bluuebunny/crossref_metadata_2025_split huggingface dataset:
The 5′ untranslated regions (UTRs) of CCN1, CCN2, and CCN4 exhibit cryptic promoter activity
Authors: Huang Bau‐Lin , Dornbach Lisa M. , Lyons Karen M. 
Published: March 2007

AbstractCCNs are structurally related matricellular proteins that are highly expressed in many embryonic and adult tissues, including the skeletal system and tumors, where canonical cap‐dependent translation is suppressed under hypoxic environments. CCNs are encoded by mRNAs containing long G/C rich 5′‐untranslated regions (5′‐UTRs). Given that they are expressed under conditions of cellular stress, it has been suggested that the long G/C‐rich regions contain internal ribosomal entry sites (IRES) that allow these mRNAS to be translated under conditions where cap‐dependent translation is suppressed. Previously published work supported this possibility. However, recent studies have shown that a number of previously reported cellular IRES elements do not in fact possess IRES activity. Here we aimed to reveal whether the 5′UTRs of CCNs harbor IRES activities. The 5′UTRs of CCN1, 2, and 4 were tested in this study. Our results showed that the 5′UTRs of these genes do not contain IRES elements, but instead appear to contain cryptic promoters. Both promoterless and hairpin‐containing dicistronic tests showed that transcription was initiated by cryptic promoter elements in 5′UTRs of CCN1, 2, and 4. When dicistronic mRNAs were translated in vitro or in vivo, no IRES activities were detected in the 5′UTRs of CCN1, 2, and 4. Furthermore, these cryptic promoter activities from 5′UTRs of CCN1, 2, and 4 could be detected in various cell types, including chondrocytes, osteoblasts, and endothelial cells, where the cryptic promoter permitted varying degrees of activation. In addition, the core promoter element of the CCN2 5′UTR was identified. CCNs are expressed under conditions of cellular stress, and it has been suggested that some CCN family members utilize IRES‐mediated translation initiation to facilitate this expression. We found no evidence for IRES activity, but rather found that the unusually long 5′UTRs of CCNs 1, 2, and 4 harbor cryptic promoters that showed varying degrees of activity in different cell types. These results suggest that these promoters may contribute to the regulation of CCN genes in vivo.
The diagnostic efficacy of urinary fractionated metanephrines measured by tandem mass spectrometry in detection of pheochromocytoma
Authors: Perry C. G. , Sawka A. M. , Singh R. , Thabane L. , Bajnarek J. , Young W. F. 
Published: March 2007

SummaryBackground  There are limitations to currently available biochemical tests for pheochromocytoma. Our objective was to evaluate the diagnostic efficacy of a novel tandem mass spectrometry assay for the measurement of fractionated urinary metanephrines in patients suspected to have a pheochromocytoma. We also developed clinically based cut‐offs for positivity of this measurement.Methods  We examined the medical records of 506 patients (including 102 patients with a catecholamine‐producing tumour) who underwent measurement of 24‐h urinary fractionated metanephrines using tandem mass spectrometry as well as adrenal imaging at Mayo Clinic, Rochester. The cut‐offs for positivity were defined as follows: total metanephrines (sum of the metanephrine fractions) 5163 nmol/day, normetanephrine fraction 4001 nmol/day, metanephrine fraction 1531 nmol/day. Receiver operating characteristic (ROC) curves were constructed.Results  The diagnostic efficacy was as follows: normetanephrine fraction sensitivity 87·3% [(95% confidence interval (CI) 79·4–92·4%], specificity 95·0% (92·5–96·8); metanephrine fraction sensitivity 56·9% (47·2–66·1), specificity 95·0% (92·5–96·8); elevation of either normetanephrine or metanephrine fraction sensitivity 97·1% (91·7–99·0) and specificity 91·1% (87·9–93·5). Areas under the ROC curves (AUCs) were 0·972 (95% CI 0·955–0·990) for the normetanephrine fraction, 0·800 (0·741–0·858) for the metanephrine fraction, 0·991 (0·985–0·996) for total metanephrines, and 0·991 (0·985–0·996) for a regression‐derived ROC curve incorporating both the metanephrine and normetanephrine fractions.Conclusion  Measurement of 24‐h urinary fractionated metanephrines by a tandem mass spectrometry assay appears to be an effective biochemical technique in the investigation of pheochromocytoma.
A novel MEN1 intronic mutation associated with multiple endocrine neoplasia type 1
Authors: Lemos Manuel C. , Harding Brian , Shalet Stephen M. , Thakker Rajesh V. 
Published: March 2007

