bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stat3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer
Authors: Berishaj Marjan , Gao Sizhi Paul , Ahmed Simi , Leslie Kenneth , Al-Ahmadie Hikmat , Gerald William L , Bornmann William , Bromberg Jacqueline F 
Published: May 2007

Abstract
Introduction
Signal transducer and activator of transcription 3 (Stat3) is constitutively tyrosine-phosphorylated in approximately 50% of primary breast carcinomas. A number of different mechanisms responsible for Stat3 activation, including abnormal activation of receptor tyrosine kinases, Src, and Janus kinases (Jaks), have been implicated in breast cancer.

Methods
We examined six breast cancer-derived cell lines expressing high or low levels of tyrosine-phosphorylated Stat3 (pStat3) as well as primary breast cancer specimens.

Results
Inhibition of Src or EGFR (epidermal growth factor receptor) tyrosine kinases had no effect on pStat3 levels, whereas pan-Jak inhibitor P6 resulted in complete abrogation of Stat3 phosphorylation and inhibition of growth. Jaks are required for cytokine signaling, and the glycoprotein 130 (gp130) receptor-associated Jaks are known mediators of Stat3 phosphorylation. Blockade of the gp130 receptor or sequestration of the interleukin-6 (IL-6) ligand led to a decrease of pStat3 levels. Conditioned media from those cell lines expressing high levels of pStat3 contained IL-6 and were capable of stimulating Stat3 phosphorylation. We examined IL-6 levels in primary breast tumors and found a positive correlation between pStat3 and IL-6 expression.

Conclusion
In summary, a principal mechanism of Stat3 activation in breast cancer is through the IL-6/gp130/Jak pathway.
Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages
Authors: del Sol Antonio , Araúzo-Bravo Marcos J , Amoros Dolors , Nussinov Ruth 
Published: May 2007

Abstract
Background
Allosteric communications are vital for cellular signaling. Here we explore a relationship between protein architectural organization and shortcuts in signaling pathways.

Results
We show that protein domains consist of modules interconnected by residues that mediate signaling through the shortest pathways. These mediating residues tend to be located at the inter-modular boundaries, which are more rigid and display a larger number of long-range interactions than intra-modular regions. The inter-modular boundaries contain most of the residues centrally conserved in the protein fold, which may be crucial for information transfer between amino acids. Our approach to modular decomposition relies on a representation of protein structures as residue-interacting networks, and removal of the most central residue contacts, which are assumed to be crucial for allosteric communications. The modular decomposition of 100 multi-domain protein structures indicates that modules constitute the building blocks of domains. The analysis of 13 allosteric proteins revealed that modules characterize experimentally identified functional regions. Based on the study of an additional functionally annotated dataset of 115 proteins, we propose that high-modularity modules include functional sites and are the basic functional units. We provide examples (the Gα
s
subunit and P450 cytochromes) to illustrate that the modular architecture of active sites is linked to their functional specialization.

Conclusion
Our method decomposes protein structures into modules, allowing the study of signal transmission between functional sites. A modular configuration might be advantageous: it allows signaling proteins to expand their regulatory linkages and may elicit a broader range of control mechanisms either via modular combinations or through modulation of inter-modular linkages.
Local Anaesthetic Infusion with Elastomeric Pump After Arthroscopic Subacromial Decompression
Authors: Little Kevin , Pillai Anand , Fazzi Umberto , Storey Neil 
Published: May 2007

INTRODUCTION The use of extended local anaesthesia for postoperative pain has previously been reported, and has several advantages over other methods, including ease of placement, safety, reliability, lower cost and effective analgesia. We present our experience with a portable elastomeric infusion device in patients undergoing arthroscopic subacromial decompression, and make a case for its potential to allow same-day discharge. PATIENTS AND METHODS Forty patients undergoing arthroscopic subacromial decompression were followed-up. At the end of the procedure, an epidural catheter connected to a portable elastomeric local anaesthetic infusion system was inserted into the subacromial space. All patients were electively admitted for overnight stay postoperatively and assessed using a visual analogue scale (VAS) to evaluate their level of pain. RESULTS No patient reported severe pain at any stage. None of the patients required any parenteral opiate analgesia with the pump in situ. CONCLUSIONS These findings suggest that the use of this elastomeric infusion device following shoulder surgery allows safe and early discharge of patients with decreased need for parenteral opiate analgesia.
Impact of HIV and AIDS on Surgical Practice
Authors: Dua RS , Wajed SA , Winslet MC 
Published: May 2007

