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At least 127 records · Page 7Linked to original sources

The current state of research with peripheral tissues in Huntington disease.

Huntington disease is a neurological autosomal dominant disease of unknown origin and the search for a suitable diagnostic marker has been extended to the peripheral tissues. It is generally believed that a membrane defect exists in Huntington disease although the evidence is controversial. It is the aim of this review to examine the validity of these claims for each of the peripheral tissues and techniques involved, and it is not intended to include all other aspects of research into Huntington disease.

Antibody-Dependent Cell Cytotoxicity↗

Peripheral tissue release of interleukin-6 in patients with chronic kidney diseases: effects of end-stage renal disease and microinflammatory state.

To examine if uremia influences muscle interleukin-6 (IL-6) metabolism we studied the exchange of IL-6 across the forearm in 16 patients with chronic kidney disease (CKD) (stages 3 and 4), in 15 hemodialysis (HD)-treated end-stage renal disease (ESRD) patients (n=15), and in six healthy controls. In addition, we performed an analysis of both IL-6 protein and IL-6 mRNA expression in muscle of CKD (stage 4) patients showing evidence of inflammation and in controls. A release of IL-6 from the forearm was observed in patients with elevated IL-6 plasma levels. Arterial IL-6 was directly related to released IL-6 (r=0.69; P<0.004) in HD patients. Both IL-6 protein and IL-6 mRNA expression were increased in muscle of inflamed CKD patients vs controls (P<0.05). Although muscle net protein balance was similar in all patients, it was significantly more negative in HD patients with high than in those with low IL-6 plasma levels (P<0.05). In addition, net protein balance was related to the forearm release of IL-6 in HD patients only (r=0.47; P<0.038). These data demonstrate that IL-6 expression is upregulated in muscle, and that muscle tissue, by releasing this cytokine, may contribute to the inflammatory response in HD patients. The release of IL-6 from peripheral tissues is associated with an increase in muscle protein loss in HD patients, suggesting that muscle release of IL-6 is linked to protein catabolism in these patients. The release of IL-6 from peripheral tissues may act as a signal for the inflammatory response and contribute to functional dysregulation in uremia.

Aged↗

Resetting of circadian time in peripheral tissues by glucocorticoid signaling.

In mammals, circadian oscillators reside not only in the suprachiasmatic nucleus of the brain, which harbors the central pacemaker, but also in most peripheral tissues. Here, we show that the glucocorticoid hormone analog dexamethasone induces circadian gene expression in cultured rat-1 fibroblasts and transiently changes the phase of circadian gene expression in liver, kidney, and heart. However, dexamethasone does not affect cyclic gene expression in neurons of the suprachiasmatic nucleus. This enabled us to establish an apparent phase-shift response curve specifically for peripheral clocks in intact animals. In contrast to the central clock, circadian oscillators in peripheral tissues appear to remain responsive to phase resetting throughout the day.

Animals↗

Localization of leptin receptor mRNA splice variants in murine peripheral tissues by RT-PCR and in situ hybridization.

Expression of leptin receptor splice variants, including the long form variant (Ob-Rb), has been examined in murine peripheral tissues. RT-PCR indicates that the leptin receptor, Ob-R, and in particular the Ob-Ra splice variant are expressed in a wide range of tissues. Expression of the Ob-R receptor was localized by in situ hybridization to specific sites in the spleen, testes, kidney, liver, lung, and adrenal. However, the long form leptin receptor, Ob-Rb, was only expressed at significant levels in the medulla of the adrenal and the inner zone of the medulla of the kidney. The specific sites of expression of different splice variants within peripheral tissues has important implications with regard to the function of leptin.

Animals↗

Effect of diabetes on the levels of two forms of Met-enkephalin in plasma and peripheral tissues of the rat.

