bluuebunny/crossref_metadata_2025 huggingface dataset:
Oligonucleotide Microarrays Reveal Regulated Genes Related to Inward Arterial Remodeling Induced by Urokinase Plasminogen Activator
Authors: Plekhanova Olga , Berk Bradford C. , Bashtrykov Pavel , Brooks Andrew I. , Tkachuk Vsevolod , Parfyonova Yelena
Published: October 2008

Accumulating evidence suggests that urokinase plasminogen activator (uPA) is involved in vascular remodeling and lumen stenosis after angioplasty and stenting. We have shown previously that increased uPA expression greatly promotes neointima formation and inward arterial remodeling after balloon injury. To evaluate the role of inflammation in early mechanisms responsible for inward arterial remodeling induced by uPA and elucidate the mechanisms of remodeling, we characterized changes in the expression profiles of 8,799 genes in injured rat carotid arteries 1 and 4 days after recombinant uPA treatment compared to vehicle. We used a standard model of the balloon catheter injury of the rat carotid followed by periadventitial application to the injured vessel of either uPA dissolved in Pluronic gel, or plain gel. Vessels were harvested and analyzed by immunohistochemistry, morphometry, microarray gene expression profiling and quantitative RT-PCR. Periadventitial application of uPA significantly reduced lumen size and vessel area encompassed by the external elastic lamina at both 1 and 4 days after treatment. Inflammatory cells accumulated in the arterial adventitia at both 1 and 4 days after uPA treatment. On the 4th day, increases in the areas and arterial cell numbers of all arterial layers were found. Among 79 differentially expressed known genes 1 day after uPA application, 12 proinflammatory genes, including TNF-α and TACE, and 15 genes related to mitochondrial metabolism and oxidative stress regulation were identified. Four days after injury in uPA-treated arteries, 3 proinflammatory and 2 oxidation-related genes were differentially expressed. We conclude that uPA likely promotes inward arterial remodeling by regulating oxidative stress and inflammation after arterial injury.
Increased Expression of Renal Cyclooxygenase-2 and Neuronal Nitric Oxide Synthase in Hypertensive Cx40-Deficient Mice
Authors: Krattinger Nathalie , Alonso Florian , Capponi Alessandro , Mazzolai Lucia , Nicod Pascal , Meda Paolo , Haefliger Jacques-Antoine
Published: October 2008

Cx40-deficient mice (Cx40–/–) are hypertensive due to increased renin secretion. We evaluated the renal expression of neuronal nitric oxide synthase (nNOS) and cyclooxygenases COX-1 and COX-2, three macula densa enzymes. The levels of nNOS were increased in kidneys of Cx40–/– mice, as well as in those of wild-type (WT) mice subjected to the two-kidney one-clip model of hypertension. In contrast, the levels of COX-2 expression were only increased in the hypoperfused kidney of Cx40–/– mice. Treatment with indomethacin lowered blood pressure and renin mRNA in Cx40–/– mice without affecting renin levels, indicating that changes in COX-2 do not cause the altered secretion of renin. Suppression of NOS activity by NG-nitro-L-arginine methyl ester (L-NAME) decreased renin levels in Cx40–/– animals, indicating that NO regulates renin expression in the absence of Cx40. Treatment with candesartan normalized blood pressure in Cx40–/– mice, and decreased the levels of both COX-2 and nNOS. After a treatment combining candesartan and L-NAME, the blood pressure of Cx40–/– mice was higher than that of WT mice, showing that NO may counterbalance the vasoconstrictor effects of angiotensin II in Cx40–/– mice. These data document that renal COX-2 and nNOS are differentially regulated due to the elevation of renin-dependent blood pressure in mice lacking Cx40.
Long-Term Cinacalcet HCl Treatment Improved Bone Metabolism in Japanese Hemodialysis Patients with Secondary Hyperparathyroidism
Authors: Shigematsu Takashi , Akizawa Tadao , Uchida Eiji , Tsukamoto Yusuke , Iwasaki Manabu , Koshikawa Shouzo
Published: October 2008

Background/Aims: Few clinical trials conducted with cinacalcet have thoroughly addressed its effects of on bone metabolism. We assessed the effects of cinacalcet on bone markers in Japanese hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). Methods: 200 Japanese HD patients with intact PTH (iPTH) levels ≥300 pg/ml were enrolled. The dose of cinacalcet was titrated from 25 up to 100 mg/day to achieve iPTH levels ≤250 pg/ml for 52 weeks. Results: At the end of the study visit, 57.8% of patients (115/199) had achieved iPTH levels ≤250 pg/ml. Serum Ca, phosphorus (P) and Ca × P levels decreased rapidly and were maintained throughout the study. At week 52, all bone metabolic markers levels had decreased significantly from baseline. Although bone resorption markers gradually decreased throughout the study period, bone alkaline phosphatase significantly increased during the first 4 weeks and then gradually decreased. Conclusions: The time courses of changes in bone markers after cinacalcet treatment resembled those observed after surgical parathyroidectomy (PTx), sometimes described as the hungry bone syndrome, indicating that cinacalcet treatment induces a rapid recovery in bone response to calcium. In addition, long-term efficacy and safety of cinacalcet were also observed in Japanese patients undertaking long-term hemodialysis (167.0 ± 81.4 months).
Berberine-Induced Upregulation of Circulating Endothelial Progenitor Cells Is Related to Nitric Oxide Production in Healthy Subjects
Authors: Xu Ming-Guo , Wang Jie-Mei , Chen Long , Wang Yan , Yang Zhen , Tao Jun
Published: October 2008