INTRODUCTION Surgical intervention has become a common component in the management of patients infected with the human immunodeficiency virus (HIV) or suffering from the clinical consequences of acquired immunodeficiency syndrome (AIDS). We investigated the evolution of this involvement at a tertiary referral centre for this condition over a 16-year period. PATIENTS AND METHODS Detailed retrospective examination of the medical records of HIV-positive patients treated at the Royal Free Hospital between 1986 and 2002 was undertaken. Clinical, pathological and operative details of those patients who underwent surgical intervention were recorded. RESULTS Of the 2100 cases reviewed, 477 patients underwent a combined total of 772 surgical procedures. Of the 772 operations, 95 (12.3%) were performed as emergencies. Anorectal surgery represented the highest group with a total of 195 procedures (25.26%) being undertaken. The majority of patients (59%) had AIDS at the time of surgery, and 27.04% had a significant co-existing medical problem. Overall postoperative complication rate was 10.1%, with the risk being significantly greater in those undergoing intra-abdominal surgery and emergency procedures. CONCLUSIONS This is the largest study to audit the impact of HIV/AIDS in general surgical practice in the UK retrospectively. Surgery for HIV patients can be safely conducted with a low complication rate for the diagnostic and anorectal procedures that comprise the vast majority of surgery in HIV/AIDS patients. Medical treatment for patients with HIV/AIDS has developed dramatically over the last two decades. In parallel, this has resulted in a heavy, new and varied workload for general surgeons, who have also had to adapt in order to deal with the challenging spectrum of this disease.
Functional Expression of Ion Channels in Mesenchymal Stem Cells Derived from Umbilical Cord Vein
Authors: Park Kyoung Sun , Jung Kyoung Hwa , Kim Seung Hyun , Kim Kyung Suk , Choi Mi Ran , Kim Yangmi , Chai Young Gyu 
Published: May 2007

Abstract
Mesenchymal stem cells have the ability to renew and differentiate into various lineages of mesenchymal tissues. We used undifferentiated human mesenchymal-like stem cells from human umbilical cord vein (hUC-MSCs), a cell line which contains several mesenchymal cell markers. We characterized functional ion channels in cultured hUC-MSCs with whole-cell patch clamp and reverse transcription-polymerase chain reaction (RT-PCR). Three types of outward current were found in these cells: the Ca2+-activated K+ channel (IKCa), a transient outward K+ current (Ito), and a delayed rectifier K+ current (IKDR). IKCa and IKDR were totally suppressed by tetraethylammonium, and IKCa was sensitive to a specific blocker, iberiotoxin. Ito was inhibited by 4-aminopyridine. Another type of inward rectifier K+ current (Kir) was also detected in approximately 5% of hUC-MSCs. Elevation of external potassium ion concentration increased the Kir current amplitude and positively shifted its reversal potential. In addition, inward Na+ current (INa) was found in these cells (∼30%); the current was blocked by tetrodotoxin and verapamil. In the RT-PCR analysis, Kv1.1, Kv4.2, Kv1.4, Kir2.1, heag1, MaxiK, hNE-Na, and TWIK-1 were detected. These results suggested that multiple functional ion channel currents, IKCa, IKDR, Ito, INa, and Kir, are expressed in hUC-MSCs.
Disclosure of potential conflicts of interest is found at the end of this article.
Massive Weight Loss Decreases Corticosteroid-Binding Globulin Levels and Increases Free Cortisol in Healthy Obese Patients
Authors: Manco Melania , Fernández-Real José M. , Valera-Mora Maria E. , Déchaud Henri , Nanni Giuseppe , Tondolo Vincenzo , Calvani Menotti , Castagneto Marco , Pugeat Michel , Mingrone Geltrude 
Published: May 2007

