bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of microRNA‐34a overexpression with proliferation is cell type‐dependent
Authors: Dutta Khokon Kumar , Zhong Yi , Liu Yu‐Ting , Yamada Takuji , Akatsuka Shinya , Hu Qian , Yoshihara Minako , Ohara Hiroki , Takehashi Masanori , Shinohara Takashi , Masutani Hiroshi , Onuki Janice , Toyokuni Shinya
Published: September 2007

Recently Welch et al. reported that microRNA (miRNA)‐34a functions as a potential tumor suppressor in neuroblastoma cells (Oncogene 26: 5017–22, 2007). Here, we conversely show that miRNA‐34a supports cell proliferation in rat oxidative stress‐induced renal carcinogenesis and is overexpressed in various types of human cancers. While searching for genetically unstable chromosomal areas in rat renal carcinogenesis, we found the miRNA‐34 family reciprocally overexpressed in chromosomal areas with frequent allelic loss. By in situ hybridization and reverse transcription‐polymerase chain reaction, cerebral neurons and Purkinje cells showed the highest expression of a major type, miRNA‐34a, followed by a variety of endocrine cells and proliferating cells including germinal center lymphocytes and mouse embryonic fibroblasts and stem cells. In contrast, normal renal tubules, hepatocytes and myocardial cells showed faint expression. After 3 weeks of ferric nitrilotriacetate (Fe‐NTA)‐induced oxidative stress, regenerating renal proximal tubular cells showed high miRNA‐34a expression. All of the Fe‐NTA‐induced rat renal carcinomas and an array of human cancers (151 positive cases of 177) showed high expression of miRNA‐34a. Furthermore, knockdown of miRNA‐34a with small interfering RNA significantly suppressed proliferation not only of renal carcinoma cells but also of HeLa and MCF7 cells. These results indicate that miRNA‐34a overexpression, an acquired trait during carcinogenesis, supports cell proliferation in the majority of cancers suggesting an unexpected link in the cellular metabolism between cancer and neuronal and/or endocrine cells, which warrants further investigation. (Cancer Sci 2007; 98: 1845–1852)
Effects of an open refuse pit on space use patterns of spotted hyenas
Authors: Kolowski J. M. , Holekamp K. E.
Published: September 2007

Although the use of anthropogenic food sources by carnivores is well documented, few studies have investigated the potential for these sites to influence the movements of livestock predators. We capitalized on a natural experiment in which a refuse pit, utilized by a group of intensively monitored spotted hyenas (Crocuta crocuta) in the Masai Mara National Reserve, Kenya, was closed midway through monitoring efforts. We compared hyena space use patterns before and after closure, while controlling for other variables, to investigate the influence of the pit on home range size, core area size and location, and the proximity of hyenas to dens and the refuse pit itself. We also investigated the influence of prey abundance and the social ranks of individual hyenas on variation in frequency of pit utilization. We found home range size to increase and core area size to decrease following pit closure. Space use was clearly influenced by the pit, as the group core area included the refuse site only while it was in operation, and hyenas were found closer to the pit before than after its closure. The most common rank group observed feeding at the pit were low‐ranking females, and regular pit users were more likely to be found near the pit during times of relative prey scarcity. We discuss the potential of human refuse at pastoral villages to increase livestock losses to hyenas.
The relevance of fire frequency for the floodplain vegetation of the Okavango Delta, Botswana
Authors: Heinl Michael , Sliva Jan , Tacheba Budzanani , Murray‐Hudson Michael
Published: September 2007

The study investigates the relevance of fire frequency for the floodplain vegetation of the Okavango Delta in Botswana, considering species composition, species richness, vegetation structure and tree density. Based on flood and fire frequency data derived from a series of satellite images, active and drying floodplains were separated and study plots were selected with fire frequencies up to ten burns between 1989 and 2003. Both for drying and active floodplains, no typical species assemblage could be associated with fire frequency. On drying floodplains, fire frequency showed no effect on species composition, but rather on vegetation structure. While small woody species showed higher cover values on high fire frequency, large trees showed significantly lower cover values on high fire frequency. For active floodplains, a significant response to fire frequency, both positively and negatively could be determined for specific species. But as almost none of these species appear at low or high frequency only, no differences in species composition could be associated with fire frequency. Rather flood frequency and specific annual flood cycles could be described as the determining factors for the vegetation on active floodplains.
Habitat choice of Grevy’s zebras (Equus grevyi) in Laikipia, Kenya
Authors: Sundaresan Siva R. , Fischhoff Ilya R. , Hartung Helen M. , Akilong Patrick , Rubenstein Daniel I.
Published: September 2007

Characterizing habitat choice is essential for endangered species conservation. For the endangered Grevy’s zebra (Equus grevyi), as with many widely ranging vertebrates, human activities may be an important factor affecting space use. Grevy’s zebras are grazing ungulates inhabiting the savannahs of central‐northern Kenya and Ethiopia. Past research on their social organization indicates that reproductive status shapes associations and movements. Here, we examine how habitat use varies across four reproductive classes: lactating and nonlactating females, bachelors and territorial males. We also test whether Grevy’s zebra avoid locations close to active livestock corrals, or bomas. We find that forage quality, forage quantity and habitat openness of locations used by Grevy’s zebra vary significantly depending on individual reproductive state. Lactating females and bachelors use areas with green, short grass and medium‐dense bush more frequently than nonlactating females or territorial males. We hypothesize that lactating females trade off forage quantity and safety to access nutrients in growing grass. Across reproductive classes, Grevy’s zebra choose locations further from active bomas than if they used the area randomly. Our results suggest that Grevy’s zebra may require a range of vegetation characteristics for different reproductive classes. Further, they may need areas free from competition or disturbance by livestock.
Effects of human disturbance on composition and structure of Brachystegia woodland in Arabuko‐Sokoke Forest, Kenya
Authors: Oyugi Joseph O. , Brown Joel S. , Whelan Christopher J.
Published: September 2007

