bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular resistance in the prostate evaluated by colour Doppler ultrasonography: is benign prostatic hyperplasia a vascular disease?
Authors: BERGER ANDREAS P. , HORNINGER WOLFGANG , BEKTIC JASMIN , PELZER ALEXANDRE , SPRANGER ROBERT , BARTSCH GEORGE , FRAUSCHER FERDINAND
Published: June 2006

There is a wide variety of topics in this section of the Journal this month. The papers come from Austria, Israel, Scotland, Denmark, England and Australia. I am, as ever, pleased that the Journal continues to receive papers from so many countries, and that the high standard of these papers help us to maintain a quality product of great general interest to the reader.

OBJECTIVE

To evaluate prostatic vascular resistance by measuring the resistive index (RI), and flow velocity using colour Doppler ultrasonography (CDUS), in normal prostates and in patients with benign prostatic hyperplasia (BPH) or prostate cancer, as BPH is considered to be a result of urogenital ageing and studies suggest that hyperplasia in the stromal and glandular compartments might be induced by stromal growth secondary to hypoxia, which in turn results from abnormal blood flow patterns.

PATIENTS, SUBJECTS AND METHODS

Ninety‐two men (22 with normal prostates, 45 with BPH and 25 with prostate cancer; mean age 56 years) were prospectively evaluated by CDUS. The RI values for the peripheral, central and transition zones were assessed by one investigator. The diagnosis of BPH and prostate cancer was established from histological findings.

RESULTS

The mean (sd) RI in the transition zone was significantly higher only in patients with BPH, at 0.77 (0.05), vs 0.65 (0.05) in the other two groups. In the peripheral and central zones there was no significant difference in the RI among the three groups. Arterial CDUS flow velocity was increased in the transition zone of patients with BPH, but not in the peripheral and central zones.

CONCLUSIONS

The present results support the hypothesis that an age‐related impairment of blood supply to the lower urinary tract might have a role in the development of BPH. Although prostate cancer cannot be excluded by measuring RI, high RI values (>0.75) in the transition zone are indicative of BPH.
Radical cystectomy with ileal conduit diversion: early prospective evaluation of the impact of robotic assistance
Authors: Rhee Jonathan J. , Lebeau Sam , Smolkin Mark , Theodorescu Dan
Published: June 2006

Associate Editor

Ash Tewari

Editorial Board

Ralph Clayman, USA

Inderbir Gill, USA

Roger Kirby, UK

Mani Menon, USA

OBJECTIVE

To compare the performance of radical cystectomy with ileal conduit diversion by standard methods with that using the assistance of the daVinci robotic system (Intuitive Surgical, Sunnyvale, CA, USA).

PATIENTS AND METHODS

From November 2003 to August 2005, we performed 30 radical cystectomies with ileal conduit urinary diversions on patients with bladder cancer. Seven patients (one woman) had a cystectomy with the daVinci system and 23 (nine women) had a standard cystectomy. Data were collected prospectively, including estimated blood loss (EBL), transfusion requirement, operative duration, hospital stay and body mass index (BMI), and compared.

RESULTS

The mean EBL and transfusion requirements for standard and daVinci‐assisted cases was 1109 and 479 mL (P = 0.002) and 2.7 and 1.6 units (P = 0.14), respectively. Four of seven patients received a transfusion in the robotic group, and 20 of 23 in the standard group (P = 0.084). The mean operative duration was 638 and 507 min (P = 0.005) for the daVinci and standard group, respectively, with respective mean hospital stays of 11 and 13 days (P = 0.52). There was no difference in patient BMI between the groups (P = 0.22).

CONCLUSION

The daVinci‐assisted cystectomy appears to offer some advantages over standard cystectomy. Larger randomized studies are needed to confirm these findings.
A phase II trial of imatinib mesylate in patients with biochemical relapse of prostate cancer after definitive local therapy
Authors: Lin Amy M. , Rini Brian I. , Weinberg Vivian , Fong Kristen , Ryan Charles J. , Rosenberg Jonathan E. , Fong Lawrence , Small Eric J.
Published: June 2006

OBJECTIVE

To determine the biological effects of imatinib mesylate (STI‐571, Gleevec®; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by prostate‐specific antigen (PSA) kinetics in men with biochemical relapse of prostate cancer after definitive local therapy.

PATIENTS AND METHODS

Men with prostate cancer, who had had definitive local therapy, with nonmetastatic recurrent disease as manifested by a rising PSA level, were enrolled on this phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and continuously until disease progression or unacceptable toxicity. The PSA level was measured monthly.

RESULTS

In all, 20 men with biochemically relapsed prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of the 19 evaluable men, one achieved a ≥ 50% reduction in PSA level and two had decreases of <50%. For the 16 men in whom the on‐treatment PSA doubling time (PSADT) could be calculated (those with increasing PSA level) the median PSADT did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men discontinued therapy due to toxicity and the trial was stopped early due to toxicity.

CONCLUSIONS

Based on the lack of PSA modulation and pronounced toxicities leading to early closure of this trial, further study of single‐agent imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this patient population.
Intimal media thickness, glucose intolerance and metabolic syndrome in Asian Indians—the Chennai Urban Rural Epidemiology Study (CURES −22)
Authors: Mohan V. , Gokulakrishnan K. , Sandeep S. , Srivastava B. K. , Ravikumar R. , Deepa R.
Published: June 2006

Aims  The aim of the present study was to assess carotid intimal media thickness (IMT) in different grades of glucose intolerance and the metabolic syndrome (MS) in Asian Indians, a high‐risk group for diabetes and coronary artery disease.

