tbuckley/cabot-search huggingface dataset:
GnRH-II Antagonists Induce Apoptosis in Human Endometrial, Ovarian, and Breast Cancer Cells via Activation of Stress-Induced MAPKs p38 and JNK and Proapoptotic Protein Bax
Authors: Stefanie Fister, Andreas R. Günthert, Babette Aicher, Klaus W. Paulini, Günter Emons, Carsten Gründker
Journal: Cancer Research (2009)

Abstract Recently, we could show that gonadotropin-releasing hormone (GnRH)-II antagonists induce apoptosis in human endometrial, ovarian, and breast cancer cells in vitro and in vivo. In the present study, we have ascertained receptor binding and effects of GnRH-II antagonists on mitogenic signal transduction and on activation of proapoptotic protein Bax. The GnRH-II antagonists tested showed EC50 values for GnRH-I receptor binding in the range of 1 to 2 nmol/L. The GnRH-II agonist [d-Lys6]GnRH-II showed an EC50 value for GnRH-I receptor binding of ∼1,000 nmol/L. Agonistic activity on GnRH-I receptor function with an EC50 of 13 nmol/L has been determined for [d-Lys6]GnRH-II. Antagonistic activities with EC50 values in the range of 1 nmol/L were determined for the GnRH-II antagonists. Treatment of human endometrial, ovarian, and breast cancer cells with GnRH-II antagonists resulted in time-dependent activation of stress-induced mitogen-activated protein kinases p38 and c-Jun NH2-terminal kinase. In addition, treatment with GnRH-II antagonists induced time-dependent activation of proapoptotic protein Bax. GnRH-II antagonists are not involved in activation of protein kinase B/Akt or extracellular signal-regulated kinase 1/2. The GnRH-II antagonists tested had similar binding affinities to the GnRH-I receptor comparable with that of GnRH-I antagonist Cetrorelix. Referring to the cyclic AMP response element reporter gene activation assay, the GnRH-II agonist [d-Lys6]GnRH-II has to be classified as an agonist at the GnRH-I receptor, whereas the GnRH-II antagonists tested are clear antagonists at the GnRH-I receptor. GnRH-II antagonists induce apoptotic cell death in human endometrial, ovarian, and breast cancer cells via activation of stress-induced mitogen-activated protein kinases p38 and c-Jun NH2-terminal kinase followed by activation of proapoptotic protein Bax. [Cancer Res 2009;69(16):6473–81]
Association of Albuminuria and Cancer Incidence
Authors: Lone Jørgensen, Ivar Heuch, Trond Jenssen, Bjarne K. Jacobsen
Journal: Journal of the American Society of Nephrology (2008)

Albuminuria, which is associated with noncardiovascular mortality, might be a result of altered vascular permeability caused by cytokines and other tumor cell products. The aim of this population-based, longitudinal study was to examine whether elevated albumin-to-creatinine ratio (ACR) is associated with cancer incidence. A total of 5425 participants without diabetes or previous cancer in the Tromsø Study were followed; 590 had a first diagnosis of cancer during 10.3 yr of follow-up. The ACR at baseline significantly correlated with the incidence of cancer, even after adjustment for age, gender, body mass index, physical activity, and smoking (P < 0.001). Participants with ACR in the highest quintile were 8.3- and 2.4-fold more likely to receive a diagnosis of bladder cancer and lung cancer, respectively, compared with those with ACR in the lowest quintile after similar adjustments. It is concluded that albuminuria is associated with cancer incidence in individuals without a history of diabetes, macroalbuminuria, or previous cancer and that it might confer risks of varying magnitude for different types of cancer.
Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women
Authors: K H Costenbader, D Feskanich, M Holmes, E W Karlson, E Benito-Garcia
Journal: Annals of the Rheumatic Diseases (2007)

Vitamin D has immune-modulating effects and may protect against the development of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).We identified incident cases of SLE and RA among 186 389 women followed from 1980 to 2002 in the Nurses' Health Study and Nurses' Health Study II cohorts. We excluded subjects where SLE or RA was not confirmed by medical record review, and those who failed to return questionnaires. Semi-quantitative food frequency questionnaires assessed vitamin D intake from food and supplements. We used cumulative-updated total energy-adjusted dietary exposures for each 2-year cycle. Relationships between vitamin D intake and incident SLE and RA were examined in age-adjusted and Cox proportional hazards models, adjusted for confounders. Results were pooled using meta-analysis random effects models.We confirmed 190 incident cases of SLE and 722 of RA with dietary information. Increasing levels of vitamin D intake had no relationship to the relative risk of developing either SLE or RA.Vitamin D intake was not associated with risk of SLE or RA in these large prospective cohorts of women.
High-Viscosity Hydroxypropylmethylcellulose Blunts Postprandial Glucose and Insulin Responses
Authors: Kevin C. Maki, Michael L. Carson, Marvin P. Miller, Maciej Turowski, Marjorie Bell, Donna M. Wilder, Matthew S. Reeves
Journal: Diabetes Care (2007)

