bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sunlight, Immunosuppression And Skin Cancer: Role Of Histamine And Mast Cells
Authors: Hart Prue H , Grimbaldeston Michele A , Finlay‐Jones John J 
Published: March 2003

SUMMARY1. The development into tumours of skin cells transformed by ultraviolet (UV) B radiation of wavelengths 290–320 nm is enhanced by the ability of UVB to suppress an immune response that would otherwise destroy them. Ultraviolet B‐induced immunomodulation may be by multiple mechanisms, but generally manifests in an antigen‐presenting cell defect and an altered cytokine environment in the draining lymph nodes.2. Immune responses to microbial or self‐antigens may be dysfunctional by similar mechanisms following UVB exposure.3. Earliest‐acting intermediates in the initiation of UVB‐induced immunosuppression are the UVB absorbers (photoreceptors) of the skin, notably DNA resulting in immunoregulatory cytokine production, and trans‐urocanic acid (UCA), which, upon isomerization to its cis isomer, signals downstream immunosuppressive events.4. In mice, dermal mast cells are critical to UVB‐induced systemic immunomodulation. In mice, there is a functional link as well as a linear relationship between the prevalence of histamine‐staining dermal mast cells and the log of the dose of UVB required for 50% immunosuppression. Studies with histamine receptor antagonists support histamine as the main product of mast cells involved. Histamine acts in large part via a prostanoid‐dependent pathway.5. Approximately 50% of humans and greater than 90% of patients with non‐melanoma skin cancer are UVB susceptible for suppression of a contact hypersensitivity response. Neither cytokine polymorphisms nor UVB‐induced levels of cis‐UCA in irradiated skin have been linked to UVB susceptibility. Patients with basal cell carcinomas (BCC) have an increased dermal mast cell prevalence in non‐sun‐exposed buttock skin. We propose that mast cells function in humans, as in mice, by initiating immunosuppression and, thereby, allowing a permissive environment for BCC development.
Sites of Epidermal Growth Factor Synthesis and Action in the Pituitary: Paracrine and Autocrine Interactions
Authors: Childs Gwen V , Armstrong Jennifer 
Published: March 2003

SUMMARY1. Epidermal growth factor (EGF) is produced by growth hormone (GH) cells and gonadotropes in normal pituitary cell populations. The studies were initiated to determine whether EGF is a paracrine or autocrine regulator of gonadotrope function.2. The first group of studies tested for the presence of EGF receptors in gonadotropes from cycling female rats by immunolabelling. Expression varied with the stage of the cycle. At the highest point (metoestrus), only a few EGF target cells are gonadotropes, identified by their content of luteinizing hormone (LH)‐β mRNA. Expression by gonadotropes then increased to reach a peak of 50% of cells during pro‐oestrus.3. Studies investigating the regulation of expression of EGF receptor (R) showed that all culture conditions (in media with or without serum) and EGF itself both stimulated expression of the receptor by gonadotropes in populations from oestrus or metoestrus rats. Gonadotropin‐releasing hormone (GnRH) also stimulated EGFR expression in follicle‐stimulating hormone (FSH) gonadotropes from oestrus animals. Additional tests of expression of immediate early genes (c‐fos) showed that, after 15 min, EGF stimulated expression in cells with FSH antigens.4. Epidermal growth factor also stimulated gonadotrope proliferation, as detected by the MTT cell growth/cell death assays and bromodeoxyuridine uptake by gonadotropes during the S phase (DNA synthesis) of the cell cycle.5. Epidermal growth factor and GnRH both stimulated a significant increase in the percentage of mitotic gonadotropes. Epidermal growth factor may be an autocrine or a paracrine growth factor to maintain and develop the gonadotrope population and EGF may also be involved in early differentiation events that prepare cells to support the LH surge.
Cardiac Output In Mice Overexpressing β2‐Adrenoceptors Or With Myocardial Infarct
Authors: Gao Xiao‐Ming , Lambert Elisabeth , Dart Anthony M , Du Xiao‐Jun 
Published: March 2003

