bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Network Branching in Eliciting Differential Short‐Term Signaling Responses in the Hypersensitive Epidermal Growth Factor Receptor Mutants Implicated in Lung Cancer
Authors: Purvis Jeremy , Ilango Vibitha , Radhakrishnan Ravi 
Published: April 2008

AbstractWe study the effects of EGFR inhibition in wild‐type and mutant cell lines upon tyrosine kinase inhibitor TKI treatment through a systems level deterministic and spatially homogeneous model to help characterize the hypersensitive response of the cancer cell lines harboring constitutively active mutant kinases to inhibitor treatment. By introducing a molecularly resolved branched network systems model (the molecular resolution is introduced for EGFR reactions and interactions in order to distinguish differences in activation between wild‐type and mutants), we are able to quantify differences in (1) short‐term signaling in downstream ERK and Akt activation, (2) the changes in the cellular inhibition EC50 associated with receptor phosphorylation (i.e., 50% inhibition of receptor phosphorylation in the cellular context), and (3) EC50 for the inhibition of activated downstream markers ERK‐(p) and Akt‐(p), where (p) denotes phosphorylated, upon treatment with the inhibitors in cell lines carrying both wild‐type and mutant forms of the receptor. Using the branched signaling model, we illustrate a possible mechanism for preferential Akt activation in the cell lines harboring the oncogenic mutants of EGFR implicated in non‐small‐cell lung cancer and the enhanced efficacy of the inhibitor erlotinib especially in ablating the cellular Akt‐(p) response. Using a simple phenomenological model to describe the effect of Akt activation on cellular decisions, we discuss how this preferential Akt activation is conducive to cellular oncogene addiction and how its disruption can lead to dramatic apoptotic response and hence remarkable inhibitor efficacies. We also identify key network nodes of our branched signaling model through sensitivity analysis as those rendering the network hypersensitive to enhanced ERK‐(p) and Akt‐(p); intriguingly, the identified nodes have a strong correlation with species implicated in oncogenic transformations in human cancers as well as in drug resistance mechanisms identified for the inhibitors in non‐small‐cell lung cancer therapy.
Effects of Obesity Phenotype on Coronary Heart Disease Risk Factors in Response to Weight Loss
Authors: Okura Tomohiro , Tanaka Kiyoji , Nakanishi Tomoko , Lee Dong Jun , Nakata Yoshio , Wee Seung Wan , Shimokata Hiroshi 
Published: April 2008

AbstractObjective: To determine whether there is a difference in risk‐factor improvement for coronary heart disease (CHD) between the intra‐abdominal fat (IF) and subcutaneous fat (SF) obesity phenotypes after weight loss.Research Methods and Procedures: Subjects included 55 mildly obese women (body mass index, 25 to 36 kg/m2; age range, 34 to 63 years) who had at least two of three CHD risk factors [systolic blood pressure (SBP), >140 mm Hg; total cholesterol (TC), >220 mg/dL; fasting plasma glucose, >110 mg/dL). Using computed tomography, IF obesity was classified as ≥110 cm2 of the IF area measured; subjects with <110 cm2 were classified as having SF obesity. The IF and SF obesity groups were divided into diet‐only and diet‐plus‐exercise groups. Assays and measurements were performed before and after a 14‐week (98‐day) intervention.Results: Weight was reduced by 7 to 10 kg in each group. The IF and SF areas, SBP, diastolic blood pressure, TC, and low‐density lipoprotein‐cholesterol were significantly reduced in all groups (p < 0.01). Reduction in IF area was greater in IF obesity than in SF obesity, whereas no differences were observed in the improvement of CHD risk factors. Sample sizes needed for observing a significant difference for SBP, TC, triglycerides, and fasting plasma glucose were greater than the number of subjects in this study.Discussion: Our results suggest that the influence of the obesity phenotype on improving CHD risk factors is not apparent. A larger study is needed to prove the validity of this finding.
Preferential Stimulation of Abdominal Subcutaneous Lipolysis after Prednisolone Exposure in Humans
Authors: Gravholt Claus Højbjerg , Dall Rolf , Christiansen Jens Sandahl , Møller Niels , Schmitz Ole 
Published: April 2008

