bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the Mitogenic Activity of Human Epidermal Growth Factor 1-53 and Epidermal Growth Factor 1-48 in Vitro and in Vivo
Authors: Goodlad R. A. , Boulton R. , Playford R. J. 
Published: August 2015

1. Epidermal growth factor is secreted into the gut lumen as a 53 amino acid peptide in vivo. Several preliminary studies have examined the clinical benefit of recombinant epidermal growth factor in intestinal disease, but there is inconsistency in the form of epidermal growth factor used (some using epidermal growth factor 1–48 and some epidermal growth factor 1–53), making comparisons difficult to evaluate.
2. We therefore examined the relative potency of recombinant epidermal growth factor 1–48 and epidermal growth factor 1–53 in stimulating [3H]thymidine uptake into primary rat hepatocytes at various doses in vitro and on various parameters of proliferation within the gastrointestinal tract when infused intravenously at 50 nmol day−1 kg−1 into rats receiving total parenteral nutrition.
3. Epidermal growth factor 1–53 was about twice as potent as epidermal growth factor 1–48 in its ability to stimulate [3H]thymidine incorporation into rat hepatocytes in vitro. In vivo studies supported this finding as, in both the small and large intestine, epidermal growth factor 1–53 caused about a 30% greater stimulation of intestinal growth than epidermal growth factor 1–48 (P &lt; 0.001).
4. The 1–48 truncated form of epidermal growth factor is less active than the full-length molecule in vitro and in vivo. This must be borne in mind when comparing clinical trials that use different forms of recombinant epidermal growth factor.
Skin Microcirculation of the Foot in Diabetic Neuropathy
Authors: Netten Paetrick M. , Wollersheim Hub , Thien Theo , Lutterman Jos A. 
Published: August 2015

1. In the feet of patients with diabetic neuropathy, total skin blood flow is increased due to an increased shunt flow. The question is, does this increased anastomotic shunt flow lead to either under- or overperfused nutritive capillaries.
2. To solve this question, skin microcirculation tests of the left big toe were performed in 20 healthy control subjects and in 40 insulin-dependent diabetic patients without macroangiopathy, 20 without and 20 with neuropathy. Skin temperature measurements and laser Doppler fluxmetry were performed to record mainly shunt flow and capillaroscopy to study nailfold capillary blood flow.
3. The insulin-dependent diabetic patients with neuropathy had a higher baseline skin temperature (mean ± SEM; 30.0 ± 0.6°C) and laser Doppler fluxmetry [26.2 ± 2.2 perfusion units (pu)] than patients without neuropathy (27.2 ± 0.8°C, P &lt; 0.01; 16.1 ± 2.0 pu, P &lt; 0.01) and healthy control subjects (27.9 ± 0.7°C, P &lt; 0.05; 18.6 ± 2.8 pu, P &lt; 0.05). Sympathetic stimulation (inspiratory gasp) resulted in a smaller laser Doppler fluxmetry decrease in the neuropathic patients (31.4 ± 4.6%) compared with non-neuropathic patients (48.2 ± 5.1%, P &lt; 0.05) and control subjects (49.0 ± 3.8%, P &lt; 0.05), while no difference between the three groups was seen in the laser Doppler fluxmetry decrease during a postural vasoconstriction test. The number of visible capillaries was highest in the neuropathic patients (10.2 ± 0.6/0.5 mm2), when compared with non-neuropathic patients (8.7 ± 1.2/0.5 mm2, P &lt; 0.05) and control subjects (8.3 ± 0.3/0.5 mm2, P &lt; 0.001). Capillary blood-cell velocity was significantly higher in the neuropathic patients (0.32 ± 0.05 mm/s) compared with non-neuropathic patients (0.23 ± 0.03 mm/s, P &lt; 0.05) and control subjects (0.23 ± 0.02 mm/s, P &lt; 0.01).
4. We conclude that there is an overperfused nutritive capillary circulation in the feet of patients with diabetic neuropathy. This is in contradiction to the capillary steal phenomenon and favours the hyperdynamic hypothesis to explain the decreased healing potential in diabetic neuropathic foot ulceration.
Effects of Hormone Replacement Therapy on Muscle Performance and Balance in Post-Menopausal Women
Authors: Armstrong Alison L. , Oborne Janet , Coupland Carol A. C. , MacPherson Marion B. , Bassey E. Joan , Wallace W. Angus 
Published: August 2015

