bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-6 Induces Proteolysis by Activating Intracellular Proteases (Cathepsins B and L, Proteasome) in C2C12 Myotubes
Authors: Ebisui Chikara , Tsujinaka Toshimasa , Morimoto Takashi , Kan Kazuomi , Iijima Shouhei , Yano Masahiko , Kominami Eiki , Tanaka Keiji , Monden Morito 
Published: August 2015

1. A cell culture system of C2C12 myotubes was established as a model of the muscle. With the aid of this model, the half-lives of intracellular proteins as well as the activities and mRNA levels of proteasomes (26S and 20S) and cathepsins (B, L, and H) were examined in the presence of various amounts of cytokines.
2. It was found that 100 units/ml recombinant human interleukin-6 somewhat shortened the half-life of long-lived proteins to 23.79 ± 1.55 h (control: 25.60 ± 1.87 h). When 1% fetal bovine serum contained in the culture medium was replaced by 0.5 mg/ml bovine serum albumin, interleukin-6 was more effective since 10 units/ml of interleukin-6 shortened the half-life to 19.09 ± 2.87 h (control: 22.26 ± 321 h). Interleukin-6 (100 units/ml) increased the activity of 26S proteasome by 31.5%, of cathepsin B by 53.5% and of cathepsin B + L by 21.3%. These increases occurred in association with an increase in their transcription.
3. On the other hand, 1000 units/ml of recombinant human tumour necrosis factor α prolonged the half-life of long-lived proteins while reducing the protease activities of 20S proteasome (−27.1%), cathepsins B (−64.6%) and B + L (−54.9%).
4. These results suggest that interleukin-6 induces degradation of long-lived intracellular proteins by activating both the non-lysosomal (proteasomes) and lysosomal (cathepsins) proteolytic pathways. It is therefore concluded that interleukin-6 is a candidate for a proteolysis-inducing factor in myotubes and may play an important role in the progression of muscle degradation in systemic inflammatory responses induced by sepsis or severe injury.
Effects of Different Lipoproteins on the Proliferative Response of Interleukin-2-Activated T Lymphocytes and Large Granular Lymphocytes
Authors: De Sanctis Juan B. , Blanca Isaac , Bianco Nicholas E. 
Published: August 2015

1. T lymphocytes and large granular lymphocytes internalized chylomicrons, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein and acetyl modified low-density lipoprotein through different receptors as assessed by flow cytometry. The observed internalization ranged from 8% to 20%.
2. All lipoproteins induced proliferative responses in T lymphocytes and large granular lymphocytes at optimum concentrations (40 μg of protein/ml for all lipoproteins except high-density lipoprotein). Chylomicrons, very low-density lipoprotein and low-density lipoprotein increased T-lymphocyte proliferative response by fourfold while inducing respectively a seven-, nine- and sevenfold increment in large granular lymphocytes. Similarly, high-density lipoprotein and acetyl modified low-density lipoprotein respectively induced a nine- and sevenfold increment in T cells and a 17- and eightfold increment in large granular lymphocyte proliferative response.
3. Both cell types internalized more lipoprotein when they were stimulated with interleukin 2. Chylomicrons and low-density lipoprotein internalization was increased threefold and very low-density lipoprotein internalization twofold, while high-density lipoprotein internalization was unchanged in both cell types. Acetyl modified low-density lipoprotein internalization was fourfold higher in large granular lymphocytes only.
4. The proliferative response of interleukin-2 stimulated cells was different from that of unstimulated cells. Chylomicrons and very low-density lipoprotein induced a sixfold increment in T-cell proliferative response but only a fourfold increment in large granular lymphocytes. Low-density lipoprotein and acetyl modified low-density lipoprotein induced respectively a sevenfold and eightfold increment in T cells and a eightfold and threefold increment in large granular lymphocyte proliferative response. Highdensity lipoprotein did not affect T-lymphocyte proliferative response while inducing a twofold increase in large granular lymphocytes.
5. Lipoproteins are important in the proliferative response of unstimulated and interleukin-2-stimulated cells.
On the Quantification of Heart Rate Changes in Autonomic Function Tests: Relations between Measures in Beats per Minute, Seconds and Dimensionless Ratios
Authors: Faes Theo J. C. , De Neeling Nico N. D. , Kingma Rene , TenVoorde Ben J. , Karemaker John M. 
Published: August 2015

