tbuckley/cabot-search huggingface dataset:
Fat Intake, Serum Cholesterol Concentration, and Atherosclerosis in the South African Bantu. Part I. Low Fat Intake and the Age Trend of Serum Cholesterol Concentration in the South African Bantu1
Authors: Alexander R. P. Walker, Ulla B. Arvidsson
Journal: Journal of Clinical Investigation (1954)

During the past few decades, interest in the ef- fects of overnutrition and undernutrition on blood cholesterol values, and their bearing on the pathogenesis of atherosclerosis, has led to the carrying out of numerous experimental studies on both ani- mals and man (1, 2).Several studies have shown that diets characterized by reduced fat intake, are associated with, or give rise to reductions in serum cholesterol levels (3,4).Dealing specifically with changes in fat intake, Keys, Mickelsen, Miller, and Chapman (5), using iso-caloric diets, found that when fat intake is substantially altered, well- marked changes appear in serum cholesterol con- centration, which, moreover, are independent of cholesterol intake.Confirmation of the correlation between fat in- take and cholesterol values is afforded by two types of evidence.Firstly, populations subjected to dietary restrictions, which invariably include reduced fat intake, have been shown to have lower cholesterol levels than when the relevant conditions returned to normal.Thus, in the last war, very low cholesterol values were observed among the inmates of various European concentration camps (6-8).Conversely, a significant rise in mean blood cholesterol level occurred in groups of Ger- man subjects from 1947 to 1949, this change being attributed to dietary improvements, including in- creased fat intake (9).The second type of evidence is provided by pop- ulations habituated to a high fat intake, e.g., the inhabitants of the United States (10) and Den- mark (11), who have higher mean serum choles- terol values than peoples accustomed to a lower fat intake, e.g., population groups in Italy (12), Spain (13), China (14), India (15), Belgian Congo
Cerebrovascular disease associated with sickle cell pulmonary hypertension
Authors: Gregory J. Kato, Matthew Hsieh, Roberto Machado, James Taylor, Jane Little, John A. Butman, Tanya Lehky, John Tisdale, Mark T. Gladwin
Journal: American Journal of Hematology (2006)

In patients with sickle cell disease, anemia is a recognized risk factor for stroke, death, and the development of pulmonary hypertension. We have proposed that hemolytic anemia results in endothelial dysfunction and vascular instability and can ultimately lead to a proliferative vasculopathy leading to pulmonary hypertension. Consistent with this mechanism of disease, we now report a case series of six patients with obliterative central nervous system vasculopathy who also have pulmonary hypertension and high hemolytic rate. These patients, identified in the course of a prospective screening study for pulmonary hypertension, presented with neurological symptoms prompting neuroimaging studies. Compared to 164 other patients of similar age in the screened population, those with newly diagnosed or clinically active cerebrovascular disease have significantly lower hemoglobin levels and higher levels of lactate dehydrogenase. A review of the literature suggests that many clinical, epidemiological, and physiological features of the arteriopathy of pulmonary hypertension closely overlap with those of stroke in sickle cell disease, both known to involve proliferative vascular intimal and smooth muscle hypertrophy and thrombosis. These cases suggest that cerebrovascular disease and pulmonary hypertension in sickle cell disease share common mechanisms, in particular, reduced nitric oxide bioactivity associated with particularly high-grade hemolysis. Clinicians should suspect occult cerebrovascular disease in sickle cell patients with pulmonary hypertension. Am. J. Hematol. 81:503–510, 2006. Published 2006 Wiley-Liss, Inc.
Genome-Wide Linkage Analyses of Systolic Blood Pressure Using Highly Discordant Siblings
Authors: Julia Krushkal, Robert Ferrell, Stephen C. Mockrin, Stephen T. Turner, Charles F. Sing, Eric Boerwinkle
Journal: Circulation (1999)