OBJECTIVE—Obesity, insulin resistance, and weight loss have been associated with changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data relating to this association are available. In this study, we aim to investigate the effects of massive weight loss on cortisol suppressibility, cortisol-binding globulin (CBG), and free cortisol index (FCI) in formerly obese women.
RESEARCH DESIGN AND METHODS—Ten glucose-normotolerant, fertile, obese women (BMI &gt;40 kg/m2, aged 38.66 ± 13.35 years) were studied before and 2 years after biliopancreatic diversion (BPD) when stable weight was achieved and were compared with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic-hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide deconvolution method.
RESULTS—No difference was found in cortisol suppression after DEX-ST before or after weight loss. A decrease in ACTH was significantly greater in control subjects than in obese (P = 0.05) and postobese women (P ≤ 0.01) as was the decrease in dehydroepiandrosterone (P ≤ 0.05 and P ≤ 0.01, respectively). CBG decreased from 51.50 ± 12.76 to 34.33 ± 7.24 mg/l (P ≤ 0.01) following BPD. FCI increased from 11.15 ± 2.85 to 18.16 ± 6.82 (P ≤ 0.05). Insulin secretion decreased (52.04 ± 16.71 vs. 30.62 ± 16.32 nmol/m−2; P ≤ 0.05), and insulin sensitivity increased by 163% (P ≤ 0.0001). Serum CBG was related to BMI (r0 = 0.708; P = 0.0001), body weight (r0 = 0.643; P = 0.0001), body fat percent (r0 = 0.462; P = 0.001), C-reactive protein (r0 = 0.619; P = 0.004), and leptin (r0 = 0.579; P = 0.007) and negatively to M value (r0 = −0.603; P = 0.005).
CONCLUSIONS—After massive weight loss in morbidly obese subjects, an increase of free cortisol was associated with a simultaneous decrease in CBG levels, which might be an adaptive phenomenon relating to environmental changes. This topic, not addressed before, adds new insight into the complex mechanisms linking HPA activity to obesity.
Orange Juice or Fructose Intake Does Not Induce Oxidative and Inflammatory Response
Authors: Ghanim Husam , Mohanty Priya , Pathak Ram , Chaudhuri Ajay , Sia Chang Ling , Dandona Paresh 
Published: May 2007

OBJECTIVE—We have previously shown that 300 kcal from glucose intake induces a significant increase in reactive oxygen species (ROS) generation and nuclear factor-κB (NF-κB) binding in the circulating mononuclear cells in healthy normal subjects. We hypothesized that the intake of 300 calories as orange juice or fructose, the other major carbohydrate in orange juice, would induce a significantly smaller response than that of glucose.
RESEARCH DESIGN AND METHODS— Four groups (eight subjects each) of normal-weight subjects were given a 300-cal drink of glucose (75 g), fructose (75 g), or orange juice or water sweetened with saccharin (control group) to drink, and then blood samples were collected.
RESULTS—There was a significant increase in ROS generation by mononuclear cells (by 130 ± 18%, P &lt; 0.001), polymorph nuclear cells (by 95 ± 22%, P &lt; 0.01), and in NF-κB binding in mononuclear cells by 82 ± 16% (P &lt; 0.01) over the baseline after 2 h of glucose intake. These changes were absent following fructose, orange juice, or water intake. There was significantly lower ROS generation and NF-κB binding following orange juice, fructose, and water compared with glucose (P &lt; 0.001 for all). Furthermore, incubation of mononuclear cells in vitro with 50 mmol/l of the flavonoids hesperetin or naringenin reduced ROS generation by 52 ± 7% and 77 ± 8% (P &lt; 0.01), respectively, while fructose or ascorbic acid did not cause any change.
CONCLUSIONS—Caloric intake in the form of orange juice or fructose does not induce either oxidative or inflammatory stress, possibly due to its flavonoids content and might, therefore, represent a potentially safe energy source.
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Topiramate Controlled Release in the Treatment of Obese Type 2 Diabetic Patients
Authors: Rosenstock Julio , Hollander Priscilla , Gadde Kishore M. , Sun Xiang , Strauss Richard , Leung Albert ,   for the OBD-202 Study Group
Published: May 2007

OBJECTIVE—This is a randomized, placebo-controlled study of the weight-loss efficacy and safety of a controlled-release (CR) formulation of topiramate in overweight and obese patients with type 2 diabetes treated with diet and exercise alone or in combination with metformin.
RESEARCH DESIGN AND METHODS—Patients with type 2 diabetes, BMI ≥27 kg/m2, A1C &gt;6.5 and &lt;11.0%, treated with diet and exercise alone or in combination with metformin monotherapy were enrolled. Patients were randomized to placebo or topiramate CR titrated up to 175 mg/day. Treatment consisted of a 7-week titration phase followed by a 9-week maintenance phase.
RESULTS—A total of 111 subjects were randomized and analyzed. By the end of week 16, patients in the placebo and topiramate groups lost 2.5 and 6.0 kg, which represented 2.3 and 5.8%, respectively, of their baseline body weight (P &lt; 0.001 vs. placebo). A1C improved from a baseline of 7.4% in the placebo and 7.6% in the topiramate groups to 7.1 and 6.7%, respectively, representing a 0.4 and 0.9% reduction from baseline, respectively (P &lt; 0.001 vs. placebo). Topiramate also significantly reduced blood pressure and urinary albumin excretion. Adverse events were predominantly neuropsychiatric or central and peripheral nervous system related.
CONCLUSIONS—Topiramate CR treatment produced significant weight loss and meaningful improvements in A1C and blood pressure in obese patients with type 2 diabetes treated with diet and exercise or in combination with metformin. However, the central nervous system and psychiatric adverse event profile of topiramate CR makes it unsuitable for the treatment of obesity and diabetes.
Strong Association Between Time Watching Television and Blood Glucose Control in Children and Adolescents With Type 1 Diabetes
Authors: Margeirsdottir Hanna D. , Larsen Jakob R. , Brunborg Cathrine , Sandvik Leiv , Dahl-Jørgensen Knut ,   for the Norwegian Study Group for Childhood Diabetes
Published: May 2007

