bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeletal and cardiac myopathy in HIV-1 transgenic rats
Authors: Pruznak Anne M. , Hong-Brown Ly , Lantry Rachel , She Pengxiang , Frost Robert A. , Vary Thomas C. , Lang Charles H.
Published: August 2008

The mechanism by which human immunodeficiency virus (HIV)-1 infection in humans leads to the erosion of lean body mass is poorly defined. Therefore, the purpose of the present study was to determine whether transgenic (Tg) rats that constitutively overexpress HIV-1 viral proteins exhibit muscle wasting and to elucidate putative mechanisms. Over 7 mo, Tg rats gained less body weight than pair-fed controls exclusively as a result of a proportional reduction in lean, not fat, mass. Fast- and slow-twitch muscle atrophy in Tg rats did not result from a reduction in the in vivo-determined rate of protein synthesis. In contrast, urinary excretion of 3-methylhistidine, as well as the content of atrogin-1 and the 14-kDa actin fragment, was elevated in gastrocnemius of Tg rats, suggesting increased muscle proteolysis. Similarly, Tg rats had reduced cardiac mass, which was independent of a change in protein synthesis. This decreased cardiac mass was associated with a reduction in stroke volume, but cardiac output was maintained by a compensatory increase in heart rate. The HIV-induced muscle atrophy was associated with increased whole body energy expenditure, which was not due to an elevated body temperature or secondary bacterial infection. Furthermore, the atrophic response could not be attributed to the development of insulin resistance, decreased levels of circulating amino acids, or increased tissue cytokines. However, skeletal muscle and, to a lesser extent, circulating insulin-like growth factor I was reduced in Tg rats. Although hepatic injury was implicated by increased plasma levels of aspartate and alanine aminotransferases, hepatic protein synthesis was not different between control and Tg rats. Hence, HIV-1 Tg rats develop atrophy of cardiac and skeletal muscle, the latter of which results primarily from an increased protein degradation and may be related to the marked reduction in muscle insulin-like growth factor I.
Synaptotagmins bind calcium to release insulin
Authors: Gauthier Benoit R. , Wollheim Claes B.
Published: August 2008

Plasma insulin levels are determined mainly by the rate of exocytosis of the insulin-containing large dense core vesicles (LDCVs) of pancreatic islet β-cells. This process involves the recruitment of LDCVs to the plasma membrane, where they are docked by the assembly of multiprotein SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes. However, fusion of the two membranes will proceed only in the presence of Ca2+ions, implicating a Ca2+sensor protein. The synaptotagmin gene family, comprising 15 members, was proposed to act as such Ca2+sensor in regulated exocytosis in neurons and neuroendocrine and endocrine cells. Herein, we review the physiological function of the various synaptotagmins with reference to their impact on insulin exocytosis. Cumulating evidence emphasizes the crucial role of synaptotagmin VII and IX as mediators of glucose-induced insulin secretion.
Renal function and structure in a rat model of arterial calcification and increased pulse pressure
Authors: Gaillard Virginie , Jover Bernard , Casellas Daniel , Cordaillat Magali , Atkinson Jeffrey , Lartaud Isabelle
Published: August 2008

Clinical studies suggest a strong link between tissue calcification and pressure hyperpulsatility in end stage renal disease patients. Using a Wistar rat model of arterial elastocalcinosis and hyperpulsatility [vitamin D and nicotine (VDN) treatment], we evaluated the relative importance of tissue calcification and hyperpulsatility in the etiology of renal failure. VDN rats showed significant increases in aortic wall calcium content (50 times; 992 ± 171 vs. control 19 ± 1 μmol/g dry wt) and pulse pressure (1.5 times; 61 ± 4 vs. control 40 ± 2 mmHg). Significant renal calcification (16 times; 124 ± 27 vs. control 8.1 ± 0.7 μmol/g dry wt) occurred mainly within the media of the preglomerular vasculature and in the areas of interstitial fibrosis in VDN. Extensive renal damages (5 times; 26 ± 5% of collapsed-atrophic or sclerotic glomeruli, or glomerular cysts vs. control 5.2 ± 0.3%; 28 times; 61 ± 12% areas of focal, cortical areas exhibiting interstitial fibrosis per section vs. control 2.2 ± 0.6%) were observed histologically. The glomerular filtration rate significantly decreased (880 ± 40 vs. control 1,058 ± 44 μl·min−1·g kidney wt−1). Albuminuria increased six times (1.6 ± 0.4 vs. control 0.27 ± 0.04 mg/24 h). There were significant linear relationships between albuminuria and pulse pressure ( r2 = 0.408; n = 24) or renal calcium content ( r2 = 0.328; n = 24; P < 0.05) and between glomerular filtration rate and pulse pressure ( r2 = 0.168; n = 27). To our knowledge, this study provides the first evidence of links between both 1) hyperpulsatility and renal dysfunction, and 2) renal calcification and renal dysfunction. Given the increasing frequency of end-stage renal disease, this model could prove useful for preclinical evaluation of drugs that prevent or attenuate hyperpulsatility and/or tissue calcification.
Urea transporters UT-A1 and UT-A3 accumulate in the plasma membrane in response to increased hypertonicity
Authors: Blessing Nathan W. , Blount Mitsi A. , Sands Jeff M. , Martin Christopher F. , Klein Janet D.
Published: August 2008

