bluuebunny/crossref_metadata_2025_split huggingface dataset:
Observing pretibial myxedema in patients with Graves' disease using digital infrared thermal imaging and high-resolution ultrasonography: for better records, early detection, and further investigation
Authors: Shih Shyang-Rong , Lin Mao-Shin , Li Hung-Yuan , Yang Hsin-Yi , Hsiao Yung-Lien , Chang Met-Ting , Chen Chung-Ming , Chang Tien-Chun 
Published: January 2011

ObjectivePretibial myxedema (PM) is a manifestation of Graves' disease (GD). Currently, its diagnosis depends on physicians' observation and biopsy. No satisfactory, objective, and non-invasive tool is available to record and investigate lesions. Digital infrared thermal imaging (DITI) detects surface temperature, and sonography reflects composition changes in soft tissue. This study was aimed to observe changes in DITI and sonography in PM, and to evaluate their clinical usefulness.MethodsNineteen GD patients with PM, 22 GD patients with mild diffuse non-pitting edema over lower legs, 46 GD patients with normal appearance of lower legs, and 14 normal volunteers were recruited for observation with DITI; 8, 21, 21, and 11 of them respectively also received soft tissue sonography for investigating the pathogenesis of DITI change.ResultsLower leg temperatures of normal volunteers decreased gradually from proximal to distal parts. In all 19 patients with PM, DITI showed abnormally low focal temperatures over the lesions. In GD patients with mild diffuse non-pitting edema and GD patients with normal appearance of lower legs, DITI showed abnormally low focal temperature in 90.9 and 65.2% of the patients respectively. Areas of clinically visible PM and low focal temperature detected by DITI were sonographically characterized with increased skin thickness, hypoechoic substance deposition in the cutaneous tissue, and blurred boundary lines between dermis and subcutaneous tissue. TSH receptor antibody level correlated positively and significantly with skin thickness change and adjusted temperature difference between the center of temperature defect and the surrounding skin (P=0.046 and 0.033 respectively).ConclusionsBy using DITI and sonography, we detected characteristic changes in PM. These techniques are helpful in recording and may be useful tools to detect early changes of PM.
A Comparative Study on the Measurements of Palatal Shelf Area and Gradient for Adult Patients with Unoperated Cleft Palate
Authors: Ye Bin , Ruan Changhu , Hu Jing , Yang Yunqiang , Thomas Jimy , Zhang Guozhi 
Published: January 2011

Objective To determine the maxillary growth potential of cleft palate patients compared with the normal population. Methods By using a three-dimensional computed tomography scanning and imaging system, the gradient and surface area of the palatal shelves were measured and analyzed statistically among 30 adults with normal occlusion, 30 adult patients with operated unilateral complete cleft lip and palate, and 30 adults with unoperated unilateral complete cleft lip and palate. Results In comparison with the control group, for the unoperated unilateral complete cleft lip and palate subjects, the gradient of the palatal shelves at both the cleft and noncleft sides was larger, meaning that the palatal shelves were rotated cranially and were more vertically positioned. The palatal surface area was significantly smaller in the unoperated and operated unilateral complete cleft lip and palate groups than in the noncleft control group; although, there was no significant difference between the unoperated and operated unilateral complete cleft lip and palate groups. Conclusions There is an intrinsic tissue deficiency in the palate/maxilla of unilateral complete cleft lip and palate patients.
Sodium Supplementation in Neonates with Pierre Robin Sequence Significantly Improves Weight Gain if Urinary Sodium is Low
Authors: Skillman J. , Cole A. , Slator R. 
Published: January 2011

