bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide detection of segmental duplications and potential assembly errors in the human genome sequence
Authors: Cheung Joseph , Estivill Xavier , Khaja Razi , MacDonald Jeffrey R , Lau Ken , Tsui Lap-Chee , Scherer Stephen W 
Published: May 2003

Abstract
Background
Previous studies have suggested that recent segmental duplications, which are often involved in chromosome rearrangements underlying genomic disease, account for some 5% of the human genome. We have developed rapid computational heuristics based on BLAST analysis to detect segmental duplications, as well as regions containing potential sequence misassignments in the human genome assemblies.

Results
Our analysis of the June 2002 public human genome assembly revealed that 107.4 of 3,043.1 megabases (Mb) (3.53%) of sequence contained segmental duplications, each with size equal or more than 5 kb and 90% identity. We have also detected that 38.9 Mb (1.28%) of sequence within this assembly is likely to be involved in sequence misassignment errors. Furthermore, we have identified a significant subset (199,965 of 2,327,473 or 8.6%) of single-nucleotide polymorphisms (SNPs) in the public databases that are not true SNPs but are potential paralogous sequence variants.

Conclusion
Using two distinct computational approaches, we have identified most of the sequences in the human genome that have undergone recent segmental duplications. Near-identical segmental duplications present a major challenge to the completion of the human genome sequence. Potential sequence misassignments detected in this study would require additional efforts to resolve.
GoMiner: a resource for biological interpretation of genomic and proteomic data
Authors: Zeeberg Barry R , Feng Weimin , Wang Geoffrey , Wang May D , Fojo Anthony T , Sunshine Margot , Narasimhan Sudarshan , Kane David W , Reinhold William C , Lababidi Samir , Bussey Kimberly J , Riss Joseph , Barrett J Carl , Weinstein John N 
Published: May 2003

AbstractWe have developed GoMiner, a program package that organizes lists of 'interesting' genes (for example, under- and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. GoMiner provides quantitative and statistical output files and two useful visualizations. The first is a tree-like structure analogous to that in the AmiGO browser and the second is a compact, dynamically interactive 'directed acyclic graph'. Genes displayed in GoMiner are linked to major public bioinformatics resources.
ProSplicer: a database of putative alternative splicing information derived from protein, mRNA and expressed sequence tag sequence data
Authors: Huang Hsien-Da , Horng Jorng-Tzong , Lee Chau-Chin , Liu Baw-Jhiune 
Published: May 2003

AbstractProSplicer is a database of putative alternative splicing information derived from the alignment of proteins, mRNA sequences and expressed sequence tags (ESTs) against human genomic DNA sequences. Proteins, mRNA and ESTs provide valuable evidence that can reveal splice variants of genes. The alternative splicing information in the database can help users investigate the alternative splicing and tissue-specific expression of genes.
The role of hypertonic saline dextran in trauma resuscitation
Authors: Perera AM , Porter KM 
Published: May 2003

Modern trauma management has recognized the importance of using conservative fluid resuscitation regimes in order to prevent complications from fluid overload arising. Hypertonic/hyperoncotic fluids appear to provide an ideal means of facilitating this, requiring only small volumes to rapidly elevate blood pressure. Hypertonic saline dextran (HSD) was introduced in 1985 but its take up has been slow, a large part of this has been due to the lack of human trials and concerns about complications.The current evidence has been reviewed and it is clear that HSD is an efficient means of correcting hypotension, doing so mainly by the mobilizing endogenous water. It is becoming apparent that early administration has the potential to modulate the inflammatory cascade in patients at risk of developing adult respiratory distress syndrome (ARDS) and multiorgan failure. This is reflected in the handful of human trials that show a trend towards increased survival (particularly for head injuries) and a possible reduction in ARDS. The side effect profile appears to be good, even in the presence of dehydration or penetrating trauma.Published human trials have methodological problems and lack of power of study this has led to a reliance on animal studies. Clearly there is great potential, but before large-scale prehospital usage can be justified further well-conducted randomized human trials are needed.
Structural disconnectivity in schizophrenia: a diffusion tensor magnetic resonance imaging study
Authors: Burns J. , Job D. , Bastin M. E. , Whalley H. , Macgillivray T. , Johnstone E. C. , Lawrie S M. 
Published: May 2003