The UT-A1 and UT-A3 urea transporters are expressed in the terminal inner medullary collecting duct (IMCD) and play an important role in the production of concentrated urine. We showed that both hyperosmolarity and vasopressin increase urea permeability in perfused rat terminal IMCDs and that UT-A1 and UT-A3 accumulate in the plasma membrane in response to vasopressin. In this study, we investigated whether hyperosmolarity causes UT-A1 and/or UT-A3 to accumulate in the plasma membrane or represents a complimentary stimulatory pathway. Rat IMCD suspensions were incubated in 450 vs. 900 mosM solutions. We biotinylated the IMCD surface proteins, collected, and analyzed them. Membrane accumulation was assessed by Western blotting of the biotinylated protein pool probed with anti-UT-A1 or anti-UT-A3. We studied the effect of NaCl, urea, and sucrose as osmotic agents. Membrane-associated UT-A1 and UT-A3 increased relative to control levels when either NaCl (UT-A1 increased 37 ± 6%; UT-A3 increased 46 ± 13%) or sucrose (UT-A1 increased 81 ± 13%; UT-A3 increased 60 ± 8%) was used to increase osmolarity. There was no increase in membrane UT-A1 or UT-A3 when urea was added. Analogously, UT-A1 phosphorylation was increased in NaCl- and sucrose- but not in urea-based hyperosmolar solutions. Hypertonicity also increased UT-A3 phosphorylation. We conclude that the increase in the urea permeability in response to hyperosmolarity reflects both UT-A1 and UT-A3 movement to the plasma membrane and may be a direct response to tonicity. Furthermore, this movement is accompanied by, and may require, increased phosphorylation in response to hypertonicity.
Different Roles of Related Currents in Fast and Slow Spiking of Model Neurons From Two Phyla
Authors: Hong En , Gurel Kazanci Fatma , Prinz Astrid A.
Published: August 2008

Neuronal activity arises from the interplay of membrane and synaptic currents. Although many channel proteins conducting these currents are phylogenetically conserved, channels of the same type in different animals can have different voltage dependencies and dynamics. What does this mean for our ability to derive rules about the role of different types of ion channels in neuronal activity? Can results about the role of a particular channel type in a particular type of neuron be generalized to other neuron types? We compare spiking model neurons in two databases constructed by exploring the maximal conductance spaces of two models. The first is a model of crustacean stomatogastric neurons, and the second is a model of rodent thalamocortical neurons, but both models contain similar types of membrane currents. Spiking neurons in both databases show distinct fast and slow subpopulations, but our analysis reveals that related currents play different roles in fast and slow spiking in the stomatogastric versus thalamocortical neurons. This analysis involved conductance-space visualization and comparison of voltage traces, current traces, and frequency-current relationships from all spiker subpopulations. Our results are consistent with previous work indicating that the role a membrane current plays in shaping a neuron's behavior depends on the voltage dependence and dynamics of that current and may be different in different neuron types depending on the properties of other currents it is interacting with. Conclusions about the function of a type of membrane current based on experiments or simulations in one type of neuron may therefore not generalize to other neuron types.
Structural MR Imaging Studies of the Brain in Children: Issues and Opportunities
Authors: Wilke Marko , Holland Scott K.
Published: August 2008

Structural magnetic resonance imaging has gained widespread attention over the last decade, especially following the advances in automated image processing algorithms. It is an interesting approach that, among other applications, allows investigating and describing normal and disturbed human brain development. With this overview, we aim to point out special aspects that may arise when imaging children, with regard to study design, data acquisition and data processing. We conclude with shortly addressing the potential insights to be gained from such studies.
Imaging of the Developing Brain
Authors: Antonio Gregory E. , Chu Winnie C.W. , Yeung David K.W. , Ahuja Anil T.
Published: August 2008

The human brain undergoes changes in morphology, volume, composition and function during brain maturation. Of the various available medical imaging investigations, ultrasound and MRI are most commonly used for assessing the developing brain. Being radiation-free and non-invasive, both imaging modalities allow in vivo serial examinations of the brain during maturation without health risks. In addition, MRI has the benefit of demonstrating certain functional aspects of the brain aside from examining morphology, further adding to the knowledge of brain development. This paper reviews the current main imaging investigations used for assessing the developing human brain, from the fetal stages to childhood.
Imaging of the Developing Central Nervous System in the Fetus
Authors: Xu Jie , Kwong W.H. , Wai Maria Sen Mun , Forster E. Lucy , Jiang Yan-ling , Kung Hsiang-fu , Yew David T.
Published: August 2008

The development of the brain was studied by MRI in living fetuses of pregnant women (performed because of medical reasons or in volunteers). They were from 21 to 37 weeks of gestation. At 21 weeks, diencephalic condensations were evident. By 25 weeks, high-density areas appeared in the prefrontal, central parietal and temporal cortices. The lentiform nucleus began to separate from the diencephalic mass between 26 and 28 weeks. The caudate nucleus, corpus callosum and septal areas were observed by 28 weeks, where the hippocampus was definitively identified by 29 weeks. By 30 weeks, the fornix was evident. Profuse CSF circulation with genesis of new gyri was noted at that stage. By 37 weeks, the brain of the fetus was much the same as that of the child except the insula did not show significant gyri.
Morphometric Measurements of Fetal and Neonatal Eyes Using MRI and Ultrasound
Authors: Ying Xi , Li Hai-tao , Yew David T.
Published: August 2008