1. Disorders of the autonomic nervous system are frequently diagnosed by measuring heart rate changes in response to deep-breathing and lying-to-standing manoeuvres. The heart rate changes in these manoeuvres are quantified in measures using various units, like beats per minute, seconds and dimensionless ratios.
2. In the present study we mathematically derived relationships between the measures which quantify heart rate changes in beats per minute, seconds and dimensionless ratios. The theoretical outcomes were experimentally confirmed by the results of the deep-breathing and the lying-to-standing test in 525 healthy and diabetic subjects. The measures were found to be non-equivalent, because the mean RR interval duration influenced the measures in different ways.
3. It is argued that measures in seconds are preferable to measures in beats per minute or ratios, because the physiological interpretation of this measure is easier, and the sensitivity of measures in seconds is expected to be greater.
4. Finally, we recommend that measures of heart rate variation in the deep-breathing and lying-to-standing manoeuvre are accompanied by information on the mean RR interval duration or mean heart rate to allow correct interpretation of the measures.
Calf Muscle Mitochondrial and Glycogenolytic Atp Synthesis in Patients with Claudication Due to Peripheral Vascular Disease Analysed Using 31P Magnetic Resonance Spectroscopy
Authors: Kemp G. J. , Hands L. J. , Ramaswami G. , Taylor D. J. , Nicolaides A. , Amato A. , Radda G. K. 
Published: August 2015

1. We set out to define abnormalities of oxidative ATP synthesis, cellular proton efflux and the efficiency of ATP usage in gastrocnemius muscle of patients with claudication due to peripheral vascular disease, using data obtained by 31P magnetic resonance spectroscopy during aerobic exercise and recovery.
2. Eleven patients with moderate claudication were studied and results were compared with 25 age-matched control subjects. Changes in pH and phosphocreatine concentration during recovery were used to calculate the maximum rate of oxidative ATP synthesis (Qmax.) and the capacity of net proton efflux. Changes in pH and phosphocreatine concentration were used to estimate rates of non-oxidative and (indirectly) oxidative ATP synthesis throughout exercise, taking account of abnormalities in proton efflux during exercise.
3. In patients with claudication, slow post-exercise phosphocreatine recovery showed a 42 ± 9% decrease in Qmax., and the slow ADP recovery was consistent with this. pH recovery was slow, showing a 77 ± 9% decrease in the capacity for proton efflux. Both abnormalities are compatible with a substantial reduction in muscle blood flow.
4. During exercise, increased phosphocreatine depletion and intracellular acidification were a consequence of impaired oxidative ATP synthesis and the consequent increase in non-oxidative ATP synthesis, compounded by reduced proton efflux. The acidification prevented an increase in ADP concentration which could otherwise partially compensate for the oxidative defect. All these abnormalities are compatible with a reduced muscle blood flow.
5. In addition, initial-exercise changes in pH and phosphocreatine concentration implied a 44 ± 5% reduction in ‘effective muscle mass’, necessitating an ATP turnover (per litre of muscle water) twice as high for given power output as in control muscle. Some of this is probably due to a localized loss of muscle fibres, but the rest appears to reflect reduced metabolic efficiency of the muscle. This is not a direct consequence of reduced blood flow, and may be related to change in muscle fibre type.
Effect of Ozone Exposure on Maximal Airway Narrowing in Non-Asthmatic and Asthmatic Subjects
Authors: Hiltermann T. J. N. , Stolk J. , Hiemstra P. S. , Fokkens P. H. B. , Rombout P. J. A. , Sont J. K. , Sterk P. J. , Dijkman J. H. 
Published: August 2015

1. Ozone is a major constituent of air pollution in the summer. Epidemiological studies have demonstrated that there is an increase in hospital admissions for respiratory diseases 1 day after peak levels of ambient ozone. This may be due to an increase in the responsiveness of the airways to bronchoconstrictor stimuli.
2. In the present study we therefore studied the effect of a controlled exposure to ozone on the maximal degree of airway narrowing to a non-specific bronchoconstrictor, methacholine, 12 h after exposure. Both non-asthmatic and mild-asthmatic volunteers were exposed to ozone.
3. The study had a single blind design. Experimental exposures were to filtered air, 0.40 ppm ozone and filtered air respectively, at 1-week intervals. The duration of each exposure was 2 h with alternating periods of 15 min rest and exercise. At 12 h after exposure, methacholine inhalation challenge tests and sputum induction were performed.
4. Twelve hours after exposure to ozone there was a significant increase in the maximal degree of airway narrowing to methacholine (P &lt; 0.02) compared with exposure to air, in non-asthmatic as well as asthmatic subjects. These physiological changes were accompanied by a significant rise in the percentage of neutrophils in induced sputum (P &lt; 0.02). All changes had returned to baseline values 1 week after exposure to ozone.
5. Exposure to ozone causes a transient increase in the maximal degree of airway narrowing to methacholine in both non-asthmatic and asthmatic subjects. These laboratory results, obtained using relatively high ozone exposure in carefully selected subjects, might provide an explanation for the temporal relationship between ambient ozone levels and hospital admissions for asthma.
Metabolic Acidosis Does Not Contribute to Chronic Renal Injury in the Rat
Authors: Throssell D. , Brown J. , Harris K. P. G. , Walls J. 
Published: August 2015

