tbuckley/cabot-search huggingface dataset:
Blocking potassium channels: a new principle for treating restenosis?
Authors: A. Olschewski
Journal: Cardiovascular Research (2010)

This editorial refers to ‘Potent suppression of vascular smooth muscle cell migration and human neointimal hyperplasia by KV1.3 channel blockers’ by A. Cheong et al ., pp. 282–289, this issue.

Vascular smooth muscle cells are important for the structural integrity of the tunica media, but they are also central to vascular remodelling in response to injury. Although they are highly differentiated cells with the ability to regulate vascular tone and synthesize extracellular matrix, smooth muscle cells are also very plastic cells. This enables them to switch from a contractile to an invasive, migrating, and proliferating phenotype in response to local injury. Ion channels in the plasmalemma of smooth muscle cells have been implicated in this active process. There is evidence of profound changes in the types of ion channels that are expressed or functionally important during vascular smooth muscle cell transition resulting in occlusive vascular pathologies. In the systemic circulation, vessel restenosis remains a major factor limiting the success of balloon angioplasty/stenting of coronary, carotid, and femoral arteries.1 A critical event seems to be replacement of the KCa1.1 (BKCa) with the intermediate-conductance Ca2+-activated potassium channel KCa3.12 and the loss of Cav1.2 (the L-type voltage-dependent) calcium channels.3 This event confers functional dominance on other types of calcium channels, including the channel components transient receptor potential (TRP) C(canonical)1, …
Club doctors and physiotherapists
Authors: Rob Mackay
Journal: British Journal of Sports Medicine (2001)

Club doctors and physiotherapistsEDITOR,-Waddington et al 1 are to be congratulated on highlighting the need to provide the best available care to professional footballers.Their paper is, however, inherently biased by factors that detract from the validity of their conclusions.For example, they have provided no evidence for their postulation that non-chartered physiotherapists are more vulnerable to threats to their clinical autonomy than other qualified professionals.Published quotations from the semistructured interviews are of an emotive nature, and the quoted questions posed by the interviewer are clearly leading.It is well recognised that responses in such interviews can be greatly influenced by the manner in which they are posed.The authors make no comparison of methods used by chartered and non-chartered physiotherapists, and their outcomes.Similarly there has been no comparison between the performance of club doctors with or without postgraduate qualifications in sports medicine, and, moreover, no evidence produced of actual harm resulting.Indeed, in recent months in Scottish League football, the Dundee club doctor restored circulation to the foot of a player following a serious ankle injury, and the Dumbarton club doctor restarted the breathing of an apnoeic player.In a recent survey of 15 players in a Scottish football club (unpublished work), 13 stated that they had been discouraged by the (non-chartered) physiotherapist and nine by the (non-specialist) club doctor from training or competing while injured, and none had been encouraged by either to return to playing before complete recovery.Indeed, 10 confessed to concealment of the true severity of injuries, perhaps reflecting the ethos at that particular club.Care oVered to professional footballers merits careful evaluation.However, this should be detailed, methodical, and independent of bias, such as that which can arise when studies are commissioned and funded by interested parties.
Thyroid Neoplasia as Late Effect of Exposure to Radioactive Iodine in Fallout
Authors: Robert A. Conard
Journal: JAMA (1970)

Accidental exposure of people of Rongelap Island to radioactive fallout and particularly to radioactive iodines in the fallout has resulted in the development of thyroid abnormalities in 21 of 67 of these people, 3 with malignant lesions, 16 with benign adenomatous nodules, and 2 with atrophy of the gland with hypothyroidism. The preponderance of lesions occurred in children exposed at less than 10 years of age who had received a greater thyroid exposure. Growth retardation associated with hypothyroid tendency was noted in some children who appear to be responding favorably to thyroid hormone medication. Thyroidectomy, partial to complete, has been carried out on 18 patients. Risk for thyroid cancer from radioactive iodine exposure in this group does not appear to be very different from that reported following x-irradiation.
Identification and characterization of an endogenous chemotactic ligand specific for FPRL2
Authors: Isabelle Migeotte, Elena Riboldi, Jean-Denis Franssen, Françoise Grégoire, Cécile Loison, Valérie Wittamer, Michel Detheux, Patrick Robberecht, Sabine Costagliola, Gilbert Vassart, Silvano Sozzani, Marc Parmentier, David Communi
Journal: The Journal of Experimental Medicine (2004)

