bluuebunny/crossref_metadata_2025_split huggingface dataset:
cDNA cloning, chromosome assignment, and genomic structure of a human gene encoding a novel member of the RBM family
Authors: Stover C. , Gradl G. , Jentsch I. , Speicher M.R. , Wieser R. , Schwaeble W. 
Published: April 2003

We have cloned and characterised a novel human gene mapping to chromosome 20q11.2. A partial transcript was initially isolated from a human cDNA library transcribed from RNA of the colon carcinoma cell line T-84. In order to determine the full coding sequence of this novel mRNA, we isolated seven cDNA clones from a human cDNA library transcribed from RNA of the acute monocytic leukemia cell line THP1 by colony hybridization. On Northern blot analysis of four human cell lines, the cDNAs isolated hybridize with an abundantly expressed mRNA species of 3.5 kb. A full-length cDNA transcript of this novel mRNA has an open reading frame of 2,796 bp encoding a protein with a calculated molecular weight of 97 kDa. Two repetitive structural consensus motifs are contained within the deduced protein sequence, namely five distinct RNA binding motifs and two proline rich regions. The derived protein sequence also contains putative transmembrane domains. These structural motifs identify this novel protein as a member of an expanding protein family containing RNA binding motifs (RBM). As seen from recently completed sequence of the genomic area encoding this novel mRNA by the Sanger Centre Human Genome Project, the coding region of this gene, RBM12, is intronless.
Antisense Inhibition of Cyclooxygenase-2 Causes a Selective Suppression of the Na<sup>+</sup>-H<sup>+</sup> Exchanger Isoform 3 in Rat Kidney in Experimental Colitis
Authors: Khan Islam 
Published: April 2003

<i>Background:</i> Experimental colitis induces the expression of Na<sup>+</sup>-H<sup>+</sup> exchanger (NHE) isoforms 1 and 3 in the rat colon, however, their status in rat kidney is not established. <i>Objectives:</i> The renal cortical NHE-1 and -3 expression was examined in the colitic rats. Since cyclooxygenase-2 (cox-2) plays an important role in inflammation, its regulatory role on these isoforms was also investigated by using a cox-2-selective phosphorothioated antisense oligonucleotide (S-oligo). <i>Methods:</i> Male Sprague-Dawley rats having colitis induced by acetic acid or trinitrobenzenesulfonic acid (TNBS) were given injection of S-oligo (3 mg/kg, i.p.) and a mismatched control oligonucleotide (C-oligo) daily 2 h before inducing colitis. Colonic myeloperoxidase activity (MPO) was used to indicate colitis. The renal cortical levels of NHE-1, NHE-3 and α-actin, an internal control, were estimated by the Western blot analysis. <i>Results:</i> Colonic MPO activity was increased and urine output was decreased in both models of colitis. Serum, but not the renal cortical level of TNF-α, was increased in both cases. Only TNBS condition showed an increased PGE<sub>2</sub> level and a decreased body weight. Water intake and renal histology remained unchanged in either case. The NHE-3 protein, localized on the proximal tubules, was increased significantly without any change in NHE-1 and α-actin in both cases. These changes, except the body weight, were significantly reversed by the S-oligo. <i>Conclusions:</i> Selective induction of NHE-3 and TNF-α, and their reversal by cox-2 inhibition, suggest a cox-2-dependent regulation of NHE-3, which possibly involves TNF-α released from the site of inflammation and not from the kidney in colitis. The induction of NHE-3 is independent of the nature of colitides, and might be important to compensate for the loss of electrolyte and water in experimental colitis.
Evaluation of Valaciclovir Dosage Reduction in Continuous Ambulatory Peritoneal Dialysis Patients
Authors: Stathoulopoulou F. , Dhillon S. , Thodis H. , Stathakis C. , Vargemezis V. 
Published: April 2003

In continuous ambulatory peritoneal dialysis (CAPD) patients, acyclovir-induced neurotoxicity is reported to be associated with high serum drug levels even when following the recommended reduced doses for this renal failure population. In view of the high oral bioavailability of valaciclovir (the <i>L</i>-valyl ester of acyclovir) the risk of neurotoxicity becomes more prominent. The present study was conducted in 12 CAPD patients who were administered a single oral dose of 500 mg valaciclovir. Acyclovir was analyzed by high-performance liquid chromatography. Relative pharmacokinetic parameters were estimated based on acyclovir concentrations at 8, 12 and 24 h post-dose. High inter-patient variations were observed with acyclovir apparent total clearance 7.238 ± 4 l/h and half-life (T<sub>1/2</sub>) 22.27 ± 16.82 h. However, dosage simulations confirmed supratherapeutic acyclovir concentrations for all participants when following the recommended dose of 1,000 mg valaciclovir/24 h for varicella zoster infections.
A Rapid, Quantitative Immunofunctional Assay for Measuring Human Leptin
Authors: Kratzsch Jürgen , Berthold Antje , Lammert Alexander , Reuter Wolfgang , Keller Eberhard , Kiess Wieland 
Published: April 2003

