bluuebunny/crossref_metadata_2025 huggingface dataset:
Second transplant with two unrelated cord blood units for early graft failure after haematopoietic stem cell transplantation
Authors: Fernandes Juliana , Rocha Vanderson , Robin Marie , De Latour Régis Peffault , Traineau Richard , Devergie Agnès , Ribaud Patricia , Réa Delphine , Larghero Jérôme , Gluckman Eliane , Socié Gérard
Published: April 2007

Graft failure (GF) can be a fatal complication following haematopoietic stem cell transplantation (HSCT). We report four patients who developed early GF after unrelated HSCT and who subsequently received a double unrelated cord blood transplant (dUCBT) after reduced‐intensity conditioning, at a median 15 d after the decision to perform a second transplant. Neutrophil recovery was observed in all four patients between day +15 and +31 with full donor chimaerism of one unit. Acute GVHD grades II–IV was observed in three patients. Three are alive, between 12 and 25 months after dUCBT. In conclusion, dUCBT is a promising procedure to treat early GF.
Interleukin‐10 gene polymorphism influences the prognosis of T‐cell non‐Hodgkin lymphomas
Authors: Lee Je‐Jung , Kim Dong Hwan , Lee Nan Young , Sohn Sang Kyun , Kim Jong Gwang , Kim Hyeoung‐Joon , Do Young Rok , Park Yeon Hee
Published: April 2007

Interleukin‐10 (IL‐10) is one of the cytokines implicated in the pathogenesis of diffuse large B‐cell lymphoma (DLBCL) in which it acts as auto/paracrine growth factor for lymphoma growth. T‐cell non‐Hodgkin lymphoma (NHL) is a heterogeneous disease, the biological basis of which is not fully understood. Some evidence suggests that IL‐10 might be associated with the progression of T‐cell NHLs and that IL‐10 may be involved in a rescue effect, protecting T cells from apoptotic cell death associated with upregulated bcl‐2 expression. The current study evaluated the impact of IL‐10 gene (IL10) polymorphism on the response to chemotherapy and survival in T‐cell NHL. IL10 polymorphisms were determined in 108 patients with T‐cell NHL. The response to chemotherapy was not dependent on IL10 polymorphism, while survival differed significantly according to IL10 polymorphism. The group with ATA haplotype showed superior overall survival (61·2 ± 5·9% vs. 21·2 ± 11·7%, P = 0·001) and failure‐free survival (35·0 ± 5·7% vs. 13·2 ± 8·7%, P = 0·001) compared to those without ATA haplotype. The ATA haplotype was identified as a favourable prognostic factor compared to non‐ATA haplotype (P = 0·037, hazard ratio 2·1), together with international prognostic index (IPI) in a multivariate model for overall survival. In conclusion, IL10 polymorphism may affect the survival of T‐cell NHL patients.
The Asp727Glu polymorphism in the TSH receptor is associated with insulin resistance in healthy elderly men
Authors: Peeters Robin P. , Van Der Deure Wendy M. , Van Den Beld Annewieke W. , Van Toor Hans , Lamberts Steven W. J. , Janssen Joop A. M. J. L. , Uitterlinden André G. , Visser Theo J.
Published: April 2007

Background  Variations in thyroid function within the normal range are associated with differences in metabolism and body composition. For instance, TSH is positively associated with body mass index (BMI). This could be due to alterations in thyroid hormone activity, or to direct effects of TSH, as the TSH receptor (TSHR) is also expressed in adipose tissue. The TSHR‐Asp727Glu polymorphism is associated with lower serum TSH levels in vivo. In this study, we analysed whether serum thyroid parameters and the TSHR‐Asp727Glu polymorphism were associated with glucose metabolism and insulin resistance. In addition, we analysed the Thr92Ala polymorphism in the type 2 deiodinase (D2), which was recently associated with insulin resistance.

Methods  Genotypes were determined in a population of 349 elderly men (age 77·7 ± 3·5 years), for whom serum thyroid parameters and data on insulin resistance, such as fasting blood glucose, serum insulin and homeostasis model assessment (HOMA) values, were available.

Results  In nondiabetic, euthyroid subjects, TSH was positively associated with leptin levels, whereas FT4 and rT3 were significantly negatively correlated with insulin and HOMA. Carriers of the TSHR‐Glu727 allele had a significantly higher glucose (P = 0·01), insulin (P = 0·001), glycated haemoglobin (HbA1c) (P = 0·002), HOMA (P = 0·001) and leptin (P = 0·008). The D2‐Ala92 allele showed a trend towards higher levels of insulin (P = 0·07) and a higher HOMA (P = 0·09).

Conclusion  In this population of nondiabetic elderly men, serum thyroid parameters and the TSHR‐Asp727Glu polymorphism were associated with relative insulin resistance. Our study suggests that genetic variation in TSHR plays a role in insulin resistance and thereby influences glucose metabolism.
Complete androgen insensitivity without Wolffian duct development: the AR‐A form of the androgen receptor is not sufficient for male genital development
Authors: Barbaro Michela , Oscarson Mikael , Almskog Ingrid , Hamberg Hans , Wedell Anna
Published: April 2007

Background  The androgen receptor (AR) is essential for the differentiation of male external and internal genitalia. It is normally present in two forms, a full‐length form B and an N‐terminal truncated form A with still unknown function. Mutations in the AR gene cause androgen insensitivity syndrome (AIS), which is divided into subgroups according to the degree of undermasculinization. Patients with completely female external genitalia are classified as complete AIS (CAIS). However, a recent study has shown that some CAIS patients have signs of internal male genital differentiation due to missense mutations that show some degree of residual function.