Using MRI, the ratios of the anterior posterior (AP) lengths of the eyes versus the AP lengths of the corneae to the external occipital protuberances were found to decrease from 28 weeks of gestation onwards, while the ratios of the transverse diameters of the eyes versus the transverse diameters of the zygomatic bone to the nasal cavity increased till term. No further change in the ratios of the AP or transverse diameters was observed even till three years of age.
Gastric Varices with Remarkable Collateral Veins in Valpronic Acid-Induced Chronic Pancreatitis
Authors: Hattori Y. , Higurashi T. , Takahashi H. , Inamori M. , Abe Y. , Rino Y. , Nakajima A.
Published: August 2008

Valproic acid (VPA) is a commonly prescribed and approved treatment for epilepsy, including Angelman syndrome, throughout the world. However, the long-term administration of drugs like VPA is associated with the possible development of gastric varices and splenic obstruction as a result of chronic pancreatitis. Such cases can be difficult to treat using endoscopy or interventional radiology because of hemodynamic abnormalities; therefore, surgical treatment is often necessary.
ALS2/Alsin Knockout Mice and Motor Neuron Diseases
Authors: Cai Huaibin , Shim Hoon , Lai Chen , Xie Chengsong , Lin Xian , Yang Wan Jou , Chandran Jayanth
Published: August 2008

Autosomal recessive mutations in the ALS2 gene have been linked to juvenile-onset amyotrophic lateral sclerosis (ALS2), primary lateral sclerosis and juvenile-onset ascending hereditary spastic paraplegia. Except for two recently identified missense mutations, all other mutations in the ALS2 gene lead to a premature stop codon and likely abrogate all the potential functions of alsin, the protein encoded by the ALS2 gene. To study the pathologic mechanisms of ALS2 deficiency, four different lines of ALS2 knockout (ALS2–/–) mice have been generated by independent groups. The loss of ALS2/alsin does not have a drastic effect on the survival or function of motor neurons in mice. However, subtle deficits observed in the behavior and pathology of these mice have aided in our understanding of the relationship between alsin and motor neuron dysfunction. In this review, we summarize and reconcile major findings of ALS2–/– mice and attempt to place these results within the larger context of modeling recessive movement disorders in mice.
Comorbidity in Disease-Free Survivors of Cervical Cancer Compared with the General Female Population
Authors: Shin Dong Wook , Nam Joo Hyun , Kwon Yong Chul , Park Sang Yoon , Bae Duk-Soo , Park Chong Taik , Cho Chi-Heum , Lee Jong Min , Park Sang Min , Yun Young Ho
Published: August 2008

Objectives: We aimed to investigate the prevalence of comorbidities in cervical cancer survivors compared with the general population and to identify risk factors and impact on their quality of life (QoL). Methods: 860 female cervical cancer survivors enrolled at six tertiary hospitals and 994 women from the general population were surveyed on current comorbidities and QoL (EORTC QLQ-C30 and QLQ-CX24). Results: Compared with the general female population, the cervical cancer survivors reported higher prevalence of comorbidities (0.93 ± 2.91 vs. 0.37 ± 0.67, p < 0.01), significantly more heart disease (adjusted odds ratio (aOR), 2.64; 95% confidence interval (CI), 1.38–5.07), liver disease (aOR, 3.29; 95% CI, 1.54–7.02), hypertension (aOR, 1.72; 95% CI, 1.30–2.27), gastrointestinal disease (aOR, 1.79; 95% CI, 1.37–2.33) and musculoskeletal disease (aOR, 1.94; 95% CI, 1.45–2.59). Heart and renal disease significantly influenced QoL in many subscales. Patients with diabetes or cerebrovascular disease had an increased likelihood of sexual problems. Conclusions: The cervical cancer survivors had more comorbidities than the general population, and that in turn affected their QoL. Vigilant follow-up of comorbidities should be incorporated into in the care of cancer survivors.
Prospective Comparison of Sorafenib and Sunitinib for Second-Line Treatment of Cytokine-Refractory Kidney Cancer Patients
Authors: Herrmann Edwin , Bierer Stefan , Gerss Joachim , Köpke Thomas , Hertle Lothar , Wülfing Christian
Published: August 2008

Objectives: It was the aim of this study to investigate the clinical differences between the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib as second-line treatment for cytokine-refractory kidney cancer patients. Methods: Twenty consecutive patients received continuous treatment of oral sorafenib at a dose of 400 mg twice daily in 6-week cycles. Sunitinib was administered to the remaining 20 patients at 50 mg once daily in repeated 6-week cycles consisting of daily therapy for 4 weeks, followed by a 2-week off-treatment period. We correlated best treatment responses and progression-free survival (PFS) with either TKI treatment. Adverse events were evaluated and differences were compared between both treatment groups. Results:In the sorafenib group, 2 (10%) patients showed a partial response (PR) and 4 (20%) patients had progressive disease (PD) versus 6 (30%) PRs and 3 (15%) PDs in the sunitinib group, respectively (p = 0.195). The median PFS was 6.4 months for sorafenib and 7.4 months for sunitinib (p = 0.969). In contrast to gender, age and the number of prior cytokine therapy cycles, the Eastern Cooperative Oncology Group performance status (p = 0.024) and the Memorial Sloan-Kettering Cancer Center risk groups for second-line treatments (p = 0.015) were independent predictive parameters of PFS. Gastrointestinal symptoms were found to occur with greater frequency in the sunitinib group (p = 0.03). Conclusions: Both TKIs showed comparable clinical benefits. The Eastern Cooperative Oncology Group performance status and the Memorial Sloan-Kettering Cancer Center risk groups can help determine which patients might benefit from alternative drug treatments.
Prednisone plus Gefitinib versus Prednisone plus Placebo in the Treatment of Hormone-Refractory Prostate Cancer: A Randomized Phase II Trial
Authors: Boccardo Francesco , Rubagotti Alessandra , Conti Giario , Battaglia Michele , Cruciani Giorgio , Manganelli Antonio , Ricci Sergio , Lapini Alberto
Published: August 2008