Methods  Subjects with normal glucose tolerance (NGT) (n = 1600), impaired glucose tolerance (IGT) (n = 330), newly diagnosed diabetes (NDD) (n = 330) and known diabetes (KD) (n = 1170) were recruited from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing study on a representative population of Chennai (formerly Madras), in southern India. Assessment of carotid IMT was performed using high‐resolution B‐mode ultrasonography. MS was defined using modified adult treatment parel (ATP) III guidelines. Subjects with self‐reported diabetes, hypertension and dyslipidaemia were excluded from the analysis on MS.

Results  Subjects with glucose intolerance had significantly higher mean carotid IMT values compared with subjects with normal glucose tolerance (NGT 0.69 ± 0.12 mm, IGT 0.75 ± 0.16 mm, NDD 0.79 ± 0.19 mm and KD 0.87 ± 0.24 mm, P < 0.001). Regression analysis showed that there was a linear increase in mean IMT values with increasing severity of glucose intolerance, even after adjusting for age and gender. Mean IMT values were higher in those with MS and increased with increase in number of metabolic abnormalities (subjects without any metabolic abnormality 0.66 ± 0.12 mm, one abnormality 0.67 ± 0.13 mm, two 0.70 ± 0.12 mm, three 0.72 ± 0.12 mm, four 0.77 ± 0.15 mm, five 0.76 ± 0.13 mm). Regression models showed MS to be associated with IMT, even after adjusting for age, gender and presence of diabetes (P = 0.021).

Conclusio  In Asian Indians, carotid IMT increases progressively with increasing severity of glucose intolerance and is also associated with the metabolic syndrome, independent of age, gender and presence of diabetes.
Quality of care in diabetic patients attending routine primary care clinics compared with those attending GP specialist clinics
Authors: Ismail H. , Wright J. , Rhodes P. , Scally A.
Published: June 2006

Aim  To determine the impact on clinical outcomes of specialist diabetes clinics compared with routine primary care clinics.

Methods  Observational study measuring clinical performance (process/outcome measures) in the primary care sector. A cohort of patients attending specialist diabetes clinics was compared with a control cohort of patients attending routine primary care clinics.

Results  Patients seen in specialist diabetes clinics had a significantly higher HbA1c than patients in routine primary care clinics (mean difference 0.58%; P < 0.001) but there was no significant difference in rate of improvement with visits compared with primary care clinics. In contrast, patients seen in the routine primary care clinics had significantly higher cholesterol levels (mean difference 0.24 mmol/l; P < 0.001) compared with patients in specialist diabetes clinics and their improvement was significantly greater over time (mean difference 0.14 mmol/l per visit compared with 0.10 mmol/l; P < 0.006). Patients in routine primary care clinics also had significantly higher diastolic blood pressure (mean difference 1.6 mmHg; P < 0.007) but there was no difference in improvement with time compared with specialist diabetes clinics. Uptake of podiatry and retinal screening was significantly lower in patients attending routine primary care clinics, but this difference disappeared with time, with significant increases in uptake in the primary care clinic group. Weight increased in both groups significantly with time, but more so in the specialist clinic patients (mean increase 0.18 kg per visit more compared with routine clinic primary care patients; P < 0.001).

Conclusions  This study provides evidence that the provision of primary care services for patients with diabetes, whether traditional general practitioner clinics or diabetes clinics run by general practitioners with special interests, is effective in reducing HbA1c, cholesterol and blood pressure. However, the same provision of care was unable to prevent increasing weight or creatinine over time. No evidence was found that patients in specialist clinics do better than patients in routine primary care clinics.
Structured patient education: the Diabetes X‐PERT Programme makes a difference
Authors: Deakin T. A. , Cade J. E. , Williams R. , Greenwood D. C.
Published: June 2006

Aims  To develop a patient‐centred, group‐based self‐management programme (X‐PERT), based on theories of empowerment and discovery learning, and to assess the effectiveness of the programme on clinical, lifestyle and psychosocial outcomes.

Methods  Adults with Type 2 diabetes (n = 314), living in Burnley, Pendle or Rossendale, Lancashire, UK were randomized to either individual appointments (control group) (n = 157) or the X‐PERT Programme (n = 157). X‐PERT patients were invited to attend six 2‐h group sessions of self‐management education. Outcomes were assessed at baseline, 4 and 14 months.

Results  One hundred and forty‐nine participants (95%) attended the X‐PERT Programme, with 128 (82%) attending four or more sessions. By 14 months the X‐PERT group compared with the control group showed significant improvements in the mean HbA1c (− 0.6% vs. + 0.1%, repeated measures anova, P < 0.001). The number needed to treat (NNT) for preventing diabetes medication increase was 4 [95% confidence interval (CI) 3, 7] and NNT for reducing diabetes medication was 7 (95% CI 5, 11). Statistically significant improvements were also shown in the X‐PERT patients compared with the control patients for body weight, body mass index (BMI), waist circumference, total cholesterol, self‐empowerment, diabetes knowledge, physical activity levels, foot care, fruit and vegetable intake, enjoyment of food and treatment satisfaction.