Objective  We aimed to study the expression of the different forms of the AR in two CAIS patients in relation to the development of male internal genital structures. One patient had a mutation (L7fsX33) that affects only the full‐length AR‐B form of the AR, whereas the other had a nonsense mutation (Q733X) affecting both isoforms.

Measurements and results  We thoroughly analysed internal genitalia at surgery and by histological examination. No signs of Wolffian duct (WD) development were present in any of the patients. Western blotting of proteins from gonadal and genital skin fibroblasts was performed with AR antibodies directed against different AR epitopes. The N‐terminally truncated A form was expressed in normal amounts in the patient with the L7fsX33 mutation while no AR was detected in the other patient.

Conclusion  The presence of the AR‐A form does not seem to be sufficient for WD maintenance and differentiation.
The impact of a TSH receptor gene polymorphism on thyroid‐related phenotypes in a healthy Danish twin population
Authors: Hansen Pia Skov , Van Der Deure Wendy M. , Peeters Robin P. , Iachine Ivan , Fenger Mogens , Sørensen Thorkild I. A. , Kyvik Kirsten O. , Visser Theo J. , Hegedüs Laszlo
Published: April 2007

Objectives The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size, serum levels of TSH, thyroid hormones, and thyroid antibodies in 1241 healthy Danish twin individuals and (2) assessed the contribution of the polymorphism to the trait variation and the genetic variance.

Measurements The effect of the genotype on the traits (mean ± SD) was established; associations between the TSHR‐Asp727Glu polymorphism and measures of thyroid homeostasis were assessed and the effect of the polymorphism on the trait's phenotypic variability was quantified by incorporating the genotype information in structural equation modelling.

Results The genotype distribution was Asp/Asp 84·9%; Asp/Glu 14·5% and Glu/Glu 0·6%. Carriers of the TSHR‐Glu727 allele had lower TSH levels (noncarriersvs.carriers: 1·78 ± 0·93vs.1·60 ± 0·84 mU/l,P = 0·04). Regression analysis showed an association between the TSHR‐Asp727Glu polymorphism and serum TSH (P = 0·007). The polymorphism accounted for 0·91% of the total phenotypic variance in serum TSH levels. Including the genotype in quantitative genetic modelling improved the model fit (P = 0·001); however, the genetic influence on serum TSH not attributable to this specific genetic variant was only reduced from 68·2% to 67·8%. The polymorphism was not significantly associated with thyroid size, thyroid hormones or thyroid antibody levels.

Conclusions The TSHR‐727Glu allele was associated with decreasing TSH levels; however, the contribution to the genetic variance was very small. No association was found with other thyroid‐related measures.
Quality of life and psychiatric sequelae following aneurysmal subarachnoid haemorrhage: does neuroendocrine dysfunction play a role?
Authors: Kreitschmann‐Andermahr Ilonka , Poll Eva , Hutter Bernd O. , Reineke Andrea , Kristes Sabine , Gilsbach Joachim M. , Saller Bernhard
Published: April 2007

Objective  Patients who have sustained aneurysmal subarachnoid haemorrhage (SAH) often suffer persistent impairments in their quality of life (QoL) and psychological disturbances despite a good neurological outcome. In the light of the high prevalence of partial hypopituitarism in SAH survivors demonstrated in recent investigations, we aimed to determine whether neuroendocrine dysfunction has an impact on QoL and neurobehavioural symptoms in these patients.

Design/patients  QoL, depression and psychological distress were assessed in 40 SAH survivors who had undergone endocrine function testing at least 1 year after the haemorrhage.

Measurements  QoL was assessed using the Nottingham Health Profile (NHP), the Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL‐AGHDA) and the Short Form‐36 questionnaire (SF‐36). The Beck Depression Inventory (BDI) and the Impact of Event Scale (IES) were used to evaluate depression and symptoms of current subjective distress in response to the SAH as a stressful life event, respectively.

Results  In a stepwise multiple regression analysis, basal cortisol level was included as the first and often only predictor for several QoL domains assessing psychological aspects of well‐being and depression whereas physical aspects of QoL were predicted primarily by neurological recovery from the SAH. Severe GH deficiency (GHD) was the first predictor for the criterion NHP subscale ‘Energy’ and highest stimulated ACTH level in the insulin tolerance test (ITT) was the first predictor for disturbed sleep as assessed with the NHP subscale ‘Sleep’.

Conclusion  Our results provide preliminary data that neuroendocrine disturbances contribute to disturbed QoL, depression and sleeping disturbances in SAH patients.
Mixed lineage kinases (MLKs): a role in dendritic cells, inflammation and immunity?
Authors: Handley Matthew E. , Rasaiyaah Jane , Chain Benjamin M. , Katz David R.
Published: April 2007