1. A randomized controlled trial of the effect of oral hormone replacement therapy plus calcium compared with calcium alone on balance, muscle performance and falls was conducted over 48 weeks in 116 post-menopausal women (aged 45–70 years), all of whom had suffered a distal radial fracture during the previous 3 months. Treatment was with Prempak C or Premarin 0.625 mg in the test group with 1 g calcium daily (Sandocal) in both groups. Measurements were made of balance, assessed as sway, leg extensor power and self-paced walking speed, at 12-week intervals over 24 weeks. Hand grip strength was measured every 12 weeks for 48 weeks, and falls in the preceding 12 weeks were recorded at each visit.
2. There was no relation between initial levels of oestradiol and any other variable assessed, except body mass. Levels of follicle-stimulating hormone in the test group were in the premenopausal range. There was no significant change attributable to hormone replacement therapy at any time point in any of the outcome variables. The only significant difference was an increase of 4.2% (95% confidence interval 0.7–7.6%) in leg extensor power in the control group (calcium alone) compared with the group treated with hormone replacement therapy.
3. Of the total group, 37% fell again during the year, with three patients suffering a further fracture. Frequent fallers swayed significantly more often than the others, but there was no evidence that their muscle strength was poorer or that the group treated with hormone replacement therapy fell less frequently.
4. Hormone replacement therapy did not increase muscle performance, improve balance or reduce falls over a year in middle-aged women.
Association of Antral Mucosal Levels of Interleukin 8 and Reactive Oxygen Radicals in Patients Infected with Helicobacter Pylori
Authors: Zhang Q. B. , Dawodu J. B. , Husain A. , Etolhi G. , Gemmell C. G. , Russell R. I. 
Published: August 2015

1. Helicobacter pylori infection is characterized by an infiltration of neutrophils in the gastric mucosa. Neutrophil activation is an important source of reactive oxygen radicals, which cause tissue damage. Studies have shown that in Helicobacter pylori-infected patients there is increased mucosal production of interleukin 8. However, the role of interleukin 8 in the Helicobacter pylori-related inflammatory process and its relationship with reactive oxygen radicals remains to be clarified. The aims of this study were to investigate if there is any association between antral mucosal levels of interleukin 8 and reactive oxygen radicals and their relationship to gastric antral inflammation.
2. Fifty-two patients referred for endoscopy were recruited into the study. Gastric antral biopsies were taken for histology, culture and measurement of interleukin 8 and chemiluminescence (measuring reactive oxygen radicals). Interleukin 8 was measured by ELISA and the result expressed as pg/mg biopsy. Luminol-enhanced chemiluminescence was measured as mV min−1 mg−1 biopsy. Antral inflammation was assessed by a pathologist in a blinded fashion.
3. Antral mucosal levels of interleukin 8 and reactive oxygen radicals were significantly higher in Helicobacter pylori-colonized mucosa than in Helicobacter pylori-negative mucosa. After the eradication of Helicobacter pylori in patients with duodenal ulcer the median values (ranges) of interleukin 8 and reactive oxygen radicals fell from 1.21 (0.10-2.40) to 0.65 (0.00-1.60) and from 110.0 (10.0-959.0) to 14.5 (0.0-85.0) respectively. There was a positive correlation between interleukin 8 concentration and chemiluminescence response in the antral mucosa (r = 0.72). A higher interleukin 8 concentration was associated with greater neutrophil infiltration (r = 0.72) and mononuclear cell infiltration (r = 0.55); the magnitude of the chemiluminescence response was also positively associated with neutrophil (r = 0.77) and mononuclear cell infiltration (r = 0.59).
4. Interleukin 8 concentration is associated with an infiltration of neutrophils and mononuclear cells and is correlated with the production of reactive oxygen radicals in antral gastric mucosa infected with Helicobacter pylori. These findings suggest that interleukin 8 may be important in attracting and activating phagocytes to release reactive oxygen radicals, thereby causing mucosal damage.
Endothelial Function in Subcutaneous Resistance Arteries from Elderly Hypertensive and Normotensive Subjects
Authors: James Martin A. , Watt Pamela A. C. , Potter John F. , Thurston Herbert , Swales John D. 
Published: August 2015