Conclusions  Participation in the X‐PERT Programme by adults with Type 2 diabetes was shown at 14 months to have led to improved glycaemic control, reduced total cholesterol level, body weight, BMI and waist circumference, reduced requirement for diabetes medication, increased consumption of fruit and vegetables, enjoyment of food, knowledge of diabetes, self‐empowerment, self‐management skills and treatment satisfaction.
Diabetes service provision: a qualitative study of the experiences and views of Pakistani and Indian patients with Type 2 diabetes
Authors: Lawton J. , Ahmad N. , Hanna L. , Douglas M. , Hallowell N.
Published: June 2006

Aims  To explore Pakistani and Indian patients’ experiences of, and views about, diabetes services in order to inform the development of culturally sensitive services.

Design  Qualitative, interview study involving 23 Pakistani and nine Indian patients with Type 2 diabetes recruited from general practices and the local community in Edinburgh, Scotland. Data collection and analysis occurred concurrently and recruitment continued until no new themes emerged from the interviews.

Results  Respondents expressed gratitude for the availability of free diabetes services in Britain, as they were used to having to pay to access health care on the Indian subcontinent. Most looked to services for the prompt detection and treatment of complications, rather than the provision of advice about managing their condition. As respondents attached importance to receiving physical examinations, they could be disappointed when these were not offered by health‐care professionals. They disliked relying on interpreters and identified a need for bilingual professionals with whom they could discuss their diabetes care directly.

Conclusions  Gratitude for free services in Britain may instil a sense of indebtedness which makes it difficult for Pakistanis and Indians to be critical of their diabetes care. Health‐care professionals may need to describe their roles carefully, and explain how different diabetes services fit together, to avoid Pakistani and Indian patients perceiving treatment as unsatisfactory. Whilst linkworker schemes may meet patients’ need to receive culturally sensitive information in their first language, work is needed to assess their effectiveness and sustainability.
Incidence and trends of childhood Type 1 diabetes worldwide 1990–1999
Authors:   The DIAMOND Project Group
Published: June 2006

Aims  To examine incidence and trends of Type 1 diabetes worldwide for the period 1990–1999.

Methods  The incidence of Type 1 diabetes (per 100 000/year) was analysed in children aged ≤ 14 years from 114 populations in 112 centres in 57 countries. Trends in the incidence of Type 1 diabetes were analysed by fitting Poisson regression models to the dataset.

Results  A total of 43 013 cases were diagnosed in the study populations of 84 million children. The age‐adjusted incidence of Type 1 diabetes among 112 centres (114 populations) varied from 0.1 per 100 000/year in China and Venezuela to 40.9 per 100 000/year in Finland. The average annual increase in incidence calculated from 103 centres was 2.8% (95% CI 2.4–3.2%). During the years 1990–1994, this increase was 2.4% (95% CI 1.3–3.4%) and during the second study period of 1995–1999 it was slightly higher at 3.4% (95% CI 2.7–4.3%). The trends estimated for continents showed statistically significant increases all over the world (4.0% in Asia, 3.2% in Europe and 5.3% in North America), except in Central America and the West Indies where the trend was a decrease of 3.6%. Only among the European populations did the trend in incidence diminish with age.

Conclusions  The rising incidence of Type 1 diabetes globally suggests the need for continuous monitoring of incidence by using standardized methods in order to plan or assess prevention strategies.
Promoting group talk and higher‐order thinking in pupils by ‘coaching’ secondary English trainee teachers
Authors: Sutherland Julia
Published: June 2006

One hundred and eighty British secondary school pupils aged 11–12 and their six trainee teachers in five schools participated in an action research project, designed to improve the quality of children's group talk in English lessons, particularly their engagement in higher‐order thinking through ‘exploratory’ talk. The programme, supported by the Teacher Training Agency (TTA), now Training and Development Agency, was devised by a team of mentors and an Initial Teacher Educator from Sussex University. It aimed to develop the trainees' skills both in planning challenging tasks for, and sustaining effective group talk, using ‘ground rules’ and varied teacher discourse strategies. The data include qualitative comparative analysis of discourse audiotaped before and after the intervention, taken from 66 pupils. Findings indicate a clear improvement in the quality of talk, in terms of pupils' collaborative engagement in higher‐order thinking. Further evidence from observations and interviews with all participants suggests confirmation of the programme's effectiveness in improving trainees' and pupils' skills in, and understanding of how to use group talk to reason.
The problem with English: the exploration and development of student teachers' English subject knowledge in primary classrooms
Authors: Twiselton Samantha
Published: June 2006

This paper explores the relationship between student teachers' behaviour and their underlying thoughts and beliefs as they learn to teach English in the primary school. It draws on data from a study involving student teachers at a range of points in their Initial Teacher Education programmes at a university in England. It uses these data to explore the knowledge frameworks that appear to underpin the actions that participants take in the classroom as they teach primary English. This is related to an exploration of the values, beliefs and professional identity held by the student teachers, and conclusions are drawn concerning key factors to be considered in the construction of Initial Teacher Education programmes.
Linking literacy teaching with assessment: a continuing professional development initiative for secondary schools
Authors: Fisher Douglas , Lapp Diane , Flood James , Moore Kelly
Published: June 2006

As part of a professional development initiative helping secondary school teachers use assessment data to guide their instruction, teachers in this study changed their knowledge, skills and dispositions. Over time, they were able to identify assessments, administer these assessments, interpret the results and plan instruction. As a result, the students who were tutored by these teachers increased their achievement compared with a control group.
Non‐intrusive monitoring of otters (Lutra lutra) using infrared technology
Authors: Garcia de Leaniz C. , Forman D. W. , Davies S. , Thomson A.
Published: June 2006