Objectives: Berberine (BR) has a beneficial effect on endothelial function by increasing nitric oxide (NO), as NO plays a pivotal role in the regulation of endothelial progenitor cell (EPC) mobilization and function. The aim of the present study was to investigate whether BR-induced upregulation of circulating EPCs is related to NO production in healthy subjects. Methods: Twenty volunteers were recruited and received 400 mg of BR 3 times a day for 30 days. We assessed the number of EPC colony-forming units (EPC-CFUs), as well as the proliferative, adhesive and migratory activities of circulating EPCs before and after the 30-day BR therapy. The level of plasma NO was also measured before and after the 30-day BR therapy. Results: After 30 days of BR therapy, the number of EPC-CFUs was increased and the function of EPCs, including proliferation, adhesion and migration, was augmented. In parallel, BR therapy enhanced the plasma NO level. There was a significant linear regression relationship between the enhanced plasma NO level and the increased number and function of circulating EPCs. Conclusions: BR-induced upregulation of the number and function of circulating EPCs in healthy subjects is related to NO production.
Comparative Study of TPep-Like Immunoreactive Neurons in the Central Nervous System of Nudibranch Molluscs
Authors: Baltzley Michael J. , Lohmann Kenneth J.
Published: October 2008

In the sea slug Tritonia diomedea, mucociliary crawling is controlled partly by two pairs of bilaterally symmetrical neurons located in the pedal ganglia. These neurons, known as the Pedal 5 and Pedal 6 cells, produce a class of neuropeptides called TPeps. Using immunohistochemistry we identified TPep-like immunoreactive (TPep-LIR) neurons in diverse nudibranch species. All species examined had 2–7 large, TPep-LIR cells located in each pedal ganglion. The absolute size of the largest TPep-LIR neuron was correlated with foot size. Species with a bigger foot size tended to have larger TPep-LIR cells. However, the number of cells in a given species was not correlated with the size of the adult foot. The presence of large, TPep-LIR cells across the nudibranchs suggests that part of the neural circuitry controlling mucociliary locomotion has been conserved, although the size and number of cells is variable across species. We conclude that the motor circuit underlying crawling might adapt to changes in foot size by changing the size of motor neurons in the circuit, but that changes in cell number are not directly related to foot size.
Noradrenergic Deficits Alter Processing of Communication Signals in Female Songbirds
Authors: Lynch Kathleen S. , Ball Gregory F.
Published: October 2008

During acoustic communication, animals must attend to sounds from a particular source while simultaneously rejecting intrusion from other sources. One possible candidate mechanism for this process is the noradrenergic system. Noradrenaline is a neuromodulator that tunes sensory processing systems and regulates attention. We examined whether pharmacological degradation of the noradrenergic system using N-(2-chloroethyl)-N-2-bromobenzyl-amine hydrochloride (DSP-4) modifies processing of species-typical auditory signals in female canaries (Serinus canaria). We measured auditory responses to conspecific and heterospecific songs using ZENK protein expression within the caudomedial nidopallium (NCM) and the mesopallium caudomedial (CMM). Song-induced ZENK expression in these auditory forebrain areas is typically higher in birds exposed to conspecific songs as opposed to heterospecific songs. Our results reveal that this differential ZENK induction is abolished specifically within dNCM and CMM in female canaries treated with DSP-4. Furthermore, in DSP-4-treated birds, conspecific song-induced ZENK expression is significantly reduced when compared to saline-treated birds. This suggests that the noradrenergic system modifies auditory processing by enhancing neuronal responses to signals relevant to survival and reproduction rather than inhibiting neuronal responses to signals that are less relevant. Overall, our results reveal that noradrenaline plays a significant neuromodulatory role during the reception of species-typical communication signals.
Adrenarche: Postnatal Adrenal Zonation and Hormonal and Metabolic Regulation
Authors: Belgorosky Alicia , Baquedano María Sonia , Guercio Gabriela , Rivarola Marco A.
Published: October 2008

Adrenarche is the direct consequence of the organogenesis of the zona reticularis (ZR). Proliferation of cortical cells could take place in the outermost layers of the adrenal cortex. Cells could then migrate to differentiate the zona glomerulosa (ZG) and zona fasciculata (ZF) during fetal life, and the ZR during postnatal life. After adrenarche, there are detectable increases in circulating DHEA and DHEA-S. Adrenarche could result from an increase in 17,20-lyase activity of P450c17 secondary to high levels of cytochrome b5 expression, and from a decrease in 3βHSD2 expression along with an increase in the expression of SULT2A1 in the ZR. The GH-IGF system and insulin, among other factors, might also modulate adrenal androgen production. Furthermore, high concentrations of estradiol enhance basal and ACTH-stimulated DHEA-S production, while aromatase expression was observed in the human adrenal medulla but not in the ZR, suggesting that estrogens produced in the adrenal medulla might be involved in the regulation of androgen production in the ZR. Premature adrenarche might be associated with ovarian hyperandrogenism and polycystic ovarian syndrome in females, as well as with insulin resistance in both sexes. However, many questions remain, transforming adrenal androgens into markers of diseases important for human health.
High-Molecular-Weight Adiponectin and Leptin Levels in Cord Blood Are Associated with Anthropometric Measurements at Birth
Authors: Inoue Makoto , Itabashi Kazuo , Nakano Yuya , Nakano Yasuko , Tobe Takashi
Published: October 2008