OBJECTIVE—High-viscosity hydroxypropylmethylcellulose (HV-HPMC) is a modified cellulose fiber that produces a viscous gel in the gastrointestinal tract. Clinical trials demonstrate that consumption of HV-HPMC significantly lowers cholesterol, but limited information has been available on the influence of HV-HPMC on postprandial insulin and glucose responses. The objective of this investigation was to assess the influence of HV-HPMC on postprandial glucose and insulin responses in overweight and obese men and women. RESEARCH DESIGN AND METHODS—Participants were 31 overweight or obese men and women without diabetes who underwent three breakfast meal tests in random order, separated by ≥72 h. Test meals containing 75 g carbohydrate plus 4 or 8 g HV-HPMC or control meals containing 8 g cellulose were delivered in a double-blind fashion. RESULTS—Peak glucose was significantly lower (P &amp;lt; 0.001) after both HV-HPMC–containing meals (7.4 mmol/l [4 g] and 7.4 mmol/l [8 g]) compared with the control meal (8.6 mmol/l). Peak insulin concentrations and the incremental areas for glucose and insulin from 0 to 120 min were also significantly reduced after both HV-HPMC doses versus control (all P &amp;lt; 0.01). CONCLUSIONS—These findings indicate that HV-HPMC consumption reduces postprandial glucose and insulin excursions, which may favorably alter risks for diabetes and cardiovascular disease.
THE EFFECT OF FORMALDEHYDE ON PNEUMOCOCCI
Authors: René J. Dubos
Journal: The Journal of Experimental Medicine (1938)

When used in low concentration, formaldehyde increases the rate of autolytic disintegration of pneumococci whereas in large concentrations it completely inhibits autolysis and preserves both the morphological and staining characteristics of the cells. Pneumococci treated with large concentrations of formaldehyde, then washed free of the antiseptic and resuspended in physiological solutions, rapidly undergo a change which renders them Gram-negative and smaller. The lysis is only partial, however, and is not accompanied by an actual disintegration of the cell. It is caused by the autolytic enzyme of the cell which remains inactive in the presence of an excess of formaldehyde but recovers its activity when the cells are resuspended in a neutral medium after removal of the antiseptic. If the autolytic enzyme is irreversibly inactivated by heating, or maintained inactive in acid or alkaline reaction, the formolized cells retain their staining characteristics and morphological integrity. Formolized pneumococci which have become Gram-negative owing to the action of their autolytic enzyme, fail to elicit the type specific carbohydrate antibodies in rabbits. Formolized pneumococci in which the autolytic enzyme has been destroyed or maintained inactive, and which have retained their Gram-positive character, function as a very effective type specific antigen in the rabbit. These observations emphasize once more the close relation between the Gram-positive structure of pneumococci and the capsular polysaccharide antigen of the cell. They can be used as a basis for the preparation of suspensions of formolized pneumococci which are stable and very effective as type specific antigens.
It's high time: Cognitive neuroscience lives
Authors: Karl Pribram
Journal: Behavioral and Brain Sciences (2008)

Abstract Neuroconstructivism (Mareschal et al. 2007a) heralds a departure from the standard “associationism” that has dominated the English speaking cognitive and neuroscience community for generations. Its central concept is context dependency: encellment, embrainment, embodiment and ensocioment. This reviewer welcomes the breath of fresh air in overcoming the “deconstructions” of postmodernism. The program is carried out with a carefully selected sample of empirical evidence with an emphasis on development. This review points to some of the books' strengths and shortcomings, and adds a few observations that carry the program further.
Idiopathic lobular panniculitis with specific pleural involvement
Authors: N Kumagai-Kurata, H Kunitoh, M Nagamine-Nishizawa, K Watanbe, N Nakamura
Journal: European Respiratory Journal (1995)

