bluuebunny/crossref_metadata_2025 huggingface dataset:
cAMP-induced PKCζ activation increases functional CXCR4 expression on human CD34+ hematopoietic progenitors
Authors: Goichberg Polina , Kalinkovich Alexander , Borodovsky Nataliya , Tesio Melania , Petit Isabelle , Nagler Arnon , Hardan Izhar , Lapidot Tsvee
Published: October 2005

Chemokines are key regulators of hematopoiesis and host defense. We report here that functional expression of the chemokine receptor CXCR4 on human immature CD34+ hematopoietic progenitors was increased as a result of sustained elevation in cellular cAMP by dbcAMP and prostaglandin E2. This effect of cAMP was specifically mediated by PKCζ activity. CXCR4 expression and PKCζ activation by cAMP were decreased after the inhibition of cAMP effector-Rap1 by Spa1 overexpression. Interference with the activation of Rac1, a downstream target of Rap1, prevented the cAMP-induced increase in PKCζ activity and CXCR4 levels. Functional manifestation of the effects of cAMP-elevating agents revealed an increased ability of human CD34+ cells to transmigrate the bone marrow (BM) endothelial layer and adhere to BM stroma in vitro, and it augmented the homing potential to the BM and spleens of immunodeficient mice in a Rac1- and a PKCζ-dependent manner. cAMP- and TNFα-stimulated pathways converged in PKCζ-activated CXCR4 expression and MMP-2/MMP-9 secretion. cAMP treatment had a beneficial effect on CD34+ cell survival in a PKCζ-mediated fashion. Taken together, our data reveal major roles for cAMP-induced PKCζ activation in signaling governing the motility and development of CD34+ cells.
Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury
Authors: Arimura Akira , Li Min , Batuman Vecihi
Published: October 2005

The most common type of renal injury in multiple myeloma is chronic tubulointerstitial nephropathy associated with casts in tubule lumens, an entity referred to as “myeloma kidney” that often progresses to end-stage kidney diseases. Myeloma kidney is associated with a significant increase in all-cause mortality, yet no effective intervention, except a limited use of steroid, is available. Here, we report that pituitary adenylate cyclase-activating polypeptide with 38 residues (PACAP38) dramatically prevents injury of cultured renal proximal tubule cells caused by myeloma light chains through suppression of proinflammatory cytokines production, by inhibiting p38 MAPK and translocation of NFκB via both PAC1 and VPAC1 receptors. The suppressive effects of PACAP was as effective as dexamethasone in all of their cytokine assays and demonstrated both in vitro and in vivo. Furthermore, PACAP38 inhibits myeloma cell growth directly and may also indirectly by suppressing production of the growth factor, IL-6, from bone marrow stromal cells, that is stimulated by adhesion of myeloma cells. These findings render PACAP38 worth evaluation as a promising candidate for an effective and safe renoprotectant in myeloma kidney, and possibly other nephropathy, and also as a new antitumor agent in multiple myeloma.
Length of patient-physician relationship and patients' satisfaction and preventive service use in the rural south: a cross-sectional telephone study
Authors: Donahue Katrina E , Ashkin Evan , Pathman Donald E
Published: October 2005

Background

Physicians and patients highly value continuity in health care. Continuity can be measured in several ways but few studies have examined the specific association between the duration of the patient-doctor relationship and patient outcomes. This study (1) examines characteristics of rural adults who have had longer relationships with their physicians and (2) assesses if the length of relationship is associated with patients' satisfaction and likelihood of receiving recommended preventive services.

Methods

Cross-sectional telephone survey of health care access indicators of adults in selected non-metropolitan counties of eight U.S. predominantly southern states. Analyses were restricted to adults who see a particular physician for their care and weighted for demographics and county sampling probabilities.

Results

Of 3176 eligible respondents, 10.8% saw the same physician for the past 12 months, 11.8% for the previous 13–24 months, 20.7% for the past 25–60 months and 56.7% for more than 60 months. Compared to persons with one year or less continuity with the same physician, respondents with over five years continuity more often were Caucasian, insured, a high school graduate, and more often reported good to excellent health and an income above $25,000. Compared to those with more than five years of continuity, participants with either less than one year or one to two years of continuity with the same physician were more often not satisfied with their overall health care (OR 2.34; OR 1.78), participants with less than one year continuity were more often not satisfied with the concern shown them by their physician (O.R. 1.90) and having their health questions answered, and those with one to two years continuity were more often not satisfied with the quality of their care (OR 2.37). No significant associations were found between physician continuity and use rates of any of the queried preventive services.

Conclusion

Over half of this rural population has seen the same physician for more than five years. Longer continuity of care was associated with greater patient satisfaction and confidence in one's physician, but not with a greater likelihood of receiving recommended preventive services.
Alteration of protein expression pattern of vascular endothelial growth factor (VEGF) from soluble to cell-associated isoform during tumourigenesis
Authors: Cressey Ratchada , Wattananupong Onusa , Lertprasertsuke Nirush , Vinitketkumnuen Usanee
Published: October 2005

Background

Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells, and its expression has been correlated with increased tumour angiogenesis. Although numerous publications dealing with the measurement of circulating VEGF for diagnostic and therapeutic monitoring have been published, the relationship between the production of tissue VEGF and its concentration in blood is still unclear. The aims of this study were to determine: 1) The expression pattern of VEGF isoforms at the protein level in colorectal and lung adenocarcinoma in comparison to the pattern in corresponding adjacent normal tissues 2) The relationship between the expression pattern of VEGF and total level of circulating VEGF in the blood to clarify whether the results of measuring circulating VEGF can be used to predict VEGF expression in tumour tissues.

