bluuebunny/crossref_metadata_2025_split huggingface dataset:
Part‐time consultants in radiation oncology
Authors: Vinod Shalini K , Jalaludin Bin B , Rodger Alan , Turner Sandra , Kelly Lyndell , Thornton Deborah , Clark Catherine 
Published: March 2003

SummaryThe aim of this study was to evaluate the attitudes and experiences of staff towards radiation oncologists who work part‐time. A questionnaire was sent to all radiation oncologists, radiation oncology registrars and radiation therapists, and a nursing and clerical representative working in all radiation oncology departments throughout Australia and New Zealand. Of 1242 questionnaires, 446 (35.9%) were returned. Of these, 323 out of 435 respondents (74.2%) supported the concept of a radiation oncologist working part‐time. The main barriers to part‐time work were inadequate provision of cover, the inability to be contacted when not rostered on, and perceived reduced quality of patient care. The majority of respondents supported part‐time employment in radiation oncology. However, the conclusions made from this survey are limited by the poor response rate. For a successful part‐time career in radiation oncology, the following points need to be ensured: (i) an equitable pro‐rata workload that encompasses both clinical and non‐clinical duties; (ii) a clear and well‐publicised timetable that is strictly adhered to with special emphasis on completing work prior to non‐rostered days; (iii) clear mechanisms in place to deal with patient or other queries on non‐rostered days; (iv) a mechanism for being contacted for urgent problems; and (v) good communication between the part‐time radiation oncologist, other staff and patients.
MR imaging of a ruptured intraspinal dermoid tumour with fat droplets in the central spinal canal
Authors: Karadag Demet , Karagülle Ayşe Tuba , Erden Ayşe , Erden Ilhan 
Published: March 2003

SummaryWe report a patient with intramedullary ruptured spinal dermoid tumour. The MR imaging revealed an intra­medullary lumbar mass heterogenous in intensity in all sequences. Fat droplets were observed in the subarachnoid space as well as in the dilated central spinal canal. Fat droplets in the subarachnoid space are frequently seen in the rupture of intraspinal dermoid tumours; however, fat droplets within the central canal is quite rare and was unexpected. Magnetic resonance imaging is a useful tool in the determination of spinal pathologies before they become large enough to cause severe symptoms and/or morbidity.
RAT RENOMEDULLARY INTERSTITIAL CELLS POSSESS BRADYKININ B2 RECEPTORS IN VIVO AND IN VITRO
Authors: Dean Rachael , Maric Christine , Aldred G Peter , Casley David , Zhuo Jialong , Harris Peter , Alcorn Daine , Mendelsohn Frederick Ao 
Published: March 2003

1. Renomedullary interstitial cells (RMIC), abundant throughout the medulla of the kidney, have been demonstrated to have binding sites for many vasoactive peptides, including atrial natriuretic peptide, endothelin, angiotensin II and bradykinin (BK). These observations would support the hypothesis that interactions between RMIC and vasoactive peptides are important in the regulation of renal function.2. We aimed to localize the BK B2 receptor binding site to RMIC in vivo and to also demonstrate that these receptors are biologically active in vitro.3. The present study demonstrates BK B2 binding sites on RMIC of the inner stripe of the outer medulla and the inner medulla of the rat kidney in vivo.4. We further demonstrate that the BK B2 radioligand [125I]‐HPP‐Hoe140 specifically bound to rat RMIC in vitro. In addition, reverse transcription–polymerase chain reaction detected the mRNA for the BK B2 receptor subtype in cell extracts.5. For RMIC in vitro, cAMP levels were increased at 1 min and cGMP levels were increased at 2 min after treatment with 10–10 and 10–7 mol/L BK, respectively. Inositol 1,4,5‐trisphosphate was increased at 10 s treatment with both 10–6 and 10–7 mol/L BK.6. For RMIC in vitro, BK induced an increase in cell proliferation ([3H]‐thymidine incorporation) and an increase in extracellular matrix synthesis (ECM; trans‐[35S] incorporation), both effects mediated by BK B2 receptors.7. We conclude that BK B2 receptors are present on RMIC both in vivo and in vitro. These receptors are coupled to intracellular second messenger systems and, in vitro, their stimulation results in cellular proliferation and synthesis of ECM.
UPPER AIRWAY FUNCTION AND DYSFUNCTION IN RESPIRATION
Authors: Pierce RJ , Worsnop CJ 
Published: March 2003

