bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Organization of Human Nuclei
Authors: Hassan A. B. 
Published: August 2015

1. Despite much progress in deciphering nuclear functions at the molecular level, our understanding of how these processes occur in vivo has been limited by the technologies presently available. I have used and developed a permeabilized cell system that retains most of the RNA- and DNA-polymerizing activities of HeLa cells.
2. Focal sites of transcription were visualized after incubation with bromouridine-UTP and immunolabelling with an antibody that reacts with bromouridine-RNA. Focal sites of replication were directly visualized by incubation with fluorochrome—dUTP conjugates. Approximately 300 transcription and 150 replication fluorescent foci were visualized in human cells. Foci resisted nucleolytic removal of 90% of chromatin. Experiments using laser scanning confocal microscopy show co-localization of sites of transcription with both splicing and replication sites, the latter particularly at the onset of S phase. Sites of replication were localized to discrete ovoid bodies when chromatin-depleted nuclei were visualized by thick section (resinless) electron microscopy.
3. These results suggest that active polymerases are focally concentrated (approximately 40 per focus) in ‘factories’ within nuclei. This higher-order organization may be important for both the initiation of replication and transcription in vivo.
Effect of Dietary Salt Restriction on Renal Sensitivity to Vasopressin in Man
Authors: Sutters M. , Duncan R. , Peart W. S. 
Published: August 2015

1. We have previously described a progressive antidiuresis in response to low-dose vasopressin infusion during salt restriction in man, despite stable or even declining plasma vasopressin concentration. In the present study we examine the hypothesis that renal sensitivity to the antidiuretic effect of arginine vasopressin may be enhanced by salt restriction.
2. Extremely low-dose infusions of arginine vasopressin were given to normal subjects after equilibration to high (260 mmol/day) and low (20 mmol/day) sodium intakes.
3. Salt restriction increased the antidiuretic effect of arginine vasopressin (2 fmol min−1 kg−1 arginine vasopressin increased urine osmolality from 67.8 ± 2.6 to 196.3 ± 35.7 mosmol/l in the high-salt study and from 268.3 ± 49 mosmol/l in the low-salt study; P &lt; 0.05 between sodium intakes). Glomerular filtration rate, estimated from inulin clearance, was unchanged during arginine vasopressin infusion irrespective of salt intake (high salt 116.5 ± 9.4 to 118.9 ± 6.4 ml/min; low salt, 135.1 ± 9.2 to 111.2 ± 12.4 ml/min). Renal plasma flow, estimated from para-aminohippurate clearance, fell further during infusion of 2 fmol min−1 kg−1 arginine vasopressin in the low-salt study than in the high-salt study (low salt, from 555.7 ± 22.7 to 298.3 ± 27.6 ml/min; high salt, from 544.5 ± 30.2 to 452.9 ± 28.9 ml/min; P &lt; 0.05 between sodium intakes).
4. Plasma atrial natriuretic peptide concentration increased during infusion of 2 fmol min−1 kg−1 arginine vasopressin in the low-salt study (to 136.5% ± 19.9% of baseline, P &lt; 0.05), if anything falling in the high-salt study (to 90.5% ± 13.6% of baseline). Packed cell volume fell during arginine vasopressin infusion in the low-salt study (high salt, to 98.2% ± 0.4% of baseline; low salt, to 95.7% ± 0.4% of baseline, P &lt; 0.05 for the low-salt study only).
5. Plasma arginine vasopressin concentration was constant throughout each study (high salt 0.48 ± 0.12 to 0.48 ± 0.1 pmol/l; low salt, 0.38 ± 0.05 to 0.4 ± 0.04 pmol/l).
6. Our findings suggest that renal sensitivity to the hydro-osmotic and vascular effects of arginine vasopressin is enhanced by salt restriction.
Tissue Inhibitor of Metalloproteinase-1 and Interstitial Collagenase Expression in Autoimmune Chronic Active Hepatitis and Activated Human Hepatic Lipocytes
Authors: Iredale J. P. , Goddard S. , Murphy G. , Benyon R. C. , Arthur M. J. P. 
Published: August 2015

