Choir singing and health status in people affected by cancer.

Cancer survival rates have improved dramatically over recent years, however, health-related quality of life (HRQoL) for many patients, survivors and their families remains low even after successful treatment. This mixed-methods observational study explored the effects of participation in community choirs on HRQoL in individuals who have had cancer (patients) or have been affected by cancer (non-patients). This included a longitudinal analysis of choristers commencing the Tenovus Cancer Care "Sing with Us" choirs across Wales and a series of semi-structured interviews and focus groups. Participants completed the Short-form 36 and the Hospital Anxiety and Depression Scale on commencement of the choir and 3 and 6 months later. On joining the choir, several domains of the SF36 were lower, indicating worse HRQoL and greater depression in patients than non-patients (p < .05). In patients, choir participation improved vitality, overall mental health and anxiety. In non-patients, choir participation improved anxiety (p < .05). Participants experienced the choirs as both an uplifting musical activity and a supportive community group. The results support the provision of a spectrum of support options to meet the different needs and preferences of people affected by cancer.

Review of the Philippine taxa formerly assigned to the genus Amphicnemis Selys, II. Genus Sangabasis with descriptions of eight new species (Odonata: Coenagrionidae).

The Philippine genus Sangabasis Villanueva is reviewed. Eight new species are described: S. bukid sp. nov., S. bulba sp. nov., S. cahilogi sp. nov., S. carmelae sp. nov., S. feliculoi sp. nov., S. hamis sp. nov., S. janvantoli sp. nov., and S. zamboanga sp. nov.

Cyclic and geographic trends in seawater temperature and abundance of american lobster.

In Maine, fluctuations in the abundance of American lobster (Homarus americanus) and in seawater temperature have correlated well during the years since the first temperature measurements were made in 1905. Recent record catches in chronological sequence from the northern limit of range in Newfoundland to New York, while temperatures measured in Maine declined from higher to lower than optimum, suggest that at the present rate optimum conditions should reach the southern limit of the lobster's range by the mid-1970's.

Cognitive and language functions of the human cerebellum.

Traditionally, the human cerebellum has been regarded as a motor mechanism, but this view of its function is being challenged by a growing body of data on the non-motor functions of the cerebellum. Some of these data are presented in this article, which reviews neuroanatomical, neuroimaging and behavioral reports of cerebellar involvement in cognitive and language functions. The article proposes that this functional expansion is a consequence of specific cerebellar structural changes that evolved during hominid evolution and that could have been a prerequisite for the evolution of human language.

Taxonomy and molecular phylogeny of the Platystictidae of Sri Lanka (Insecta: Odonata).

The 22 Sri Lankan representatives of the family Platystictidae, all endemic to the island and belonging to the distinct endemic subfamily Platystictinae, are revised, and a new reconstruction of the phylogeny based on molecular characters is provided. Five new species are described: Ceylonosticta venusta sp. nov. (holotype ♂: Rambodde Falls, at the tunnel; Nuwara Eliya District, Central Province; N7.0489, E80.6961; 12-vii-2012; to be deposited at National Museum of Natural History, Colombo, Sri Lanka), C. inferioreducta sp. nov. (holotype ♂: Norton Bridge, stream on the B43 road 1.5km WNW of Norton Bridge; Nuwara Eliya District, Central Province; N6.9171, E80.5075; 28-vii-2009; to be deposited at National Museum of Natural History, Colombo, Sri Lanka), C. mirifica sp. nov. (holotype ♂: Uwella, primary forest on the road Uwella-Ratnapura, 11.5km NW of Balangoda; Ratnapura District, Sabaragamuwa Province; N6.6968, E80.6059; 16-vii-2012; to be deposited at National Museum of Natural History, Colombo, Sri Lanka), Platysticta secreta sp. nov. (holotype ♂: Hasalaka; Kandy District, Central Province; N7.3535, E80.9509; 31-v-1975; deposited at National Museum of Natural History, Smithsonian Institution, Washington, USA) and P. serendibica sp. nov. (holotype ♂: Kanneliya; Galle District, Southern Province; N6.2291, E80.3834; 8 & 9-vi-1975; deposited at National Museum of Natural History, Smithsonian Institution, Washington, USA). Additionally, a determination key, figures showing morphological details and coloration in life, as well as distribution maps for all species are presented. Based on molecular analysis of 21 taxa, the phylogeny of Platystictinae is presented and discussed from the zoogeographical and paleogeographical point of view. Sri Lankan species, traditionally placed in the genera Platysticta Selys and Drepanosticta Laidlaw / Ceylonosticta Fraser, separated into distinct clades within the subfamily as presently defined, but the monophyletic nature of the Platystictinae and its Sri Lankan endemicity is confirmed. For the South Indian species, formerly known as Platysticta deccanensis, morphological and molecular analyses demonstrated that it does not belong to the Sri Lankan clade and a new genus Indosticta gen. nov. is erected to accommodate it.