1. Previous studies have indicated that younger hypertensive subjects may have abnormal endothelium-dependent relaxation, which could contribute to the elevated peripheral resistance seen in established hypertension. This study was designed to examine the functional behaviour of the endothelium of small arteries from elderly hypertensive and normotensive subjects.
2. Resistance arteries were obtained from gluteal biopsies taken under local anaesthesia in 28 subjects of mean age 70 (range 60–76) years, and studied in an isometric myograph. Eighteen subjects had untreated essential hypertension, and 10 were normotensive.
3. After measurement of the contractile response to noradrenaline, relaxation responses to a variety of endothelium-dependent (acetylcholine and bradykinin) and endothelium-independent (iloprost and sodium nitroprusside) mechanisms were assessed in vessels precontracted with noradrenaline. Endothelium-dependent responses were also studied after incubation with NG-nitro-l-arginine to inhibit nitric oxide synthase.
4. There were no significant differences in the contraction or relaxation responses between elderly subjects with or without high blood pressure. Inhibition of nitric oxide synthase prevented any relaxation with acetylcholine and significantly attenuated the relaxation with bradykinin. Near-complete relaxation was however achieved with the endothelium-independent vasodilator sodium nitroprusside.
5. Hypertension in elderly subjects is not associated with a reduction in endothelial vasodilating function in the subcutaneous vessels of the gluteal region compared with age-matched normotensive controls. The results of this study do not support the hypothesis of a defect of resistance artery endothelium-dependent relaxation in the pathophysiology of hypertension in the elderly.
Phagocytic Degradation of Chylomicron Remnants by Fibroblasts from Subjects with Homozygous Familial Hypercholesterolemia
Authors: Yu Kenneth C.-W. , Smith Darrin , Yamamoto Akira , Kawaguchi Akito , Harada-Shiba Mariko , Yamamura Taku , Mamo John C. L. 
Published: August 2015

1. Familial hypercholesterolaemia is a common genetic abnormality in man characterized by premature atherogenesis as a consequence of disturbed lipoprotein metabolism. Chylomicrons, which represent intestinally derived lipoproteins, are cleared poorly in familial hypercholesterolaemia which may explain the increased retention of chylomicron remnants in arterial fatty lesions. However, cellular uptake of chylomicron remnants in familial hypercholesterolaemia remains unclear. This study determined the quantitative significance of non-low-density lipoprotein receptor-mediated uptake in fibroblasts from subjects with homozygous familial hypercholesterolaemia.
2. The metabolism of chylomicron remnants was assessed in fibroblasts from subjects with homozygous familial hypercholesterolaemia who lack low-density lipoprotein receptors. Compared with fibroblasts from normolipidaemic subjects, binding and degradation of chylomicron remnants was reduced by about two-thirds. Nevertheless, degradation of chylomicron remnants in cells from subjects with familial hypercholesterolaemia persisted in the absence of functioning low-density lipoprotein receptors.
3. Binding of chylomicron remnants to fibroblasts from subjects with familial hypercholesterolaemia was saturable. Unlabelled chylomicron remnants competed efficiently for binding but unlabelled low-density lipoprotein or a monoclonal antibody specific to the human low-density lipoprotein receptor had little effect on binding or degradation.
4. Polyinosinic acid did not alter binding and degradation of chylomicron remnants by fibroblasts from subjects with familial hypercholesterolaemia, ruling out involvement of the scavenger receptor. Lactoferrin was found to inhibit binding and degradation of chylomicron remnants by fibroblasts from subjects with familial hypercholesterolaemia by approximately 50%, implicating involvement of the α2-macroglobulin receptor.
5. Cytochalasin D blocked degradation of chylomicron remnants at 37°C in fibroblasts from subjects with familial hypercholesterolaemia by more than 80% but had no effect on binding at 4°C, consistent with a phagocytic uptake pathway. Collectively, the data suggest that chylomicron remnants bind to a cell-surface protein which initiates phagocytosis and that lactoferrin interferes with binding to this putative cell-surface protein. Phagocytic uptake of chylomicron remnants provides an additional mechanism whereby cells from subjects with familial hypercholesterolaemia can accumulate lipid.
Effect of two Forms of Granulocyte-Colony-Stimulating Factor on Hepatic Regeneration after 70% Partial Hepatectomy in Rats
Authors: Theocharis Stamatios E. , Agapitos Emmanuel B. , Margeli Alexandra P. , Goutas Nicolaos D. , Kittas Christos N. , Davaris Panayiotis S. 
Published: August 2015