Levels of native and cryptic or peptidase-derivable (after being digested with trypsin and carboxypeptidase) Met-enkephalin were measured by a specific radioimmunoassay method in plasma, anterior and neurointermediate lobes of pituitary and various peripheral tissues of streptozotocin (STZ) diabetic rats. The results show that the highest concentration of native and cryptic Met-enkephalin were found in the neurointermediate lobe of pituitary. Streptozotocine-induced diabetes alters the concentration of either or both forms of Met-enkephalin in plasma, the anterior and neurointermediate lobes of the pituitary, heart, lung, spleen, liver, seminal vesicle, vas deferens, kidney, bladder detrusor, and duodenum. One of the most pronounced effects of diabetes observed in this study is seen in the seminal vesicles where native Met-enkephalin was depleted to less than 10% of the control value. The uneven distribution of Met-enkephalin in peripheral tissues may suggest that these tissues process and/or metabolize Met-enkephalin to different degrees. Our data also suggest that STZ-induced diabetes alters the enkephalinergic activity in some of these tissues. It is suggested that some of the peripheral pathophysiological symptoms associated with diabetes may be attributed, in part, to altered activity of enkephalinergic systems.

Animals↗

Effect of age on vitamin E concentrations in various regions of the brain and a few selected peripheral tissues of the rat, and on the uptake of radioactive vitamin E by various regions of rat brain.

The concentrations of tocopherols in selected areas of the brains and a few peripheral tissues of 3-, 14-, and 30-month-old male Fischer 344 rats were determined by a high-performance liquid chromatographic method. Throughout the time period studied, alpha-tocopherol was the only tocopherol detected in the brain. Concentrations of alpha-tocopherol increased significantly with age in medulla and spinal cord whereas no such change was seen in other brain areas. Among the peripheral tissues, total tocopherol concentrations increased with age in the liver and adipose tissue while no significant changes were observed in the heart. The pattern of uptake of radioactive alpha-tocopherol from the serum by the various areas of the brain was similar for the 3- and 14-month-old animals even though the brains from the 14-month-old animals took up less of the radioactive compound. Measurable amounts of tocopherol esters were not present in the tissues of the 30-month-old animals.

Adipose Tissue↗

Prolactin receptor gene expression in the brain and peripheral tissues in broody and nonbroody breeds of domestic hen.

The objective of this study was to establish whether the gene encoding prolactin receptor (PRLR) is expressed in the hypothalamus and peripheral tissues of the domestic chicken and, if so, to determine whether there are breed differences in the structure or expression of the gene which might account for the observation that broodiness does not occur in the White Leghorn hen but does occur in other breeds of domestic hens, including the bantam. A preliminary experiment demonstrated that the absence of broodiness in White Leghorns is not due to a lack of a prolactin response to the avian prolactin-releasing hormone vasoactive intestinal polypeptide. The largest amounts of PRLR mRNA in the brain, which did not differ significantly between laying White Leghorns and bantams, were found in the pituitary gland and basal and preoptic hypothalamus. Small or nondetectable amounts were found in both breeds in the forebrain, cerebellum, and optic lobes. Prolactin receptor mRNA was widely distributed in peripheral tissues in both breeds, in the following descending order of abundance: kidney, leg skin, brood patch, duodenum, intestine > thyroid gland > adrenal gland, liver, ovary >> adipose tissue > thymus, spleen > muscle > blood. Southern blotting analysis using four restriction enzymes and a chicken PRLR cDNA probe demonstrated identical digestion patterns for White Leghorn and bantam genomic DNA. Northern blotting analysis identified two sizes of chicken PRLR mRNA transcripts (7.5 and 3.3 kb) in hypothalami from laying White Leghorn and bantam hens. It is concluded that differences in the expression of broodiness in White Leghorn and bantam hens cannot be explained by differences in the amounts of PRLR mRNA in the hypothalamus or in the transcription or gross structure of the PRLR gene.

Animals↗

Flow-mediated vasodilation of a conduit artery in relation to downstream peripheral tissue blood flow during reactive hyperemia in humans.

Arterial conduit vessels dilate in response to increased blood flow stimuli. Our objective was to determine precisely how a change in large arterial diameter results in a change in peripheral tissue blood flow. Using high-resolution ultrasound Doppler echography, we measured the diameter of the right femoral artery at rest, during reactive hyperemia, and after administration of 2.5 mg of sublingual isosorbide dinitrate in 10 healthy young men. Reactive hyperemia was induced by distal circulatory arrest followed by reperfusion of the leg ipsilateral (right) or contralateral (left) to the side of arterial diameter measurements. Femoral arterial blood flow was calculated by simultaneous measurement of femoral arterial diameter and blood velocity. The change in skin blood flow was also analyzed simultaneously by laser Doppler flowmetry. Reactive hyperemia induced a 2-fold increase in femoral arterial blood velocity 30 sec after cuff release. During this flow augmentation, the femoral artery dilated. The peak of skin blood flow was coincident with the peak of femoral arterial vasodilation. The time required for the return of arterial diameter to baseline was longer than that for blood flow in both the conduit artery and the peripheral skin tissue. Equivalent cuff occlusion and release of the contralateral limb had no effect on ipsilateral arterial diameter. Isosorbide dinitrate induced dilation in all subjects, despite the absence of a significant increase in blood velocity. These results indicate that the human femoral artery dilates in response to increased blood velocity, and that the flow-mediated vasodilation of a large conduit artery is involved in the adjustments of blood flow in the downstream peripheral tissue.

