tbuckley/cabot-search huggingface dataset:
Can We Say What Diet Is Best for Health?
Authors: D.L. Katz, S. Meller
Journal: Annual Review of Public Health (2014)

Diet is established among the most important influences on health in modern societies. Injudicious diet figures among the leading causes of premature death and chronic disease. Optimal eating is associated with increased life expectancy, dramatic reduction in lifetime risk of all chronic disease, and amelioration of gene expression. In this context, claims abound for the competitive merits of various diets relative to one another. Whereas such claims, particularly when attached to commercial interests, emphasize distinctions, the fundamentals of virtually all eating patterns associated with meaningful evidence of health benefit overlap substantially. There have been no rigorous, long-term studies comparing contenders for best diet laurels using methodology that precludes bias and confounding, and for many reasons such studies are unlikely. In the absence of such direct comparisons, claims for the established superiority of any one specific diet over others are exaggerated. The weight of evidence strongly supports a theme of healthful eating while allowing for variations on that theme. A diet of minimally processed foods close to nature, predominantly plants, is decisively associated with health promotion and disease prevention and is consistent with the salient components of seemingly distinct dietary approaches. Efforts to improve public health through diet are forestalled not for want of knowledge about the optimal feeding of Homo sapiens but for distractions associated with exaggerated claims, and our failure to convert what we reliably know into what we routinely do. Knowledge in this case is not, as of yet, power; would that it were so.
BILATERAL THORACIC ZOSTEROID SPREADING MARGINATE TELANGIECTASIA — PROBABLY A VARIETY OF "CARCINOMA ERYSIPELATODES" (C. RASCH) — ASSOCIATED WITH UNILATERAL MAMMARY CARCINOMA, AND BETTER TERMED "CARCINOMA TELANGIECTATICUM". *
Authors: F. PARKES WEBER
Journal: British Journal of Dermatology (1933)
Angiogenesis Ischemic and Neoplastic Disorders
Authors: Gregg L. Semenza
Journal: Annual Review of Medicine (2003)

Vascular development involves vasculogenesis, in which endothelial cells form a primary tubular network, as well as angiogenesis, in which vessel size and structure are modified based upon flow and branching occurs to insure that all cells receive adequate O 2 delivery. In adults, angiogenesis occurs in response to tissue hypoxia/ischemia and plays an important role in determining the progression of ischemic heart disease and cancer. A critical molecular pathway induced by hypoxia/ischemia is the activation of hypoxia-inducible factor 1, a transcriptional activator of genes encoding vascular endothelial growth factor and other important mediators of angiogenesis. Novel therapeutic approaches that involve stimulating angiogenesis in ischemic tissue and inhibiting angiogenesis in neoplastic tissue are currently being evaluated in clinical trials.
The Addition of AG-013736 to Fractionated Radiation Improves Tumor Response without Functionally Normalizing the Tumor Vasculature
Authors: Bruce M. Fenton, Scott F. Paoni
Journal: Cancer Research (2007)

Abstract Although antiangiogenic strategies have proven highly promising in preclinical studies and some recent clinical trials, generally only combinations with cytotoxic therapies have shown clinical effectiveness. An ongoing question has been whether conventional therapies are enhanced or compromised by antiangiogenic agents. The present studies were designed to determine the pathophysiologic consequences of both single and combined treatments using fractionated radiotherapy plus AG-013736, a receptor tyrosine kinase inhibitor that preferentially inhibits vascular endothelial growth factor receptors. DU145 human prostate xenograft tumors were treated with (a) vehicle alone, (b) AG-013736, (c) 5 × 2 Gy/wk radiotherapy fractions, or (d) the combination. Automated image processing of immunohistochemical images was used to determine total and perfused blood vessel spacing, overall hypoxia, pericyte/collagen coverage, proliferation, and apoptosis. Combination therapy produced an increased tumor response compared with either monotherapy alone. Vascular density progressively declined in concert with slightly increased α-smooth muscle actin–positive pericyte coverage and increased overall tumor hypoxia (compared with controls). Although functional vessel endothelial apoptosis was selectively increased, reductions in total and perfused vessels were generally proportionate, suggesting that functional vasculature was not specifically targeted by combination therapy. These results argue against either an AG-013736- or a combination treatment–induced functional normalization of the tumor vasculature. Vascular ablation was mirrored by the increased appearance of dissociated pericytes and empty type IV collagen sleeves. Despite the progressive decrease in tumor oxygenation over 3 weeks of treatment, combination therapy remained effective and tumor progression was minimal. [Cancer Res 2007;67(20):9921–8]
Insulin Sensitivity, Vascular Reactivity, and Clamp-Induced Vasodilatation in Essential Hypertension
Authors: Andrea Natali, Stefano Taddei, Alfredo Quiñones Galvan, Stefania Camastra, Simona Baldi, Silvia Frascerra, Agostino Virdis, Isabella Sudano, Antonio Salvetti, Ele Ferrannini
Journal: Circulation (1997)

