tbuckley/cabot-search huggingface dataset:
Outcome of case finding among relatives of patients with known heterozygous familial
Authors: D Bhatnagar
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To assess the feasibility of detecting new cases of heterozygous familial hypercholesterolaemia by using a nurse led genetic register. <b>Design:</b> Case finding among relatives of patients with familial hypercholesterolaemia. <b>Setting:</b> Two lipid clinics in central and south Manchester. <b>Subjects:</b> 259 (137 men and 122 women) probands and 285 first degree relatives. <b>Results:</b> Of the 200 first degree relatives tested, 121 (60%) had inherited familial hypercholesterolaemia. The newly diagnosed patients were younger than the probands and were generally detected before they had clinically overt atherosclerosis. Concentrations of serum cholesterol were, respectively, 8.4 (1.7 SD) mmol/l and 8.1 (1.9 SD) mmol/l in affected men and women and 5.6 (1.0 SD) mmol/l and 5.6 (1.1 SD) mmol/l in unaffected men and women. Screening for risk factors as recommended in recent guidelines for coronary heart disease prevention would have failed to identify most of the affected relatives in whom hypertension, diabetes mellitus, cigarette smoking, and obesity were uncommon. <b>Conclusions:</b> By performing cholesterol tests on 200 relatives, 121 new patients with familial hypercholesterolaemia were discovered. Because 1 in 500 people in the UK are affected by this condition, to detect a similar number by population screening over 60 000 tests would be required, and only a few of these patients would have been detected had cholesterol testing been restricted to those with other risk factors for coronary heart disease. A case exists for organising a genetic register approach, linking lipid clinics nationally.
In medio stat virtus: Theoretical and methodological extremes regarding reciprocity will not explain complex social behaviors
Authors: Claudia Civai, Alan Langus
Journal: Behavioral and Brain Sciences (2012)

Abstract Guala contests the validity of strong reciprocity as a key element in shaping social behavior by contrasting evidence from experimental games to that of natural and historic data. He suggests that in order to understand the evolution of social behavior researchers should focus on natural data and weak reciprocity. We disagree with Guala's proposal to shift the focus of the study from one extreme of the spectrum (strong reciprocity) to the other extreme (weak reciprocity). We argue that the study of the evolution of social behavior must be comparative in nature, and we point out experimental evidence that shows that social behavior is not cooperation determined by a set of fixed factors. We argue for a model that sees social behavior as a dynamic interaction of genetic and environmental factors.
Synergy between the pre–T cell receptor and Notch: cementing the αβ lineage choice
Authors: Cynthia J. Guidos
Journal: The Journal of Experimental Medicine (2006)

Notch1 signaling suppresses B cell development and promotes T lineage commitment in thymus-seeding hematopoietic progenitors. Notch1 is also activated in early T cell progenitors, but the functions of these later Notch signals have not been clearly defined. Recent studies reveal that Notch signaling is not essential for pre–T cell receptor (TCR) expression or γδ lineage choice. Rather, pre-TCR signaling enhances progenitor competitiveness for limiting Notch ligands, leading to preferential expansion of TCRβ-bearing progenitors.
Direct Evidence for Epithelial-Mesenchymal Transitions in Breast Cancer
Authors: Anthony J. Trimboli, Koichi Fukino, Alain de Bruin, Guo Wei, Lei Shen, Stephan M. Tanner, Nicholas Creasap, Thomas J. Rosol, Michael L. Robinson, Charis Eng, Michael C. Ostrowski, Gustavo Leone
Journal: Cancer Research (2008)