AbstractObjective: The role of cortisol in the regulation of lipolysis is not clear. This study was undertaken to explore whether a standard dose of prednisolone for 1 week would influence lipolysis in abdominal and femoral tissue.Research Methods and Procedures: We used the microdialysis technique, the forearm technique, and indirect calorimetry, in the fasting state, after 1 week of treatment with prednisolone (30 mg daily) or placebo. Eight healthy young men (age: 25 ± 3 years; height: 181 ± 1 cm; body mass index [BMI]: 23.3 ± 0.7 kg/m2) were studied.Results: Treatment with prednisolone induced insulin resistance (Homeostasis Model Assessment index: placebo vs. prednisolone: 7.15 ± 1.63 vs. 17.00 ± 14.26, p = 0.03), hyperinsulinemia (p = 0.01), and hyperglucagonemia (p = 0.001), whereas growth hormone concentrations were unaffected. Abdominal adipose tissue interstitial glycerol was increased during treatment with prednisolone in the face of significant hyperinsulinemia, although it barely reached statistical significance (p = 0.06). At the femoral adipose tissue depot, no difference in lipolysis was found. Arterial and venous free fatty acids (FFA) were comparable in the two situations, whereas the arteriovenous difference across the forearm was significantly decreased during treatment with prednisolone, indicating increased uptake, or decreased release of FFA. Energy expenditure (p = 0.3), repiratory quotient (p = 0.9), glucose oxidation (p = 0.9), lipid oxidation (p = 1.0), and protein oxidation (p = 0.1) were unaltered on the 2 study days.Discussion: Short‐term treatment with a standard dose of corticosteroids induces increased abdominal adipose tissue lipolysis, as well as hyperinsulinemia, hyperglucagonemia, and insulin resistance.
Predicting Incident Diabetes in Jamaica: The Role of Anthropometry
Authors: Sargeant Lincoln A. , Bennett Franklyn I. , Forrester Terrence E. , Cooper Richard S. , Wilks Rainford J. 
Published: April 2008

AbstractObjective: To evaluate the performance of the body mass index (BMI), waist circumference, waist‐to‐hip ratio (WHR), and waist‐to‐height ratio (WHTR) in predicting incident diabetes in Jamaica.Research Methods and Procedures: A cohort of 728 nondiabetic adults (290 men and 438 women), ages 25 to 74 years and residents of Spanish Town, Jamaica, were followed for a mean of 4 years. Participants had fasting and 2‐hour postchallenge glucose concentrations measured at baseline and follow‐up.Results: There were 51 cases of incident diabetes (17 men and 34 women). All indices were independent predictors of diabetes, and none was clearly superior. The area under the receiver operating characteristics curves (95% confidence interval) for BMI was 0.74 (0.59 to 0.88) for men and 0.62 (0.51 to 0.72) for women. For waist circumference, these values were 0.78 (0.65 to 0.91) in men and 0.61 (0.50 to 0.71) in women. Similar results were obtained for WHR and WHTR. “Optimal” cut‐off points for BMI were 24.8 kg/m2 (men) and 29.3 kg/m2 (women). For waist circumference, these were 88 cm and 84.5 cm for men and women, respectively. Corresponding values for WHR were 0.87 and 0.80 and for WHTR were 0.51 and 0.54, respectively.Discussion: Cut‐off points for waist circumference and WHR were similar to those proposed in developed countries for women but lower in men. Waist circumference could be useful in health promotion as an alternative to BMI.
Obesity Affects Nursing‐Care Facility Admission among Whites but Not Blacks
Authors: Zizza Claire A. , Herring Amy , Stevens June , Popkin Barry M. 
Published: April 2008