We examined tree species diversity, density, dispersion patterns and size class distributions in Brachystegia woodland of Arabuko‐Sokoke Forest, Kenya. The metrics varied with human disturbance (disturbed versus relatively undisturbed areas). Julbernardia magnistipulata Harms occurred only in the undisturbed site. Brachystegia spiciformis Benth. had the highest importance value (IV) at both study sites, whereas the IVs for the other tree species were greater within the undisturbed than the disturbed sites. Simpson’s Diversity Index and tree densities were greater in the undisturbed site than in the disturbed site. All seven tree species exhibited random dispersions in the disturbed site, but three species were clumped in the undisturbed areas. Smaller individuals of B. spiciformis were over‐represented in the disturbed habitat relative to the undisturbed habitat. In contrast, J. magnistipulata, Lannea schweinfurthii Engl. and Mimusops obtusifolia Wall. exhibited a greater proportion of smaller trees in the undisturbed site. The tree size class distributions may provide an index of regeneration for these four tree species in the disturbed and undisturbed sites respectively. Active management and restoration may be desirable for J. magnistipulata but appears unnecessary for the remaining common tree species. Illegal logging has persisted in the forest despite its conservation status over many decades. If logging activities cease, it would be instructive to document changes in vegetation composition and structure over time.
Mesozoic–Cenozoic exhumation events in the eastern North Sea Basin: a multi‐disciplinary study based on palaeothermal, palaeoburial, stratigraphic and seismic data
Authors: Japsen Peter , Green Paul F. , Nielsen Lars Henrik , Rasmussen Erik S. , Bidstrup Torben
Published: September 2007

Four Mesozoic–Cenozoic palaeothermal episodes related to deeper burial and subsequent exhumation and one reflecting climate change during the Eocene have been identified in a study of new apatite fission‐track analysis (AFTA®) and vitrinite reflectance data in eight Danish wells. The study combined thermal‐history reconstruction with exhumation studies based on palaeoburial data (sonic velocities) and stratigraphic and seismic data. Mid‐Jurassic exhumation (ca. 175 Ma) was caused by regional doming of the North Sea area, broadly contemporaneous with deep exhumation in Scandinavia. A palaeogeothermal gradient of 45 °C km−1 at that time may be related to a mantle plume rising before rifting in the North Sea. Mid‐Cretaceous exhumation affecting the Sorgenfrei–Tornquist Zone is probably related to late Albian tectonic movements (ca. 100 Ma). The Sole Pit axis in the southern North Sea experienced similar inversion and this suggests a plate‐scale response along crustal weakness zones across NW Europe. Mid‐Cenozoic exhumation affected the eastern North Sea Basin and the onset of this event correlates with a latest Oligocene unconformity (ca. 24 Ma), which indicates a major Scandinavian uplift phase. The deeper burial that caused the late Oligocene thermal event recognized in the AFTA data reflect progradation of lower Oligocene wedges derived from the uplifting Scandinavian landmass. The onset of Scandinavian uplift is represented by an earliest Oligocene unconformity (ca. 33 Ma). Late Neogene exhumation affected the eastern (and western) North Sea Basin including Scandinavia. The sedimentation pattern in the central North Sea Basin shows that this phase began in the early Pliocene (ca. 4 Ma), in good agreement with the AFTA data. These three phases of Cenozoic uplift of Scandinavia also affected the NE Atlantic margin, whereas an intra‐Miocene unconformity (ca. 15 Ma) on the NE Atlantic margin reflects tectonic movements of only minor amplitude in that area. The study demonstrates that only by considering episodic exhumation as an inherent aspect of the sedimentary record can the tectonic evolution be accurately reconstructed.
Constraining the burial history of the Ghadames Basin, North Africa: an integrated analysis using sonic velocities, vitrinite reflectance data and apatite fission track ages
Authors: Underdown R. , Redfern J. , Lisker F.
Published: September 2007

Constraining the burial history of a sedimentary basin is crucial for accurate prediction of hydrocarbon generation and migration. Although the Ghadames Basin is a prolific hydrocarbon province, with recoverable oil discovered to date in excess of 3.5 billion bbl, exploration on the eastern margin is still limited and the prospectivity of the area depends on the identification of effective source rocks and the timing of hydrocarbon generation. Sonic velocity, apatite fission track (FT) and vitrinite reflectance analysis offer three complementary methods to determine burial history and provide independent analytical techniques to evaluate the timing and amount of exhumation. The results indicate that two phases of tectonic activity had the biggest influence on basin evolution: the Hercynian (Late Carboniferous–Triassic) and Alpine (Late Mesozoic/Cenozoic) tectonic events. Exhumation during the Hercynian tectonic event increases from the SE, where an almost complete Palaeozoic section is preserved, towards the NW. This study quantifies the significant regional Alpine exhumation of the southern and eastern margins of the basin, with important implications for the timing of hydrocarbon maturation and expulsion, particularly for the Silurian source rock interval. Incorporating elevated Alpine exhumation values into burial history models for wells in the eastern (Libyan) part of the basin allows calibration with available maturity (Roeq) data using moderate values of Hercynian erosion. The result is preservation of the generation potential of Silurian (Tanezzuft) source rocks until maximum burial during Mesozoic/Cenozoic time, which improves the chance for preservation of hydrocarbon accumulations following entrapment.
Early weaning is related to weight and rate of weight gain in infancy
Authors: Sloan S. , Gildea A. , Stewart M. , Sneddon H. , Iwaniec D.
Published: September 2007

Background  Evidence relating to the effect of early weaning on infant weight and weight gain is conflicting. The aim of this paper is to compare weight and weight gain in two groups of infants; one group weaned before 4 months (early weaned), the other weaned at 4 months or after.

