bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of Bone Mineral Density in Human Immunodeficiency Virus‐1 Infected Children
Authors: Jacobson Denise L , Spiegelman Donna , Duggan Christopher , Weinberg Geoffrey A , Bechard Lori , Furuta Lauren , Nicchitta Jeanne , Gorbach Sherwood L , Miller Tracie L 
Published: August 2005

ABSTRACTObjectives:To compare bone mineral density (BMD) among human immunodeficiency virus (HIV)‐infected children with population norms and to determine predictors of BMD in HIV‐infected children.Methods:Total body BMD was measured by dual energy x‐ray absorptiometry in 37 HIV‐infected children and nine sibling controls at baseline. Clinical, dietary and anthropometric data were obtained at the time of the dual energy x‐ray absorptiometry examination. Age‐ and gender‐adjusted z scores were calculated for BMD, body mass index, weight and height from population standards. Age‐adjusted percentiles were determined for dietary intake of calcium and vitamin D. Differences in BMD z scores between HIV‐infected children and sibling controls were determined and adjusted for height and weight, as were independent risk factors for lower BMD among infected children. Eighteen HIV‐infected children and 5 controls had serial BMD measures.Results:Compared with population norms, HIV‐infected children had significantly lower BMD z scores (‐0.51 SD, P = 0.004), in contrast with controls who had normal z scores (0.38 SD, P = 1.0). However, there was no difference in BMD z scores between HIV‐infected children and the small number of sibling controls, adjusted for height and weight. Among HIV‐infected children, lower BMD z scores were independently associated with lower weight z scores (P < 0.0001), lower height z scores (P = 0.01), advanced (stage B or C) HIV stage (P = 0.01) and age greater than 8 years (P < 0.0001). In the same model, multivitamin use (P = 0.009) and African American race (P = 0.001) were associated with better BMD z scores, with nevirapine use showing borderline positive effect (P = 0.06). All results were adjusted for Tanner stage. Change in BMD z score over time showed that there was no change or an increase in BMD in 100% of controls but in only 44% of the HIV‐infected children (P = 0.09).Conclusion:When compared with population norms, HIV‐infected children had lower than expected bone mass for their age and gender that may be attributable to delays in growth, sexual maturity, time (length of HIV infection), ethnicity and disease severity. Dietary intake of calcium and vitamin D were not associated with bone loss, but most children had suboptimal intake. However, multivitamin use was strongly associated with better bone mineral density.
Screening Detected Celiac Disease in Children with Type 1 Diabetes Mellitus: Effect on the Clinical Course (A Case Control Study)
Authors: Rami Birgit , Sumnik Zdenek , Schober Edith , Waldhör Thomas , Battelino Tadej , Bratanic Nina , Kürti Kalman , Lebl Jan , Limbert Catarina , Madacsy Laszlo , Odink Roetloef J. H , Paskova Magdalena , Soltesz Gyula 
Published: August 2005

ABSTRACTObjective:To investigate clinical and metabolic characteristics of diabetic children with screening detected celiac disease in a multicenter case‐control study.Methods:Cases: 98 diabetic patients were diagnosed as having silent celiac disease by screening with endomysial antibodies and subsequent biopsy. Controls: two controls in the same center were chosen, (stratified by age and age‐at‐diabetes onset) who were negative for endomysial antibodies (n = 195). Height, weight, HbA1c, insulin dosage and acute complications were documented for at least 1 year of follow up.Results:Mean age of diabetes manifestation was 6.5 ± 4.1 years and diagnosis of celiac disease was made at 10.0 ± 5.4 years. Biopsy showed total or subtotal mucosal atrophy in 74 patients. The mean observation period after the diagnosis of celiac disease was 3.3 ± 1.9 years. Mean HbA1c levels were similar between cases and controls (8.63% ± 1.45% versus 8.50% ± 1.39%; P = 0.35). There was also no difference in the frequency of severe hypoglycemia, ketoacidosis and the applied insulin dosage (P = 0.45). Body mass index‐standard deviation score at celiac disease diagnosis (0.57 ± 1.24 versus 0.52 ± 1.07) and height‐standard deviation score (0.14 ± 1.13 versus 0.30 ± 0.95) did not differ between cases and controls. After diagnosis of celiac disease, weight gain was diminished in boys with celiac disease compared with their controls (P < 0.05). Female cases also had a lower body mass index than female controls (P = 0.067).Conclusion:In a cohort of diabetic children, silent celiac disease had no obvious effect on metabolic control but negatively influenced weight gain.
Control of Gastrointestinal Motility by the “Gut Brain” ‐ The Enteric Nervous System
Authors: Schemann Michael 
Published: August 2005