Methods

Ninety-four tissue samples were obtained from patients, 76 colorectal tumour tissues and 18 lung tumour tissues. VEGF protein expression pattern and total circulating VEGF were examined using western blot and capture ELISA, respectively.

Results

Three major protein bands were predominately detected in tumour samples with an apparent molecular mass under reducing conditions of 18, 23 and 26 kDa. The 18 kDa VEGF protein was expressed equally in both normal and colorectal tumour tissues and predominately expressed in normal tissues of lung, whereas the 23 and 26 kDa protein was only detected at higher levels in tumour tissues. The 18, 23 and 26 kDa proteins are believed to represent the VEGF121, the VEGF165 and the VEGF189, respectively. There was a significant correlation of the expression of VEGF165 with a smaller tumour size maximum diameter <5 cm (p < 0.05), and there was a significant correlation of VEGF189 with advanced clinical stage of colorectal tumours. The measurement of total circulating VEGF in serum revealed that cancer patients significantly (p < 0.001) possessed a higher level of circulating VEGF (1081 ± 652 pg/ml in colorectal and 1,251 ± 568 pg/ml in lung) than a healthy volunteer group (543 ± 344 pg/ml). No correlation between the level of circulating VEGF and the pathologic features of tumours was observed.

Conclusion

Our findings indicate that the expression patterns of VEGF isoforms are altered during tumourigenesis as certain isoform overexpression in tumour tissues correlated with tumour progression indicating their important role in tumour development. However, measurement of VEGF in the circulation as a prognostic marker needs to be carefully evaluated as the cell-associated isoform (VEGF189), but not the soluble isoform (VEGF121 and VEGF165) appears to play important role in tumour progression.
Ultra-sensitive detection of prion protein fibrils by flow cytometry in blood from cattle affected with bovine spongiform encephalopathy
Authors: Trieschmann Lothar , Santos Alexander Navarrete , Kaschig Katja , Torkler Sandra , Maas Elke , Schätzl Hermann , Böhm Gerald
Published: October 2005

Background

The definite diagnosis of prion diseases such as Creutzfeldt-Jakob disease (CJD) in humans or bovine spongiform encephalopathy (BSE) in cattle currently relies on the post mortem detection of the pathological form of the prion protein (PrPSc) in brain tissue. Infectivity studies indicate that PrPSc may also be present in body fluids, even at presymptomatic stages of the disease, albeit at concentrations well below the detection limits of currently available analytical methods.

Results

We developed a highly sensitive method for detecting prion protein aggregates that takes advantage of kinetic differences between seeded and unseeded polymerization of prion protein monomers. Detection of the aggregates was carried out by flow cytometry. In the presence of prion seeds, the association of labelled recombinant PrP monomers in plasma and serum proceeds much more efficiently than in the absence of seeds. In a diagnostic model system, synthetic PrP aggregates were detected down to a concentration of approximately 10-8 nM [0.24 fg/ml]. A specific signal was detected in six out of six available serum samples from BSE-positive cattle.

Conclusion

We have developed a method based on seed-dependent PrP fibril formation that shows promising results in differentiating a small number of BSE-positive serum samples from healthy controls. This method may provide the basis for an ante mortem diagnostic test for prion diseases.
Activation of focal adhesion kinase enhances the adhesion and invasion of pancreatic cancer cells via extracellular signal-regulated kinase-1/2 signaling pathway activation
Authors: Sawai Hirozumi , Okada Yuji , Funahashi Hitoshi , Matsuo Yoichi , Takahashi Hiroki , Takeyama Hiromitsu , Manabe Tadao
Published: October 2005

Background

Interaction with integrin and focal adhesion kinase (FAK) regulates the cancer cell adhesion and invasion into extracellular matrix (ECM). In addition, phosphorylation of FAK correlates with the increase of cell motility and invasion. Adhesion and spreading of cancer cells on a variety of ECM proteins, including collagen type IV (Coll IV), leads to an increase in tyrosine phosphorylation and activation of FAK. In this study, we investigated the mechanism of activation of FAK and its downstream extracellular signal-regulated kinase (ERK)-1/2 signaling following stimulation by interleukin (IL)-1α and adhesion to ECM with subsequent enhancement of pancreatic cancer cell adhesion and invasion.

Results

In immunoblotting analysis, all three pancreatic cancer cell lines (AsPC-1, BxPC-3, and Capan-2) expressed the protein of FAK and β1 integrin. Enhancement of FAK protein association with β1 integrin when cells were plated on Coll IV was more increased by stimulation with IL-1α. Preincubation with anti-β1 integrin antibody and FAK siRNA transfection inhibited the association of FAK with β1 integrin of pancreatic cancer cells. FAK phosphorylation was observed by adhesion to Coll IV, furthermore, stronger FAK phosphorylation was observed by stimulation with IL-1α of pancreatic cancer cells adhered to Coll IV in time-dependent manner. Genistein, a tyrosine kinase inhibitor, markedly inhibited the FAK phosphorylation. IL-1α stimulation and Coll IV adhesion enhanced the activation of Ras, as evidenced by the increased Ras-GTP levels in pancreatic cancer cells. Activation of Ras correlated with the phosphorylation of ERK. While not statistical affecting the apoptosis of pancreatic cancer cells, IL-1α-induced adhesion and invasion on Coll IV were inhibited with FAK gene silencing by siRNA, β1 integrin blocking, and inhibition of FAK phosphorylation. PD98059, a MEK inhibitor, also inhibited IL-1α-induced enhancement of adhesion and invasion in pancreatic cancer cells.