Methods  Feeding practices were assessed through semistructured interviews with mothers of 1‐year‐old infants. Weight at birth, 8 weeks and 7 months were taken from an administrative database (Child Health System), and an additional measure of weight was taken at 14 months.

Results  Infants weaned early were heavier at 7 and 14 months, and gained more weight between 8 weeks and 14 months, even after breastfeeding was controlled for.

Conclusion  Early weaning is related to rapid weight gain in infancy. This may have implications for childhood obesity.
A review of local practice regarding investigations in children attending obesity clinics and a comparison of the results with other studies
Authors: Leigh‐Hunt N. , Rudolf M.
Published: September 2007

Background  Obese children are at high risk of developing co‐morbidities, with a prevalence of abnormal tests ranging from 30 to 58%. Recent guidance recommends that all children with a body mass index (BMI) above the 95th centile be investigated. This study aimed to determine the prevalence of abnormal results in an urban paediatric population and to compare local practice against these recommendations.

Methods  Patient records of children attending either a community or hospital‐based obesity clinic were analysed retrospectively to obtain anthropometric data and laboratory results; from this, the frequency of investigation and the prevalence of abnormal results were calculated. Investigations considered were alanine aminotransferase, thyroid‐stimulating hormone (TSH), and fasting glucose, insulin and lipid profiles.

Results  One hundred thirty‐six children (75 girls, 61 boys) were identified, with mean BMI z‐score of 3.27 and mean age of 11.4 years (range 1.4–20.4). Children with BMI z‐score >3 were more likely to be investigated, but otherwise, the frequency was similar for both sex and age. The prevalence of abnormal results was liver function tests, 14.3%; TSH, 0.0%; glucose, 0.0%; insulin, 31.6%; triglycerides, 10.0%; cholesterol, 15.6%. The sample size was small, but there did not appear to be a significant difference in the percentage abnormal results found for sex, age, or BMI z‐score.

Conclusion  The prevalence of abnormal results was less than that identified in another UK study carried out in a tertiary centre, suggesting that the true population‐based prevalence is lower than believed. This might be especially so because fewer tests were performed in these clinics than currently recommended and children at highest risk were more likely to be investigated. Therefore, further research is indicated to determine the true figure as well as to identify risk factors for co‐morbidity, before costly recommendations to test all children with a BMI above the 95th centile are implemented.
An exploration of children's views of bed‐wetting at 9 years
Authors: Butler R. , Heron J.
Published: September 2007

Background  Although some empirical investigations have explored the impact of nocturnal enuresis for sufferers, little is known about how children in general understand nocturnal enuresis. This study employed a large cohort of children at 9 years, asking directly about the perceived difficulty of bed‐wetting in relation to an extensive range of life events.

Method  The sample comprised 8209 children, 4012 (48.9%) male and 4197 (51.1%) female who, as part of the Avon Longitudinal Study of Parents and Children survey, completed a booklet called ‘My World’ which included a section of 21 items concerned with childhood difficulties.

Results  Bed‐wetting was highly endorsed as a difficulty for children, and factor analysis revealed it to be construed as a social problem. Girls were more likely to consider events of a social and emotional nature to be difficult, whereas boys rated antisocial events as more problematic. Boys and those who suffer from nocturnal enuresis were significantly more likely to view bed‐wetting as more difficult for children.

Conclusion  Bed‐wetting, which is construed as a social issue, tends to be rated as a major difficulty for children, increasingly so for boys and those who suffer from nocturnal enuresis.
Children's understanding of mental illness: an exploratory study
Authors: Fox C. , Buchanan‐Barrow E. , Barrett M.
Published: September 2007

Background  This study aimed to investigate children's thinking about mental illness by employing a well‐established framework of adult illness understanding.

Methods  The study adopted a semistructured interview technique and a card selection task to assess children's responses to causes, consequences, timeline and curability of the different types of mental illness. The children were aged between 5 and 11 years.

Results  Results indicated a developmental trend in the children's thinking about mental illness; there was an increase in the children's understanding of the causes, consequences, curability and timeline of mental illness with age. The older children demonstrated a more sophisticated and accurate thinking about mental illness compared with the younger children, who tended to rely on a medical model in order to comprehend novel mental illnesses. Furthermore, the girls exhibited more compassion, showing greater social acceptance compared with the boys.

Conclusions  The Leventhal model provides a useful framework within which to investigate children's knowledge and understanding of mental illness. Limitations of the study and implications for future research are discussed.
Variation in the IGF1 gene and growth in foetal life and infancy. The Generation R Study
Authors: Geelhoed J. J. Miranda , Mook‐Kanamori Dennis O. , Witteman Jacqueline C. M. , Hofman Albert , Van Duijn Cornelia M. , Moll Henriëtte A. , Steegers Eric A. P. , Hokken‐Koelega Anita C. S. , Jaddoe Vincent W. V.
Published: September 2007

Objective  The objective of this study was to examine whether variants of the IGF1 gene are associated with growth patterns from foetal life until infancy.

