tbuckley/cabot-search huggingface dataset:
Maternal Metabolic Control and Perinatal Outcome in Women With Gestational Diabetes Mellitus Treated With Lispro or Aspart Insulin
Authors: Graziano Di Cianni, Laura Volpe, Alessandra Ghio, Cristina Lencioni, Ilaria Cuccuru, Luca Benzi, Stefano Del Prato
Journal: Diabetes Care (2007)

Gestational diabetes mellitus (GDM) is associated with increased risk of maternal and neonatal morbidity with macrosomia being the most common neonatal complication (1). The risk of macrosomia and/or disproportionate fetal growth is closely related to 1-h postprandial glucose concentration (2).

Therefore, the treatment of GDM should be aimed at normalizing maternal glycemia including the early postprandial response. Insulin therapy is needed whenever strict normoglycemia cannot be achieved by medical nutritional therapy alone (3). Because of their pharmacokinetic properties, short-acting insulin analogs (Insulin Aspart [ASP] and Insulin Lispro [LIS]) could be more effective in pregnancy than human regular insulin (HI) (4). Nevertheless, data …
Resources could be spent better than on saving children
Authors: A. Savage
Journal: Journal of the Royal Society of Medicine (2007)

Most doctors who have worked in Africa will agree with the late Imre Loefler that the preferential treatment of children is misplaced (JRSM 2007; 100: 110-111). In fact, I wrote a piece in 1983 entitled ‘Should Charity always begin with Children?’, which pleaded for more help for women with vesico-vaginal fistulae. But incontinent women are not as photogenic as wide-eyed children and, as fundraisers well know, rational argument rarely wins over emotion.

I found the avoidable deaths of young adults much harder to take than the high child mortality for two reasons. My first reason is that the best security for a child in Africa, where the welfare state is rudimentary, is to have two healthy parents. My second reason will be considered more controversial, but I came to realise that some of the children who returned to my clinic time after time were not meant to live. In a survey of 1200 consecutive admissions to the children's ward, done primarily to assess the effect of measles vaccine, the mortality was 21.5%, and of those 77.7% died with 24 hours of admission. In an area where abortion was unthinkable and Children's Homes a rarity, unwanted babies just faded away. Even in this rich country a judgement has to be made about the allocation of resources, and that is even more important in Africa.
Socioeconomic differences in general practice consultation rates in patients aged 65 and over: prospective cohort study
Authors: R. McNiece, A. Majeed
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To examine socioeconomic differences in general practice consultation rates among patients aged 65 years and over. <b>Design:</b> Secondary analysis of data from the fourth national survey of morbidity in general practice. <b>Setting:</b> 60 general practices in England and Wales. <b>Subjects:</b> 71 984 people aged 65 years and over. <b>Main outcome measures:</b> Annual contact rates and home visiting rates with general practitioners and practice nurses. <b>Results:</b> Social class differences in contact rates were greatest in 65-74 year olds, with rates 23% higher in patients from social class V than in class I (4.82 <i>v</i> 3.93 per person). In 75-84 year olds there was no clear association between social class and contact rates, and in people aged ≥85 years contact rates were highest in patients from class I. Home visiting rates were twice as high in patients from class V as in patients from class I (1.38 <i>v</i> 0.66 per person). Contact rates were 17% higher in people living in communal establishments and 8% higher in those living alone than in those living with others but not in a communal establishment. 66% of contacts with patients in communal establishments and 26% of those with patients living alone were in patients9 homes compared with 18% with those living in standard accommodation. These differences persisted after adjustment in a generalised linear model. <b>Conclusions:</b> Elderly people show socioeconomic differences in consultation rates. The extra workload generated by elderly people living alone and in communal establishments suggests additional payments to general practitioners are needed. <h3>Key messages</h3> Little is known about the effect of socioeconomic status on use of general practice services by elderly people In this national study contact rates were 14% higher and home visiting rates 109% higher in elderly patients from social class V than in patients from class I Contact rates were 17% higher in elderly people living in communal establishments and 8% higher in elderly people living alone than in those living in standard accommodation 66% of contacts with patients in communal establishments and 26% with those living alone were in patients9 homes compared with 18% of contacts with those in standard accommodation
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Authors: Carey N. Lumeng, Jennifer L. Bodzin, Alan R. Saltiel
Journal: Journal of Clinical Investigation (2007)

Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80+CD11c+ population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or “alternatively activated” macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-α and iNOS that are characteristic of M1 or “classically activated” macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2–KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-α–induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.
Aerobic Glycolysis Suppresses p53 Activity to Provide Selective Protection from Apoptosis upon Loss of Growth Signals or Inhibition of BCR-Abl
Authors: Emily F. Mason, Yuxing Zhao, Pankuri Goraksha-Hicks, Jonathan L. Coloff, Hugh Gannon, Stephen N. Jones, Jeffrey C. Rathmell
Journal: Cancer Research (2010)

Abstract Unlike the growth factor dependence of normal cells, cancer cells can maintain growth factor–independent glycolysis and survival through expression of oncogenic kinases, such as BCR-Abl. Although targeted kinase inhibition can promote cancer cell death, therapeutic resistance develops frequently, and further mechanistic understanding is needed. Cell metabolism may be central to this cell death pathway, as we have shown that growth factor deprivation leads to decreased glycolysis that promotes apoptosis via p53 activation and induction of the proapoptotic protein Puma. Here, we extend these findings to show that elevated glucose metabolism, characteristic of cancer cells, can suppress protein kinase Cδ (PKCδ)–dependent p53 activation to maintain cell survival after growth factor withdrawal. In contrast, DNA damage–induced p53 activation was PKCδ independent and was not metabolically sensitive. Both stresses required p53 Ser18 phosphorylation for maximal activity but led to unique patterns of p53 target gene expression, showing distinct activation and response pathways for p53 that were differentially regulated by metabolism. Consistent with oncogenic kinases acting to replace growth factors, treatment of BCR-Abl–expressing cells with the kinase inhibitor imatinib led to reduced metabolism and p53- and Puma-dependent cell death. Accordingly, maintenance of glucose uptake inhibited p53 activation and promoted imatinib resistance. Furthermore, inhibition of glycolysis enhanced imatinib sensitivity in BCR-Abl–expressing cells with wild-type p53 but had little effect on p53-null cells. These data show that distinct pathways regulate p53 after DNA damage and metabolic stress and that inhibiting glucose metabolism may enhance the efficacy of and overcome resistance to targeted molecular cancer therapies. Cancer Res; 70(20); 8066–76. ©2010 AACR.
Effects of hyperkalaemia on sinus nodal function in dogs: sino-ventricular conduction
Authors: R. J HARIMAN, C.-M. CHEN
Journal: Cardiovascular Research (1983)

The effects of hyperkalaemia on electrograms recorded from the sinus node, crista terminalis, Bachmann bundle, right and left atria and His bundle were studied in anaesthetised dogs. Increasing hyperkalaemia up to about 8.5 mol·litre−1 produced: 1) a gradual prolongation of the sino-crista terminalis interval, and 2) a shift in sinus pacemaker location. Hyperkalaemia between 8.5 and 10.0 mmol·litre−1 produced arrest of most of the atria but persistence of electrical activity of the sinus node, crista terminalis, Bachmann bundle, His bundle and ventricles and sustained sino-ventricular conduction. During the course of increasing hyperkalaemia, right atrial electrograms from sites closer to the crista terminalis disappeared later than those from sites more remote from the crista terminalis. Decremental conduction through sites progressively remote from the axis of the crista terminalis (and possibly also other "preferential pathways") seemed to be the basis of hyperkalaemic atrial arrest.
Exhaled nitric oxide after lung transplantation: impact of the native lung
Authors: G.M. Verleden, L.J. Dupont, M. Delcroix, D. Van Raemdonck, J. Vanhaecke, T. Lerut, M. Demedts
Journal: European Respiratory Journal (2003)