Conclusion

Our results demonstrated that activation of FAK is involved with the aggressive capability in pancreatic cancer through Ras/ERK signaling pathway. Based on our results, we suggest that the modification of IL-1, FAK, and integrins functions might be a novel therapeutic approach to aggressive spread of pancreatic cancer.
The influence of walking performed immediately before meals with moderate fat content on postprandial lipemia
Authors: Pfeiffer Martina , Ludwig Tanja , Wenk Caspar , Colombani Paolo C
Published: October 2005

Background

Postprandial lipemia is an independent risk factor for coronary heart disease. Single bouts of moderate exercise may lower this risk, but the minimum duration of moderate intensity exercise that still lowers postprandial lipemia is not known. We, therefore, performed a dose-response study with a normal, daily life setting, to identify the minimum duration of moderate intensity walking that lowers postprandial lipemia in sedentary, healthy young men.

Methods

Sixteen men performed three activity trials (30, 60, or 90 min of treadmill walking at 50% of their individual VO2max) and a control trial with no physical activity in a repeated measures crossover design. The subjects walked immediately before ingestion of the first of two mixed meals, which were served 3 h apart. The meals had a moderate fat content (0.5 g per kg body mass and 33% of total energy per meal) and a macronutrient composition corresponding to current recommendations. Each meal provided one third of the subject's estimated daily energy requirement. Venous blood samples were taken in the fasted state, and then hourly for 6 h after the first meal to assess the postprandial phase. Postprandial lipemia (the incremental area under the curve (dAUC) of triacylglycerol) was compared with a mixed model analysis and Tukey's adjustment.

Results

Postprandial lipemia (dAUC of triacylglycerol) was, compared to the control trial, +2% (P = 1.00), -14% (P = 0.24), and -15% (P = 0.23) in the 30, 60, and 90 min walking trials, respectively.

Conclusion

Moderate intensity walking of 60 and 90 min duration slightly, but insignificantly, reduced postprandial lipemia after two mixed meals with moderate fat content in sedentary, healthy young men, compared to inactivity. Therefore, it should be reconsidered if the acute exercise-induced reduction in postprandial lipemia usually observed in studies using high fat meals is of importance in a real, daily life setting.
School lunch and snacking patterns among high school students: Associations with school food environment and policies
Authors: Neumark-Sztainer Dianne , French Simone A , Hannan Peter J , Story Mary , Fulkerson Jayne A
Published: October 2005

Objectives

This study examined associations between high school students' lunch patterns and vending machine purchases and the school food environment and policies.

Methods

A randomly selected sample of 1088 high school students from 20 schools completed surveys about their lunch practices and vending machine purchases. School food policies were assessed by principal and food director surveys. The number of vending machines and their hours of operation were assessed by trained research staff.

Results

Students at schools with open campus policies during lunchtime were significantly more likely to eat lunch at a fast food restaurant than students at schools with closed campus policies (0.7 days/week vs. 0.2 days/week, p < .001). Student snack food purchases at school were significantly associated with the number of snack machines at schools (p < .001) and policies about the types of food that can be sold. In schools with policies, students reported making snack food purchases an average of 0.5 ± 1.1 days/week as compared to an average of 0.9 ± 1.3 days/week in schools without policies (p < .001). In schools in which soft drink machines were turned off during lunch time, students purchased soft drinks from vending machines 1.4 ± 1.6 days/week as compared to 1.9 ± 1.8 days/week in schools in which soft drink machines were turned on during lunch (p = .040).

Conclusion

School food policies that decrease access to foods high in fats and sugars are associated with less frequent purchase of these items in school among high school students. Schools should examine their food-related policies and decrease access to foods that are low in nutrients and high in fats and sugars.
Hybrid dynamic/static method for large-scale simulation of metabolism
Authors: Yugi Katsuyuki , Nakayama Yoichi , Kinoshita Ayako , Tomita Masaru
Published: October 2005

Background

Many computer studies have employed either dynamic simulation or metabolic flux analysis (MFA) to predict the behaviour of biochemical pathways. Dynamic simulation determines the time evolution of pathway properties in response to environmental changes, whereas MFA provides only a snapshot of pathway properties within a particular set of environmental conditions. However, owing to the large amount of kinetic data required for dynamic simulation, MFA, which requires less information, has been used to manipulate large-scale pathways to determine metabolic outcomes.

Results

Here we describe a simulation method based on cooperation between kinetics-based dynamic models and MFA-based static models. This hybrid method enables quasi-dynamic simulations of large-scale metabolic pathways, while drastically reducing the number of kinetics assays needed for dynamic simulations. The dynamic behaviour of metabolic pathways predicted by our method is almost identical to that determined by dynamic kinetic simulation.