Abstract We developed stromal- and epithelial-specific cre-transgenic mice to directly visualize epithelial-mesenchymal transition (EMT) during cancer progression in vivo. Using three different oncogene-driven mouse mammary tumor models and cell-fate mapping strategies, we show in vivo evidence for the existence of EMT in breast cancer and show that myc can specifically elicit this process. Hierarchical cluster analysis of genome-wide loss of heterozygosity reveals that the incidence of EMT in invasive human breast carcinomas is rare, but when it occurs it is associated with the amplification of MYC. These data provide the first direct evidence for EMT in breast cancer and suggest that its development is favored by myc-initiated events. [Cancer Res 2008;68(3):937–45]
CRABP1 is associated with a poor prognosis in breast cancer: adding to the complexity of breast cancer cell response to retinoic acid
Authors: Rong-Zong Liu, Elizabeth Garcia, Darryl D. Glubrecht, Ho Yin Poon, John R. Mackey, Roseline Godbout
Journal: Molecular Cancer (2015)

Clinical trials designed to test the efficacy of retinoic acid (RA) as an adjuvant for the treatment of solid cancers have been disappointing, primarily due to RA resistance. Estrogen receptor (ER)-negative breast cancer cells are more resistant to RA than ER-positive cells. The expression and subcellular distribution of two RA-binding proteins, FABP5 and CRABP2, has already been shown to play critical roles in breast cancer cell response to RA. CRABP1, a third member of the RA-binding protein family, has not previously been investigated as a possible mediator of RA action in breast cancer. CRABP1 and CRABP2 expression in primary breast tumor tissues was analyzed using gene expression and tissue microarrays. CRABP1 levels were manipulated using siRNAs and by transient overexpression. RA-induced subcellular translocation of CRABPs was examined by immunofluorescence microscopy and immunoblotting. RA-induced transactivation of RAR was analyzed using a RA response element (RARE)-driven luciferase reporter system. Effects of CRABP1 expression and RA treatment on downstream gene expression were investigated by semi-quantitative RT-PCR analysis. Compared to normal mammary tissues, CRABP1 expression is significantly down-regulated in ER+ breast tumors, but maintained in triple-negative breast cancers. Elevated CRABP1 levels are associated with poor patient prognosis, high Ki67 immunoreactivity and high tumor grade in breast cancer. The prognostic significance of CRABP1 is attributed to its cytoplasmic localization. We demonstrate that CRABP1 expression attenuates RA-induced cell growth arrest and inhibits RA signalling in breast cancer cells by sequestering RA in the cytoplasm. We also show that CRABP1 affects the expression of genes involved in RA biosynthesis, trafficking and metabolism. CRABP1 is an adverse factor for clinical outcome in triple-negative breast cancer and a potent inhibitor of RA signalling in breast cancer cells. Our data indicate that CRABP1, in conjunction with previously identified CRABP2 and FABP5, plays a key role in breast cancer cell response to RA. We propose that these three RA-binding proteins can serve as biomarkers for predicting triple-negative breast cancer response to RA, with elevated levels of either cytoplasmic CRABP1 or FABP5 associated with RA resistance, and elevated levels of nuclear CRABP2 associated with sensitivity to RA.
Dietary preparation and per cent fat measurement by hydrostatic weighing.
Authors: T R Thomas, L D Crough, J Araujo
Journal: British Journal of Sports Medicine (1988)