It has already been demonstrated that exhaled nitric oxide (eNO) is increased in lung transplant patients with chronic rejection, although it is not known whether the diseased native lung after single lung transplantation (SLTx) contributes to the increased eNO values. This study aimed to compare the eNO values in stable lung transplant patients (SLTx <i>versus</i> sequential (S)SLTx and heart (H)LTx) and in patients with established chronic rejection. Altogether, 42 LTx patients (25 females, 13 SLTx, 18 SSLTx, 11 HLTx), with a mean follow­up of 1149 days and a mean age of 44.6 yrs at transplantation, were included. Twenty­six patients had no signs of chronic rejection (five SLTx and 21 SSLTx/HLTx). There was no difference in their eNO values (10.2 in SLTx <i>versus</i> 12.2 (parts per billion) ppb in SSLTx/HLTx). Sixteen patients (eight SLTx and eight SSLTx/HLTx) had a chronic rejection (eight bronchiolitis obliterans syndrome (BOS) potential stage, four BOS stage 1, three BOS stage 2 and one BOS stage 3). Their eNOs were 18.1 (SLTx) and 17.0 (SSLTx/HLTx) ppb, respectively, which were significantly different to the stable LTx patients and showed a trend towards significance for SSLTx/HLTx. There was no significant difference in eNO between the patients with chronic rejection who underwent SLTx and those who underwent SSLTx/HLTx. The diseased native lung after single lung transplantation probably does not contribute much to the exhaled nitric oxide values, either in stable lung transplant patients or in lung transplant patients with chronic rejection.
Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak syndrome, encodes a novel component of the BLOC-1 complex
Authors: Babette Gwynn, Jose A. Martina, Juan S. Bonifacino, Elena V. Sviderskaya, M. Lynn Lamoreux, Dorothy C. Bennett, Kengo Moriyama, Marjan Huizing, Amanda Helip-Wooley, William A. Gahl, Lisa S. Webb, Amy J. Lambert, Luanne L. Peters
Journal: Blood (2004)
Inhibition of human megakaryocytopoiesis in vitro by platelet factor 4 (PF4) and a synthetic COOH-terminal PF4 peptide.
Authors: A M Gewirtz, B Calabretta, B Rucinski, S Niewiarowski, W Y Xu
Journal: Journal of Clinical Investigation (1989)

We report that highly purified human platelet factor 4 (PF4) inhibits human megakaryocytopoiesis in vitro. At greater than or equal to 25 micrograms/ml, PF4 inhibited megakaryocyte colony formation approximately 80% in unstimulated cultures, and approximately 58% in cultures containing recombinant human IL 3 and granulocyte-macrophage colony-stimulating factor. Because PF4 (25 micrograms/ml) had no effect on either myeloid or erythroid colony formation lineage specificity of this effect was suggested. A synthetic COOH-terminal PF4 peptide of 24, but not 13 residues, also inhibited megakaryocyte colony formation, whereas a synthetic 18-residue beta-thromboglobulin (beta-TG) peptide and native beta-TG had no such effect when assayed at similar concentrations. The mechanism of PF4-mediated inhibition was investigated. First, we enumerated total cell number, and examined cell maturation in control colonies (n = 200) and colonies (n = 100) that arose in PF4-containing cultures. Total cells per colony did not differ dramatically in the two groups (6.1 +/- 3.0 vs. 4.2 +/- 1.6, respectively), but the numbers of mature large cells per colony was significantly decreased in the presence of PF4 when compared with controls (1.6 +/- 1.5 vs. 3.9 +/- 2.3; P less than 0.001). Second, by using the human leukemia cell line HEL as a model for primitive megakaryocytic cells, we studied the effect of PF4 on cell doubling time, on the expression of both growth-regulated (H3, p53, c-myc,and c-myb), and non-growth-regulated (beta 2-microglobulin) genes. At high concentrations of native PF4 (50 micrograms/ml), no effect on cell doubling time, or H3 or p53 expression was discerned. In contrast, c-myc and c-myb were both upregulated. These results suggested the PF4 inhibited colony formation by impeding cell maturation, as opposed to cell proliferation, perhaps by inducing expression of c-myc and c-myb. The ability of PF4 to inhibit a normal cell maturation function was then tested. Megakaryocytes were incubated in synthetic PF4, or beta-TG peptides for 18 h and effect on Factor V steady-state mRNA levels was determined in 600 individual cells by in situ hybridization. beta-TG peptide had no effect on FV mRNA levels, whereas a approximately 60% decrease in expression of Factor V mRNA was found in megakaryocytes exposed to greater than or equal 100 ng/ml synthetic COOH-terminal PF4 peptide. Accordingly, PF4 modulates megakaryocyte maturation in vitro, and may function as a negative autocrine regulator of human megakaryocytopoiesis.
Effect of a high omega-3 fatty acid diet on cardiac contractile performance in Oncorhynchus mykiss
Authors: J. A. Paige, R. Liao, R. J. Hajjar, R. L. Foisy, C.R. Cory, P. J. O'Brien, J. K. Gwathmey
Journal: Cardiovascular Research (1996)