Background Insulin resistance and vascular abnormalities have both been described in patients with essential hypertension. Whether these defects are associated with one another in the same individual has not been established. Methods and Results Whole-body insulin sensitivity (by the insulin clamp technique), forearm minimal vascular resistances, and the dose-response curve to acetylcholine, sodium-nitroprusside, and norepinephrine were measured in a group of 29 male patients with untreated essential hypertension. When the patients were divided into tertiles according to their level of insulin sensitivity, resistant and sensitive hypertensives were matched on several potential confounders of insulin action and vascular function. These subgroups showed similar minimal vascular resistances (2.5±0.2 versus 3.2±0.6 mm Hg per mL · min −1 · dL −1 ) and superimposable responses to graded intraarterial infusions of acetylcholine, sodium-nitroprusside, and norepinephrine. No correlation was found between the vascular parameters (slope of the curve or maximal response) and insulin-mediated glucose uptake in the whole group. During the clamp, insulin sensitive patients tended to have greater increments in forearm blood flow when compared to their insulin resistant counterparts (+53±21 versus +9±7%, P =.06); in the whole group, clamp-induced vasodilatation was weakly related to insulin-mediated glucose uptake ( r =.44, P &lt;.02) as well as to the slope of the acetylcholine dose-response curve ( r =.40, P &lt;.04). Together, these two responses explained 30% (multiple r =.55, P &lt;.01) of the variability in insulin-induced vasodilatation. Conclusions Metabolic insulin resistance in essential hypertension is not associated with abnormalities in vascular structure, acetylcholine or nitroprusside-induced vasodilatation, or vascular adrenergic reactivity. Degree of insulin sensitivity and acetylcholine sensitivity explain a small portion of the variability of the clamp-induced vasodilatation in hypertensive patients.
ZINC AND BRAIN INJURY
Authors: Dennis W. Choi, Jae Y. Koh
Journal: Annual Review of Neuroscience (1998)

▪ Abstract Zinc is an essential catalytic or structural element of many proteins, and a signaling messenger that is released by neural activity at many central excitatory synapses. Growing evidence suggests that zinc may also be a key mediator and modulator of the neuronal death associated with transient global ischemia and sustained seizures, as well as perhaps other neurological disease states. Manipulations aimed at reducing extracellular zinc accumulation, or cellular vulnerability to toxic zinc exposure, may provide a novel therapeutic approach toward ameliorating pathological neuronal death in these settings.
Pediatric Bipolar Disorder
Authors: Ellen Leibenluft, Brendan A. Rich
Journal: Annual Review of Clinical Psychology (2008)

In the past decade, interest in and research on pediatric bipolar disorder (BD) has increased substantially. Prevalence rates of the disorder have doubled in outpatient settings, while twice as many research articles on pediatric BD were published in the past five years as in the prior decade. This review focuses on recent developments in the study of pediatric BD. We examine current research on the diagnostic boundaries of BD in youths, in particular the issues of episodicity and irritability, and provide assessment guidelines. We review data elucidating the pathophysiology of pediatric BD, with a focus on how these results may inform diagnosis. Finally, we discuss treatment approaches for pediatric BD, particularly psychotherapeutic interventions. Throughout the review, we pay particular attention to youths with severe chronic irritability, hyperarousal, and hyperreactivity, who reflect the population in whom the diagnosis of BD is most debated.
The oxysterol–CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils
Authors: Laura Raccosta, Raffaella Fontana, Daniela Maggioni, Claudia Lanterna, Eduardo J. Villablanca, Aida Paniccia, Andrea Musumeci, Elena Chiricozzi, Maria Letizia Trincavelli, Simona Daniele, Claudia Martini, Jan-Ake Gustafsson, Claudio Doglioni, Safiyè Gonzalvo Feo, Andrea Leiva, Maria Grazia Ciampa, Laura Mauri, Cristina Sensi, Alessandro Prinetti, Ivano Eberini, J. Rodrigo Mora, Claudio Bordignon, Knut R. Steffensen, Sandro Sonnino, Silvano Sozzani, Catia Traversari, Vincenzo Russo
Journal: The Journal of Experimental Medicine (2013)