Elevated blood pressure is a risk factor for cardiovascular, cerebrovascular, and renal diseases. Complex mechanisms of blood pressure regulation pose a challenge to identifying genetic factors that influence interindividual blood pressure variation in the population at large.We performed a genome-wide linkage analysis of systolic blood pressure in humans using an efficient, highly discordant, full-sibling design. We identified 4 regions of the human genome that show statistical significant linkage to genes that influence interindividual systolic blood pressure variation (2p22.1 to 2p21, 5q33.3 to 5q34, 6q23.1 to 6q24.1, and 15q25.1 to 15q26.1). These regions contain a number of candidate genes that are involved in physiological mechanisms of blood pressure regulation.These results provide both novel information about genome regions in humans that influence interindividual blood pressure variation and a basis for identifying the contributing genes. Identification of the functional mutations in these genes may uncover novel mechanisms for blood pressure regulation and suggest new therapies and prevention strategies.
Targeting the Nuclear Factor-κB Rescue Pathway Has Promising Future in Human Renal Cell Carcinoma Therapy
Authors: Carole Sourbier, Sabrina Danilin, Véronique Lindner, Jacques Steger, Sylvie Rothhut, Nicolas Meyer, Didier Jacqmin, Jean-Jacques Helwig, Hervé Lang, Thierry Massfelder
Journal: Cancer Research (2007)

Abstract Metastatic renal cell carcinoma (RCC) remains refractory to therapies. The nuclear factor-κB (NF-κB) transcription factor is involved in cell growth, cell motility, and vascularization. We evaluated whether targeting NF-κB could be of therapeutic and prognostic values in human RCC. The activation of the NF-κB pathway in human RCC cells and tumors was investigated by Western blot. In vitro, the effects of BAY 11-7085 and sulfasalazine, two NF-κB inhibitors, on tumor cell growth were investigated by cell counting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling, and fluorescence-activated cell sorting. Their specificity toward NF-κB was analyzed by Western blot, confocal microscopy, NF-κB small interfering RNA, and NF-κB transcription assay. In vivo, the effects of BAY 11-7085 on the growth of human RCC tumors were investigated in nude mice. A tissue microarray (TMA) containing 241 cases of human RCC with 12 to 22 years of clinical follow-up and corresponding normal tissues was built up to assess prognostic significance of activated NF-κB. NF-κB is constitutively activated in cultured cells expressing or not the von Hippel-Lindau (VHL) tumor suppressor gene as a consequence of Akt kinase activation and in tumors. In vitro and in vivo NF-κB inhibition blocked tumor cell growth by inducing cell apoptosis. On the TMA, NF-κB activation was correlated with tumor dimension but was not found to be an independent prognostic factor for patient survival. This report provides strong evidence that the mechanisms responsible for the intrinsic resistance of RCC cells to apoptosis converge on NF-κB independently of VHL expression and that targeting this pathway has great anticancer potential. [Cancer Res 2007;67(24):11668–76]
298. Gene Therapy Against Prostate Cancer Using the HSV-tk/Prodrug System Followed by Prostatectomy
Authors: Augusto Rojas-Martinez, Laura K. Aguilar, Rocio Ortiz-Lopez, Jacinto Esteban-Maria, Juan F. Gonzalez-Guerrero, Raquel Garza-Guajardo, Juan P. Flores-Gutierrez, E. Brian Butler, Hugo A. Barrera-Saldana, Estuardo Aguilar-Cordova
Journal: Molecular Therapy (2005)

The authors present the first Phase I gene transfer clinical trial initiated in Latin America. The study population was low to high risk prostate cancer patients scheduled to undergo surgical tumor removal. The study was designed to evaluate the safety of the procedure, vector distribution within the tumor and pathologic effects of a four quadrant transrectal intra-prostatic injection of a non-replicating adenoviral vector carrying the HSV-tk gene (AdV-tk). Differences in these parameters after treatment with intravenous ganciclovir (GCV) vs oral valacyclovir (VCV) were also evaluated. Each subject received 1X1011 vector particles followed by 14 days of GCV or VCV prior to radical prostatectomy. No significant vector related toxicity was observed any of the ten analyzed patients; one subject abandoned the study prior to surgery for personal reasons. Vector sequences were detected in all tumors, with 30% to 85% positive distribution-cores from each gland, even in a specimen removed 15 weeks after vector injection. Pathological analyses demonstrated zones of regional tumor necrosis and inflammation of tumor tissue associated with significant CD8+ T-cell infiltration. Biological activity of the vector was evidenced by a spike in circulating PSA levels shortly after injection followed by an overall decrease from starting PSA concentration to the level observed just prior to surgery in seven of ten patients. No differences were observed between the two prodrugs. Patient follow-up has continued for an average of 52.8 months (range: 38 to 64 months) with encouraging results. These data demonstrate the safety and distribution-efficacy of simple outpatient procedure and oral prodrug for AdV-tk in prostate cancer.
Bcl-XL displays restricted distribution during T cell development and inhibits multiple forms of apoptosis but not clonal deletion in transgenic mice.
Authors: D A Grillot, R Merino, G Núñez
Journal: The Journal of Experimental Medicine (1995)