1. The upper airway not only provides a passage for air to be breathed in and out of the lungs, but it also heats, humidifies and filters the air and is involved in cough, swallowing and speech.2. The complex muscle structure of the upper airway that produces speech and swallowing in humans also modulates respiratory airflow throughout the respiratory cycle, but is vulnerable to functional problems that may compromise respiration.3. Even in normals, there is some collapse of the upper airway and increased upper airway resistance during sleep.4. A substantial proportion of people suffer from obstructive sleep apnoea, in which the collapse of the upper airway is so great that respiration is compromised to the extent that arousal from sleep is required to restore adequate ventilation; the resulting disturbed sleep and hypoxia produce daytime sleepiness and neuropsychological and cardiorespiratory morbidity.5. Functional abnormalities of the larynx can also occur, including prolonged inspiratory laryngeal dysfunction, brief upper airway dysfunction and expiratory laryngeal dysfunction or factitious asthma.
ENDOTHELIAL CELL RESPONSES TO HYPOXIC STRESS
Authors: Faller Douglas V 
Published: March 2003

1. Changes in the environmental oxygen tension to which cells are exposed in vivo result in physiological and sometimes pathological consequences that are associated with differential expression of specific genes.2. Low oxygen tension (hypoxia) affects endothelial cellular physiology in vivo and in vitro in a number of ways, including the transcriptionally regulated expression of vasoactive substances and matrix proteins involved in modulating vascular tone or remodelling the vasculature and surrounding tissue.3. Hypoxia results in the transcriptional induction of genes encoding vasoconstrictors and smooth muscle mitogens (PDGF‐B, endothelin‐1, VEGF, thrombospondin‐1) and genes encoding matrix or remodelling molecules (collagenase IV (MMP‐9), thrombospondin‐1) and reciprocal transcriptional inhibition of vasodilatory or anti‐mitogenic effectors (eNOS).4. Oxygen appears to signal through a novel haem‐containing sensor and signals initiated by this sensor alter the levels and DNA‐binding activity of transcription factors such as activating protein (AP)‐1, nuclear factor‐κB and hypoxia‐inducible transcription factor‐1.5. The genes encoding vasoactive factors regulated by oxygen tension are themselves also regulated by the vasoactive agent nitric oxide (NO).6. Nitric oxide and oxygen transduce similar signals (i.e. their absence results in identical patterns of gene expression in endothelial cells and other cell types).7. Thus, NO can feedback on and modulate signals induced by hypoxia and vice versa. For example, NO, which can act directly on smooth muscle cells as a vasodilator, can also facilitate vasodilation indirectly by reversing the production of vasoconstrictors induced by hypoxia.8. Short‐term exposure of endothelial cells to low oxygen tension results in the elaboration of predominantly vasoconstricting effectors, while longer‐term and more severe hypoxic exposure generates factors that can induce smooth muscle proliferation and remodelling.9. Thus, the endothelial cell response to hypoxic stress can result in two different consequences in the surrounding tissues, depending on the duration of the exposure: short‐term exposure causes physiological and reversible modulation of vascular tone and blood flow; chronic hypoxic stress results in irreversible remodelling of the vasculature and surrounding tissues, with smooth muscle proliferation and fibrosis.10. This dichotomy of responses to hypoxia may explain, in part, both the acute and chronic pathophysiological sequelae of diseases characterized by regional hypoxia, including atherosclerosis, pulmonary hypertension, sickle cell disease and systemic sclerosis (scleroderma).
VASCULAR BIOLOGY OF ENDOTHELIN SIGNAL TRANSDUCTION
Authors: Neylon Craig B 
Published: March 2003