Aims: High-molecular-weight adiponectin (HMW-ad) is an active form of adiponectin. No information is available with respect to HMW-ad in neonates. The aims of this study were to examine whether HMW-ad is present in cord blood, to define the association between the concentrations of cord blood HMW-ad and leptin, and their correlation with anthropometric measurements of term neonates at birth. Methods: Venous cord blood samples were obtained from 135 term healthy neonates (birth weight 2,261–4,164 g) born at Showa University Hospital. Total adiponectin (T-ad), HMW-ad and leptin levels were measured by ELISA. Results: HMW-ad levels were 14.9 ± 5.8 µg/ml and the ratio of HMW-ad to T-ad was 0.49 ± 0.15. In a multiple regression analysis, cord blood HMW-ad levels were a significant predictor of birth weight and birth length, and leptin level was a significant predictor of birth weight and birth weight to body length ratio. There was a significant relationship between concentrations of HMW-ad and leptin controlling for sex, gestational age and birth weight. Conclusion: These results show that HMW-ad exists as a half of T-ad in the cord blood. Leptin and HMW-ad may regulate synergistically fetal growth.
The ‘Functional Muscle-Cartilage Unit’: A Reasonable Approach to Describe a Putative Relationship between Muscle Force and Longitudinal Growth at the Forearm in Children and Adolescents?
Authors: Fricke Oliver , Beccard Ralf , Semler Oliver , Land Christof , Stabrey Angelika , Tutlewski Baerbel , Remer Thomas , Schoenau Eckhard
Published: October 2008

Background: Several reports give evidence that the perichondral ossificiation of bone tubes (modeling) strongly depends on muscular forces in children and adolescents. The present analyses intend to investigate the hypothesis that muscular forces also partly determine enchondral ossification and, therefore, longitudinal growth of bone tubes. Subjects and Methods: Analyses were based on a single cross-sectional investigation with peripheral quantitative computed tomography in 296 individuals (age 5–19 years) participating in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study. Results: Forearm length (FL) was correlated with body height in gender-related subgroups of prepubertal and pubertal individuals (rs between 0.76 and 0.86). Cross-sectional muscle area (MA) increased faster than FL and faster than cross-sectional bone area (BA) close to the distal growth plate in puberty. Close to the growth plate, longitudinal growth was faster than perichondral ossification in females. The ratio MA/BA (surrogate of pressure on the distal growth plate) was correlated with FL in prepubertal boys (r = –0.249, p = 0.043) and pubertal individuals (r = 0.153, p = 0.051). Conclusions: Results support the hypothesis that longitudinal growth precedes modeling at the distal forearm. Confounding variables such as puberty may modify the relationship between muscle forces and longitudinal growth at the forearm in boys.
Usefulness of Transcription Factors Ad4BP/SF-1 and DAX-1 as Immunohistologic Markers for Diagnosis of Advanced Adrenocortical Carcinoma
Authors: Kaneko Tomoyoshi , Kojima Yoshiyuki , Umemoto Yukihiro , Sasaki Shoichi , Hayashi Yutaro , Kohri Kenjiro
Published: October 2008

Background: We examined the expressions of Ad4BP/SF-1 and DAX-1 in primary and metastatic lesions of advanced adrenocortical carcinoma with normal hormonal findings by immunohistochemistry and discussed their usefulness as immunohistochemical markers for diagnosis. Patients and Methods: Four patients (average age 54.3 ± 3.9) with retroperitoneal and metastatic tumors were enrolled in this study. All patients had normal hormonal findings. Ad4BP/SF-1 and DAX-1 underwent immunohistochemical study using needle biopsy specimens from the retroperitoneal tumor or metastatic tumor of these patients to diagnose primary adrenocortical carcinoma. Results: Immunoreactivity for Ad4BP/SF-1 and DAX-1 indicated that it was localized exclusively in the nuclei. Ad4BP/SF-1 immunoreactivity was observed in the carcinoma cells of 2 patients, but not in the others, whereas DAX-1 immunoreactivity was observed in the carcinoma cells of all 4 patients. Conclusion: The expressions of Ad4BP/SF-1 and DAX-1 are considered essential to maintain the biological characteristics of adrenocortical cells even without abnormal hormonal findings or even after malignant transformation and metastasis. These markers are useful to distinguish other retroperitoneal tumors, especially in patients with bulky tumors, and to diagnose the metastatic site of origin as adrenocortical carcinoma in patients clinically presenting with widespread metastasis.
Impact of Patient Characteristics and Clinical Factors on the Decision to Initiate Growth Hormone Treatment in Turner Syndrome
Authors: Khatchadourian Karine , Huot Céline , Alos Nathalie , Van Vliet Guy , Deal Cheri
Published: October 2008

Background/Aims: To evaluate factors contributing to the decision to initiate treatment with growth hormone (GH) in patients with Turner syndrome (TS). Methods: Data collected included ethnicity, parents’ education and work status, mid-parental height, age at diagnosis, karyotype, pubertal development, clinical severity score, bone age, height SDS and ages when GH was proposed and initiated. Results: GH was proposed to 59 of 72 patients >6 years (82%), and of these 46 (78%) accepted. Reasons for not proposing GH included late diagnosis, good growth and loss to follow-up. GH-treated and untreated girls differed by age at diagnosis (mean ± SD: 6.8 ± 4.7 vs. 4.3 ± 5.1 years; p = 0.04), TS-specific height SDS (0.08 ± 0.81 vs. 066 ± 0.87; p = 0.01) and spontaneous puberty (5/46 vs. 4/26, p = 0.024). Mean age at which it was suggested to begin GH was 9.2 ± 2.9 years. Reasons for parental refusal of GH were not related to reimbursement issues since GH treatment is covered fully by our insurance plan but included concern with other medical issues, mental health problems and fear of injections or unknown side effects. Conclusion: GH treatment was not acceptable to all patients with TS.
Birth Weight and Long-Term Metabolic Outcomes: Does the Definition of Smallness Matter?
Authors: Verkauskiene R. , Figueras F. , Deghmoun S. , Chevenne D. , Gardosi J. , Levy-Marchal M.
Published: October 2008