Adult↗

Concurrent aortic and mitral valve echocardiography permits measurement of systolic time intervals as an index of peripheral tissue thyroid functional status.

Systolic time intervals (STI) were measured directly from concurrent aortic and mitral valve echocardiographic tracings in 127 subjects to assess their utility as an index of peripheral tissue thyroid functional status. The subjects were categorized according to clinical symptoms and the results of thyroid function tests into the following 7 study groups: normal subjects (n = 34), overt hyperthyroid subgroup I (n = 12), overt hyperthyroid subgroup II (n = 28), subclinical hyperthyroid (n = 15), subclinical hypothyroid (n = 22), overt hypothyroid subgroup II (n = 6), and overt hypothyroidism subgroup I (n = 10). Compared with normal subjects, overt hyperthyroid subgroup I patients had a significantly shortened mean isovolumetric contraction time (ICT), preejection period (PEP), and PEP/LVET (LVET = left ventricular ejection time; P less than or equal to 0.0005); the overt hypothyroid subgroup I patients also had significantly lengthened mean ICT (P less than or equal to 0.005), PEP, and PEP/LVET (P less than or equal to 0.0005). Compared with normal subjects, overt hyperthyroidism subgroup II patients also had a very significant shortening of ICT (P less than 0.0005) as well as a significantly shortened PEP and PEP/LVET (P less than or equal to 0.005), whereas subclinical hyperthyroid patients (with normal serum free T4 index and total T3, and suppressed TSH by immunoradiometric assay) also had ICT, PEP, and PEP/LVET STI values which were significantly shortened (P less than 0.05) values. Compared to normal subjects, the overt hypothyroid subgroup II patients (who were clinically asymptomatic with reduced serum free T4 index and elevated TSH) had a prolongation of ICT, PEP, and PEP/LVET (P less than or equal to 0.05), whereas the values in subclinical hypothyroid patients were similar to those in normal subjects. From these observations we conclude that in the absence of underlying heart disease, the echocardiographic method used is a rapid, reliable, and sensitive technique for determining STI and provides direct information on peripheral tissue thyroid functional status.

Adult↗

Melatonin receptors in peripheral tissues: a new area of melatonin research.

Melatonin is synthesized and secreted by pineal gland, retina, harderian gland, lacrimal gland, and gut. It is a lipid-soluble molecule with ubiquitous distribution and multifarious functions. Thus, along with the better established sites of melatonin action, such as brain, retina, and pituitary, direct melatonin actions on other peripheral tissues should also be considered. The presence of melatonin receptors in peripheral tissues was rightfully hypothesized. Earlier studies on melatonin receptors had limited success. The advent of 2-[125I]iodomelatonin, a labelled melatonin agonist with a specific activity as high as 2,200 Ci/mmol, has allowed the studies of melatonin receptors with picomolar affinity and femtomolar density. Putative melatonin receptors demonstrated by autoradiography and/or radioreceptor assay in gut, kidney, lung, heart, vas deferens, and blood vessels are discussed.

Animals↗

Distribution of aromatase activity in brain and peripheral tissues of male sheep: effect of nutrition.

Conversion of testosterone to oestradiol plays a major role in the feedback inhibition of gonadotrophin secretion in male sheep but little is known of the distribution or control of aromatase activity among central and peripheral tissues. Changes in activity at those sites may mediate alterations in the effectiveness of negative feedback following, for example, a change in nutrition. Using a tritiated-water assay, we quantified aromatase in several tissues in mature male sheep, assessed their contribution to oestradiol production, and tested whether activity at each site was affected by a nutritional treatment that stimulates gonadotrophin secretion. Among the brain tissues, the preoptic area had the highest concentration of activity, followed by the hypothalamus, amygdala and cortex. Among the peripheral tissues, liver and testis had the highest activity and, due to their mass, they are the major sources of circulating oestradiol. Pituitary, muscle, kidney and adipose tissues had very low aromatase levels. The nutritional stimulus increased activity in testis but not in liver or brain. We conclude that changes in aromatase activity do not mediate the effects of nutrition on steroid feedback, but aromatisation in testis, liver and brain is important in the endocrine regulation of reproduction in the mature ram.