SummaryObjective  To investigate a family with an unusual combination of multiple endocrine neoplasia (MEN1) and the McCune–Albright syndrome for MEN1 mutations and activating GNAS1 mutations at codons Arg201 and Gln227.Methods  DNA sequences analyses were performed of the MEN1 gene and codons Arg201 and Gln227 of the GNAS1 gene, using leucocyte and endocrine tissue DNA.Results  A c→g transversion at position −9 bp in intron 9 of the MEN1 gene was identified. This resulted in the generation of a BmrI restriction endonuclease site, and its presence and segregation with MEN1 in the family was demonstrated by restriction endonuclease analysis. The c→g transversion was shown to result in the generation of a novel acceptor splice site (ccag) using reverse transcriptase‐polymerase chain reaction (RT‐PCR) and ribonucleic acid (RNA) obtained from Epstein‐Barr virus (EBV)‐transformed lymphoblasts. Utilization of this splice site resulted in an abnormal messenger RNA (mRNA) transcript that contained an additional eight bases. This predicted a frameshift that would result in nine missense amino acids followed by a premature termination signal. GNAS1 mutations were not detected in the patient with McCune–Albright syndrome.Conclusions  The occurrence of MEN1 and the McCune–Albright syndrome in this family are coincidental findings and not due to a common genetic aetiology. However, our results have identified a novel MEN1 mutation that occurs in intron 9 and generates a novel acceptor splice site. Such splicing‐affecting genomic variants (SpaGVs) are increasingly being recognized as a cause of human disease, and are likely to be of significance in the 10% of MEN1 patients who do not have coding region mutations.
Growth hormone excess with onset in adolescence: clinical appearance and long‐term treatment outcome
Authors: Colao Annamaria , Pivonello Rosario , Di Somma Carolina , Tauchmanovà Libuse , Savastano Silvia , Lombardi Gaetano 
Published: March 2007

SummaryBackground  Limited data are available on clinical presentation and treatment strategy in patients with GH‐secreting adenomas with onset in adolescence.Objective  To report results of diagnosis and treatment in adolescents with GH and IGF‐I excess.Design  Analytical, observational, retrospective.Subjects  Thirteen patients (five females and eight males, age 15–20 years) all with macroadenoma (two extrasellar, 11 invasive).Main outcome measures  Height, body mass index (BMI), GH and IGF‐I levels, tumour volume at diagnosis and after treatment.Interventions  Transsphenoidal surgery, octreotide subcutaneous (OCT, 0·3–0·8 mg/day), octreotide‐LAR i.m. (LAR, 20–30 mg/q28 days), lanreotide i.m. (LAN, 60–90 mg/q28 days), bromocriptine (BRC, 5 mg/day), cabergoline (CAB, 1–2 mg/week).Results  Concomitant hyperprolactinaemia was found in eight patients (61·5%). All girls presented with amenorrhoea, which was associated with galactorrhoea in two patients; all boys presented with symptoms of tumour mass compression such as visual disturbance or headache; two girls also had these symptoms. Height at diagnosis was above the 97th centile in four of five girls and in six of eight boys. None of the patients had altered lipid profile while homeostasis model assessment of insulin resistance (HOMA‐IR; 2·8 ± 0·9) and β‐cell function (HOMA‐β, 207·6 ± 98·1%) were higher than predicted (1% and 100%, respectively). First‐line treatment was surgery in two patients and somatostatin analogues associated with dopaminergic drugs in 11 patients. None of the patients operated on were cured while six of 11 patients receiving pharmacotherapy (6–24 months) were controlled. In these six, tumour volume was reduced by 51·0 ± 25·2% (median 51·5%). As second‐line treatment, all the 11 patients treated with somatostatin analogues underwent surgical removal of their tumours. Surgery was successful in four patients and second‐line pharmacotherapy in six patients. One patient was lost at follow‐up and two patients maintained active acromegaly despite different treatment schedules; both patients were then treated with radiotherapy. At the last follow‐up, there was a significant decrease in insulin levels, HOMA‐IR and HOMA‐β without any change in lipid profile.Conclusions  The clinical presentation of GH‐secreting adenomas in adolescent girls is associated with menstrual disturbances and in boys with symptoms of mass effects; tall stature is characteristic in both. First‐line treatment with depot somatostatin analogues followed by surgery and then by a second course of somatostatin analogues was successful and safe in 11 of 13 patients.
Withdrawal of somatostatin analogue therapy in patients with acromegaly is associated with an increased risk of acute biliary problems
Authors: Paisley A. N. , Roberts M. E. , Trainer P. J. 
Published: March 2007