This review summarizes current knowledge about the mixed lineage kinases (MLKs) and explores their potential role in inflammation and immunity. MLKs were identified initially as signalling molecules in the nervous system. They were also shown to play a role in the cell cycle. Further studies documented three groups of MLKs, and showed that they may be activated via the c‐Jun NH2terminal kinase (JNK) pathway, and by Rho GTPases. The biochemistry of the MLKs has been investigated in considerable detail. Homodimerization and heterodimerization can occur, and both autophosphorylation and autoinhibition are seen. The interaction between MLKs and JNK interacting protein (JIP) scaffolds, and the resultant effects on mitogen activated protein kinases, have been identified. Clearly, there is some redundancy within the MLK pathway(s), since mice which lack the MLK3 molecule are not abnormal. However, using a combination of biochemical analysis and pharmacological inhibitors, several recent studiesin vitrohave suggested that MLKs are not only expressed in cells of the immune system (as well as in the nervous system), but also may be implicated selectively in the signalling pathway that follows on toll‐like receptor ligation in innate sentinel cells, such as the dendritic cell.
Nitric oxide mediates the inhibitory effect of ethanol on the motility of isolated longitudinal muscle of proximal colon in rats
Authors: Wang S. L. , Xie D. P. , Liu K. J. , Qin J. F. , Feng M. , Kunze W. , Liu C. Y.
Published: April 2007

Abstract The aim of the present study was to investigate the effect of ethanol on colon motility in rats and to test the possibility that nitric oxide (NO) mediates this effect. Proximal colon longitudinal muscle strips (LM) (8 × 3 mm) cut parallel to the longitudinal muscle fibres of the colon were isolated and mounted in an organ bath. Ethanol (0.57, 0.87 and 1.30 mmol L−1) dose‐dependently inhibited the motility of LM. Longitudinal muscle strips from female rats were more sensitive to the inhibitory effect of ethanol than that from male rats. L‐NAME (N‐nitro‐l‐arginine methyl ester) (100 μmol L−1), AG (aminoguanidine) (10 μmol L−1), ODQ (1H‐[1,2,4]Oxadiazolo[4,3‐a]quinoxalin‐1‐one) (10 μmol L−1) and PTIO (2‐Phenyl‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl 3‐oxide) (200 μmol L−1) partly blocked the inhibitory effect of ethanol on LM. Pretreatment with L‐NAME, AG, ODQ and PTIO abolished the sex difference of the inhibitory effect of ethanol on LM. Tetrodotoxin (TTX) (10 μmol L−1) partly blocked the inhibitory effect but did not influence the sex difference. The relaxation of LM induced by SNP (sodium nitroprusside) (0.1–10 μmol L−1) in female rats was greater than that in male rats. In conclusion, ethanol inhibited the colon motilityin vitro. This inhibitory effect on LM was mediated by NO through the iNOS – NO – cGMP pathway.
Intestinal permeability and irritable bowel syndrome
Authors: Camilleri M. , Gorman H.
Published: April 2007

Abstract Based on a systematic PubMed search, this short review addresses why intestinal permeability may be important in the pathobiology of irritable bowel syndrome (IBS), the evidence of abnormal permeability in patients with IBS, and the pros and cons of the different probe molecules available to assess intestinal permeability. While a subgroup of patients with IBS appears to have evidence of increased intestinal permeability, improvements in the methods and validation are key to further research in this field in order to better understand intestinal barrier functions in IBS.
A potential role for the vanilloid receptor TRPV1 in the therapeutic effect of curcumin in dinitrobenzene sulphonic acid‐induced colitis in mice
Authors: Martelli L. , Ragazzi E. , Di Mario F. , Martelli M. , Castagliuolo I. , Dal Maschio M. , Palù G. , Maschietto M. , Scorzeto M. , Vassanelli S. , Brun P.
Published: April 2007

Abstract  A protective role of the transient potential vanilloid receptor 1 (TRPV1) in intestinal inflammation induced by dinitrobenzene sulphonic acid (DNBS) has been recently demonstrated. Curcumin, the major active component of turmeric, is also able to prevent and ameliorate the severity of the damage in DNBS‐induced colitis. We evaluated the possibility that curcumin (45 mg kg−1 day p.o. for 2 days before and 5 days after the induction of colitis) was able to reduce DNBS‐induced colitis in mice, by acting as a TRPV1 agonist. Macroscopic damage score, histological damage score and colonic myeloperoxidase (MPO) activity were significantly lower (by 71%, 65% and 73%, respectively; P < 0.01), in animals treated with curcumin compared with untreated animals. Capsazepine (30 mg kg−1, i.p.), a TRPV1 receptor antagonist, completely abolished the protective effects of curcumin. To extend these data in vitro, Xenopus oocytes expressing rat TRPV1 were examined. Capsaicin‐evoked currents (3.3 μmol L−1) disappeared subsequent either to removal of the agonist or subsequent to the addition of capsazepine. However, curcumin (30 μmol L−1) was ineffective both as regard direct modification of cell membrane currents and as regard interference with capsaicin‐mediated effects. As sensitization of the TRPV1 receptor by mediators of inflammation in damaged tissues has been shown previously, our results suggest that in inflamed, but not in normal tissue, curcumin can interact with the TRPV1 receptor to mediate its protective action in DNBS‐induced colitis.
Angiotensin II receptor subtypes in the kidney: Distribution and function
Authors: ZHUO Jialong , ALCORN Daine , HARRIS Peter J , McCAUSLAND Jane , ALDRED G Peter , MENDELSOHN Frederick AO
Published: April 2007