Conclusion

The discrepancies between the dynamic and the hybrid models were sufficiently small to prove that an MFA-based static module is capable of performing dynamic simulations as accurately as kinetic models. Our hybrid method reduces the number of biochemical experiments required for dynamic models of large-scale metabolic pathways by replacing suitable enzyme reactions with a static module.
Ultrafine particles cause cytoskeletal dysfunctions in macrophages: role of intracellular calcium
Authors: Möller Winfried , Brown David M , Kreyling Wolfgang G , Stone Vicki
Published: October 2005

Background

Particulate air pollution is reported to cause adverse health effects in susceptible individuals. Since most of these particles are derived form combustion processes, the primary composition product is carbon with a very small diameter (ultrafine, less than 100 nm in diameter). Besides the induction of reactive oxygen species and inflammation, ultrafine particles (UFP) can cause intracellular calcium transients and suppression of defense mechanisms of alveolar macrophages, such as impaired migration or phagocytosis.

Methods

In this study the role of intracellular calcium transients caused by UFP was studied on cytoskeleton related functions in J774A.1 macrophages. Different types of fine and ultrafine carbon black particles (CB and ufCB, respectively), such as elemental carbon (EC90), commercial carbon (Printex 90), diesel particulate matter (DEP) and urban dust (UD), were investigated. Phagosome transport mechanisms and mechanical cytoskeletal integrity were studied by cytomagnetometry and cell viability was studied by fluorescence microscopy. Macrophages were exposed in vitro with 100 and 320μg UFP/ml/million cells for 4 hours in serum free medium. Calcium antagonists Verapamil, BAPTA-AM and W-7 were used to block calcium channels in the membrane, to chelate intracellular calcium or to inhibit the calmodulin signaling pathways, respectively.

Results

Impaired phagosome transport and increased cytoskeletal stiffness occurred at EC90 and P90 concentrations of 100μg/ml/million cells and above, but not with DEP or UD. Verapamil and W-7, but not BAPTA-AM inhibited the cytoskeletal dysfunctions caused by EC90 or P90. Additionally the presence of 5% serum or 1% bovine serum albumin (BSA) suppressed the cytoskeletal dysfunctions. Cell viability showed similar results, where co-culture of ufCB together with Verapamil, W-7, FCS or BSA produced less cell dead compared to the particles only.
Calmodulin kinase II regulates the maturation and antigen presentation of human dendritic cells
Authors: Herrmann Tara L , Morita Craig T , Lee Kelvin , Kusner David J
Published: October 2005

Dendritic cells (DC) are professional antigen-presenting cells, which activate the adaptive immune system. Upon receiving a danger signal, they undergo a maturation process, which increases their antigen presentation capacity, but the responsible regulatory mechanisms remain incompletely understood. A Ca2+-calmodulin (Cam)-Cam kinase II (CamK II) pathway regulates phagosome maturation in macrophages, and this pathway is inhibited by pathogenic microbes. Our hypothesis is that signal transduction events which control phagosome maturation also regulate antigen presentation. Stimulation of primary human DC or the human DC line KG-1, with particulate antigen, resulted in the activation of CamK II and its localization to the phagosome and plasma membrane. Two mechanistically distinct inhibitors of CamK II significantly reduced DC maturation, as determined by up-regulation of surface costimulatory and major histocompatibility complex (MHC) class II molecules and secretion of cytokines. Confocal microscopy demonstrated that the CamK II inhibitors blocked the antigen-induced increase in total cellular MHC class molecules as well as their trafficking to the plasma membrane. Inhibition of CamK II was associated with decreased presentation of particulate and soluble MHC class II-restricted antigen, with a greater effect on the former. These data support a model in which CamK II regulates critical stages of the maturation and antigen presentation capacity of human DC, particularly in response to stimulation via phagocytosis.
The low-toxicity versions of LPS, MPL® adjuvant and RC529, are efficient adjuvants for CD4+ T cells
Authors: Thompson Bruce S , Chilton Paula M , Ward Jon R , Evans Jay T , Mitchell Thomas C
Published: October 2005

Lipopolysaccharide (LPS) has long been known to enhance innate and adaptive immune responses; however, its extreme toxicity precludes its use in clinical settings. The combined toxicity and adjuvanticity of LPS have contributed to the view that immunological adjuvants need to be highly inflammatory to be maximally effective. Here, we compared the effects of LPS with its less-toxic derivatives, monophosphoryl lipid A (MPL) and a chemical mimetic, RC529, on CD4+ T cell clonal expansion, long-term survival, and T helper cell type 1 (Th1) differentiation. We found that LPS, MPL, and RC529 had similar effects on CD4+ T cell clonal expansion, cell division, and ex vivo survival. Analysis of the ability of activated CD4+ T cells to produce interferon-γ following a 21-day immunization and challenge protocol with LPS and MPL resulted in similar Th1 differentiation. In contrast, we found that LPS was more effective in promoting long-term CD4+ T cell responses, as we recovered nearly sixfold more cells following immunization/challenge as compared with treatment with MPL. Our results indicate that low-inflammation adjuvants, such as MPL and RC529, are capable of enhancing short-term CD4+ T cell clonal expansion and Th1 differentiation, but inflammatory signaling aids in the long-term retention of antigen-specific T cells.
Crosstalk between chemokines and neuronal receptors bridges immune and nervous systems
Authors: Zhang Ning , Oppenheim Joost J
Published: October 2005