Study design and measurements  This study was embedded in the Generation R Study, a population‐based prospective cohort study of foetal life. Foetal growth (head circumference, abdominal circumference, femur length, estimated foetal weight) was assessed by ultrasound in early, mid‐ and late pregnancy. Growth in infancy was assessed at birth (weight) and at the ages of 6 weeks, 6 months and 14 months (head circumference, length, weight). The IGF1 promoter region genotype was determined in 738 children.

Results  Eight alleles of the IGF1 promoter region were identified. In total, 43% of the subjects were homozygous for the most common 192‐bp allele (wild‐type), 45% were heterozygous, and 12% were noncarriers of the 192‐bp allele. No differences were found in birthweight between the three groups. However, noncarriers had a lower estimated foetal weight in mid‐pregnancy (P = 0·040), followed by an increased growth rate until 6 months (P < 0·005) in comparison to the 192‐bp homozygotes. A similar difference in growth rate was found for length (P < 0·001).

Conclusions  Variants of the IGF1 promoter region are not associated with birthweight. However, noncarriers of the 192‐bp allele tend to have a smaller foetal size, followed by an increased growth rate from mid‐pregnancy to early infancy. Studies in larger cohorts are necessary to replicate our findings and to examine whether these effects persist throughout childhood.
Biological variation of total testosterone, free androgen index and bioavailable testosterone in polycystic ovarian syndrome: implications for identifying hyperandrogenaemia
Authors: Cho L. W. , Kilpatrick E. S. , Jayagopal V. , Diver M. J. , Atkin S. L.
Published: September 2007

Objective  Hyperandrogenaemia is one of the three Rotterdam consensus diagnostic criteria for polycystic ovarian syndrome (PCOS) and may be measured by estimation of total testosterone, free androgen index (FAI) or bioavailable testosterone (BioT). The aim of this study was to compare the biological variability of total testosterone with that of the biological variability of both the FAI and BioT, to determine the least variable measurement for clinical practice.

Design  Comparative study.

Patients  Blood samples were collected after an overnight fast at 4‐day intervals on 10 consecutive occasions from 12 PCOS patients and 11 weight‐ and age‐matched control women.

Measurements  Duplicate samples of stored serum were analysed for total testosterone, SHBG and BioT in a single batch.

Results  The PCOS group had a significantly higher median BioT, FAI and total testosterone than controls. In both the PCOS and control groups, the intraindividual variance was small and similar for BioT and FAI. There was no significant difference between the within‐subject biological coefficient of variation (CVI) for BioT, FAI and total testosterone. The maximum and minimum critical differences were +58% and –37% for BioT and +70% and –40% for FAI, respectively.

Conclusion  FAI appears to be the better diagnostic marker to distinguish hyperandrogenism in patients with PCOS, but once diagnosis has been made, all three methods should be equally good in monitoring further changes in the androgen status.
Higher serum free testosterone is associated with better cognitive function in older men, while total testosterone is not. The Health In Men Study
Authors: Yeap Bu B. , Almeida Osvaldo P. , Hyde Zoë , Chubb S. A. Paul , Hankey Graeme J. , Jamrozik Konrad , Flicker Leon
Published: September 2007

Objective  To determine the relationship of total and free serum testosterone to cognitive performance in older men.

Design  Cross‐sectional study of a population‐based sample.

Participants  A total of 2932 men aged 70–89 years.

Measurements  Cognitive function was assessed using the Standardized Mini‐Mental State Examination (SMMSE). Early morning sera were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using the Vermeulen method.

Results  There were weak positive correlations between SMMSE score and serum free testosterone (Spearman's rho = 0·06, P = 0·001) and total testosterone (r = 0·04, P = 0·027), and a weak negative correlation with LH (r = −0·07, P < 0·001). Men with SMMSE scores in the top quintile had higher serum free testosterone compared with those in the lowest quintile [median (interquartile range, IQR): 278 (228–335) vs. 262 (212–320) pmol/l, P = 0·003], but similar total testosterone [15·2 (11·9–18·8) vs. 14·8 (11·6–18·3) nmol/l, P = 0·118]. Increasing age, non‐English‐speaking background, lower educational attainment, presence of clinically significant depressive symptoms, and cardiovascular morbidity were associated with the lowest cognitive performance quintile. After their effects were taken into account in a multivariate analysis, serum free testosterone ≥ 210 pmol/l was associated with reduced likelihood of poor cognitive performance on the SMMSE [odds ratio (OR) 0·71, 95% confidence interval (CI) 0·52–0·97].

Conclusions  In community‐dwelling older men, serum free testosterone ≥ 210 pmol/l is associated with better cognitive performance. In this context, calculated free testosterone seems to be a more informative measure of androgen status than total testosterone. Studies examining the contribution of androgens to age‐related cognitive decline should incorporate an assessment of free testosterone concentration.
Effects of exercise‐induced weight loss on acylated and unacylated ghrelin in overweight children
Authors: Kim Hyun Jun , Lee Sangyeoup , Kim Tae Wun , Kim Hyoung Hoi , Jeon Tae Yong , Yoon Yeong Sook , Oh Sang Woo , Kwak Hyun , Lee Jae Gue
Published: September 2007

Objective  Controversial data on ghrelin concentration during exercise in human subjects have been published. We tested the hypothesis that exercise could affect acylated ghrelin (AG) and unacylated ghrelin (UAG), which could partly explain the previously reported inconsistent findings on the association of exercise with changes in ghrelin.