Background: Abnormal epidermal growth factor receptor expression and pre-clinical data prompted us to investigate the activity of gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, in hormone-refractory prostate cancer. Methods: Eighty-two patients were randomly assigned to receive prednisone plus gefitinib (pG; n = 44) or prednisone plus placebo (ppl; n = 38). On progression, patients initially assigned to placebo were offered the possibility to receive gefitinib. Best prostate-specific antigen response was the primary endpoint. Results: At a median follow-up time of 29.0 months (26.0–32.0), 77 patients progressed and 51 died. Prostate-specific antigen response was recorded in 6/38 (15.8%; 95% CI 4.2–27.4) and in 5/44 (11.4%; 95% CI 2.0–20.8) patients in pG and ppl groups, respectively. There was no difference between groups in time to progression (median pG 4.0 months, range 3.5–4.5; median ppl 4.5 months, range 3.5–5.0) and survival (median pG 26.5 months, range 16.0–37.0; median ppl 20.5 months, range 14.0–27.0). Adverse events occurred in 19 patients in each arm and were generally mild. Conclusions: pG showed a good tolerability profile but only a limited therapeutic activity in hormone-refractory prostate cancer.
Infectious Port Complications Are More Frequent in Younger Patients with Hematologic Malignancies than in Solid Tumor Patients
Authors: Samaras Panagiotis , Dold Stefan , Braun Julia , Kestenholz Peter , Breitenstein Stefan , Imhof Alexander , Renner Christoph , Stenner-Liewen Frank , Pestalozzi Bernhard C.
Published: August 2008

Background: We assessed longevity and complications of totally implantable venous access devices in oncology patients. Methods: 197 patients received a total of 201 port devices via the subclavian vein for delivery of chemotherapy between January 1, 2005, and December 31, 2006. We reviewed the patient charts for port-related complications and risk factors until July 31, 2007. Results:A total of 47,781 catheter days were analyzed (median, 175 days; range, 1–831). Forty-six different complications occurred (0.96 complications/1,000 catheter days). The only risk factor significantly associated with a higher complication rate was younger age. Older patients had a lower risk for developing complications with a risk reduction of 2.4% for each year. There were no differences regarding underlying tumor, gender, access side, method of placement (subclavian/cephalic vein) or implanting team (thoracic versus visceral surgery). A trend was seen for shorter port longevity in hematologic patients compared to oncologic patients (p = 0.059). The former developed significantly more port-associated infections than solid tumor patients [11/53 cases (21%) versus 2/148 cases (1.4%); p < 0.0001]. Conclusions: Port-associated infections were mostly observed in younger patients with hematologic neoplasms. Prospective trials should be performed to evaluate the benefit of a prophylactic antimicrobial lock in these selected patients.
Homogeneous Blue Pattern in an Acral Congenital Melanocytic Nevus
Authors: Garrido-Ríos Anastasia A. , Carrera Cristina , Puig Susana , Aguilera Paula , Salerni Gabriel , Malvehy Josep
Published: August 2008

Dermoscopy in acquired acral melanocytic nevi has been widely studied. This is in contrast with the little information about the dermoscopic characteristics in congenital acral melanocytic nevi. We report a 46-year-old man who was referred due to a lesion on his right sole present since childhood corresponding to an acral congenital nevus. Dermoscopy showed a homogeneous blue pattern not previously described in acral benign tumors. The homogeneous blue pattern has previously been associated with blue nevus and skin metastasis of melanoma. The recognition of this pattern in benign acral congenital nevi is relevant in the clinical decision making concerning acral tumors.
Age-Related Macular Degeneration and Mortality: The Beijing Eye Study
Authors: Xu Liang , Li Yi Bin , Wang Ya Xing , Jonas Jost B.
Published: August 2008

Purpose: To assess the association between age-related macular degeneration (AMD) and mortality in a population-based setting. Procedures: At baseline in 2001, the Beijing Eye Study examined 4,378 subjects for AMD with a detected frequency of 110/4,378 (2.5%) subjects for early AMD and of 12/4,378 (0.3%) subjects for late AMD. In 2006, all study participants were re-invited for a follow-up examination. Results: Out of the 4,378 subjects, 3,218 (73.5%) returned for a follow-up examination while 138 (3.2%) were dead and 1,022 (23.3%) did not agree to be re-examined or had moved away. Early AMD and late AMD were not significantly associated with mortality (p = 0.40 and 0.33, respectively), neither in univariate analysis nor in multivariate analysis. Conclusions: AMD may not be associated with an increased mortality in adult Chinese.
Food Consumption Analysis in Spanish Elderly Based upon the Mini Nutritional Assessment Test
Authors: Cuervo M. , Ansorena D. , García A. , Astiasarán I. , Martínez J.A.
Published: August 2008