AbstractObjective:This study examines whether obese individuals have a greater rate of nursing care facility admission than normal weight individuals.Research Methods and Procedures:Data from the National Health and Nutrition Examination Survey Epidemiological Follow‐up Survey were analyzed. Cox proportional hazards models were used to examine the relationship between baseline weight status and subsequent time to first nursing home admission while adjusting for sex, age, race, marital status, height, presence of children, smoking status, education, region, urban residence, income, and physical activity.Results:Of 5960 adults 45 to 74 years old, 989 individuals were admitted to a nursing care facility over the subsequent 20 years. Body mass index (BMI) was studied using five categories: < 18.5, 18.5 to <25, 25.0 to <30, 30.0 to <35, ≥35 kg/m2. The effects of BMI differed by race: compared with those with a BMI of 18.5 to < 25 kg/m2, adults with a BMI ≥30 kg/m2or a BMI <18.5 kg/m2had a greater rate of nursing home admission in whites, whereas no relationship was found in blacks. The inclusion of time to death with nursing home admission as a joint outcome yielded similar results.Discussion:The large increase in the prevalence of obesity coupled with the rapid expansion of the number of older Americans will likely increase the demand for nursing facility use. More research is needed to understand differences in factors related to nursing home admission among ethnic groups.
Immunomanipulation of Appetite and Body Temperature through the Functional Mimicry of Leptin
Authors: de Fanti Brant A. , Milagro Fermin I. , Lamas Oscar , Martínez‐Ansó Eduardo , Martínez J. Alfredo 
Published: April 2008

AbstractObjective: Although current obesity therapies produce some benefits, there is a need for new strategies to treat obesity. A novel proposal is the use of anti‐idiotypic antibodies as surrogate ligands or hormones. These anti‐idiotypic antibodies carry an internal motif that imitates or mimics an epitope in the antigen (i.e., hormone or ligand). Thus, anti‐idiotypic antibodies to several ligands may mimic them in transducing signals when binding to their receptors.Research Methods and Procedures: We developed an anti‐idiotypic polyclonal antibody against the region of a leptin monoclonal antibody that competitively binds leptin, mimicking the active site structure of leptin. To test whether our anti‐idiotype could also reproduce leptin functions, we examined food intake, body weight, and colonic temperature in male Wistar rats (n = 9) in response to intracerebroventricular administration of the leptin anti‐idiotype.Results: Our leptin anti‐idiotype induced a significant reduction in food intake coupled with an increase in body temperature comparable to that of leptin. That is, the intracerebroventricular administration of 8.0 μg of leptin anti‐idiotype or 5.0 μg leptin significantly increased colonic temperature (Δ 1.9 ± 0.11 °C and Δ1.7 ± 0.12 °C, respectively). In addition, both decreased 24‐hour food intake (−26.4 ± 2.4% and −21.9 ± 2.2%) compared with the control. The gain in body weight was also decreased by acute administration of the anti‐idiotype (−1.4 ± 0.28%) and leptin (−1.1 ± 0.17%) vs. the phosphate‐buffered saline control (1.3 ± 0.15%).Discussion: These studies revealed that the leptin anti‐idiotype inhibited food intake and enhanced heat production, mimicking leptin's central actions.
Effect of Postpartum Exercise on Mothers and their Offspring: A Review of the Literature
Authors: Larson‐Meyer Dawnine Enette 
Published: April 2008