Chemotaxis of dendritic cells (DCs) and monocytes is a key step in the initiation of an adequate immune response. Formyl peptide receptor (FPR) and FPR-like receptor (FPRL)1, two G protein–coupled receptors belonging to the FPR family, play an essential role in host defense mechanisms against bacterial infection and in the regulation of inflammatory reactions. FPRL2, the third member of this structural family of chemoattractant receptors, is characterized by its specific expression on monocytes and DCs. Here, we present the isolation from a spleen extract and the functional characterization of F2L, a novel chemoattractant peptide acting specifically through FPRL2. F2L is an acetylated amino-terminal peptide derived from the cleavage of the human heme-binding protein, an intracellular tetrapyrolle-binding protein. The peptide binds and activates FPRL2 in the low nanomolar range, which triggers intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of extracellular signal–regulated kinase 1/2 mitogen-activated protein kinases through the Gi class of heterotrimeric G proteins. When tested on monocytes and monocyte-derived DCs, F2L promotes calcium mobilization and chemotaxis. Therefore, F2L appears as a new natural chemoattractant peptide for DCs and monocytes, and the first potent and specific agonist of FPRL2.
Medical Director Responsibilities for Outpatient Cardiac Rehabilitation/Secondary Prevention Programs
Authors: Marjorie L. King, Mark A. Williams, Gerald F. Fletcher, Neil F. Gordon, Meg Gulanick, Carl N. King, Arthur S. Leon, Benjamin D. Levine, Fernando Costa, Nanette K. Wenger
Journal: Circulation (2005)

HomeCirculationVol. 112, No. 21Medical Director Responsibilities for Outpatient Cardiac Rehabilitation/Secondary Prevention Programs
Cadmium Exposure and Breast Cancer Risk
Authors: Jane A. McElroy, Martin M. Shafer, Amy Trentham-Dietz, John M. Hampton, Polly A. Newcomb
Journal: JNCI Journal of the National Cancer Institute (2006)

Cadmium, a highly persistent heavy metal, has been categorized as a probable human carcinogen by the U.S. Environmental Protection Agency. Primary exposure sources include food and tobacco smoke. We carried out a population-based case-control study of 246 women, aged 20-69 years, with breast cancer and 254 age-matched control subjects. We measured cadmium levels in urine samples by inductively coupled plasma mass spectrometry and conducted interviews by telephone to obtain information on known breast cancer risk factors. Odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer by creatinine-adjusted cadmium levels were calculated by multivariable analysis. Statistical tests were two-sided. Women in the highest quartile of creatinine-adjusted cadmium level (> or = 0.58 microg/g) had twice the breast cancer risk of those in the lowest quartile (<0.26 microg/g; OR = 2.29, 95% CI = 1.3 to 4.2) after adjustment for established risk factors, and there was a statistically significant increase in risk with increasing cadmium level (P(trend) = .01). Based on this study, the absolute risk difference is 45 (95% CI = 0 to 77) per 100,000 given an overall breast cancer rate of 124 per 100,000. Whether increased cadmium is a causal factor for breast cancer or reflects the effects of treatment or disease remains to be determined.
Household Income Is Associated With the Risk of Metabolic Syndrome in a Sex-Specific Manner
Authors: Jean Dallongeville, Dominique Cottel, Jean Ferrières, Dominique Arveiler, Annie Bingham, Jean Bernard Ruidavets, Bernadette Haas, Pierre Ducimetière, Philippe Amouyel
Journal: Diabetes Care (2005)