Design   A prospective randomized study.

Patients and measurements  We randomized 17 overweight volunteers (11‐year‐old boys) to a 12‐week combined exercise group (EG, n = 8) or control group (CG, n = 9). At baseline, 1, 4 and 12 weeks, we measured body weight and composition, insulin, leptin, total ghrelin and acylated ghrelin.

Results  Compared with the CG, body weight, percentage body fat and homeostatic model assessment (HOMA) indices were significantly lower throughout the 12 weeks in the EG. Total ghrelin and UAG levels gradually increased to 131·9 ± 5·2% and 130·4 ± 5·2% of baseline, respectively, at week 12 in the EG, whereas AG concentration remained unchanged throughout the 12 weeks both within each group and between the groups. At week 12, there were differences in the total ghrelin level and UAG level between the groups.

Conclusions  This study shows an increase in unacylated acylated ghrelin and unchanged acylated ghrelin after a 12‐week combined exercise programme in overweight children. These findings provide evidence of favourable effects of exercise on improving energy metabolism.
Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort
Authors: Panicker V. , Wilson S. G. , Spector T. D. , Brown S. J. , Falchi M. , Richards J. B. , Surdulescu G. L. , Lim E. M. , Fletcher S. J. , Walsh J. P.
Published: September 2007

Objective  Thyroid hormone action influences many metabolic and synthetic processes, but the degree of regulation attributed to genes and environmental factors affecting normal variation remains controversial.

Design  We investigated the magnitude of the genetic and environmental determination of serum concentrations of free (f) T3, fT4, TSH and the fT4 × TSH product and their variation, in a large cohort of twin pairs. Female dizygous and monozygous twins (849 and 213 pairs, respectively) from the TwinsUK registry (mean age 45·5, range 18–80 years) were studied.

Results  Comparison of thyroid parameters within various groups showed no differences between smoking categories, and higher serum TSH and lower fT3 in subjects with positive thyroid antibodies. Using structural equation modelling, we estimated the heritable contribution to serum thyroid parameters (with 95% confidence intervals) to be 65% (58%–71%) for TSH, 65% (58%–71%) for the fT4 × TSH product, 39% (20%–55%) for fT4 and 23% (3%–41%) for fT3.

Conclusions  We conclude that genetic regulation is a particularly important determinant of TSH and the fT4 × TSH product, and is a less important determinant of fT4 and fT3 concentrations in Caucasian women. These data from a large well‐characterized cohort suggest that while there is a strong heritable contribution to serum TSH, variation in fT4 and fT3 concentrations may be less explained by genetic factors and more driven by environmental effects than previously thought.
Short‐term treatment with ezetimibe, simvastatin or their combination does not alter circulating adiponectin, resistin or leptin levels in healthy men
Authors: Gouni‐Berthold Ioanna , Berthold Heiner K. , Chamberland John P. , Krone Wilhelm , Mantzoros Christos S.
Published: September 2007

Objective  Statin therapy decreases cardiovascular morbidity and mortality, and ezetimibe, a novel cholesterol absorption inhibitor has both lipid‐lowering and anti‐atherosclerotic effects in animal models. As several adipokines, that is, adiponectin, high molecular weight (HMW) adiponectin, leptin and/or possibly resistin are involved in the pathogenesis of insulin resistance (IR), dyslipidaemia and atherosclerosis, we investigated whether ezetimibe and/or statin treatment may modulate serum concentrations of these four major adipokines.

Research design and methods  One‐centre, randomized, parallel three‐group study in 72 healthy men [mean age 32 ± 9 years, mean body mass index (BMI) 25·7 ± 3·2 kg/m2].

Patients  Seventy‐two healthy men. Each group of 24 subjects received a 14‐day treatment with either ezetimibe (10 mg/day), simvastatin (40 mg/day) or their combination. Blood was drawn before and after the 14‐day treatment period.

Measurements  Lipid levels, IR indices, serum leptin, adiponectin, HMW adiponectin and resistin concentrations.

Results  Neither ezetimibe nor simvastatin or their combination had any effect on serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Baseline leptin levels correlated positively, while adiponectin and HMW adiponectin negatively, with BMI. Leptin concentrations correlated negatively while adiponectin and HMW adiponectin positively with plasma high‐density lipoprotein‐cholesterol concentrations. Resistin concentrations were not associated with BMI, lipid levels or indicators of IR.

Conclusions  Treatment with ezetimibe, simvastatin or their combination does not alter circulating levels of adiponectin, leptin or resistin in adult healthy men.
A systematic review of the gonadal effects of therapeutic radioactive iodine in male thyroid cancer survivors
Authors: Sawka Anna M. , Lea Jane , Alshehri Bandar , Straus Sharon , Tsang Richard W. , Brierley James D. , Thabane Lehana , Rotstein Lorne , Gafni Amiram , Ezzat Shereen , Goldstein David P.
Published: September 2007

Background  For patients with well‐differentiated thyroid carcinoma (WDTC), the gonadal effects of radioactive iodine (RAI) therapy is an important consideration.

