bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Urinary F1 Activation Peptide of Human Prothrombin is a Potent Inhibitor of Calcium Oxalate Crystallization in Undiluted Human Urine in Vitro
Authors: Ryall Rosemary L. , Grover Phulwinder K. , Stapleton Alan M. F. , Barrell Dianne K. , Tang Yulu , Moritz Robert L. , Simpson Richard J. 
Published: August 2015

1. The urinary F1 activation peptide of prothrombin is the predominant protein incorporated into calcium oxalate crystals precipitated from human urine. The aim of this study was to examine the effect of pure urinary prothrombin F1 on calcium oxalate crystallization in human urine.
2. Urinary prothrombin F1 was purified from demineralized calcium oxalate crystals precipitated from human urine, and its effects on calcium oxalate crystallization induced by addition of an oxalate load were tested in undiluted, ultrafiltered urine from healthy men, at final concentrations of 0 to 10 mg/l.
3. Urinary prothrombin F1 did not affect the amount of oxalate required to induce crystallization, but the volume of material deposited increased in proportion to increasing concentrations of urinary prothrombin F1. However, the mean particle size decreased in reverse order: this was confirmed by scanning electron microscopy, which showed it to be the result of a reduction in crystal aggregation rather than in the size of individual crystals. Analysis of 14C-oxalate data revealed a dose-dependent decrease in calcium oxalate deposition with an increase in urinary prothrombin F1 concentration, indicating that the increase in particle volume recorded by the Coulter Counter resulted from inclusion of urinary prothrombin F1 into the crystalline architecture, rather than increased deposition of calcium oxalate.
4. It was concluded that urinary prothrombin F1 may be an important macromolecular determinant of stone formation.
Septic Patients in Multiple Organ Failure Can Oxidize Infused Glucose, but Non-Oxidative Disposal (Storage) is Impaired
Authors: Green Ceri J. , Campbell I. T. , O'sullivan Ellen , Underhill S. , McLaren D. P. M. , Hipkin L. J. , MacDonald I. A. , Russell Jean 
Published: August 2015

1. Patients suffering trauma and sepsis are insulin resistant, but no studies have specifically been made of patients suffering multiple organ failure.
2. We have studied exogenous glucose utilization in multiple organ failure using a combination of the hyperglycaemic glucose clamp and indirect calorimetry to quantify glucose utilization in multiple organ failure, partitioning it into oxidative and non-oxidative disposal (storage).
3. Fourteen septic patients with multiple organ failure were studied. APACHE II (Acute Physiological and Chronic Health Evaluation Mark II) scores on the day of the study ranged from 11 to 31 (median 16). Twenty percent d-glucose was infused and blood glucose was clamped at 12 mmol/l for 3 h. The results were compared with those obtained on seven healthy control subjects.
4. Glucose utilization and energy expenditure were similar in the two groups for the first 90 min of the clamp, after which glucose utilization and energy expenditure increased steadily in the control subjects but did not change in the patients. Respiratory exchange ratio rose in both groups; considered over the whole of the clamp period, respiratory exchange ratio was slightly lower in the patients than in the control subjects (P &lt; 0.05) but not at any specific time point. Glucose oxidation rose in both groups but non-oxidative glucose disposal (storage) rose only in the control subjects. Glucose oxidation was slightly lower in the patients (P &lt; 0.05) but not at any specific time point and there was no difference between the groups in the amount by which glucose oxidation increased. Non-oxidative disposal in the patients fell significantly (P &lt; 0.01) over the course of the clamp and was significantly lower than in the control subjects (P &lt; 0.01)
5. Growth hormone increased in response to glucose infusion in the patients but not in the control subjects.
6. Like patients suffering uncomplicated sepsis or trauma, patients with multiple organ failure are also insulin resistant. The defect appears to lie in an impairment of the ability to store glucose rather than oxidize it, and this may be due in part to the increase in growth hormone in patients with multiple organ failure.
Insulin-Like Growth Factor I is a Major Fibroblast Mitogen Produced by Primary Cultures of Human Airway Epithelial Cells
Authors: Cambrey A. D. , Kwon O. J. , Gray A. J. , Harrison N. K. , Yacoub M. , Barnes P.J. , Laurent G.J. , Chung K. F. 
Published: August 2015