<i>Background:</i> We have developed a rapid, sensitive and quantitative in vitro assay for leptin based upon its ability to bind to the soluble extracellular domain of the leptin receptor (sOB-R). Such an assay is theoretically capable of differentiating between physiologically active leptin molecules from those with modified, either enhanced or reduced, binding activity. <i>Methods:</i> A preparation of sOB-R was immobilized to capture leptin from serum samples or standards. Anti-leptin antibodies that had been raised in rabbits were added in a second incubation step to identify leptin molecules bound to sOB-R. Signal detection was performed in a third incubation step by anti-rabbit IgG labeled with peroxidase. The immunofunctional assay (IFA) was clinically validated by the comparison of leptin levels in adolescents (n = 41, age range 9–18 years, BMI range 13.4–33.8 kg/m<sup>2</sup>) and adults (n = 80, age range 18–77 years, BMI range 16.4–54.7 kg/m<sup>2</sup>) measured using the IFA with data of an in-house RIA performed with the same standards and leptin antibodies. <i>Results:</i> The functional sensitivity of the IFA was 0.4 ng/ml and comparable to the data of the RIA. Intra- and interassay coefficients of variation were below 12.5 % in both methods. Leptin levels correlated well with the BMI of the subjects studied (r = 0.70 for RIA, r = 0.72 for IFA; p < 0.0001) as well as between IFA (y) and RIA (x) (y = x –1.31 ng/ml; r = 0.97, p < 0.0001). The median of the quotient between IFA and RIA levels was 0.86 (quartile range 0.60–1.10) for all samples.<i></i><i>Conclusions:</i> So far, only at the most minor differences between leptin measurements using the newly developed IFA and those using a conventional RIA have been detected. Additional studies using the IFA method are required to investigate whether or not discrepant results with the IFA will be seen in various states of relative leptin resistance and whether or not such differences are of biological relevance.
Recognition of Resveratrol by the Human Estrogen Receptor-Alpha: A Molecular Modeling Approach to Understand Its Biological Actions
Authors: El-Mowafy Abdalla M. , Abou-Zeid Laila A. , Edafiogho Ivan 
Published: April 2003

<i>Objectives:</i> Resveratrol (RSVL) is an edible phytoestrogen with multifaceted health benefits that may originate from binding to the estrogen receptors. Despite its structural similarity to the estrogen receptor-α (ERα) agonist diethylstilbestrol (DES), RSVL showed distinct biological profiles in estrogen-responsive biological systems. The molecular basis of such biological profiles has been undefined. <i>Methods:</i> We considered possible orientations for RSVL in ERα binding pocket. These conformations have been analyzed based on: (i) alignment with the key pharmacophoric elements of DES; (ii) computational energy of interaction, and (iii) pattern of accommodation at the ERα binding pocket. The characteristics of the most favored RSVL orientation have been compared with those of DES. <i>Results:</i> Both RSVL and DES interacted with the catalytic amino acid triad of the ERα pocket (His524, Arg394 and Glu 353). However, unlike the Erα agonists DES and estradiol (E<sub>2</sub>), RSVL formed three additional hydrogen bonds with Gly521 and Leu525, two paramount ligand recognition residues, and with Met343 at the ERα binding cavity. Lastly, RSVL displayed a more favorable energy of interaction with the ERα binding cavity. <i>Conclusions:</i> The present study suggests, for the first time, that RSVL is well recognized by the human ERα but in a manner distinct from the pure agonists DES and E<sub>2</sub>. These variations may well entail the unique biological responses of RSVL in ER-responsive systems.
Clinical Characteristics of α-Blocker Responders in Men with Benign Prostatic Hyperplasia
Authors: Mimata Hiromitsu , Satoh Fuminori , Ohno Hitoshi , Miyoshi Midori , Nomura Yoshio 
Published: April 2003