A 19 year old man presented with fever and left pleural effusion. Biopsy of a subcutaneous nodule and bone marrow led to the diagnosis of idiopathic lobular panniculitis (Weber-Christian disease). Thoracoscopically guided biopsy of the visceral pleura also revealed panniculitis change in the pleural adipose tissue.
Extreme Variation of mtDNA Neutral Substitution Rate across Mammalian Species - the Longevity Hypothesis
Authors: B Nabholz, S Glemin, N Galtier
Journal: Molecular Biology and Evolution (2008)

Numerical values in the last paragraph of the Results section (p.124) are false. The paragraph should read : ‘‘Mitochondrial lineage-specific substitution rates were estimated from amino-acid sequences for comparative purposes. Non-synonymous and third codon position substitution rates were well correlated (R 5 0.442, p-val , 0.0001). The median estimated rate was 0.002 amino-acid substitution per site per million year. The Rodentia average was 0.0044 i.e. ;10 times faster than in Lagomorpha (0.0004). This shows that non-synonymous substitution rates are less variable between mammalian lineages than synonymous substitution rates.’’
Increased Mortality of Patients With Diabetes Reporting Severe Hypoglycemia
Authors: Rozalina G. McCoy, Holly K. Van Houten, Jeanette Y. Ziegenfuss, Nilay D. Shah, Robert A. Wermers, Steven A. Smith
Journal: Diabetes Care (2012)

OBJECTIVE Hypoglycemia is a cause of significant morbidity among patients with diabetes and may be associated with greater risk of death. We conducted a retrospective study to determine whether patient self-report of severe hypoglycemia is associated with increased mortality. RESEARCH DESIGN AND METHODS Adult patients (N = 1,020) seen in a specialty diabetes clinic between August 2005 and July 2006 were questioned about frequency of hypoglycemia during a preencounter interview; 7 were lost to follow-up and excluded from analysis. Mild hypoglycemia was defined as symptoms managed without assistance, and severe hypoglycemia was defined as symptoms requiring external assistance. Mortality data, demographics, clinical characteristics, and Charlson comorbidity index (CCI) were obtained from the electronic medical record after 5 years. Patients were stratified by self-report of hypoglycemia at baseline, demographics were compared using the two-sample t test, and risk of death was expressed as odds ratio (95% CI). Associations were controlled for age, sex, diabetes type and duration, CCI, HbA1c, and report of severe hypoglycemia. RESULTS In total, 1,013 patients with type 1 (21.3%) and type 2 (78.7%) diabetes were questioned about hypoglycemia. Among these, 625 (61.7%) reported any hypoglycemia, and 76 (7.5%) reported severe hypoglycemia. After 5 years, patients who reported severe hypoglycemia had 3.4-fold higher mortality (95% CI 1.5–7.4; P = 0.005) compared with those who reported mild/no hypoglycemia. CONCLUSIONS Self-report of severe hypoglycemia is associated with 3.4-fold increased risk of death. Patient-reported outcomes, including patient-reported hypoglycemia, may therefore augment risk stratification and disease management of patients with diabetes.
BIOMECHANICAL ASYMETRIES AND SPINAL LOADING IN ELIT ROWERS WITH AND WITHOUT LOW BACK PAIN
Authors: K Steenman, K Wielaard, H Lezeman, M Hofmijster, G Faber, J Dieen
Journal: British Journal of Sports Medicine (2014)

Background Being the first most common site for injury in junior elite (24.2%) and elite rowers (31.8%), low back pain (LBP) prevalence is still increasing. Of the rowers with LBP, 15.8% report LBP to be the reason to end their rowing careers. However, the exact extent of the factors associated with this problem is not well understood, making management and prevention of LBP in elite rowers difficult. Objective The aim of this study was to establish whether spinal loading, mediolateral seat drift, and asymmetry in force generation between left and right legs during an incremental rowing performance was more prominent in rowers with a history of low back pain (LBP) as compared to a control group of rowers without LBP. Design Cross-sectional study. Setting Laboratory setup, elite rowers. Patients This study examined forty-two elite rowers (21 with a history of LBP; 21 without). Risk factor assessment A 3-D motion analysis system was used during an incremental protocol on an instrumented rowing ergometer to measure spinal loading, mediolateral seat drift, and left-right leg force generation. Main outcome measurements Mediolateral seat drift in millimeters, spinal loading in Newton and difference between left and right leg force generation in Newton. T-test and Man Whitney U tests where used to compare data of the two groups. Results Significant differences in mediolateral seat drift were shown between groups in the first two steps of the protocol (step 1: U:130 Z:-2.277 with P=.023; step 2: U:116 Z: −2.629 with P=.09). No significant difference was found in spinal loading or left-right leg force generation. Conclusions The greater mediolateral seat drift in rowers with a history of LBP is a start for preventing en managing LBP in elite rowers. But first, future research should focus on the origin of this mediolateral seat drift.
Louis Ignarro
Authors: Ruth Williams
Journal: Circulation Research (2010)