Remote, non‐intrusive monitoring of elusive mammals remains problematic, particularly in running waters. The utility of using submerged infrared counters for monitoring non‐intrusively the activity of Eurasian ottersLutra lutrawas assessed in three tributaries of the River Dee (Beltie, Cattie, Feardar; Scotland) during 2003–2004. Otters passing through the infrared counters were strongly nocturnal and displayed a bimodal diel activity pattern. Seasonal activity indices varied fourfold between tributaries and peaked during the salmonid breeding season. The median time elapsing between consecutive night visits was 2.02±0.79 days and did not differ between tributaries. The median head–body length of adult otters was estimated at 75.0±1.1 cm, whereas median upstream swimming speed was calculated at 0.97±0.01 m s−1. Minimum census estimates revealed the activity of at least two adults in the Beltie, two adults and three juveniles in the Cattie, and two adults with one juvenile in the Feardar. Our study indicates that, under suitable conditions, infrared technology can be used effectively to examine non‐intrusively the activity of free‐ranging otters in running waters, offering some advantages over previous, more intrusive techniques that relied on the collection of spraints, the use of radioisotopes or the tracking of marked individuals.
A genetic study of sika (Cervus nippon) in the New Forest and in the Purbeck region, southern England: is there evidence of recent or past hybridization with red deer (Cervus elaphus)?
Authors: Diaz A. , Hughes S. , Putman R. , Mogg R. , Bond J. M.
Published: June 2006

Sika Cervus nippon are native to Japan and East Asia but are now naturalized in many parks of the world, including Britain. In contrast to the substantial body of research on the extent of hybridization between sika and red deer Cervus elaphus in Scottish populations, there has been little genetic analysis of the English populations of sika. Sika in England still have a patchy and discontinuous distribution; populations are thus still genetically isolated and may be expected to show higher variability in genetic type. The current paper uses DNA‐based techniques to explore the genetic composition of sika in the New Forest (Hampshire) and that of sika from the largest population in England, in the Purbeck region (Dorset). The study aims were to determine whether New Forest sika show signs of recent interbreeding with New Forest red deer populations, whether New Forest sika are genetically distinct from Purbeck sika, and whether New Forest and Purbeck sika show evidence of past hybridization or whether they are pure (non‐hybrid) strains. Microsatellite analysis was used to compare the genetic profiles of individual deer. Results showed that sika and red deer in the New Forest were genetically distinct, indicating that there is no large‐scale in situ hybridization occurring between these feral populations. In terms of overall genetic composition, there was no significant difference between the sika in the New Forest and Purbeck. However, a more detailed analysis found that New Forest sika showed a lower level of introgression with red deer compared with the Purbeck sika. We conclude that, overall, the New Forest sika deer do appear to be more genetically pure bred than the Purbeck sika.
Woodpecker pecking: how woodpeckers avoid brain injury
Authors: Gibson L. J.
Published: June 2006

Woodpeckers are capable of repeated pecking on a tree at remarkably high decelerations (on the order of 10 000 m s−2 or 1000 g). In this paper, I re‐examine previous studies of pecking and scaling effects in brain injury. I find that there are three keys to woodpeckers' ability to withstand high decelerations: their small size, which reduces the stress on the brain for a given acceleration; the short duration of the impact, which increases the tolerable acceleration; and the orientation of the brain within the skull, which increases the area of contact between the brain and the skull.
Variation of cranial and dental measurements and dental correlations in the pampean fox (Dusicyon gymnocercus)
Authors: Prevosti F. J. , Lamas L.
Published: June 2006

The knowledge of the craniodental variability of South American canids is mainly anecdotal, and the variability and dental correlation of living canids have only been studied in several species of holarctic foxes (Vulpes vulpes, Vulpes lagopus and Urocyon cinereoargeteus) and Canis lupus. These studies have shown that the last molars, canines and incisors are the most variable and the central molars and premolars are the least variable, and that correlations are highest among the posterior premolars. This pattern has been accounted for by developmental factors, functional utility and tooth complexity. In this paper the pattern of dental correlation and variability of craniodental measurements in the South American fox Dusicyon gymnocercus is studied, with the aim of checking the extension of the pattern observed in other species and contrasting previous hypotheses. The most variable in D. gymnocercus measurements are some cranial widths, width of the incisors, lower canine and lower last molar, whereas others such as width of the braincase, length of the upper carnassials, and first and second lower and upper molars have lower variability. The premolar region is the most correlated, in terms of values and number of significant correlation coefficients. The results show that measurement error is negatively correlated with size of the variables, which could explain the bias found in this index as earlier authors have suggested, but the pattern captured by this index cannot be completely considered to be an artefact. The observed results confirm that the patterns of variability and correlation found in holarctic foxes are widespread in the family Canidae, and suggest the presence of an evolutionary constraint.
Implication of the proprotein convertase NARC‐1/PCSK9 in the development of the nervous system
Authors: Poirier Steve , Prat Annik , Marcinkiewicz Edwige , Paquin Joanne , Chitramuthu Babykumari P. , Baranowski David , Cadieux Benoit , Bennett Hugh P. J. , Seidah Nabil G.
Published: June 2006