A splice variant of Skp2 is retained in the cytoplasm and fails to direct cyclin D1 ubiquitination in the uterine cancer cell line SK-UT.

Cyclin D1 is an important regulator of the transition from G1 into S phase of the cell cycle. The level to which cyclin D1 accumulates is tightly regulated. One mechanism contributing to the control of cyclin D1 levels is the regulation of its ubiquitination. SK-UT-1B cells are deficient in the degradation of D-type cyclins. We show here that p27, a substrate of the SCF(Skp2) ubiquitin ligase complex, is coordinately stabilized in SK-UT-1B cells. Further, we show that expression of Skp2 in SK-UT-1B cells rescues the cyclin D1 and p27 degradation defect observed in this cell line. These results therefore indicate that the SCF(Skp2) ubiquitin ligase complex affects the ubiquitination of cyclin D1. In addition, we show that SK-UT-1B cells express a novel splice variant of Skp2 that localizes to the cytoplasm and that cyclin D1 ubiquitination takes place in the nucleus. We propose that the translocation of Skp2 into the nucleus is required for the ubiquitination of cyclin D1 and that the absence of the SCF(Skp2) complex in the nucleus of SK-UT-1B cells is the mechanism underlying the ubiquitination defect observed in this cell line. Finally, our data indicates that differential splicing of F-box proteins may represent an additional level of regulation of the F-box mediated ubiquitination pathway.

Risks of morbidity and mortality in dialysis patients undergoing coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Although dialysis patients are undergoing CABG with increasing frequency, large studies specifically comparing patient characteristics and procedure-related risks in this population have not been performed. METHODS AND RESULTS: We conducted a regional prospective cohort study of 15,500 consecutive patients undergoing CABG in northern New England from 1992 to 1997. We used multiple logistic regression analysis to examine associations between preoperative dialysis-dependent renal failure and postoperative events and to adjust for potentially confounding variables. The 279 dialysis-dependent renal failure patients (1.8%) were 4.4 times more likely to experience in-hospital mortality than were other CABG patients (12.2% versus 3.0%, respectively; P:<0.001). Dialysis-dependent renal failure patients were older and had more comorbidities and more severe cardiac disease than did other CABG patients. After adjusting for these factors in multivariate analysis, however, dialysis-dependent renal failure patients remained 3.1 times more likely to die after CABG (adjusted odds ratio [OR] 3.1, 95% CI 2.1 to 4.7; P:<0.001). Dialysis-dependent renal failure patients compared with other CABG patients also had a substantially increased risk of postoperative mediastinitis (3.6% versus 1.2%, respectively; adjusted OR 2.4, 95% CI 1.2 to 4.7; P:=0.011) and postoperative stroke (4.3% versus 1.7%, respectively; adjusted OR 2. 1, 95% CI 1.1 to 3.9; P:=0.016), even after controlling for potentially confounding variables. Risks of reexploration for bleeding were similar for patients with and without dialysis-dependent renal failure. CONCLUSIONS: Preoperative dialysis-dependent renal failure is a strong independent risk factor for in-hospital mortality and mediastinitis after CABG.

Diabetes mellitus and optic atrophy in two siblings: a report on a new association and a review of the literature.

Two siblings with diabetes mellitus and optic atrophy (Wolfram syndrome) are described. As often noted, they also had atonic urinary bladders. Only one of the siblings had some impairment of hearing. Other findings not previously reported that appeared in each subject were esophageal dysphagia and vertigo. An autopsy in one revealed brain stem hypoplasia and thinning and flattening of the optic nerves with atrophy of the lateral geniculate bodies.

The effects of adrenalectomy and ovariectomy on the behavioral and hypothermic responses of rats to 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT).

The aim of this study was to determine the effects of sex, corticosterone and oestradiol-17 beta on the hypothermia and motor behavioural syndrome induced by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat. The hypothermia, but not the behavioural syndrome induced by 8-OH-DPAT was significantly greater in female compared with male rats. Adrenalectomy in male rats enhanced the hypothermic response, an effect prevented by corticosterone implants. Ovariectomy significantly attenuated the hypothermia induced by 8-OH-DPAT, an effect prevented by oestradiol-17 beta implants. Neither type of steroid manipulation affected the behavioural syndrome. These results show that sex, corticosterone and oestradiol-17 beta modulate the hypothermic response to 8-OH-DPAT in the rat, with corticosterone and oestradiol-17 beta having opposing effects.