1. The ability of airway epithelial cells to produce insulin-like growth factor I may be important in the pathogenesis of subepithelial fibrosis observed in the airways of patients with asthma. We determined whether human airway epithelial cells are capable of producing polypeptide mediators that could induce fibroblast proliferative activity, in particular insulin-like growth factor I.
2. We examined 12 primary cultures of human airway epithelial cells grown to confluence on collagen gel-coated dishes. Using a colorimetric assay based on the uptake and subsequent release of Methylene Blue, increased proliferation of human fetal lung fibroblasts was detected in conditioned media from airway epithelial cells. The median stimulation of fibroblast proliferation was 49.9% (range 25.6 −113.3%) above control values (observed at 1:2 dilution of media).
3. A neutralizing antiserum to insulin-like growth factor I partly inhibited fibroblast proliferation induced by epithelial cell conditioned media by 52.2% (49.9–109%; n = 5).
4. Radioimmunoassay for insulin-like growth factor I in conditioned media demonstrated a median concentration of 54.1 ng/ml (32.4–96.8 ng/ml).
5. Insulin-like growth factor I mRNA was detected in epithelial cell monolayers by Northern blot analysis using an insulin-like growth factor I cDNA probe.
6. The insulin-like growth factor I gene is expressed in cultured human airway epithelial cells, which also secrete insulin-like growth factor I protein. Insulinlike growth factor I also accounts for the major mitogenic activity for fibroblasts of cultured human epithelial cell conditioned media. Insulin-like growth factor I may function in a paracrine manner to modulate fibroblast behaviour and may be involved in airway processes, such as those occurring in asthma.
Are Himalayan Sherpas Better Protected against Brain Damage Associated with Extreme Altitude Climbs?
Authors: Garrido Eduardo , Segura Ramón , Capdevila Antoni , Pujol Jesús , Javierre Casimiro , Li Ventura Josep 
Published: August 2015

1. The potential risk of brain damage when low-landers attempt to climb the highest summits is a well-known fact. However, very little is known about what occurs to Himalayan natives, perfectly adapted to high altitude, when performing the same type of activity.
2. Taking into account their long-life climbing experience at extreme altitudes, we examined seven of the most recognized Sherpas with the aim of performing a comprehensive neurological evaluation based on medical history, physical examination and magnetic resonance brain imaging. We compared them with one group of 21 lowland elite climbers who had ascended to altitudes of over 8000 m, and another control group of 21 healthy individuals who had never been exposed to high altitude.
3. While all of the lowland climbers presented psychoneurological symptoms during or after the expeditions, and 13 of them (61%) showed magnetic resonance abnormalities (signs of mild cortical atrophy and/or periventricular high-intensity signal areas in the white matter), only one Sherpa (14%) showed similar changes in the scans, presenting neurological symptoms at extreme altitude. The neurological examination was normal in all three groups, and no neuroimaging abnormalities were detected in the control group.
4. The significant differences, in both clinical and neuroimaging terms, suggest that Sherpa highlanders have better brain protection when exposed to extreme altitude. Although the key to protection against cerebral hypoxia cannot be established, it is possible that an increase in the usually short period of acclimatization could minimize brain damage in those low-landers who attempt the highest summits without supplementary oxygen.
Length-Specific Impairment of Skeletal Muscle Contractile Function after Eccentric Muscle Actions in Man
Authors: Saxton J. M. , Donnelly A. E. 
Published: August 2015