SUMMARY1. The aims of the present study were to characterize cardiac output (CO) in transgenic mice that overexpress the β2‐adrenoceptor and to evaluate ultrasonic flowmetery for continuous CO measurement in the mouse in vivo.2. Under conditions of anaesthesia, open chest and positive ventilation, CO was determined with a transonic flowmeter at baseline and during dobutamine administration and intravenous volume loading in wild‐type mice (n = 17) and β2‐adrenoceptor transgenic (n = 9) and wild‐type mice with chronic myocardial infarct (n = 16).3. Compared with wild‐type mice, β2‐adrenoceptor transgenic mice with markedly enhanced ventricular contractility had a significantly higher CO, heart rate (HR) and maximal acceleration of aortic flow. Both dobutamine and volume loading increased CO in the two groups and higher levels of CO were measured in transgenic mice during the interventions. At baseline or during interventions, stroke volume was similar between β2‐adrenoceptor transgenic and wild‐type mice. Infarcted mice with impaired cardiac function had a significantly lower CO under basal and stress conditions.4. Thus, β2‐adrenoceptor transgenic mice revealed higher CO that was largely attributable to a significantly higher HR but not to an increase in stroke volume. Transonic flowmetery can detect differences in CO among mice in various functional states and is suitable for evaluation of cardiac functional reserve in mice in vivo by continuous monitoring of CO responses to different interventions.
Multiple Inert Gas Elimination Technique For Determining Ventilation/Perfusion Distributions In Rat During Normoxia, Hypoxia And Hyperoxia
Authors: Alfaro V , Roca‐Acín J , Palacios L , Guitart R 
Published: March 2003

SUMMARY1. The use of the multiple inert gas elimination technique (MIGET) in quantifying ventilation/perfusion distributions (V•A/Q•) in small animals, such as the rat, may cause results to be biased due to haemodilution produced by the large volume of liquid infused intravenously.2. We tested two methods of administering inert gases in rats using the MIGET: (i) standard continuous intravenous administration of inert gases (method A); and (ii) a new method based on the physicochemical properties of each inert gas (method B). This method included acute simultaneous inert gas administration using three pathways: inhalation, intravenous infusion and rectal infusion. Both MIGET methods were applied to obtain data while breathing three different inspiratory fractions of oxygen (FIO2): normoxia, hypoxia and hyperoxia.3. Inert gas levels obtained from blood or expired air samples were sufficient for chromatographic measurement, at least during a 2 h period. The V•A/Q• distributions reported using both methods were acceptable for all the physiological conditions studied; therefore, the alternative method used here may be useful in further MIGET studies in rats because haemodilution resulting from continuous intravenous infusion of less‐soluble gases can be avoided.4. Normoxic rats showed lower mean values of the V•A/Q• ratio of ventilation distribution and higher mean values of the V•A/Q• ratio of perfusion distribution with the usual method of inert gas administration (method A). These non‐significant differences were observed under almost all physiological conditions studied and they could be caused by haemodilution. Nevertheless, the effect of interindividual differences cannot be discarded. An additional effect of the low haematocrit on cardiovascular changes due to low FIO2, such as pulmonary vasoconstriction or increased cardiac output, may explain the lower dispersion of perfusion distributions found in group A during hypoxia.
Endothelium‐Dependent Changes In Arterial Diameter In Old Normotensive Rats
Authors: Safar Me , Duriez M , Corman B , Levy Bi 
Published: March 2003

SUMMARY1. In normotensive rats, removal of carotid artery endothelium results in an acute increase in diameter. This finding, observed in young animals, has not been investigated in old animals. The present study was undertaken to assess the contribution of endothelial function in the regulation of arterial stiffness in aged rats.2. In normotensive female WAG/Rij rats, isobaric (100 mmHg transmural pressure) carotid diameter was measured in vitro in situ, using a previously described arterial preparation associated with a high‐resolution echotracking technique allowing non‐invasive diameter measurements under baseline conditions, after removal of the endothelium and after total relaxation of vascular smooth muscle by potassium cyanide. Histomorphometry of the carotid wall was studied after pressure fixation (100 mmHg) of the arteries.3. Compared with younger animals (10 months), older animals (30 months) had the same baseline carotid isobaric diameter but significantly higher values of wall thickness and collagen content. In older animals, whereas total relaxation by potassium cyanide was associated with a slight but significant increase of isobaric diameter, no increase was observed after endothelium removal.4. The results of the presnt study provide evidence that, in old normotensive rats, endothelium‐dependent increases in isobaric carotid diameter are blunted. This endothelium alteration may contribute to the age‐dependent increase in isobaric carotid stiffness observed in old rats.
Nitric Oxide Reduces Pressor Responsiveness During Ovine Hypoadrenocorticism
Authors: Orbach Pini , Wood Charles E , Keller‐Wood Maureen 
Published: March 2003