Identification of tricyclic analogs related to ellagic acid as potent/selective tyrosine protein kinase inhibitors.

The plant-derived natural product ellagic acid (1) has recently been identified as a potent, though nonselective, inhibitor of the tyrosine-specific protein kinase pp60src. This report details efforts directed toward the identification of tricyclic structures related to ellagic acid, with enhanced specificity for inhibition of pp60src over other protein kinases. Phenanthridinone and carbazole core structures were selected for investigation, since N-functionalization allows for the synthesis of numerous analogs which can be utilized to probe enzyme-inhibitor interactions. These ring systems were prepared via a general sequence of biaryl bond formation followed by cyclization to form the desired tricyclic ring systems. N-Alkylation, -acylation, or -sulfonylation and deprotection with boron tribromide afford the target tetraphenolic phenanthridinones 5 and carbazoles 9. Several analogs from both of these series have potencies comparable to that of 1 and exhibit substantially enhanced selectivities for inhibition of pp60src relative to protein kinase A (PKA), a serine/threonine protein kinase. Carbazole-based analogs 9j,m,p are submicromolar inhibitors of pp60src, with potency for the target tyrosine kinase comparable to that of ellagic acid (1), however with 2 orders of magnitude greater selectivity versus that for PKA. As seen for ellagic acid, members of the phenanthridinone-based series (e.g., 5a) exhibited inhibition of pp60src in a manner which is partial mixed noncompetitive with respect to ATP, while analogs in the carbazole series (e.g., 9a) inhibit pp60src in an ATP competitive manner.

Benzyloxazolidine-2,4-diones as potent hypoglycemic agents.

A series of benzyloxazolidine-2,4-diones, containing oxazole-based side chains, were found to lower blood glucose levels in the genetically obese ob/ob mouse. Incorporation of a benzofuran structural element in these compounds provides greatly enhanced in vivo potency. The syntheses and structure-activity relationships for this series are detailed.

Uptake and release of [3H]dopamine by the median eminence: evidence for presynaptic dopaminergic receptors and for dopaminergic feedback inhibition.

The accumulation and release of [3H]dopamine by the median eminence in vitro was studied after treatments with different pharmacological agents, to determine whether such a procedure would be useful for measuring neuronal activity in the tuberoinfundibular dopaminergic system. The accumulation of [3H]dopamine was temperature, time, and sodium dependent, and reduced by unlabelled dopamine and by a potent dopamine uptake blocker, nomifensine. The outflow of tritium was studied after blocking the oxidative deamination of dopamine by nialamide. The outflow of tritium was elicited consistently by biphasic square wave electrical pulses and by high molarity potassium ions. The response to electrical stimulation was dependent largely on calcium and partially on sodium. The response to high molarity potassium ions was reduced in the absence of calcium ions. The response to electrical stimulation was increased by nomifensine and by a dopaminergic antagonist, haloperidol, and was reduced by dopamine and by a dopaminergic agonist, piribedil. The inhibitory action of dopamine was antagonized by haloperidol. These results indicate the existence of uptake and release mechanisms in the tuberoinfundibular dopamine neurons, and suggest that dopamine may inhibit its own release via dopaminergic receptors. This in vitro method may be useful for measuring dopamine uptake and release by tuberoinfundibular dopaminergic neurons.

Uptake of 5-hydroxytryptamine in different parts of the brain of the rabbit after intraventricular injection.

1 The uptake of 5-hydroxytryptamine (5-HT) was investigated in different areas of the rabbit brain (anterior hypothalamus, the raphe, the region of the substantia nigra, several cortical areas and the medulla oblongata) after intraventricular injection in pargyline pretreated animals by the formaldehyde-induced histochemical fluorescence method. 2 The distribution of fluorescence showed that the uptake of 5-HT, after circulation in the cerebrospinal fluid, caused a general increase in intensity of green yellow to yellow background fluorescence. There was an increased fluorescence in the nerve terminals, but no uptake occurred either in the cell bodies of neurones or in the glial cells.

Cellular localization of the uptake of 5-hydroxytryptamine in the area postrema of the rabbit after injection into a lateral ventricle.