Chemokine receptors, a family of Gi protein-coupled receptors responsible for cell migration, are widely expressed by cells of immune and nervous systems. Activation of receptors on the surface of leukocytes, such as opioid, vasoactive intestinal peptide, or adenosine receptors, often has inhibitory effects on chemokine receptors by a mechanism termed heterologous desensitization, resulting in suppression of immune responses. Conversely, activation of chemokine receptors also induces heterologous desensitization of μ-opioid receptors (MOR), a class of key analgesic receptors on neurons. Furthermore, prior exposure of neuronal cells to chemokine treatment enhances the sensitivity of transient receptor potential vanilloid 1 (TRPV1), a heat- and ligand-gated calcium channel, which is critical for sensing of pain. Consequently, during inflammation, activation of chemokine receptors on neurons contributes to hyperalgesia by inhibiting MOR and concomitantly sensitizing TRPV1 via Gi protein-mediated signaling pathways. These observations suggest that the crosstalk between chemokine receptors and neuropeptide membrane receptors serves as a bridge between the immune and nervous systems.
Repeated [131I]Metaiodobenzylguanidine Therapy in Two Patients with Malignant Pheochromocytoma
Authors: Lam Marnix G. E. H. , Lips Cornelis J. M. , Jager Pieter L. , Dullaart Robin P. F. , Lentjes Eef G. W. M. , van Rijk Peter P. , de Klerk John M. H.
Published: October 2005

Context: Approximately 10% of pheochromocytomas are malignant with a 5-yr survival rate of less than 40%. Promising results have been published on single high-dosage [131I]metaiodobenzylguanidine ([131I]MIBG) treatment for malignant pheochromocytoma. We present our experience with multiple intermediate-dosage [131I]MIBG therapy instead of single high-dosage therapy.

Setting and Patients: The study took place at University Medical Centers and included two patients (one male, 36 yr of age, and one female, 43 yr of age) with widely spread metastatic pheochromocytoma and bad prognosis because of liver and lung metastases.

Interventions: Instead of a single high dosage, these two patients were treated with multiple intermediate dosages of [131I]MIBG. The first patient received 37 GBq (1 Ci) [131I]MIBG in five sessions [7400 MBq (200 mCi) each; interval range, 2–11 months]; the second patient received 66.6 GBq (1.8 Ci) [131I]MIBG in 12 sessions [5550 MBq (150 mCi) each; interval range, 2–14 months].

Outcome Measures: We measured efficacy, toxicity, and survival.

Results: Both patients had a complete symptomatic response and a partial tumor volume response. The first patient had a partial biochemical response, the second a complete biochemical response. In both cases, toxicity has been confined to nausea during treatment. Hematological toxicity was minimal, and both patients stayed euthyroid. The survival (so far) of these patients was 5 yr (clinical case 1) and 16 yr (clinical case 2) after initial diagnosis.

Conclusions: Repeated intermediate-dosage [131I]MIBG treatment appears to be a reliable and well-tolerated radionuclide therapy and might be a useful adjunct in patients with malignant pheochromocytoma, providing longstanding palliation and prolonged survival.
Changes in Plasma Concentrations of Osteoprotegerin before and after Levothyroxine Replacement Therapy in Hypothyroid Patients
Authors: Guang-da Xiang , Hui-ling Sun , Zhi-song Cheng , Lin-shuang Zhao
Published: October 2005

Context: Recent study has shown that overt hypothyroidism (oHT) is associated with increased plasma osteoprotegerin (OPG) levels.

Objective: Our objective was to examine the plasma OPG level alteration before and after levothyroxine (l-T4) treatment in oHT and subclinical hypothyroidism (sHT).

Patients: The study subjects included oHT and sHT patients and healthy individuals (20 subjects in each group).

Methods: All patients were given l-T4 therapy to maintain a euthyroid state. Plasma OPG concentration was measured in duplicate by a sandwich ELISA.

Results: Plasma OPG levels in oHT and sHT before treatment were significantly higher than levels in controls (P < 0.01). After normalization of thyroid function, OPG levels in both groups decreased markedly (P < 0.01). The absolute changes in OPG showed a significant positive correlation with the changes in TSH (P < 0.05) and negative correlation with the changes in endothelium-dependent arterial dilation (P < 0.01) in hypothyroid patients during the course of treatment.

Conclusion: OPG may be involved in the development of vascular dysfunction in hypothyroid patients.
Functional Coupling of β3-Adrenoceptors and Large Conductance Calcium-Activated Potassium Channels in Human Uterine Myocytes
Authors: Doheny Helen C. , Lynch Caoimhe M. , Smith Terry J. , Morrison John J.
Published: October 2005

Context: β3-Adrenoreceptor modulation in human myometrium during pregnancy is linked functionally to myometrial inhibition. Maxi-K+ channels (BKCa) play a significant role in modulating cell membrane potential and excitability.

Objective: This study was designed to investigate the potential involvement of BKCa channel function in the response of human myometrium to β3-adrenoceptor activation.

Design: Single and whole-cell electrophysiological BKCa channel recordings from freshly dispersed myocytes were obtained in the presence and absence of BRL37344, a specific β3-adrenoreceptor agonist. The in vitro effects of BRL37344 on isolated myometrial contractions, in the presence and absence of the specific BKCa channel blocker, iberiotoxin (IbTX), were investigated.

Setting: The study was carried out at the Clinical Science Institute.

Patients or Other Participants: Myometrial biopsies were obtained at elective cesarean delivery.

Intervention: No intervention was applied.

Main Outcome Measures: Open state probability of single channel recordings, whole cell currents, and myometrial contractile activity were measured.