Animal Nutritional Physiological Phenomena↗

Endogenous inhibitors of [3H] Ro 5-4864 binding to "peripheral-type" binding sites for benzodiazepines are present in peripheral tissues and brain.

Recent observations have shown that "peripheral-type" binding sites for benzodiazepines (PBS) are under neural and/or hormonal control in the pineal gland, olfactory bulb, and kidney. These studies resulted in a search for endogenous substances which might physiologically subserve PBS. Acidified methanol or trichloroacetic acid extraction of both peripheral tissues and brain followed by ultrafiltration and/or gel filtration and high performance liquid chromatography revealed the presence of both high (Mr greater than 10,000) and low (Mr less than 500) molecular weight substances which inhibit the binding of [3H] Ro 5-4864 to PBS while only slightly inhibiting the binding of [3H] diazepam to classical "brain-type" benzodiazepine receptors.

Animals↗

Beta-adrenoceptor modulation of transiently overexpressed alpha 2-adrenoceptors in brain and peripheral tissues: cellular mechanisms underlying the developmental toxicity of terbutaline.

Terbutaline, a selective beta(2)-adrenoceptor (beta(2)AR) agonist, is widely used as a tocolytic to arrest preterm labor but recent studies indicate that excessive betaAR stimulation can alter the expression and function of other neurotransmitter receptors that are essential to fetal/neonatal development. In many immature tissues, alpha(2)-adrenergic receptors (alpha(2)ARs) are overexpressed and the receptors are thought to play a role in cell proliferation and architectural assembly. We evaluated whether betaAR agonists perturb the expression of alpha(2)ARs in central and peripheral tissues during various developmental stages in the fetal and neonatal rat. In peripheral tissues (heart, liver, kidney) administration of terbutaline (10mg/kg s.c. for 4 days) elicited decrements in alpha(2)AR expression only during a critical developmental window that differed for each tissue; terbutaline was more effective than isoproterenol, a mixed beta(1)/beta(2) agonist. Neonatal destruction of sympathetic nerves with 6-hydroxydopamine (6-OHDA) had a biphasic effect, initially reducing alpha(2)ARs but subsequently elevating receptor expression. In contrast to the effects in the periphery, terbutaline administration promoted alpha(2)AR expression in neonatal brain regions with effects preferential to males. As the rat is an altricial species, these results during late gestation and the early neonatal period indicate that betaAR input modulates alpha(2)AR expression during developmental stages in which betaAR tocolytics are likely to be used. Disruption of alpha(2)AR expression and function may therefore contribute to adverse effects that have been noted in the offspring of pregnant women treated with terbutaline.

Adrenergic alpha-2 Receptor Agonists↗

[Delivery of macromolecular drugs to the vitreous and its peripheral tissues].

We evaluated the release behavior of FITC-dextran with an average molecular weight of 4,400(FD4), as a model peptide drug, from poly(DL-lactic acid) (PLA) implant. The drug level in the vitreous and its peripheral tissues were measured following the implantation in the rabbit vitreous. The release profile of FD4 from the PLA implant was biphasic; a fraction of the drug molecules incorporated in the polymer implant was swiftly released; then slowly or even negligibly for a certain period of time and finally complete bursting release probably due to bulk erosion of the polymer. The time-course of drug concentration in the vitreous and aqueous humor after implantation showed a constant level for 14 days and then parabola, where the highest concentration appeared around 28 days. The drug concentrations in the retina/ choroid was maintained a constant level for 28 days. After an injection of FD4 in the rabbit vitreous, the drug concentration in those tissues approximately decreased mono-exponentially. These findings suggest that the present implant could be a useful carrier for delivery of macromolecular drugs to the vitreous and its peripheral tissues.

Animals↗

Muscle sensory neurons require neurotrophin-3 from peripheral tissues during the period of normal cell death.