Neural apoptosis‐regulated convertase‐1/proprotein convertase subtilisin‐kexin like‐9 (NARC‐1/PCSK9) is a proprotein convertase recently described to play a major role in cholesterol homeostasis through enhanced degradation of the low‐density lipoprotein receptor (LDLR) and possibly in neural development. Herein, we investigated the potential involvement of this proteinase in the development of the CNS using mouse embryonal pluripotent P19 cells and the zebrafish as models. Time course quantitative RT–PCR analyses were performed following retinoic acid (RA)‐induced neuroectodermal differentiation of P19 cells. Accordingly, the mRNA levels of NARC‐1/PCSK9 peaked at day 2 of differentiation and fell off thereafter. In contrast, the expression of the proprotein convertases subtilisin kexin isozyme 1/site 1 protease and Furin was unaffected by RA, whereas that of PC5/6 and PC2 increased within and/or after the first 4 days of the differentiation period respectively. This pattern was not affected by the cholesterogenic transcription factor sterol regulatory element‐binding protein‐2, which normally up‐regulates NARC‐1/PCSK9 mRNA levels in liver. Furthermore, in P19 cells, RA treatment did not affect the protein level of the endogenous LDLR. This agrees with the unique expression pattern of NARC‐1/PCSK9 in the rodent CNS, including the cerebellum, where the LDLR is not significantly expressed. Whole‐mount in situ hybridization revealed that the pattern of expression of zebrafish NARC‐1/PCSK9 is similar to that of mouse both in the CNS and periphery. Specific knockdown of zebrafish NARC‐1/PCSK9 mRNA resulted in a general disorganization of cerebellar neurons and loss of hindbrain–midbrain boundaries, leading to embryonic death at ∼ 96 h after fertilization. These data support a novel role for NARC‐1/PCSK9 in CNS development, distinct from that in cholesterogenic organs such as liver.
Induction of microglial apoptosis by corticotropin‐releasing hormone
Authors: Ock Jiyeon , Lee Heasuk , Kim Sangseop , Lee Won‐Ha , Choi Dong‐Kug , Park Eun Jung , Kim Sang‐Hyun , Kim In Kyeom , Suk Kyoungho
Published: June 2006

Neuropeptides are short‐chain peptides found in brain tissue, some of which function as neurotransmitters and others as hormones. Neuropeptides may directly or indirectly modulate glial functions in the CNS. In the present study, effects of various neuropeptides on the viability and inflammatory activation of cultured microglia were investigated. Vasoactive intestinal peptide, substance P, cholecystokinin and neuropeptide Y did not affect microglial cell viability, whereas corticotropin‐releasing hormone (CRH) induced a classical apoptosis of mouse microglia in culture as shown by nuclear condensation and fragmentation, terminal deoxynucleotidyl transferase dUTP nick‐end labeling, and cleavage of caspase 3 and poly(ADP‐ribose) polymerase protein. CRH, however, did not influence nitric oxide production or expression of inflammatory genes including those encoding cytokines and chemokines, indicating that CRH did not affect the inflammatory activation of microglia. The CRH‐induced microglial apoptosis appeared to involve a mitochondrial pathway and reactive oxygen species, based on the mitochondrial membrane potential change, caspase 9 activation and sensitivity to antioxidants. Taken together, our results indicate that the stress neuropeptide CRH may regulate neuroinflammation by inducing the apoptosis of microglia, the major cellular source of inflammatory mediators in the CNS.
Region‐specific regulation of glucocorticoid receptor/HSP90 expression and interaction in brain
Authors: Furay A. R. , Murphy E. K. , Mattson M. P. , Guo Z. , Herman J. P.
Published: June 2006

The hippocampal glucocorticoid receptor (GR) is involved in negative feedback regulation of the hypothalamo‐pituitary‐adrenal axis and is believed to transduce the deleterious effects of glucocorticoids in depression and age‐related memory loss. Regulation and intracellular trafficking of the GR are critical determinants of GR action in both health and disease. Here, we show dynamic regulation of GR and its interaction with its principal intracellular chaperone, heat‐shock protein (HSP) 90, across the circadian cycle. Our initial experiments indicate that cytosolic hippocampal GR protein is elevated in the evening (PM), whereas nuclear GR and cytosolic HSP90, HSP70 and heat‐shock cognate 70 (HSC70), are unchanged. In contrast, there are no changes in examined proteins in the hypothalamus. Immunoprecipitation experiments reveal increased GR–HSP90 associations in the hippocampus in the PM, whereas binding in the hypothalamus is decreased in the PM. Given that GR requires HSP90 for ligand binding, the data suggest that circadian GR signaling capacity is regulated in a region‐specific pattern.
Short interfering RNA‐induced gene silencing is transmitted between cells from the mammalian central nervous system
Authors: Zhao Tian‐Yong , Zou Shi‐Ping , Alimova Yelena V. , Wang Guoying , Hauser Kurt F. , Ghandour M. Said , Knapp Pamela E.
Published: June 2006

Although short interfering RNA (siRNA)‐induced gene silencing can be transmitted between cells in plants and in Caenorhabditis elegans, this phenomenon has been barely studied in mammalian cells. Both immortalized oligodendrocytes and SNB19 glioblastoma cells were transfected with siRNA constructs for phosphatase and tensin homolog deleted on chromosome 10 (PTEN) or Akt/protein kinase B (Akt). Co‐cultures were established between silenced cells and non‐silenced cells which were hygromycin resistant and/or expressed green fluorescent protein. After fluorescence sorting or hygromycin selection to remove the silenced cells, the expression of PTEN or Akt genes in the originally unsilenced cells was in all cases significantly decreased. Importantly, silencing did not occur in transwell culture studies, suggesting that transmission of the silencing signal requires a close association between cells. These results provide the first direct demonstration that an siRNA‐induced silencing signal can be transmitted between mammalian CNS cells.
Copper‐dependent co‐internalization of the prion protein and glypican‐1
Authors: Cheng Fang , Lindqvist Josefin , Haigh Cathryn L. , Brown David R. , Mani Katrin
Published: June 2006