1. The purpose of this study was to determine whether the commercially available forms of granulocyte-colony-stimulating factor exert the same beneficial effect on hepatic regeneration after 70% partial hepatectomy in rats. Adult male Wistar rats received either the two commercially available forms of granulocyte-colony-stimulating factor (Filgrastim or Lenograstim), or saline, simultaneously with partial hepatectomy. Hepatic regeneration was documented by determining [3H] thymidine incorporation into hepatic DNA, liver thymidine kinase activity, mitotic index and proliferating cell nuclear antigen immunostaining, at various time points after partial hepatectomy.
2. DNA biosynthesis, liver thymidine kinase activity and mitotic index of hepatocytes were not only enhanced (P &lt; 0.001) in rats that received 150 μg of Filgrastim or Lenograstim/kg of body weight, but occurred earlier than in saline-treated partially hepatectomized rats. The administration of both forms of granulocyte-colony-stimulating factor, at the dose of 15 μg/kg of body weight, did not affect liver proliferative capacity, compared with observations in simply partially hepatectomized rats. High mitotic and proliferating cell nuclear antigen indices appeared earlier than those estimated in simply partially hepatectomized rats, when 150 μg of Filgrastim or Lenograstim/kg of body weight were administered.
3. These findings suggest that both pharmacologically available forms of granulocyte-colony-stimulating factor at a dose of 150 μg/kg of body weight are able to augment liver regenerative capacity, to the same extent, in this animal model of controlled hepatie proliferation.
Tissue Expression of Components of the Renin—Angiotensin System in Experimental Post-Infarction Heart Failure in Rats: Effects of Heart Failure and Angiotensin-Converting Enzyme Inhibitor Treatment
Authors: Kelly Martin P. , Kahr OLE , Aalkjaer Christian , Cumin Frederic , Samani Nilesh J 
Published: August 2015

1. It has been suggested that local tissue renin—angiotensin systems may be activated in heart failure and that effects on such systems may, at least partially, explain the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in this syndrome. To investigate these hypotheses, we examined expression of renin-angiotensin system components in several tissues in a rodent model of post-myocardial infarction (MI) heart failure, and analysed whether such expression is modified by ACE inhibitor treatment.
2. Four groups of rats (n = 8–12 per group) were studied 30 days after surgery: (A) sham-operated rats with no treatment, (B) rats with post-MI heart failure induced by ligation of the left coronary artery, (C) sham-operated rats treated with the ACE inhibitor perindopril (1.5 mg day−1 kg−1), and (D) rats as per B, but treated with perindopril. Expression of renin, angiotensinogen, ACE and angiotensin subtype 1 receptor was assessed by quantification of their respective mRNAs by Northern blotting.
3. Renal renin mRNA increased 2-fold in animals with MI (group B) compared with controls (group A) (P &lt; 0.05) and between 50 and 100-fold after ACE inhibitor treatment (P &lt; 0.001). No change in renin gene expression was found in any extra-renal site either following MI or after ACE inhibitor treatment. Hepatic angiotensinogen mRNA level was similar in all groups, but kidney angiotensinogen mRNA level was increased 1.6-fold (P &lt; 0.01) in the groups receiving perindopril. ACE mRNA level in the lung was not affected by ACE inhibitor treatment but decreased by 50% following MI (groups B and D, P &lt; 0.01). This was associated with a similar (50%, P &lt; 0.01) fall in lung ACE activity and was correlated with the severity of heart failure. Angiotensin subtype 1 receptor mRNA level was not affected in any tissue by either MI or ACE inhibitor treatment.
4. We did not find a systematic activation of tissue renin-angiotensin systems, as assessed by steady-state mRNA levels of key components of the system in experimental post-MI heart failure, or a major effect of ACE inhibitor treatment on expression of these components. However, we observed tissue-specific changes in expression of selected components of the renin-angiotensin system in the kidney and the lung in post-MI heart failure and after ACE inhibitor treatment, which may be of relevance to the pathophysiology of the syndrome and the effects of ACE inhibition.
Female sex Hormones do not Influence Arterial wall Properties during the Normal Menstrual Cycle
Authors: Willekes Christine , Hoogland Henk J. , Keizer Hans A. , Hoeks Arnold P. , Reneman Robert S. 
Published: August 2015

1. In previous studies, the elastic properties of the common carotid artery were found to differ between men and women. In these studies, however, the phase of the menstrual cycle was not taken into consideration. It was the aim of the present study to investigate the effect of changing ovarian hormone levels during the normal menstrual cycle on the arterial wall properties of female large arteries.
2. We investigated the elastic right common carotid artery and the muscular right common femoral artery of normotensive young (18–35 years) female subjects (n = 12). The arterial distensibility and cross-sectional compliance coefficients were determined by the use of a specially designed ultrasonic wall-tracking device and measurements of automatic brachial artery cuff blood pressure. The phase of the menstrual cycle was assessed by ultrasonographic evaluation and measurement of 17β-oestradiol and progesterone blood plasma levels.
3. The distensibility coefficient and the cross-sectional compliance coefficient of both the common carotid and the common femoral artery did not change significantly during the normal menstrual cycle despite evidently changing ovarian hormone levels.
4. We conclude that the menstrual cycle does not influence the arterial wall properties of either the elastic common carotid artery or the muscular common femoral artery.
Microdialysis of Human Breast Tissue during the Menstrual Cycle
Authors: Dabrosin Charlotta , Hallström Åse , Ungerstedt Urban , Hammar Mats 
Published: August 2015