Background/Aims: Aged people are an increasing population group worldwide, and nutritional impairments may contribute to additional health problems. The characterization of food consumption of elderly people is a good approach to implementing adequate nutritional policies in order to improve their nutritional status. The aim of this study was to describe and analyze specific aspects of food intake based upon the Mini Nutritional Assessment (MNA) test in a representative country sample. Methods: The survey consisted of a cross-sectional study assessing the nutritional status of 22,007 Spanish people aged 65 years or older using the MNA test. These data, including dietary information, were obtained by health professionals specifically trained to carry out the questionnaire. A multiple regression analysis was used to evaluate the contributing impact of the diet-related MNA questions on the total MNA score. Results: Differences in the food choices between men and women were found, but not in the mode of feeding. Obese and non-obese individuals, categorized by a body mass index (BMI) more or less than 30, showed similar intake patterns of protein-rich foods, but differences in fruits, vegetables and fluids. On the other hand, undernourished and non-undernourished subjects, according to the MNA criteria, revealed different food consumption. Loss of appetite and mode of feeding were the items with the highest influence the MNA total score. Conclusions: While age, gender and BMI considered together are responsible for 11.3% of the total MNA score, dietary-related items can predict the 62.4% of the total MNA classification in the overall elderly Spanish population.
Methylenetetrahydrofolate Reductase 677CT Polymorphism and Cobalamin, Folate, and Homocysteine Status in Spanish Adolescents
Authors: Al-Tahan Jasmin , Sola Ricardo , Ruiz Jonatan R. , Breidenassel Christina , García-Fuentes Miguel , Moreno Luis A. , Castillo Manuel , Pietrzik Klaus , González-Gross Marcela
Published: August 2008

Background: Folate and cobalamin are responsible for healthy growth. However, the B-vitamin and homocysteine status of adolescents is not well known. The aim was to assess the status of folate, cobalamin, and homocysteine in healthy Spanish adolescents. Methods: Serum cobalamin, serum folate, homocysteine, methylenetetrahydrofolate reductase 677C>T variant, BMI, smoking habits, and Tanner stage were determined according to gender in 165 adolescents (84 females, 81 males; 13–18.5 years) using the Student’s t test, Mann-Whitney U test and χ2 test, respectively. Interactions between socioeconomic status, age group, methylenetetrahydrofolate reductase polymorphism, BMI, smoking habits, Tanner stage, and vitamin status, respectively, were examined by ANOVA or Kruskal-Wallis H test (p < 0.05). Results: Boys had markedly higher homocysteine (males 8.92 (5.51–22.94) µmol/l; females 7.91 (5.09–13.86) µmol/l), whereas girls showed higher serum cobalamin concentrations (males 540.00 (268.00–946.47) pmol/l; females 594.82 (280.63–1,559.64) pmol/l). Data are shown as medians and the 2.5th to 97.5th percentiles in parentheses. Adolescents with the homozygous variant of methylenetetrahydrofolate reductase displayed significantly higher homocysteine and lower serum folate: normal 5.73 (3.09–10.73) ng/ml serum folate, 7.57 (4.94–12.94) µmol/l homocysteine; homozygous 4.10 (2.75–7.88) ng/ml serum folate, 10.83 (7.00–22.82) µmol/l homocysteine. Conclusion: The present study provides data on the folate, cobalamin, and homocysteine status of Spanish adolescents. To assure a better assessment, revision of references for adolescents is still needed.
Effect of Oral L-Carnitine Administration on Insulin Sensitivity and Lipid Profile in Type 2 Diabetes Mellitus Patients
Authors: González-Ortiz Manuel , Hernández-González Sandra O. , Hernández-Salazar Eduardo , Martínez-Abundis Esperanza
Published: August 2008

Aim: It was the aim of this study to evaluate the effect of oral L-carnitine administration on insulin sensitivity and lipid profile in subjects with type 2 diabetes mellitus. Subjects and Methods: A randomized, double-blind, placebo-controlled clinical trial was carried out in 12 subjects with type 2 diabetes. Six subjects received L-carnitine 1 g orally 3 times a day before meals for a period of 4 weeks. Six other individuals took a placebo for the same period of time, as the control group. Before and after the intervention, insulin sensitivity and the lipid profile were estimated. To assess insulin sensitivity, the euglycemic-hyperinsulinemic clamp technique was performed. Wilcoxon’s signed rank and the Mann-Whitney U test were used for the statistical analyses. Results: There were no significant differences in basal clinical characteristics between the 2 groups. Insulin sensitivity and the basal lipid profile were similar. There were no significant changes in either group after the intervention in insulin sensitivity (3.2 ± 1.2 vs. 4.5 ± 1.7 mg/kg/min, p = 0.115, and 3.5 ± 0.6 vs. 3.5 ± 0.4 mg/kg/min, p = 0.917, for the placebo and L-carnitine groups, respectively) and in lipid profile. Conclusion:L-Carnitine orally administered for a period of 4 weeks did not modify insulin sensitivity or the lipid profile.
High-Dose Chemotherapy without Stem Cell Transplantation for Refractory Childhood Systemic Lupus Erythematosus
Authors: Luo Xue-Qun , Mo Ying , Ke Zhi-Yong , Xu Ling , Jiang Xiao-Yun , Zhang Ting-Ting , Chen Shu-Mei
Published: August 2008