SummaryBackground  The prevalence of gallstones (GS) is increased in acromegaly and further increased by somatostatin analogue (SA) therapy. The incidence is reported at 10–63%, but they are often asymptomatic and rarely require definitive management. Evidence suggests discontinuation of SA may precipitate acute biliary problems.Objective  To determine the frequency of symptomatic gallstones in patients treated with SA.Design  Retrospective analysis of prospectively followed patients in our centre.Results  Fifty patients (30 male, mean age 54 ± 16 years) were on treatment with SA on 1 January 2003. Fifteen (11 male, mean age 50 ± 17 years) have since discontinued SA with three proceeding to develop acute cholecystitis and two, biliary colic necessitating cholecystectomy. Three of the five had abnormal liver enzymes at or within 3 months of symptomatic presentation. Two of the remaining 35 patients experienced biliary colic necessitating cholecystectomy. These data indicate a highly significant increase in acute biliary problems on discontinuing SA (5 in 27·67 patient ‘off‐treatment’ years vs. 2 in 299 patient treatment years, χ2, P < 0·0001). All seven patients experiencing problems were male (P = 0·01).Conclusion  This analysis demonstrates the high incidence of symptomatic GS following SA withdrawal, particularly in men. Although liver enzymes were raised no common abnormality was evident to aid as a predictor of future symptoms. We recommend all patients due to stop SA be forewarned of the risk of acute biliary problems. Further work is required to confirm if there is a gender‐related difference in the incidence of acute biliary problems on discontinuing SA therapy.
Ischaemia and reperfusion effects on skeletal muscle tissue: morphological and histochemical studies
Authors: Carmo‐Araújo Edna Maria , Dal‐Pai‐Silva Maeli , Dal‐Pai Vitalino , Cecchini Rubens , Anjos Ferreira Ana Lucia 
Published: March 2007

SummaryThis was a study on the oxidative stress due to ischaemia (I) and reperfusion (R) in skeletal muscle tissue. Using a tourniquet, groups of rats were submitted to ischaemia for 4 h, followed by different reperfusion periods. The animals were divided in four groups: control; 4 h of ischaemia (IR); 4 h of ischaemia plus 1 h reperfusion (IR‐1 h); 4 h of ischaemia plus 24 h reperfusion (IR‐24 h); and 4 h of ischaemia plus 72 h reperfusion (IR‐72 h). At the end of the procedures, samples of soleus muscle were collected and frozen in n‐hexane at −70 °C. Cryostat sections were submitted to haematoxylin–eosin, succinate dehydrogenase (SDH) and nicotinamide adenine dinucleotide‐tetrazolium reductase (NADH‐TR) stains. An additional muscle sample was processed for electron microscopy. No alterations were found in control animals. IR group showed fibres had normal aspect besides some round, acidophilic and hypertrophic fibres. There were several fibres with angular outlines and smaller diameters in this group compared with control group. NADH‐TR/SDH reaction was moderately intense in most fibres. In some fibres, cytoplasm showed areas without activity and other fibres had very intense reactivity. IR‐1 h group showed oedema hypercontracted fibres with disorganized myofibrils, mitochondria with focal lesions and dilated sarcoplasmic reticulum. NADH‐TR/SDH reaction was moderate to weak. IR‐24 h showed intense inflammatory infiltrate in the endomysium and perimysium. NADH‐TR/SDH reaction was similar to IR‐1 h. IR‐72 h showed necrotic fibres, areas with inflammatory infiltrate, reduced muscle fibres at different stages of necrosis and phagocytosis, and many small round and basophilic fibres characterizing a regeneration process. NADH‐TR/SDH reaction was weak to negative. Our results suggest that ischaemia and the subsequent 1‐, 24‐ and 72‐h reperfusions induced progressive histological damage. Although progressive, it may be reversible because there were ultrastructural signs of recovery after 72‐h reperfusion. This recovery could in part be due to the low oxidative stress identified by the morphological and histochemical analysis.
Evolution of Quaternary alluvial fans and terraces in the intramontane Pinjaur Dun, Sub‐Himalaya, NW India: interaction between tectonics and climate change
Authors: SURESH NARAYANAPANICKER , BAGATI TRILOKI N. , KUMAR ROHTASH , THAKUR VIKRAM C. 
Published: March 2007