Results: Single-channel recordings identified the BKCa channel as a target of BRL37344. BRL37344 significantly increased the open state probability of this channel in a concentration-dependent manner (control 0.031 ± 0.004; 50 μm BRL37344 0.073 ± 0.005 (P < 0.001); and 100 μm BRL37344 0.101 ± 0.005 (P < 0.001). This effect was completely blocked after preincubation of the cells with 1 μm bupranolol, a nonspecific β-adrenoreceptor blocker, or 100 nm SR59230a, a specific β3-adrenoreceptor antagonist. In addition, BRL37344 increased whole-cell currents over a range of membrane potentials, and this effect was reversed by 100 nm IbTX. In vitro isometric tension studies demonstrated that BRL37344 exerted a significant concentration-dependent relaxant effect on human myometrial tissue (P < 0.05), and preincubation of these strips with IbTX attenuated this effect on both spontaneous and oxytocin-induced contractions (44.44 and 57.84% at 10−5m, respectively).

Conclusions: These findings outline that activation of the BKCa channel may explain the potent uterorelaxant effect of β3-adrenoreceptor agonists.
Human T Cell Leukemia Virus Type I-Infected Patients with Hashimoto’s Thyroiditis and Graves’ Disease
Authors: Matsuda Takehiro , Tomita Mariko , Uchihara Jun-Nosuke , Okudaira Taeko , Ohshiro Kazuiku , Tomoyose Takeaki , Ikema Tomoki , Masuda Masato , Saito Mineki , Osame Mitsuhiro , Takasu Nobuyuki , Ohta Takao , Mori Naoki
Published: October 2005

Context: Autoimmune thyroid diseases have been reported to be associated with human T cell leukemia virus type I (HTLV-I) infection. HTLV-I proviral load is related to the development of HTLV-I-associated myelopathy/tropical spastic paraparesis and has also been shown to be elevated in the peripheral blood of HTLV-I-infected patients with uveitis, arthritis, and connective tissue disease.

Objective: The objective of the study was to evaluate the proviral load in HTLV-I-infected patients with Hashimoto’s thyroiditis (HT) or Graves’ disease (GD) and ascertain the ability of HTLV-I to infect thyroid cells.

Patients and Methods: A quantitative real-time PCR assay was developed to measure the proviral load of HTLV-I in peripheral blood mononuclear cells from 26 HTLV-I-infected patients with HT, eight HTLV-I-infected patients with GD, or 38 asymptomatic HTLV-I carriers. Rat FRTL-5 thyroid cells were cocultured with HTLV-I-infected T cell line MT-2 or uninfected T cell line CCRF-CEM. After coculture with T cell lines, changes in Tax and cytokine mRNA expression were studied by RT-PCR.

Results: HTLV-I proviral load was significantly higher in the peripheral blood of patients with HT and GD than asymptomatic HTLV-I carriers. In the peripheral blood from HTLV-I-infected patients with HT, HTLV-I proviral load did not correlate with the thyroid peroxidase antibody or thyroglobulin antibody titer. After coculture with MT-2 cells, FRTL-5 cells expressed HTLV-I-specific Tax mRNA. These cocultured FRTL-5 cells with MT-2 cells expressed IL-6 mRNA and proliferated more actively than those cocultured with CCRF-CEM cells.

Conclusion: Our findings suggest the role of the retrovirus in the development of autoimmune thyroid diseases in HTLV-I-infected patients.
Modulation of Thyroid-Specific Gene Expression in Normal and Nodular Human Thyroid Tissues from Adults: An in Vivo Effect of Thyrotropin
Authors: Bruno Rocco , Ferretti Elisabetta , Tosi Emanuele , Arturi Franco , Giannasio Paolo , Mattei Tiziana , Scipioni Angela , Presta Ivan , Morisi Roberta , Gulino Alberto , Filetti Sebastiano , Russo Diego
Published: October 2005

Context: Evidence from in vitro studies or animal models has shown that TSH affects thyrocytes by thyroid-specific expression modulation.

Objective: The objective of our study was to analyze the role of TSH in human thyroid gene expression in vivo.

Design/Setting: Thirty-nine normal thyroid tissues were collected at the same center.

Study Subjects: Patients were divided into two groups based on serum TSH levels: 17 with normal TSH levels (1–4 mU/liter; group 1) and 22 with TSH levels below 0.5 mU/liter (group 2).

Intervention: Group 2 underwent thyroidectomy after suppressive l-T4 therapy.

Main Outcome Measures: mRNA levels of thyroid genes such as sodium/iodide symporter (NIS), apical iodide transporter, pendrin, thyroglobulin, thyroperoxidase, TSH receptor, paired box transcription factor 8, and thyroid transcription factor-1 were evaluated by quantitative PCR.

Results: The reduction of TSH stimulation causes decreases in NIS and apical iodide transporter gene expression in normal tissues and more limited reductions in thyroglobulin, thyroperoxidase, and paired box transcription factor 8, but it has no significant effect on TSH receptor, pendrin, or thyroid transcription factor-1. Comparison of NIS levels in normal and nodular tissues from the same patient confirmed that it is differentially expressed in nodules only in the presence of normal TSH (P < 0.01). In patients with suppressed TSH, nodular NIS levels were similar to those in normal tissues.