Objective: To establish the role of individual definition of smallness at birth in the association between birth weight and long-term metabolic outcomes. Methods: Lipid profile and oral glucose tolerance test were performed in young adults (22 years) born either small (SGA) or appropriate for gestational age (AGA). AGA/SGA were defined by both population-based and customized methods adjusting for individual maternal/pregnancy characteristics. 825 individuals were classified as AGA and 575 as SGA by both methods, 131 were SGA by the population-based method only (SGApop) and 22 were SGA by the customized method only (SGAcust). Results: SGAcust subjects had higher total cholesterol and triglyceride levels and lower high-density lipoprotein cholesterol concentrations than SGApop and AGA subjects, however, insignificantly when adjusted for age, gender and body mass index. The homeostasis model assessment for insulin resistance (HOMA-IR) index was higher in the SGAcust (p = 0.05) and SGApop (p = 0.02) versus the AGA group. Controlling for the HOMA-IR index, the insulinogenic index was significantly lower in the SGAcust versus SGApop (p = 0.001) and AGA (p = 0.003) groups. In SGAcust individuals, the HOMA-IR index was clearly shifted to higher, while the insulinogenic index to lower tertiles of AGA distribution; SGApop subjects had the HOMA-IR and insulinogenic index predominantly in the highest tertiles. Conclusions: Individualized birth weight standards allow to better identify subjects who failed to reach their genetic potential of intrauterine growth and are at higher risk of metabolic disturbances and impaired insulin secretion later in life.
Thyroid Hypoplasia as a Cause of Congenital Hypothyroidism in Williams Syndrome
Authors: Stagi S. , Manoni C. , Salti R. , Cecchi C. , Chiarelli F.
Published: October 2008

In the Williams-Beuren syndrome (WBS), disorders of the thyroid function and morphology have been reported and programs of thyroid screening and surveillance are recommended. However, the frequency of biochemical thyroid assessment, particularly in the first year of life, is being debated. In this report we describe an infant with WBS and congenital hypothyroidism, due to an important thyroid hypoplasia. The patient, a 1-month-old female, negative at primary neonatal thyroid screening, was referred to our hospital for dyspnea. Thyroid function tests showed a raised TSH (42 mIU/l; normal range 0.5–4 mIU/l) with a low FT4 concentration (10.21 pmol/l; normal range: 10.29–24.45 pmol/l). Ultrasound examination of the neck showed a significant thyroid hypoplasia, whereas 99mTc-pertechnetate thyroid scintigraphy evidenced a thyroid gland in normal position, with reduced shape and overall weak fixation. Therefore, treatment with L-thyroxinewas started. Thyroid hypoplasia is a frequent characteristic of WBS and abnormalities of thyroid function are common in patients with this feature. Therefore, the possibility of congenital hypothyroidism should always be taken into consideration too and, even if congenital hypothyroidism neonatal screening is negative, thyroid (morphology and function) evaluation should be regularly assessed when the diagnosis is made and, thereafter, every year in the first years of life.
Interferon-β1b in Multiple Sclerosis: Effect on Progression of Disability and Clinical Markers of Treatment Response
Authors: Carmona Olga , Casado Virginia , Moral Ester , Alonso-Magdalena Lucía , Martínez-Yélamos Antonio , Martínez-Yélamos Sergio , Martín-Ozaeta Gisela , Arbizu Txomin
Published: October 2008

There is limited long-term data on the effect of interferon-β1b (IFN-β1b) on disability progression in patients with multiple sclerosis (MS). There is also no reliable way of predicting individual responses to IFN-β1b treatment. This prospective study investigated early clinical prognostic markers of disease activity and progression in 115 patients with relapsing-remitting MS (RRMS) treated with IFN-β1b for almost 5 years. The study also compared progression of disability in IFN-β1b-treated patients with a historic untreated cohort of MS patients (n = 44). The number of relapses in the first 2 years of MS and in the 2 years before treatment predicted an early relapse after IFN-β1b treatment. The IFN-β1b-treated group experienced a slower progression of disability than the untreated cohort, suggesting that IFN-β1b treatment delays progression of disability in RRMS.
Short-Term Cognitive Training Improves Mental Efficiency and Mood in Patients with Multiple Sclerosis
Authors: Brenk A. , Laun K. , Haase C.G.
Published: October 2008

Objectives: The aim of this study was to evaluate a short-term non-specific home-based 6-week cognitive training for its effect on neuropsychological deficits and depression. Subjects and Methods: Cognitive and affective abilities of patients with MS were compared with healthy controls using an identical neuropsychological test battery. Re-testing was performed after 6 weeks of cognitive home-based training. Results: Patients already showed cognitive deficits at baseline. Cognitive training resulted in a significant improvement in several skills, in particular with respect to visuoconstructive and figural long-term memory. In addition, prior depressed mood and quality of life improved in MS patients during the training period and remained up to 6 months. Conclusions: Our study corroborated the early appearance of neuropsychological deficits in MS. Mental training, although unspecific, lead to improvements with respect to attention and memory functions in patients, and to some degree in control subjects, which may last for more than 6 months.
Intermittent versus Continuous Pantoprazole Infusion in Peptic Ulcer Bleeding: A Prospective Randomized Study
Authors: Yüksel İlhami , Ataseven Hilmi , Köklü Seyfettin , Ertuğrul İbrahim , Başar Ömer , Ödemiş Bülent , İbiş Mehmet , Şaşmaz Nurgül , Şahin Burhan
Published: October 2008