1. Endothelins regulate cell function by interacting with two classes of cell surface receptors, ETA and ETB receptors. Both receptor types are members of the heptahelical transmembrane‐spanning receptor superfamily and couple via G‐proteins to multiple intracellular effectors.2. Many of the cellular responses induced by endothelins are mediated by changes in cytoplasmic Ca2+ concentration. Stimulation of inositol 1,4,5‐trisphosphate (IP3) formation promotes release of Ca2+ from intracellular stores via IP3‐sensitive Ca2+ channels. This mechanism accounts for the initial transient peak of the Ca2+ elevation. The entry of Ca2+ across the plasma membrane through multiple types of Ca2+ channels is responsible for the sustained phase of Ca2+ elevation and, together, both mechanisms regulate cell function.3. Endothelin‐mediated Ca2+ signals vary markedly in duration, spatial organization and temporal pattern. The elevations in Ca2+ are sustained, transient or oscillatory and occur either globally or are localized to discrete spatial domains. These different Ca2+ signals, which are dependent on the availability of specific ion channels, control distinct cellular functions. Ryanodine‐sensitive Ca2+ release channels may be important in determining the organization of the Ca2+ signal.4. Endothelin‐induced Ca2+ elevations near the plasma membrane stimulate the opening of Ca2+‐dependent K+ and Cl− channels. These channels are key regulators of membrane potential and, consequently, regulate the activity of voltage‐ dependent Ca2+ influx pathways.5. Endothelin regulates the growth and differentiation of cells. It markedly potentiates the mitogenic response of other growth factors, an effect that involves activation of the mitogen‐activated protein kinase cascade and induction of early response genes.6. Finally, the vascular actions of endothelin are influenced by the relative expression of specific ion channels, the spatial and temporal pattern of the Ca2+ signal and the cellular composition of the vascular wall.
CYTOKINES AND THE PROGRESSION OF LIVER DAMAGE IN EXPERIMENTAL BILE DUCT LIGATION
Authors: Plebani Mario , Panozzo Maria Piera , Basso Daniela , Paoli Massimo De , Biasin Raffaella , Infantolino Domenico 
Published: March 2003

1. Cytokines are soluble factors whose action has been documented in physiological and pathological conditions. Some may be involved in the pathogenesis of cholestasis, whether of acute or chronic origin.2. The aim of the present study was to evaluate the influence of epidermal growth factor (EGF), transforming growth factor (TGF)‐β1, interleukin (IL)‐6 and tumour necrosis factor (TNF) on cholestasis. Findings from Sprague‐Dawley rats submitted to bile duct ligation for 1–28 days were compared with those from controls, which underwent laparotomy but not bile duct ligation.3. Biochemical and morphological findings confirmed that the experimental procedure was successful. At the end of each follow‐up period, the hepatic levels of the cytokines were determined and compared with liver histology findings.4. The four cytokines studied showed different patterns of activation: hepatic levels of EGF, higher in the experimental than the control group, were comparable with the proliferative picture. The TGF‐β1 pattern was correlated with data of periportal, perivenular and perineoductular fibrosis, confirming that this cytokine has a role in mediating the synthesis of matrix proteins. A fluctuating, phasic pattern was found for TNF in the experimental group, with high values on day 0, a decrease on the first and second postoperative days and then two peaks on days 8 and 14. Finally, immediately after surgical manipulation, high levels of IL‐6 were found in the experimental group, followed by a decrease in levels until zero values were obtained.5. This suggests that the obstructive condition produces several cytokine responses, each of which contributes to determine the cholestatic condition.
AGE‐RELATED CHANGES IN PLATELET MICROVISCOSITY AND AGGREGATION IN RATS
Authors: Hossain Shahdat , Hashimoto Michio , Masumura Sumio 
Published: March 2003

1. To study possible changes in platelet microviscosity in aged animals, 1,6‐diphenyl‐1,3,5‐hexatriene (DPH) was used as a non‐polar probe embedded in thrice‐washed platelets from young, adult and aged rats. With the known values of maximum limiting anisotropy and the structural parameter of DPH and by estimating the steady state of fluorescence anisotropy and the average fluorescence of lifetime, we applied the Perrin equation to calculate the microviscosity.2. We measured platelet aggregation, platelet lipids and platelet polyunsaturated fatty acids to determine any causal relationship between these parameters. Platelet aggregation, the platelet molar ratio of cholesterol to phospholipid ([C]/[PL]) and platelet microviscosity increased with age (P < 0.05) and were correlated with one another (P < 0.05).3. Age‐dependent increases in the steady state of fluorescence anisotropy, order parameters and the short component of fluorescence lifetime of the fluorophore were expressed as functions of variables, such as microviscosity or the [C]/[PL] ratio.4. Platelet concentrations of arachidonic and eicosapentaenoic acids increased with age, but were not associated with aggregation. Age‐related changes in microviscosity and the [C]/[PL] ratio seemed to be determinants affecting biophysical properties of platelet aggregation.
INHIBITION OF HUMAN CARDIAC FIBROBLAST MITOGENESIS BY BLOCKADE OF MITOGEN‐ACTIVATED PROTEIN KINASE AND PHOSPHATIDYLINOSITOL 3‐KINASE
Authors: Hafizi Sassan , Chester Adrian H , Yacoub Magdi H 
Published: March 2003