Conclusions: Our data represent the first demonstration in human thyroid tissues that TSH contributes to the regulation of thyrocyte differentiation by modulating thyroid gene levels. It exerts a particularly important effect on the transcription of NIS, which becomes very low after prolonged TSH suppression.
Protective effects of the Alisma orientalis extract on the experimental nonalcoholic fatty liver disease
Authors: Hong Xuezhi , Tang Huiqing , Wu Limao , Li Lianda
Published: October 2005

The aim of this investigation was to evaluate the efficacy of Alisma orientalis methanolic extract (AOME) on the experimental nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet. Rats were fed with high-fat diet for six weeks and then gavaged the AOME for another six weeks. Typical pathological symptoms of NAFLD occurred in the high-fat diet rats. Administration with the AOME (150,300 and 600 mg kg−1) markedly decreased the serum and liver lipids; the high level of fasting serum glucose was reduced and insulin resistance was improved. The AOME treatment was also helpful in preventing the oxidative stress by lessening lipid peroxidation and activating antioxidant enzymes. Markers of the liver injury, aminotransferase abnormalities and hepatomegaly were improved and morphological changes, such as liver steatosis, mixed inflammation and collagen deposition, were lessened in rats treated with the AOME. These results suggested that the AOME showed hepatoprotective effects on NAFLD and may be a potential clinical application for treatment of this chronic liver disease.
Preventive effect of Aegle marmelos leaf extract on isoprenaline-induced myocardial infarction in rats: biochemical evidence
Authors: Prince P Stanely Mainzen , Rajadurai M
Published: October 2005

We have evaluated the preventive effects of an aqueous Aegle marmelos leaf extract (AMLEt) in isoprenaline (isoproterenol)-induced myocardial infarction in rats. Rats were pretreated with AMLEt (50, 100 or 200 mg kg−1) for 35 days. After the treatment period, isoprenaline (200 mg kg−1) was administered subcutaneously to rats at an interval of 24 h for two days. The activity of creatine kinase (CK) and lactate dehydrogenase (LDH) was significantly increased in serum and significantly decreased in heart of isoprenaline-treated rats. Pretreatment with AMLEt decreased the activity of CK and LDH in serum and increased them in the heart. The activity of sodium-potassium dependent adenosine triphosphatase (Na+K+ATPase) was significantly decreased while the activity of calcium dependent adenosine triphosphatase (Ca2+ATPase) was simultaneously increased in the heart and aorta. AMLEt pretreatment increased the activity of Na+K+ATPase and decreased the activity of Ca2+ATPase in the heart and aorta simultaneously. The levels of cholesterol and triglycerides increased, while the levels of phospholipids decreased in the heart and aorta of isoprenaline-treated rats. In AMLEt-pretreated rats the levels of cholesterol and triglycerides decreased whereas phospholipids increased in heart and aorta. All the deranged biochemical parameters were restored with 200 mg kg−1 AMLEt. Similarly α-tocopherol (60 mg kg−1)-pretreatment to isoprenaline-treated rats exhibited a significant effect on all the parameters studied. The results from this study may have clinical relevance.
Oral administration of a decaffeinated green tea (Camellia sinensis) extract did not alter urinary 8-epi-prostaglandin F2α, a biomarker for in-vivo lipid peroxidation
Authors: Donovan Jennifer L , De Vane Lindsay , Chavin Kenneth D , Fiorini Ryan N , Oates James C , Njoku Chinedu , Patrick Kennerly S , Markowitz John S
Published: October 2005

Oxidative stress is involved in the pathogenesis of numerous chronic human diseases. The objective of this study was to determine whether administration of a decaffeinated green tea extract providing 844 mg flavonoids daily reduced the urinary excretion of 8-epi-prostaglandin F2α (8-epi-PGF2α), a product of lipid peroxidation in cellular membranes and of low-density lipoprotein (LDL). Nine healthy male and female subjects were studied at baseline and after 14 days of green tea supplementation. Analysis of urinary 8-epi-PGF2α was performed using immunoaffinity extraction-gas chromatography-negative ion chemical ionization-mass spectrometry (GC-NICI-MS). Urinary 8-epi-PGF2α concentrations were 0.286±0.120 nmol (mmol creatinine)−1 at baseline and 0.244±0.177 nmol mmol−1 creatinine after green tea supplementation. There were no significant differences in the excretion of urinary 8-epi-PGF2α after treatment with green tea. We conclude that 14 days of green tea supplementation did not significantly alter in-vivo lipid peroxidation.
Visual control of flight speed in honeybees
Authors: Baird Emily , Srinivasan Mandyam V. , Zhang Shaowu , Cowling Ann
Published: October 2005

Visual control of flight speed in honeybees (Apis mellifera L.)was investigated by training them to fly through a specially constructed tunnel in which the motion, contrast and texture of the patterns lining the walls could be varied. Manipulation of pattern motion revealed that the speed of flight is controlled by regulating the image motion that is experienced by the eyes. Flight speed is surprisingly robust to changes in the contrast and/or spatial texture of the visual environment, suggesting that the underlying movement-detecting mechanisms estimate the speed of image motion in the eye largely independently of these parameters. This ensures that flight speed depends primarily on the distances to nearby surfaces and not upon their particular visual properties, such as contrast or visual texture. The removal of image motion cues drastically compromises the regulation of flight speed,underscoring their role in this function.
Mechanical and morphological properties of different muscle–tendon units in the lower extremity and running mechanics: effect of aging and physical activity
Authors: Karamanidis Kiros , Arampatzis Adamantios
Published: October 2005

The objectives of this work were (i) to investigate whether chronic endurance running is a sufficient stimulus to counteract the age-related changes in the mechanical and morphological properties of human triceps surae(TS) and quadriceps femoris (QF) muscle–tendon units (MTUs) by comparing runners and non-active subjects at different ages (young and old), (ii) to identify adaptational phenomena in running mechanics due to age-related changes in the mechanical and morphological properties of the TS and QF MTUs,and finally (iii) to examine whether chronic endurance-running exercise is associated with adaptational effects on running characteristics in old and young adults.