<i>Background:</i> Currently, α-blocker is becoming first-line drug therapy for benign prostatic hyperplasia (BPH). Although highly effective results are obtained with this therapy, a difference between the objective and subjective response rates is reported. To prevent unnecessary medical treatment and to predict the α-blocker response, we characterized the clinical features of α-blocker responders in men with BPH. <i>Methods:</i> Twenty-two men were consecutively enrolled in this study and received tamsulosin 0.2 mg once daily for 4–6 weeks. The primary measures of efficacy were maximum urinary flow rate (Q<sub>max</sub>) determined from the flow measurements and international prostate symptom score (IPSS). Those with an increase in Q<sub>max</sub> of ≧30% from baseline and a decrease in IPSS of ≧25% from baseline were defined as Q<sub>max</sub> responders and IPSS responders, respectively. Clinical findings such as age, pretreatment IPSS and Q<sub>max</sub>, serum prostate-specific antigen (PSA), total prostate volume, transition zone (TZ) volume, TZ index and T<sub>2</sub>-weighted magnetic resonance image (MRI) of the prostate TZ were compared between responders and non-responders for both criteria. <i>Results:</i> In 17 of 22 (77.2%) patients IPSS improved by ≧25%. In 9 of 22 (40.9%) patients Q<sub>max</sub> improved by ≧30%. There were no differences in clinical findings between IPSS responders and non-responders. On the contrary, Q<sub>max</sub> responders showed smaller total prostate and TZ volumes, a smaller TZ index and a lower intensity of the TZ in MRI than Q<sub>max</sub> non-responders. <i>Conclusions:</i> Determination of the prostate volume and MRI findings of the inner prostate gland were useful in predicting Q<sub>max</sub> responders to the α-blocker in men with BPH. In contrast, there were no clinical characteristics of the IPSS responders. IPSS responders without a Q<sub>max</sub> response should be closely followed while continuing the α-blocker therapy for a long duration.
Progress Report on the Palliative Therapy of 100 Patients with Neoplastic Effusions by Intracavitary Low-Dose Interleukin-2
Authors: Lissoni Paolo , Mandalà Mario , Curigliano Giuseppe , Ferretti Gianluigi , Moro Cecilia , Ardizzoia Antonio , Malugani Fabio , Tancini Gabriele , Tisi Elisabetta , Arrigoni Carlo , Barni Sandro 
Published: April 2003

<i>Objective:</i> Several cytokines, particularly IL-2 and interferons, are thought to be effective in the palliative therapy of neoplastic effusions. We report on the activity and toxicity of intracavitary administration of low-dose IL-2 in a case series of 100 cancer patients with neoplastic effusions. <i>Methods:</i> One hundred patients with advanced solid tumors and neoplastic effusions underwent IL-2 intracavitary injection as first-line treatment. The most common sites of fluid accumulation were pleura (n = 68), peritoneum (n = 21) and pericardium (n = 11). Breast cancer, lung cancer and mesothelioma were the most frequent neoplasms in our series. One cycle consisted of intracavitary IL-2 at 6,000,000 IU on days 1 and 7. <i>Results:</i> According to Paladine’s criteria, an objective clinical response was achieved in 72% (complete response in 27% and partial response in 45%), with a median duration of 5 months (range: 1–11 months). The peritoneum was the least responsive site for neoplastic effusion reduction. IL-2 intracavitary injection was well tolerated in all patients; the only toxicity observed was fever >38°C in 6% of the patients. <i>Conclusion:</i> This study shows that intracavitary injection of IL-2 represents a feasible, well-tolerated and effective therapy of neoplastic fluid accumulation. Further studies are needed in order to compare the effectiveness of intracavitary IL-2 with other standard treatments.
Interleukin-12 p40 Gene Expression Is Induced in Lipopolysaccharide-Activated Pituitary Glands in vivo
Authors: Yang Young , Han Seung Hyun , Kim Hyun , Kim Changmee , Kim Kun-yong , Shin Sun Mi , Choi Inpyo , Pyun Kwang Ho 
Published: April 2003

Proinflammatory cytokines have several functions including activation of the hypothalamo-pituitary-adrenal (HPA) axis and regulation of the immune system. The present study focuses on the regulation of interleukin 12 (IL-12) and its receptor gene expression in the HPA axis under artificially induced immune stress, brought on by administration of lipopolysaccharide (LPS) to Sprague-Dawley (SD) rats. RT-PCR analyses showed that expression of the IL-12 p40 gene was significantly increased and peaked at 2 h in the pituitary gland, but not in the hypothalamus. LPS-induced IL-12 p40 gene induction in the pituitary gland was suppressed after β-adrenoceptor agonist pretreatment in vivo. Both IL-12 p40 gene induction and IL-12 production were also observed when freshly isolated pituitary glands from non-treated SD rats were incubated with LPS in vitro. Furthermore, CD14, which is known as a LPS receptor, was found to be expressed in the pituitary gland. Gel mobility shift assays using nuclear extracts prepared from the pituitary glands of rats administered LPS showed induction of NF-ĸB and AP-1 DNA-binding activity. These results suggest that LPS stimulates the pituitary gland directly in vivo to increase IL-12 p40 gene expression and IL-12 protein production.
Blood Pressure Is Correlated with Vitamin D<sub>3</sub> Serum Levels in Dialysis Patients
Authors: Argilés Àngel , Lorho Ronan , Servel Marie-Françoise , Couret Isabelle , Chong Guillaume , Mourad Georges 
Published: April 2003