1. Interstitial fibroblast proliferation is an elemental feature in the development of cardiac fibrosis. The effects of inhibitors of the intracellular signalling proteins, MEK, a kinase involved in the mitogen‐activated protein kinase (MAPK) pathway and phosphatidylinositol 3‐kinase (PI3‐K), were tested on growth of cultured human cardiac fibroblasts.2. Cardiac fibroblasts were isolated from transplant recipient myocardium and made quiescent by serum deprivation for 48 h. Cells were incubated for 24 h with the inhibitors PD 098059 (0.3–30 μmol/L) and LY294002 (1–25 μmol/L) in the presence and absence of platelet‐derived growth factor‐AB (PDGF‐AB, 10 ng/mL). DNA synthesis was measured by [3H]‐thymidine incorporation assay (20–24 h).3. Both compounds markedly inhibited both basal and PDGF‐stimulated increases in DNA synthesis in a concentration‐dependent manner. Cardiac fibroblast DNA synthesis was reduced to near control levels by PD 098059, while it was inhibited completely by LY294002.4. These results implicate the importance of MAPK and PI3‐K activation in the signal transduction pathways necessary for cardiac fibroblast replication.
NITRIC OXIDE‐DEPENDENT ENDOTHELIAL FUNCTION IS UNAFFECTED BY ALLOPURINOL IN HYPERCHOLESTEROLAEMIC SUBJECTS
Authors: O’Driscoll JG , Green DJ , Rankin JM , Taylor RR 
Published: March 2003

SUMMARY1. Hypercholesterolaemia is associated with abnormal endothelium‐related vasodilator function, possibly due to increased destruction •NO by superoxide anions (•O2–). Oxypurinol, a xanthine oxidase (XO) inhibitor with anti‐oxidant properties and the active metabolite of the commonly used drug allopurinol, reduces •NO quenching in vitro and has been reported to acutely improve endothelial function in hypercholesterolaemic subjects.2. The purpose of the present study was to determine whether oral allopurinol improves •NO dilator function in hypercholesterolaemic subjects.3. A randomized double‐blind, placebo‐controlled cross‐over design evaluated the effect of allopurinol (300 mg daily for 4 weeks) on forearm blood flow (FBF) responses to intrabrachial infusion of acetylcholine (ACh), sodium nitroprusside (SNP) and NG‐monomethyl‐
L‐arginine (
L‐NMMA) in nine hypercholesterolaemic subjects.4. Endothelium‐dependent vascular responses to ACh and L‐NMMA were not significantly altered by allopurinol. The endothelium‐independent vasodilator response to SNP was similarly unchanged.5. These results indicate that allopurinol does not influence basal or stimulated activity of the •NO dilator system in hypercholesterolaemic subjects. If intracellular •O2– inactivation •NO is responsible for endothelial dysfunction in hypercholesterolaemia, the source may be other than XO dependent. However, generation of •O2– during the conversion of allopurinol to oxypurinol could offer an alternative, and probably more likely, explanation for the ineffectiveness of allopurinol in vivo.
EFFECT OF HOMOCYSTEINE ON THE PRODUCTION OF NITRIC OXIDE IN ENDOTHELIAL CELLS
Authors: Chow KIT , Cheung FILLY , Lao TERENCE TH , O KARMIN 
Published: March 2003

SUMMARY1. Homocysteine decreased the release of nitric oxide in cultured human umbilical vein endothelial cells.2. Homocysteine did not affect constitutive and inducible nitric oxide synthase activity.
ELECTRICALLY INDUCED INTRACELLULAR Ca2+ TRANSIENT IN SINGLE VENTRICULAR MYOCYTES: A USEFUL PARAMETER FOR THE STUDY OF CARDIAC DRUGS
Authors: Wang H‐X , Kwan CY , Wong TM 
Published: March 2003