Objective and methods  We systematically reviewed the controlled studies examining the gonadal effects of RAI therapy in male WDTC survivors. We searched in nine electronic databases. All abstracts and papers were independently reviewed by two reviewers.

Results  After reviewing 334 abstracts and 59 full‐text papers, seven papers were included. In longitudinal studies examining the effect of single primary RAI dose activities of ≤ 150 mCi, serum FSH and LH rose between months 2 and 6, with normalization by 18 months; serum testosterone did not significantly decrease. In one study, 18 months after RAI, the rates of elevated serum FSH were: 27% for 351–594 mCi and 81% for > 594 mCi. Cumulative RAI dose correlated with FSH measurements at long‐term follow‐up. In one study, approximately one in eight men experienced oligospermia 1 year after RAI therapy. Rates of infertility, pregnancy loss and offspring congenital malformation were not elevated, but studies were limited by small size and self‐reported outcomes.

Conclusions  Abnormalities in testicular function are common within several months of a single therapeutic dose of RAI for WDTC. Biochemical abnormalities usually resolve within 18 months after administration of a single activity of < 150 mCi of RAI. The risk of persistent gonadal dysfunction is increased after repeated or high cumulative RAI activities. Controlled, prospective studies, with long‐term follow‐up, examining male gonadal and offspring effects of RAI therapy are needed.
Bilateral laparoscopic adrenalectomy for corticotrophin–dependent Cushing's syndrome: a review of the Mayo Clinic experience
Authors: Chow John T. , Thompson Geoffrey B. , Grant Clive S. , Farley David R. , Richards Melanie L. , Young William F.
Published: September 2007

Background  There has been a rapid shift from open to laparoscopic approaches in adrenal surgery, but the safety and efficacy of bilateral laparoscopic adrenalectomy (BLA) in patients with corticotrophin (ACTH)‐dependent Cushing's syndrome continues to be defined.

Objective  Review outcomes in the largest series of patients reported to date undergoing BLA for ACTH‐dependent Cushing's syndrome.

Design  Retrospective review study.

Patients  Between January of 1995 and October of 2006, BLA was attempted in 68 patients with ACTH‐dependent Cushing's syndrome (26 ectopic ACTH syndrome; 42 persistent pituitary‐dependent Cushing's syndrome following pituitary surgery).

Measurements  Review of peri‐operative morbidity and mortality, biochemical parameters and patient‐reported symptom response from chart review and mailed questionnaire.

Results  BLA was successfully completed in 59 of 68 patients (87%); nine (13%) required conversion to open adrenalectomy (OA). Intra‐operative complications occurred in three patients (4·4%) (two BLA, one OA), and non‐operative complications occurred in 11 (16%) patients (eight BLA, three OA). There were no peri‐operative deaths. Median hospitalization was 5·5 days (range, 3–28) and 11·9 days (range, 4–29) for the BLA and OA groups, respectively. In patients with follow‐up data available, all achieved biochemical resolution and at least partial clinical resolution of signs and symptoms associated with hypercortisolism. Resolution of hypertension, diabetes and obesity was achieved in 64%, 29% and 35% of patients carrying those diagnoses prior to surgery, respectively.

Conclusions  This study further supports the role of BLA as an effective treatment option for patients with ACTH‐dependent Cushing's syndrome.
Association of genetic variants in GABRA3 gene and thyrotoxic hypokalaemic periodic paralysis in Thai population
Authors: Jongjaroenprasert Wallaya , Chanprasertyotin Suwannee , Butadej Siriwan , Nakasatien Soontaree , Charatcharoenwitthaya Natthinee , Himathongkam Thep , Ongphiphadhanakul Boonsong
Published: September 2007

Background  Genetic predisposition has been suggested to play role in the pathogenesis of thyrotoxic hypokalaemic periodic paralysis (THPP).

Objectives  In this study, we assessed the differences of single‐nucleotide polymorphisms (SNP) allelic frequency between THPP patients and well‐characterized controls in order to find the susceptibility genetic variants related to THPP using microarray‐based assessments on pooled DNA.

Methods  Fifty cases of THPP and 50 male hyperthyroid patients without hypokalaemia as controls were recruited. Equal amounts of individual genomic DNA were pooled from each group. Estimated allele frequencies of SNPs were derived by averaging relative allele signal score obtained by Affymetrix GeneChip® Mapping 10K Arrays.

Results  Sixty‐nine loci that display robust allele frequency differences between THPP and controls were identified. SNP rs750841 (A > T) in intron 3 of the gamma‐aminobutyric acid (GABA) receptor α3 subunit (GABRA3) gene possessed the most significant difference in allele frequency (27% in THPP case and 5% in controls, P = 0·007). Actual allele frequencies obtained from genotyping in each individual were very similar to the estimated frequency from the pools (28% in THPP and 2% in controls, and P = 0·0002). Nearby DNA sequences of GABRA3 were sequenced and an additional two SNPs were found (A > C at exon 1 and G > T of rs12688128). Allele A of rs750841 and allele G of rs12688128 in intron 3 were predominantly found in THPP with significant genetic relative risk of 19 (P < 0·0002; 95%CI 2·4–151·6).