BackgroundThere is growing evidence that schizophrenia is a disorder of cortical connectivity Specifically, frontotemporal and frontoparietal connections are thought to be functionally impaired. Diffusion tensor magnetic resonance imaging (DT–MRI) is a technique that has the potential to demonstrate structural disconnectivity in schizophrenia.AimsTo investigate the structural integrity of frontotemporal and frontoparietal white matter tracts in schizophrenia.MethodThirty patients with DSM–IV schizophrenia and thirty matched control subjects underwent DT–MRI and structural MRI. Fractional anisotropy – an index of the integrity of white matter tracts – was determined in the uncinate fasciculus, the anterior cingulum and the arcuate fasciculus and analysed using voxel-based morphometry.ResultsThere was reduced fractional anisotropy in the left uncinate fasciculus and left arcuate fasciculus in patients with schizophrenia compared with controls.ConclusionsThe findings of reduced white matter tract integrity in the left uncinate fasciculus and left arcuate fasciculus suggest that there is frontotemporal and frontoparietal structural disconnectivity in schizophrenia.
Mild cognitive impairment: prevalence and incidence according to different diagnostic criteria
Authors: Busse Anja , Bischkopf Jeannette , Riedel-Heller Steffi G. , Angermeyer Matthias C. 
Published: May 2003

BackgroundAlthough mild cognitive impairment is associated with an increased risk of developing dementia, there has been little work on its incidence and prevalence.AimsTo report age-specific prevalence, incidence and predictive validities for four diagnostic concepts of mild cognitive impairment.MethodA community sample of 1045 dementia-free individuals aged 75 years and over was examined by neuropsychological testing in a three-wave longitudinal study.ResultsPrevalence rates ranged from 3% to 20%, depending on the concept applied. The annual incidence rates applying different case definitions varied from 8 to 77 per 1000 person-years. Rates of conversion to dementia over 2.6 years ranged from 23% to 47%.ConclusionsMild cognitive impairment is frequent in older people. Prevalence, incidence and predictive validities are highly dependent on the diagnostic criteria applied.
A survey of methadone prescribing at an inner-city drug service and a comparison with national data
Authors: Dunn John 
Published: May 2003

Aims and MethodSurveys suggest that UK drug services under-prescribe methadone to opiate-dependent patients. This study investigated methadone prescribing for 169 patients on long-term methadone at a specialist drug service.ResultsThe mean methadone dose for patients on maintenance was 65.8 mg, and 67.7% were taking 50 mg or more. Mean doses in relation to methadone formulation varied substantially: mixture 57.4 mg, tablets 81.8 mg and ampoules 113.0 mg. These figures are higher than those reported from national surveys. The proportion of urine screens positive for illicit opiates was inversely related both to methadone dose and length of time in treatment.Clinical ImplicationsThis survey shows the levels of methadone prescribing at an inner-city drug service and gives support to the effectiveness of high-dose methadone maintenance.
Implementation of the Care Programme Approach in prison
Authors: Pyszora Natalie M , Telfer Julia 
Published: May 2003

Aims and MethodRecent government legislation has highlighted the importance of implementation of the Care Programme Approach (CPA) within prisons, as part of the expectation that prisoners receive equivalent standards of healthcare to those provided by the National Health Service. To effectively plan the service provision at HMP Belmarsh, we retrospectively established the number of prisoners in a one-year period who would have fulfilled the criteria for enhanced CPA.ResultsOf the 91 prisoners found to fulfil the criteria for enhanced CPA, the majority (77%) had a diagnosis of schizophrenia, schizoaffective or delusional disorder, and 58% required transfer to a psychiatric hospital. Of those who required hospital treatment, 75% needed conditions of high- or medium-security.Clinical ImplicationsSuccessful implementation of the CPA for all prisoners who meet enhanced CPA criteria is likely to have significant resource implications, both for mental health teams working within prisons and local psychiatric services.
A Model to Determine Workforce Needs for Endocrinologists in the United States Until 20201
Authors: Rizza Robert A. , Vigersky Robert A. , Rodbard Helena W. , Ladenson Paul W. , Young Jr. William F. , Surks Martin I. , Kahn Richard , Hogan Paul F. 
Published: May 2003