Circulation Research is pleased to inaugurate "Profiles in Cardiovascular Science" with this interview with Lou Ignarro, the son of poor Italian immigrants, who won the 1998 Nobel Prize.Lou is one of my favorite people, a wonderful combination of scientific prowess, human richness, genuineness, and unassumingness, that is both refreshing and rare among medical researchers.Perhaps the most poignant part of the interview is the end, when Lou states that neither of his parents ever attended school; that their son rose to become a Nobel laureate is not only extraordinary but also deeply inspiring.
Extended field radiotherapy, combined modality treatment or involved field radiotherapy for patients with stage IA lymphocyte-predominant Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Study Group (GHSG)
Authors: L. Nogová, T. Reineke, H.T. Eich, A. Josting, H.K. Müller-Hermelink, K. Wingbermühle, C. Brillant, A. Gossmann, J. Oertel, M.V. Bollen, R.-P. Müller, V. Diehl, A. Engert
Journal: Annals of Oncology (2005)
Proliferative activity of neuroendocrine tumours of the gastroenteropancreatic endocrine system: DNA flow cytometric and immunohistological investigations.
Authors: A von Herbay, B Sieg, G Schurmann, W J Hofmann, M Betzler, H F Otto
Journal: Gut (1991)

The proliferative activity of 16 tumour specimens from 13 patients with neuroendocrine tumours of the gastroenteropancreatic endocrine system was studied by DNA flow cytometry and immunohistology for the nuclear Ki67 proliferation antigen. Equivalent results were obtained with both methods, which showed the proliferative activity of gastroenteropancreatic neuroendocrine tumours to be heterogeneous. In four malignant small intestinal carcinoids and one extravisceral carcinoid localised in the retroperitoneum the percentage (index) of proliferating tumour cells as measured by DNA flow cytometry ranged from 2.9 to 36.2% corresponding to low, moderate, or high proliferative activity. In four malignant pancreatic endocrine tumours and their metastases indices ranged from 8.7 to 18.3%, corresponding to low, moderate, or high proliferative activity. In four benign pancreatic endocrine tumours indices ranged from 4.3 to 7.7%, all corresponding to low proliferative activity. This heterogeneity of proliferative activity may in part explain the heterogeneous results reported of chemotherapy treatment. As chemotherapy of tumours is largely affected by favourable cell cycling kinetics, individual diagnostic investigations of the proliferative activity of these neuroendocrine tumours may be of value for identifying patients suitable for this treatment.
O-Glycosylation of Serum IgD in IgA Nephropathy
Authors: Alice C. Smith, Jacob F. de Wolff, Karen Molyneux, John Feehally, Jonathan Barratt
Journal: Journal of the American Society of Nephrology (2006)

In IgA nephropathy (IgAN), serum IgA1 with abnormal O-glycosylation preferentially deposits in the glomerular mesangium. The control of O-glycosylation is poorly understood. Among Ig isotypes, only IgD, produced early in B cell development, and IgA1, produced by mature B cells, are O-glycosylated. For investigation of the stage of B cell maturation at which the defect seen in IgAN arises, the O-glycosylation of serum IgA1 and IgD was studied in IgAN and controls. Serum was obtained from 20 patients with IgAN and 20 control subjects. The O-glycosylation profiles of native and desialylated IgA1 and IgD were measured in an ELISA-type system using the lectins Helix aspersa and peanut agglutinin, which bind to alternative forms of O-glycan moieties. The lectin-binding patterns of the two immunoglobulins differed in all participants, with that of IgD suggesting that it is more heavily galactosylated than IgA1. Defective O-glycosylation of IgA1, probably taking the form of reduced galactosylation, was confirmed in IgAN in this study. This undergalactosylation was not shared by IgD; in contrast, IgD carried more galactosylated O-glycans in IgAN than controls. The contrasting lectin-binding patterns of IgA1 and IgD shows that Ig O-glycosylation is differentially controlled during B cell maturation. Compared with controls, O-glycosylation in IgAN is incomplete in IgA1 but more complete in IgD. These observations show that abnormal IgA1 O-glycosylation in IgAN is not due to an inherent defect in glycosylation mechanisms but arises only at a later stage in B cell development and may be secondary to aberrant immunoregulation.
Respiratory chain defects in the mitochondria of cultured skin fibroblasts from three patients with lacticacidemia.
Authors: B H Robinson, J Ward, P Goodyer, A Baudet
Journal: Journal of Clinical Investigation (1986)