The survival of T lymphocytes is tightly controlled during development. Here, we show that Bcl-xL, a protein homologue of Bcl-2, is highly regulated in the thymus in a pattern different than that of Bcl-2. The maximum expression was in CD4+CD8+ thymocytes, a developmental stage where Bcl-2 is downregulated. To assess the role of Bcl-xL in thymocyte apoptosis, we generated mice overexpressing an E mu-bcl-x transgene within the T cell compartment. Constitutive expression of Bcl-xL resulted in accumulation of thymocytes and mature T cells in lymphoid organs. Thymocytes overexpressing Bcl-xL exhibited increased viability in vitro and were resistant to apoptosis induced by different signals, including glucocorticoid, gamma irradiation, calcium ionophore, and CD3 cross-linking. However, Bcl-xL was unable to block clonal deletion of thymocytes reactive with self-superantigens or H-Y antigen. These studies demonstrate that Bcl-2 and Bcl-xL, two functionally related proteins, are regulated independently during T cell development. In contrast to Bcl-2, which has been implicated in the maintenance of mature T cells, Bcl-xL appears to provide a survival signal for the maintenance of more immature CD4+CD8+ thymocytes before positive selection.
Behavioral Sexual Dimorphism in School-Age Children and Early Developmental Exposure to Dioxins and PCBs: A Follow-Up Study of the Duisburg Cohort
Authors: Gerhard Winneke, Ulrich Ranft, Jürgen Wittsiepe, Monika Kasper-Sonnenberg, Peter Fürst, Ursula Krämer, Gabriele Seitner, Michael Wilhelm
Journal: Environmental Health Perspectives (2013)

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that have been characterized as endocrine-disrupting chemicals (EDCs).Within the Duisburg birth cohort study, we studied associations of prenatal exposure to PCDD/Fs and PCBs with parent-reported sexually dimorphic behavior in children.We measured lipid-based and WHO2005-TEQ (toxic equivalents established in 2005 by the World Health Organization)-standardized PCDD/Fs and PCBs in maternal blood samples and in early breast milk using gas chromatography/high-resolution mass spectrometry. At the child's age of 6-8 years, parents (mostly mothers) reported sex-typical characteristics, preferred toys, and play activities using the Pre-School Activities Inventory (PSAI), which was used to derive feminine, masculine, and difference (feminine - masculine) scores. We estimated exposure-outcome associations using multivariate linear regression. A total of 91-109 children were included in this follow-up.Mean blood levels of summed WHO2005-TEQ-standardized dioxins (ΣPCDD/Fs) were 14.5 ± 6.4 pg/g blood lipids, and ΣPCBs were 6.9 ± 3.8 pg/g blood lipids, with similar values for milk lipids. Regression analyses revealed some highly significant interactions between sex and exposure-such as for ΣPCBs in milk, pronounced positive (boys: β = 3.24; CI = 1.35, 5.14) or negative (girls: β = -3.59; CI = -1.10, -6.08) associations with reported femininity. Less pronounced and mostly insignificant but consistent associations were found for the masculinity score, positive for boys and negative for girls.Given our results and the findings of previous studies, we conclude that there is sufficient evidence that these EDCs modify behavioral sexual dimorphism in children, presumably by interacting with the hypothalamic-pituitary-gonadal axis.Winneke G, Ranft U, Wittsiepe J, Kasper-Sonnenberg M, Fürst P, Krämer U, Seitner G, Wilhelm M. 2014. Behavioral sexual dimorphism in school-age children and early developmental exposure to dioxins and PCBs: a follow-up study of the Duisburg Cohort. Environ Health Perspect 122:292-298; http://dx.doi.org/10.1289/ehp.1306533.
Cetuximab, a Monoclonal Antibody Targeting the Epidermal Growth Factor Receptor, in Combination With Gemcitabine for Advanced Pancreatic Cancer: A Multicenter Phase II Trial
Authors: Henry Q. Xiong, Arthur Rosenberg, Albert LoBuglio, William Schmidt, Robert A. Wolff, John Deutsch, Michael Needle, James L. Abbruzzese
Journal: Journal of Clinical Oncology (2004)