1. Previously it has been impossible to perform studies of human breast tissue in vivo. In this study, we investigated whether the microdialysis technique is applicable in human breast tissue and whether the concentrations of amino acids, lactate and pyruvate change during the menstrual cycle.
2. Microdialysis was performed twice during the menstrual cycle in eight healthy women, in the breast and subcutaneous fat. Amino acids, lactate and pyruvate were analysed by HPLC.
3. None of the women showed any complications, such as bleeding or infection, after the experiments. The concentrations of aspartic acid, asparagine, serine, glycine, threonine, tyrosine and ornithine were decreased in the breast late in the menstrual cycle. In the subcutaneous fat, the concentration of glycine decreased late in the cycle.
4. This study has shown that microdialysis is a safe technique and is suitable for investigations of human breast tissue. Our data indicate that metabolism in the breast changes during the menstrual cycle. The lower levels of specific amino acids late in the menstrual cycle could indicate a higher proliferative and/or apoptotic activity during this period. However, the data we have obtained cannot yet be fully explained.
Compound Heterozygote for Both Rare Apolipoprotein E1(Gly127→Asp, Arg158→Cys) and E3(Cys112 → Arg, Arg251 → Gly) Alleles in a Multigeneration Pedigree with Hyperlipoproteinaemia
Authors: Richard Pascale , Beucler Isabelle , De Zulueta Maria Pascual , Biteau Nicolas , De Gennes Jean-Luc , Iron Albert 
Published: August 2015

1. A French multigeneration pedigree with hyperlipoproteinaemia was investigated for the transmission of the rare apolipoprotein E1(Gly127 → Asp, Arg158 → Cys) variant. The proband, a 46-year-old male carrying the rare apoE1 variant, presented a severe type III hyperlipoproteinaemia like his three brothers and his sister.
2. ApoE phenotyping and genotyping showed a discrepancy in the second allele carried by the proband's wife and two of her children, thus suggesting another apoE gene mutation. Cloning and sequencing of the entire exon 4 demonstrated a point mutation at codon 251, leading to an apoE3(Cys112 → Arg, Arg251 → Gly) allele. The proband's wife was normolipaemic and heterozygous for this rare isoform and the common apoE3 protein. The rare apoE3(Cys112 → Arg, Arg251 → Gly) allele has been transmitted to her two daughters. The first, aged 19, was normolipaemic and heterozygous for this allele and the common apoE2 allele. The second, carrying both the rare isoforms apoE1(Gly127 → Asp, Arg158 → Cys) and apoE3(Cys112 → Arg, Arg251 → Gly), presented a hypertriglyceridaemia at the age of 10.
3. The exploration of apoE status associated with plasma lipid levels and lipoprotein profiles in this three-generation pedigree made it possible to describe a compound heterozygote for two mutated alleles, one mutation being located in the N-terminal domain of the apoE protein and the other arising in the C-terminal domain.
Cough Frequency and Cough-Receptor Sensitivity are Increased in Man at Altitude
Authors: Barry P.W. , Mason N.P. , Riordan M. , O'Callaghan C. 
Published: August 2015

1. Travellers to high altitude often complain of paroxysmal cough, which has not been previously investigated. We recorded overnight cough frequency and cough-receptor sensitivity to inhaled citric acid in a group of climbers travelling to 5300 m or higher.
2. Cough frequency, monitored in ten subjects, increased from a median of 0 coughs at sea level (range 0–1) to 5 coughs at 5000 m (range 0–13) and to over 60 coughs in subjects ascending to 7000 m. Citric acid cough threshold, measured in 42 subjects, was unchanged on arrival at 5300 m compared with sea level (geometric mean difference 1.26, 95% confidence intervals 0.84–1.89, P = 0.25), but was significantly reduced after 6 days, or more, at altitude compared with sea level (geometric mean difference 2.2, 95% confidence intervals 1.54–3.15, P = 0.0002). Cough threshold was not related to symptoms of acute mountain sickness, oxygen saturation, carbon dioxide tension or lung function.
3. These results indicate an increase in cough and cough-receptor sensitivity after some days at altitude. This may be due to respiratory tract damage from breathing cold dry air at increased ventilatory rates. Other explanations, such as sub-clinical pulmonary oedema or an effect on the cough centre of acclimatization to altitude, cannot be excluded.