The cultured skin fibroblasts from three patients with lacticacidemia were found to have low rates of 1-[14C]pyruvate oxidation in the face of normal pyruvate dehydrogenase activity. After incubation with 1 mM glucose, these three cell strains also exhibited lactate/pyruvate ratios which were three times greater than those of controls. In two of the patients, both ATP and oxygen consumption in fibroblast mitochondrial preparations was deficient with NAD-linked substrates but normal with succinate and ascorbate/N'N'N'N' tetramethyl phenylene diamine. In the third patient, ATP synthesis in mitochondrial preparations was deficient with all substrates tested. Measurement of Rotenone-sensitive NADH-cytochrome c reductase in mitochondrial preparations from skin fibroblasts showed that two of the patients had 14 and 18%, respectively, of control activity. In the third patient, cytochrome oxidase activity was 15% of that in controls. We conclude that respiratory chain defects can be demonstrated in cultured skin fibroblasts with consistency using a number of different techniques.
Age-related valvular regurgitation: a study by pulsed Doppler echocardiography.
Authors: T Akasaka, J Yoshikawa, K Yoshida, F Okumachi, K Koizumi, K Shiratori, S Takao, M Shakudo, H Kato
Journal: Circulation (1987)

To assess the prevalence of valvular regurgitation in the aged, we studied 176 apparently healthy volunteers with no history or physical evidence of cardiac abnormality. Their ages ranged from 40 to 90 (66 +/- 14, mean +/- SD) years. We examined these subjects by pulsed Doppler echocardiography combined with two-dimensional echocardiography to determine the prevalence of valvular regurgitation. Regurgitation began to appear in subjects in their fifties, increasing in prevalence with advancing age (r = .81, p less than .001), and was documented in all over age 80. Similarly, regurgitation involving more than one valve appeared in those 60 years and older, and was very common (89%) in subjects in their eighties. With each type of valvular regurgitation, the prevalence of each type of regurgitation increased with aging, but this tendency was most prominent for aortic regurgitation. We conclude that (1) single or multivalvular regurgitation as detected by pulsed Doppler echocardiography is very common in the aged and may be considered a normal finding in the absence of other evidence of heart disease, and (2) the high prevalence of regurgitation in the aged must be taken into account when Doppler examinations are being performed.
Chemokines and Chemokine Receptors: Positioning Cells for Host Defense and Immunity
Authors: Jason W. Griffith, Caroline L. Sokol, Andrew D. Luster
Journal: Annual Review of Immunology (2014)

Chemokines are chemotactic cytokines that control the migratory patterns and positioning of all immune cells. Although chemokines were initially appreciated as important mediators of acute inflammation, we now know that this complex system of approximately 50 endogenous chemokine ligands and 20 G protein–coupled seven-transmembrane signaling receptors is also critical for the generation of primary and secondary adaptive cellular and humoral immune responses. Recent studies demonstrate important roles for the chemokine system in the priming of naive T cells, in cell fate decisions such as effector and memory cell differentiation, and in regulatory T cell function. In this review, we focus on recent advances in understanding how the chemokine system orchestrates immune cell migration and positioning at the organismic level in homeostasis, in acute inflammation, and during the generation and regulation of adoptive primary and secondary immune responses in the lymphoid system and peripheral nonlymphoid tissue.
Cytotoxic minor histocompatibility antigen HA-1–specific CD8+ effector memory T cells: artificial APCs pave the way for clinical application by potent primary in vitro induction
Authors: Karin Schilbach, Gunter Kerst, Steffen Walter, Matthias Eyrich, Dorothee Wernet, Rupert Handgretinger, Weidong Xie, Hans-Georg Rammensee, Ingo Müller, Hans-Jörg Bühring, Dietrich Niethammer
Journal: Blood (2005)