SUMMARY1. Hypoadrenocorticism frequently results in critical hypotension, hypovolaemia, hyponatraemia and hyperkalaemia. Perhaps even more important, hypoadrenocorticoid humans experience decreased vasoconstriction in response to exogenous administration of vasoconstrictors, such as noradrenaline.2. We studied chronically adrenalectomized adult sheep to test the hypothesis that the reduction in pressor responsiveness is the result of increased production of nitric oxide (NO) during hypoadrenocorticism.3. Withdrawal of steroid replacement resulted in reduced blood pressure, reduced pressor responsiveness, as well as hyperkalaemia and hyponatraemia.4. Inhibition of NO production by NG‐nitro‐L‐arginine methyl ester in the hypoadrenocorticoid ewes restored mean arterial pressure and pressor responsiveness response to normal values.5. The results of these experiments support the hypothesis that reduced pressor responsiveness in the hypoadrenocorticoid state is mediated by the overproduction of NO.
Effect of epomediol on ethinyloestradiol‐induced changes in bile acid and cholesterol metabolism in rats
Authors: Cuevas María J , Mauriz José L , Almar Mar , Collado Pilar S , González‐Gallego Javier 
Published: March 2003

SUMMARY1. Epomediol is a terpenoid compound that has been reported to stimulate bile acid synthesis and to reverse 17α‐ ethinyloestradiol‐induced cholestasis. The aim of the present study was to investigate the contribution of changes in bile acid and cholesterol metabolism to the protective effects of epomediol in ethinyloestradiol‐treated rats. Animals received epomediol for 5 days at 100 mg/kg daily, i.p., ethinyloestradiol for 5 days at 5 mg/kg, s.c., or a combination of both drugs.2. When compared with control animals, epomediol treatment resulted in a significant increase in bile flow (+42%) and in the secretion of bile acids (+74%) and cholesterol (+42%). Ethinyloestradiol administration caused a significant decrease in bile flow (–43%), bile acid secretion (–37%) and cholesterol secretion (–45%). Bile flow, bile acid secretion and cholesterol secretion were significantly increased in animals receiving ethinyloestradiol plus epomediol compared with ethinyloestradiol‐treated rats (+13, +29 and +31%, respectively).3. Both cholesterol 7α‐hydroxylase and hydroxy‐3‐ methylglutaryl coenzyme A reductase activities were significantly increased in epomediol‐treated rats (+30 and +96%, respectively). Cholesterol 7α‐hydroxylase activity was significantly reduced by ethinyloestradiol (–22%) and did not differ from control values in animals receiving epomediol plus ethinyloestradiol. Levels of cholesterol 7α‐hydroxylase mRNA were elevated (+41%) by epomediol, but were not significantly modified by ethinyloestradiol or ethinyloestradiol plus epomediol.4. It is concluded that epomediol enhances bile acid secretion by increasing the expression of cholesterol 7α‐hydroxylase. Changes in bile acid metabolism contribute to the effects of epomediol in rats with ethinyloestradiol‐induced cholestasis.
Large Artery Stiffness: Structural And Genetic Aspects
Authors: Kingwell Bronwyn A , Medley Tanya L , Waddell Tamara K , Cole Timothy J , Dart Anthony M , Jennings Garry L 
Published: March 2003

SUMMARY1. Large artery stiffness is a principal determinant of pulse pressure and both are related to cardiovascular mortality independently of other major risk factors. A clearer understanding of the structural and genetic processes that contribute to large artery properties may provide novel approaches to therapy.2. Age, atherosclerosis and gender are three important factors that contribute to large artery stiffening. Each influences the artery elastic matrix and its relationship to medial smooth muscle cells. Genetic and hormonal modulation of the extracellular matrix proteins and their regulators, including matrix metalloproteinases (MMPs), may account for some interindividual differences.3. In a study of 213 healthy individuals and 105 patients with coronary artery disease (CAD), we examined whether stromelysin‐1 (MMP‐3) genotype, determined by the 5A/6A promoter polymorphism, influences large artery stiffening. In healthy individuals, the 5A/5A genotype was linked with stiffer large arteries and higher systolic blood pressure compared with other genotypes.4. Genetic variation in the extracellular matrix protein fibrillin‐1, using a pentanucleotide repeat polymorphism, was assessed as a potential determinant of large artery stiffness in patients with CAD. The 2–3 genotype was associated with stiffer large arteries, higher pulse pressure and more severe CAD than other genotypes.5. Females experience a greater increase in large artery stiffness with age than males, with a time‐course suggestive of sex steroid modulation. The mechanisms mediating such gender differences have not been established, but the known regulatory role of sex steroids with respect to MMPs likely contributes.6. The demonstration that genetic and hormonal modulation of extracellular matrix components and MMPs contributes to age, atherosclerotic and gender‐related differences in large artery mechanical properties suggests these proteins may be important targets for therapy.
Large Artery Stiffness: Implications For Exercise Capacity And Cardiovascular Risk
Authors: Kingwell Bronwyn A 
Published: March 2003