To determine if muscle sensory neurons require neurotrophin-3 (NT3) during the period of normal cell death, we used an NT3-specific antiserum to deplete NT3 from peripheral tissues during this period in chick embryos. DiI staining of dorsal roots indicated that limb injections of anti-NT3 reduced the spinal projection of muscle spindle afferents. In contrast, injection of the antiserum into the spinal cord had no demonstrable effect, indicating that the reduced projection following limb injection was due to peripheral blockade of NT3 signaling. Counts of neurons retrogradely labeled from muscle and cutaneous nerves showed that peripheral blockade of NT3 selectively reduced the survival of muscle sensory neurons without affecting the survival of cutaneous sensory neurons or motoneurons. In situ hybridization with trkC probes indicated that, during the period of cell death, most large diameter muscle sensory neurons express trkC transcripts, whereas few cutaneous neurons express this receptor for NT3. We conclude that large diameter muscle afferents, including spindle afferents, require NT3 from peripheral tissues to survive the normal period of sensory neuron death in vivo.

Animals↗

Antiphase circadian expression between BMAL1 and period homologue mRNA in the suprachiasmatic nucleus and peripheral tissues of rats.

BMAL1 is a putative transcription factor which is involved in circadian rhythm generation in Drosophila. Northern blot analysis was performed to investigate the expression of rat BMAL1 mRNA in the suprachiasmatic nucleus (SCN) and peripheral tissues. In the SCN, circadian expression of BMAL1 mRNA which reaches its peak level at the time of dark-light transition was observed, and the expression pattern was antiphase to those of two period (per) homologues, rPer1 and rPer2. However, no circadian oscillation for rat Clock mRNA was detected. The circadian expression of BMAL1 mRNA was also observed in peripheral tissues such as brain (excluding the SCN), eye, heart, kidney, and lung. The amplitudes of BMAL1 and rPer2 mRNA expression levels were correlated between the different tissues, suggesting that the circadian expression of BMAL1 mRNA plays an important role in generating the circadian expression of per homologue genes in mammals.

ARNTL Transcription Factors↗

Inhibition of inositol 1,4,5-trisphosphate-mediated Ca2+ release by Ca2+ in cells from peripheral tissues.

Permeabilized cells attached to culture plates were used to evaluate the inhibition of inositol 1,4,5-trisphosphate-mediated release (IPMCR) by Ca2+. In AR42J cells, a pancreatic acinar cell line, when permeabilization and Ca2+ uptake were carried out at low ionized Ca2+ (0.06 microM), Ca2+ had little effect on IPMCR. On the other hand, when permeabilization and Ca2+ uptake were performed at 5 microM Ca2+, IPMCR was inhibited by Ca2+ with an apparent affinity of 0.24 microM. This inhibition could be modified by exposing the cytosol of permeabilized cells to low Ca2+. Hence, permeabilizing the cells in the presence of 5 microM Ca2+ and then exposing them to Ca2+ concentrations between 0.01 and 5 microM before washing and Ca2+ uptake in the presence of 5 microM Ca2+ resulted in a Ca2(+)-dependent loss of inhibitory activity. The loss of inhibitory activity occurred with an apparent affinity for Ca2+ of 0.21 microM. A similar phenomenon with a comparable apparent dissociation constant for Ca2+ was found with three other cell types from peripheral tissues: the osteosarcoma cell line UMR-106-01, the kidney inner medullary cell line IMCD, and primary culture of urinary bladder smooth muscle cells. The properties of inhibition of IPMCR by Ca2+ in cells from peripheral tissues differ from those previously described in neuronal tissues and suggest that a different factor(s) mediates the inhibition of IPMCR by Ca2+ in cells from peripheral and neuronal tissues.

Animals↗

GABA-receptors in peripheral tissues.

Gamma-aminobutyric acid (GABA) and its receptors are found in a wide range of peripheral tissues, including parts of the peripheral nervous system, endocrines, and non-neural tissues such as smooth muscle and the female reproductive system. In all these, both GABAA- and GABAB-receptor types are found, with good evidence for a physiological role in the gut, pancreatic islets and the urinary bladder. In some tissues, the pharmacology of GABA-induced actions is quite atypical and should be further explored with the newer ligands and modulators for GABAA- and GABAB-receptors.

Animals↗