Summary: Angirotensin II (AII) is a powerful humoral regulator of body fluid and electrolyte balance and arterial blood pressure. In the kidney, All influences renal haemodynamics and proximal tubular reabsorption of sodium through activation of All that mediate complex signal transduction pathways. Angiotensin II is also implicated in the pathophysiological process of some progressive renal diseases. Pharmacological characterization and molecular cloning of All receptor reveals at least two major subtypes of All receptors, AT1 and AT2, in the kidney and other tissues. the AT1 receptor cDNA encodes a 359 amino acid protein with structure typical of seven transmembrane G‐protein coupled receptors. Two isoforms of AT1 receptor, AT1A and AT1B, are known in rodents, but probably only one occurs in other mammals including humans. the AT2 receptor cDNA, a 363 amino acid protein, shares only 32% identical amino acid residues with AT1 receptor, although it also has a seven transmembrane domain topology. In adult mammalian kidneys, AT1 receptors predominate in the glomerular mesangium, proximal tubular epithelium, renomedullary interstitial cells in the inner stripe of the outer medulla and large preglomerular vessels except those in human and monkey where AT2 receptors predominate. By contrast, in foetal kidneys, AT2 receptors are the major subtype; however, this shows dramatic regulation during development. Physiological studies using AT1 selective antagonists show that the known actions of All on renal haemodynamics, glomerular filtration, and tubular sodium and water transport are mediated by this subtype of All receptors. In addition, AT1 receptors also mediate hypertrophic and mitogenic actions of All on cultured glomerular mesangial cells and proximal tubular epithelial cells, and on extra‐cellular matrix accumulation in animal models of progressive renal diseases. By contrast, blockade of AT2 receptors has no effect on renal haemodynamics, tubular sodium reabsorption or growth properties of All. Overall, All exerts multiple actions in the kidney by interacting with different subtypes of All receptors located on multiple cellular sites.
Systemic lupus erythematosus: A follow‐up study of Japanese patients with end‐stage renal failure treated with haemodialysis
Authors: SATO Atsuhisa , SUZUKI Hiromichi , MURAKAMI Marohito , KANNO Yoshihiko , NAITOH Mareo , SARUTA Takao
Published: April 2007

Summary: In order to explore the clinical course of Japanese patients with systemic lupus erythematosus (SLE) in end‐stage renal failure, the clinical findings from 26 patients who had received haemodialysis were analysed. Each patient was followed for 72 months from the onset of clinical lupus nephritis to the initiation of haemodialysis. In most patients, renal disease progressed to end‐stage renal failure despite clinical quiescence of SLE, which remained inactive throughout haemodialysis treatment. Seven patients (27%) had clinically active SLE with high dose prednisolone (mean; 49.3 mg per day) at initiation of haemodialysis. These patients had relatively rapid progression of their renal failure and 2 patients died within 1 month of their first haemodialysis. During the follow‐up period from starting haemodialysis for an average of 44 months, most patients received ongoing haemodialysis while their SLE remained clinically inactive. Six patients (23%) died, 5 of those within 1 month from starting hemodialysis. the results of this long‐term follow up of a large number of haemodialysis patients with lupus nephritis indicate that: (i) most patients with lupus nephritis undergoing haemodialysis have an excellent survival rate; and (ii) patients with active SLE at initiation of haemodialysis have a high mortality rate (within 1 month). We therefore conclude that more effective treatment for SLE in the presence of renal failure is required for these patients.
Risk factors and outcome of hypertension in living related renal transplant recipients
Authors: SUD K , RAO M , JACOB CK , SHASTRY JCM
Published: April 2007

Summary: Impaired allograft function is an important cause of hypertension in cadaveric renal transplant recipients. the risk factors for post‐tranplant hypertension in living related transplant recipients with inherent good graft functions are likely to be different and have not been studied. In addition, controversy surrounds any independent effect hypertension might have on renal allograft functions. Four hundred and seventy three living related renal allograft recipients were retrospectively analysed to study the risk factors for development of post‐transplant hypertension and its effect on graft outcome. Prevalence of hypertension was 76.1%. the presence of pre‐transplantation hypertension was the most important independent risk factor for development of hypertension after transplantation. This suggests an important role of retained native diseased kidneys as a cause of hypertension. Other risk factors included: cyclosporin A immunosuppression, patient age less than 40 years and the presence of renal insufficiency at last follow up. Hypertension did not have any effect on patient or graft survival during the mean follow‐up period of 20.1 ± 13.7 months; however, it was associated with an independent risk for the presence of renal insufficiency in the post‐transplant period.
Effects of dietary cholesterol on the fatty acid composition of glomerular phospholipids in the rat
Authors: OU Zhouluo , NATORI Yumiko , YASUGI Etsuko , NAKANISHI Kazuko , DOHI Taeko , OSHIMA Mieko , NATORI Yasuhiro
Published: April 2007

Summary: Hypercholesterolaemia is considered to be an exacerbating factor in glomerular diseases. This study was designed to assess the effects of dietary cholesterol on the fatty acid composition of glomerular phospholipids and, in particular, on the level of arachidonic acid, since eicosanoids play an important role in the control of glomerular function. High dietary levels of cholesterol for a 3‐week period induced a high level of cholesterol in liver microsomes and hypercholesterolaemia in rats. the level of arachidonic acid in liver microsomes and serum decreased by 32 and 39%, respectively, when compared to controls. the cholesterol content of glomeruli was unchanged by the high cholesterol diet. However, the level of arachidonic acid in glomerular total phospholipids was significantly reduced (by 93%) in cholesterol‐fed rats. the decrease in arachidonic acid content was more marked (20%) in the phosphatidylcholine fraction of glomeruli. the level of linoleic acid increased in total phospholipids and phosphatidylcholine fraction of glomeruli by 15 and 12%, respectively. These results indicate that dietary cholesterol alters the fatty acid composition of glomerular phospholipids, which might contribute to the progression of glomerular diseases.
Expression of transforming growth factor‐β type II receptor mRNA in embryonic and adult rat kidney
Authors: CLARK Amander T , FORD Miriam D , NURCOMBE Victor , ALCORN Daine , KEY Brian , PUCHE Adam C , BERTRAM John F
Published: April 2007