Background:Intensive chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) is effective for refractory systemic lupus erythematosus (SLE). When intensive chemotherapy is immunoablative but nonmyeloablative, ASCT for hematopoietic reconstitution, with the risk of reinfusing autoreactive lymphocytes, is unnecessary. Methods:Four children aged 12–16 years were enrolled, 3 with WHO class IV nephritis, 2 with hemolytic anemia and 1 with thrombocytopenia. Median disease duration prior to the study was 4 years (range 1–6). Previous therapy, including intravenous bolus cyclophosphamide (Cy) with a median accumulated dose of 6.5 g/m2 and high-dose methylprednisolone with a median accumulated dose of 370 mg/kg, had failed. The protocol included: Cy 1.2 g/m2 daily for 4 days, fludarabine 30 mg/m2 daily for 4 days, porcine antilymphocyte globulin 25 mg/kg daily for 3 days. Results:Themedian duration of absolute neutrophil count <0.5 × 109/l was 5.5 days after treatment. The median SLE Disease Activity Index and urine protein decreased from 8.5 and 3.4 to 1.0 and 0.1 g/day at the date of last follow-up (median 20 months), respectively. Two cases with hemolytic anemia and 1 with thrombocytopenia before treatment recovered to normal or near normal hemogram, respectively. All patients achieved complete or partial remission within 10–28 months of follow-up. Conclusion:Intensive chemotherapy leads to rapid hematopoietic reconstitution without ASCT and appears beneficial in refractory childhood SLE. Further study is needed.
Vincristine-Induced Neuropathy in the Rat Is Not Modified by Drug-Drug Interactions with the P-Glycoprotein Inhibitor Verapamil
Authors: Balayssac David , Cayre Anne , Ling Bing , Maublant Jean , Penault-Llorca Frederique , Eschalier Alain , Coudore François , Authier Nicolas
Published: August 2008

Background: Cancer patients can be exposed to drug interactions during treatment with toxic anticancer drugs. The peripheral nervous system is a target for neurotoxic anticancer drugs. P-glycoprotein is essential for the functional integrity of blood-tissue barriers, and P-glycoprotein inhibition due to possible drug interactions could lead to adverse neurotoxic reactions. Methods: In a rat model of vincristine-induced neuropathy, we assessed the consequences of potential drug interactions of vincristine with some P-glycoprotein-inhibiting drugs, chosen because of their potency to increase the incorporation of 99mTc-sestamibi in nervous tissue. Results: Quinidine (30 mg/kg) increased 99mTc-sestamibi incorporation in dorsal root ganglia (DRG) but was toxic for rats. Verapamil (30 mg/kg) increased the tracer incorporation in the spinal cord, DRG and sciatic nerve. Combination treatment with the verapamil-vincristine regimen had a tendency to lower weight gain and altered nociceptive thresholds of neuropathic animals. Conclusion: Behavioral pain tests did not reveal an increase in vincristine neurotoxicity following combination treatment with verapamil and vincristine. This regimen only led to a slight increase in general toxicity.
Characterization of 5-Fluorouracil-Resistant Cholangiocarcinoma Cell Lines
Authors: Namwat Nisana , Amimanan Piyawan , Loilome Watcharin , Jearanaikoon Patcharee , Sripa Banchob , Bhudhisawasdi Vajarabhongsa , Tassaneeyakul Wichittra
Published: August 2008

Background: Although 5-fluorouracil (5-FU) is the drug of choice for the palliative treatment of cholangiocarcinoma (CCA), resistance to the drug is a therapeutic obstacle. The aim of this study was to explore the mechanisms underlying 5-FU resistance of CCA using cell lines derived from CCA associated with liver fluke infection. Methods: A stepwise exposure was used for inducing 5-FU-resistant CCA cell lines, and the expression of nine genes associated with 5-FU resistance was analyzed using real-time (RT)-PCR. Results: Altered expression of several genes involved in 5-FU resistance in CCA cell lines was observed. The expression levels of almost all target genes investigated including TP, DPD, ENT1, UNG1, TOP2A, BIRC5, TP73 and DeltaNp73 appeared to be significantly altered in these resistant strains. The expression of the TS gene tended to be increased but the fold change was not significantly different from their parental cell lines. UNG1 (a DNA repairing enzyme) and BIRC5 (an apoptotic inhibitor) expressions were increased whereas TP73 (a proapoptotic factor) expression levels decreased concomitantly. Conclusion: Our study showed that increases in UNG1 and BIRC5 expression and concomitant decreases in TP73 expression may be associated with development of acquired 5-FU resistance in CCA lines and their phenotypes.
Estradiol Enables Cortisol to Act Directly upon the Pituitary to Suppress Pituitary Responsiveness to GnRH in Sheep
Authors: Pierce B.N. , Stackpole C.A. , Breen K.M. , Clarke I.J. , Karsch F.J. , Rivalland E.T.A. , Turner A.I. , Caddy D.J. , Wagenmaker E.R. , Oakley A.E. , Tilbrook A.J.
Published: August 2008

