decreased sodium appetite and stimulated water intake after sodium depletion. This increased water and salt intake after peripheral inhibition of converting enzyme was reversed, however, by concurrent central blockade of angiotensin receptors. These data support the hypothesis that angiotensin participates in sodium appetite associated with acute alteration in body fluids. Furthermore, the brain is the site at which angiotensin exerts its influence on sodium appetite. While the involvement of angiotensin of brain origin is not ruled out, the change in sodium appetite after peripheral blockade of converting enzyme suggests that circulating angiotensin derived from renal renin may interact with central angiotensin receptors regulating sodium appetite.
Angiotensin II↗