Conclusions  Whole‐genome scanning on pooled DNA provides an accurate, useful screening tool for elucidating genetic underpinnings of THPP. SNPs at intron 3 of GABRA3 are found to be associated with THPP.
The future of cytopathology in Europe. Will the wider use of HPV testing have an impact on the provision of cervical screening?
Authors: Gray W. , Bayer‐Pietsch E. , Chieco P. , Cochand Priollet B. , Desai M. , Drijkoningen M. , Griffin M. , Hagmar B. , Kapila K. , Kloboves‐Prevodnik V. , Kobayashi T. , Krogerus L. , Majak B. , Mihailovici M. , Olszewski W. , Schenck U. , Schmitt F. , Shabalova I. , Shapiro N. , Smith J. , Tani E. , Totsch M. , Vass L. , Wiener H. , Herbert A.
Published: September 2007

Abstract:  The emphasis of the EFCS Congress held in Venice in October 2006 was on the future of Cytopathology in relation to events in Europe. Much of the discussion centred on the role of human papilloma virus testing and its impact on the provision of cervical screening. The following is a transcript of the discussion that took place at the Advisory Board Meeting for the journal Cytopathology, with some additional written comments received prior to the meeting. A brief summary has been provided as a conclusion by Dr A. Herbert.
Prediction of aggressiveness of gastrointestinal stromal tumours based on immunostaining with bcl‐2, Ki‐67 and p53
Authors: Meara R. S. , Cangiarella J. , Simsir A. , Horton D. , Eltoum I. , Chhieng D. C.
Published: September 2007

Objective:  While the use of fine needle aspiration (FNA) in the diagnosis of gastrointestinal stromal tumours (GISTs) is well‐established, it can be difficult to predict the prognosis of GIST based on morphology alone. The objective of the current study was to determine if expression of bcl‐2, Ki‐67 and p53 correlated with the outcome of GISTs based on cytological material.

Methods:  Cell‐blocks from 14 GISTs diagnosed by FNA were retrieved. Immunostaining was performed with antibodies against bcl‐2, Ki‐67 and p53. All cytological diagnoses were confirmed by positive immunostaining with c‐kit and/or subsequent histological evaluation. Positivity for bcl‐2, Ki‐67 and p53 was defined as the presence of ≥10% cytoplasmic staining, ≥5% nuclear staining and ≥5% nuclear staining respectively.

Results:  The 14 patients consisted of seven males and seven females with a mean age of 58 years. The average follow‐up interval was 46 months. Six had a benign course and eight developed recurrences/metastases. Thirteen (93%) cases showed positive staining for bcl‐2. Positive Ki‐67 and p53 staining was noted in one (7%) and seven (50%) cases respectively. The difference in staining for p53 between aggressive and non‐aggressive GISTs was statistically significant. No statistically significant difference was noted for bcl‐2 staining or Ki‐67 labelling index between the two groups.

Conclusions:  According to our observations, p53 immunostaining may be useful in predicting the outcome of GIST diagnosed by FNA; Ki‐67 and bcl‐2 are not useful as prognostic markers for GIST in FNA specimens.
Pancreas transcription factor 1α expression is regulated in pancreatitis
Authors: Molero X. , Adell T. , Skoudy A. , Padilla M. A. , Gómez J. A. , Chalaux E. , Malagelada J. R. , Real F. X.
Published: September 2007

Background  Expression of acinar cell‐specific genes requires the pancreas transcription factor 1α (Ptf1α). p48 is the only component of Ptf1α that is involved in both acinar gene regulation and pancreatic ontogenesis.

Materials and methods  To determine whether Ptf1α/p48 expression is regulated during pancreatitis, acute pancreatitis was induced in rats by repeated caerulein injections; early chronic pancreatitis by the combined administration of caerulein and cyclosporin A; and focal pancreas fibrosis by trinitrobenzene sulfonic acid infusion into the pancreatic duct. AR42J cells were used to examine caerulein effects on acinar cells. Ptf1α/p48 expression was examined using immunohistochemistry, Western blotting, and qRT‐PCR methods.

Results  In acute pancreatitis, Ptf1α/p48 decreased markedly within 6 h as determined by Western blotting and immunohistochemistry. After 24 h, Ptf1α/p48 increased continuously and normalized at day six. In contrast, pancreas amylase reached a nadir at 48 h, when Ptf1α/p48 had largely recovered. In the early chronic pancreatitis model Ptf1α/p48 levels did not completely recover even at day 14, and this was associated with a failure to restore normal histology and amylase content. qRT‐PCR showed that p48 mRNA were reduced after pancreatitis induction and were followed by a decrease in elastase mRNA. In the focal pancreas fibrosis model, Ptf1α/p48 expression was undetectable in areas with substantial acinar cell loss and tubular complexes. Caerulein did not affect Ptf1α/p48 expression in AR42J cells.

Conclusions  Ptf1α/p48 protein and mRNA levels are regulated in acute and chronic experimental pancreatitis. Inability to re‐express Ptf1α/p48 after injury may preclude acinar cell differentiation and appropriate pancreatic regeneration.
Effects of free fatty acids on carbohydrate metabolism and insulin signalling in perfused rat liver
Authors: Anderwald C. , Brunmair B. , Stadlbauer K. , Krebs M. , Fürnsinn C. , Roden M.
Published: September 2007

Background  Elevated circulating free fatty acids (FFAs) induce insulin resistance and play a crucial role in the development of type 2 diabetes, in which fasting hepatic glucose production (HGP) is increased. However, direct effects of FFAs on fasting HGP are still unclear because indirect endocrine and metabolic effects contribute to FFA action. Thus, we aimed to investigate acute direct effects of specific FFAs on fasting HGP, lactate uptake, and insulin signalling.

Materials and methods  Isolated livers obtained from 20 h fasted rats were perfused with albumin‐bound palmitate or oleate (200 µmol L−1 each) or vehicle (control) for 180 min (n = 5–7/group).