ABSTRACTThe enteric nervous system (ENS) as the “brain of the gut” is pivotal for normal muscle activity in the gut. Neuronal circuits within the ENS are designed to control gut motility independent of central inputs. To fulfill this task the ENS contains all necessary elements for coding mechanical and chemical stimuli, interneuronal communication and efferent output to the muscle. This review provides a summary of the ENS circuits that control muscle activity, the main transmitters and neuromodulators involved and the functional implications for the normal and diseased gut.
Sensory Signals from the Gastrointestinal Tract
Authors: Grundy David 
Published: August 2005

ABSTRACTThe sensory input to the CNS provides a basis for reflexes that control and coordinate gut function, integrates this with behavioral responses such as the regulation of food intake and also mediate sensations. Diverse sub‐populations of afferents have been identified according to the morphologic appearance of their terminal distribution in mucosa, muscle and mesentery, their pathway to the CNS and their functional properties in detecting mechanical activity and the local chemical environment. Mechanosensitivity to distension shows remarkable plasticity and can be influenced by a wide range of chemical mediators released as a consequence of ischemia, injury and inflammation. Chemosensitivity is also a property of vagal mucosal afferents that sample the chemical milieu within the lamina propria for chemicals absorbed across the epithelium or released from enteroendocrine cells that are strategically positioned to “taste” luminal contents. A complex interplay between ion channels and receptors underlies gastrointestinal sensing mechanisms and determines appropriate responses during normal digestion and in pathophysiology.
Simple evolutionary pathways to complex proteins
Authors: Lynch Michael 
Published: August 2005

AbstractA recent paper in this journal has challenged the idea that complex adaptive features of proteins can be explained by known molecular, genetic, and evolutionary mechanisms. It is shown here that the conclusions of this prior work are an artifact of unwarranted biological assumptions, inappropriate mathematical modeling, and faulty logic. Numerous simple pathways exist by which adaptive multi‐residue functions can evolve on time scales of a million years (or much less) in populations of only moderate size. Thus, the classical evolutionary trajectory of descent with modification is adequate to explain the diversification of protein functions.
Specificity inversion of Ochrobactrum anthropi D‐aminopeptidase to a D,D‐carboxypeptidase with new penicillin binding activity by directed mutagenesis
Authors: Delmarcelle Michaël , Boursoit Marie‐Caroline , Filée Patrice , Baurin Stéphane Lucius , Frère Jean‐Marie , Joris Bernard 
Published: August 2005

AbstractThe serine penicillin‐recognizing proteins have been extensively studied. They show a wide range of substrate specificities accompanied by multidomain features. Their adaptation capacity has resulted in the emergence of pathogenic bacteria resistant to β‐lactam antibiotics. The most divergent enzymatic activities in this protein family are those of the Ochrobactrum anthropi D‐aminopeptidase and of the Streptomyces R61 D,D‐carboxypeptidase/transpeptidase. With the help of structural data, we have attempted to identify the factors responsible for this opposite specificity. A loop deletion mutant of the Ochrobactrum anthropi D‐aminopeptidase lost its original activity in favor of a new penicillin‐binding activity. D‐aminopeptidase activity of the deletion mutant can be restored by complementation with another deletion mutant corresponding to the noncatalytic domain of the wild‐type enzyme. By a second step site‐directed mutagenesis, the specificity of the Ochrobactrum anthropi D‐aminopeptidase was inverted to a D,D‐carboxypeptidase specificity. These results imply a core enzyme with high diversity potential surrounded by specificity modulators. It is the first example of drastic specificity change in the serine penicillin‐recognizing proteins. These results open new perspectives in the conception of new enzymes with nonnatural specificities. The structure/specificity relationship in the serine penicillin‐recognizing proteins are discussed.
Aggregation of granulocyte‐colony stimulating factor in vitro involves a conformationally altered monomeric state
Authors: Raso Stephen W. , Abel Jeff , Barnes Jesse M. , Maloney Kevin M. , Pipes Gary , Treuheit Michael J. , King Jonathan , Brems David N. 
Published: August 2005