We have shown that cortisol infusion reduced the luteinizing hormone (LH) response to fixed hourly GnRH injections in ovariectomized ewes treated with estradiol during the non-breeding season (pituitary-clamp model). In contrast, cortisol did not affect the response to 2 hourly invariant GnRH injections in hypothalamo-pituitary disconnected ovariectomized ewes during the breeding season. To understand the differing results in these animal models and to determine if cortisol can act directly at the pituitary to suppress responsiveness to GnRH, we investigated the importance of the frequency of GnRH stimulus, the presence of estradiol and stage of the circannual breeding season. In experiment 1, during the non-breeding season, ovariectomized ewes were treated with estradiol, and pulsatile LH secretion was restored with i.v. GnRH injections either hourly or 2 hourly in the presence or absence of exogenous cortisol. Experiments 2 and 3 were conducted in hypothalamo-pituitary disconnected ovariectomized ewes in which GnRH was injected i.v. every 2 h. Experiment 2 was conducted during the non-breeding season and saline or cortisol was infused for 30 h in a cross-over design. Experiment 3 was conducted during the non-breeding and breeding seasons and saline or cortisol was infused for 30 h in the absence and presence of estradiol using a cross-over design. Samples were taken from all animals to measure plasma LH. LH pulse amplitude was reduced by cortisol in the pituitary clamp model with no difference between the hourly and 2-hourly GnRH pulse mode. In the absence of estradiol, there was no effect of cortisol on LH pulse amplitude in GnRH-replaced ovariectomized hypothalamo-pituitary disconnected ewes in either season. The LH pulse amplitude was reduced in both seasons in experiment 3 when cortisol was infused during estradiol treatment. We conclude that the ability of cortisol to reduce LH secretion does not depend upon the frequency of GnRH stimulus and that estradiol enables cortisol to act directly on the pituitary of ovariectomized hypothalamo-pituitary disconnected ewes to suppress the responsiveness to GnRH; this effect occurs in the breeding and non-breeding seasons.
Equity Norms in Global Environmental Governance
Authors: Okereke Chukwumerije
Published: August 2008

Contestations over justice and equity in international environmental regimes present striking evidence of the struggle to create institutions for global environmental governance that are based on widely shared ethical standards of responsibility and accountability. Focusing on two key equity norms—the common heritage of mankind (CHM) and common but differentiated responsibility (CDR)—this paper highlights four factors that affect the influence of moral responsibility norms in global environmental regimes: (i) source and force of articulation; (ii) nature of issue-area; (iii) “moral temper” of the international community; and (iv) “fitness” of norms with the prevailing neoliberal economic idea and structure. Consequent upon the argument that the most important of all these factors is the “fitness” with the extant neoliberal order, the paper questions the assumptions of the burgeoning constructivist scholarship that tends to overemphasize the independent role of intersubjective beliefs in international politics. Further, it is suggested that the abiding “responsibility deficit” in institutions for global environmental governance is due mostly to the successful co-optation of equity norms for neoliberal ends.
Responsibility in Uncertain Times: An Institutional Perspective on Precaution
Authors: Pellizzoni Luigi , Ylönen Marja
Published: August 2008

Precaution is a key issue in environmental governance. Variously defined, intensively debated and introduced in many regulations, its meaning, scope and application remain problematic. This article argues that the controversy on precaution is a matter of culturally patterned expectations concerning the production and use of knowledge and the related social positions and responsibilities. The way uncertainty and its role in the policy process are understood is crucial. For some precaution is a flawed concept, to be accommodated to the current expert-based cooperative scheme. For others it is a major innovation requiring a rearrangement of the latter. Precautionary policies may evolve in different directions. They may either strengthen the role of means-ends rationality, increasing people's dependence on expert knowledge and shrinking the opportunity and scope of public debate or, on the contrary, enhance the role of value-commitments, leading to a decline in the legitimacy of established hierarchies and an intensification of intractable controversies.
Paleoclimate Reconstructions of Tropical Sea Surface Temperatures from Precipitation Proxies: Methods, Uncertainties, and Nonstationarity
Authors: Furtado Jason C. , Di Lorenzo Emanuele , Cobb Kim M. , Bracco Annalisa
Published: August 2008

Proxy-based paleoclimate reconstructions of tropical sea surface temperature (SST) fields may lead to better constraints of tropical climate variability in climate model projections. In this study, the authors quantify uncertainties associated with two popular SST anomaly reconstruction methods that have been applied over the last millennium. The first reconstruction method exploits the high correlation between the leading modes of variability of global precipitation and SSTs; the second method uses a multiregression model that exploits the multiple modes of covariability between precipitation and SSTs. Regardless of the proxy network density, the first method has skill only in the tropical eastern Pacific and misses some ENSO events. By contrast, the multiregression approach demonstrates high skill throughout the tropical Indo-Pacific region and predicts all ENSO events correctly. The advantage of the multiregression method lies in the second mode of covariability between SSTs and precipitation, which explains nearly 15% of the covariability between the two variables. However, when the period 1950–2000 is considered, the authors find that the nonstationarity in the second mode of covariability between SST and precipitation leads to a significant reduction of skill in the Indian Ocean and the warm pool region. This change suggests that the underlying stationarity assumption common in most climate field reconstruction methods needs to be treated more carefully, particularly in the tropics.
The Summer North Atlantic Oscillation: Past, Present, and Future
Authors: Folland Chris K. , Knight Jeff , Linderholm Hans W. , Fereday David , Ineson Sarah , Hurrell James W.
Published: August 2008

Summer climate in the North Atlantic–European sector possesses a principal pattern of year-to-year variability that is the parallel to the well-known North Atlantic Oscillation in winter. This summer North Atlantic Oscillation (SNAO) is defined here as the first empirical orthogonal function (EOF) of observed summertime extratropical North Atlantic pressure at mean sea level. It is shown to be characterized by a more northerly location and smaller spatial scale than its winter counterpart. The SNAO is also detected by cluster analysis and has a near-equivalent barotropic structure on daily and monthly time scales. Although of lesser amplitude than its wintertime counterpart, the SNAO exerts a strong influence on northern European rainfall, temperature, and cloudiness through changes in the position of the North Atlantic storm track. It is, therefore, of key importance in generating summer climate extremes, including flooding, drought, and heat stress in northwestern Europe. The El Niño–Southern Oscillation (ENSO) phenomenon is known to influence summertime European climate; however, interannual variations of the SNAO are only weakly influenced by ENSO. On interdecadal time scales, both modeling and observational results indicate that SNAO variations are partly related to the Atlantic multidecadal oscillation. It is shown that SNAO variations extend far back in time, as evidenced by reconstructions of SNAO variations back to 1706 using tree-ring records. Very long instrumental records, such as central England temperature, are used to validate the reconstruction. Finally, two climate models are shown to simulate the present-day SNAO and predict a trend toward a more positive index phase in the future under increasing greenhouse gas concentrations. This implies the long-term likelihood of increased summer drought for northwestern Europe.
Observations of Tidal Internal Wave Beams at Kauai Channel, Hawaii
Authors: Cole S. T. , Rudnick D. L. , Hodges B. A. , Martin J. P.
Published: August 2008