To examine if the dietary preparation for hydrostatic weighing (HW) alters the % fat measurement, seven men and three women (age 29 +/- 6, Males 11.7 +/- 7.3% fat and Females 24.1 +/- 5.4% fat, mean +/- SD) were assessed before and after three meals. On separate days and in random order, each subject (1) ate a salad with toppings (600 g) with small beverage, (2) ate two bean burritos and one bean tostada (900 g) with small beverage, and (3) drank 800 ml of carbonated beverage. The subject was reweighted 45 min after the meals and immediately after the beverage ingestion. Functional residual capacity was assessed simultaneously with underwater weight. Dependent t-tests indicated that body weight in air increased after each of the three means (Bean 0.78, Salad 0.92, Beverage 0.90 kg, all p less than 0.05), but underwater weights were unchanged. Following the salad, body density (1064.6 vs 1061.8 kg.m-3) and % fat (15.0 vs 16.3%, p less than 0.05) were significantly different pre-meal vs post-meal. Likewise, beverage ingestion resulted in decreased body density (1064.7 vs 1061.2 kg.m-3) and increased % fat (15.0 vs 16.5%, p less than 0.05). The bean meal did not cause a change in measured body density (1062.8 vs 1062.8 kg.m-3) or % fat (15.8 vs 15.8%). These results indicate that for the most accurate analysis, preliminary dietary preparation for HW should include food and beverage restriction.
A double blind, randomised, controlled trial of glutamine supplementation in parenteral nutrition
Authors: J Powell-Tuck, C P Jamieson, G E A Bettany, O Obeid, H V Fawcett, C Archer, D L Murphy
Journal: Gut (1999)

To determine whether the inclusion of 20 g free glutamine as part of the nitrogen source of parenteral feeds reduces length of hospital stay or mortality.In a randomised, double blind, controlled trial in 168 patients clinically accepted for parenteral nutrition, standard feeds were compared with feeds in which 3.8 g of the total nitrogen was replaced with the equivalent 20 g glutamine. A minimum of 11 g nitrogen/day was used in all patients. Daily intakes of energy and nitrogen were determined using a validated computer protocol and were similar for the two groups. All feeds included trace elements, vitamins, electrolytes, and minerals.A total of 85 patients received a median of eight (interquartile range 5-13) daily feeds containing glutamine while 83 received a median of eight (5-15) standard feeds. No difference between groups was detected for infective complications. Twenty control patients and 14 who had received glutamine died during their hospital stay (NS). Median length of stay was 32 (23-52) days on glutamine, which was not significantly different from the control value of 35 (25-55) days. Glutamine was associated with a significant (p<0.03) reduction in length of stay in surgical patients (45 days (range 29-81) versus 30 days (range 19-54)).The benefit from glutamine supplementation of parenteral feeds as used in this trial has not been proved. Supplementation may have advantages in surgical patients and in haematological malignancy. Further trials are required.
Chronic manganism. Neurologic and laboratory studies during treatment with levodopa
Authors: H. A. Rosenstock
Journal: JAMA (1971)

A case of chronic manganese intoxication emphasizes that the disorder, while uncommon, is not rare, and that the psychiatrist as well as the neurologist may be the first physician consulted. Diagnostic evaluations included urine assays for manganese following edetic acid infusion and analyses of scalp and chest hair. The analysis for chest hair manganese is thought to be reported for the first time. The concentration of manganese in chest hair was more than three times the concentration in scalp hair. Clinical experience with a four-month therapeutic trial of levodopa converted abnormal reflex patterns to normal, improved mentation and speech, and reduced dysdiadochokinesia and bradykinesia. Dystonia was not improved.
An A13 Repeat within the 3′-Untranslated Region of Epidermal Growth Factor Receptor (EGFR) Is Frequently Mutated in Microsatellite Instability Colon Cancers and Is Associated with Increased EGFR Expression
Authors: Ziqiang Yuan, Joongho Shin, Andrew Wilson, Sanjay Goel, Yi-He Ling, Naseem Ahmed, Higinio Dopeso, Minaxi Jhawer, Shannon Nasser, Cristina Montagna, Kenneth Fordyce, Leonard H. Augenlicht, Lauri A. Aaltonen, Diego Arango, Thomas K. Weber, John M. Mariadason
Journal: Cancer Research (2009)