Objective To investigate whether sodium supplementation increases weight gain in babies with grade 3 Pierre Robin sequence if their urinary sodium is low. Design Retrospective review of all medical, dietitian, and nursing notes of babies admitted from 2000 to 2007, inclusive. Setting Tertiary center for cleft care. Patients A total of 33 babies requiring nasogastric and nasopharangeal intubation for Pierre Robin sequence were identified. Those for whom weights could not be measured accurately (n = 4) were excluded from further study. Interventions Urinary sodium was low and weight gain poor in 21 of the remaining 29 babies (72%), and oral sodium supplementation was given to establish and maintain a normal urinary sodium (10 to 20 mmol/L). Main Outcome Measure Mean daily weight gain. Results The mean daily weight gain of the 18 babies with low urinary sodium admitted in the first few days of life improved from 20 to 34 g ( p < .001) following oral sodium supplementation. This gave a mean difference of 14 g (lower quartile = 6 g, upper quartile = 25 g, 95% confidence interval = 20, 90% confidence interval = 10). The mean daily weight gain of the eight patients who did not require sodium supplementation was 33.6 g. Conclusions Urinary sodium tests are simple and noninvasive and allow monitoring of urinary sodium. If low, adequate supplementation improved weight gain ( p < .001), reversing failure to thrive in babies with severe Pierre Robin sequence. These findings have been unreported previously.
Does the Breast Cancer Age at Diagnosis Differ by Ethnicity? A Study on Immigrants to Sweden
Authors: Hemminki Kari , Mousavi Seyed Mohsen , Sundquist Jan , Brandt Andreas 
Published: January 2011

Abstract

Background.
Age-specific incidence rates for breast cancer in low-risk and high-risk ethnic populations differ by age at which the incidence maximum is reached: around 50 years in low-risk populations and over 60 years in high-risk populations. The interpretation of these differences remains unsettled, one line primarily referring to biological differences, the second one to cohort effects of rapidly increasing rates in young populations, and the third one to incomplete registration of cancer in the elderly.

Methods.
The nationwide Family-Cancer Database was used to analyze standardized incidence ratios (SIRs) and age at diagnosis of breast cancer in female immigrants to Sweden by their region of origin compared with women native to Sweden matched on birth year and other relevant factors.

Results.
We showed first that the SIRs for breast cancer were lower in many immigrant groups compared with natives of Sweden; women from Turkey had the lowest SIR of 0.45, followed by those from Chile (0.54) and Southeast Asia (0.57). Women from nine regions showed an earlier mean age at diagnosis than their matched Swedish controls, the largest differences being 5.5 years for women from Turkey, 5.1 years for those from Asian Arab and “Other African” countries, 4.3 years for those from Iran, and 4.0 years for those from Iraq.

Conclusions.
The results show that in many immigrant groups, the diagnostic age is earlier (&lt;50 years) than in natives of Sweden (&gt;50 years), suggesting that true biological factors underlie the differences. These factors may explain much of the international variation in breast cancer incidence. Identifying these factors should advance understanding of breast cancer etiology and prevention.
Treatment Outcome and Prognostic Factors for Patients with Bone-Only Metastases of Breast Cancer: A Single-Institution Retrospective Analysis
Authors: Niikura Naoki , Liu Jun , Hayashi Naoki , Palla Shana L. , Tokuda Yutaka , Hortobagyi Gabriel N. , Ueno Naoto T. , Theriault Richard L. 
Published: January 2011

Abstract

Purpose.
Limited information is available about the optimal management and clinical outcome of bone-only metastases in breast cancer patients. The objective of this study was to define prognostic factors for patients with bone-only metastases. Our second objective was to compare progression-free survival (PFS) and overall survival (OS) between patients with hormone receptor (HR)+ tumors and bone-only metastases who received combinatory therapy (chemotherapy followed by endocrine therapy, or endocrine therapy combined with molecular targeted therapy) and those treated with endocrine or chemotherapy alone.

Patients and Methods.
We retrospectively identified 351 breast cancer patients diagnosed with bone-only metastasis in 1997–2008 at our institution.

