tbuckley/cabot-search huggingface dataset:
Herceptin Sensitizes ErbB2–Overexpressing Cells to Apoptosis by Reducing Antiapoptotic Mcl-1 Expression
Authors: Elizabeth S. Henson, Xiaojie Hu, Spencer B. Gibson
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Monoclonal antibodies, such as herceptin and trastuzumab, against the epidermal growth factor receptor ErbB2 (also known as HER2/neu) are an effective therapy for breast cancer patients with overexpression of ErbB2. Herceptin, in combination with standard chemotherapy, such as taxol or etoposide, gives a synergistically apoptotic response in breast tumors. Experimental Design: The mechanism underlying this synergy between chemotherapy and herceptin treatment is not well understood. Herein, we have determined that addition of herceptin, sensitized breast cancer cell lines MDA-MB-231 and MCF-7 to etoposide- or taxol-induced apoptosis. Results: This treatment resulted in reduced expression of ErbB2 and the antiapoptotic Bcl-2 family member Mcl-1 in MDA-MB-231 cells. Using antisense oligonucleotides against Mcl-1, MDA-MB-231 cells were rendered sensitive to etoposide-induced apoptosis similar to herceptin, but combined treatment of antisense against Mcl-1 and herceptin failed to give a significant increase in apoptosis. In 29 human breast tumors immunostained for ErbB2 and Mcl-1, we found that when ErbB2 was overexpressed, there was a corresponding increase in Mcl-1 expression. Discussion: Using murine fibroblasts that express human ErbB2, but no other ErbB family member (NE2), these cells showed resistance to both taxol- and etoposide-induced apoptosis compared with parental cells. In addition, NE2 cells preferentially express the antiapoptotic Bcl-2 family member Mcl-1 compared with parental cells, and treatment with herceptin reduces Mcl-1 expression. Taken together, these results suggest that herceptin sensitizes ErbB2-overexpressing cells to apoptosis by reducing antiapoptotic Mcl-1 protein levels.
Perilipin Gene Variation Determines Higher Susceptibility to Insulin Resistance in Asian Women When Consuming a High–Saturated Fat, Low-Carbohydrate Diet
Authors: Dolores Corella, Lu Qi, E. Shyong Tai, Mabel Deurenberg-Yap, Chee Eng Tan, Suok Kai Chew, Jose M. Ordovas
Journal: Diabetes Care (2006)

To investigate the association between genetic variation in the adipocyte protein perilipin (PLIN) and insulin resistance in an Asian population as well as to examine their modulation by macronutrient intake.A nationally representative sample (Chinese, Malays, and Indians) was selected in the Singapore National Health Survey following the World Health Organization-recommended model for field surveys of diabetes. A total of 1,909 men and 2,198 women (aged 18-69 years) were studied. Genetic (PLIN 11482G-->A and 14995A-->T), lifestyle, clinical, and biochemical data were obtained. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate insulin resistance. Diet was measured by a validated food frequency questionnaire in one of every two subjects.We did not find a significant between-genotype difference in insulin resistance measures. However, in women we found statistically significant gene-diet interactions (recessive model) between PLIN 11482G-->A/14995A-->T polymorphisms (in high linkage disequilibrium) and saturated fatty acids (SFAs; P = 0.003/0.005) and carbohydrate (P = 0.004/0.012) in determining HOMA-IR. These interactions were in opposite directions and were more significant for 11482G-->A, considered the tag polymorphism. Thus, women in the highest SFA tertile (11.8-19%) had higher HOMA-IR (48% increase; P trend = 0.006) than women in the lowest (3.1-9.4%) only if they were homozygotes for the PLIN minor allele. Conversely, HOMA-IR decreased (-24%; P trend = 0.046) as carbohydrate intake increased. These effects were stronger when SFAs and carbohydrate were combined as an SFA-to-carbohydrate ratio. Moreover, this gene-diet interaction was homogeneously found across the three ethnic groups.PLIN 11482G-->A/14995A-->T polymorphisms modulate the association between SFAs/carbohydrate in diet and insulin resistance in Asian women.
N‐isobutyrylcysteine, a donor of systemic thiols, does not reduce the exacerbation rate in chronic bronchitis
Authors: A. Ekberg-Jansson, M. Larson, W MacNee, A. Tunek, L Wahlgren, E.F.m Wouters, S. Larsson, None for the N-isobutyrylcysteine Study Group
Journal: European Respiratory Journal (1999)