Colorectal cancers (CRC) with microsatellite instability (MSI) have clinical, pathologic, genetic, and epigenetic features distinct from microsatellite-stable CRC. Examination of epidermal growth factor receptor (EGFR) mRNA and protein expression levels in a panel of colon cancer cell lines identified strong expression of EGFR in multiple cell lines with MSI. Although no relationship between EGFR overexpression and the length of a CA dinucleotide repeat in intron 1 was observed, a variant A13/A14 repeat sequence within the 3'-untranslated region (3'-UTR) of the EGFR gene was identified, which was mutated by either mononucleotide or dinucleotide adenosine deletions in 64% of MSI cell lines and 69% of MSI colon tumors. Using a Tet-Off system, we show that this mutation increases EGFR mRNA stability in colon cancer cells, providing a mechanistic basis for EGFR overexpression in MSI colon cancer cell lines. To determine whether this mutation is a driver or a bystander event in MSI colon cancer, we examined the effect of pharmacologic and molecular inhibition of EGFR in EGFR 3'-UTR mutant MSI cell lines. Cell lines with an EGFR 3'-UTR mutation and that were wild-type (WT) for downstream signaling mediators in the Ras/BRAF and PIK3CA/PTEN pathways were sensitive to EGFR inhibition, whereas those harboring mutations in these signaling mediators were not. Furthermore, in cell lines WT for downstream signaling mediators, those with EGFR 3'-UTR mutations were more sensitive to EGFR inhibition than EGFR 3'-UTR WT cells, suggesting that this mutation provides a growth advantage to this subset of MSI colon tumors.
Solitary pulmonary nodule evaluation with 99mTc-methoxy isobutyl isonitrile in a tuberculosis-endemic area
Authors: M. M. Schuurmans, A. Ellmann, H. Bouma, A. H. Diacon, K. Dyckmans, C. T. Bolliger
Journal: European Respiratory Journal (2007)

High prevalence of tuberculosis increases the odds for nonmalignant solitary pulmonary nodules (SPNs). Positron emission tomography (PET) using <sup>18</sup>F-fluorodeoxyglucose is the method of choice for the identification of malignant SPNs requiring curative surgery. However, PET is not widely available. Technetium-99m methoxy isobutyl isonitrile (MIBI) is inexpensive, widely available and shows increased uptake in malignant SPNs. The aim of the present study was to prospectively evaluate the diagnostic value of MIBI single photon emission computed tomography to distinguish between benign and malignant SPNs in a tuberculosis-endemic area. In total, 49 patients with radiologically indeterminate SPNs (single lesion ≤6 cm in diameter) were prospectively evaluated with MIBI. The final diagnosis was established with bronchoscopy, fine-needle aspiration, surgical resection or clinical follow-up for ≥2 yrs. A total of 12 (92%) out of 13 malignant lesions showed increased uptake of MIBI, while no uptake was observed in 33 (92%) out of 36 benign lesions. MIBI uptake indicated malignancy with a sensitivity and specificity of 92% and a negative predictive value of 97%. In this tuberculosis-endemic area, technetium-99m methoxy isobutyl isonitrile single photon emission computed tomography evaluation of solitary pulmonary nodules had a high negative predictive value. Therefore, it has the potential to prevent unnecessary surgical resections of benign nodules and serve as a low-cost alternative when positron emission tomography is not available.
Relationship between Survival and Edema in Malignant Gliomas: Role of Vascular Endothelial Growth Factor and Neuronal Pentraxin 2
Authors: Marc R.J. Carlson, Whitney B. Pope, Steve Horvath, Jerome G. Braunstein, Phioanh Nghiemphu, Cho-Lea Tso, Ingo Mellinghoff, Albert Lai, Linda M. Liau, Paul S. Mischel, Jun Dong, Stanley F. Nelson, Timothy F. Cloughesy
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Vascular endothelial growth factor (VEGF) is a potent mediator of vascular permeability. VEGF inhibition reduces edema and tumor burden in some patients with malignant glioma, whereas others show no response. The role of VEGF expression in edema production and the relationship to survival is not well understood. Experimental Design: Using DNA microarray analysis, we examined VEGF and related gene expression in 71 newly diagnosed malignant gliomas and analyzed the relationship to edema and survival. Results and Conclusions: VEGF expression was predictive of survival in tumors with little or no edema [Cox proportional hazard model, 6.88; 95% confidence interval (95% CI), 2.61-18.1; P &amp;lt; 0.0001], but not in tumors with extensive edema. The expression of several proangiogenic genes, including adrenomedullin (correlation coefficient, 0.80), hypoxia-inducible factor-1A (0.51), and angiopoietin-2 (0.44), was correlated with VEGF expression (all with P &amp;lt; 0.0001), whereas that of several antiangiogenic genes was inversely correlated. The expression of six genes was increased greater than 3-fold in edematous versus nonedematous tumors in the absence of increased VEGF expression. The most increased, neuronal pentraxin 2 (NPTX2, 7-fold change), was predictive of survival in tumors with the highest levels of edema, in contrast to VEGF (hazard ratio, 2.73; 95% CI, 1.49-5.02; P = 0.049). NPTX2 was tightly correlated with expression of the water channel aquaporin-3 (0.74, P &amp;lt; 0.0001). These results suggest that there are both VEGF-dependent and VEGF-independent pathways of edema production in gliomas and may explain why edema is not reduced in some patients following anti-VEGF treatment.
Behavioural counselling to increase consumption of fruit and vegetables in low income adults: randomised trial
Authors: A. Steptoe
Journal: BMJ (2003)