Results.
Patients with metastasis detected at the time of their primary breast cancer diagnosis (rather than at recurrence), a single metastasis, or asymptomatic bone disease had a longer PFS interval, and patients with a performance status of 0–1, a single metastasis, or asymptomatic bone disease had a longer OS time. Among patients with HR+ human epidermal growth factor receptor (HER)-2− disease, combinatory therapy was associated with longer PFS and OS times than with endocrine therapy. In multivariate analyses, combinatory therapy was not associated with longer PFS or OS times than with endocrine therapy. Among patients with HER-2+ disease, trastuzumab led to a longer PFS interval but no difference in the OS time.

Conclusion.
Our results indicate that, for HR+ disease, a prospective trial of chemotherapy followed by endocrine therapy is warranted to determine whether it prolongs survival more than endocrine therapy alone in patients with bone-only metastases.
Adiponectin Pretreatment Counteracts the Detrimental Effect of a Diabetic Environment on Endothelial Progenitors
Authors: Leicht Simon F. , Schwarz Theresa M. , Hermann Patrick C. , Seissler Jochen , Aicher Alexandra , Heeschen Christopher 
Published: January 2011

OBJECTIVE
It has been shown that vascular progenitors from patients with diabetes are dysfunctional. However, therapeutic strategies to counteract their reduced functional capacity are still lacking. Because adiponectin has reported salutary effects on endothelial function, we investigated the functional effects of globular adiponectin (gAcrp), the active domain of adiponectin, on isolated endothelial colony-forming cells (ECFC).

RESEARCH DESIGN AND METHODS
ECFC were isolated from peripheral blood of type 2 diabetic patients (dmECFC) and compared with ECFC of healthy young volunteers (yECFC) and nondiabetic age-matched control subjects (hECFC). Cells were treated with gAcrp for 48 h followed by assessment of cell counts, cell cycle analysis, and migration capacity. For in vivo evaluation, human ECFC were injected into normoglycemic or streptozotocin-induced hyperglycemic nu/nu mice after hind limb ischemia.

RESULTS
Whereas dmECFC were functionally impaired compared with yECFC and hECFC, gAcrp significantly enhanced their in vitro proliferation and migratory activity. In vitro effects were significantly stronger in hECFC compared with dmECFC and were mediated through the cyclooxygenase-2 pathway. Most important, however, we observed a profound and sustained increase of the in vivo neovascularization in mice receiving gAcrp-pretreated dmECFC compared with untreated dmECFC under both normoglycemic and hyperglycemic conditions.

CONCLUSIONS
Pretreatment of ECFC with gAcrp enhanced the functional capacity of ECFC in vitro and in vivo in normoglycemic and hyperglycemic environments. Therefore, preconditioning of dmECFC with gAcrp may be a novel approach to counteract their functional impairment in diabetes.
The Adipocyte-Expressed Forkhead Transcription Factor Foxc2 Regulates Metabolism Through Altered Mitochondrial Function
Authors: Lidell Martin E. , Seifert Erin L. , Westergren Rickard , Heglind Mikael , Gowing Adrienne , Sukonina Valentina , Arani Zahra , Itkonen Paula , Wallin Simonetta , Westberg Fredrik , Fernandez-Rodriguez Julia , Laakso Markku , Nilsson Tommy , Peng Xiao-Rong , Harper Mary-Ellen , Enerbäck Sven 
Published: January 2011

OBJECTIVE
Previous findings demonstrate that enhanced expression of the forkhead transcription factor Foxc2 in adipose tissue leads to a lean and insulin-sensitive phenotype. These findings prompted us to further investigate the role of Foxc2 in the regulation of genes of fundamental importance for metabolism and mitochondrial function.

RESEARCH DESIGN AND METHODS
The effects of Foxc2 on expression of genes involved in mitochondriogenesis and mitochondrial function were assessed by quantitative real-time PCR. The potential of a direct transcriptional regulation of regulated genes was tested in promoter assays, and mitochondrial morphology was investigated by electron microscopy. Mitochondrial function was tested by measuring oxygen consumption and extracellular acidification rates as well as palmitate oxidation.