The objective of this study was to define the workforce needs for the specialty of endocrinology, diabetes, and metabolism in the United States between 1999 and 2020.
An interactive model of factors likely to influence the balance between the supply and demand of endocrinologists during the next 20 yr was constructed. The model used data from a wide range of sources and was developed under the guidance of a panel of experts derived from sponsoring organizations of endocrinologists. We determined current and projected numbers and demographics of endocrinologists in the United States workforce and the anticipated balance between supply and demand from 1999 to 2020. There were 3,623 adult endocrinologists in the workforce in 1999, of which 2,389 (66%) were in office-based practice. Their median age was 49 yr. Both total office visits and services performed by endocrinologists (particularly for diabetes) increased substantially during the 1990s. Waiting time for an initial appointment is presently longer for endocrinologists than for other physicians. Compared with a balanced, largely closed-staff health maintenance organization, the current national supply of endocrinologists is estimated to be 12% lower than demand. The number of endocrinologists entering the market has continuously fallen over the previous 5 yr, from 200 in 1995 to 171 in 1999. Even if this downward trend were abruptly stopped, the model predicts that demand will exceed supply from now until 2020. Whereas this gap narrows from 2000 to 2008 due to projected growth of managed care, it widens thereafter due to the aging of both the population and the endocrine workforce. Inclusion of other factors such as projected real income growth and increased prevalence of age-related endocrine disorders (e.g. diabetes and osteoporosis) further accentuates the deficit. If the number of endocrinologists entering the workforce remains at 1999 levels, demand will continue to exceed supply from now through 2020 for adult endocrinologists, and the gap will widen progressively from 2010 onward. The present analysis indicates that the number of endocrinologists entering the workforce will not be sufficient to meet future demand. These data suggest that steps should be taken to stop the ongoing decline in the number of endocrinologists in training and consideration should be given to actions designed to increase the number of endocrinologists in practice in the years ahead.
Nephrolithiasis in Cushing’s Disease: Prevalence, Etiopathogenesis, and Modification after Disease Cure
Authors: Faggiano Antongiulio , Pivonello Rosario , Melis Daniela , Filippella Mariagiovanna , Di Somma Carolina , Petretta Mario , Lombardi Gaetano , Colao Annamaria 
Published: May 2003

The pathogenesis of nephrolithiasis in Cushing’s syndrome is still not completely clarified. The current study aimed at investigating prevalence of nephrolithiasis and role of different lithogenic factors in Cushing’s disease (CD). Forty-six CD patients (24 with active and 22 with cured disease) and 46 sex- and age-matched controls entered the study. Body mass index, blood pressure, fasting glucose and insulin, serum and urinary creatinine, urea, uric acid, electrolytes, and cystine, urinary volume, pH, oxalate, and citrate levels, and renal ultrasonography (US) were performed in all patients and controls. Nephrolithiasis was found in 50% of active patients, 27.3% of cured patients, and 6.5% of controls (P &lt; 0.001). Compared with controls, patients with active disease had a significantly increased prevalence of obesity, arterial hypertension, diabetes mellitus, hypercalciuria, hypocitraturia, and hyperuricosuria, significantly higher levels of serum and urinary cystine, urinary creatinine, urea, uric acid, potassium, calcium, phosphorus, and oxalate, significantly lower levels of urinary citrate levels. Compared with controls, patients cured from CD had a significantly increased prevalence of obesity, systemic arterial hypertension, and diabetes mellitus, whereas urinary citrate was significantly decreased. At multivariate analysis, a significantly increased risk to develop kidney stones was independently associated with urinary excretion of uric acid (odds ratio = 1.6, confidence interval = 1.0–2.5) and systemic arterial blood pressure (odds ratio = 2.6, confidence interval = 1.1–6.6).
In conclusion, patients with active CD have an increased prevalence of nephrolithiasis compared with general population, which decreases but not disappears in patients successfully cured from the disease. This complication is likely caused by the synergic effect of different hypercortisolism-dependent metabolic and hemodynamic abnormalities, among which systemic arterial hypertension and excessive urinary uric acid excretion seem to play a pivotal role.
Resveratrol transport and metabolism by human intestinal Caco-2 cells
Authors: Kaldas Mark I , Walle U Kristina , Walle Thomas 
Published: May 2003