Background and Aim: Rebleeding has remained the most important determinant of poor prognosis in peptic ulcer bleeding. Gastric acid plays an important role in the pathogenesis of rebleeding. We aimed to compare the efficiency of intermittent and continuous pantoprazole infusion treatment on peptic ulcer rebleeding after endoscopic therapy. Materials and Method: In this prospective study, patients with active peptic ulcer bleeding or non-bleeding visible vessel were treated initially with endoscopic therapy. They were randomized to receive intermittent or continuous intravenous pantoprazole treatment. Rebleeding rate, duration of hospital stay, need for total blood transfusion and need for urgent surgery were compared among both groups. Results: Rebleeding rate (6.1 vs. 8.3%), duration of hospital stay (4.17 vs. 4.41), need for total blood transfusion (2.18 vs. 2.59) and need for urgent surgery (4.1 vs. 4.2%) were similar in intermittent and continuous pantoprazole infusion therapy groups, respectively. There was no bleeding-related death in either group. Conclusion: In patients with peptic ulcer bleeding, intermittent and continuous pantoprazole infusion after successful endoscopic therapy have comparable outcomes in reducing rebleeding. Both have similar effects on hospital stay, need for blood transfusion and urgent surgery. Intermittent administration has application and cost advantages over continuous infusion.
Loss of the Sense of Self-Ownership for Perceptions of Objects in a Case of Right Inferior Temporal, Parieto-Occipital and Precentral Hypometabolism
Authors: Zahn Roland , Talazko Jochen , Ebert Dieter
Published: October 2008

Philosophers define the ‘minimal self’ as the immediate awareness of being the agent and owner of one’s actions and perceptions. Here, we describe a patient with a selective loss of one part of this ‘minimal self’, namely the immediate sense of self-ownership for perceptions of objects. In contrast, his sense of self-ownership for body perceptions and for self-agency during actions remained intact. 18-Fluorodeoxyglucose positron emission tomography revealed predominantly right inferior temporal hypometabolism in comparison with healthy controls (parahippocampal and fusiform gyri). In addition, dysfunction of the right parieto-occipital junction and precentral cortex were detected. Taken together, we demonstrate selective changes in the quality of the sense of self-ownership for perceptions of objects but not actions and an intact sense of self-agency, which points to anatomically separable systems underpinning different aspects of the ‘minimal self’. The associated hypometabolism in inferior temporal, parieto-occipital and motor regions, but not in medial prefrontal areas most consistently associated with self-referential processing, are most parsimoniously explained when self-consciousness is not assumed to be an anatomically localized cognitive function, but instead is conceived as emerging from integration across anatomically distributed networks of regions with different functional specializations, not all of which need to be special for the ‘self’.
Prenatal Detection of a Subtle Unbalanced Chromosome Rearrangement by Karyotyping, FISH and Array Comparative Genomic Hybridization
Authors: Cain Colyn Cargile , Saul Daniel O. , Oehler Erin , Blakemore Karin , Stetten Gail
Published: October 2008

Objectives: To explore the advantages and limitations of comparative genomic hybridization to BAC arrays (array CGH) for prenatal diagnosis of a fetus with anomalies and a chromosome abnormality. Methods: We used karyotype analysis, FISH and array CGH to investigate an unbalanced chromosome rearrangement. Results: We report a case of a fetus with ultrasound anomalies at 11 weeks’ gestation and an unbalanced chromosome translocation [46,XX,der(13)t(2;13)(p25.1;q32)pat]. Initially, a chromosome 13 deletion was reported from G-banded chromosome analysis and 13q subtelomere FISH. The involvement of chromosome 2 was determined after a balanced translocation was identified in the father, 46,XY,t(2;13)(p25.1;q32). Array CGH confirmed the fetal abnormality as partial trisomy of the short arm chromosome 2 and partial monosomy of the long arm of chromosome 13. The abnormalities identified by ultrasound studies and autopsy appear to be most consistent with 13q deletion syndrome. Conclusions: Array CGH successfully identified a subtle unbalanced chromosome complement in a fetus with multiple ultrasound anomalies. If array CGH had been performed along with the fetal karyotype, the cryptic partial trisomy 2 could have been identified in a more timely manner to assist in the prenatal counseling of this family.
Functional Characterization of Hepatitis B Virus X Protein Based on the Inhibition of Tumorigenesis in Nude Mice Injected with CCL13-HBx Cells
Authors: Kuo Chan-Yen , Wang Jing-Chyi , Hsu Shih-Lan , Hwang Guang-Yuh
Published: October 2008

Objective: This study aimed to determine the effects of HBx on the inhibition of tumorigenesis in nude mice injected with CCL13-HBx cells. Therefore, the characteristics of the induced tumors and the phenomenon of apoptosis were assessed. Methods: The induced tumors were identified using the specific marker of hepatocellular carcinoma (HCC), anti-α-fetoprotein (AFP), and their characteristics were pathologically examined. Apoptosis was detected by DNA fragmentation, and the expression of the proapoptotic proteins p53, Bax, Bad, caspase-3, and caspase-8 and the anti-apoptotic protein Bcl-2 was detected by Western blotting. To identify possible molecules involved in the inhibition of tumorigenesis, extracts of the induced tumors were separated by 2D-PAGE, and the proteins were identified by MS. Results: The tumors of the nude mice injected with CCL13 and CCL13-HBx cells were identified as HCCs. Moreover, HBx was found to suppress tumor growth via apoptosis in the nude mice injected with CCL13-HBx cells. The MS findings revealed that phosphorylated myosin light chain was a candidate molecule involved in the inhibition of tumorigenesis. Conclusion: HBx suppressed tumorigenesis in the nude mice injected with CCL13-HBx cells, which proved to be a good animal model for the in vivo study of the effects of HBx on tumorigenesis.
Food Competition in a Semi-Free-Ranging Cebus apella Group
Authors: Ferreira Renata G. , Lee Phyllis C. , Izar Patrícia
Published: October 2008