Heparan sulfate chains have been found to be associated with amyloid deposits in a number of diseases including transmissible spongiform encephalopathies. Diverse lines of evidence have linked proteoglycans and their glycosaminoglycan chains, and especially heparan sulfate, to the metabolism of the prion protein isoforms. Glypicans are a family of glycosylphosphatidylinositol‐anchored, heparan sulfate‐containing, cell‐associated proteoglycans. Cysteines in glypican‐1 can become nitrosylated by endogenously produced nitric oxide. When glypican‐1 is exposed to a reducing agent, such as ascorbate, nitric oxide is released and autocatalyses deaminative cleavage of heparan sulfate chains. These processes take place while glypican‐1 recycles via a non‐classical, caveolin‐associated pathway. We have previously demonstrated that prion protein provides the Cu2+ ions required to nitrosylate thiol groups in the core protein of glypican‐1. By using confocal immunofluorescence microscopy and immunomagnetic techniques, we now show that copper induces co‐internalization of prion protein and glypican‐1 from the cell surface to perinuclear compartments. We find that prion protein is controlling both the internalization of glypican‐1 and its nitric oxide‐dependent autoprocessing. Silencing glypican‐1 expression has no effect on copper‐stimulated prion protein endocytosis, but in cells expressing a prion protein construct lacking the copper binding domain internalization of glypican‐1 is much reduced and autoprocessing is abrogated. We also demonstrate that heparan sulfate chains of glypican‐1 are poorly degraded in prion null fibroblasts. The addition of either Cu2+ ions, nitric oxide donors, ascorbate or ectopic expression of prion protein restores heparan sulfate degradation. These results indicate that the interaction between glypican‐1 and Cu2+‐loaded prion protein is required both for co‐internalization and glypican‐1 self‐pruning.
Genotype‐dependent priming to self‐ and xeno‐cannibalism in heterozygous and homozygous lymphoblasts from patients with Huntington's disease
Authors: Mormone Elisabetta , Matarrese Paola , Tinari Antonella , Cannella Milena , Maglione Vittorio , Farrace Maria Grazia , Piacentini Mauro , Frati Luigi , Malorni Walter , Squitieri Ferdinando
Published: June 2006

In the present work, we studied the mitochondrial function and cell death pathway(s) in heterozygous and homozygous immortalized cell lines from patients with Huntington's disease (HD). Heterozygosis was characterized by specific alterations in mitochondrial membrane potential, a constitutive hyperpolarization state of mitochondria, and was correlated with an increased susceptibility to apoptosis. Lymphoblasts from homozygous patients, on the other hand, were characterized by a significant percentage of cells displaying autophagic vacuoles. These cells also demonstrated a striking attitude towards significant cannibalistic activity. Considering the pathogenic role of cell death in HD, our study provides new and useful insights into the role of mitochondrial dysfunction, i.e. hyperpolarization, in hijacking HD heterozygous cells towards apoptosis and HD homozygous cells towards a peculiar phenotype characterized by both self‐ and xeno‐cannibalism. These events can, however, be viewed as an ultimate attempt to survive rather than a way to die. The present work underlines the possibility that HD‐associated mitochondrial defects could tentatively be by‐passed by the cells by activating cellular ‘phagic’ activities, including so‐called ‘mitophagy’ and ‘cannibalism’, that only finally lead to cell death.
Characterization of the potent neuroprotective properties of the natural vitamin E α‐tocotrienol
Authors: Khanna Savita , Roy Sashwati , Parinandi Narasimham L. , Maurer Mariah , Sen Chandan K.
Published: June 2006

The natural vitamin E tocotrienols possess properties not shared by tocopherols. Nanomolar α‐tocotrienol, not α‐tocopherol, is potently neuroprotective. On a concentration basis, this finding represents the most potent of all biological functions exhibited by any natural vitamin E molecule. We sought to dissect the antioxidant‐independent and ‐dependent neuroprotective properties of α‐tocotrienol by using two different triggers of neurotoxicity, homocysteic acid (HCA) and linoleic acid. Both HCA and linoleic acid caused neurotoxicity with comparable features, such as increased ratio of oxidized to reduced glutathionone GSSG/GSH, raised intracelular calcium concentration and compromised mitochondrial membrane potential. Mechanisms underlying HCA‐induced neurodegeneration were comparable to those in the path implicated in glutamate‐induced neurotoxicity. Inducible activation of c‐Src and 12‐lipoxygenase (12‐Lox) represented early events in that pathway. Overexpression of active c‐Src or 12‐Lox sensitized cells to HCA‐induced death. Nanomolar α‐tocotrienol was protective. Knock‐down of c‐Src or 12‐Lox attenuated HCA‐induced neurotoxicity. Oxidative stress represented a late event in HCA‐induced death. The observation that micromolar, but not nanomolar, α‐tocotrienol functions as an antioxidant was verified in a model involving linoleic acid‐induced oxidative stress and cell death. Oral supplementation of α‐tocotrienol to humans results in a peak plasma concentration of 3 μm. Thus, oral α‐tocotrienol may be neuroprotective by antioxidant‐independent as well as antioxidant‐dependent mechanisms.
Breeding dispersal of Northern FlickersColaptes auratusin relation to natural nest predation and experimentally increased perception of predation risk
Authors: FISHER RYAN J. , WIEBE KAREN L.
Published: June 2006