1. Activated hepatic lipocytes are central to the pathogenesis of liver fibrosis as the principal source of both interstitial collagens and matrix-degrading metalloproteinases. In progressive fibrosis there is a failure to degrade interstitial collagens with a reported decrease in collagenase activity. In these studies we investigate expression of the potent collagenase inhibitor, tissue inhibitor of metalloproteinase-1, and interstitial collagenase in end-stage autoimmune chronic active hepatitis and activated human hepatic lipocytes in culture.
2. Messenger RNA transcripts for interstitial collagenase and tissue inhibitor of metalloproteinase-1 in explanted human liver were quantified by ribonuclease protection assay and densitometric analysis. This indicated that tissue inhibitor of metalloproteinase-1 and interstitial collagenase expression in autoimmune chronic active hepatitis were also co-ordinately up-regulated.
3. Using Northern analysis of RNA from human lipocytes in primary culture on plastic, mRNA for interstitial collagenase could not be detected in unstimulated cells but was present after stimulation with tumour necrosis factor alpha. Tissue inhibitor of metalloproteinase-1 mRNA was present in unstimulated lipocytes and up-regulated fivefold in response to tumour necrosis factor alpha. Using activity assay of serum-free conditioned media, interstitial collagenase could not be detected in unstimulated primary cultures, primary cultures stimulated with tumour necrosis factor alpha or transforming growth factor beta-1 (n = 3 and n = 4 respectively) or in passaged lipocytes (n = 6). In contrast, free tissue inhibitor of metalloproteinase-1 activity was present in unstimulated and passaged cultures and this was increased in response to tumour necrosis factor alpha and transforming growth factor beta-1.
4. These data indicate that for culture-activated lipocytes there is a net inhibition of matrix degradation mediated by excess tissue inhibitor of metalloproteinase-1 expression relative to interstitial collagenase. In autoimmune chronic active hepatitis, our messenger RNA studies demonstrate a similar up-regulation of tissue inhibitor of metalloproteinase-1 in addition to interstitial collagenase. This may contribute to the accumulation of interstitial collagens and progression of liver fibrosis in this disease.
Role of α-Adrenoceptors in the Maintenance of Core Temperature in Humans
Authors: Frank Steven M. , El-Gamal Nader , Raja Srinivasa N. , Wu Peter K. , Afifi Osama 
Published: August 2015

1. Although α-adrenoceptor antagonists have been shown to induce core hypothermia in animals, it is unclear whether the primary mechanism is increased heat loss or decreased heat production. Furthermore, studies have not been performed in humans to determine the role of α-adrenoceptors in the maintenance of core temperature.
2. α-Adrenoceptor blockade was achieved with three doses of phentolamine given by random assignment on three different study days in five male and five female healthy subjects. Core temperature, mean skin-surface temperature, fingertip capillary blood flow and metabolic heat production were measured. Dose—response curves were plotted for all measured variables, and males and females were compared to identify potential gender differences.
3. Core temperature decreased with all doses of phentolamine. At the completion of the phentolamine infusion, the decrease in core temperature was more significant with high-dose (0.3 ± 0.1°C, P = 0.03) and with medium-dose (0.2 ± 0.0deg;C, P = 0.05) phentolamine than with low-dose phentolamine (0.1 ± 0.0deg;C). The maximum core temperature decrease during the study was more significant with high dose (0.6 ± 1°C) than with medium (0.3 ± 1deg;C, P = 0.04) or low (0.3 ± 1°C, P = 0.005) doses. Mean skin-surface temperature was increased with all doses. Fingertip blood flow was increased (approximately 60% above baseline) with the medium and high doses, but was unchanged with the low dose. Total body oxygen consumption was unchanged regardless of dose. Although females had a higher core temperature at baseline, changes in core temperature, skin-surface temperature and fingertip blood flow were similar in males and females.
4. These findings suggest that α-adrenergic-antagonist-induced hypothermia results from a dose-dependent redistribution of heat from the core to the periphery, and not from a decrease in metabolic heat production. This leads us to conclude that baseline α-adrenergic ‘tone’ serves to maintain core temperature by constraining heat to the core thermal compartment.
Effect of Hypoxia and β2-Agonists on the Activity of the Renin-Angiotensin System in Normal Subjects
Authors: Millar Evelyn A. , Angus Robert M. , Nally Jane E. , Clayton Robin , Thomson Neil C. 
Published: August 2015