The competitive regime faced by individuals is fundamental to modelling the evolution of social organization. In this paper, we assess the relative importance of contest and scramble food competition on the social dynamics of a provisioned semi-free-ranging Cebus apella group (n = 18). Individuals competed directly for provisioned and clumped foods. Effects of indirect competition were apparent with individuals foraging in different areas and with increased group dispersion during periods of low food abundance. We suggest that both forms of competition can act simultaneously and to some extent synergistically in their influence on social dynamics; the combination of social and ecological opportunities for competition and how those opportunities are exploited both influence the nature of the relationships within social groups of primates and underlie the evolved social structure.
Early Detection of Chronic Kidney Disease: Results of the PolNef Study
Authors: Król Ewa , Rutkowski Bolesław , Czarniak Piotr , Kraszewska Ewa , Lizakowski Sławomir , Szubert Radosław , Czekalski Stanisław , Sułowicz Władysław , Więcek Andrzej
Published: October 2008

Background: Continuous increase in the number of patients with end-stage renal disease demands early detection of chronic kidney disease (CKD). The aim of the present study was to diagnose CKD in its earliest stages in a randomly selected population using a diagnostic algorithm developed by the working group. Methods: An algorithm for the diagnostic procedure was created to identify patients with CKD requiring further nephrological care. Randomly chosen adult inhabitants of a city with a population of 60,000 were invited to participate in this study. Screening procedures included a microalbuminuria dipstick test accompanied by blood pressure measurement and medical questionnaire. In further diagnosis of CKD, estimated glomerular filtration rate (eGFR), albumin concentration in urine, urinalysis and ultrasound examination were used according to the algorithm. Multivariate logistic regression was performed to identify associations between participants’ characteristics and albuminuria. Results: Out of 9,700 invited subjects, 2,471 individuals participated in the PolNef study. Albuminuria was detected in 15.6% of the investigated population using the dipstick test and thereafter confirmed in 11.9% by the turbidimetric method. The modeling of multivariate logistic regression indicated the following independent predictors of albuminuria: male sex, diabetes, nocturia and hypertension. For people without diabetes and without hypertension, nocturia independently predicted detection of albuminuria. 481 people received a consultation with a nephrologist, and 96% of them were recognized as having CKD. At least 9% of patients with CKD had eGFR by MDRD <60 ml/min/1.73 m2. Six persons were referred for further treatment because of newly diagnosed kidney tumor. Conclusions: CKD in early stages occurs frequently in the studied population. The proposed diagnostic algorithm seems to be a powerful tool to identify subjects at risk of CKD. The role of nocturia as an independent predictor of albuminuria, both in the general population and in people without diabetes or hypertension, should be further examined.
Auditory Brainstem Correlates of Basilar Membrane Nonlinearity in Humans
Authors: Krishnan Ananthanarayan , Plack Christopher J.
Published: October 2008

A behavioral measure of the basilar membrane response can be obtained by comparing the growth in forward masking for maskers at, and well below, the signal frequency. Since the off-frequency masker is assumed to be processed linearly at the signal place, the difference in masking growth with level is thought to reflect the compressive response to the on-frequency masker. The present experiment used an electrophysiological analog of this technique, based on measurements of the latency of wave V of the auditory brainstem response elicited by a 4-kHz, 4-ms pure tone, presented at 65 dB SPL. Responses were obtained in quiet and in the presence of either an on-frequency (4 kHz) or an off-frequency (1.8 kHz) pure-tone forward masker. Wave V latency increased with masker level, although the increase was greater for the off-frequency masker than for the on-frequency masker, consistent with a more compressive response to the latter. Response functions generated from the data showed the characteristic shape, with a nearly linear response at lower levels and 4:1 compression at higher levels. However, the breakpoint between the linear region and the compressive region was at about 60 dB SPL, higher than expected on the basis of previous physiological and psychophysical measures.
Iron Supplementation during Treatment with Erythropoiesis-Stimulating Agents for Cancer-Related Anemia
Authors: Schiavetto Ilaria , Pedrazzoli Paolo , Basilico Vera , Siena Salvatore
Published: October 2008

Unresponsiveness to erythropoiesis-stimulating agents is a major limitation to the treatment of chemotherapy-related anemia. This is often related to a disregulation of iron metabolism leading to functional iron deficiency. However, the use of iron supplementation during treatment with erythropoiesis-stimulating agents has not been as rigorously pursued in anemic patients with cancer as it has in chronic kidney disease. In this article, we review and discuss the role of iron supplementation in the setting of chemotherapy-related anemia in view of recently published clinical trials addressing this issue.
Molecular Imaging Suggests Efficacy of Bevacizumab beyond the Second Line in Advanced Colorectal Cancer Patients
Authors: Brandi G. , Nannini M. , Pantaleo M.A. , Fanello S. , Farsad M. , Fanti S. , Ercolani G. , Maleddu A. , Di Battista M. , Biasco G.
Published: October 2008