1. The effects of maximum voluntary eccentric muscle actions on forearm flexor strength were studied at three different elbow joint angles (0.87, 1.57 and 2.79 rad) to examine whether subsequent impairment of contractile function is muscle length-specific.
2. A bout of 70 maximum voluntary eccentric muscle actions performed with the forearm flexors elicited delayed muscle soreness, efflux of creatine kinase into the blood, loss of elbow joint range of motion and a prolonged decline in maximum voluntary isometric contraction torque at the three elbow angles monitored (P &lt; 0.01) in 30 subjects.
3. The relative decline in maximum voluntary isometric contraction torque after eccentric exercise differed between elbow angles (P &lt; 0.01). The greatest decline in strength relative to baseline was observed at the most acute elbow angle of 0.87 rad, followed by 1.57 and 2.79 rad respectively. Superimposed electrical stimulation in a subgroup of eight subjects did not increase the torque elicited by the forearm flexors during maximum voluntary contraction tests at the most acute elbow angle (0.87 rad) at any time-point after eccentric exercise, suggesting the disproportionate loss of strength at short muscle length was not due to the inhibitory effects of muscle soreness.
4. Measures of arm circumference and ability to fully flex the elbow (in the same subgroup of eight subjects) suggested the greater decline in strength at the acute elbow angle was not due to the possible confounding influences of muscle swelling and/or impaired muscle shortening ability on strength measurements at short muscle length.
5. These data suggest a shift in the forearm flexor length—tension relationship could account for the disparate decline in strength between elbow angles after eccentric exercise. The disproportionate loss of strength at short muscle length suggests that eccentric exercise evoked a subtle increase in muscle length, perhaps attributable to the cumulative effects of regions of lengthened sarcomeres and/or series elastic elements.
Rheological and Microvascular Parameters in Diabetic Peripheral Neuropathy
Authors: Young M. J. , Bennett J. L. , Liderth S. A. , Veves A. , Boulton A. J. M. , Douglas J. T. 
Published: August 2015

1. In order to determine whether rheological changes occur in neuropathic diabetic patients in the absence of smoking, proteinuria, retinopathy or other factors thought to influence haemorheology, three groups of subjects were studied; 24 non-diabetic control subjects (C), 24 non-neuropathic (D) and 24 neuropathic (N) diabetic patients. The groups were matched for age, sex, type and duration of diabetes. No patient or control was a current smoker. No patient had clinically detectable retinopathy or microalbuminuria. Neuropathy was defined as a peroneal conduction velocity &lt; 40 ms−1. All subjects were tested resting semi-recumbent after a light breakfast.
2. There were no significant differences in rheological or microvascular parameters between uncomplicated diabetic patients and non-diabetic control subjects, although peroneal nerve motor conduction velocity was significantly reduced in otherwise uncomplicated diabetic patients [C 51.7 ± 6.0 ms−1 (mean ± SD) versus D 45.1 ± 5.2 ms−1 (P&lt;0.05 C versus D)].
3. Transcutaneous oxygen and laser Doppler flux measured at 44°C were higher in control subjects than in neuropathic diabetic patients [C 76 ± 16 mmHg versus D 71 ± 10 mmHg versus N 63 ± 9 mmHg, and C 72 ± 40 flow units versus D 64 ± 41 flow units versus N 50 ± 26 flow units respectively (both P not significant C versus D, P&lt;0.05 N versus C).
4. Erythrocyte aggregation, plasma viscosity and plasma fibrinogen were all significantly higher in the neuropathic diabetic patients compared with non-diabetic control subjects (all P&lt;0.05 N versus C). Erythrocyte filtration was not significantly different between groups but was lower in diabetic patients. Whole-blood viscosity (corrected to 45% haematocrit) was significantly higher at both high (100 s−1) and low (1 s−1) shear rates in neuropathic diabetic patients than in non-diabetic control subjects (both P not significant C versus D, P&lt;0.05 N versus C). There were no significant differences in whole-blood viscosity at a shear rate of 0.01 s−1.
5. In summary, there were no significant differences in rheological or microvascular parameters between matched groups of uncomplicated diabetic patients and control subjects, but erythrocyte aggregation, fibrinogen and plasma and corrected whole-blood viscosity were all significantly different in neuropathic diabetic patients compared with control subjects, as were assessments of microvascular flow. These results suggest that haemorheological changes are associated with disturbances of microvascular flow and diabetic peripheral neuropathy in the absence of other diabetic complications.
Influence of Treatment with Beclomethasone, Cromoglycate and Theophylline on Perception of Bronchoconstriction in Patients with Bronchial Asthma
Authors: Higgs C. M. B. , Laszlo G. 
Published: August 2015