SUMMARY1. Large artery stiffness, or its inverse, compliance, determines pulse pressure, which, in turn, influences myocardial work capacity and coronary perfusion, both of which impact on exercise capacity and cardiovascular risk.2. In support of a role for arterial properties in exercise performance, aerobically trained athletes (aged 30–59 years) have lower arterial stiffness than their sedentary counterparts. Furthermore, in healthy older subjects (aged 57–80 years), time to exhaustion on treadmill testing correlated positively with arterial compliance.3. Arterial stiffness is more closely linked to exercise capacity and myocardial risk in patients with coronary disease where, independently of degree of coronary disease, those with stiffer proximal arteries have a lower exercise‐induced ischaemic threshold.4. Moderate aerobic training elevates resting arterial compliance by approximately 30%, independently of mean pressure reduction, in young healthy individuals but not in isolated systolic hypertensive patients. Rat training studies support a role for exercise training in structural remodelling of the large arteries.5. High‐resistance strength training is associated with stiffer large arteries and higher pulse pressure than matched controls.6. Large artery stiffness is an important modulator of the myocardial blood supply and demand equation, with significant ramifications for athletic performance and ischaemic threshold in coronary disease patients. Moderate aerobic training, but not high‐resistance strength training, reduces large artery stiffness in young individuals whereas older subjects with established isolated systolic hypertension are resistant to such adaptation.
Opioid Signalling In The Rat Rostral Ventrolateral Medulla
Authors: Guyenet Patrice G , Stornetta Ruth L , Schreihofer Ann M , Pelaez Nicole M , Hayar Abdallah , Aicher Sue , Llewellyn‐Smith Ida J 
Published: March 2003

SUMMARY1. The present article reviews several aspects of opioid signalling in the rostral ventrolateral medulla (RVLM) and their implications for the neural control of blood pressure.2. In the RVLM, preproenkephalin (PPE) mRNA is expressed by bulbospinal cells that are strongly barosensitive. These putative presympathetic neurons includes C1 and non‐C1 neurons.3. In the RVLM, PPE mRNA is also present in GABAergic neurons that do not project to the thoracic spinal cord.4. Rostral ventrolateral medulla presympathetic cells receive enkephalinergic inputs and express μ‐opioid receptors (MOR). Some of their synaptic inputs also contain MOR.5. Pre‐ and post‐synaptic modulation of RVLM presympathetic neurons by MOR agonists has been demonstrated in slices of neonate brain. The post‐synaptic effect is inhibitory (increased gK). Presynaptic effects include disfacilitation (reduction of glutamate release) and possibly dishinhibition (reduction of GABA release).6. In conclusion, opioid signalling plays a pervasive role in the medullospinal network that controls sympathetic tone and arterial pressure. Opioid peptides are made by the presympathetic, presumably excitatory, cells of the RVLM and by local GABAergic inhibitory neurons. In addition, RVLM presympathetic neurons are also controlled by opioid peptides at the pre‐ and post‐synaptic level. μ‐Opioid receptors
are found post‐synaptically, whereas presynaptic receptors probably include both
μ and δ subtypes. Conditions that trigger the release of opioid peptides by presympathetic neurons or by inputs to these cells are not fully understood and may include decompensated haemorrhage and certain types of peripheral sensory stimulation related to acupuncture.
Heterogeneity In The Distribution Of Vascular Gap Junctions And Connexins: Implications For Function
Authors: Hill CE , Rummery N , Hickey H , Sandow SL 
Published: March 2003