1. Metabolic acidosis invariably accompanies chronic renal failure, and short periods of metabolic acidosis cause renal growth and proteinuria in normal rats. Rates of ammoniagenesis are increased in chronic renal failure, and it has been suggested that this contributes to disease progression. This study assessed (i) whether prolonged acidosis causes chronic renal injury in the normal kidney and (ii) whether abrogation of acidosis slows disease progression in the remnant kidney.
2. Metabolic acidosis was induced in normal rats by dietary hydrochloric acid. Urinary excretion of total protein, lysozyme and albumin increased, peaking at week 8 but returning to baseline by week 14. At killing after 14 weeks, kidney weights, glomerular filtration rates and serum creatinine were the same in both groups, but kidney/body weight and kidney/heart weight ratios were greater in the acidotic group. All kidneys were normal by light microscopy.
3. Rats subjected to five-sixths nephrectomy were given sufficient dietary bicarbonate to abolish uraemic acidosis, and their outcome was compared with that of non-alkalinized remnants (controls). Proteinuria, glomerular filtration rates, blood pressure, histological injury and time to the development of terminal uraemia were no better in bicarbonate-supplemented animals than in controls.
4. These data demonstrate that metabolic acidosis neither causes nor exacerbates chronic renal injury. We conclude that the treatment of uraemic acidosis is unlikely to influence disease progression in patients with chronic renal failure.
Seasonal Variation in Blood Pressure in Normotensive Women Studied by Home Measurements
Authors: Imai Yutaka , Munakata Masanori , Tsuji Ichiro , Ohkubo Takayoshi , Satoh Hiroshi , Yoshino Hiroshi , Watanabe Noriko , Nishiyama Akimitsu , Onodera Noriko , Kato Junko , Sekino Makoto , Aihara Akiko , Kasai Yutaka , Abe Keishi 
Published: August 2015

1. The factors influencing the seasonal variation in blood pressure measured at home in normotensive women were examined.
2. Sixteen female subjects (56.3 ± 7.9 years old, mean ± SD) measured their blood pressure and pulse rate at home each morning for more than 20 times per month for at least 1.5 years. Blood pressure and body weight were also determined in the office once or twice a month in that period. Monthly means of outdoor and indoor temperatures and daytime length were obtained from the Meteorological Observatory. The single cosinor method was used to evaluate circannual rhythm.
3. We observed a biphasic seasonal variation in self-recorded blood pressure measured at home, environmental temperature and daytime length but found no apparent seasonal variation in body weight and blood pressure measured in the office. The lowest levels of systolic and diastolic blood pressure measured at home were observed in July. The longest daytime length was recorded in June, while the highest outdoor temperature and indoor temperature were recorded in August, indicating that the longest daytime length preceded and the highest environmental temperature lagged behind the lowest level of blood pressure. The shortest daytime length is in December. The lowest outdoor and indoor temperature were observed in January, while the highest levels of self-recorded systolic blood pressure and diastolic blood pressure were in January and December, respectively. Half-amplitudes of self-recorded systolic and diastolic blood pressure were 2.6 ± 1.0 mmHg and 2.0 ± 0.8 mmHg, respectively.
4. These findings indicate the importance of a seasonal effect, i.e. daytime length and the environmental temperature, on the blood pressure of individuals.
Renal Effects of Angiotensin I-Receptor Blockade and Angiotensin Convertase Inhibition in Man
Authors: Schmitt Francois , Natov Svetlozar , Martinez Frank , Lacour Bernard , Hannedouche Thierry P. 
Published: August 2015