1. We have reported that the renin-angiotensin system is activated in acute asthma, and also by high-dose nebulized β2-agonists. The contribution of other possible stimuli such as hypoxia is unknown. The present study examined the effect of hypoxia alone and also combined with β2-agonists on the activity of the renin-angiotensin system.
2. In a double-blind crossover study, eight healthy subjects were randomized to inhale a hypoxic (FiO2 = 12%) or normoxic mixture for a period of 30 min, with either nebulized salbutamol (5 mg) or placebo administered into the circuit after 10 min. Plasma renin, angiotensin II and serum angiotensin-converting enzyme were measured at baseline and at intervals up to 2 h. Pulse rate and oxygen saturation were monitored continuously throughout the study.
3. After hypoxia alone, there was no change in the levels of plasma renin or angiotensin II. When salbutamol was added to the hypoxic mixture, there was a significant rise in plasma renin and angiotensin II [mean (SEM) maximal increase in angiotensin II of 5.6 (2.9)pg/ml and renin of 15.5 (6.3) μ-units/ml at 60 min, P &lt; 0.05 compared with normoxia]. When salbutamol was administered in the normoxic mixture, plasma renin and angiotensin II also increased but this effect was similar to the effect of salbutamol in the hypoxic mixture. Serum angiotensin-converting enzyme levels were unaffected by hypoxia or salbutamol.
4. We conclude from these results that there is activation of the renin—angiotensin system in healthy subjects by salbutamol, but not hypoxia. In addition, the effect of salbutamol on the renin—angiotensin system is not influenced by the presence of hypoxia. As similar levels of hypoxia occur in acute exacerbations of asthma, it seems unlikely that hypoxia is contributing to activation of the renin—angiotensin system in acute severe asthma.
Influence of Blood Group and Secretor Status on Carbohydrate Structures in Human Gastric Mucins: Implications for Peptic Ulcer
Authors: Sidebotham R. L. , Baron J. H. , Schrager J. , Spencer J. , Clamp J. R. , Hough L. 
Published: August 2015

1. The content and distribution of carbohydrate was examined in mucus glycopolypeptides from human antral mucosae.
2. The mean amount of carbohydrate per 1000 amino acid residues was found to be similar in glycopolypeptides with A, B or H activity. It was slightly, though significantly, less in glycopolypeptides lacking these determinants, because carbohydrate chains were of a shorter average length than in the A-, B- or H-active preparations. This difference was reflected in the sizes of oligosaccharide—alcohols released from representative glycopolypeptides with alkaline borohydride.
3. Differences between A-, B- or H-active and non-secretor glycopolypeptides in terms of the mean number of carbohydrate chains per 1000 amino acid residues were found to be small, and without significance.
4. The average number of peripheral monosaccharide units per 1000 amino acid residues was greater in A-active than in H-active, and least in non-secretor, glycopolypeptides. This order was reversed for monosaccharide units incorporated into skeletal (core plus backbone) structures. The difference in each case was statistically significant.
5. These findings suggest that the increased risk of peptic ulcer associated with blood group O and non-secretor status is unlikely to be attributable to an inherent deficiency in the protective mucus layer, linked to differences between mucins that are associated with A, B or H activity. Other hypotheses linked to infection with Helicobacter pylori are examined.
Systemic Treatment with Epidermal Growth Factor Induces Anaemia in Goettingen Minipigs
Authors: Juhl Claus Orloff , Vinter-Jensen Lars , Myhre-Jensen Olaf , Jensen Lone Susanne , Dajani Esam Zapher 
Published: August 2015

1. From two independent experimental studies conducted in 48 minipigs with oesophageal sclerotherapy and concomitant treatment with epidermal growth factor, blood samples together with bone marrow biopsies were analysed for safety data.
2. Four to five weeks of systemic treatment with epidermal growth factor induced a decline in blood haemoglobin concentration in a time- and dose-dependent and reversible manner but without an effect on leucocyte or platelet counts.
3. The bone marrow expressed decreased amounts of haematopoietic tissue and reduced numbers of erythropoietic cells.
4. Four to five weeks of systemic treatment with epidermal growth factor induced reversible increases in serum concentrations of creatinine and urea, most likely reflecting renal impairment.
5. Groups in which creatinine and urea were not increased also had reduced blood haemoglobin concentrations.
6. These findings suggest that epidermal growth factor selectively impaired the erythropoiesis and stress the importance of risk-benefit analysis concerning the potential therapeutic applications of epidermal growth factor.
Abnormal Left Ventricular Diastolic Function during Cold Pressor Test in Uncomplicated Insulin-Dependent Diabetes Mellitus
Authors: Gøtzsche Ole , Darwish Ahmed , Hansen Lars Peter , Gøtzsche Liv 
Published: August 2015