Summary: The transforming growth factor‐β (TGF‐β) family of growth factors regulates cell proliferation, differentiation, extracellular matrix synthesis and angiogenesis in many developing tissues. Transforming growth factor‐β1 was recently shown to affect the branching of ureteric epithelium and nephron formation in cultured rat metanephroi. As the TGF‐β type II receptor is specific for the TGF‐β family, the present study used in situ hybridization to localize mRNA for this receptor in metanephroi from Sprague‐Dawley rat embryos. Transforming growth factor‐β type II receptor mRNA was located in ureteric duct epithelium, undifferentiated mesenchymal cells in the nephrogenic zone, vesicles, comma‐shaped bodies and S‐shaped bodies. In some S‐shaped bodies, TGF‐β type II receptor mRNA was not expressed in the lower limb, which subsequently forms the renal corpuscle. Expression was not observed in capillary loop stage glomeruli and maturing glomeruli, or in proximal tubules and interstitial cells. In adult rat kidney, TGF‐β type II receptor mRNA was expressed in cortical collecting ducts and distal tubules but not in glomeruli or proximal tubules. These findings demonstrate that the prominent expression of TGF‐β type II receptor mRNA decreases as glomeruli and tubules develop. Expression then remains undetectable in adult glomeruli and proximal tubules. the developmentally‐regulated expression of this receptor suggests a key role in glomerular and nephron development.
Interleukin‐1α and tumour necrosis factor‐α modulate the production of monocyte chemoattractant protein‐1 by cultured human glomerular visceral epithelial cells
Authors: PRODJOSUDJADI Wiguno , VAN DET Nicole F , VERHAGEN Nicole AM , GERRITSMA Jort SJ , BRUIJN Jan A , DAHA Mohamed R , VAN ES Leendert A
Published: April 2007

Summary: Mediators released by glomerular macrophages may stimulate glomerular visceral epithelial cells (GVEC) to produce cytokines, growth factors or extracellular matrix components. This study describes that human GVEC produce monocyte chemoattractant protein‐1 (MCP‐1), a monocyte‐specific chemotactic factor, and the effects of interleukin‐lα (IL‐1α) and tumour necrosis factor‐α (TNF‐a) on the production of MCP‐1 by GVEC.

We observed that the intensity of MCP‐1 staining in GVEC is stronger in membranous nephropathy and glomerulosclerosis than in normal kidneys. Various cell lines of GVEC produced significant amounts of MCP‐1, as assessed by inhibition radio‐immunoassay. the presence of IL‐1α and TNF‐α during culture of GVEC enhanced the production of MCP‐1 in a dose‐ and time‐dependent manner. Glomerular visceral epithelial cells in culture express mRNA for MCP‐1 and the expression is upregulated 2.0‐ and 1.4‐fold in the presence of optimal concentration of IL‐1α and TNF‐α, respectively. De novo synthesis of MCP‐1 is supported by the observation that MCP‐1 production is fully inhibited by cydoheximide. Monocyte chemoattractant protein‐1 isolated from GVEC supernatants exhibits a molecular size of 12 and 10 kDa as determined by gel filtration chromatography. Both sizes of MCP‐1 is chemotactically active for monocytes.

This study shows increased MCP‐1 production by cultured human GVEC after stimulation with the inflammatory cytokines IL‐1α and TNF‐α. the expression of MCP‐1 in GVEC was found to be upregulated in membranous nephropathy and glomerulosclerosis. These findings suggest that MCP‐1 may be involved in glomerular injury in these diseases. the possible role of MCP‐1 in the pathogenesis of human glomerulonephritis is discussed.
Expression of basic fibroblast growth factor and its receptor in the progression of rat crescentic glomerulonephritis
Authors: NG Yee‐Yung , NIKOLIC‐PATERSON David J , MU Wei , ATKINS Robert C , LAN Hui Y
Published: April 2007

Summary: The aim of this study was to examine the relationship of basic fibroblast growth factor (FGF‐2) and its receptor (FGF‐R) to tubular proliferation, interstitial fibrosis, glomerular cell proliferation and crescent formation in the development of anti glomerular basement membrane (GBM) glomerulonephrids in the rat. Using new microwave‐based histochemistry techniques, weak constitutive expression of mRNA and protein for FGF‐2 and FGF‐R was evident in tubules and glomeruli of normal rat kidney. Double and triple staining with the proliferating cell nuclear antigen (PCNA) demonstrated that in disease there was focal up‐regulation of FGF‐2 and FGF‐R mRNA and protein expression within proliferating tubules and fibroblast‐like cells in areas of interstitial fibrosis. In contrast, tubules in non‐inflamed areas of kidney showed no change in FGF‐2 and FGF‐R expression or cellular proliferation. In addition, many FGF‐2+PCNA+ and FGF‐R+PCNA+ cells, probably mesangial cells and podocytes, were evident within glomerular segmental proliferative lesions. of particular interest was the observation that many epithelial cells within cellular crescents, inculding proliferating (PCNA+) epithelial cells, strongly expressed both FGF‐2 and FGF‐R. Furthermore, there was strong FGF‐2 and FGF‐R expression by proliferating fibroblast‐like cells within fibrocellular crescents suggesting that FGF‐2 is involved in the formation and fibrotic progression of glomerular crescents. In conclusion, this study provides evidence that increased expression of FGF‐2 and its receptor may participate in the proliferative/fibrotic response in progressive crescentic glomerulonephritis.
Changes in blood pressure and vasoactive hormones during volume expansion in stable patients on chronic haemodialysis
Authors: VOSS David M , LYNN Kelvin L , BUTTIMORE Adrian L , ESPINER Eric A
Published: April 2007

