bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytotoxic T-lymphocytes against malaria and tuberculosis: from natural immunity to vaccine design
Authors: LALVANI Ajit , HILL Adrian V. S. 
Published: August 2015

1. Mycobacterium tuberculosis and the liver stage of Plasmodium falciparum are intracellular pathogens which are potentially susceptible to cytotoxic T-lymphocytes, a crucial component of the protective immune response to viral infections. Evidence from animal models points to a protective role for cytotoxic T-lymphocytes against M. tuberculosis and P. falciparum, but cytotoxic T-lymphocytes specific for these pathogens have been difficult to identify in man.
2.Using a reverse immunogenetic approach, candidate epitopes from selected antigens of P. falciparum and M. tuberculosis were used to detect peptide-specific cytotoxic T-lymphocyte responses in individuals exposed to these pathogens. Cytotoxic T-lymphocyte activity was detected by the 51Cr release cytotoxicity assay and a sensitive ELISPOT assay for single-cell interferon-γ release.
3.In naturally exposed, partially immune Africans in The Gambia, eight largely conserved cytotoxic T-lymphocyte epitopes in P. falciparum, restricted by several different HLA class I alleles, were identified. Several epitopes were also recognized in Tanzanians and cytotoxic T-lymphocytes recognized endogenously processed antigen.
4.In tuberculosis patients with HLA-B52, a CD8+ cytotoxic T-lymphocyte epitope was identified in ESAT-6, a secreted antigen specific for M. tuberculosis complex but absent in BCG. Cytotoxic T-lymphocytes exhibited HLA-B52-restricted peptide-specific interferon-γ release and lytic activity and recognized endogenously processed antigen.
5.These studies demonstrate that CD8+ cytotoxic T-lymphocytes specific for mycobacterial and protozoal antigens are induced during natural infections in humans. The identification of these T-cells endorses current strategies to develop cytotoxic T-lymphocyte-inducing vaccines against P. falciparum and M. tuberculosis and highlights candidate antigens for inclusion in subunit vaccines.
Aminoguanidine ameliorates splanchnic hyposensitivity to glypressin in a haemorrhage-transfused rat model of portal hypertension
Authors: CHU Chi-Jen , LEE Fa-Yauh , WANG Sun-Sang , CHANG Full-Young , LIN Han-Chieh , HOU Ming-Chih , WU Shwu-Ling , TAI Chung-Ching , CHAN Che-Chang , LEE Shou-Dong 
Published: August 2015

1.Hyposensitivity to vasopressin is a well-documented phenomenon in animals with portal hypertension and patients with cirrhosis subjected to haemorrhage. Excessive formation of nitric oxide is at least partly responsible for the vascular hyporesponsiveness to vasoconstrictors observed in experimental portal hypertension or in rats with haemorrhagic shock. This study investigated whether addition of aminoguanidine, a preferential inducible nitric oxide synthase inhibitor, to glypressin (a long-acting vasopressin analogue) could enhance its portal hypotensive effect in portal-hypertensive rats with bleeding.
2.Portal hypertension was induced by partial portal vein ligation. Fourteen days after operation, systemic and portal haemodynamics were measured in stable or bleeding portal vein-ligated rats receiving intravenous glypressin (0.07 ;mg/kg) or aminoguanidine (70 ;mg/kg) followed by glypressin infusion. In rats with a hypotensive haemorrhage, 4.5 ;ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin or aminoguanidine.
3.Glypressin resulted in a significantly greater decrease in portal pressure in portal vein-ligated rats without bleeding than in those with bleeding (P&lt; 0.001). In contrast, glypressin induced similar changes in mean arterial pressure between the two groups (P&gt; 0.05). The addition of aminoguanidine significantly potentiated the portal-hypotensive effect of glypressin in bleeding portal vein-ligated rats (P&lt; 0.005) without an effect on the changes in mean arterial pressure induced by glypressin infusion (P&gt; 0.05).
4.Splanchnic hyposensitivity to glypressin exists in a haemorrhage-transfused rat model of portal hypertension. This hyposensitivity can be ameliorated by the administration of aminoguanidine.
Biliary lactoferrin concentrations are increased in active inflammatory bowel disease: a factor in the pathogenesis of primary sclerosing cholangitis?
Authors: PEREIRA S. P. , RHODES J. M. , CAMPBELL B. J. , KUMAR D. , BAIN I. M. , MURPHY G. M. , DOWLING R. H. 
Published: August 2015