Abstract
Resveratrol is a dietary constituent suggested to have protective effects against cancer as well as cardiovascular disease. The purpose of the study was to learn whether this agent could be absorbed in man and enter the systemic circulation. This was examined by measuring transport and metabolism of resveratrol (5–40 μM) by the human intestinal epithelial cell line Caco-2 cultured in Transwells. Transport across the Caco-2 monolayer occurred in a direction-independent manner with Papp values of ≅ 7 times 10−6 cm s−1, much higher than for the paracellular transport marker mannitol (≅ 0.4 times 10−6 cms−1), suggesting efficient absorption in-vivo. At the highest resveratrol concentration, the absorption increased, possibly due to saturation of metabolism. In sharp contrast to previous findings in the rat, the metabolism of resveratrol in Caco-2 cells involved mainly sulfation and, to a minor extent, glucuronidation. At low resveratrol concentrations, most of the sulfate conjugate was exported to the apical side, presumably by MRP2, which is well expressed in these cells. At high concentrations, there was a shift towards the basolateral side, possibly involving MRP3, which was recently shown also to be expressed in Caco-2 cells. These results indicate that absorption of resveratrol in-vivo may be high but with limited bioavailability due to efficient sulfate conjugation. Extensive accumulation of resveratrol in the Caco-2 cells, demonstrated in additional experiments, suggests enterocytes as a major target site for this cancer preventive agent.
Quercetin, a phytoestrogen and dietary flavonoid, activates different membrane-bound guanylate cyclase isoforms in LLC-PK1 and PC12 cells
Authors: Chen Zi-Jiang , Vetter Michael , Chang Geen-Dong , Liu Shiguo , Chang Chung-Ho 
Published: May 2003

Abstract
Accumulated evidence suggests that quercetin, a dietary flavonoid, has beneficial effects in protection against cardiovascular diseases and in the inhibition of tumour growth. We have recently shown that antioxidants such as 17β-estradiol, resveratrol, dithiothreitol and vitamin C activate membrane-bound guanylate cyclase GC-A, a receptor for atrial natriuretic factor (ANF). Since quercetin is a phytoestrogen and potent antioxidant, it is possible that it may activate GC-A or other guanylate cyclase isoforms. We examined whether quercetin activates GC-A or GC-B (the receptor for C-type natriuretic peptide, CNP) in PC12 and porcine kidney proximal tubular LLC-PK1 cells. The results showed that quercetin activated a guanylate cyclase isoform in both cell types. Quercetin inhibited CNP-stimulated GC-B activity, but had little effect on ANF-stimulated GC-A activity in PC12 cells, suggesting that quercetin mainly activates GC-B in PC12 cells. In contrast, CNP had no effect on guanylate cyclase activity in LLC-PK1 cells, indicating that GC-B is not expressed in LLC-PK1 cells. Furthermore, quercetin had a small effect on ANF-stimulated GC-A activity and had no effect on soluble guanylate cyclase activity in LLC-PK1 cells, suggesting that quercetin does not activate GC-A, GC-B or soluble guanylate cyclase in LLC-PK1 cells. However, quercetin did stimulate membrane-bound guanylate cyclase activity in LLC-PK1 cell membranes. These results indicate that quercetin activates the GC-B isoform in PC12 cells, but activates an unknown membrane-bound guanylate cyclase isoform in LLC-PK1 cells.
Endothelium-dependent and -independent vasodilator effects of eugenol in the rat mesenteric vascular bed
Authors: Criddle David Neil , Madeira Socorro Vanesca Frota , de Moura Roberto Soares 
Published: May 2003