AbstractEpidemiological studies suggest that childbearing may contribute to the development of obesity. In the past 12 years, several cross‐sectional and randomized trials have addressed the effect of postpartum exercise on weight loss and/or energy balance in mostly lactating women. These studies suggest that moderate exercise without specific calorie restriction does not promote greater weight or fat loss. This may be because exercise may promote greater energy intake and/or reduced energy expenditure from nonexercise physical activity (thus preventing negative energy balance), but further research is needed. Regular exercise, however, is likely to have other important health benefits after childbirth. A few published studies suggest that postpartum exercise improves aerobic fitness, high‐density lipoprotein‐cholesterol levels, and insulin sensitivity. Exercise may also enhance psychological well‐being, but controlled clinical studies are needed. Although two published studies have addressed whether exercise training attenuates lactation‐induced bone loss, better controlled studies are needed to determine whether postpartum weight‐bearing exercise can improve bone mineral density in lactating and nonlactating women alike. In lactating women, several studies have collectively determined that neither acute nor regular exercise has adverse effects on a mother's ability to successfully breast‐feed. It needs to be determined whether a woman's participation in regular exercise after childbirth will improve her ability to mother or instill lifetime habits of regular physical activity in either herself or her offspring. Overall, published studies have established the importance of regular exercise during the postpartum period. More research, however, is needed in this important area.
Liver‐Fat Accumulation and Insulin Resistance in Obese Women with Previous Gestational Diabetes
Authors: Tiikkainen Mirja , Tamminen Marjo , Häkkinen Anna‐Maija , Bergholm Robert , Vehkavaara Satu , Halavaara Juha , Teramo Kari , Rissanen Aila , Yki‐Järvinen Hannele 
Published: April 2008

AbstractObjective:We determined whether fat accumulation in the liver is associated with features of insulin resistance independent of obesity.Research Methods and Procedures:We recruited 27 obese nondiabetic women in whom liver fat (LFAT) content was determined by proton spectroscopy, intra‐abdominal and subcutaneous fat by magnetic resonance imaging, and insulin sensitivity by the euglycemic insulin clamp technique. The women were divided based on their median LFAT content (5%) to groups with low (3.2 ± 0.3%) and high (9.8 ± 1.5%) liver fat. The groups were almost identical with respect to age (36 ± 1 vs. 38 ± 1 years in low vs. high‐LFAT), body mass index (32.2 ± 0.6 vs. 32.8 ± 0.5 kg/m2), waist‐to‐hip ratio, intra‐abdominal, subcutaneous, and total fat content.Results:Women with high LFAT had features of insulin resistance including higher fasting serum triglyceride (1.93 ± 0.21 vs. 1.11 ± 0.09 mM,p< 0.01) and insulin (14 ± 3 vs. 10 ± 1 mU/L,p< 0.05) concentrations than women with low LFAT. The group with high LFAT also had higher 24‐hour blood pressures, and lower whole‐body insulin sensitivity compared with the low‐LFAT group.Discussion:In obese women with previous gestational diabetes, LFAT, rather than any measure of body composition, is associated with features of insulin resistance.
Lipid Profile in the Severely Obese: Changes with Weight Loss after Lap‐Band Surgery
Authors: Dixon John B. , O'Brien Paul E. 
Published: April 2008

AbstractObjective: To characterize dyslipidemia before and after weight loss in the severely obese.Research Methods and Procedures: Five hundred fifteen subjects who had Lap‐Band surgery were followed with yearly conventional lipid profiles for up to 4 years. Preoperative data were collected from the most recent 381 subjects, and predictors of dyslipidemia were sought. One hundred seventy‐one subjects completed a 1‐year review, providing data to assess predictors of change in lipids.Results: Favorable changes in fasting triglycerides (TG), high‐density lipoprotein‐cholesterol (HDL‐C), and total cholesterol (TC):HDL‐C ratio occurred within 1 year. All improvements were maintained up to 4 years. Male gender, central obesity, elevated fasting glucose, and insulin resistance were associated with less favorable lipid levels. Fasting plasma glucose best predicted TG (r = 0.46, p < 0.001), whereas insulin sensitivity using the homeostatic model assessment (HOMA %S) correlated best with the HDL‐C (r =0.34, p < 0.001). Higher preoperative fasting glucose best predicted the decrease in TG; improved HOMA %S with weight loss correlated best with HDL‐C. The extent of weight loss had limited influence on lipid changes. However, low preoperative HOMA %S was associated with lower weight loss. Greater weight loss was associated with more favorable lipid measures after controlling for preoperative HOMA %S.Discussion: Dyslipidemia of obesity is related to weight distribution, insulin sensitivity, and impaired glucose tolerance. Improvement with weight loss is related to the decrease in fasting glucose, improvement in insulin sensitivity, and the extent of weight lost. Improvement in dyslipidemia is sustained with long‐term weight loss.
Human Leptin Stimulates Systemic Nitric Oxide Production in the Rat
Authors: Beltowski Jerzy , Wójcicka Grażyna , Borkowska Ewa 
Published: April 2008