<i>Background/Aim:</i> The blood pressure, the most influencing factor in cardiovascular disease in end-stage renal failure patients, follows a seasonal variation during the year. Since vitamin D<sub>3</sub> is known to be related to sun exposure, we wanted to evaluate the putative participation of the vitamin D<sub>3</sub> metabolism in blood pressure modifications. <i>Methods:</i> We studied 22 stable hemodialysis patients (11 females and 11 males, mean age ± SD 56 ± 1 year) who had been continuously treated in our dialysis unit for more than 1 year between 1994 and 1997 and did not receive pulse vitamin D<sub>3</sub> treatment. Supine systolic and diastolic blood pressures were measured before every dialysis session (>12,000 measurements) and the intact parathormone (iPTH), 25-hydroxyvitamin D<sub>3</sub> [25(OH)D<sub>3</sub>], and 1,25-dihydroxyvitamin D<sub>3</sub> [1,25(OH)<sub>2</sub>D<sub>3</sub>] levels every 3 months (>300 determinations). The mean values of blood pressure per season and per patient were taken for analysis using a 4-year longitudinal study design. <i>Results:</i> The blood pressure varied during the years studied following a seasonal trend. It was highest during autumn and tended to decrease during spring and warmer months. Systolic as well as diastolic blood pressures were significantly correlated with the 25(OH)D<sub>3</sub> levels (p = 0.0291 and p = 0.0327, respectively). No correlation was observed between blood pressure and 1,25(OH)<sub>2</sub>D<sub>3</sub> or iPTH levels. <i>Conclusions:</i> There is a link between blood pressure and 25(OH)D<sub>3</sub> level. This interrelation is not secondary to a iPTH modulation. Although it cannot be excluded that vitamin D<sub>3</sub> and blood pressure vary following a third factor with seasonal variations, since vitamin D<sub>3</sub> varies during the year, mainly following sun exposure, we suggest that vitamin D<sub>3</sub> is one of the factors participating in the seasonal variation of the blood pressure. Other factors known to control the blood pressure and particularly the extracellular volume overload may also participate.
Lymphopenia in Wegener’s Granulomatosis
Authors: Izzedine Hassane , Cacoub Patrice , Launay-Vacher Vincent , Bagnis Corinne , Deray Gilbert 
Published: April 2003

<i>Background:</i> Significant lymphopenia is a prominent feature in systemic erythematous lupus, but has not been described in Wegener’s granulomatosis (WG). We suggest from a retrospective analysis that lymphopenia may also be an index of WG disease activity. <i>Methods:</i> Medical charts form 19 patients diagnosed with systemic active WG between 1990 and 2000 were reviewed retrospectively. All patients had crescentic glomerulonephritis and alveolar hemorrhage. Clinical and biological markers were reviewed at three different time points: diagnosis, time of relapse, and during remission. <i>Results:</i> Average lymphocyte count was significantly lower at diagnosis and relapse than during remission times (p < 0.008 and p < 0.000002, respectively). During disease activity either at diagnosis and during relapses, ANCA titers were highly positive (≧50 IU/ml) in 27.5% of patients (8/29). The corresponding lymphocyte counts were below normal (1,500/min<sup>3</sup>) in 28 of 29 patients (96.5%). In patients with either negative or weakly positive ANCA, mean lymphocyte count was 728.5, 744.2 and 2,551/ml at diagnosis, during relapse and remission times, respectively. There was a clear negative correlation between the lymphocyte count and disease activity. <i>Conclusion:</i> Lymphopenia appears to be a good marker of WG activity. This index might be useful in all patients including those with negative ANCA.
Economical Aspects of High-Sensitivity C-Reactive Protein as Predictor of Coronary Heart Disease
Authors: Ess Silvia M. , Szucs Thomas D. 
Published: April 2003