Tumor-infiltrating immune cells can be conditioned by molecules released within the microenvironment to thwart antitumor immune responses, thereby facilitating tumor growth. Among immune cells, neutrophils play an important protumorigenic role by favoring neoangiogenesis and/or by suppressing antitumor immune responses. Tumor-derived oxysterols have recently been shown to favor tumor growth by inhibiting dendritic cell migration toward lymphoid organs. We report that tumor-derived oxysterols recruit protumor neutrophils in a liver X receptor (LXR)–independent, CXCR2-dependent manner, thus favoring tumor growth by promoting neoangiogenesis and immunosuppression. We demonstrate that interfering with the oxysterol–CXCR2 axis delays tumor growth and prolongs the overall survival of tumor-bearing mice. These results identify an unanticipated protumor function of the oxysterol–CXCR2 axis and a possible target for cancer therapy.
Altered Cardiac Sarcoplasmic Reticulum Function of Intact Myocytes of Rat Ventricle During Metabolic Inhibition
Authors: C. L. Overend, D. A. Eisner, S. C. O’Neill
Journal: Circulation Research (2001)

Abstract —Changes in the behavior of the sarcoplasmic reticulum (SR) in rat ventricular myocytes were investigated under conditions of metabolic inhibition using laser-scanning confocal microscopy to measure intracellular Ca 2+ and the perforated patch-clamp technique to measure SR Ca 2+ content. Metabolic inhibition had several effects on SR function, including reduced frequency of spontaneous releases of Ca 2+ (sparks and waves of Ca 2+ -induced Ca 2+ release), increased SR Ca 2+ content (79.4±5.7 to 115.2±6.6 μmol/L cell volume [mean±SEM; P &lt;0.001]), and, after a wave of Ca 2+ release, slower reuptake of Ca 2+ into the SR (rate constant of fall of Ca 2+ reduced from 8.5±1.1 s − 1 in control to 5.2±0.4 s − 1 in metabolic inhibition [ P &lt;0.01]). Inhibition of L-type Ca 2+ channels with Cd 2+ (100 μmol/L) did not reproduce the effects of metabolic inhibition on spontaneous Ca 2+ sparks. These results are evidence of inhibition of both Ca 2+ release and reuptake mechanisms. Reduced frequency of release could be attributable to either of these effects, but the increased SR Ca 2+ content at the time of reduced frequency of spontaneous release of Ca 2+ shows that the dominant effect of metabolic inhibition is to inhibit release of Ca 2+ from the SR, allowing the accumulation of greater than normal amounts of Ca 2+ . In the context of ischemia, this extra accumulation of Ca 2+ would present a risk of potentially arrhythmogenic, spontaneous release of Ca 2+ on reperfusion of the tissue.
A multicenter cohort study to compare quality of life in breast cancer patients according to sentinel lymph node biopsy or axillary lymph node dissection
Authors: T.S. Dabakuyo, J. Fraisse, S. Causeret, S. Gouy, M.-M. Padeano, C. Loustalot, J. Cuisenier, J.-M. Sauzedde, M. Smail, J.-P. Combier, P. Chevillote, C. Rosburger, S. Boulet, P. Arveux, F. Bonnetain
Journal: Annals of Oncology (2009)
Pentoxifylline in treatment of sarcoidosis.
Authors: P Zabel, P Entzian, K Dalhoff, M Schlaak
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The optimal therapy for sarcoidosis remains unclear. Most patients show a short-term response to corticosteroid therapy, but they have to face the risk of significant side effects. Because tumor necrosis factor alpha (TNF) plays a critical role in granuloma formation and sustenance as well as in the progression of sarcoidosis, we investigated pentoxifylline (POF), which exerts TNF-inhibitory activity, as a therapeutic agent in active pulmonary sarcoidosis. Twenty-three previously untreated patients with documented disease progression during the preceding 3 mo were treated with POF (25 mg/kg daily) and followed for 6 mo of therapy. Two patients were lost to follow-up, and three patients discontinued POF therapy because of gastrointestinal side effects; 18 patients were thus evaluated. Eleven patients improved, seven remained stable and, most importantly, none deteriorated. Lung function tests-DL(CO), Pa(O2) and Pa(O2)[exercise]-were significantly improved in the patient group as a whole and increased in a highly significant manner in those who improved. Three patients with corticosteroid-resistant disease progression were additionally treated with a combination of corticosteroids with POF. In all three patients the combination therapy resulted in an immediate complete decrease of disease activity, even after tapering prednisone to 7.5 mg daily or tapering off corticosteroids. These promising results suggest that POF may improve therapeutic regimens in pulmonary sarcoidosis either by sparing or replacing corticosteroids.
The Effect of Paroxetine on 5-HT<sub>2A</sub> Receptors in Depression: An [<sup>18</sup>F]Setoperone PET Imaging Study
Authors: J H Meyer, S Kapur, B Eisfeld, G M Brown, S Houle, J DaSilva, A A Wilson, S Rafi-Tari, H S Mayberg, S H Kennedy
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: In the cortex of animals, serotonin (5-HT) levels increase after several weeks of treatment with selective serotonin reuptake inhibitors (SSRIs). Studies using an intrasubject design to examine the effects of SSRI treatment on 5-HT2A receptors in the cortex of drug-free depressed patients are needed. In theory, agonist stimulation of 5-HT2A receptors could be relevant to SSRI treatment by promoting neuronal growth and survival as well as direct elevation of mood. The objective of this study was to evaluate the effect of 6 weeks of paroxetine treatment on 5-HT2A receptors in depressed patients. METHOD: After a medication-free period of at least 3 months, 19 depressed patients were treated for 6 weeks with paroxetine, 20 mg/day. The authors used [18F]setoperone and positron emission tomography to assess 5-HT2A receptor binding potential in the patients before and after treatment and in 19 age-matched healthy subjects. RESULTS: 5-HT2A binding potential declined with age in all cortical regions in the depressed and healthy subjects. There was a significant interaction between age and treatment effect on 5-HT2A binding potential in all cortical regions. Subjects aged 20 to 30 years had a 10% decrease in 5-HT2A binding potential after treatment, whereas subjects aged 30 to 40 had no change. No regional differences in 5-HT2A binding potential between depressed and healthy subjects were found. CONCLUSIONS: 5-HT2A receptors down-regulate in young depressed subjects after treatment with paroxetine, but this down-regulation attenuates with age. This suggests that over 6 weeks paroxetine treatment increases 5-HT agonism on 5-HT2A receptors in the cortex of young patients with depression.
Effect of 2,3-diphosphoglycerate on oxygen affinity of blood in sickle cell anemia
Authors: Samuel Charache, Santiago Grisolia, Adam J. Fiedler, Andre E. Hellegers
Journal: Journal of Clinical Investigation (1970)