1.One hypothesis for the link between inflammatory bowel disease and primary sclerosing cholangitis is that neutrophil activators, such as bacterial chemotactic peptides or neutrophil granule products themselves, pass from the inflamed colon to the liver via an enterohepatic circulation. However, there are no data on biliary concentrations of neutrophil granule products in patients with active and inactive inflammatory bowel disease.
2.Gall bladder bile was obtained at laparotomy from 42 patients with ulcerative colitis and 21 patients with Crohn's disease. Biliary lactoferrin and myeloperoxidase concentrations were quantified by ELISA.
3.In active ulcerative colitis, the mean lactoferrin concentration in gall bladder bile of 2.8±0.40 ;mg/l was higher than that seen after colectomy (1.2±0.11 ;mg/l; P&lt; 0.0001) or in patients with pouchitis (1.8±0.34 ;mg/l; P = 0.06). In active Crohn's colitis, the mean lactoferrin concentration was 3.7±0.9 ;mg/l, compared with 1.1±0.24 ;mg/l in the post-colectomy group (P&lt; 0.05) and 3.1±0.71 ;mg/l in those with active ileitis or ileocolitis. In contrast, biliary myeloperoxidase concentrations were low and comparable in all groups, with a mean concentration in the 42 patients with ulcerative colitis of 11.2±1.9 ;μg/l.
4.In contrast to myeloperoxidase, biliary lactoferrin concentrations are increased in active ulcerative colitis and Crohn's disease, and fall with colectomy and with disease remission. These findings indirectly support the hypothesis that bacterial chemotactic peptides (which induce selective degranulation of neutrophil secondary granules), and/or lactoferrin itself, undergo an enterohepatic circulation.
Erythrocyte Na+/Li+ countertransport and Na+/K+–2Cl− co-transport measurement in essential hypertension: useful diagnostic tools or failure? A meta-analysis of 17 years of literature
Authors: Tepper T. , Sluiter W. J. , Huisman R. M. , de Zeeuw D. 
Published: August 2015

1. A meta-analysis of 17 years of literature on erythrocyte Na+/Li+ countertransport (NLCT) and Na+/K+ co-transport (COT) measurements in relation to essential hypertension is presented. The analysis aimed to answer two questions: (i) Which clinical or laboratory variables influence NLCT and COT flux values? (ii) How useful are NLCT and COT measurements as a diagnostic aid in essential hypertension?
2. Regression analysis was performed on the mean flux values and relevant clinical and laboratory values. Studies in both normotensive and hypertensive subjects were stratified for variables which showed a significant association with the measured flux. For hypertensive subjects the studies were also stratified for medication. Means of strata were calculated after weighing the mean of a study by the inverse of its own variance and were compared in normotensive as well as hypertensive subjects using a t-test.
3. The analysis did not demonstrate systematic effects of laboratory variables for either NLCT or COT. It was found that essential hypertension, family history of hypertension, gender and antihypertensive medication are main determinants for the flux values of both transport systems. After stratification for these determinants, significant differences in weighed mean flux values between normotensive and hypertensive subjects were demonstrated. However, these differences are much smaller than the variance in the weighed mean flux values, suggesting the existence of other unknown variables that strongly affect the flux rates.
4. In conclusion, NLCT and COT measurements cannot be of diagnostic use in essential hypertension.
Maximization of skin capillaries during intravital video-microscopy in essential hypertension: comparison between venous congestion, reactive hyperaemia and core heat load tests
Authors: ANTONIOS Tarek F. T. , RATTRAY Fraser E. M. , SINGER Donald R. J. , MARKANDU Nirmala D. , MORTIMER Peter S. , MACGREGOR Graham A. 
Published: August 2015