AbstractAggregation of partially folded intermediates populated during protein folding processes has been described for many proteins. Likewise, partially unfolded chains, generated by perturbation of numerous proteins by heat or chemical denaturants, have also been shown to aggregate readily. However, the process of protein aggregation from native‐state conditions is less well understood. Granulocyte‐colony stimulating factor (G‐CSF), a member of the four‐helix bundle class of cytokines, is a therapeutically relevant protein involved in stimulating the growth and maturation of phagocytotic white blood cells. Under native‐like conditions (37°C [pH 7.0]), G‐CSF shows a significant propensity to aggregate. Our data suggest that under these conditions, native G‐CSF exists in equilibrium with an altered conformation, which is highly aggregation prone. This species is enriched in 1–2 M GdmCl, as determined by tryptophan fluorescence and increased aggregation kinetics. In particular, specific changes in Trp58 fluorescence report a local rearrangement in the large loop region between helices A and B. However, circular dichroism, reactivity toward cyanylation, and ANS binding demonstrate that this conformational change is subtle, having no substantial disruption of secondary and tertiary structure, reactivity of the free sulfhydryl at Cys17 or exposure of buried hydrophobic regions. There is no indication that this altered conformation is important to biological activity, making it an attractive target for rational protein stabilization.
Expression and characterization of soluble amino‐terminal domain of NR2B subunit of N‐methyl‐d‐aspartate receptor
Authors: Wong Esther , Ng Fui‐Mee , Yu Chye‐Yun , Lim Peiqi , Lim Leng‐Hiong , Traynelis Stephen F. , Low Chian‐Ming 
Published: August 2005

AbstractN‐methyl‐d‐aspartate (NMDA) receptors are involved in mediating excitatory synaptic transmissions in the brain and have been implicated in numerous neurologic disorders. The proximal amino‐terminal domains (ATDs) of NMDA receptors constitute many modulatory binding sites that may serve as potential drug targets. There are few biochemical and structural data on the ATDs of NMDA receptors, as it is difficult to produce the functional proteins. Here an optimized method was established to reconstitute the insoluble recombinant ATD of NMDA receptor NR2B subunit (ATD2B) through productive refolding of 6xHis‐ATD2B protein from inclusion bodies. Circular dichroism and dynamic light scattering characterizations revealed that the solubilized and refolded 6xHis‐ATD2B adopted well‐defined secondary structures and monodispersity. More significantly, the soluble 6xHis‐ATD2B specifically bound ifenprodil to saturation. Ifenprodil bound to 6xHis‐ATD2B with a dissociation constant (KD) of 127.5±45 nM, which was within the range of the IC50 determined electrophysiologically. This is the first report on a functional recombinant ATD2B with a characterized KD.
Effects of Phe‐to‐Trp mutation and fluorotryptophan incorporation on the solution structure of cardiac troponin C, and analysis of its suitability as a potential probe for in situ NMR studies
Authors: Wang Xu , Mercier Pascal , Letourneau Paul‐Jean , Sykes Brian D. 
Published: August 2005

Abstract19F NMR spectroscopy is potentially a powerful tool for probing protein properties in situ. However, results obtained using this technique are relevant only if the 19F probe offers minimal perturbation to the surrounding environment. In this paper, we examine the effect of 5‐fluorotryptophan (5fW) incorporation on the three‐dimensional structure of cardiac troponin‐C (cTnC), with the intention of developing a 19F‐labeled TnC for use in in situ 19FNMR. We find that, in general, 5fW does not perturb the structure of the protein significantly. Replacement of residue Phe 153 with 5fW produces no noticeable change in protein conformation. However, replacement of residue Phe 104 with 5fW produces a folding behavior that is dependent on the Escherichia coli strain used to express the mutant. The orientations of the indole rings in these mutants are such that the Trp residue adopts a χ2 of ∼90° in the F104W mutant and ∼−100° in the F153W mutant. Using results from 19F‐1H heteronuclear NOE experiment, we show the replacement of L‐Trp with 5fW at these positions does not change the orientation of the indole ring and the spread of the 5fW side‐chain dihedral angles increases moderately for the F104(5fW) mutant and not at all for the F153(5fW) mutant. Based on these structures, we conclude that the substitution of Phe by 5fW at these two positions has minimal effects on the structure of cTnC and that the 5fW indole rings in both mutants have well defined orientation, making the two mutants viable candidates for use in in situ 19F NMR spectroscopy.
Dietary intakes of fat and fatty acids and risk of breast cancer: A prospective study in Japan
Authors: Wakai Kenji , Tamakoshi Koji , Date Chigusa , Fukui Mitsuru , Suzuki Sadao , Lin Yingsong , Niwa Yoshimitsu , Nishio Kazuko , Yatsuya Hiroshi , Kondo Takaaki , Tokudome Shinkan , Yamamoto Akio , Toyoshima Hideaki , Tamakoshi Akiko ,   for the JACC Study Group
Published: August 2005