AbstractObjective:Apart from having an effect on energy balance, leptin is also involved in cardiovascular regulation and in the pathogenesis of obesity‐associated hypertension. We investigated the effect of leptin on nitric oxide (NO) production.Research Methods and Procedures:Wistar rats were placed in metabolic cages, and urine was collected in 2‐hour periods. After the control period, leptin (1 mg/kg intraperitoneal) was administered, and urine collection was continued for up to 6 hours. Blood was obtained 0.5, 1, 2, 4, and 6 hours after hormone injection.Results:Leptin increased plasma concentrations of NO metabolites (nitrates + nitrites, NOx) by 32.5%, 58.0%, and 29.7% at 1, 2, and 4 hours, respectively. Urinary NOxexcretion increased by 28.8% in the first and by 20.1% in the second 2‐hour period after injection. The plasma concentration of the NO second messenger, cyclic guanosine 3′,5′‐monophosphate (cGMP), increased by 83% and 50.6% at 2 and 4 hours after leptin administration, respectively. Urinary excretion of cyclic GMP increased by 36.1% in the first and by 43.1% in the second 2‐hour period. Leptin had no effect on the plasma concentration of atrial natriuretic peptide (ANP). The effect of leptin on plasma and urinary NOxwas abolished by the NO synthase inhibitor,NG‐nitro‐l‐arginine methyl ester (l‐NAME) (30 mg/kg intraperitoneal) administered 15 minutes before leptin injection.l‐NAME alone caused a 32.2% increase in systolic blood pressure, but this increase was not observed in rats receivingl‐NAME and leptin.Discussion:The results indicate that leptin stimulates systemic NO production; leptin prevents blood pressure elevation induced by acute NO blockade, suggesting that leptin also triggers additional hypotensive mechanisms; and ANP is not involved in renal and vascular effects of leptin.
Dietary Weight Loss Decreases Serum Angiotensin‐Converting Enzyme Activity in Obese Adults
Authors: Harp Joyce B. , Henry Steven A. , DiGirolamo Mario 
Published: April 2008

AbstractObjective: To study the effect of dietary weight loss, postural change, and an oral glucose load on serum angiotensin‐converting enzyme (ACE) activity in obese adults.Research Methods and Procedures: Sixteen obese adult men and women with a mean body mass index of 35.7 ± 4.3 kg/m2 were studied after 1 week on a maintenance energy lead‐in diet and after 5 weeks on an identical but 40% reduced‐energy diet provided by the General Clinical Research Center (GCRC). ACE activity was measured spectrophotometrically. Plasma renin activity and serum aldosterone were measured by radioimmunoassay.Results: All subjects lost weight, with a mean decrease in body weight of 7.0 ± 2.1 kg or 6 ± 3% of initial body weight (p < 0.00001). Systolic and diastolic blood pressure, supine plasma renin activity, and serum aldosterone levels decreased with weight loss (p < 0.05). Supine ACE activity decreased 23 ± 12% with weight loss (p < 0.00001). Standing ACE activity, which was significantly higher than supine ACE activity before and after weight loss (p < 0.05), also decreased 18 ± 17% with weight loss (p = 0.0007). A 75‐g oral glucose load had no effect on serum ACE activity over a 3‐hour period.Discussion: In obese adults, serum ACE activity declines with modest weight loss, increases with postural change, and is unaffected by an oral glucose load.
Hypophysectomy Prevents Ghrelin‐Induced Adiposity and Increases Gastric Ghrelin Secretion in Rats
Authors: Tschöp Matthias , Flora David B. , Mayer John P. , Heiman Mark L. 
Published: April 2008