1. The objective was to compare two means of inhibition of the renin—angiotensin system [angiotensin-converting enzyme inhibition and selective antagonism of angiotensin II subtype 1 (AT1) receptor] on renal function in 10 healthy normotensive volunteers on a normal sodium diet. Since mechanisms of action may differ between both drugs, a synergistic action was further studied by combining the two drugs.
2. The design was a double-blind randomized acute administration of either placebo or a single oral dose of enalapril, 20 mg, followed in each case by administration of the AT1 selective antagonist losartan potassium, 50 mg orally.
3. The methods included measurements of hormones (plasma renin activity, plasma aldosterone), blood pressure and renal function from 45 to 135 min after administration of placebo or enalapril, and from 45 to 135 min after losartan and placebo or losartan and enalapril. Renal function was studied using clearance of sodium, lithium, uric acid, inulin and para-aminohippuric acid. To examine further the determinants of glomerular filtration at the microcirculation level, fractional clearance of neutral dextran was determined and sieving curves were applied on a hydrodynamic model of ultrafiltration.
4. Losartan did not change plasma renin activity, blood pressure or glomerular filtration rate, but increased significantly renal plasma flow and urinary excretion of sodium and uric acid. Enalapril increased plasma renin activity and renal plasma flow, and decreased blood pressure without natriuretic, lithiuretic or uricosuric effects. The renal vasodilatation was potentiated when losartan and enalapril were combined, despite a further rise in plasma renin. In contrast to enalapril, losartan either alone or in combination with enalapril significantly depressed fractional clearances of dextran of small radii (34–42 Å). These changes in fractional clearances of dextran were presumably related to the rise in glomerular plasma flow since the other major determinants of filtration, i.e. transcapillary glomerular pressure gradient, ultrafiltration coefficient and membrane property, were computed as unchanged by either losartan, enalapril or a combination of both.
5. In conclusion, these findings suggest that in normal sodium-repleted man the renal, hormonal and blood pressure effects of AT1 antagonism and angiotensin-converting enzyme inhibition are not strictly similar and could be synergistic.
Salvage of Exogenous Urea Nitrogen Enhances Nitrogen Balance in Normal Men Consuming Marginally Inadequate Protein Diets
Authors: Meakins Tracey S. , Jackson Alan A. 
Published: August 2015

1. Urea kinetics were measured in six healthy men using prime/intermittent oral doses of [15N15N] urea, after five days consuming one of four diets which varied in their nitrogen content: a reference diet (REF, 70 g of protein and 11.2 g of N); a low-protein diet (LP, 30 g of protein and 4.8 g of N); a low-protein diet with 6.9 g of urea added (LP-U1, 30 g of protein and 8 g of N); a low-protein diet with 13.7 g of urea added (LP-U2, 30 g of protein and 11.2 g of N).
2. Apparent nitrogen balance on the REF diet was significantly better than on the LP or the LP-U1 diets. The addition of the higher level of urea in the LP-U2 diet enhanced apparent nitrogen balance compared with the LP or LP-U1 diets, and was not different to apparent nitrogen balance on the REF diet.
3. On the LP, LP-U1 and LP-U2 diets, the rate of endogenous urea production was not different, and was about 60% of that on the REF diet, a statistically significant difference. The addition of a dietary supplement of urea increased the rate of urea appearance in the urea pool in direct relation to the dose of urea taken. There was no difference in the rate of appearance between the REF and LP-U2 diets, for both of which the rate of appearance was significantly greater than on the LP diet.
4. The excretion of urea in urine on the LP diet was 62% of that on the REF diet, a significant difference. There was no significant difference in the rate of urea excretion between the REF, LP-U1 and LP-U2 diets.
5. The rate of urea hydrolysis by the colonic microflora on the REF diet was more than twice that on the LP or LP-U1 diets. Supplementation with urea at the higher level, LP-U2, significantly increased hydrolysis to the same level as on the REF diet. Most of the nitrogen derived from urea hydrolysis was retained in the metabolic pool (&gt;80%), with no difference in the rate of retention between the REF and LP-U2 diets, both greater than the LP or LP-U1 diets.
6. The dietary supplements of urea increased the size of the body urea pool significantly. Renal clearance of urea was highest on the REF diet and decreased 13–29% on the low-protein diets. Bowel clearance was highest on the REF diet and decreased 46–55% on the low-protein diets. Neither urinary excretion of urea nor urea hydrolysis in the bowel were related simply to the concentration of urea in blood. Urea hydrolysis related most closely to the rate of appearance of urea in the urea pool.
7. The salvage of urea nitrogen was increased on the highest level of supplementation, but the overall sensitivity of the system was low, suggesting that other factors might be limiting for effective urea hydrolysis and the salvage of urea nitrogen.
Antioxidant Status and Lipid Peroxidation in Type II Diabetes Mellitus with and without Complications
Authors: Sundaram Ranjini K. , Bhaskar Anusha , Vijayalingam Selvamani , Viswanathan Moopil , Mohan Rema , Shanmugasundaram Kalathinkal R. 
Published: August 2015