To determine the response rate, time to disease progression, survival duration and rate, and toxicity with the combination of cetuximab and gemcitabine in patients with epidermal growth factor receptor (EGFR)-expressing advanced pancreatic cancer.Patients with measurable locally advanced or metastatic pancreatic cancer who had never received chemotherapy for their advanced disease and had immunohistochemical evidence of EGFR expression were eligible for the multicenter phase II trial. Patients were treated with cetuximab at an initial dose of 400 mg/m(2), followed by 250 mg/m(2) weekly for 7 weeks. Gemcitabine was administered at 1,000 mg/m(2) for 7 weeks, followed by 1 week of rest. In subsequent cycles, cetuximab was administered weekly, and gemcitabine was administered weekly for 3 weeks every 4 weeks.Sixty-one patients were screened for EGFR expression, 58 patients (95%) had at least 1+ staining, and 41 were enrolled onto the trial. Five patients (12.2%) achieved a partial response, and 26 (63.4%) had stable disease. The median time to disease progression was 3.8 months, and the median overall survival duration was 7.1 months. One-year progression-free survival and overall survival rates were 12% and 31.7%, respectively. The most frequently reported grade 3 or 4 adverse events were neutropenia (39.0%), asthenia (22.0%), abdominal pain (22.0%), and thrombocytopenia (17.1%).Cetuximab in combination with gemcitabine showed promising activity against advanced pancreatic cancer. Further clinical investigation is warranted.
Understanding the molecular sensitization for <scp>C</scp>ypress pollen and peach in the <scp>L</scp>anguedoc‐<scp>R</scp>oussillon area
Authors: D. Caimmi, D. Barber, K. Hoffmann‐Sommergruber, H. Amrane, P.‐J. Bousquet, H. Dhivert‐Donnadieu, P. Demoly
Journal: Allergy (2012)

Abstract Background Cypress allergy is a typical winter pollinosis and the most frequent one in the S outh of F rance. Main symptoms are rhinitis, conjunctivitis, and asthma. Peach allergy is common too in S outhern E urope. Allergic cross‐reactions between cypress and peach have been reported, including an oral allergy syndrome. We wanted to investigate whether a cross‐reactive allergen between cypress and peach might be responsible for the observed clinical association. Methods We analyzed 127 patients included over a 3‐month period, outside the pollen season, and we dosed specific I g E levels, for selected, individual allergens. Results Patients sensitized to peach were mainly positive for the peach‐nonspecific lipid‐transfer protein. Conclusions Profilins or thaumatins could not explain the observed clinical association between cypress and peach.
Informed consent and research
Authors: D. Benatar, S. R Benatar
Journal: BMJ (1998)

In the debate opened by the BMJ on whether research is ethical if it meets the standards of the Declaration of Helsinki but is conducted without informed consent, Len Doyal provides some powerful arguments for why the request for informed consent should be inviolable.1

While vigorously defending the inviolability of informed consent, he concedes that it is not necessary in certain circumstances. An uncontroversial case is that of incompetent patients (although even here other rigorous requirements must be met). However, the other exceptional cases he mentions seem to have some unfortunate implications for his defence of informed consent. He thinks that for epidemiological research on patient records the informed consent requirement may be waived if certain conditions are met: ( a ) that access to the clinical record is essential to the research; ( b ) that consent is not practicable; ( c ) that the research is of sufficient merit; ( d ) that it may benefit the patient whose records are studied; ( e ) that, when possible, the researchers are unable to connect the records with the patient's identity, but that where this …
The Labile Properties of the Pulmonary Vascular Bed in Patients with Pulmonary Emphysema.
Authors: R. H. Behnke
Journal: Annals of Internal Medicine (1961)