After nest predation, breeding dispersal can be an effective strategy to avoid local nest predators. Furthermore, encounters with predators at a nest during the pre‐laying stage may be used by parents to judge future risk, such that they may abandon a nest when a nest predator has been encountered. We studied whether the between‐ and within‐year breeding dispersal of Northern FlickersColaptes auratuswas dependent upon the outcome of the previous nesting attempt. We also tested whether pairs presented with a model predator prior to egg‐laying were more likely to abandon their nests than were pairs presented with a control model. Between years, males moved significantly further after having their nest depredated than did successful males, and females showed the same trend. However, these movements did not result in greater reproductive success. More pairs switched sites within years after having their nest depredated, but those that remained and those that moved had equal subsequent nest success. Stressful encounters with predators involving nest defence may trigger dispersal both between and within years, although reproductive benefits are unclear. The proportion of pairs abandoning nests did not differ between parents presented with control or predator models, suggesting that a single encounter with a predator is not a sufficient deterrent against continued use of a particular nest.
Movement patterns of Common Crossbills Loxia curvirostra in Europe
Authors: NEWTON IAN
Published: June 2006

Over much of Europe, Common Crossbills Loxia curvirostra depend primarily on the seeds of Norway Spruce Picea abies, and their breeding and movement patterns are governed largely by the cropping patterns of this tree species. Good cone crops occur only every few years in particular areas, but in different years in different areas. The main period of movement is in summer, when the previous year's crop is coming to an end, and a new crop is forming in different areas. In years when the Norway Spruce crop is poor over a wide area, and when Common Crossbills are abundant, they leave the boreal forest in large numbers, and appear as irruptive migrants in southwest Europe, with at least 40 invasions reaching Britain in the 120‐year period 1881–2000. On irruptions the main migration axis is from northeast to southwest or west. Recoveries of birds ringed mainly in Germany confirm that these birds do not return to the boreal forest in northern Russia in the same calendar year as their irruption, but do so only in a later calendar year, when a new Norway Spruce crop is becoming available. The findings agree with an earlier interpretation of Common Crossbill movements, but not with an alternative hypothesis that irrupting Common Crossbills return to their region of origin in the same calendar year as the outward movement. Recoveries also suggest that some individual Common Crossbills may have bred in widely separated localities in different years (records up to 3170 km apart), and sometimes in localities far removed from their natal sites (records up to 2950 km apart).
Dynamics of the male germline stem cell population during aging of Drosophila melanogaster
Authors: Wallenfang Matthew R. , Nayak Renuka , DiNardo Stephen
Published: June 2006

Drosophila melanogaster has emerged as an important model system for the study of both stem cell biology and aging. Much is known about how molecular signals from the somatic niche regulate adult stem cells in the germline, and a variety of environmental factors as well as single point mutations have been shown to affect lifespan. Relatively little is known, however, about how aging affects specific populations of cells, particularly adult stem cells that may be susceptible to aging‐related damage. Here we show that male germline stem cells (GSCs) are lost from the stem cell niche during aging, but are efficiently replaced to maintain overall stem cell number. We also find that the division rate of GSCs slows significantly during aging, and that this slowing correlates with a reduction in the number of somatic hub cells that contribute to the stem cell niche. Interestingly, slowing of stem cell division rate was not observed in long‐lived methuselah mutant flies. We finally investigated whether two mechanisms that are thought to be used in other adult stem cell types to minimize the effects of aging were operative in this system. First, in many adult tissues stem cells exhibit markedly fewer cell cycles relative to transit‐amplifying cells, presumably protecting the stem cell pool from replication‐associated damage. Second, at any given time not all stem cells actively cycle, leading to ‘clonal succession’ from the reserve pool of initially quiescent stem cells. We find that neither of these mechanisms is used in Drosophila male GSCs.
Reconstructing P–T paths during continental collision using multi‐stage garnet (Gran Paradiso nappe, Western Alps)
Authors: LE BAYON B. , PITRA P. , BALLEVRE M. , BOHN M.
Published: June 2006

Garnet–chloritoid‐bearing micaschists from the Gran Paradiso massif (Western Alps) contain evidence of a polymetamorphic evolution. Detailed textural observations reveal that two stages of garnet growth are present in the micaschists, interpreted as: (i) relics of an early metamorphism of pre‐Alpine age and (ii) newly grown Alpine garnet, respectively. Both generations of garnet preserve growth zoning. From thermocalc‐based numerical modelling of mineral assemblages in pressure–temperature (P–T) pseudosections, we infer that garnet 1 grew at increasing temperature and slightly increasing pressure, whereas garnet 2 grew at decreasing pressure and slightly increasing temperature. Estimated P–T conditions are ∼620 °C, 6 kbar for the peak of the pre‐Alpine event, and of 490 °C, 18–20 kbar for the pressure peak of the Alpine event. Modelling of the modal proportion and chemical composition of garnet (i) shows that the subsequent decompression (to 14–15 kbar at 550 °C) must have been accompanied by moderate heating and (ii) does not support a stage of final temperature increase following decompressional cooling. This argues against a late thermal pulse associated with mantle delamination. Preservation of growth zoning in both generations of garnet and the limited amount of diffusive re‐equilibration at the boundary between the two garnets suggests that the rocks were subjected to fast burial and exhumation rates, consistent with data obtained from other internal Alpine units.
A randomized trial of blood donor recruitment strategies
Authors: Reich Pascale , Roberts Paula , Laabs Nancy , Chinn Artina , McEvoy Patrick , Hirschler Nora , Murphy Edward L.
Published: June 2006

BACKGROUND:  Improvement in donor return rates, especially among first‐time donors, may significantly improve the blood supply. There are few rigorous studies of the effectiveness of various approaches to donor recruitment, however.