N-isobutyrylcysteine (NIC), a new thiol compound that is not rapidly hydrolysed to give higher levels of free thiols in the body than N-acetylcysteine (NAC), was used to test if the effect of NAC on exacerbations in chronic bronchitis was an effect of the unhydrolysed thiol compound. Smokers or exsmokers with chronic bronchitis forced expiratory volume in one second (FEV1) &gt;40% and reversibility &lt; or = 10% predicted were treated with oral NIC 300 mg b.i.d. or placebo for 24 weeks. Steroids, NAC, antibiotics, and nonsteroid anti-inflammatory drugs use were restricted. Exacerbations were recorded by a respiratory symptom diary card and the time to onset of the first exacerbation after the start of treatment was measured using life-table analysis. Spirometry was performed at each visit. Six hundred and thirty-seven patients were randomized to treatment with NIC (n=316) or placebo (n=321). NIC did not prolong the time to first exacerbation (life-table analysis, p=0.59) and no increase in FEV1 or forced vital capacity was observed. Altered taste perception, taste loss and anosmia occurred more often in the NIC group (p&lt;0.001). In conclusion, N-isobutyrylcysteine, a N-acetylcysteine-like drug with a greater bioavailability has, contrary to N-acetylcysteine, no effect on exacerbations in chronic bronchitis. This suggests that the effect of N-acetylcysteine on exacerbations in chronic bronchitis is not due to the relatively low free thiol levels (other than glutathione) produced by N-acetylcysteine therapy.
Small Leucine-Rich Proteoglycans in Kidney Disease
Authors: Liliana Schaefer
Journal: Journal of the American Society of Nephrology (2011)

Research over the past 2 decades provides ample evidence that small leucine-rich proteoglycans (SLRPs; such as decorin, biglycan, fibromodulin, and lumican) of the extracellular matrix are deeply involved in the regulation of inflammatory and fibrotic renal disorders. Initial efforts in SLRP research focused on the interaction between decorin and TGF-β because it had been unequivocally demonstrated that decorin treatment exerts beneficial effects in fibrotic disorders involving TGF-β overproduction in the kidney. This was followed by a paradigm shift in our understanding of SLRP biology, with new evidence showing that in addition to their role as structural matrix components, soluble SLRPs also act as signaling molecules regulating various complex biologic processes in a molecule- and cell-specific manner. With the identification of SLRP-derived endogenous ligands of Toll-like receptors, the general question regarding the mechanisms of SLRP-derived signaling in pathogen-dependent and independent renal inflammation arose. This led to the fascinating concept of SLRPs as autonomous triggers of sterile renal inflammation in response to renal stress or injury. This review focuses on the key biologic roles of SLRPs in the normal and diseased kidney with special emphasis on newly described signaling events triggered by these proteoglycans.
Preventive effect of pre-dive hydration on bubble formation in divers
Authors: E Gempp, J E Blatteau, J-M Pontier, C Balestra, P Louge
Journal: British Journal of Sports Medicine (2008)