Objective: To measure the effect of brief behavioural counselling in general practice on patients' consumption of fruit and vegetables in adults from a low income population. Design: Parallel group randomised controlled trial. Setting: Primary health centre in a deprived, ethnically mixed inner city area. Participants: 271 patients aged 18-70 years without serious illness. Intervention: Brief individual behavioural counselling based on the stage of change model; time matched nutrition education counselling. Main outcome measures: Self reported number of portions of fruit and vegetables eaten per day, plasma β carotene, α tocopherol, and ascorbic acid concentrations, and 24 hour urinary potassium excretion. Assessment at baseline, eight weeks, and 12 months. Results: Consumption of fruit and vegetables increased from baseline to 12 months by 1.5 and 0.9 portions per day in the behavioural and nutrition groups (mean difference 0.6 portions, 95% confidence interval 0.1 to 1.1). The proportion of participants eating five or more portions a day increased by 42% and 27% in the two groups (mean difference 15%, 3% to 28%). Plasma β carotene and α tocopherol concentrations increased in both groups, but the rise in β carotene was greater in the behavioural group (mean difference 0.16 µmol/l, 0.001 µmol/l to 1.34 µmol/l). There were no changes in plasma ascorbic acid concentrations or urinary potassium excretion. Differences were maintained when analysis was restricted to the 177 participants with incomes £400 (€596, $640) a week. Conclusions: Brief individual counselling in primary care can elicit sustained increases in consumption of fruit and vegetables in low income adults in the general population. #### What is already known on this topic What is already known on this topic Brief interventions can be effective in increasing consumption of fruit and vegetables Biomarkers and intention to treat analyses have seldom been used in such interventions, and few studies have targeted low income populations #### What this study adds What this study adds Compared with nutritional counselling, brief behavioural counselling carried out by nurses in primary care led to greater increases in fruit and vegetable intake and in plasma β carotene concentration Favourable effects were observed in low income adults living in a deprived inner city area
Differences between asthmatics and nonasthmatics hospitalised with influenza A infection
Authors: Puja Myles, Jonathan S. Nguyen-Van-Tam, Malcolm G. Semple, Stephen J. Brett, Barbara Bannister, Robert C. Read, Bruce L. Taylor, Jim McMenamin, Joanne E. Enstone, Karl G. Nicholson, Peter J. Openshaw, Wei Shen Lim
Journal: European Respiratory Journal (2012)