AbstractQuaternary alluvial fans in the tectonically active Pinjaur Dun, an intramontane valley in the Sub‐Himalaya, were deposited in front of the Nalagarh Thrust and were influenced both by tectonics and glacial climate fluctuations. The surface morphology indicates that an earlier set of first‐order fans (Qf1) became entrenched and onlapped by a series of second‐order fans (Qf2). The younger fan segments were then cut by a pair of terraces (T1 and T2). Quartz optically stimulated luminescence dating establishes that the Qf1 aggradational phase was initiated before 96·5 ± 25·3 ka and terminated after 83·7 ± 16·3 ka. This was followed by a period of incision, before Qf2 fan deposition started at 72·4 ± 13·4 ka and continued until 24·5 ± 4·9 ka. Sediment was deposited on the T1 (upper) and T2 (lower) terraces at 16·3 ± 2·1 and 4·5 ka, respectively, recording a return to overall degradation punctuated by minor deposition on terraces. The period of incision separating the younger and older fan deposits coincided with enhanced SW monsoon precipitation. The subsequent development of the Qf2 fans and their progradation until 20 ka suggest erosional unloading of the thrust hangingwall during a tectonically quiescent phase. Toe cutting, deposition of axial river and lacustrine facies, and retreat of Qf2 around 45 ka, indicate fanward shift of the axial river due to tilting of the valley towards the NE in response to reactivation of the Nalagarh Thrust. The cessation of Qf2 deposition around 20 ka and the onset of through‐fan entrenchment suggest reduced sediment supply but relatively high stream power during the last glacial maxima (LGM). The prolonged stream incision since the cessation of Qf2 deposition, with only minor depositional phases at 16·3 ± 2·1 and 4·5 ka, resulted from high water discharge and low sediment input during intensification of the SW monsoon and vegetation changes in the hinterland.
Turbidite bed thickness distributions: methods and pitfalls of analysis and modelling
Authors: SYLVESTER ZOLTÁN 
Published: March 2007

AbstractTurbidite bed thickness distributions are often interpreted in terms of power laws, even when there are significant departures from a single straight line on a log–log exceedence probability plot. Alternatively, these distributions have been described by a lognormal mixture model. Statistical methods used to analyse and distinguish the two models (power law and lognormal mixture) are presented here. In addition, the shortcomings of some frequently applied techniques are discussed, using a new data set from the Tarcău Sandstone of the East Carpathians, Romania, and published data from the Marnoso‐Arenacea Formation of Italy. Log–log exceedence plots and least squares fitting by themselves are inappropriate tools for the analysis of bed thickness distributions; they must be accompanied by the assessment of other types of diagrams (cumulative probability, histogram of log‐transformed values, q–q plots) and the use of a measure of goodness‐of‐fit other thanR2, such as the chi‐square or the Kolmogorov–Smirnov statistics. When interpreting data that do not follow a single straight line on a log–log exceedence plot, it is important to take into account that ‘segmented’ power laws are not simple mixtures of power law populations with arbitrary parameters. Although a simple model of flow confinement does result in segmented plots at the centre of a basin, the segmented shape of the exceedence curve breaks down as the sampling location moves away from the basin centre. The lognormal mixture model is a sedimentologically intuitive alternative to the power law distribution. The expectation–maximization algorithm can be used to estimate the parameters and thus to model lognormal bed thickness mixtures. Taking into account these observations, the bed thickness data from the Tarcău Sandstone are best described by a lognormal mixture model with two components. Compared with the Marnoso‐Arenacea Formation, in which bed thicknesses of thin beds have a larger variability than thicknesses of the thicker beds, the thinner‐bedded population of the Tarcău Sandstone has a lower variability than the thicker‐bedded population. Such differences might reflect contrasting depositional settings, such as the difference between channel levées and basin plains.
Shared or Unshared Parental Care in Overwintering Brent Geese (Branta bernicla hrota)
Authors: Tinkler Evelynne , Ian Montgomery W. , Elwood Robert W. 
Published: March 2007