To investigate whether prehydration 90 min before a dive could decrease bubble formation, and to evaluate the consequent adjustments in plasma volume (PV), water balance and plasma surface tension (ST).Eight military divers participated in a crossover trial of pre-dive hydration using saline-glucose beverage (protocol 1) and a control dive with no prehydration (protocol 2). Drink volume was 1300 ml (osmolality 324 mOsm/l) and drinking time was 50-60 min. The diving protocol consisted of an open sea field air dive at 30 msw depth for 30 min followed by a 9 min stop at 3 msw. Haemodynamic parameters, body weight measurements, urine volume and blood samples were taken before/after fluid intake and after the dive. Decompression bubbles were examined by a precordial pulsed Doppler.Bubble activity was significantly lower for protocol 1 than for protocol 2. PV increased after fluid ingestion by 3.5% and returned toward baseline after diving for protocol 1, whereas it decreased by 2.2% after diving for protocol 2. Differences in post-dive PV between the two conditions were highly significant. Body weight loss before/after diving and post-dive urine volume after diving were significant in both protocols, but the relative decline in weight remained lower for protocol 1 than for protocol 2, with reduction of negative water balance due to higher fluid retention. There were no differences in ST after fluid intake and after diving for the two protocols.Pre-dive oral hydration decreases circulatory bubbles, thus offering a relatively easy means of reducing decompression sickness risk. The prehydration condition allowed attenuation of dehydration and prevention of hypovolaemia induced by the diving session. Hydration and diving did not change plasma surface tension in this study.
THE ATTENUATION OF THE VIRUS OF EPIZOOTIC HEMORRHAGIC DISEASE OF DEER BY ITS SERIAL PASSAGE IN THE BRAINS OF NEWBORN MICE
Authors: Richard E. Shope, Lester G. MacNamara, Norma E. Mettler
Journal: The Journal of Experimental Medicine (1963)

Serial passage through the brains of newborn mice markedly attenuates the New Jersey strain of EHD virus. Deer inoculated with this attenuated virus show no clinical evidence of illness, but do develop virus-neutralizing antibodies in their sera. They also become solidly immune to infection with the regularly fatal unattenuated virus.
Survival Curve of a Human Melanoma in Nude Mice
Authors: Marcelle Guichard, Charles Gosse, Edmond-Philippe Malaise
Journal: JNCI Journal of the National Cancer Institute (1977)

Using cells from our tissue culture of human melanoma cell line Na 11, we transplanted 1 X 10)6) tumor cells sc into athymic nude mice. Tumors appeared after a latent period of 4-10 days; when they reached a mean volume of 100 mm3 we irradiated them with various doses of X-rays. Some tumors were irradiated while the mice were still alive; others were treated 10 minutes after the animals had been asphyxiated with nitrogen. All irradiation was done in the presence of oxygen. These tumors were excised, and cell suspensions were prepared; the cells formed colonies with a mean plating efficiency of 29%. In another series of experiments, we irradiated tumor cells in vitro 2 hours after excision, when most cells were fixed and presumably oxygenated. We then calculated survival curves for the tumor cells irradiated under these three conditions and found an average anoxic cell fraction of 85%, which was much higher than that reported in many other tumor systems. We explored several possible explanations for this phenomenon.
Physical Activity Before and During Pregnancy and Risk of Gestational Diabetes Mellitus
Authors: Deirdre K. Tobias, Cuilin Zhang, Rob M. van Dam, Katherine Bowers, Frank B. Hu
Journal: Diabetes Care (2010)

OBJECTIVE Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and is associated with a substantially elevated risk of adverse health outcomes for both mothers and offspring. Physical activity may contribute to the prevention of GDM and thus is crucial for dissecting the vicious circle involving GDM, childhood obesity, and adulthood obesity, and diabetes. Therefore, we aimed to systematically review and synthesize the current evidence on the relation between physical activity and the development of GDM. RESEARCH DESIGN AND METHODS Medline, EMBASE, and Cochrane Reviews were searched from inception to 31 March 2010. Studies assessing the relationship between physical activity and subsequent development of GDM were included. Characteristics including study design, country, GDM diagnostic criteria, ascertainment of physical activity, timing of exposure (prepregnancy or early pregnancy), adjusted relative risks, CIs, and statistical methods were extracted independently by two reviewers. RESULTS Our search identified seven prepregnancy and five early pregnancy studies, including five prospective cohorts, two retrospective case-control studies, and two cross-sectional study designs. Prepregnancy physical activity was assessed in 34,929 total participants, which included 2,813 cases of GDM, giving a pooled odds ratio (OR) of 0.45 (95% CI 0.28–0.75) when the highest versus lowest categories were compared. Exercise in early pregnancy was assessed in 4,401 total participants, which included 361 cases of GDM, and was also significantly protective (0.76 [95% CI 0.70–0.83]). CONCLUSIONS Higher levels of physical activity before pregnancy or in early pregnancy are associated with a significantly lower risk of developing GDM.
Escalation of Drug Use in Early-Onset Cannabis Users vs Co-twin Controls
Authors: Michael T. Lynskey, Andrew C. Heath, Kathleen K. Bucholz, Wendy S. Slutske, Pamela A. F. Madden, Elliot C. Nelson, Dixie J. Statham, Nicholas G. Martin
Journal: JAMA (2003)