1. This study was conducted on 467 cases of non-insulin-dependent diabetes mellitus and 180 healthy controls. Lipid peroxidation products in plasma and erythrocytes were assayed as thiobarbituric acid reactive substances, along with the erythrocyte antioxidant enzymes, namely superoxide dismutase, catalase and glutathione peroxidase. In addition, scavenger vitamins A, C and E and reduced glutathione levels in blood were also measured.
2. Lipid peroxidation was significantly raised within the first 2 years of diagnosis, and superoxide dismutase, catalase, reduced glutathione and vitamins C and E were significantly lowered.
3. These changes were correlated with the duration of the disease and were of a higher magnitude with the development of complications.
4. The results suggest that the antioxidant deficiency and excessive peroxide-mediated damage may appear early on in non-insulin-dependent diabetes mellitus, before the development of secondary complications.
Differential Regulation of Cyclo-Oxygenase-1 and Cyclo-Oxygenase-2 Gene Expression by Lipopolysaccharide Treatment in vivo in the Rat
Authors: Liu Shu Fang , Newton Robert , Evans Timothy W. , Barnes Peter J. 
Published: August 2015

1. Prostaglandins are important regulatory mediators of cardiovascular and pulmonary functions which may become disordered in patients with sepsis. The mechanisms controlling their synthesis and release under these circumstances remain unclear. Cyclo-oxygenase (COX, prostaglandin G/H synthase) is a key enzyme in prostaglandin synthesis and has two isoforms (COX-1 and COX-2). COX-1 is constitutively expressed and is probably responsible for prostaglandin release under physiological conditions, whereas COX-2 is expressed at high levels upon induction.
2. We investigated the effect of lipopolysaccharide treatment in vivo on differential COX-1 and COX-2 mRNA expression in the rat.
3. The 2.8 kb COX-1 message was detected in all lungs and seven hearts of eight control rats. In lipopolysaccharide-treated animals, COX-1 expression was reduced by approximately 5-fold in lungs and 2-fold in hearts as quantified by densitometry. In parallel, a marked upregulation of COX-2 mRNA expression was observed. The 4.4 kb COX-2 transcript was absent or expressed at low level in control lungs and hearts, but was increased by approximately 7- and 12-fold in lipopolysaccharide-treated lungs and hearts respectively. Neither the down-regulation of COX-1 nor the upregulation of COX-2 mRNA induced by lipopolysaccharide was significantly affected by pretreatment with dexamethasone in lung and heart, although expression of inducible nitric oxide synthase, induced by lipopolysaccharide, was markedly inhibited in the same tissues.
4. The down-regulation of COX-1 and upregulation of COX-2 may contribute to the multi-organ failure seen in sepsis.
Failure of Thrombin Inhibition to Prevent Intracoronary Thrombosis in the Dog
Authors: Belcher Philip R. , Drake-Holland Angela J. , Hynd John W. , Noble Mark I. M. 
Published: August 2015

1. Recurrent occlusion after thrombolysis may be caused by thrombin receptor-mediated platelet thrombosis occurring in a residual stenosis. To test the relative importance of the platelet thrombin receptor under conditions of high shear and endothelial damage (the Folts model of intracoronary thrombosis) we used the specific thrombin inhibitor recombinant hirudin.
2. A critical coronary artery stenosis overlying an area of crushed endothelium was used in a repeated measures study of eight open-chest anaesthetized dogs. In the control period, recurrent thrombosis occurred at an average rate (± SD) of 4.4 ± 1.4 ml/min2. Infusion of recombinant hirudin at 1.6 mg h−1 kg−1 abolished recurrent thrombosis in three dogs, but the thrombosis rate averaged 4.7 ± 2.9 ml/min2 in the remaining five animals.
3. Haematological measurements demonstrated the activity of recombinant hirudin: thrombin time rose from 13 ± 3 s to&gt;165 s universally (P&lt;0.01), partial thromboplastin time rose from 14 ± 2 s to 29 ± 10 s (P&lt;0.01). Bleeding time rose from 2.3 ± 0.8 min to 4.7 ± 1.8 min (P&lt;0.05).
4. It is concluded that specific thrombin inhibition, despite affecting coagulation, is relatively ineffective in preventing intracoronary thrombosis under conditions of high shear.