Asthmatics hospitalised because of influenza A infection are less likely to require intensive care or die compared with nonasthmatics. The reasons for this are unknown. We performed a retrospective analysis of data on 1520 patients admitted to 75 UK hospitals with confirmed influenza A/H1N1 2009 infection. A multivariable model was used to investigate reasons for the association between asthma and severe outcomes (intensive care unit support or death). Asthmatics were less likely than nonasthmatics to have severe outcome (11.2% versus 19.8%, unadjusted OR 0.51, 95% CI 0.36-0.72) despite a greater proportion requiring oxygen on admission (36.4% versus 26%, unadjusted OR 1.63) and similar rates of pneumonia (17.1% versus 16.6%, unadjusted OR 1.04). The results of multivariable logistic regression suggest the association of asthma with outcome (adjusted OR 0.62, 95% CI 0.36-1.05; p=0.075) are explained by pre-admission inhaled corticosteroid use (adjusted OR 0.34, 95% CI 0.18-0.66) and earlier admission (≤ 4 days from symptom onset) (adjusted OR 0.60, 95% CI 0.38-0.94). In asthmatics, systemic corticosteroids were associated with a decreased likelihood of severe outcomes (adjusted OR 0.36, 95% CI 0.18-0.72). Corticosteroid use and earlier hospital admission explained the association of asthma with less severe outcomes in hospitalised patients.
Invariant Chain–independent Function of H-2M in the Formation of Endogenous Peptide–Major Histocompatibility Complex Class II Complexes In Vivo
Authors: Susan Kovats, Catherine E. Grubin, Susan Eastman, Paul deRoos, Ashok Dongre, Luc Van Kaer, Alexander Y. Rudensky
Journal: The Journal of Experimental Medicine (1998)

Efficient loading of major histocompatibility complex class II molecules with peptides requires the invariant chain (Ii) and the class II–like molecule H-2M. Recent in vitro biochemical studies suggest that H2-M may function as a chaperone to rescue empty class II dimers. To test this hypothesis in vivo, we generated mice lacking both Ii and H-2M (Ii−/−M−/−). Antigen presenting cells (APCs) from Ii−/−M−/− mice, as compared with APCs from Ii−/− mice, exhibit a significant reduction in their ability to present self-peptides to a panel of class II I-Ab–restricted T cells. As a consequence of this defect in the loading of self peptides, CD4+ thymocyte development is profoundly impaired in Ii−/−M−/− mice, resulting in a peripheral CD4+ T cell population with low levels of T cell receptor expression. These findings are consistent with the idea that H-2M functions as a chaperone in the peptide loading of class II molecules in vivo.
Abnormal early left ventricular filling as a marker of coronary artery disease during dobutamine stress echocardiography: a color M-mode doppler analysis
Authors: C. Selton-Suly, P. Houplon, A. Grentzinger, J.-P. Preiss, Y. Juillère, N. Danchin, F. Cherrier
Journal: Journal of the American College of Cardiology (1998)
Conventional in-vitro fertilisation versus intracytoplasmic sperm injection for the treatment of non-male-factor infertility: a randomised controlled trial
Authors: S Bhattacharya, MPR Hamilton, M Shaaban, Y Khalaf, M Seddler, T Ghobara, P Braude, R Kennedy, A Rutherford, G Hartshorne, A Templeton
Journal: The Lancet (2001)
Liaison Psychiatry in a Breast Cancer Unit
Authors: A J Ramirez
Journal: Journal of the Royal Society of Medicine (1989)

The first 50 referrals to a newly established liaison psychiatry service for the breast cancer unit at Guy's Hospital, London, have been examined. The majority of referrals were for psychological reactions to malignant disease, most of these were mood disturbances. Patients with sustained psychological reactions to their malignant disease were more likely to have had treatment for previous psychiatric illness and to lack a confiding relationship compared with those whose psychological reactions were transient. Teaching doctors and nurses to deal effectively with the transient psychological reactions of patients to their malignant disease is an important task of liaison psychiatry.