<h3>Context</h3> Previous studies have reported that early initiation of cannabis (marijuana) use is a significant risk factor for other drug use and drug-related problems. <h3>Objective</h3> To examine whether the association between early cannabis use and subsequent progression to use of other drugs and drug abuse/dependence persists after controlling for genetic and shared environmental influences. <h3>Design</h3> Cross-sectional survey conducted in 1996-2000 among an Australian national volunteer sample of 311 young adult (median age, 30 years) monozygotic and dizygotic same-sex twin pairs discordant for early cannabis use (before age 17 years). <h3>Main Outcome Measures</h3> Self-reported subsequent nonmedical use of prescription sedatives, hallucinogens, cocaine/other stimulants, and opioids; abuse or dependence on these drugs (including cannabis abuse/dependence); and alcohol dependence. <h3>Results</h3> Individuals who used cannabis by age 17 years had odds of other drug use, alcohol dependence, and drug abuse/dependence that were 2.1 to 5.2 times higher than those of their co-twin, who did not use cannabis before age 17 years. Controlling for known risk factors (early-onset alcohol or tobacco use, parental conflict/separation, childhood sexual abuse, conduct disorder, major depression, and social anxiety) had only negligible effects on these results. These associations did not differ significantly between monozygotic and dizygotic twins. <h3>Conclusions</h3> Associations between early cannabis use and later drug use and abuse/dependence cannot solely be explained by common predisposing genetic or shared environmental factors. The association may arise from the effects of the peer and social context within which cannabis is used and obtained. In particular, early access to and use of cannabis may reduce perceived barriers against the use of other illegal drugs and provide access to these drugs.
Effect of exercise-induced dehydration on time-trial exercise performance: a meta-analysis
Authors: Eric D B Goulet
Journal: British Journal of Sports Medicine (2011)

Objective To use the meta-analytical procedures to determine the magnitude of the effect of exercise-induced dehydration (EID) upon time-trial (TT) exercise performance. Methods Studies were located via database searches and cross-referencing. TT performance outcomes were converted to mean percentage changes in power output. Random-effects model meta-regressions, analogue to the ANOVA and weighted mean effect summaries were used to delineate the effect of the EID-associated body weight (BW) loss on TT performance. Results Five research articles, all using cycling TTs, were included, producing 13 effect estimates and representing 39 subjects. The mean ambient temperature, relative humidity, exercise intensity and duration of the exercise trials were 26.0±6.7°C, 61±9%, 68±14% of VO2max and 86±34 min, respectively. The effect of EID (mean BW loss of 2.20±1.0%) during self-paced exercise conditions was to produce a non-significant increase in endurance performance of 0.06±2.72% (p=0.94), compared with the maintenance of euhydration (mean BW loss of 0.44±0.48%). Meta-regression analyses revealed a statistically significant relationship between the percentage changes in power output and exercise intensity and duration, but not with the EID-associated percentage changes in BW loss. Drinking according to the dictate of thirst was associated with an increase in TT performance compared with a rate of drinking below (+5.2±4.6%, p=0.01) or above (+2.4±5.0%, p=0.40) thirst. The probability that drinking to thirst confers a real and meaningful advantage on TT performances conducted under field conditions compared with a rate of drinking below and above thirst sensation is of the order of 98% and 62%, respectively. Conclusions (1) Compared with euhydration, EID (up to 4% BW loss) does not alter cycling performances during out-of-door exercise conditions; (2) exercise intensity and duration have a much greater impact on cycling TT performances than EID and; (3) relying on thirst sensation to gauge the need for fluid replacement maximises cycling TT performances.
Incidence and prevalence of complaints of the neck and upper extremity in general practice
Authors: S D M Bot
Journal: Annals of the Rheumatic Diseases (2004)