OBJECTIVE—To assess the relationship between household income and metabolic syndrome in men and women. RESEARCH DESIGN AND METHODS—A total of 1,695 men and 1,664 women, aged 35–64 years, from three distinct geographical areas of France were investigated. Waist girth, plasma triglycerides, HDL cholesterol, glucose, and systolic blood pressure were used to define metabolic syndrome according to the National Cholesterol Education Program (NCEP)/Adult Treatment Panel III (ATPIII) guidelines. Household income, educational level, occupational category, working status, consumption of psychotropic drugs, accommodation status, household composition, physical activity at work and during leisure time, alcohol consumption, and smoking habits were recorded with a standardized questionnaire. RESULTS—There were 390 (23.0%) men and 381 (16.9%) women who satisfied NCEP/ATPIII criteria for metabolic syndrome. Household income (P &amp;lt; 0.0001) and consumption of psychotropic drugs (P = 0.0005) were associated with metabolic syndrome in women but not in men. In contrast, educational level, occupational category, working status, and accommodation status were associated with metabolic syndrome in both men and women. After adjustment on lifestyle variables, household income (interaction P &amp;lt; 0.004) remained inversely associated with metabolic syndrome in women but not in men. CONCLUSIONS—These data suggest that limited household income, which reflects a complex unfavorable social and economic environment, may increase the risk of metabolic syndrome in a sex-specific manner.
Randomized Study of Lapatinib Alone or in Combination With Trastuzumab in Women With ErbB2-Positive, Trastuzumab-Refractory Metastatic Breast Cancer
Authors: Kimberly L. Blackwell, Harold J. Burstein, Anna Maria Storniolo, Hope Rugo, George Sledge, Maria Koehler, Catherine Ellis, Michelle Casey, Svetislava Vukelja, Joachim Bischoff, Jose Baselga, Joyce O'Shaughnessy
Journal: Journal of Clinical Oncology (2010)

Purpose Preclinical studies in ErbB2-positive cell lines demonstrated a synergistic interaction between lapatinib and trastuzumab, suggesting that dual blockade is more effective than a single agent alone. EGF104900 compared the activity of lapatinib alone or in combination with trastuzumab in patients with ErbB2-positive, trastuzumab-refractory metastatic breast cancer (MBC). Patients and Methods Patients with ErbB2-positive MBC who experienced progression on prior trastuzumab-containing regimens were randomly assigned to receive either lapatinib alone or in combination with trastuzumab. The primary end point was progression-free survival (PFS). Secondary efficacy end points included overall response rate (ORR), clinical benefit rate (CBR; complete response, partial response, and stable disease for ≥ 24 weeks), and overall survival (OS). Results In the intent-to-treat population (N = 296) who received a median of three prior trastuzumab-containing regimens, the combination of lapatinib with trastuzumab was superior to lapatinib alone for PFS (hazard ratio [HR] = 0.73; 95% CI, 0.57 to 0.93; P = .008) and CBR (24.7% in the combination arm v 12.4% in the monotherapy arm; P = .01). A trend for improved OS in the combination arm was observed (HR = 0.75; 95% CI, 0.53 to 1.07; P = .106). There was no difference in ORR (10.3% in the combination arm v 6.9% in the monotherapy arm; P = .46). The most frequent adverse events were diarrhea, rash, nausea, and fatigue; diarrhea was higher in the combination arm (P = .03). The incidence of symptomatic and asymptomatic cardiac events was low (combination therapy = 2% and 3.4%; monotherapy = 0.7% and 1.4%, respectively). Conclusion Despite disease progression on prior trastuzumab-based therapy, lapatinib in combination with trastuzumab significantly improved PFS and CBR versus lapatinib alone, thus offering a chemotherapy-free option with an acceptable safety profile to patients with ErbB2-positive MBC.
Sex-specific effect of body weight gain on systemic inflammation in subjects with COPD: results from the SAPALDIA cohort study 2
Authors: P-O. Bridevaux, M. W. Gerbase, C. Schindler, D. Felber Dietrich, I. Curjuric, J. Dratva, U. Ackermann-Liebrich, N. M. Probst-Hensch, J-M. Gaspoz, T. Rochat
Journal: European Respiratory Journal (2009)