Summary: We studied changes in blood pressure (BP) and plasma hormones (atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], endothelin [ET], angiotensin [AII] and renin [PRA]) in four stable haemodialysis patients 48 h after a routine dialysis (basal stat), after volume expansion (4–7% above dry bodyweight) for 4 days then 48 h later following ultrafiltration. Blood pressure rose and plasma AII and PRA values fell with volume expansion and returned to baseline at the end of the study. Endothelin values were unchanged. Plasma ANP and BNP rose similarly in three patients and returned to near baseline levels after ultrafiltration. Sustained volume expansion over 4 days in dialysis patients is associated with an increase in BP, a marked elevation in plasma ANP and BNP but without change in ET.
HVC interneurons are not renewed in adult male zebra finches
Authors: Scotto‐Lomassese Sophie , Rochefort Christelle , Nshdejan Arpenik , Scharff Constance
Published: April 2007

Adult neurogenesis is a widespread phenomenon in many species, from invertebrates to humans. In songbirds, the telencephalic region, high vocal center (HVC), continuously integrates new neurons in adulthood. This nucleus consists of a heterogenous population of inhibitory interneurons (HVCIN) and two populations of projection neurons that send axons towards either the robust nucleus of the arcopallium (HVCRA) or the striatal nucleus area X (HVCX). New HVC neurons were initially inferred to be interneurons, because they lacked retrograde labelling from the HVC's targets. Later studies using different tracers demonstrated that HVCRA are replaced but HVCX are not. Whether interneurons are also renewed became an open question. As the HVC's neuronal populations display different physiological properties and functions, we asked whether adult HVC indeed recruits two neuronal populations or whether only the HVCRA undergo renewal in adult male zebra finches. We show that one month after being born in the lateral ventricle, 42% of the newborn HVC neurons were retrogradely labelled by tracer injections into the RA. However, the remaining 58% were not immunoreactive for the neurotransmitter GABA, nor for the calcium‐binding proteins, parvalbumin (PA), calbindin (CB) and calretinin (CR) that characterize different classes of HVCIN. We further established that simultaneous application of parvalbumin, calbindin and calretinin antibodies to HVC revealed approximately the same fraction of HVC neurons, i.e. 10%, as could be detected by GABA immunoreactivity. This implies that the sum of HVCIN expressing the different calcium‐binding proteins constitute all inhibitory HVCIN. Together these results strongly suggest that only HVCRA are recruited into the adult HVC.
Endocannabinoids mediate muscarine‐induced synaptic depression at the vertebrate neuromuscular junction
Authors: Newman Zachary , Malik Priya , Wu Tse‐Yu , Ochoa Christopher , Watsa Nayantara , Lindgren Clark
Published: April 2007

Endocannabinoids (eCBs) inhibit neurotransmitter release throughout the central nervous system. Using theCeratomandibularismuscle from the lizardAnolis carolinensiswe asked whether eCBs play a similar role at the vertebrate neuromuscular junction. We report here that the CB1cannabinoid receptor is concentrated on motor terminals and that eCBs mediate the inhibition of neurotransmitter release induced by the activation of M3muscarinic acetylcholine (ACh) receptors.N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide, a CB1antagonist, prevents muscarine from inhibiting release and arachidonylcyclopropylamide (ACPA), a CB1receptor agonist, mimics M3activation and occludes the effect of muscarine. As for its mechanism of action, ACPA reduces the action‐potential‐evoked calcium transient in the nerve terminal and this decrease is more than sufficient to account for the observed inhibition of neurotransmitter release. Similar to muscarine, the inhibition of synaptic transmission by ACPA requires nitric oxide, acting via the synthesis of cGMP and the activation of cGMP‐dependent protein kinase. 2‐Arachidonoylglycerol (2‐AG) is responsible for the majority of the effects of eCB as inhibitors of phospholipase C and diacylglycerol lipase, two enzymes responsible for synthesis of 2‐AG, significantly limit muscarine‐induced inhibition of neurotransmitter release. Lastly, the injection of (5Z,8Z,11Z,14Z)‐N‐(4‐hydroxy‐2‐methylphenyl)‐5,8,11,14‐eicosatetraenamide (an inhibitor of eCB transport) into the muscle prevents muscarine, but not ACPA, from inhibiting ACh release. These results collectively lead to a model of the vertebrate neuromuscular junction whereby 2‐AG mediates the muscarine‐induced inhibition of ACh release. To demonstrate the physiological relevance of this model we show that the CB1antagonistN‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide prevents synaptic inhibition induced by 20 min of 1‐Hz stimulation.
Facilitation of spontaneous glycine release by anoxia potentiates NMDA receptor current in the hypoglossal motor neurons of the rat
Authors: Kono Yu , Shigetomi Eiji , Inoue Kiyoharu , Kato Fusao
Published: April 2007