Intravital capillary video-microscopy is a dynamic method for studying skin capillaries. The technique of direct intravital microscopy (without dyes) depends on the presence of red blood cells inside capillaries for their identification. The aim of the present study was to compare different techniques to try to establish the best method for maximizing the number of visible perfused capillaries during intravital capillary microscopy. We compared the effects of venous congestion with those of post-occlusive reactive hyperaemia (Study 1). We also investigated venous congestion followed first by post-occlusive reactive hyperaemia and then by a core heat load test (Study 2). Finally we investigated venous congestion followed by post-occlusive reactive hyperaemia combined with venous congestion (Study 3). In Study 1, capillary density increased with venous congestion from a baseline value of 74±2 (mean±S.E.M.) per field to 82±3 per field (P< 0.0001; analysis of variance). With reactive hyperaemia, there was an apparent decrease in visible capillary density to 69±2 per field. In Study 2, baseline capillary density was 69±4 per field, and this increased significantly with venous congestion to 74±4 per field (P = 0.01). With both reactive hyperaemia and core heat load, the apparent density was 62±4 per field. In Study 3 the baseline density was 70±2 per field, and this increased significantly with venous congestion to 80±3 per field (P< 0.0001). With reactive hyperaemia combined with venous congestion, the density was 81±3 per field (P = 0.328 compared with venous congestion alone). The results show that venous congestion at 60 mmHg for 2 min is the most effective method for visualization of the maximal number of perfused skin capillaries during intravital video-microscopy.
Markers of systemic inflammation predicting organ failure in community-acquired septic shock
Authors: TAKALA Annika , JOUSELA Irma , JANSSON Sten-Erik , OLKKOLA Klaus T. , TAKKUNEN Olli , ORPANA Arto , KARONEN Sirkka-Liisa , REPO Heikki 
Published: August 2015

To obtain predictors of organ failure (OF), we studied markers of systemic inflammation [circulating levels of interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R), soluble E-selectin and C-reactive protein, and neutrophil and monocyte CD11b expression] and routine blood cell counts in 20 patients with systemic inflammatory response syndrome and positive blood culture. Eight patients with shock due to community-acquired infection developed OF, whereas 11 normotensive patients and one patient with shock did not (NOF group). The first blood sample was collected within 48 h after taking the blood culture (T1). OF patients, as compared with NOF patients, had at T1 a lower monocyte count, a lower platelet count, higher levels of CD11b expression on both neutrophils and monocytes, and higher concentrations of IL-6, IL-8 and sIL-2R. C-reactive protein and soluble E-selectin concentrations did not differ between groups. No parameter alone identified all patients that subsequently developed OF. However, a sepsis-related inflammation severity score (SISS), developed on the basis of the presence or absence of shock and on the levels of markers at T1, identified each patient that developed OF. The maximum SISS value was 7. The range of SISS values in OF patients was 2–5, and that in NOF patients was 0–1. In conclusion, high levels of CD11b expression, depressed platelet and monocyte counts, and high concentrations of IL-6, IL-8 and sIL-2R predict OF in patients with community-acquired septic shock, and the combination of these markers may provide the means to identify sepsis patients who will develop OF.
Oxygen uptake kinetics during exercise in chronic heart failure: influence of peripheral vascular reserve
Authors: HEPPLE Russell T. , LIU Peter. P. , PLYLEY Michael J. , GOODMAN Jack M. 
Published: August 2015