Objective: Omega-3 fatty acids have been implicated in the amelioration of cardiovascular disease in humans. Since these fatty acids are found in salmonid fish and are known to be essential for all salmonids, this study was undertaken to determine the effect of a high dietary intake of omega-3 fatty acids on the function of trout myocardium. Methods: Rainbow trout (Oncorhynchus mykiss) from a single stock population were divided into two groups and fed either a diet high in omega-3 fatty acids (i.e. 4.0%) or low in omega-3 fatty acids (i.e. 2.1%) for 3 months. Heart function was studied at the whole heart and isolated muscle level. Results: In whole heart preparations, peak developed pressures in freely ejecting hearts from salmonids fed the high omega-3 fatty acid diet were significantly greater than the hearts from salmonids fed the low omega-3 fatty acid diet (21 ± 1.5 vs. 11.5 ± 0.9 mmHg respectively, P < 0.05). These data correlated with results from isolated muscle preparations of myocardium from fish fed high and low omega-3 fatty acid diets (4.12 ± 0.32 vs. 3.08 ± 0.28 mN/mm2 respectively, P < 0.05). The calcium uptake rate of heart homogenates from fish fed the high omega-3 diet was slower and sarcoplasmic reticulum Ca2+ ATPase activity was lower. The myofilament force-calcium relationship in myocardium from trout fed the low omega-3 diet was shifted leftward on the calcium axis to lower intracellular calcium concentrations (Δ0.4 pCa units) compared to mammalian myocardium. This resulted in greater activation at lower intracellular calcium concentrations. However, trouts fed diets high in omega-3 fatty acids had [Ca2+] required for half maximal activation more similar to what has been reported for mammalian myocardium (Δ0.1 pCa unit). Furthermore, the myofilaments of trout hearts appear to show less cooperativity (Hill coefficient ~ 1) than has been found in mammalian myocardium (Hill coefficient ≥ 2). Conclusions: Our experimental results demonstrate for the first time that dietary omega-3 fatty acid content affects myocardial force of contraction by affecting calcium metabolism and myofilament calcium-activation.
The life span of naive alpha/beta T cells in secondary lymphoid organs.
Authors: H von Boehmer, K Hafen
Journal: The Journal of Experimental Medicine (1993)

We have determined the life span of naive CD4-8+ T cells in T cell receptor transgenic mice. We find that such cells do not divide in secondary lymphoid organs in both normal euthymic mice and T cell-deficient mice. By both continuous labeling and by chasing pulse-labeled cells, we find that the minimum life span of the naive T cells is in the order of 8 wk.
Isolated U Wave Negativity
Authors: J. H. PALMER
Journal: Circulation (1953)

Inversion of U as the only abnormal electrocardiographic finding is here shown to be the first change to occur in certain cases of hypertension, coronary artery sclerosis, and other organic heart disease. It is also found in association with certain metabolic and electrolyte changes. Its recognition will enhance the value of the electrocardiogram in clinical diagnosis.
Influence of personal characteristics of individual women on sensitivity and specificity of mammography in the Million Women Study: cohort study
Authors: Emily Banks, Gillian Reeves, Valerie Beral, Diana Bull, Barbara Crossley, Moya Simmonds, Elizabeth Hilton, Stephen Bailey, Nigel Barrett, Peter Briers, Ruth English, Alan Jackson, Elizabeth Kutt, Janet Lavelle, Linda Rockall, Matthew G Wallis, Mary Wilson, Julietta Patnick
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> To examine how lifestyle, hormonal, and other factors influence the sensitivity and specificity of mammography. <b>Methods</b> Women recruited into the Million Women Study completed a questionnaire about various personal factors before routine mammographic screening. A sample of 122 355 women aged 50-64 years were followed for outcome of screening and incident breast cancer in the next 12 months. Sensitivity and specificity were calculated by using standard definitions, with adjustment for potential confounding factors. <b>Results</b> Breast cancer was diagnosed in 726 (0.6%) women, 629 in screen positive and 97 in screen negative women; 3885 (3.2%) were screen positive but had no subsequent diagnosis of breast cancer. Overall sensitivity was 86.6% and specificity was 96.8%. Three factors had an adverse effect on both measures: use of hormone replacement therapy (sensitivity: 83.0% (95% confidence interval 77.4% to 87.6%), 84.7% (73.9% to 91.6%), and 92.1% (87.6% to 95.0%); specificity: 96.8% (96.6% to 97.0%), 97.8% (97.5% to 98.0%), and 98.1% (98.0% to 98.2%), respectively, for current, past, and never use); previous breast surgery <i>v</i> no previous breast surgery (sensitivity: 83.5% (75.7% to 89.1%) <i>v</i> 89.4% (86.5% to 91.8%); specificity: 96.2% (95.8% to 96.5%) <i>v</i> 97.4% (97.3% to 97.5%), respectively); and body mass index &lt; 25 <i>v</i> ≥ 25 (sensitivity: 85.7% (81.2% to 89.3%) <i>v</i> 91.0% (87.5% to 93.6%); specificity: 97.2% (97.0% to 97.3%) <i>v</i> 97.4% (97.3% to 97.6%), respectively). Neither sensitivity nor specificity varied significantly according to age, family history of breast cancer, parity, past oral contraceptive use, tubal ligation, physical activity, smoking, or alcohol consumption. <b>Conclusions</b> The efficiency, and possibly the effectiveness, of mammographic screening is lower in users of hormone replacement therapy, in women with previous breast surgery, and in thin women compared with other women.
Long Noncoding RNAs in Cardiovascular Diseases
Authors: Shizuka Uchida, Stefanie Dimmeler
Journal: Circulation Research (2015)