Systemic inflammation may mediate the association between chronic obstructive pulmonary disease (COPD) and extrapulmonary comorbidities. We measured high-sensitivity C-reactive protein (hs-CRP) in COPD and quantified the effect modification by body weight change and sex. Using data from the Swiss study on Air Pollution and Lung Diseases in Adults (SAPALDIA; n = 5,479) with measurements of forced expiratory volume in 1 s (FEV 1 ), body weight and hs-CRP, we examined the association of hs-CRP and categories of body weight change (lost weight and weight gained 0–5%, 5–9%, 9–14% and &gt;14%) with fast FEV 1 decline. hs-CRP was elevated both in association with fast FEV 1 decline and body weight gain. Subjects with fast FEV 1 decline and weight gain (&gt;14%) had higher hs-CRP (2.0 mg·L −1 for females versus 1.6 mg·L −1 for males). After adjustment for age, smoking, physical activity, hormonal therapy and diabetes, elevated hs-CRP (&gt;3 mg) was found to be more likely in subjects with fast FEV 1 decline (OR males 1.38, OR females 1.42) and in those with weight gain &gt;14% (OR males 2.04, OR females 4.51). The association of weight gain and fast FEV 1 decline predicts a higher level of systemic inflammation. Since the effect of weight gain on systemic inflammation is larger in females than in males, weight gain may be a risk factor for extrapulmonary comorbidities in females with COPD.
Oral administration of a dominant T-cell determinant peptide inhibits allergen-specific TH1 and TH2 cell responses in Cry j 2–primed mice☆☆☆★
Authors: Kazuki Hirahara, Saburo Saito, Nobufusa Serizawa, Reiko Sasaki, Masahiro Sakaguchi, Sakae Inouye, Yoshifumi Taniguchi, Shuichi Kaminogawa, Akio Shiraishi
Journal: Journal of Allergy and Clinical Immunology (1998)
Survival after Treatment of Rabies with Induction of Coma
Authors: Rodney E. Willoughby, Kelly S. Tieves, George M. Hoffman, Nancy S. Ghanayem, Catherine M. Amlie-Lefond, Michael J. Schwabe, Michael J. Chusid, Charles E. Rupprecht
Journal: New England Journal of Medicine (2005)

We report the survival of a 15-year-old girl in whom clinical rabies developed one month after she was bitten by a bat. Treatment included induction of coma while a native immune response matured; rabies vaccine was not administered. The patient was treated with ketamine, midazolam, ribavirin, and amantadine. Probable drug-related toxic effects included hemolysis, pancreatitis, acidosis, and hepatotoxicity. Lumbar puncture after eight days showed an increased level of rabies antibody, and sedation was tapered. Paresis and sensory denervation then resolved. The patient was removed from isolation after 31 days and discharged to her home after 76 days. At nearly five months after her initial hospitalization, she was alert and communicative, but with choreoathetosis, dysarthria, and an unsteady gait.
A Polymorphism in the <b> <i>CDKN1B</i> </b> Gene Is Associated with Increased Risk of Hereditary Prostate Cancer
Authors: Bao-li Chang, Siqun L Zheng, Sarah D. Isaacs, Kathy E. Wiley, Aubrey Turner, Ge Li, Patrick C. Walsh, Deborah A. Meyers, William B. Isaacs, Jianfeng Xu
Journal: Cancer Research (2004)