1. Insulin-dependent diabetes mellitus is a known risk factor for congestive heart failure and an early diastolic dysfunction has been described. In order to see if diabetes itself and not complications like hypertension, nephropathy or ischaemic heart disease can be considered responsible for the abnormal diastolic function of the left ventricle, 17 young patients with uncomplicated insulin-dependent diabetes mellitus and 12 control subjects were exposed to a cold pressor test.
2. Blinded echo-Doppler examination was performed before and during the test. During basal conditions, left ventricular dimensions and volumes were smaller in diabetes and atrial contributions to left ventricular filling were increased.
3. During the cold pressor test, isovolumic relaxation time increased, peak early filling velocity (E) decreased, E deceleration time decreased and atrial contribution (A) increased significantly in diabetes, while only A increased in the control group. A marked increase in left atrial ejection force was seen in diabetes only (P &lt; 0.002). This difference was seen in spite of comparable reductions in mitral area and atrioventricular compliance in the two groups.
4. The hyperfunction of the left atrium in diabetes is hypothesized to be due to reduced size of the left ventricle combined with incipient autonomic neuropathy.
Potent Inhibitory Effect of Sr 49059, An Orally Active Non-Peptide Vasopressin via Receptor Antagonist, on Human Arterial Coronary Bypass Graft
Authors: Liu James J. , Chen Joan R. , Buxton Brian B. , Johnston Colin I. , Burrell Louise M. 
Published: August 2015

1. The effect of vasopressin receptor antagonists varies between analogues (peptide, non-peptide) and across species. In this study the effect of the novel non-peptide vasopressin V1a receptor antagonist SR 49059 on human internal mammary arteries was investigated.
2. SR 49059 produced a potent, concentration-dependent, inhibitory effect on vasopressin-induced contraction of human coronary bypass graft internal mammary arteries. Both SR 49059 (1 μmol/l) and a peptide selective V1a antagonist {[d(CH2)5sarcosine7]arginine vasopressin} (1 μmol/l) abolished vasopressin-induced contraction. The non-peptide V1a receptor antagonist OPC-21268 (1 μmol/l) had no effect on vasopressin-induced contraction.
3. The effect of SR 49059 was specific to vascular vasopressin receptors as noradrenaline-induced contraction was not influenced by SR 49059.
4. The results of this study in vitro indicate that the non-peptide SR 49059 is a potent, specific vasopressin V1a receptor antagonist in the human internal mammary artery and suggest that it may be a useful tool for studying the pathophysiological role of vasopressin in man.
Differences in Transcription and Translation of Long and Short GSα, the Stimulatory G-Protein, in Human Atrium
Authors: Monteith M. Susan , Wang Tao , Brown Morris J. 
Published: August 2015

1. We have previously reported the relative mRNA and protein level of the long and short splice variants of Gsα (GsαL and GsαS) in human atrium. We have now measured the relative proportions of the serine+ and serine− variants of GsαL and GsαS in human atrium, and assessed, indirectly, whether their differential expression may (i) regulate Gsα phosphorylation, and (ii) be regulated by atrial cyclic AMP levels.
2. The serine+ and serine− variants of GsαL and GsαS were estimated by single nucleotide primer extension in 36 right atrial strips of which half were from β-adrenoceptor-blocked patients. The ratio of serine+ to serine− variants was 0.06 ± 0.12 for GsαL, compared with 8.04 ± 12.16 for GsαS (P &lt; 0.001).
3. Isoelectric points of GsαL and GsαS in the atria of four β-adrenoceptor-blocked and four non-β-adrenoceptor-blocked patients were estimated by two-dimensional gel electrophoresis. Two-dimensional gel analysis gave a consistent pattern with several spots for both GsαL and GsαS; however, the isoelectric points of GsαS were more acid (5.18 ± 0.24) than those of GsαL (5.87 ± 0.17, P &lt; 0.001).
4. No significant difference in either the serine variants or isoelectric point value was observed between β-adrenoceptor-blocked and non-β-adrenoceptor-blocked patients.
5. In conclusion, all four Gsα variants were expressed in human atrium, but GsαL is almost entirely of the serine− form. GsαS has a more acidic isoelectric point than GsαL, indicating a possible post-translational modification. The lack of difference in our results between β-adrenoceptor-blocked and non-β-adrenoceptor-blocked patients suggests indirectly that cyclic AMP is an unlikely candidate for regulating splicing or post-translational modification of Gsα in vivo.
Effects of Fish Oil Supplementation on Atherosclerosis in Different Regions of the Aorta of Rabbits with Diet-Induced Hypercholesterolaemia
Authors: Chen Ming-Fong , Hsu Hsiu-Ching , Lee Yuan-Teh 
Published: August 2015