Deficiency in energy supply, such as occurs during hypoxia, anoxia, metabolic stress and mitochondrial failure, strongly affects the excitability of central neurons. Such lowered energy supply evokes various changes in spontaneous synaptic input to the hippocampal and cortical neurons. However, how this energy deprivation affects synaptic input to motor neurons, which are also vulnerable to energy deprivation, has never been addressed. Here we report for the first time the effect of metabolic stress on synaptic input to motor neurons by recording postsynaptic currents in the hypoglossal nucleus. Chemical anoxia with NaCN (1 mm) and anoxia with 95% N2 induced a persistent inward current and a marked and robust increase in action potential‐independent synaptic input. This increase was abolished by strychnine, but not by picrotoxin, CNQX or MK‐801, indicating glycine release facilitation. Blockade of voltage‐dependent Ca2+ channels and extracellular Ca2+ deprivation strongly attenuated this facilitation. The amplitude of inward currents evoked by local application of NMDA to the motor neurons in the presence of strychnine was significantly increased during NaCN application. A saturating concentration of d‐serine occluded this potentiation, suggesting that released glycine activated the glycine‐binding sites of NMDA receptors. By contrast, neurons in the dorsal motor nucleus of the vagus showed no detectable change in synaptic input in response to NaCN. These data suggest that increase in synaptically released glycine in response to metabolic stress may play an exacerbating role in NMDA receptor‐mediated excitotoxicity in motor neurons.
Chronic cocaine sensitizes striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptors
Authors: Centonze Diego , Rossi Silvia , De Chiara Valentina , Prosperetti Chiara , Battista Natalia , Bernardi Giorgio , Mercuri Nicola B. , Usiello Alessandro , Maccarrone Mauro
Published: April 2007

Behavioural studies indicate that cannabinoid receptors are implicated in cocaine addiction. The synaptic underpinning of cocaine–cannabinoid receptor interaction is however, obscure. We have studied electrophysiologically the sensitivity of cannabinoid receptors modulating synaptic transmission in the striatum of rats exposed to cocaine. One‐day treatment with cocaine did not modify the synaptic response to HU210, a cannabinoid CB1 receptor agonist. Seven days cocaine‐treatment, conversely, caused conditioned place preference, and sensitized striatal GABAergic synapses to the presynaptic effect of cannabinoid CB1 receptor stimulation. The cannabinoid receptor‐induced modulation of glutamate transmission was unaltered by cocaine. Furthermore, the effects of chronic cocaine on cannabinoid‐mediated regulation of striatal GABA synapses were attenuated one week after the discontinuation of cocaine, and absent two weeks later, indicating the progressive reversibility of the adaptations of cannabinoid system during abstinence of drug consumption. Our data support the concept that modulation of cannabinoid receptors might be useful against drug abuse.
Signalling pathways underlying neural cell adhesion molecule‐mediated survival of dopaminergic neurons
Authors: Ditlevsen Dorte Kornerup , Berezin Vladimir , Bock Elisabeth
Published: April 2007

Stimulation of the neural cell adhesion molecule (NCAM) by homophilic interactions is known to lead to neurite outgrowth as well as to neuronal survival. Whereas a complex network of signalling molecules is known to be of importance to NCAM‐mediated neurite extension, only limited information is available regarding signalling underlying NCAM‐mediated neuroprotection. Here, we present data suggesting a difference in the signalling events required for survival of rat dopaminergic neurons as compared with neurite outgrowth from the same cell type. Whereas Fyn, fibroblast growth factor receptor, mitogen‐activated protein and ERK kinase, protein kinase A and protein kinase C are required for both responses to NCAM‐induced signalling, phospholipase C and Ca2+‐calmodulin‐dependent kinase II are only necessary for the neurite outgrowth response, but dispensable for neuroprotection.
Neural adaptation reveals state‐dependent effects of transcranial magnetic stimulation
Authors: Silvanto Juha , Muggleton Neil G. , Cowey Alan , Walsh Vincent
Published: April 2007

Transcranial magnetic stimulation (TMS) is now widely used as a ‘virtual’ lesion paradigm to investigate behavioural functions, but the mechanisms through which it influences neural processing are unclear. To understand the differential effects of TMS on spatially overlapping populations of neurons we manipulated the relative activity levels of visual neurons by adapting subjects to a range of visual stimuli. By applying TMS to the visual cortex representing the central visual field we have shown in two experiments that the behavioural and perceptual effects of TMS depend on the state of adaptation of the neural population stimulated by TMS. Specifically, we have demonstrated that within the stimulated area TMS perceptually facilitates the attributes encoded by the less active neural population. We have demonstrated the generality of this principle for both suprathreshold and subthreshold TMS as well as for colour and orientation‐contingent colour using both subjective reports and psychophsyical measures. These findings can explain how TMS disrupts cognitive functions and therefore have implications for all studies which use TMS to disrupt behaviour.
Ministers in Ulster: The Machinery of Direct Rule
Authors: WINDLESHAM LORD
Published: April 2007

Lord Windlesham Lord Privy Seal and Leader of the House of Lords, was until recently Minister of State for Northern Ireland. This article is the revised text of a lecture he gave at The New University of Ulster on 26 April 1973. The lecture was delivered as one of a series of six, arranged by the Department of Social Administration at The New University, which have since been published as Occasional Papers. I would like to acknowledge the kindness of Professor H. Griffiths in agreeing so readily to the proposal to reproduce Lord Windlesham's contribution to this series of lectures in ‘Public Administration‘. (Hon. Editor.)
Local Government Finance: Assessing the Central Governmant's Contribution
Authors: CRISPIN A.
Published: April 2007