Exercise performance in chronic heart failure is severely impaired, due in part to a peripherally mediated limitation. In addition to impaired maximal exercise capacity, the O2 uptake (O2) response during submaximal exercise may be affected, with a greater reliance on anaerobiosis leading to early fatigue. However, the response of O2 kinetics to submaximal exercise in chronic heart failure has not been studied extensively; in particular, the relationship between oxygen utilization and the peripheral response to exercise has not been studied. The present investigation examined the time-constant (τ, corresponding to 63% of the total response fitted from exercise onset) of the O2 kinetics on-response to submaximal exercise and its relationship to maximal peripheral blood flow in patients with chronic heart failure, and compared responses with those in healthy sedentary subjects. Subjects were 10 patients with chronic heart failure (NYHA class II/III). The mean age was 50±12 years, with a mean resting left ventricular ejection fraction of 25±9%. Controls were 10 age-matched healthy subjects. O2(max) was first determined for all subjects. Repeated transitions from rest to exercise were performed on a cycle ergometer while measuring breath-by-breath responses of O2 at a fixed work rate of 50% of O2(max) (heart failure patients and healthy controls) and at a work rate equivalent to the average in heart failure patients (65 W; healthy controls only). On a separate occasion, post-maximal ischaemic exercise calf blood flow was measured (strain-gauge plethysmography).Whereas heart failure subjects displayed a significantly prolonged O2 kinetics response at a similar absolute workload (i.e. 65 W), as indicated by a longer τ value (42 s, compared with 22 s in controls; P< 0.01), there was no difference in τ at a similar relative work rate [50% of O2(max)]. In addition, heart failure subjects demonstrated a lower maximal calf blood flow (P< 0.05) than control subjects. These results indicate that patients with heart failure have a prolonged O2 kinetics on-response compared with healthy subjects at a similar absolute work rate (i.e. 65 W), but not at a similar relative work rate [50% of O2(max)]. Thus, despite a reduced maximal calf blood flow response associated with heart failure, it does not appear that this contributes to an impairment of the submaximal exercise response beyond that explained by a reduced maximal exercise capacity [O2(max)].
Baseline heart rate variability in healthy centenarians: differences compared with aged subjects (>75 years old)
Authors: PAOLISSO Giuseppe , MANZELLA Daniela , BARBIERI Michelangela , RIZZO Maria Rosaria , GAMBARDELLA Antonio , VARRICCHIO Michele 
Published: August 2015

Healthy centenarians have better anthropometric, endocrine, metabolic and immunological parameters than aged subjects (> 75 years old). Heart rate variability (HRV) has been demonstrated to be a good index of the cardiac autonomic nervous system. It is not known whether there are any differences in cardiac autonomic nervous system activity between aged subjects and healthy centenarians. It is possible that differences in cardiac autonomic nervous system activity could represent one of a cluster of factors explaining the extreme survival of centenarians. Thus we aimed to answer the following question: is there any difference in baseline HRV parameters between aged subjects and healthy centenarians? Therefore power spectral analysis of HRV at baseline was investigated in 25 aged subjects (age ⩾ 75 years) and 30 healthy centenarians (age ⩾ 100 years). Anthropometric measurements were made in all subjects, fasting blood samples were drawn for metabolite determinations, and HRV was determined. Independent of age, gender, body mass index and fasting plasma noradrenaline and free 3,3′,5-tri-iodothyronine concentrations, healthy centenarians had lower basal values for total power (1318±546 compared with 1918±818 ms2; P< 0.01) and the low-frequency component (33±21 compared with 50±11 normalized units; P< 0.03) and a higher value for the high-frequency component (77±15 compared with 61±18 normalized units; P< 0.05) than aged subjects. Consequently, the low-frequency/high-frequency ratio (0.43±0.07 compared with 0.91±0.05; P< 0.02) was also lower in the healthy centenarians than in the aged subjects. Our study demonstrates that the basal low-frequency/high-frequency ratio, an indirect index of cardiac sympathovagal balance, is lower in healthy centenarians than in aged subjects.
Amino acid nutrition and immune function in tumour-bearing rats: a comparison of glutamine-, arginine- and ornithine 2-oxoglutarate-supplemented diets
Authors: ROBINSON Lindsay E. , BUSSIÈRE Françoise I. , LE BOUCHER Jacques , FARGES Marie-Chantal , CYNOBER Luc A. , FIELD Catherine J. , BARACOS Vickie E. 
Published: August 2015

Dietary supplementation with glutamine (Gln), arginine (Arg) or ornithine 2-oxoglutarate (α-ketoglutarate; OKG) has attracted recent attention for the potential to improve anti-cancer immune function. However, since these compounds have not been compared systematically in an internally controlled study, their relative efficacy is difficult to estimate. Buffalo rats were fed on nutritionally complete semi-purified diets supplemented with Gln, Arg or OKG for 14 days after implantation of the Morris hepatoma 7777 (n⩾ 7 per diet). The control diet was made isonitrogenous and isoenergetic by addition of a mixture of non-essential amino acids. After 14 days, peritoneal macrophages and splenocytes were isolated to determine cell phenotypes, macrophage cytostatic activity and natural killer (NK) cell cytotoxicity, as well as nitric oxide (NO) and cytokine production. Diet had no effect on tumour weight (1.6±0.2 g; n = 59). However, rats fed OKG had increased macrophage cytostatic activity and NK cell cytotoxicity (P< 0.05). Although enhanced killing ability by NK cells was associated with higher splenocyte NO production (P< 0.04), increased cytotoxicity was not inhibited by a specific inhibitor of inducible NO synthase. The proportion of interleukin-2-receptor-positive T cells after stimulation increased in rats fed OKG (P< 0.05); however, cytokine production was not affected by diet. None of OKG, Gln or Arg altered tumour growth compared with a control mixture of non-essential amino acids. These results suggest no net advantage for anti-cancer immunity, but do not preclude benefits in immune responses to disease recurrence or metastasis, therapy or secondary infection.
Genetic analysis of the atrial natriuretic peptide gene in essential hypertension
Authors: KATO Norihiro , SUGIYAMA Takao , MORITA Hiroyuki , NABIKA Toru , KURIHARA Hiroki , YAMORI Yukio , YAZAKI Yoshio 
Published: August 2015