We report the clinical history of a female affected by advanced colorectal cancer (CRC). The patient was treated with five subsequent therapeutic schedules (FOLFIRI, FOLFOXIRI, FOLFIRI, FOLFOX4, FOLFOX4 plus cetuximab) because of the progression of the disease. The sixth treatment was bevacizumab in combination with 5-fluorouracil and irinotecan (FOLFIRI). The CT scan and the FDG-PET/CT performed 3 months after the beginning of the treatment showed that some, even if not all, lesions had a reduction of both size and metabolic activity. After the second revaluation the disease progressed. This short report suggests that the response of CRC to antiangiogenetic therapy may also occur after several unsuccessful antineoplastic treatments. Different biological features may explain the nonhomogeneous objective response of the metastatic lesions. Molecular imaging techniques seem to be mandatory in the era of tailored therapy since it is useful to have an in vivo ‘biological picture’ of the neoplastic disease.
Comparison of Tinzaparin™ and Unfractionated Heparin as Anticoagulation on Haemodialysis: Equal Safety, Efficacy and Economical Parity
Authors: Bramham Kate , Varrier Matthew , Asgari Elham , Makanjuola David
Published: October 2008

Background: The European Best Practice Guidelines on anticoagulation in chronic haemodialysis recommend the use of low-molecular-weight heparins (LMWH) over unfractionated heparin (UFH), based on previous small-scale studies and a meta-analysis which demonstrated equal efficacy of anticoagulation without an increase in hemorrhagic events. Method: We performed a prospective single-centre study where all stable patients on chronic in-hospital haemodialysis were converted from UFH to Tinzaparin™. Patients were monitored for 2 months before and 2 months after the switch. Access failures due to thrombosis, clotted circuits and hemorrhagic events were recorded. Results: 1,489 and 1,823 dialysis sessions took place on UFH and LMWH, respectively, in 108 patients (65 male). The total number of clotted circuits tended to decrease after the switch to LMWH (34 vs. 13) but was not statistically significant. There were four minor non-access-related episodes of haemorrhage while on treatment with UFH and none with Tinzaparin, and the length of bleeding time post needle removal was shorter with Tinzaparin than UFH. The cost-analysis demonstrated parity of Tinzaparin with UFH; using a median of 10,000 U of UFH versus 2,500 U of LMWH, each therapy cost GBP 10,783 (EUR 15,942; USD 20,446) per annum. Conclusion: Our findings suggest comparable safety and efficacy of Tinzaparin, parity of cost in comparison with UFH.
Pegylated Interferon plus Ribavirin Combination Therapy for Chronic Hepatitis C in Patients with Congenital Coagulation Disorders
Authors: Katsarou O. , Theodosiades G. , Ioannidou P. , Nomikou E. , Tsevrenis B. , Kouraba A. , Deutch M. , Terpos E. , Dourakis S. , Karafoulidou A.
Published: October 2008

Chronic hepatitis C (CHC) and end-stage liver disease are becoming an increasingly common cause of mortality in patients with congenital bleeding disorders, especially in the HIV-coinfected group. Combination of pegylated interferon (Peg-IFN) and ribavirin has recently become the treatment of choice for CHC. In this study, we evaluated the safety and efficacy of combination therapy with Peg-IFN plus ribavirin for the treatment of CHC in human immunodeficiency virus (HIV)– and HIV+ patients with congenital bleeding disorders. Between 2000 and 2004, 50 (18–68 years old) patients with CHC (19 HIV+) from two hemophilia centers were included in the study. They were treated with weekly subcutaneous administration of Peg-INF-α combined with 800–1,200 mg ribavirin daily, for 24–48 weeks depending on viral genotype. Response was evaluated at weeks 12, 24, 48 (end of treatment response) and 72 had sustained virological response). Overall, 22/50 patients (43.8%) had end of treatment response and 20/50 (40%) sustained virological response. HIV– patients responded similarly to the general population (58.1%), while HIV+ patients had very low response rates (10.5%). The high rate of discontinuation (36.9%) as a result of side effects contributed to the observed low response rate in the HIV+ group. The only factor strongly associated with sustained virological response in the HIV– patients was the reduction of HCV RNA at 12 weeks (p = 0.001). Patients with viral genotypes other than 1 had higher SVR rates, but this was not found to be statistically significant. Peg-INF plus ribavirin is safe for the treatment of CHC monoinfected patients with inherited bleeding disorders, with similar response rates to nonhemophiliacs. On the contrary, in HIV coinfected hemophilic patients under highly active antiretroviral therapy it is associated with severe toxicity and very poor sustained virological response rates. Careful evaluation and several considerations are needed before starting treatment in this population.
Deferasirox Treatment Improved the Hemoglobin Level and Decreased Transfusion Requirements in Four Patients with the Myelodysplastic Syndrome and Primary Myelofibrosis
Authors: Messa E. , Cilloni D. , Messa F. , Arruga F. , Roetto A. , Saglio G.
Published: October 2008

Transfusion-induced iron overload is a frequent problem that clinicians have to face in the treatment of patients affected by both myelodysplastic syndrome (MDS) and primary myelofibrosis (PMF). Different options are currently available for chelation therapy, e.g. oral once-daily administration of the iron chelator deferasirox. In 3 patients with MDS and 1 patient with PMF, deferasirox therapy resulted in an improvement in the hemoglobin level and a reduction in transfusion dependence. Our data open new insights regarding the benefit of iron chelation therapy not only for transfusional iron overload of myelodysplastic and myelofibrotic patients but also for the increase in hemoglobin levels. The biological mechanism of action of deferasirox, an effect which is not shared by other iron chelators, is still obscure and requires further investigations
Serum Homocysteine: Relationship with Circulating Levels of Cortisol and Ascorbate
Authors: Cascalheira José F. , Parreira Mónica C. , Viegas Andreza N. , Faria Maria C. , Domingues Fernanda C.
Published: October 2008