It is widely believed that between 60 to 66 per cent. of local authority expenditure (or income) is met by grants from central government alone. This popularly held view is challenged in this paper through a consideration of the current system of funding. We begin with the rate support grant procedure and identify some common sources of misunderstanding; these concern the definition of the rate support grant itself and the true nature of relevant expenditure. This leads us to examine the question of local authority miscellaneous income from fees, sales, rents and other sources from which we conclude that its contribution is underestimated. However it is general knowledge that besides miscellaneous income local authorities derive their income from two other principal sources namely, government grants and local rates. Accordingly the remainder of the paper examines in turn the contribution of these three sources towards (i) local authority revenue expenditure in respect of rate fund services, (ii) local authority revenue income and (iii) local authority income including both revenue and capital receipts. In no instance does central government's share approach 60 per cent. Thus, it would appear that the contribution of government is being overestimated while that of miscellaneous income underestimated. The implications of this are discussed.
Reforming the Parliamentary Commissioner
Authors: MARSHALL GEOFFREY
Published: April 2007

For the most part reforms in administrative procedures in England are not produced by rational argument. So the fact that a Committee of Justice has enumerated the deficiencies in the Parliamentary Commissioner legislation gives one no great confidence that the deficiencies will be remedied. Nevertheless the Committee chaired by David Widdicombe QC has performed a useful service by setting out the obvious flaws in the British Ombudsman machinery.* They can be summed up under five headings.
FISCAL FEDERALISM, PROFESSIONALISM AND THE TRANSFORMATION OF AMERICAN STATE GOVERNMENT
Authors: McKAY DAVID H.
Published: April 2007

A combination of political and economic forces have helped to return the states to the centre of the political stage. Whether measured by objective indicators (employment, share of government expenditure, elasticity of state revenues) or political institutional changes (the rise of career governors, the increasing influence of the intergovernmental lobby and the spread of state responsibilities), the states have become increasingly important in the formulation and implementation of American domestic policies. However, these changes have by no means reduced the level of intergovernmental conflict. On the contrary, cuts in federal expenditure, the introduction of block grants and public opposition to increases in state and local taxation are likely to intensify debate on distributional questions at the state level.
NATIONALIZED INDUSTRIES AS ORGANIZED INTERESTS
Authors: TIVEY LEONARD
Published: April 2007

The nationalized industries are usually regarded as bodies to be ‘controlled’ in some way by governments; but they have now developed sufficient autonomy to be able to exert influence on their own behalf within the political system. The emergence of the Nationalized Industries Chairman's Group is one aspect of their activity; the separate industries are also more outspoken in their own concerns. These developments deserve some consideration on both political and economic grounds. In the end the justification lies in their need to compete politically with other industrial interest groups. In the contemporary polity no one else will act for them, and so their leaders have a right, and perhaps a duty, to sustain their industries by ‘pressure‐group’ tactics. Clearly the industries can be seen as ‘state corporatist’ bodies in the usual conceptualizations, but the development of political autonomy could contribute to a more open structure of the public sector.
MANAGEMENT INFORMATION FOR MINISTERS: THE MINIS SYSTEM IN THE DEPARTMENT OF THE ENVIRONMENT
Authors: LIKIERMAN ANDREW
Published: April 2007

MINIS, a management information system for ministers in the Department of the Enviroment, was introduced by Michael Heseltine in 1980. The article summarizes the main features of the system and analyses some of the issues arising from its introduction, in particular, whether it is likely to be adopted by other government departments or public bodies. The reasons offered by departments as to why it is difficult to transfer are examined, together with other factors which are likely to inhibit transfer to other public sector bodies. The mechanism for promoting the spread of such systems is also discussed. The conclusion is that MINIS ought to be considered by other bodies and it has almost certainly already had some impact on systems elsewhere in central government, but without a central initiative, more widespread adoption is on past evidence unlikely, although parts of it may be adopted.
CONSULTATIVE PROCESSES IN HEALTH POLICY IN THE UNITED KINGDOM: A VIEW FROM THE CENTRE
Authors: HAYWOOD STUART , HUNTER DAVID J.
Published: April 2007

Health policy at national level is the product of a series of continuous and complex interactions between interest groups operating both inside and outside government. It is generally thought that these consultative processes are closed, elitist and dominated by the prestigious medical specialties. Yet there has been a rapid growth in the number of groups representing various interests, professions and care groups. Drawing on recent examples from the national health service, the paper explores the extent to which consultative processes in health policy have remained closed or have been opened up to new influences. The analysis suggests that consultation within the health department is more pluralistic than is usually appreciated. Also, while the closed, elitist mode of consultation with external interests has been eroded marginally, it remains more or less intact. Nevertheless, the ability of powerful medical interests to get their own way to the exclusion of other interests depends on the resources and sanctions available to other groups and on the particular policy issue. It can no longer just be assumed.
THE OMBUDSMAN IN BRITAIN: A QUALIFIED SUCCESS IN GOVERNMENT REFORM
Authors: GWYN WILLIAM B.
Published: April 2007

The Parliamentary Commissioner for Administration has not been the dismal failure forecast by critics at the time the office was established in 1967. One alleged defect — not criticizing the substance of administrators’ discretionary decisions — is characteristic to a large degree of other admired ombudsmen. Recruiting the Commissioner and his investigators from the civil service has not had expected harmful effects. On the other hand, the office has fallen short of the performance of other ombudsmen with regard to the public's access to the Commissioner (the MP filter), the efficiency of his investigative methods, and certain limitations on his jurisdiction. Failure so far to remove these defects appears to be the result of inadequate comparative research and analysis in support of reformers’ proposals, the overly cautious and consensual style of civil service policy formulation, and opposition from members of existing institutions (MPS and the officers of civil service unions) who mistakenly believe that their complaint handling activities are threatened by proposed changes.