The investigation was conducted on 30 old and 19 young adult males divided into two subgroups according to their running activity: endurance-runners vs non-active. To analyse the properties of the MTUs, all subjects performed isometric maximal voluntary (MVC) ankle plantarflexion and knee extension contractions at 11 different MTU lengths on a dynamometer. The activation of the TS and QF during MVC was estimated by surface electromyography. The gastrocnemius medialis and the vastus lateralis and their distal aponeuroses were visualized by ultrasonography at rest and during MVC, respectively. Ground reaction forces and kinematic data were recorded during running trials at 2.7 m s–1.

The TS and QF MTU capacities were reduced with aging (lower muscle strength and lower tendon stiffness). Runners and non-active subjects had similar MTU properties, suggesting that chronic endurance-running exercise does not counteract the age-related degeneration of the MTUs. Runners showed a higher mechanical advantage for the QF MTU while running (lower gear ratio) compared to non-active subjects, indicating a task-specific adaptation even at old age. Older adults reacted to the reduced capacities of their MTUs by increasing running safety (higher duty factor, lower flight time) and benefitting from a mechanical advantage for the TS MTU, lower rate of force generation and force generation per meter distance. We suggest that the improvement in running mechanics in the older adults happens due to a perceptual motor recalibration and a feed-forward adaptation of the motor task aimed at decreasing the disparity between the reduced capacity of the MTUs and the running effort.
Synthesis of Polycrystalline Spherical SnO2 Microparticles via Hydrothermal Treatment in the Presence of Mixed Surfactants
Authors: Sakai Go , Nakatani Tomoe , Yoshimura Takumi , Uota Masafumi , Kijima Tsuyoshi
Published: October 2005

The spherical microparticles of SnO2 were synthesized successfully by hydrothermal treatment of their precursor consisting of SnCl4 and mixed surfactants, followed by calcination at 500 °C.
Improvements and Comparison of Heuristics for Solving the Uncapacitated Multisource Weber Problem
Authors: Brimberg Jack , Hansen Pierre , Mladenović Nenad , Taillard Eric D.
Published: October 2005

The multisource Weber problem is to locate simultaneously m facilities in the Euclidean plane to minimize the total transportation cost for satisfying the demand of n fixed users, each supplied from its closest facility. Many heuristics have been proposed for this problem, as well as a few exact algorithms. Heuristics are needed to solve quickly large problems and to provide good initial solutions for exact algorithms. We compare various heuristics, i.e., alternative location-allocation (Cooper 1964), projection (Bongartz et al. 1994), Tabu search (Brimberg and Mladenović 1996a), p-Median plus Weber (Hansen et al. 1996), Genetic search and several versions of Variable Neighbourhood search. Based on empirical tests that are reported, it is found that most traditional and some recent heuristics give poor results when the number of facilities to locate is large and that Variable Neighbourhood search gives consistently best results, on average, in moderate computing time.
The equal environments assumption of classical twin studies may not hold
Authors: Richardson Ken , Norgate Sarah
Published: October 2005

The classical twin method ‐ comprising comparisons of monozygotic (MZ) and dizygotic (DZ) twins ‐ in the domain of cognitive abilities and attainments has led to wide acceptance of results suggesting a large amount of additive genetic variance, with far‐reaching implications both for the nature of future studies on the causes of cognitive variance and for intervention policies, as in education. However, this interpretation is only valid if the method observes a number of conditions, which have to hold. Here, we show that the most crucial of these, namely, the equal environments assumption (EEA), may not hold. Consequently, differences in twin correlations might be at least partly explained by treatment effects from parents, teachers, peers, and so on. In addition, well‐known interactions at various levels confound the model of simple additive effects on which the classical twin method is predicated and results are interpreted. For example, at a socio‐cognitive level, DZ twins may respond to treatments differently from MZ twins. This interaction may further explain MZ—DZ correlation differences. There is abundant evidence for such interactive effects in published twin data. We suggest that there is a need for a more thorough examination of these problems.
The relationship between autobiographical memory specificity and depressed mood following a stressful life event: A prospective study
Authors: van Minnen Agnes , Wessel Ineke , Verhaak Chris , Smeenk Jesper
Published: October 2005

Objectives. In the present prospective study, the relationship between autobiographical memory specificity and the emotional reactions to a stressful event was investigated.

Design and methods. The Autobiographical Memory Test (AMT) was administered to 74 women before they underwent an in vitro fertilization (IVF) treatment, which subsequently failed. Symptoms of emotional reactions – depression and anxiety – were measured both before and after the (failed) IVF treatment.

Results. It was found that the number of reported specific memories at baseline was negatively related to depressive and anxiety symptoms after the treatment, even when initial depressive and anxiety symptoms and verbal fluency were controlled for.

Conclusions. Taken together, the findings indicate that a lack of autobiographical memory specificity predicts changes in depressive mood after a stressful event.