STUDY DESIGN AND METHODS:  By use of a single‐blind, randomized trial design, 6919 post‐September 11, 2001, first‐time donors were randomly assigned into the following intervention arms: T‐shirt incentive versus none, recruitment scripts with a patient story (Script A) versus a complimentary message including the donor’s blood type (Script B), and telephone versus e‐mail recruitment. Our primary outcome was a second donation within 6 months. Rate ratios (RRs) and 95 percent confidence intervals (95% CIs) were calculated with Taylor series methods.

RESULTS:  A total of 1421 (20.5%) first‐time donors returned within the 6 months, including 1252 with a second and 169 with both second and third donations. The T‐shirt incentive was not effective in increasing returns compared to no incentive (20.5% vs. 20.6%; RR, 0.99; 95% CI, 0.91‐1.09). Script A was significantly more effective than Script B (22.2% vs. 18.9%; RR, 1.18; 95% CI, 1.07‐1.29). E‐mail was substantially less effective than telephone recruitment (13.2% vs. 27.8%; RR, 0.48; 95% CI, 0.40‐0.57).

CONCLUSIONS:  A T‐shirt incentive had no apparent effect, but an empathetic message significantly improved the return donation rate. E‐mail recruitment was substantially less effective than telephone recruitment, perhaps due to technical problems. The study illustrates the utility of the randomized clinical trial study design for testing donor recruitment strategies.
Acute normovolemic hemodilution in moderate blood loss surgery: a randomized controlled trial
Authors: Bennett Joanne , Haynes Sarah , Torella Francesco , Grainger Hannah , McCollum Charles
Published: June 2006

BACKGROUND:  The risks associated with allogeneic blood transfusion are increasingly recognized. More blood is cross‐matched for moderate blood loss surgery than any other indication. The role of acute normovolemic hemodilution (ANH) as a blood transfusion strategy was evaluated in a prospective randomized controlled trial.

STUDY DESIGN AND METHODS:  A total of 155 patients undergoing elective hip surgery were randomly assigned to either “ANH” (n = 78) or “standard transfusion” (n = 77). ANH on induction of anesthesia was to a target hemoglobin (Hb) level of 110 g per L with return of autologous blood on wound closure. Allogeneic blood was prescribed by an objective transfusion trigger based on an Hb level of less than 80 g per L. Transfusion requirements and postoperative complications were recorded.

RESULTS:  Allogeneic transfusion was necessary in 22 (29%) standard transfusion patients and 15 (19%) ANH (odds ratio [OR], 0.6; 95% CI, 0.28‐1.3; p = 0.23) with 63 and 33 units transfused, respectively (p = 0.1). Significant postoperative complications occurred in 30 (38%) standard transfusion patients compared with 14 (18%) of those randomly assigned to ANH (OR, 0.3; 95% CI, 0.14‐0.65; p = 0.009). The major difference between the groups was the frequency of infective complications.

CONCLUSION:  Despite modest allogeneic transfusion requirements in hip surgery, ANH reduced postoperative complications.
Acute and long‐term effects of modified hemoglobin (HBOC‐201) in a rat model of hypertension and chronic kidney disease
Authors: Baylis Chris
Published: June 2006

BACKGROUND:  The goal was to determine whether administration of the oxygen‐therapeutic blood substitute HBOC‐201 had any deleterious effect on renal function and/or structure in a rat model of chronic kidney disease (CKD).

STUDY DESIGN AND METHODS:  Longitudinal studies were conducted in the conscious chronically catheterized male Sprague‐Dawley rat with rapidly progressing CKD produced by ablation‐infarction of 5/6th of the functional renal mass. Experimental rats received a loading dose (after acute removal of 10% blood volume) and six subsequent daily maintenance doses of HBOC‐201 at Weeks 4 to 5 after induction of CKD and were studied again at 6 weeks. Controls received isoosmotic human serum albumin (HSA, 13%) over the same period. Blood pressure (BP) and renal function were measured in acute experiments at Weeks 4, 5, and 6. Proteinuria and 24‐hour creatinine clearance was measured longitudinally and renal pathology was assessed at killing.

RESULTS:  There were differences in the acute response to the infusions, with rats given HBOC‐201 exhibiting an increase in BP and renal vascular resistance, whereas rats given HSA showed a decrease in BP. These changes did not persist, however, because mean BP, glomerular filtration rate, level of proteinuria, and glomerular pathology were all similar at the end of the study (6 weeks after induction of CKD) in rats given HBOC‐201 and HSA.

CONCLUSION:  In this model of CKD, daily doses of HBOC‐201 had no long‐term damaging effects on renal function or structure, compared to rats given the osmotic control agent, 13 percent HSA.