Abstract
The possible involvement of the endothelium in the vasodilator action of eugenol was investigated in the mesenteric vascular bed (MVB) of the rat. Bolus injections of eugenol (0.2, 2 and 20 μmol) and acetylcholine (ACh; 10, 30 and 100 pmol) induced dose-dependent vasodilator responses in noradrenaline-precontracted beds that were partially inhibited by pretreatment of the MVB with deoxycholate (1 mg mL−1) to remove the endothelium (˜ 14% and ˜ 30% of the control response remaining at the lowest doses of ACh and eugenol, respectively). The vasodilator effect of glyceryl trinitrate (1 μmol) was unaltered by deoxycholate. In the presence of either Nω-nitro-L-arginine methyl ester (300 μM) or tetra-ethylammonium (1 mM) the response to ACh was partially reduced, whereas eugenol-induced vasodilation was unaffected. Similarly the vasodilator effect of eugenol was not inhibited by indometacin (3 μM). Under calcium-free conditions the vasoconstrictor response elicited by bolus injections of noradrenaline (10 nmol) was dose-dependently and completely inhibited by eugenol (0.1–1 mM). Additionally, the pressor effects of bolus injections of calcium chloride in potassium-depolarized MVBs were greatly reduced in the presence of eugenol (0.1 mM), with a maximal reduction of ˜ 71% of the control response. Our data showed that eugenol induced dose-dependent, reversible vasodilator responses in the rat MVB, that were partially dependent on the endothelium, although apparently independent of nitric oxide, endothelium-derived hyperpolarizing factor or prostacyclin. Furthermore, an endothelium-independent intracellular site of action seemed likely to participate in its smooth muscle relaxant properties.
Dual effect of agmatine in the bisected rat vas deferens
Authors: Santos Wilson C , Smaili Soraya S , Jurkiewicz Aron , Piçarro Ivan , Garcez-do-Carmo Lúcia 
Published: May 2003

Abstract
The functional effects of the amine agmatine, the putative endogenous ligand for α2-adrenoceptors and imidazoline receptors, in rat vas deferens were investigated by using the epididymal and prostatic portions. Tissues were contracted by electrical stimulation or by exogenous drugs. In electrically stimulated portions, agmatine caused a dual effect on contractions. In the epididymal portion an inhibition on twitch contractions was observed, which was partially antagonised by idazoxan and yohimbine, indicating the involvement of at least a presynaptic α2-adrenoceptor-mediated mechanism, without the interference of imidazoline receptors. In the prostatic portion, agmatine enhanced the amplitude of twitches. In contractions induced by exogenous drugs, agmatine potentiated, only in the prostatic segment, the effects of noradrenaline (norepinephrine) or ATP; it also enhanced the effect of low concentrations of KCl and blocked the maximum effect of the higher concentrations. Effects induced by agmatine on the exogenous ATP in the prostatic portion were blocked by cromakalim, suggesting a blocking action on the postsynaptic K+ channels, which explains, in part, the potentiation of the twitch amplitude. It was concluded that agmatine interferes with sympathetic neurotransmission, but the physiological relevance of this needs to be better understood because of the high doses employed to induce its effects.
Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir
Authors: Weemhoff James L , von Moltke Lisa L , Richert Clemens , Hesse Leah M , Harmatz Jerold S , Greenblatt David J 
Published: May 2003

Abstract
The influence of the viral protease inhibitor lopinavir on the activity of six human cytochrome P450 (CYP) enzymes was evaluated in a model system using human liver microsomes. Column chromatography methodology was developed to separate lopinavir from ritonavir starting from the commercially available lopinavir-ritonavir combination dosage form. Lopinavir produced negligible or weak inhibition of human CYP1A2, 2B6, 2C9, 2C19 and 2D6. However, lopinavir was an inhibitor of CYP3A. At 250 μM triazolam (the CYP3A index substrate), the mean (± s.e., n = 4) IC50 versus triazolam α-hydroxylation (where IC50 is the concentration producing a 50% decrement in reaction velocity) was 7.3 (± 0.5) μM. Pre-incubation of lopinavir with microsomes prior to addition of triazolam yielded a significantly lower IC50 of 4.1 (± 0.5) μM. This is consistent with mechanism-based inhibition of human CYP3A by lopinavir. Although lopinavir is less potent than ritonavir as an inhibitor of CYP3A, lopinavir is nonetheless likely to contribute to net CYP3A inhibition in-vivo during treatment with the lopinavir-ritonavir combination.