SUMMARY1. Gap junctions, which are comprised of members of a family of membrane proteins called connexins (Cx), permit the transfer of electrical and chemical information between adjacent cells in a wide variety of tissues. The aim of the present study was to compare the expression of Cx37, 40 and 43 in the smooth muscle and endothelium of a large elastic artery and two smaller muscular arteries of the rat. Serial section electron microscopy was also used to determine the presence of pentalaminar gap junctions in the smooth muscle and the incidence of myoendothelial gap junctions between the smooth muscle and endothelial cells in muscular arteries of different size.2. Using immunohistochemistry, Cx37, 40 and 43 were found in the endothelium of the aorta, caudal and basilar arteries, with Cx43 being the least abundant. Connexin 43 was readily observed throughout the muscle layers of the aorta, but was not detected in the media of the caudal or basilar arteries. Connexin 40 was not detected in the media of any of the arteries, while very fine punctate staining was observed with Cx37 antibodies in the media of the caudal and basilar arteries, but not in the aorta.3. Real‐time polymerase chain reaction showed that the expression of mRNA for Cx43 was 15‐fold greater in the aorta than in the caudal artery of the rat.4. At the ultrastructural level, small pentalaminar gap junctions (< 100 nm) were found between the fine processes of adjacent smooth muscle cells and also between the smooth muscle and endothelial cells. The incidence of myoendothelial gap junctions in the mesenteric vascular bed and in the caudal artery increased as vessel size decreased.5. In summary, heterogeneity exists within the vascular system with regard to the distribution of gap junctions and their constituent Cx. Such variation will have important consequences for the coordination and propagation of vascular responses. In muscular arteries, in comparison with elastic arteries, Cx37 may be more important than Cx43 for cell coupling within the smooth muscle layers. The correlation between the incidence of myoendothelial gap junctions and the role of endothelium‐derived hyperpolarizing factor, relative to nitric oxide, in vasodilatory responses suggests that myoendothelial gap junctions play an important physiological role in the regulation of vascular tone.
Effect Of Training On Activation Of Extracellular Signal‐Regulated Kinase 1/2 And P38 Mitogen‐Activated Protein Kinase Pathways In Rat Soleus Muscle
Authors: Lee Jong Sam , Bruce Clinton R , Spurrell Brian E , Hawley John A 
Published: March 2003

SUMMARY1. The effect of a chronic programme of either low‐ or moderate‐to‐high‐intensity treadmill running on the activation of the extracellular‐signal regulated protein kinase (ERK1/2) and the p38 mitogen‐activated protein kinase (MAPK) pathways was determined in rat muscle.2. Sprague‐Dawley rats were assigned to one of three groups: (i) sedentary (NT; n = 8); (ii) low‐intensity training (8 m/min; LIT; n = 16); and (iii) moderate‐to‐high‐intensity training (28 m/min; HIT; n = 16). The training regimens were planned so that animals covered the same distance and had similar glycogen utilization for both LIT and HIT exercise sessions.3. A single bout of LIT or HIT following 8 weeks of training led to a twofold increase in the phosphorylation of ERK1/2 (P = 0.048) and a two‐ to threefold increase in p38 MAPK (P = 0.005). Extracellular signal‐regulated kinase 1/2 phosphorylation in muscle sampled 48 h after the last exercise bout was similar to sedentary values, while p38 MAPK phosphorylation was 70–80% lower than sedentary. One bout of LIT or HIT increased total ERK1/2 and p38 MAPK expression, with the magnitude of this increase being independent of prior exercise intensity or duration. Extracellular signal‐ regulated kinase 1/2 expression was increased three‐ to fourfold in muscle sampled 48 h after the last exercise bout irrespective of the prior training programme (P = 0.027), but p38 MAPK expression was approximately 90% lower than sedentary values.4. In conclusion, exercise‐training of different intensities/ durations results in selective postexercise activation of intracellular signalling pathways, which may be one mechanism regulating specific adaptations induced by diverse training programmes.
Toxic marine dinoflagellates in Singapore waters that cause seafood poisonings
Authors: Holmes Michael James , Teo Serena Lay Ming 
Published: March 2003

Summary1. The present paper reviews the toxic dinoflagellates found in Singapore waters that produce toxins that can accumulate through marine food chains to cause seafood poisonings.2. Singapore waters contain dinoflagellate species linked to three types of seafood poisoning: paralytic shellfish poisoning, diarrhetic shellfish poisoning (DSP) and ciguatera.3. Paralytic shellfish poisoning and DSP occur by eating bivalve shellfish contaminated with saxitoxins and okadaic acid analogues, respectively. Shellfish accumulate these toxins from filter feeding on a number of species of (mostly) planktonic dinoflagellates.4. In contrast, benthic species of dinoflagellates of the genus Gambierdiscus produce the ciguatoxins that are bioaccumulated into finfish to cause ciguatera.5. Paralytic shellfish poisoning and DSP are the major concern for local and regionally produced seafood. To the best of our knowledge, ciguatera poisoning in Singapore only originates from imported reef fish.