SUMMARY1. Fluorescent Ca2+ indicators, such as fura‐2/AM and calcium green‐1, have become one of the most popular tools for measuring intracellular calcium ([Ca2+]i).2. Electrical stimulation triggers a cascade of events in the cardiac muscle, which results in a [Ca2+]i transient and, eventually, contraction. The events that occur in electrically induced cardiac myocytes mimic the normal physiological events in vivo.3. The electrically induced [Ca2+]i transient represents influx of Ca2+ from outside and mobilization of Ca2+ from the intracellular store and is directly related to contraction. Thus, it is more important to determine the electrically induced [Ca2+]i transient than [Ca2+]i. The [Ca2+]i transient can be easily measured with the spectrofluorescence method using fura 2/AM as the Ca2+ indicator in a single ventricular myocyte preparation.4. We made use of the results of studies on carbachol, tetrandrine and cardiotoxin to illustrate the usefulness of the electrically induced [Ca2+]i transient in the study of actions of cardiac drugs.
ROLE OF COMPLEMENT IN XENOTRANSPLANTATION
Authors: Saadi Soheyla , Platt Jeffrey L 
Published: March 2003

SUMMARY1. Xenotransplantation, or transplantation across species, leads to rejection, which destroys the xenograft within hours to days of transplantation.2. Complement is a major barrier to xenotransplantation of vascularized organs and is believed to play an important role in the rejection process.3. The present paper reviews three aspects of complement in xenotransplantation. These include the mechanisms and regulation of complement activation as well as tissue injury mediated by complement activation.
POTENTIAL USE OF GENETICALLY MODIFIED PIGS AS ORGAN DONORS FOR TRANSPLANTATION INTO HUMANS
Authors: Logan John S , Sharma Ajay 
Published: March 2003

SUMMARY1. Transplantation is currently viewed as a successful treatment for end‐stage organ failure. Its more widespread use is severely limited by a shortage of human organ donors. This has stimulated the scientific and medical communities to look at the potential use of animals to solve this problem. For a number of reasons, the pig appears to be the preferred species.2. The initial immunological problem encountered in pig‐to‐primate transplantation is a process of hyperacute rejection, which is mediated by the binding of antibodies to the graft endothelium followed by the activation of the complement cascade. We have sought to overcome these initial immunological challenges by focusing our attention not only on the recipient of the graft but also on the donor. Therefore, we have generated transgenic animals with specific genetic modifications designed to inhibit the activation of the complement cascade. Upon transplantation to baboons of organs derived from these transgenic pigs, we have been able to demonstrate that hyperacute rejection can be prevented. We will discuss the generation of these and other transgenic animals and their potential role in clinical xenotransplantation.
Effects Of Intra‐Uterine Growth Restriction On The Control Of Breathing And Lung Development After Birth
Authors: Harding R , Tester Ml , Moss Tj , Davey Mg , Louey S , Joyce B , Hooper Sb , Maritz G 
Published: March 2003

SUMMARY1. Low birthweight is now recognized as an important risk factor for early postnatal respiratory illness and it is becoming evident that low birthweight can increase the risk for airway dysfunction in children and adults. Our studies have been aimed at determining how low birthweight, resulting from intra‐uterine growth restriction (IUGR), affects the control of breathing and the structural and functional development of the lung.2. We have measured ventilatory responsiveness to progressive hypoxia and progressive hypercapnia during the first weeks after birth in postnatal lambs in which IUGR was induced by chronic placental insufficiency. It was found that the postnatal increase in ventilatory sensitivity to hypoxia observed in control lambs was diminished in low birthweight lambs; in contrast, the sensitivity to hypercapnia was not affected. In other studies, we found that IUGR caused by maternal anaemia led to elevated CO2 levels during sleep and wakefulness.3. Our findings suggest that the prenatal development of the brain‐stem or respiratory chemoreceptors may be affected by intra‐uterine factors associated with IUGR, such as foetal hypoxaemia or hypoglycaemia. It is also possible that the structure of respiratory muscles and, hence, their ability to maintain a high level of ventilation may be affected by IUGR.4. Recently, we studied the influence of IUGR on foetal lung development, in particular its effects on foetal lung liquid, a major determinant of lung growth, as well as alveolar structure and pulmonary surfactant. Lung liquid secretion and volume, in relation to bodyweight, were unaffected; however, there was evidence of structural and functional immaturity in the lungs. In foetuses exposed to IUGR, the air–blood barrier was thicker and, after birth, the diffusing capacity of the lungs for carbon monoxide was lower. In contrast, surfactant protein gene expression was enhanced, particularly in foetuses with high levels of circulating cortisol.5. Further studies are needed to characterize the effects of specific types of prenatal compromise on postnatal control of ventilation and lung function, to determine mechanisms underlying these effects and to determine the capacity for postnatal recovery.