RESULTS
Enhanced expression of FOXC2 in adipocytes or in cells with no endogenous Foxc2 expression induces mitochondriogenesis and an elongated mitochondrial morphology. Together with increased aerobic metabolic capacity, increased palmitate oxidation, and upregulation of genes encoding respiratory complexes and of brown fat-related genes, Foxc2 also specifically induces mitochondrial fusion genes in adipocytes. Among tested forkhead genes, Foxc2 is unique in its ability to trans-activate the nuclear-encoded mitochondrial transcription factor A (mtTFA/Tfam) gene—a master regulator of mitochondrial biogenesis. In human adipose tissue the expression levels of mtTFA/Tfam and of fusion genes also correlate with that of Foxc2.

CONCLUSIONS
We previously showed that a high-calorie diet and insulin induce Foxc2 in adipocytes; the current findings identify a previously unknown role for Foxc2 as an important metabo-regulator of mitochondrial morphology and metabolism.
Hepatic Glycogen Supercompensation Activates AMP-Activated Protein Kinase, Impairs Insulin Signaling, and Reduces Glycogen Deposition in the Liver
Authors: Winnick Jason J. , An Zhibo , Ramnanan Christopher J. , Smith Marta , Irimia Jose M. , Neal Doss W. , Moore Mary Courtney , Roach Peter J. , Cherrington Alan D. 
Published: January 2011

OBJECTIVE
The objective of this study was to determine how increasing the hepatic glycogen content would affect the liver’s ability to take up and metabolize glucose.

RESEARCH DESIGN AND METHODS
During the first 4 h of the study, liver glycogen deposition was stimulated by intraportal fructose infusion in the presence of hyperglycemic-normoinsulinemia. This was followed by a 2-h hyperglycemic-normoinsulinemic control period, during which the fructose infusion was stopped, and a 2-h experimental period in which net hepatic glucose uptake (NHGU) and disposition (glycogen, lactate, and CO2) were measured in the absence of fructose but in the presence of a hyperglycemic-hyperinsulinemic challenge including portal vein glucose infusion.

RESULTS
Fructose infusion increased net hepatic glycogen synthesis (0.7 ± 0.5 vs. 6.4 ± 0.4 mg/kg/min; P &lt; 0.001), causing a large difference in hepatic glycogen content (62 ± 9 vs. 100 ± 3 mg/g; P &lt; 0.001). Hepatic glycogen supercompensation (fructose infusion group) did not alter NHGU, but it reduced the percent of NHGU directed to glycogen (79 ± 4 vs. 55 ± 6; P &lt; 0.01) and increased the percent directed to lactate (12 ± 3 vs. 29 ± 5; P = 0.01) and oxidation (9 ± 3 vs. 16 ± 3; P = NS). This change was associated with increased AMP-activated protein kinase phosphorylation, diminished insulin signaling, and a shift in glycogenic enzyme activity toward a state discouraging glycogen accumulation.

CONCLUSIONS
These data indicate that increases in hepatic glycogen can generate a state of hepatic insulin resistance, which is characterized by impaired glycogen synthesis despite preserved NHGU.
Phosphatidylinositol-4-Phosphate-5-Kinase α Deficiency Alters Dynamics of Glucose-Stimulated Insulin Release to Improve Glucohomeostasis and Decrease Obesity in Mice
Authors: Huang Ping , Yeku Oladapo , Zong Haihong , Tsang Phyllis , Su Wenjuan , Yu Xiao , Teng Shuzhi , Osisami Mary , Kanaho Yasunori , Pessin Jeffrey E. , Frohman Michael A. 
Published: January 2011

OBJECTIVE
Phosphatidylinositol-4-phosphate-5-kinase (PI4P5K) has been proposed to facilitate regulated exocytosis and specifically insulin secretion by generating phosphatidylinositol-4,5-bisphosphate (PIP2). We sought to examine the role of the α isoform of PI4P5K in glucohomeostasis and insulin secretion.