AbstractWe examine brood size effects on the behaviour of wintering parent and juvenile brent geese (Branta bernicla hrota) to test predictions of shared and unshared parental care models. The behaviour of both parents and offspring appear to be influenced by declining food availability over the winter. Parental vigilance increased with brood size and may be explained by vigilance having functions in addition to antipredator behaviour where the benefits are shared among the brood. There was no increase in parental aggression with brood size and this does not fit the prediction of shared care. Nevertheless, large families are able to monopolize better feeding areas compared with smaller families and large families static feed more but walk feed less than do small families, the former apparently being the preferred mode. The presence of additional young, rather than increasing the amount of parental aggression, seems to enhance the family's competitive ability. Because parents with large broods benefit from enhanced access to resources there is likely to be no additional significant cost in the parental care of larger broods (sensuTrivers 1972).
Discoloured and non‐conductive sapwood among six Fagaceae species inoculated with Raffaelea quercivora
Authors: Murata M. , Yamada T. , Matsuda Y. , Ito S. 
Published: March 2007

SummaryMass mortality of oak trees has been occurring in Japan since the late 1980s. The fungus Raffaelea quercivora has been frequently isolated from discoloured sapwood in dead or wilting trees and inoculation experiments have shown it to be capable of causing wilting and xylem discoloration in several oak species, notably Quercus crispula and Q. serrata. In this study, we inoculated seedlings of six Fagaceae species with R. quercivora and, after 56 days, measured the vertical length of the discoloration and the areas of discoloured and non‐conducting sapwood on stem cross‐sections. The sapwood discoloration and the water non‐conduction areas were larger in Q. crispula and Q. serrata than in the other species.
Pathogenic wood‐decaying fungi in China
Authors: Dai Y. C. , Cui B. K. , Yuan H. S. , Li B. D. 
Published: March 2007

SummaryWood‐decaying fungi on living trees in China were surveyed over the last 12 years. In all, 102 potentially pathogenic Basidiomycetes were found in natural forests, forest plantations, parks and gardens, and among them 20 species were recorded for the first time on living trees in China. The host(s), occurrence, type of damage, type of decay and distribution of each species in China are given. Most of these wood‐destroying fungi are polypores in the Aphyllophorales, and the majority were found in temperate and boreal forests. Of all the species detected, 88 species are known to cause white rot, and 14 cause brown rot; 25 species are considered as common, 44 occasional, and 33 rare.
Molecular and serological diagnosis of invasive aspergillosis: new answers to old questions?
Authors: Hummel Margit , Buchheidt Dieter 
Published: March 2007

SummaryOver the recent years, novel molecular and serological methods have been developed to improve diagnosis of invasive aspergillosis (IA) in patients at high risk for fungal infections, especially patients with malignant haematological diseases undergoing intensive chemotherapy. Early diagnosis and treatment are crucial in the management of fungal infections. However, diagnosis often remains difficult as most of the diagnostic tools in clinical use at present either lack specificity or acceptable sensitivity in the early phase of the infection. The clinical value, advantages and problems of current molecular and serological approaches to diagnose IA are reviewed.
Caspofungin as salvage monotherapy for invasive aspergillosis in patients with haematological malignancies or following allogeneic stem cell transplantation: efficacy and concomitant cyclosporin A
Authors: Morrissey C. O. , Slavin M. A. , O'Reilly M. A. , Daffy J. R. , Seymour J. F. , Schwarer A. P. , Szer J. 
Published: March 2007

SummaryCaspofungin (CAS) has shown efficacy as salvage monotherapy for invasive aspergillosis (IA) in two open label non‐comparative trials. The association between hepatotoxicity and concomitant use of CAS and cyclosporin A (CsA) has not been fully elucidated. We report results on CAS efficacy in the first cohort from outside Europe and USA and the interaction between CAS and CsA. We retrospectively reviewed the charts of all patients with haematological malignancies or postallogeneic haematopoietic stem cell transplant (HSCT) who received ≥1 dose of CAS as salvage monotherapy for IA as part of the Australian Special Access Scheme (4/2001‐8/2002). Outcomes were assessed at the end of CAS therapy. Favourable response (FR) was defined as >50% clinical and radiological improvement. Risk factors for elevation of liver transaminases (LTs) were examined using multivariate models. 54 patients were included in the analysis with 47 neutropenic at study entry. Proven or probable IA occurred in 11 and refractory IA in 28. An FR occurred in 26 (48.1%) and predictors for a poor response to CAS were allogeneic HSCT, graft vs. host disease and treatment with CAS for <14 days. Concomitant CAS and CsA for >7 days was an independent risk factor for laboratory hepatoxicity. The CAS efficacy results from the Australian cohort confirm those of previous studies. Close monitoring of LTs is necessary on concomitant CAS and CsA but clinically relevant hepatotoxicity is rare.