1. The cellular localization of 5-hydroxytryptamine (5-HT) was investigated in the area postrema of the rabbit after intraventricular injection under different experimental conditions.2. 5-HT was found to be accumulated in different parts in and near to the area postrema, e.g. in glial cells, dorsal surface of the area postrema and ependyma of the central canal.3. The concentrations of 5-HT and 5-hydroxy indol-3-yl acetic acid (5-HIAA) were measured in different parts of the brain and CSF in control and in 5-HT treated animals with and without pargyline pretreatment. Intraventricular injection of 5-HT increased the concentration of 5-HT and 5-HIAA in the brain and in the CSF; pretreatment with pargyline further increased the concentrations of 5-HT but decreased the concentration of 5-HIAA.

A comparison of D and L-tryptophan on the cerebral metabolism of 5-hydroxytryptamine and dopamine in the dog.

1 After D and L-tryptophan (50 mg/kg) were given intravenously in the dog, the concentration of the amino acid was increased in ventricular cerebrospinal fluid (CSF) during the subsequent 4 h or sampling, although the concentrations were significantly lower following the administration of the D-isomer. 2 There was no evidence that D-tryptophan increased the synthesis of 5-hydroxytryptamine (5-HT) in dog brain as judged by the failure to cause a change in 5-hydroxyindoleacetic acid (5-HIAA) concentrations in ventricular CSF different from that seen with controls. 3 There was no appreciable conversion of D-tryptophan to L-tryptophan in the dog. 4 D-tryptophan was cleared more rapidly from plasma than L-tryptophan. 5 No difference in plasma binding between D and L-tryptophan was detected.

Pituitary adenylate cyclase-activating peptide-38 (PACAP)-38 is released into hypophysial portal blood in the normal male and female rat.

Pituitary adenylate cyclase activating polypeptide (PACAP) was first isolated from ovine hypothalamus as two molecular forms, the basic 38 residue amidated peptide PACAP-38 and the N-terminal 27 amino acid sequence PACAP-27. A dense plexus of PACAP immunoreactive fibres is present in the internal and external layers of the median eminence and in other parts of the hypothalamus with PACAP cell bodies in the paraventricular and supraoptic nuclei. The present study shows, for the first time, that, as assessed by radioimmunoassay of extracted plasma, the amount of PACAP-38 in hypophysial portal is significantly greater than in peripheral blood, and that as assessed by reversed phase high performance liquid chromatography, PACAP 1-38 is the major form in portal blood. This evidence is crucial for the fact that PACAP-38 may be a hypothalamic-pituitary regulatory factor.

Hypothalamic release of atrial natriuretic factor and beta-endorphin into rat hypophysial portal plasma: relationship to oestrous cycle and effects of hypophysectomy.

The release of beta-endorphin and atrial natriuretic factor (ANF) into hypophysial portal plasma was investigated in male and female Wistar rats. The principal aim of the study was to investigate the possible role of beta-endorphin and ANF in the hypothalamic control of LH and prolactin secretion. In male rats, anaesthetized with urethane, the concentrations of beta-endorphin in portal blood collected immediately after hypophysectomy were within the same range as those in peripheral plasma. Furthermore, electrical stimulation of the median eminence did not increase the portal plasma concentrations of beta-endorphin. In female rats, anaesthetized with alphaxalone, the portal plasma concentrations in long-term (6-8 weeks) or acutely hypophysectomized rats were significantly greater than those in peripheral plasma. In acutely hypophysectomized female rats the concentrations and contents of beta-endorphin in portal plasma collected at 10.00-11.30 h of pro-oestrus were significantly (approximately sixfold) greater than at dioestrus or at 20.00-21.00 h of pro-oestrus, but these changes were not consistently seen in all experiments. In female rats in which the pituitary gland was not removed for portal blood collection, portal plasma contents of ANF remained unchanged throughout the day of pro-oestrus, suggesting that it is unlikely that ANF is involved in the spontaneous LH or prolactin surge. The effects of ovarian steroids on the secretion of hypothalamic ANF and beta-endorphin were determined by measuring the portal plasma concentration of ANF and beta-endorphin on the morning of presumptive pro-oestrus in rats ovariectomized 24 h previously and injected with either oil or oestradial benzoate (OB). Portal plasma contents of ANF were significantly lower in OB- compared with oil-treated rats, suggesting that oestradiol inhibits ANF release into rat hypophysial portal plasma. In contrast, there were no significant between-group differences in the content or concentration of beta-endorphin in portal plasma. Thus, the increased beta-endorphin in the portal plasma of some of the intact animals during the morning of pro-oestrus is not due to the preovulatory surge of oestradiol-17 beta. The output of beta-endorphin into portal blood in long-term hypophysectomized rats was lower than in dioestrous or pro-oestrous rats in which the pituitary gland was removed immediately before portal blood collection.(ABSTRACT TRUNCATED AT 400 WORDS)

The 11 beta-hydroxysteroid dehydrogenase inhibitor glycyrrhetinic acid affects corticosteroid feedback regulation of hypothalamic corticotrophin-releasing peptides in rats.