s1 May 1961The Labile Properties of the Pulmonary Vascular Bed in Patients with Pulmonary Emphysema.R. H. Behnke, M.D., (Assoc.), J. F. Williams Jr., M.D., D. H. White, M.D.R. H. Behnke, M.D., (Assoc.)Search for more papers by this author, J. F. Williams Jr., M.D.Search for more papers by this author, D. H. White, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-5-1059_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe factors which produce pulmonary hypertension in patients with pulmonary emphysema are poorly understood. The present study was undertaken in such patients to determine whether this vascular bed functions as a fixed rigid system or is labile as shown by pharmacologic alteration of its tone.Patients with pulmonary emphysema, established by clinical and laboratory tests, who were free of congestive heart failure, were studied at rest and with steady-state exercise prior to and during infusion of acetylcholine (2 to 8 mg./min.) and isoproterenol (.005 to .010 mg./min.) with determination of wedge, pulmonary, and systemic arterial pressures and cardiac output (CO).... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Indianapolis, Ind. (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1961Volume 54, Issue 5Page: 1059-1059KeywordsAcetylcholineBlood pressureCardiac outputClinical laboratoriesEmphysemaExerciseHeart failureIsoproterenolLaboratory testsPulmonary hypertension ePublished: 1 December 2008 Issue Published: 1 May 1961 PDF downloadLoading ...
Epidemiological study of peptic ulcer in the south of India. Observations from Madras on the changing incidence of peptic ulcer, with special reference to causation.
Authors: S L Malhotra
Journal: Gut (1967)

EDITORIAL COMMENT The evidence from this study suggests that peptic ulcer in India is no different essentially from peptic ulcer seen in western countries.This is a valuable epidemiological study with interesting speculation on aetiology.The study of regional differences may contribute towards the final solution of the ulcer problem.Big differences in the prevalence of peptic ulcer are known to exist in different parts of India (Somervell and Orr, 1936; Dogra, 1940; Hadley, 1959; and Malhotra, 1964).It is also believed that peptic ulcer is different from the disease in the west in being less acute and less likely to bleed or perforate (Somervell and Orr, 1936;Raghavachari, 1959;and Gregg, 1959).Although the geographical variations in ulcer frequency noted by previous workers are mirrored in more recent studies (Konstam, 1959; Hadley, 1959; Malhotra, 1964, 1965; Malhotra, Majumdar, and Bardoloi, 1964), it is less certain whether the disease is different from the disease in the west, and our previous study of peptic ulcer in Assam (north- east part of India) has formed the basis for the con- clusion that peptic ulcer in India is no different from peptic ulcer seen in the west (Malhotra et al., 1964).The study reported in this paper was under- taken to determine the incidence and behaviour of ulcer, as it now occurs in the south of India. MATERIAL AND METHODSThe study is confined to 30,942 railway workers, all south Indians, between the ages of 18 and 55 years, and their families who live and work in the city of Madras.This number is derived by totalling the number of railway employees on the pay-rolls for the period I January 1961 to 31 December 1964, and dividing this by 4. The hospital services for this population are provided almost exclusively by the Perambur Railway Hospital at Madras and its associated units.The services provided are comprehensive, free of charge, and include all the specialities.
Traditional Insulin-Use Practices and the Incidence of Bacterial Contamination and Infection
Authors: Laura M Borders, Pauline R Bingham, Matthew C Riddle
Journal: Diabetes Care (1984)

While complex procedures are usually recommended to prevent infection at insulin injection sites, adherence to these procedures is imperfect and their value incompletely established. Among 254 adult insulin users in two clinic populations, the reported prevalence of complete performance of four traditional insulin-use practices (handwashing, vial prep, skin prep, discarding of plastic syringes after one use) was 29%, and none of the individual practices considered was performed regularly by more than two-thirds of the subjects. Even so, there was no infection at 2828 injection sites, and there was no significant bacterial contamination of insulin or syringes. These findings fail to support the view that traditional practices provide protection to insulin users against infection or bacterial growth in insulin or syringes. The authors suggest that modification of traditional teaching methods would do no harm, and that benefits could include financial savings, improved client success with self-care, and enhanced health care provider credibility.