RESEARCH DESIGN AND METHODS
The response of PI4P5Kα−/− mice to glucose challenge and a type 2-like diabetes-inducing high-fat diet was examined in vivo. Glucose-stimulated responses and PI4P5Kα−/− pancreatic islets and β-cells were characterized in culture.

RESULTS
We show that PI4P5Kα−/− mice exhibit increased first-phase insulin release and improved glucose clearance, and resist high-fat diet-induced development of type 2-like diabetes and obesity. PI4P5Kα−/− pancreatic islets cultured in vitro exhibited decreased numbers of insulin granules docked at the plasma membrane and released less insulin under quiescent conditions, but then secreted similar amounts of insulin on glucose stimulation. Stimulation-dependent PIP2 depletion occurred on the plasma membrane of the PI4P5Kα−/− pancreatic β-cells, accompanied by a near-total loss of cortical F-actin, which was already decreased in the PI4P5Kα−/− β-cells under resting conditions.

CONCLUSIONS
Our findings suggest that PI4P5Kα plays a complex role in restricting insulin release from pancreatic β-cells through helping to maintain plasma membrane PIP2 levels and integrity of the actin cytoskeleton under both basal and stimulatory conditions. The increased first-phase glucose-stimulated release of insulin observed on the normal diet may underlie the partial protection against the elevated serum glucose and obesity seen in type 2 diabetes-like model systems.
Selective Inactivation of c-Jun NH2-Terminal Kinase in Adipose Tissue Protects Against Diet-Induced Obesity and Improves Insulin Sensitivity in Both Liver and Skeletal Muscle in Mice
Authors: Zhang Xinmei , Xu Aimin , Chung Sookja K. , Cresser Justin H.B. , Sweeney Gary , Wong Rachel L.C. , Lin Anning , Lam Karen S.L. 
Published: January 2011

OBJECTIVE
Obesity is associated with increased activation of the c-Jun NH2-terminal kinase (JNK) in several metabolic organs, including adipose tissue, liver, and skeletal muscle. In this study, we aimed to define the role of JNK activation in adipose tissue in the development of obesity-related insulin resistance.

RESEARCH DESIGN AND METHODS
Transgenic mice with adipose tissue–specific overexpression of dominant-negative JNK (ap2-dn-JNK) under the transcriptional control of the aP2 gene promoter were generated and subjected to metabolic characterization together with the wild-type littermates.

RESULTS
On a high-fat diet (HFD), the ap2-dn-JNK mice displayed a marked suppression of both JNK1 and JNK2 activation in their adipose tissue, accompanied by a marked reduction in weight gain, fat mass, and size of the adipocytes. The transgenic mice were resistant to the deleterious impact of an HFD on systemic insulin sensitivity, glucose tolerance, and hepatic steatosis. Reduced hepatic gluconeogenesis was evident in in vivo and ex vivo studies and showed greater insulin-induced glucose uptake in skeletal muscles. These changes were accompanied by reduced macrophage infiltration in adipose tissue, decreased production of proinflammatory adipokines, and increased expression of adiponectin. Indirect calorimetry analysis showed that the transgenic mice had significant increases in oxygen consumption and reductions in respiration exchange rates compared with their wild-type littermates.