1. The effects of fish oil supplementation on atherosclerosis in different regions of the aorta in rabbits with diet-induced hypercholesterolaemia were studied. Control and experimental rabbits were fed a 1% cholesterol-enriched diet with or without 10% fish oil supplementation (seven in each group), and were killed after 2 weeks of feeding. The ascending, descending and abdominal aortas as well as the pulmonary artery were harvested for analyses of prostanoid production, malondialdehyde, superoxide dismutase activity and cholesterol levels. The tissues from the other seven rabbits of each group were obtained after 6 weeks of feeding for the identification of atherosclerotic lesions by a Sudan IV stain.
2. The cholesterol-fed rabbits had a significantly higher thromboxane B2 production, a lower 6-keto-prostaglandin1α/thromboxane B2 ratio and a higher malondialdehyde level than the other two groups in the ascending and abdominal aortas as well as the pulmonary artery; this finding paralleled the severity of atherosclerotic lesions. These manifestations were most prominent in the ascending aorta. The fish oil-supplemented rabbits had the most beneficial aortic prostanoid production, attenuated lipid peroxidation and significantly suppressed atherosclerosis.
3. These results suggest that a high-cholesterol diet induces more atherosclerotic lesions, especially on the ascending aorta, in rabbits. A fish oil supplement favours prostanoid production and attenuates lipid peroxidation on all four regions of the great arteries, thus suppressing atherosclerosis in diet-induced hypercholesterolaemic rabbits.
Cardiomegaly and Vasoactive Hormones in Rats with Chronic Myocardial Infarction: Long-Term Effects of Chlorothiazide
Authors: Kohzuki Masahiro , Kanazawa Masayuki , Yoshida Kazunori , Tsutsumi Eikatsu , Yasujima Minoru , Abe Keishi , Johnston Colin I. , Sato Tokutaro 
Published: August 2015

1. The effects of prolonged chlorothiazide treatment of left ventricular failure on cardiac hypertrophy, circulating vasoactive hormones and exchangeable body sodium were examined in rats with chronic myocardial infarction induced by left coronary artery ligation. Chlorothiazide therapy commenced either immediately or 2 weeks after infarction. For 4 weeks, the rats were given either chlorothiazide (50 mg day−1 kg−1) in their drinking water or drinking water alone.
2. Cardiac weight increased in untreated rats with infarction in comparison with sham-operated controls, indicating the presence of chronic left ventricular dysfunction, although exchangeable body sodium, plasma renin activity, plasma vasopressin and plasma osmolality remained unchanged.
3. Chlorothiazide raised haematocrit and plasma renin activity equally in rats with and without infarction, although exchangeable body sodium, plasma vasopressin and plasma osmolality were not changed by the treatment. Plasma atrial natriuretic peptide was 2-fold higher in rats with infarction and this response was not affected by chlorothiazide treatment. Chlorothiazide therapy did not prevent or reverse cardiac hypertrophy.
4. Chronic diuretic therapy in this experimental model of heart failure did not reduce extracellular sodium, plasma vasopressin or the extent of ventricular hypertrophy, possibly because the condition was associated with activation of the renin—angiotensin system.
Differences in Microvascular Fluid Permeability between Long-Duration Type 1 (Insulin-Dependent) Diabetic Patients with and without Significant Microangiopathy
Authors: Jaap Alan J. , Shore Angela C. , Tooke John E. 
Published: August 2015

1. To further investigate the role of microvascular functional changes in the pathogenesis of diabetic microangiopathy in type 1 diabetes, microvascular fluid permeability was measured in nine patients with a long disease duration and no or minimal (background retinopathy alone) microangiopathy, nine age-, sex- and duration-matched patients with microalbuminuria and nine control subjects. Microvascular fluid permeability was assessed by determination of the forearm capillary filtration coefficient using a sensitive strain-gauge plethysmographic technique.
2. Microvascular fluid permeability was significantly higher in the patients with microalbuminuria [8.5 (6.8–15.2) × 10−3 ml min−1 100 g−1 of tissue mmHg−1; median (range)] than in the patients with no or minimal complications [5.2 (3.6–7.0) × 10−3 ml min−1 100 g−1 of tissue mmHg−1, P &lt; 0.001]. There was, however, no significant difference in microvascular fluid permeability between the patients with no or minimal complications and control subjects [4.5 (3.2–5.7) × 10−3 ml min−1 100 g−1 of tissue mmHg−1, P = 0.31]. Blood pressure and glycaemic control were similar in the two groups of diabetic patients.
3. These results provide further evidence that changes in microvascular permeability are found in other vascular beds in patients with incipient nephropathy, whereas no such changes are found in patients with a long disease duration and little evidence of microangiopathy.