In recent year, increasing evidence suggests that noncoding RNAs play important roles in the regulation of tissue homeostasis and pathophysiological conditions. Besides small noncoding RNAs (eg, microRNAs), &gt;200-nucleotide long transcripts, namely long noncoding RNAs (lncRNAs), can interfere with gene expressions and signaling pathways at various stages. In the cardiovascular system, studies have detected and characterized the expression of lncRNAs under normal physiological condition and in disease states. Several lncRNAs are regulated during acute myocardial infarction (eg, Novlnc6 ) and heart failure (eg, Mhrt ), whereas others control hypertrophy, mitochondrial function and apoptosis of cardiomyocytes. In the vascular system, the endothelial-expressed lncRNAs (eg, MALAT1 and Tie-1-AS) can regulate vessel growth and function, whereas the smooth-muscle–expressed lncRNA smooth muscle and endothelial cell–enriched migration/differentiation-associated long noncoding RNA was recently shown to control the contractile phenotype of smooth muscle cells. This review article summarizes the data on lncRNA expressions in mouse and human and highlights identified cardiovascular lncRNAs that might play a role in cardiovascular diseases. Although our understanding of lncRNAs is still in its infancy, these examples may provide helpful insights how lncRNAs interfere with cardiovascular diseases.
Imbalance between 95 kDa type IV collagenase and tissue inhibitor of metalloproteinases in sputum of patients with cystic fibrosis.
Authors: C Delacourt, M Le Bourgeois, M P D'Ortho, C Doit, P Scheinmann, J Navarro, A Harf, D J Hartmann, C Lafuma
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

A growing body of evidence suggests that neutrophil-derived proteinases play a major role in lung tissue damage in cystic fibrosis (CF). Most previous studies have focused on serine proteinases such as neutrophil elastase, providing no information on the extent to which metalloproteinases participate in proteolytic processes in CF. To address this issue, we evaluated the contribution of one of the major neutrophil metalloproteinases, i.e., 95 kDa gelatinase (type IV collagenase), to the total gelatinolytic activity measured in sputum specimens from 27 patients with CF. Compared with asthmatic children (n = 9), CF patients had a 6.7 times greater level of total gelatinase activity in sputum revealed by zymography. The 95 kDa gelatinase was increased 3.7-fold in the CF subjects (2,441 +/- 411 [SEM] arbitrary units [AU] x 10(6) per ml of sputum versus 665 +/- 201 in asthmatics) and the 88-kDa active form 23.2-fold (2,272 +/- 372 AU x 10(6) per ml of sputum versus 98 +/- 43, respectively). Using radiolabeled 3H-gelatin as the substrate, we demonstrated uninhibited gelatinolytic activity in all CF patients; this activity was significantly correlated to disease severity as assessed by pulmonary function tests. Western blotting using anti-tissue inhibitor of metalloproteinase (anti-TIMP) and anti-95/88-kDa gelatinase antibodies demonstrated a more than 10-fold excess of 95/88 kDa gelatinase over TIMP. Bacterial proteinases from Pseudomonas aeruginosa were shown to contribute little to the gelatinolytic activity measured in sputum supernatants from patients with CF, although culture supernatants from various P. aeruginosa strains expressed gelatinolytic activity in vitro. Finally, lung damage, as assessed by increased type IV collagen degradation products in sputum, was significantly correlated to concentrations of active 88 kDa gelatinase. These data argue for a significant role of 95/88 kDa gelatinase in airway damage in CF.