Blood of patients with sickle cell anemia (SS) exhibits decreased affinity for oxygen, although the oxygen affinity of hemoglobin S is the same as that of hemoglobin A. SS red cells contain more 2,3-diphosphoglycerate (DPG) than normal erythrocytes. The oxygen affinity of hemolyzed red cells is decreased by added DPG, and hemolysates prepared from SS red cells do not differ from normal hemolysates in this regard. Reduction of oxygen affinity to the levels found in intact SS red cells required DPG concentrations in excess of those found in most SS patients. The same was true of oxygen affinity of patients with pyruvate kinase deficiency. Other organic phosphates, as well as inorganic ions, are known to alter the oxygen affinity of dilute solutions of hemoglobin. These substances, the state of aggregation of hemoglobin molecules, and cytoarchitectural factors probably play roles in determining oxygen affinity of both normal and SS red cells.
FK 506–A promise of good things to come?
Authors: James Neuberger
Journal: Hepatology (1991)

The new immunosuppressive drug FK 506 was used from the outset with low doses of prednisone to treat 120 recipients of primary liver grafts and 20 more patients undergoing liver retransplantation. The patient survival rate after 2 to 8 months in the primary liver transplantation series is 93.3%, with original graft survival of 87.5%. Of the 20 patients in the hepatic retransplant series, 17 (85%) are living. Almost all of the surviving patients have good liver function. In addition 11 hearts, 2 double lungs, and a heart-lung have been transplanted under FK 506, with survival of all 14 patients. With all of the organ systems so far tested, including the kidney (which has been reported elsewhere), rejection usually has been controlled without additional drugs and with lower average steroid doses than in the past. Nephrotoxicity has been observed, but not to an alarming degree, and there has been a notable absence of hypertension. There is a suggestion that serum cholesterol may be lowered by FK 506, but this is unproved. Although the adverse reactions of FK 506 and the immunosuppressive mechanisms resemble those of cyclosporine, our preliminary observations suggest that FK 506 may have a more advantageous therapeutic index.
GENETIC FACTORS IN SCHIZOPHRENIA
Authors: IAN GREGORY
Journal: American Journal of Psychiatry (1960)