1. Perception of asthma by patients can be assessed from the relationship between symptom scores and peak expiratory flows. This study was designed to investigate the possibility that medication can affect perception of the sensation of asthma independently of changes in lung function.
2. Twelve subjects whose asthma was inadequately controlled by inhaled bronchodilator alone were studied during four different drug treatments over 3 months. Subjective self-assessment of asthma was scored on a 10 cm visual analogue scale and followed by three consecutive measurements of peak expiratory flow, using a coded electronic peak flow meter. This was recorded not less than three times daily on diary cards. Observations were recorded during the second week of each of four treatments:(i) a run-in period using only inhaled salbutamol as required, (ii) inhaled beclomethasone, (iii) inhaled cromoglycate and (iv) oral theophylline at a dose adjusted to achieve blood levels of 10–20 mg/l. Inhaled salbutamol was permitted during the other treatments as required. Changes in the slope and position of the regression lines of asthma scores on PEF were used to measure changes in perception of asthma on each treatment. Dynamic lung volumes were measured in the clinic before the study and after each treatment period.
3. In the group as a whole, theophylline improved lung function (mean peak flow and dynamic lung volumes) without affecting mean visual analogue scores, beclomethasone improved mean visual analogue scores with much less effect on lung function, while cromoglycate had a small though consistent effect on both.
4. Perception of asthma, measured by the relationship between peak flow rate and visual analogue scores, was unaffected by cromoglycate. On theophylline, perception of asthma was heightened in five subjects despite a definite improvement in their peak flow. On beclomethasone, perception of asthma was reduced in most subjects, often with no discernible improvement in mean peak flow or dynamic spirometry.
5. Perception of bronchoconstriction in asthma can be affected by drugs independently of control of the condition. Theophylline may produce a paradoxical increase in awareness of asthma in some individuals. With beclomethasone therapy a reduction in symptoms of asthma may occur without any improvement in tests of air flow.
Excessive Gravitational Blood Pooling Caused by Impaired Venous Tone is the Predominant Non-Cardiac Mechanism of Orthostatic Intolerance
Authors: Streeten David H. P. , Scullard Thomas F. 
Published: August 2015

1. In a group of 40 patients with orthostatic intolerance due to hypotension and/or tachycardia, we have compared the pathogenetic roles of impaired contractility of the arterioles and the veins by measuring contractile responsiveness of the arterioles, reflected by increases in diastolic blood pressure and of the veins reflected by measurements of reduction in venous diameter during intravenous noradrenaline infusions.
2. Compared with 27 healthy subjects, patients with diffuse autonomic insufficiency showed striking supersensitivity in diastolic blood pressure (six out of eight) and venous constrictive responses (seven out of eight patients) to noradrenaline, consistent with impaired arteriolar and venous innervation.
3. In contrast, the patients with hyperadrenergic orthostatic hypotension (n =16) and orthostatic tachycardia (n = 16) showed diastolic blood pressure responses to noradrenaline that were almost invariably within the 95% confidence limits of the changes in normal subjects but supersensitive constrictive responses of foot veins in 22 of 32 subjects and subnormal venous responses in two individuals. The rate of noradrenaline infusion calculated to cause 50% of maximal venous constriction (the ED50) was significantly lower in the patients [mean (SEM) 6.8 (1.9) ng/min] than in the normal subjects [mean (SEM) 23.2 (3.0) ng/min, P&lt;0.025].
4. The finding of significantly supersensitive foot vein constrictive responses to noradrenaline infusion in the patients of all three groups and supersensitive blood pressure responses exclusively in the patients with diffuse autonomic insufficiency indicates that venous pooling in the legs was the predominant pathogenetic mechanism of orthostatic intolerance in all three types of patients studied.
5. Correction of the orthostatic hypotension and/or tachycardia by external compression in virtually all patients confirmed this conclusion.
Role for the Endogenous Natriuretic Peptide System in the Control of Basal Coronary Vascular Tone in Dogs
Authors: Supaporn Thanom , Wennberg Paul W. , Wei Chi-Ming , Kinoshita Masahiko , Matsuda Yuzuru , Burnett John C. 
Published: August 2015