Steroid-metabolizing enzymes modulate the effects of androgens on brain differentiation and function, but no similar enzymatic system has been demonstrated for adrenocorticosteroids which exert feedback control on the hypothalamus. 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) rapidly metabolizes physiological glucocorticoids (corticosterone, cortisol) to inactive products, thereby regulating glucocorticoid access to peripheral mineralocorticoid and glucocorticoid receptors in a site-specific manner. Using in-situ hybridization, we found expression of 11 beta-OHSD mRNA in neurones of the hypothalamic paraventricular nucleus (PVN) where corticotrophin-releasing factor-41 (CRF-41) is synthesized and from where it is released into hypophysial portal blood. Administration of glycyrrhetinic acid (GE), a potent 11 beta-OHSD inhibitor, decreased CRF-41 release into hypophysial portal blood in the presence of unchanged circulating glucocorticoid levels, suggesting that 11 beta-OHSD regulates the effective corticosterone feedback signal to CRF-41 neurones. These effects of GE were not observed in adrenalectomized animals, demonstrating dependence on adrenal products. In contrast, GE led to two- to threefold increases in arginine vasopressin and oxytocin release into portal blood, effects also dependent upon intact adrenal glands. These results suggest that 11 beta-OHSD in the PVN, and possibly other sites, may represent a novel and important control point of corticosteroid feedback on CRF-41 release in vivo.

Atrial natriuretic peptide is involved in the ACTH response to stress and glucocorticoid negative feedback in the rat.

The role of atrial natriuretic peptide (ANP) in the ACTH response to stress and the glucocorticoid negative feedback control of ACTH release was investigated in adult male homozygous Brattleboro and adrenalectomized Wistar rats respectively, using the technique of immunoneutralization. The relatively low ACTH response to stress and the lack of arginine vasopressin make the homozygous Brattleboro rat a more rigorous and simpler preparation in which to test the hypothesis that ANP is involved in the ACTH response to stress. In both sets of experiments, blood sampling and injection of sheep anti-ANP or control serum were carried out in conscious animals through intra-atrial cannulae implanted 2 days previously under halothane anaesthesia. A 30-s exposure to ether resulted in a brisk twofold increase in the plasma ACTH concentrations in homozygous Brattleboro rats infused with anti-ANP, but not control serum. The injection of either dexamethasone, a potent glucocorticoid receptor agonist, or corticosterone resulted in a rapid and marked reduction in the plasma concentrations of ACTH in Wistar rats which had been adrenalectomized, under halothane anaesthesia, at least 21 days before experimentation. The inhibitory action of dexamethasone, but not corticosterone, was significantly reduced in animals infused with anti-ANP serum. These results show that the inhibition of ANP release into hypophysial portal blood is probably important for triggering the ACTH response to stress and that ANP may play a role in corticosteroid negative feedback control of ACTH release mediated by type II (glucocorticoid) receptors.

Atrial natriuretic peptide is a physiological inhibitor of ACTH release: evidence from immunoneutralization in vivo.

The brain is thought to exert a predominantly stimulatory action on ACTH secretion mediated mainly by corticotrophin-releasing factor-41 (CRF-41) and arginine vasopressin (AVP). Several data, however, also point to the existence of an ACTH-inhibiting factor. Atrial natriuretic peptide (ANP), at concentrations found in hypophysial portal blood, inhibits ACTH release in vitro. The aim of the present studies was to use ANP immunoneutralization to determine whether ANP does in fact inhibit ACTH release in vivo. Intracerebroventricular infusion (1 microliters/min for 30 min) of sheep anti-ANP serum into male rats anaesthetized with sodium pentobarbitone had no significant effect on jugular venous plasma concentrations of ACTH or LH but did decrease significantly the plasma concentrations of prolactin. Intravenous infusion of 0.8 ml sheep anti-ANP serum but not control (non-immune) sheep serum, through an indwelling intra-atrial cannula in conscious male rats resulted in a marked and significant increase in plasma ACTH and corticosterone concentrations. The ACTH and corticosterone response to a 30-s ether stress was not significantly potentiated in the same conscious rats infused with anti-ANP serum. Intra-atrial infusion of anti-ANP did not significantly affect plasma prolactin, LH, glucose or sodium concentrations or plasma osmolality. These results show for the first time that ANP is a potent inhibitor of ACTH secretion in the conscious male rat and that, therefore, ANP is a hypothalamic neurohormone which is likely to play an important inhibitory role in the neural control of ACTH release.