To study the incidence and prevalence of neck and upper extremity musculoskeletal complaints in Dutch general practice.Data were obtained from the second Dutch national survey of general practice. In all, 195 general practitioners (GPs) from 104 practices across the Netherlands recorded all contacts with patients during 12 consecutive months. Incidence densities and consultation rates were calculated.The total number of contacts during the registration period of one year was 1 524 470. The most commonly reported complaint was neck symptoms (incidence 23.1 per 1000 person-years), followed by shoulder symptoms (incidence 19.0 per 1000 person-years). Sixty six GP consultations per 1000 person-years were attributable to a new complaint or new episode of complaint of the neck or upper extremity (incidence density). In all, the GPs were consulted 147 times per 1000 registered persons for complaints of the neck or upper extremity. For most complaints the incidence densities and consultation rates were higher for women than for men.Neck and upper extremity symptoms are common in Dutch general practice. The GP is consulted approximately seven times each week for a complaint relating to the neck or upper extremity; of these, three are new complaints or new episodes. Attention should be paid to training GPs to deal with neck and upper limb complaints, and to research on the prognosis and treatment of these common complaints in primary care.
Effect of ventilation on resuscitation in an animal model of cardiac arrest.
Authors: A H Idris, L B Becker, R S Fuerst, V Wenzel, W J Rush, R J Melker, D J Orban
Journal: Circulation (1994)

BACKGROUND The need for ventilation during the initial management of cardiac arrest is an important public health problem that is being debated. The present study was designed to determine whether ventilation affects return of spontaneous circulation from cardiac arrest in a swine model with an interval of untreated ventricular fibrillation of 6 minutes, as reported in witnessed out-of-hospital human cardiac arrest. METHODS AND RESULTS Twenty-four animals were randomly assigned to two groups: one that received ventilation during the first 10 minutes of chest compression and one that did not. Coronary perfusion pressure and minute ventilation were continuously recorded. Arterial and mixed venous blood gases were measured at intervals. Return of spontaneous circulation was defined prospectively as an aortic systolic blood pressure of &gt; 80 mm Hg for &gt; 5 minutes and was the primary outcome variable. All animals were anesthetized, paralyzed, and intubated. Ventricular fibrillation was induced and persisted for 6 minutes without chest compression, followed by mechanical chest compression for 10 minutes and then attempted defibrillation. Animals without return of spontaneous circulation were given epinephrine, ventilation, and chest compression for an additional 3 minutes. Defibrillation was again attempted, and animals were assessed for return of spontaneous circulation. There were no significant differences between the two groups in baseline prearrest mean cardiac index, coronary perfusion pressure, or arterial and mixed venous blood gases. However, after 9 minutes of chest compression, significant differences were noted between the ventilated and nonventilated groups. The nonventilated group had significantly (P &lt; .05) lower mean arterial PO2 (38 +/- 17 mm Hg compared with 216 +/- 104 mm Hg) and higher PCO2 (62 +/- 16 mm Hg compared with 35 +/- 8 mm Hg), lower mixed venous PO2 (15 +/- 7 mm Hg compared with 60 +/- 7 mm Hg). Nine of 12 (75%) of the ventilated animals, and only 1 of 12 (8%) of the nonventilated animals had return of spontaneous circulation after cardiac arrest (P &lt; .002). CONCLUSIONS In this animal model of cardiac arrest, ventilation was important for resuscitation. The importance of ventilation could be related to the prolonged duration of untreated ventricular fibrillation and the significantly greater hypoxia and hypercarbic acidosis found in the nonventilated animals.