It is generally accepted that intelligence in the general population, and high-grade mental deficiency, are largely determined by the cumulative effects of polygenes. Simple Mendelian inheritance is well established as causative of certain forms of (usually) low-grade mental deficiency, and other degenerations involving the central nervous system, including Huntington's chorea. There is still considerable doubt concerning the significance of genetic factors in the etiology of "functional" psychiatric disorders. Schizophrenia has been extensively studied by means of twin and family data, but the extent and nature of possible genetic factors in this syndrome remain uncertain. Twin studies suggest that heredity may be slightly more important in predisposing to schizophrenia than in determining intelligence, but these studies are complicated by very serious methodological difficulties, some of which have been discussed. The frequency of schizophrenia is significantly greater in families of schizophrenics than in the general population, but observed frequencies in different classes of relatives do not conform with those expected on the basis of simple Mendelian dominance or recessivity. Expected frequencies in various classes of relatives have been examined under each of three hypotheses involving incomplete penetrance and/or expressivity (in homozygote and/or heterozygote). Data on consanguinity, assortative mating, mortality and fertility have been outlined. It has been concluded that no monogenic hypothesis is compatible with all the data recorded, and three alternatives (that are not mutually exclusive) have been briefly considered: 1. Predominantly environmental causation, 2. Genetic heterogeneity, 3. Polygenic inheritance. Statistical associations between schizophrenia and limited intelligence, inferior socio-economic status, maternal mortality, and immunological or other somatic characteristics of schizophrenics, are all compatible with the latter hypotheses. The data recorded on schizophrenia are complex and do not conform with any simple genetic hypothesis. Pending the results of considerable further investigation, theories concerning the role of possible genetic factors in the development of schizophrenia and other "functional" psychiatric disorders will remain in the realm of speculation.
1172-74 Pulmonary hypertension is strongly associated with mortality in sickle cell disease: Comparison of echocardiographic outcome predictors
Authors: Yukitaka Shizukuda, Vandana Sachdev, Inez Ernst, James S Nichols, Maria Jison, Bernice Brown, William Blackwelder, Griffin P Rodgers, Oswaldo Castro, Frederick P Ognibene, Jonathan P Plehn, Mark T Gladwin
Journal: Journal of the American College of Cardiology (2004)
Jejunal water and electrolyte absorption from two proprietary enteral feeds in man: importance of sodium content.
Authors: R C Spiller, B J Jones, D B Silk
Journal: Gut (1987)

Jejunostomy losses of Na+ and water during enteral nutrition after massive intestinal resection may be severe. We have attempted to analyse this practical problem by using an in vivo perfusion technique in healthy volunteers to study Na+, water and nutrient absorption from a short (25 cm) segment of jejunum during perfusion of an isotonic solution of the elemental diet Vivonex. Further solutions made from the amino acid and carbohydrate components of Vivonex were also perfused in part I of the study in order to determine the causes of the marked Na+ and water secretion seen during Vivonex perfusion. Low initial Na+ concentration was found to be the major determinant of net Na+ secretion, initial Na+ concentration correlating significantly with Na+ absorption (r = 0.95, n = 7 p less than 0.001). Water absorption correlated with net absorption of NaCl (r = 0.82, n = 7 p less than 0.01). There was, however, a better correlation with total absorption of NaCl plus amino acids (r = 0.99, n = 7, p less than 0.01). In part II of the study separate isotonic solutions of NaCl, glucose, and the polymeric diet, Ensure were also studied. Net sodium secretion occurred during glucose and Ensure perfusion, as predicted from their low Na+ concentration. Owing to rapid sucrose absorption from Ensure there was substantial luminal disappearance of osmotically active particles and hence marked water absorption, which was accurately predicted using the regression equation for water absorption derived in part I, substituting sucrose absorption for amino acid absorption. We conclude that the marked Na+ and water secretion observed during Vivonex perfusion is not a unique property of this amino acid based diet but is due to its low Na+ content.