OBJECTIVE—To examine the relationship between blood glucose control and the time spent watching television in Norwegian children and adolescents with type 1 diabetes in a population-based study.
RESEARCH DESIGN AND METHODS—A total of 538 children and adolescents from 9 hospitals in the eastern part of Norway participated in the study; 70% of eligible subjects participated. The time spent watching television and time using a computer was recorded separately by interview together with clinical data. Mean (±SD) age was 13.1 ± 3.7 years, mean diabetes duration was 5.4 ± 3.4 years, and mean A1C was 8.6 ± 1.3% (reference range 4.1–6.4).
RESULTS—Sixty-two patients (11%) watched television &lt;1 h daily (mean A1C 8.2 ± 0.9%), 189 patients (35%) watched television between 1 and 2 h daily (8.4 ± 1.2%), 166 patients (31%) watched television 2–3 h daily (8.7 ± 1.4%), 75 patients (14%) watched television 3–4 h daily (8.8 ± 1.2%), and 46 patients (9%) watched television ≥4 h daily (9.5 ± 1.6%). This trend was highly significant (P &lt; 0.001). The association between television viewing and A1C remained significant, even after adjusting for age and BMI and insulin dose. No correlation between A1C and the use of a personal computer was observed.
CONCLUSIONS—Extensive television watching is associated with poor blood glucose control in children and adolescents with type 1 diabetes.
Short-Term Weight Change and the Incidence of Diabetes in Midlife
Authors: Mishra Gita D. , Carrigan Gretchen , Brown Wendy J. , Barnett Adrian G. , Dobson Annette J. 
Published: May 2007

OBJECTIVE—Although there is consensus that excess adiposity is strongly associated with type 2 diabetes, its relationship with weight change is less clear. This study investigates the relative impact of BMI at baseline and short-term (2- or 3-year) weight changes on the incidence of diabetes.
RESEARCH DESIGN AND METHODS—Prospective data were collected from a population-based cohort of middle-aged women participating in the Australian Longitudinal Study on Women's Health (n = 7,239 for this report). To date, participants have completed four mailed surveys (S1, 1996; S2, 1998; S3, 2001; and S4, 2004). Generalized estimating equations were used to model binary repeated-measures data to assess the impact of BMI at S1 and weight change (S1 to S2; S2 to S3) on 3-year incidence of diabetes at S3 and S4, respectively, adjusting for sociodemographic and lifestyle factors.
RESULTS—BMI at S1 was strongly associated with the development of diabetes by S3 or S4. Compared with women who had a BMI &lt;25 kg/m2, those with BMI ≥25 kg/m2 had higher incidence of diabetes (P &lt; 0.0001), with odd ratios reaching 12.1 (95% CI 7.6–19.3) for women in the very obese group (BMI ≥35 kg/m2). There was no association between shorter-term weight gain or weight loss on first-reported diagnosis of diabetes (P = 0.08).
CONCLUSIONS—Because women's risk of developing type 2 diabetes in midlife is more closely related to their initial BMI (when aged 45–50 years) than to subsequent short-term weight change, public health initiatives should target the prevention of weight gain before and during early adulthood.
Diabetes Care in Extended-Care Facilities
Authors: Holt Rachel M. , Schwartz Frank L. , Shubrook Jay H. 
Published: May 2007