Results  Compared to control, hepatic lactate uptake was increased by palmitate and oleate (~+40%; P < 0·05), while HGP from lactate (~3 mmol L−1) and liver glycogen content were similar. Tyrosine phosphorylation (pY) of insulin‐receptor‐substrate‐(IRS)‐2 and p70S6‐kinase phosphorylation were not affected by FFAs. Palmitate decreased insulin‐receptor‐β pY, IRS‐1 pY and phosphoinositol‐3‐kinase expression by 46 ± 16%, 46 ± 11% and 20 ± 9%, respectively (P < 0·03), while oleate reduced Akt phosphorylation by 85 ± 7% (P < 0·006).

Conclusions  Isolated liver perfusion with saturated or unsaturated FFAs reduced insulin signalling protein phosphorylation at different sites and increased lactate uptake without affecting HGP or glycogen content. These results suggest that at fasting, both saturated and unsaturated FFAs increase hepatic glucose precursor uptake and may, independently of insulin's presence, accelerate protein dephosphorylation of the insulin signalling cascade at different sites.
Collagen type VIII expression in human diabetic nephropathy
Authors: Gerth J. , Cohen C. D. , Hopfer U. , Lindenmeyer M. T. , Sommer M. , Gröne H. J. , Wolf G.
Published: September 2007

Background  Collagen type VIII is a non‐fibrillar short‐chain collagen that may modulate migration, proliferation and adherence of various cells. Only very sparse information exists on collagen type VIII expression in human diabetic nephropathy.

Material and methods  We retrospectively studied mRNA expression for the two collagen type VIII chains (COL8A1 and COL8A2) in 20 biopsies with histologically confirmed diabetic nephropathy by real‐time PCR, and compared glomerular and tubular expression with normal kidney [pre‐transplant biopsies (n = 10)]. Expression of collagen type VIII was also studied in biopsies from patients with benign nephrosclerosis (BNS; n = 16) and focal‐segmental glomerulosclerosis (FSGS; n = 9).

Results  A strong specific induction of COL8A1 mRNA was found in diabetic nephropathy in both glomerular and tubular compartments. There was also a robust induction of COL8A2 in diabetic nephropathy, but overall expression was lower than that of COL8A1 transcripts. No significant increase in COL8A1 and COL8A2 mRNAs expression was found in biopsies from patients with BNS and FSGS compared with normal kidneys. The cross‐reactivity of the used anti‐α1(VIII) antibody with human tissue was confirmed by Western blots. Immunohistological analysis revealed only little staining for collagen type VIII in the normal kidney, localized to vessels. There was an up‐regulation of collagen type VIII protein expression as shown by immunohistochemistry in the diabetic nephropathy biopsies mainly localized to mesangial cells, tubules and the interstitium. Proteinuria and serum creatinine did not correlate with glomerular or tubular COL8A1 and COL8A2 mRNA expression in diabetic patients.

Conclusion  Our study systemically investigates collagen type VIII expression in human biopsies. Induction of collagen type VIII was specific for diabetic nephropathy and did not occur in the other renal diseases studied. More specific factors of the diabetic environment are likely involved in the stimulated expression because there was no correlation of collagen type VIII mRNA expression with proteinuria. Since collagen type VIII may influence proliferation and migration of cells, it is possible that an increase in renal expression of collagen type VIII initiates other pathophysiological processes (e.g. proliferation of renal fibroblasts) involved in diabetic nephropathy.
Microalbuminuria and the metabolic syndrome and its components in the Chinese population
Authors: Lin C.‐C. , Liu C.‐S. , Li T.‐C. , Chen C.‐C. , Li C.‐I. , Lin W.‐Y.
Published: September 2007

Background  Microalbuminuria and the metabolic syndrome (MetS) have both been linked to chronic kidney disease and cardiovascular disease. This study investigated the association between urinary albumin‐to‐creatinine ratio (ACR) and MetS and its components.

Materials and methods  A total of 2311 subjects aged 40 years and over were recruited in 2004 in a metropolitan city in Taiwan. The biochemical indices, such as fasting glucose levels, urinary albumin, urinary creatinine and anthropometric indices, were measured. We defined microalbuminuria as a urinary ACR ranging from 30 to 300 mg g−1 creatinine. MetS was defined using the American Heart Association and the National Heart, Lung and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF) definitions. The relationship between MetS and microalbuminuria was examined using multiple logistical regression analysis.

Results  Subjects with microalbuminuria had higher age, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose, triglycerides, total cholesterol (TCHOL)/high‐density lipoprotein cholesterol (HDL‐C) ratio, prevalence of diabetes mellitus and hypertension and lower HDL‐C than subjects with normoalbuminuria. After adjusting for age and BMI, microalbuminuria was associated with the individual components of MetS, except in central obesity in women and elevated fasting glucose in men. After adjusting for age, BMI, smoking and alcohol consumption status, multiple logistical regressions revealed that microalbuminuria is strongly associated with MetS in both genders and according to both definitions. The odds ratio of having MetS using the AHA/NHLBI and IDF definition was 1·76 (1·16–2·67) and 1·73 (1·06–2·83) in men and 2·19 (1·38–3·50) and 2·09 (1·24–3·51) in women, respectively.

Conclusions  Microalbuminuria was strongly associated with MetS and its components. There is an increased likelihood of having MetS if subjects have microalbuminuria.