Background/Aim: High serum levels of homocysteine and cortisol are independent risk factors for several pathologies and their levels can be regulated by some vitamins. Since the relationship between serum concentrations of homocysteine, cortisol and ascorbate has not been assessed in healthy individuals to date, it was the topic of the present work. Methods: The study group was composed of 20 men and 40 women aged >50 years. Blood samples were collected and serum concentrations of the analytes were quantified. Results: Serum homocysteine levels correlate positively with cortisol (r = 0.36, p <0.01) and age (r = 0.49, p < 0.001), and negatively with ascorbate (r = –0.30, p < 0.05) and folate (r = –0.31, p < 0.05). A negative correlation between serum levels of cortisol and ascorbate (r = –0.30, p < 0.05) was also observed. Multiple linear regression analysis showed that the best independent predictors of serum homocysteine concentration were cortisol (β = 0.319, p < 0.003), age (β = 0.529, p < 0.001) and folate (β = –0.338, p < 0.001). When subjects were divided into tertiles according to their homocysteine concentration, the highest tertile of homocysteine concentration has also higher cortisol (p < 0.005) and lower ascorbate (p < 0.05) concentrations compared with the lowest tertile of homocysteine concentration. Conclusion: The association between serum concentrations of homocysteine, cortisol and ascorbate suggests interaction between circulating levels of these molecules.
Comparison of the Sensititre YeastOne® Colorimetric Antifungal Panel with the Modified Clinical and Laboratory Standards Institute Broth Microdilution (M38-A) Method for Antifungal Susceptibility Testing of Dermatophytes
Authors: Castro C. , Serrano M.C. , Valverde A. , Pemán J. , Almeida C. , Martín-Mazuelos E.
Published: October 2008

Background: To compare the susceptibility of different dermatophyte species to itraconazole (I), fluconazole (F) and voriconazole (V) by the modified reference (microdilution, CLSI M38-A) and the colorimetric method Sensititre YeastOne® . The microdilution method is not very practical for use in routine susceptibility testing in the clinical laboratory, thus necessitating the use of other methods. Methods: We studied a total of 46 dermatophyte strains isolated from clinical specimens. The microdilution reference susceptibility testing was performed following the CLSI M38-A document, using I, F and V drugs. The MIC were defined as the lowest drug concentration that produced 100% (I and V) and 50% inhibition (F) after 72 h incubation at 35°C. The Sensititre MIC were detected by a change in color from pink to blue or purple. Results: Agreement levels between the 2 methods (±2 dilutions) for I, F and V were 30, 53.3 and 83.3%, 0, 12.5 and 66.6% and 37.5, 44.4 and 75% for Trichophyton mentagrophytes, Trichophyton rubrum and Microsporumgypseum, respectively. The MIC50/90 (mg/l) of I, F and V for T. mentagrophytes were 0.25/0.5, 16/64 and 0.12/0.25 by the microdilution method and 0.016/0.06, 8/16 and 0.03/0.06 by the Sensititre method. The MIC for I, F and V for T. rubrum were 0.25/1, 8/64 and 0.25/0.5 by the microdilution and 0.008/0.03, 2/8, 0.016/0.03 by the Sensititre method. For M. gypseum, MIC were 0.5/1 (I), /256 (F) and 0.25/1 (V) as well as 0.016/0.25 (I), 16/256 (F) and 0.06/0.25 (V) by the microdilution and Sensititre methods, respectively. Conclusions: The MICs obtained were lower by the Sensititre than the microdilution method. The best correlation between both methods was obtained for V in T. mentagrophytes (>80%), but was low for T. rubrum. Although the Sensititre method is easy to use in a clinical laboratory, it shows poor agreement with the reference method for dermatophytes.
Somatostatin Elevates Topoisomerase II Alpha and Enhances the Cytotoxic Effect of Doxorubicin on Gallbladder Cancer Cells
Authors: Quan Z.W. , Yue J.N. , Li J.Y. , Qin Y.Y. , Guo R.S. , Li S.G
Published: October 2008

Background: Gallbladder cancer is a common and lethal digestive malignancy which is nonsensitive to routine chemotherapy. Doxorubicin (DOX) is one of the major chemotherapeutic drugs for patients with gallbladder cancer. We tried to evaluate if combined use of somatostatin (SST) and DOX could have synergistic effect in the treatment of gallbladder cancer. Methods: Cells from the human gallbladder cancer cell line GBC-SD were treated with SST. Cell cycle analysis was determined by flow cytometry. Western blot analysis was performed to determine the protein levels of topoisomerase IIα (Topo IIα) after SST treatment. RT-PCR was utilized to detect SST receptors in GBC-SD cells. Finally, the chemotherapeutic effect of DOX combined with SST treatment on cellular growth was measured by MTT assay. Results: SST could induce cell cycle arrest in S phase and upregulate Topo IIα expression in GBC-SD cells. GBC-SD cells expressed all 5 subtypes of SST receptors. Finally, combined use of DOX with SST had a synergistic cytotoxic effect on GBC-SD cells. Conclusion: SST, a naturally occurring, nontoxic compound, may represent a novel adjuvant chemotherapeutic agent for patients with gallbladder cancer.