To observe the across-ridge structure of internal tides, density and velocity were measured using SeaSoar and a Doppler sonar over the upper 400–600 m of the ocean extending 152 km on each side of the Hawaiian Ridge at Kauai Channel. Eighteen sections were completed in about 18 days with sampling intentionally detuned from the lunar semidiurnal (M2) tide so that averaging over all sections was equivalent to phase averaging the M2 tide. Velocity and displacement variance and several covariances involving velocity and displacement showed one M2 internal wave beam on each side of the ridge and reflection of the beams off of the surface. Theoretical ray slopes aligned with the observed beams and originated from the sides of the ridge. Energy flux was in agreement with internal wave generation at the ridge. Inferred turbulent dissipation was elevated relative to open ocean values near tidal beams. Energy flux was larger than total dissipation almost everywhere across the ridge. Internal wave energy flux and dissipation at Kauai Channel were 1.5–2.5 times greater than at the average location along the Hawaiian Ridge. The upper 400–600 m was about 1/3 to 1/2 as energetic as the full-depth ocean. Tidal beams interact with each other over the entire length of the beams causing gradients along beams in almost all covariances, momentum flux divergences, and mean flows. At Kauai Channel, momentum flux divergences corresponded to mean flows of 1–4 cm s−1.
Culture and Race/Ethnicity: Bolder, Deeper, and Broader
Authors: Skrentny John D.
Published: August 2008

The role of cultural analysis in the sociology of race, ethnicity, and immigration varies across subject matter. Primarily for political reasons, it has been marginalized in the study of ethnic/racial inequality, though new work is reclaiming culture in this important context. It has an unacknowledged presence in studies of discrimination and domination, but is explicit in macro and historical studies. This article surveys these subfields and makes a call for bolder, deeper, and broader cultural analysis in the field. More work is needed on cultural assimilation, how inequality and discrimination produce racial and ethnic meanings, how ethnic and racial cultures affect interests through variations in conceptions of the meaning of life, how sending state cultures affect immigrant and ethnic cultures in the United States, and how globalization is Americanizing immigrants before they even leave their homelands.
Culture and Markets: How Economic Sociology Conceptualizes Culture
Authors: Levin Peter
Published: August 2008

Current ways of addressing culture in the sociology of markets are incomplete. One approach treats culture as constitutive of markets (markets are culture), while the other treats culture as something affecting markets (markets have culture). This division corresponds to markets that are more or less “settled.” The author outlines the history and shortcomings of this duality and proposes a more dimensional approach to culture and markets that more fully integrates culture into economic sociology.
Culture and Education
Authors: Stevens Mitchell L.
Published: August 2008

The author reviews the primary frameworks through which North American sociologists have conceived of the relation between formal education and culture and explains how sociologists' preponderant conception of formal schooling as an individual-level phenomenon and a metrical quantity has come to constrain intellectual progress in much of the subfield. The author offers two analytic strategies that might help loosen this constraint.
Culture and Microsociology: The Anthill and the Veldt
Authors: Fine Gary Alan , Fields Corey D.
Published: August 2008

The authors argue that sociologists must use the investigation of interpersonal situations as a strategy through which “culture” can be understood in practice. Culture includes a broad range of social processes, institutions, and value systems. In contrast to perspectives that treat groups and individuals as units to be shaped by powerful cultural forces, the authors contend that culture is established, manipulated, and promoted by individuals and groups. Microsituations serve as arenas of action in their own right, locations where culture is both produced and experienced. Drawing examples from five areas of microsociology—groups, cognition, identity/ self, performance, and emotion—the authors demonstrate how a distinctively microsociological perspective allows sociologists to examine how culture, across its various conceptions, has an effect on actors and, in turn, is affected by actors. By exposing the workings of culture in situ, microsociology forces us to theorize the connections between meaning, behavior, and structure.
The Failure of Race Neutral Policies: How Mandatory Terms and Sentencing Enhancements Contribute to Mass Racialized Incarceration
Authors: Schlesinger Traci
Published: August 2008

This study examines the effects of mandatory terms and sentencing enhancements on Black and White men’s state-level prison admission rates. Four major findings emerge from the analysis. First, both mandatory terms and sentencing enhancements increase prison admission rates for Black and White men. Second, these policies disproportionately increase Black men’s admissions. Third, the effects of these policies—on both scale and disparity—are strongest and most consistent on admissions for violent offenses. Finally, although sentencing enhancements increase admission rates more consistently than mandatory terms, mandatory terms have larger effects on admission rates for the categories—for example, violent admissions for Black men—where they do increase admission rates. The findings are consistent with theories of modern racism, which argue that, in the post-civil rights era, racial disparities are primarily produced and maintained by colorblind policies and practices.