To examine the possible association of dietary fat and fatty acids with breast cancer risk in a population with a low total fat intake and a high consumption of fish, we analyzed data from the Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 26 291 women aged 40–79 years completed a questionnaire on dietary and other factors. Intakes of fat or fatty acids were estimated by using a food frequency questionnaire. Rate ratios (RR) were computed by fitting proportional hazards models. During the mean follow‐up of 7.6 years, 129 breast cancer cases were documented. We found no clear association of total fat intake with breast cancer risk; the multivariate‐adjusted RR across quartiles were 1.00, 1.29, 0.95, and 0.80 (95% confidence interval [CI] 0.46–1.38). A significant decrease in the risk was detected for the highest quartile of intake compared with the lowest for fish fat and long‐chain n‐3 fatty acids; the RR were 0.56 (95% CI 0.33–0.94) and 0.50 (0.30–0.85), respectively. A decreasing trend in risk was also suggested with an increasing intake of saturated fatty acids (trendP = 0.066). Among postmenopausal women at baseline, the highest quartile of vegetable fat intake was associated with a 2.08‐fold increase in risk (95% CI 1.05–4.13). This prospective study did not support any increase in the risk of breast cancer associated with total or saturated fat intake, but it suggested the protective effects of the long‐chain n‐3 fatty acids that are abundant in fish. (Cancer Sci2005;96: 590 – 599)
A novel cinnamic acid derivative that inhibits Cdc25 dual‐specificity phosphatase activity
Authors: Aoyagi Yoshimi , Masuko Norio , Ohkubo Shuichi , Kitade Makoto , Nagai Kentaro , Okazaki Shinji , Wierzba Konstanty , Terada Tadafumi , Sugimoto Yoshikazu , Yamada Yuji 
Published: August 2005

The Cdc25 dual‐specificity phosphatases are key regulators of cell cycle progression through activation of cyclin‐dependent kinases (Cdk). Three homologs exist in humans: Cdc25A, Cdc25B, and Cdc25C. Cdc25A and Cdc25B have oncogenic properties and are overexpressed in some types of tumors. Compounds that inhibit Cdc25 dual‐specificity phosphatase activity might thus be potent anticancer agents. We screened several hundred compounds in a library using an in vitro phosphatase assay, with colorimetric measurement of the conversion of p‐nitrophenyl phosphate (pNPP) to p‐nitrophenol by the catalytic domain of recombinant human Cdc25, and discovered TPY‐835, which inhibits Cdc25A and Cdc25B activity (IC50 = 5.1 and 5.7 µM, respectively). TPY‐835 had mixed inhibition kinetics for Cdc25A and Cdc25B. TPY‐835 caused cell cycle arrest in the G1 phase in human lung cancer cells (A549 and SBC‐5) but not cell cycle arrest in the G2/M phase. After treatment with TPY‐835, the activation of Cdk2 was suppressed and phosphorylation of the retinoblastoma (Rb) protein was decreased in SBC‐5 cells. In addition, TPY‐835 induced an increase of the sub‐G1 phase cell population after 48–72 h treatment. The growth inhibitory effects of TPY‐835 against cisplatin (CDDP)‐, camptothecin‐ and 5‐FU‐resistant cell lines are comparable to the growth inhibitory effect on their parental lines, thus indicating that TPY‐835 did not show cross‐resistance to these cell lines. These results suggest that TPY‐835 is a promising candidate for constructing a novel class of antitumor agents that can control the cell cycle progression of cancer cells. (Cancer Sci 2005; 96: 614–619)
Expression and function of LAT1, a neutral amino acid exchanger, in renal porcine epithelial cell line LLC‐PK1
Authors: Soares‐da‐Silva P. , Serrão P. , Fraga S. , Pinho M. J. 
Published: August 2005