Abstract The loss of cell cycle control is believed to be an important mechanism in the promotion of carcinogenesis. CDKN1B (p27) belongs to the Cip/Kip family and functions as an important cell cycle gatekeeper. Several lines of evidence from clinical studies and laboratory experiments demonstrate that CDKN1B is an important tumor suppressor gene in prostate cancer etiology. In addition, a case-control study has shown that the 326T/G (V109G) polymorphism in CDKN1B is associated with advanced prostate cancer. In light of the evidence for linkage between the chromosomal location of the CDKN1B gene (12p13) and prostate cancer susceptibility in several hereditary prostate cancer (HPC) populations, we hypothesized that sequence variants of CDKN1B play a role in HPC. To test this hypothesis, we first resequenced this gene in 96 HPC probands to identify germ-line mutations and sequence variants. We then genotyped the identified sequence variants among all family members of 188 HPC families and tested for their cosegregation with prostate cancer. In total, 10 sequence variants were identified, including three nonsynonymous changes. A family-based test, which is free from the effects of population stratification, revealed a significant association between single nucleotide polymorphism (SNP) -79C/T and prostate cancer (with a nominal P of 0.0005). The C allele of -79C/T was overtransmitted from parents to their affected offspring. Evidence for this association was primarily contributed by affected offspring whose age at diagnosis was &amp;lt;65 years. Together with the previous association study in a sporadic prostate cancer population, our new findings additionally suggest that germ-line variants of this gene play a role in prostate cancer susceptibility.
Temperament and Character Profiles and the Dopamine D4 Receptor Gene in ADHD
Authors: Deborah E. Lynn, Gitta Lubke, May Yang, James T. McCracken, James J. McGough, Janeen Ishii, Sandra K. Loo, Stanley F. Nelson, Susan L. Smalley
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: This study was designed to investigate the link among attention deficit hyperactivity disorder (ADHD) in adults, novelty-seeking temperament, and the 48-base pair (bp) dopamine D4 receptor (DRD4) gene variant. METHOD: This study drew from a larger molecular genetic study of ADHD in which the ascertainment criterion was having an affected sibling pair with ADHD. Parents (N=171) from 96 families provided data. Of the 171 parents, 56 (33%) had a lifetime history of ADHD, with 28 (50%) continuing to meet DSM-IV criteria (i.e., "persistent" ADHD). Latent variable modeling was used to test whether the DRD4 gene variant or Temperament and Character Inventory factors could predict ADHD. RESULTS: Using latent variable modeling, the authors were able to confirm the first-order factor structure of the Temperament and Character Inventory. Furthermore, novelty seeking predicted ADHD lifetime diagnosis (R2=26%), while the DRD4 gene variant independently predicted ADHD (R2=5%) but not novelty seeking. CONCLUSIONS: In this unique sample of parents from multiply affected ADHD families, novelty seeking and the 48-bp DRD4 variant were associated with a lifetime history of ADHD. However, the association between novelty seeking and ADHD does not appear to be due to variation in the 48-bp DRD4 variant.
Is the avoiding of operant theory a Pavlovian conditioned response?
Authors: Claudia D. Cardinal, Matthew E. Andrzejewski, Philip N. Hineline
Journal: Behavioral and Brain Sciences (2000)

The proposed heavy dependence on Pavlovian conditioning to account for social behavior confounds phylogenically and ontogenically selected behavior patterns and ignores the extension of the principle of selection by consequences from biological to learning theory. Instead of acknowledging operant relations, Domjan et al. construct vaguely specified mechanisms based upon anticipatory cost-benefit considerations that are not supported by the Pavlovian conditioning literature.
Bronchial bacterial colonization in patients with resectable lung carcinoma
Authors: M. Ioanas, J. Angrill, X. Baldo, F. Arancibia, J. Gonzalez, T. Bauer, E. Canalis, A. Torres
Journal: European Respiratory Journal (2002)

The pattern and clinical implications of bronchial bacterial colonization have been widely investigated in patients with chronic lung disease, particularly chronic obstructive pulmonary disease. The main aim of this study was to determine the frequency and risk factors for bronchial colonization in lung cancer patients who have undergone surgical resection. Forty-one patients with resectable lung cancer (22 (54%) active smokers, 52±23 pack-yrs) with a mean forced expiratory volume in one second of 80±16% predicted, were studied with bilateral protected specimen brush and lung tissue biopsy during the surgical procedure. Quantitative bacterial culture, susceptibility tests and histological examination of samples were performed. Bronchial colonization with ⩾1 potential pathogenic micro-organism was found in 17 of 41 (41%) patients. The most frequent strains isolated were: Haemophilus influenzae (35%), Streptococcus pneumoniae (13%) and Pseudomonas spp. (9%). The risk factors for bronchial colonization were central location of the tumour (odds ratio (OR)=9.2, confidence interval (CI) 95%=2.1–39.6, p=0.003) and increased body mass index (OR=1.6, CI 95%=1.2–2.2, p=0.005). The frequency of postoperative infectious pulmonary complications was low (five cases (12%)) and no relationship was observed with bronchial colonization. Patients with resectable lung carcinoma had a high rate of bronchial colonization (41%), mainly with potential pathogenic microorganisms. The independent risk factors for colonization in these patients were central location of the tumour and a high body mass index.