Atrial natriuretic peptide (ANP) plays an important role in the regulation of blood pressure through sodium–water homoeostasis. Accordingly, several investigators have raised the question of whether the gene encoding ANP is involved in the aetiology of essential hypertension or related phenotypes such as salt sensitivity. Most of the studies have used anonymous polymorphic markers of the gene, and made inconclusive claims about the disease relevance of ANP. Therefore, in order to find sequence variations with potential functional significance and to characterize the pattern of linkage disequilibrium between polymorphisms, we screened a 3368-bp genomic fragment of ANP. Subsequently we tested the association of detected polymorphisms with plasma ANP levels and with hypertension status. Two new polymorphisms were identified, in the 5′-untranslated region and exon 1 respectively, as well as three previously reported polymorphisms in intron 2 and exon 3. When analysed in 102 healthy normotensive subjects, none of the polymorphisms appeared to significantly affect plasma ANP levels. A case–control study in a Japanese population (255 hypertensive and 225 normotensive individuals) revealed a marginally significant association (P = 0.026) between an ANP polymorphism located in the 5′-untranslated region (C-664G) and hypertension, but no association for the other polymorphisms. Each of the uncommon variants has an allele frequency of less than 10% in Japanese people, which may have hampered our detection of a significant association between ANP variants and hypertension status (and plasma ANP levels). The pathophysiological relevance of ANP, however, needs to be further defined in relation to hypertension-associated phenotypes, and also should be examined in different ethnic groups.
Deleterious effects of chronic clenbuterol treatment on endurance and sprint exercise performance in rats
Authors: DUNCAN Noel D. , WILLIAMS David A. , LYNCH Gordon S. 
Published: August 2015

The β2-adrenergic agonist, clenbuterol, has powerful muscle anabolic and lipolytic effects and is used by athletes to improve exercise performance; however, its use in conjunction with different forms of exercise training has received limited attention. Since previous studies have reported that chronic use of other β2-adrenergic agonists has deleterious effects on cardiac muscle structure and function, the aim of the present study was to determine whether chronic clenbuterol administration would reduce the exercise capabilities of rats subjected to long-term treadmill sprint running, endurance swimming or voluntary wheel running training. The effect of clenbuterol treatment on exercise performance in rats was evaluated in three separate studies. Different groups of male rats were assigned to an endurance swimming (2 h/day, 5/7 days, 18 weeks) group, a treadmill sprint running (8×1 min bouts, 1.05 m/s, 20 weeks) group, or a voluntary wheel running (16 weeks) group. In each study, rats were allocated into either a treated group that received clenbuterol (2 mg·kg-1·day-1) in their drinking water or an untreated control group. In each of the three studies, treated rats exhibited a reduction in exercise performance compared with untreated rats. Treated rats ran ∼ 57% less total distance than untreated rats in the voluntary running programme and were unable to complete the swimming and sprinting protocols performed by the untreated rats. In each of the studies, the treated rats exhibited cardiac hypertrophy, with absolute heart mass increased by ∼ 19% and heart mass relative to body mass increased by ∼ 20%. The hearts of sedentary rats treated with clenbuterol exhibited extensive collagen infiltration surrounding blood vessels and in the wall of the left ventricle. The results indicate strongly that chronic clenbuterol administration deleteriously affects exercise performance in rats, potentially due to alterations in cardiac muscle structure and function.