<i>Background/Objectives: </i>Measurement of high-sensitivity C-reactive protein (hs-CRP) in addition to lipid fraction measurements has been shown to improve the prediction of increased cardiovascular risk significantly. Moreover, baseline concentrations of hs-CRP seem to modulate the effectiveness of two preventive therapies: aspirin and statins. We evaluated the cost effectiveness (CE) of two primary prevention strategies, including hs-CRP determination versus no testing of hs-CRP, in three European countries: France, Spain and Switzerland. <i>Methods: </i>Using a decision analytic model, we evaluated the costs and consequences of two prevention strategies, including screening with hs-CRP in addition to standard lipid screening compared with no measurement of CRP levels. We analysed a hypothetical cohort of 100,000 apparently healthy men in three age groups (35–44, 45–54 and 55–64 years). Individuals with hs-CRP levels >3 mg/l were administered either aspirin or statin according to their lipid levels. Each cohort was followed for 5 years. The analysis was performed from the societal perspective. Extensive sensitivity analysis was performed in order to test the robustness of our conclusions. <i>Results:</i> Prevention strategies that include CRP determinations in addition to standard lipid screening improve outcomes with modest increments or even a reduction in the total expenditures. The results depended on: (1) whether statins were used more restrictively or extensively; (2) the age of the cohort, and (3) the local incidence of cardiovascular disease. Sensitivity analysis performed on the variables ‘test price’ and ‘cost of cardiovascular events’ resulted in minimal changes of the CE ratios. <i>Conclusions:</i> In the primary prevention setting, determination of CRP blood levels in addition to lipid screening can help better target individuals at higher risk, identifying those who will profit the most from existing therapies. Screening with hs-CRP can improve outcomes and result in more cost-effective prevention strategies.
Schizophrenic Patients Who Develop Postoperative Confusion Have an Increased Norepinephrine and Cortisol Response to Surgery
Authors: Kudoh Akira , Takahira Yoko , Katagai Hiroshi , Takazawa Tomoko 
Published: April 2003

The purpose of this study was to investigate the relationship between postoperative confusion and the plasma norepinephrine (NE), adrenocorticotropin (ACTH) or cortisol response to surgery in schizophrenic patients. We studied 50 schizophrenic patients and 35 control patients who underwent orthopedic surgery and perioperatively measured plasma NE, ACTH and cortisol levels. Postoperative confusion during 72 h after the end of the operation occurred in 14 of 50 schizophrenic patients (28%) and in 2 of 35 control patients (6%). Plasma NE levels 15 min after skin incision, the next day, the second day and the third day after operation in schizophrenic patients with postoperative confusion (668.0 ± 59.2, 522.0 ± 96.5, 463.2 ± 71.2 and 398.9 ± 56.2 pg/ml, respectively) were significantly higher than those in schizophrenic patients without confusion (524.1 ± 62.6, 342.4 ± 38.6, 311.2 ± 58.3 and 314.1 ± 77.1 pg/ml, respectively). Plasma cortisol levels 15 min after the skin incision and the next and second days after operation in schizophrenic patients with postoperative confusion (23.6 ± 3.2, 21.1 ± 4.3 and 19.9 ± 4.4 µg/dl, respectively) were significantly higher than those in schizophrenic patients without confusion (15.2 ± 4.5, 14.3 ± 5.1 and 13.8 ± 3.8 µg/ dl, respectively). In conclusion, the occurrence of postoperative confusion in schizophrenic patients is associated with an increase in plasma norepinephrine and cortisol levels during and after surgery.
Cortisol Response to Surgery and Postoperative Confusion in Depressed Patients under General Anesthesia with Fentanyl
Authors: Kudoh Akira , Takahira Yoko , Katagai Hiroshi , Takazawa Tomoko 
Published: April 2003

The purpose of this study was to investigate the relationship between postoperative confusion and plasma cortisol response to surgery in depressed patients. We studied 80 depressed patients and 40 control patients who had undergone orthopedic surgery and perioperatively measured plasma cortisol and adrenocorticotropin levels. Postoperative confusion in the first 3 postoperative days occurred in 5 (13%) depressed patients given fentanyl during anesthesia, 13 (33%) patients without fentanyl and 1 (3%) control patients. Plasma cortisol concentration (19.7 ± 6.9 and 19.2 ± 8.0 µg dl<sup>–1</sup>) 15 min after skin incision and 60 min after the end of surgery in depressed patients with fentanyl was significantly lower than that (24.2 ± 7.2 and 23.5 ± 8.1 µg dl<sup>–1</sup>) of depressed patients without fentanyl. Plasma cortisol levels during and after surgery in depressed patients with postoperative confusion were higher than those of depressed patients without postoperative confusion. We conclude that the occurrence of postoperative confusion in depressed patients is associated with an increase in plasma cortisol levels during and after surgery. The incidence of postoperative confusion in depressed patients with fentanyl was significantly lower than that of depressed patients without fentanyl.