OBJECTIVE—The American Diabetes Association (ADA) does not recognize different treatment goals for the institutionalized adult compared with the outpatient adult with diabetes, nor has it outlined specific recommendations for this population. The purpose of this study was to examine physician management of patients with type 1 and type 2 diabetes residing in extended-care facilities and to compare this management with ADA standards of care for the outpatient adult.RESEARCH DESIGN AND METHODS—This retrospective chart review included data from 108 residents with type 1 or type 2 diabetes at 11 extended health care facilities in the Midwestern U.S. and included a review of the medical problem list, medication list, laboratory reports, and all physician and consultation notes during the study period.RESULTS—Blood glucose was monitored in 98% of the subjects, and 38% met glucose goals. A1C goal was achieved in 67% of patients. Blood pressure was monitored in 94% of patients, with 55% meeting goal. Thirty-one percent of patients had yearly lipids checked, 37% had annual electrocardiograms, 7% had urine analyzed for microalbuminuria, 42% were on aspirin, 87% received foot exams, 42% received dilated eye exams, 89% received influenza vaccinations, and 46% received pneumoccocal vaccinations.CONCLUSIONS—Care of the institutionalized elderly with diabetes fails to meet ADA standards of care for the outpatient adult. Separate practice guidelines are needed for people with diabetes who reside in extended care facilities in order to improve quality and consistency of care.
How Doctors Choose Medications to Treat Type 2 Diabetes
Authors: Grant Richard W. , Wexler Deborah J. , Watson Alice J. , Lester William T. , Cagliero Enrico , Campbell Eric G. , Nathan David M. 
Published: May 2007

OBJECTIVE—Glycemic control remains suboptimal despite the wide range of available medications. More effective medication prescription might result in better control. However, the process by which physicians choose glucose-lowering medicines is poorly understood. We sought to study the means by which physicians choose medications for type 2 diabetic patients.
RESEARCH DESIGN AND METHODS—We surveyed 886 physician members of either the Society of General Internal Medicine (academic generalists, response rate 30%) or the American Diabetes Association (specialists, response rate 23%) currently managing patients with type 2 diabetes. Respondents weighed the importance of 15 patient, physician, and nonclinical factors when deciding which medications to prescribe for type 2 diabetic subjects at each of three management stages (initiation, use of second-line oral agents, and insulin).
RESULTS—Respondents reported using a median of five major considerations (interquartile range 4–6) at each stage. Frequently cited major considerations included overall assessment of the patient's health/comorbidity, A1C level, and patient's adherence behavior but not expert guidelines/hospital algorithms or patient age. For insulin initiation, academic generalists placed greater emphasis on patient adherence (76 vs. 60% of specialists, P &lt; 0.001). These generalists also identified patient fear of injections (68%) and patient desire to prolong noninsulin therapy (68%) as major insulin barriers. Overall, qualitative factors (e.g., adherence, motivation, overall health assessment) were somewhat more highly considered than quantitative factors (e.g., A1C, age, weight) with mean aggregate scores of 7.3 vs. 6.9 on a scale of 0–10, P &lt; 0.001.
CONCLUSIONS—The physicians in our survey considered a wide range of qualitative and quantitative factors when making medication choices for hyperglycemia management. The apparent complexity of the medication choice process contrasts with current evidence-based treatment guidelines.
Relationship of Physician Volume With Process Measures and Outcomes in Diabetes
Authors: Turchin Alexander , Shubina Maria , Pendergrass Merri L. 
Published: May 2007

OBJECTIVE—The volume of patients cared for by an individual physician (physician volume) has been linked to improved outcomes for a number of conditions. It is not known whether a similar association exists for treatment of diabetes. In this study we aimed to determine whether physician volume is associated with improved process measures and outcomes in diabetes care.
RESEARCH DESIGN AND METHODS—This retrospective cohort study analyzed electronic medical records data for 7,120 patients with diabetes treated by 368 primary care physicians at practices affiliated with two large academic hospitals. The associations between physician volume of diabetic patients (diabetes volume) and annual A1C and LDL testing, as well as blood pressure, A1C, and LDL levels, were evaluated.
RESULTS—In multivariable analysis, absolute diabetes volume was linked to decreased odds of A1C testing (4% less for each additional patient seen; P = 0.05), and relative diabetes volume (fraction of the total patients seen who had diabetes) was associated with decreased odds of both A1C (25% less for every 10% increase in the number of diabetic patients seen annually; P = 0.03) and LDL testing (20% less for every 10% increase in the number of diabetic patients; P &lt; 0.001). Physician volume was not significantly associated with the odds of blood pressure, A1C, or LDL control at the end of the study.
CONCLUSIONS—Higher physician volume in care of diabetic patients is associated with decreased adherence to surveillance guidelines and no measurable difference in treatment outcomes.