CONCLUSIONS
Selective suppression of JNK activation in adipose tissue alone is sufficient to counteract HFD-induced obesity and its associated metabolic dysregulations, in part through an increase in energy expenditure and a decrease in systemic inflammation.
Differential Lipid Partitioning Between Adipocytes and Tissue Macrophages Modulates Macrophage Lipotoxicity and M2/M1 Polarization in Obese Mice
Authors: Prieur Xavier , Mok Crystal Y.L. , Velagapudi Vidya R. , Núñez Vanessa , Fuentes Lucía , Montaner David , Ishikawa Ko , Camacho Alberto , Barbarroja Nuria , O’Rahilly Stephen , Sethi Jaswinder K. , Dopazo Joaquin , Orešič Matej , Ricote Mercedes , Vidal-Puig Antonio 
Published: January 2011

OBJECTIVE
Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macrophage (ATM) polarization, in the current study we investigated the concept of lipid-induced toxicity as the pathogenic link that could explain the trigger of this response.

RESEARCH DESIGN AND METHODS
We addressed this question using isolated ATMs and adipocytes from genetic and diet-induced murine models of obesity. Through transcriptomic and lipidomic analysis, we created a model integrating transcript and lipid species networks simultaneously occurring in adipocytes and ATMs and their reversibility by thiazolidinedione treatment.

RESULTS
We show that polarization of ATMs is associated with lipid accumulation and the consequent formation of foam cell–like cells in adipose tissue. Our study reveals that early stages of adipose tissue expansion are characterized by M2-polarized ATMs and that progressive lipid accumulation within ATMs heralds the M1 polarization, a macrophage phenotype associated with severe obesity and insulin resistance. Furthermore, rosiglitazone treatment, which promotes redistribution of lipids toward adipocytes and extends the M2 ATM polarization state, prevents the lipid alterations associated with M1 ATM polarization.

CONCLUSIONS
Our data indicate that the M1 ATM polarization in obesity might be a macrophage-specific manifestation of a more general lipotoxic pathogenic mechanism. This indicates that strategies to optimize fat deposition and repartitioning toward adipocytes might improve insulin sensitivity by preventing ATM lipotoxicity and M1 polarization.
Increased Whole-Body and Sustained Liver Cortisol Regeneration by 11β-Hydroxysteroid Dehydrogenase Type 1 in Obese Men With Type 2 Diabetes Provides a Target for Enzyme Inhibition
Authors: Stimson Roland H. , Andrew Ruth , McAvoy Norma C. , Tripathi Dhiraj , Hayes Peter C. , Walker Brian R. 
Published: January 2011

OBJECTIVE
The cortisol-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies glucocorticoid levels in liver and adipose tissue. 11β-HSD1 inhibitors are being developed to treat type 2 diabetes. In obesity, 11β-HSD1 is increased in adipose tissue but decreased in liver. The benefits of pharmacological inhibition may be reduced if hepatic 11β-HSD1 is similarly decreased in obese patients with type 2 diabetes. To examine this, we quantified in vivo whole-body, splanchnic, and hepatic 11β-HSD1 activity in obese type 2 diabetic subjects.

RESEARCH DESIGN AND METHODS
Ten obese men with type 2 diabetes and seven normal-weight control subjects were infused with 9,11,12,12-[2H]4cortisol (40%) and cortisol (60%) at 1.74 mg/h. Adrenal cortisol secretion was suppressed with dexamethasone. Samples were obtained from the hepatic vein and an arterialized hand vein at steady state and after oral administration of cortisone (5 mg) to estimate whole-body and liver 11β-HSD1 activity using tracer dilution.

RESULTS
In obese type 2 diabetic subjects, the appearance rate of 9,12,12-[2H]3cortisol in arterialized blood was increased (35 ± 2 vs. 29 ± 1 nmol/min, P &lt; 0.05), splanchnic 9,12,12-[2H]3cortisol production was not reduced (29 ± 6 vs. 29 ± 6 nmol/min), and cortisol appearance in the hepatic vein after oral cortisone was unchanged.

CONCLUSIONS
Whole-body 11β-HSD1 activity is increased in obese men with type 2 diabetes, whereas liver 11β-HSD1 activity is sustained, unlike in euglycemic obesity. This supports the concept that inhibitors of 11β-HSD1 are likely to be most effective in obese type 2 diabetic subjects.