AbstractObjective: The novel gastric hormone ghrelin has recently been identified as an important modulator of energy homeostasis. Leptin‐responsive hypothalamic neuropeptide Y/Agouti‐related protein neurons are believed to mediate afferent ghrelin signals. Little is known, however, about ghrelin‐induced efferent signals. We therefore investigated if hypothalamic‐pituitary axes have a role in transferring ghrelin‐induced changes of energy balance to the periphery.Research Methods and Procedures: We subcutaneously injected hypophysectomized, as well as adrenalectomized, thyroidectomized, and sham‐operated control rats with GH secretagogues [ghrelin, growth hormone (GH)‐releasing peptide] for 1 week. Body weight, food intake, and body composition (chemical carcass analysis) were analyzed and compared with vehicle‐treated controls. In addition, we quantified circulating levels of endogenous ghrelin in hypophysectomized and GH–treated normal rats.Results: GH‐secretagogue treatment of sham‐operated control rats dose‐proportionally increased food intake, body weight, and fat mass compared with vehicle‐injected controls (p < 0.01). These effects, however, were not observed in ghrelin‐treated hypophysectomized, thyroidectomized, or adrenalectomized rats, indicating an essential role for the pituitary axis in ghrelin‐induced adiposity. Circulating levels of endogenous ghrelin were reduced by administration of GH in normal rats and were about 3‐fold higher in hypophysectomized rats (n = 20, p = 0.001), suggesting a regulatory feedback loop involving the stomach and the pituitary to regulate gastric ghrelin secretion.Discussion: According to these results, the endocrine pituitary is mediating ghrelin‐induced changes toward a positive energy balance and is involved in the regulation of ghrelin secretion through a gastro‐hypophyseal feedback loop.
Binge Size Increases with Body Mass Index in Women with Binge‐Eating Disorder
Authors: Guss Janet L. , Kissileff Harry R. , Devlin Michael J. , Zimmerli Ellen , Walsh B. Timothy 
Published: April 2008

AbstractObjective: To determine whether meal size is related to body mass index (BMI) in obese subjects with binge‐eating disorder (BED).Research Methods and Procedures: Five groups of subjects each consumed two laboratory‐test meals on nonconsecutive days. Forty‐two women, categorized by BMI and BED diagnosis, were instructed to “binge” during one meal and to eat “normally” during another. Eighteen women had BMI values >38 kg/m2 (more‐obese) and 17 had BMI values between 28 to 32 kg/m2 (less‐obese). Twelve of the more‐obese and nine of the less‐obese individuals met Diagnostic and Statistical Manual (DSM)‐IV criteria for BED. Seven normal‐weight women also participated as controls.Results: Subjects with BED ate significantly more in both meals than subjects without BED. Binge meals were significantly larger than normal meals only among subjects with BED. The more‐obese subjects with BED ate significantly more than the less‐obese subjects with BED, but only when they were asked to binge. Intake of the binge meal was significantly, positively correlated with BMI among subjects with BED. Subjects with BED reported significantly higher satiety ratings after the binge than after the normal meal, but subjects without BED reported similar ratings after both meals. Regardless of instructions and diagnosis, obese subjects consumed a significantly higher percentage of energy from fat (38.5%) than did normal‐weight subjects (30.8%).Discussion: During binge meals, the energy intake of subjects with BED is greater than that of individuals of similar body weight without BED and is positively correlated with BMI.