AbstractAim:  The present study examined the expression of LAT1 and the functional characteristics of the inward and outward [14C] l‐leucine transporter in the renal porcine epithelial cell line LLC‐PK1.Methods:  LLC‐PK1 cells were cultured in polycarbonate filters and accumulation and transepithelial flux of the substrate monitored with [14C] l‐leucine. LAT1 transcripts were examined by RT‐PCR. LAT1 protein was detected by immunoblotting.Results:  The accumulation of [14C] l‐leucine in the cell and the [14C] l‐leucine transepithelial flux were four‐ and twofold, respectively, when the substrate was added from the basal cell side, suggesting that the basolateral membrane is endowed with a high density of transport units, when compared with the apical membrane. Increases in the transepithelial flux of [14C] l‐leucine by unlabelled l‐leucine were also more pronounced when unlabelled l‐leucine was added from the basolateral membrane. In the absence of Na+, unlabelled l‐leucine increased the basal and apical fractional outflow of [14C] l‐leucine, this being similar at pH 7.4 and pH 6.2. RT‐PCR and immunoblotting detected LAT1 transcript and protein, respectively.Conclusion:  LLC‐PK1 cells are endowed with the LAT1 transcript and protein and transport l‐leucine through the Na+‐independent and pH‐insensitive LAT1 transporter. The density of transporter units in LLC‐PK1 cells may be higher at the basolateral membranes, although be also present in the apical membranes.
Platelet activating factor (PAF) increases plasma protein extravasation and induces lowering of interstitial fluid pressure (Pif) in rat skin
Authors: Iversen V. V. , Nedrebø T. , Borge B. A. , Salvesen G. S. , Reed R. K. 
Published: August 2005

AbstractAim:  To investigate the ability of the microdialysis technique to measure capillary selectivity of different sized plasma proteins induced by local administration of platelet activating factor (PAF).Methods:  We used hollow plasmapheresis fibres with 3 cm membrane (cut off 3000 kDa) placed on the back of anaesthetized rats.Results:  Platelet activating factor (50 μg mL−1) administered locally via the fibre, increased extravasation of radiolabelled 125I‐HSA from plasma to the microdialysis fibre by approximately 900% compared both to baseline and the control fibre within 70 min (n = 6, P < 0.05). The extravasation in the control fibre did not change over time. HPLC measurement of plasma proteins in the microdialysis perfusate also demonstrated decreased capillary selectivity for proteins in the diameter range of 73 Å, 56 Å and 39 Å after local administration of PAF (n = 6, P < 0.05). PAF also significantly lowered interstitial fluid (Pif) pressure after subcutaneous administration (50 μg mL−1). Mean arterial pressure (MAP) after intravenous injection of PAF (0.4 μg kg−1) fell instantly by about 50 mmHg, and stabilized at 50 mmHg after 15 min (n = 6). MAP was unaltered when PAF was given through the microdialysis fibre (n = 4). Both total tissue water (TTW) and extravasation of albumin, measured as the plasma‐to‐tissue clearance (E‐alb) showed a significant increase after PAF (n = 7, P < 0.05).Conclusions:  The present study demonstrates that PAF induces plasma protein extravasation and decrease capillary selectivity of different sized plasma proteins. It also increases transcapillary fluid flux, and lowers Pif, indicating a role for PAF in the interstitium for generation of transcapillary transport of water and large molecules followed by formation of oedema.
Myocardial and coronary sinus purines as indicators of pig heart energy metabolism during reperfusion after extracorporeal circulation
Authors: Safranow K. , Rzeuski R. , Listewnik M. J. , Jakubowska K. , Rać M. E. , Olszewska M. , Chlubek D. 
Published: August 2005

AbstractAim  The precise understanding of myocardial metabolism is crucial for the optimization of cardiosurgical procedures. We attempted to gain a comprehensive insight into the purine metabolism of the porcine heart during reperfusion by measuring concentrations of nucleotides, nucleosides and oxypurines simultaneously in the myocardium and coronary sinus.Methods  Twenty‐five pigs were subjected to sham cardiosurgery with extracorporeal circulation and cold cardioplegic arrest of 60 min. Myocardial biopsies, as well as coronary sinus and arterial blood samples were taken before aortic clamping and at 5, 20, 60 and 120 min of reperfusion. HPLC was used to measure concentrations of 17 purines in the bioptates and of 5 in plasma.Results  Reperfusion rapidly normalized the ischaemic decrease in the adenylate energy charge of the myocardium, but during 120 min failed to restore the reduced adenylate pool, because of irreversible loss of nucleosides by cardiomyocytes. Low adenylate energy charge and depletion of the adenylate pool were accompanied by analogous changes in the guanylates and growing deficit of NAD and NADP. Reperfusion was marked by significant release of inosine and guanosine from the heart, without any noticeable effect on hypoxanthine and xanthine.Conclusions  Coronary sinus concentrations of purines provide only a limited insight into the metabolism of the porcine heart. Repeated biopsies of the heart muscle and HPLC determinations of purine profiles represent a comprehensive and unique method for the study of purine metabolism during ischaemia and reperfusion. Future research on myocardial metabolism in disease and during cardiosurgical procedures should additionally be oriented to deficits in guanine and pyridine nucleotides.