1. While the natriuretic peptides (atrial, brain and C-type) mediate potent endothelium-independent vasorelaxing actions in vitro, the role of the endogenous natriuretic peptide system in vascular regulation in vivo remains unclear.
2. HS-142-1 is a novel natriuretic peptide receptor antagonist derived from a fungus named Aureobasidium sp. which selectively blocks particulate guanylate cyclase-linked natriuretic peptide A and B receptors that bind atrial, brain and C-type natriuretic peptide, and thus attenuates the generation of cGMP.
3. To characterize the vascular actions of the endogenous natriuretic peptide system in the control of basal coronary and systemic haemodynamics, six normal male mongrel anaesthetized dogs were studied while a second group of five dogs served as a control. HS-142-1 was given as an intravenous bolus at 3 mg/kg and was studied over five 20 min periods.
4. No significant difference after HS-142-1 was observed in mean arterial pressure, heart rate, cardiac output, right atrial pressure, pulmonary capillary wedge pressure or systemic vascular resistance compared with control. In contrast, a significant increase in coronary vascular resistance and decrease in coronary blood flow were observed which were different from the baseline values and the responses of the control group.
5. These studies demonstrate that HS-142-1 produces vasoconstriction in the coronary circulation. We conclude that the endogenous natriuretic peptide system, which is of cardiac and endothelial cell origin, is an important regulator of basal coronary vascular tone.
Chemical Characterization and Quantification of Proteoglycans in Human Post-Burn Hypertrophic and Mature Scars
Authors: Scott P. G. , Dodd C. M. , Tredget E. E. , Ghahary A. , Rahemtulla F. 
Published: August 2015

1. Samples of normal skin from four patients, post-burn hypertrophic scar from five patients and post-burn mature scar from six patients were analysed for hydroxyproline, water and uronic acid and extracted with guanidinium chloride to yield the proteoglycan pool. A large chondroitin sulphate proteoglycan and biglycan were purified from one hypertrophic scar biopsy and decorin from a normal skin biopsy, by ion-exchange chromatography, gel-filtration and hydrophobic interaction chromatography. These purified proteoglycans were used in an inhibition ELISA assay to estimate the quantities of each in the tissue samples.
2. Samples of post-burn hypertrophic scar had on average 30% less hydroxyproline, 12% more water and 2.4 times as much uronic acid as normal skin. These differences were all statistically significant, whereas the small differences between mature scars and normal skin were not. The content of decorin in hypertrophic scars was only 25% of that in normal skin whereas the large chondroitin sulphate proteoglycan and biglycan were each about 6-fold higher. The mature scars had slightly elevated levels of large chondroitin sulphate proteoglycan and biglycan and a reduced content of decorin compared with normal skin but these differences were not statistically significant.
3. The results suggest that aberrant proteoglycan metabolism is a significant factor contributing to the altered physical properties of hypertrophic scars and that maturation of post-burn scars is dependent on a return of the relative proportions and concentrations of proteoglycans to those characteristic of normal dermis.
Interstitial Glycerol Concentration in Human Skeletal Muscle and Adipose Tissue is Close to the Concentration in Blood
Authors: Samra Jaswinder S. , Ravell Cate L. , Giles Sarah L. , Arner Peter , Frayn Keith N. 
Published: August 2015

1. The suggestion that the interstitial glycerol concentration in both adipose tissue and skeletal muscle is around 3 mmol/l (Maggs DG, Jacob R, Rife F, et al. J Clin Invest 1995; 96: 370–7), rather than close to the blood concentration as previously supposed, was tested by independent methods.
2. Free glycerol was infused, as part of a triacylglycerol emulsion, into six normal subjects and the arteriovenous difference for glycerol across the forearm was measured. In addition the relative interstitial glycerol concentration in subcutaneous adipose tissue was assessed simultaneously in four of the subjects by microdialysis.
3. During glycerol infusion the arterialized glycerol concentration rose from 52 ± 5 μmol/l to 250–300 μmol/l (P &lt; 0.001) in a square wave fashion. The net arteriovenous difference for glycerol across the forearm changed from negative (output) to positive (uptake) (P &lt; 0.01). In subcutaneous adipose tissue the interstitial glycerol concentration rose during glycerol infusion (P &lt; 0.001).
4. These observations are most easily explained by the movement of glycerol from plasma to interstitial fluid down a concentration gradient. We conclude that the interstitial glycerol concentration in skeletal muscle and adipose tissue is closer to the arterial concentration than to 3 mmol/l.