bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytochrome P450‐Dependent Metabolites Of Arachidonic Acid And Renal Function In The Rat
Authors: Oyekan AO 
Published: March 2003

SUMMARY1. The present study examined whether renal cytochrome P450 (CYP450)‐derived eicosanoids influence the pressure– natriuretic and haemodynamic responses to elevated renal perfusion pressure (RPP) in the rat.2. Natriuresis and diuresis, as well as changes in renal blood flow (RBF) and glomerular filtration rate (GFR) following step‐wise elevations in RPP from 75 to 125 mmHg were compared in control rats and in rats treated with 12,12‐dibromodecenoic acid (DBDD; 2.5 mg/kg per h; n = 5), an inhibitor of ω/ω‐1 hydroxylase, or miconazole (1.3 mg/kg per h; n = 7), an inhibitor of epoxygenase.3. In control rats, sodium excretion (UNaV) and urine volume (UV) increased five‐fold when RPP was increased from 75 to 125 mmHg, while RBF and GFR increased two‐fold when RPP increased from 75 to 100 mmHg, with no further increase between 100 and 125 mmHg, the autoregulatory range.4. Miconazole, but not DBDD, altered the pressure– natriuresis relationship, exaggerating the increases in UNaV and UV three‐ to four‐fold when RPP was increased from 100 to 125 mmHg.5. In contrast, DBDD eliminated the autoregulatory response because it abolished the plateau in RBF and GFR when RPP was increased from 100 to 125 mmHg, whereas miconazole was without effect.6. These results suggest that CYP450‐dependent ω/ω‐1 hydroxylase metabolites of arachidonic acid contribute to vascular responses, while epoxygenase metabolites contribute to renal tubular responses to alterations in RPP in the rat.
Identification Of New Single‐Nucleotide Polymorphisms In The Thrombin Receptor Gene And Their Effects On Coronary Artery Diseases In Koreans
Authors: Park H‐Y , Nabika T , Jang Y , Kim D , Kim H‐S , Masuda J 
Published: March 2003

SUMMARY1. The thrombin receptor (the protease‐activated receptor‐1; PAR‐1) is located on vascular cells as well as platelets and may play important roles in atherosclerotic disorders, such as coronary artery diseases (CAD). In the present study, we searched for genetic polymorphisms of the PAR‐1 gene and evaluated their effects on CAD by association analysis.2. We identified six polymorphisms in the 5′‐untranslated region of the PAR‐1 gene by polymerase chain reaction–single‐strand conformation polymorphism (PCR‐SSCP); five single‐nucleotide polymorphisms (SNP) at –2355 (A to G), –2333 (T to G), –1428 (G to A), –1071 (C to T) and –561 (A to G) and a simple sequence repeat (SSR) polymorphism between –1935 and –1841. Five SNP were in strong linkage disequilibrium with each other to make three major haplotypes, the frequency of which was over 90% of all possible haplotypes.3. For association analysis, 150 patients who had CAD (CAD+), 58 subjects who had no stenosis on the coronary angiogram and 186 reference subjects who had no clinical evidence of CAD were used from the Korean population. The genotype frequencies of the SNP were in Hardy–Weinberg equilibrium, except A‐561G in CAD+. The association of these SNP as well as of the SSR with CAD was not evident. This result suggests no major roles of the PAR‐1 gene in CAD in Koreans.
Cystic Fibrosis Transmembrane Conductance Regulator And The Outwardly Rectifying Chloride Channel: A Relationship Between Two Chloride Channels Expressed In Epithelial Cells
Authors: Hryciw Deanne H , Guggino William B 
Published: March 2003

SUMMARY1. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) result in the primary defect observed in patients with cystic fibrosis.2. The CFTR is a member of the ATPase‐binding cassette (ABC) transporter family but, unlike other members of this group, CFTR conducts a chloride current that is activated by cAMP.3. In epithelial cells, the cAMP‐stimulated chloride current is conducted by both CFTR and the outwardly rectifying chloride channel (ORCC).4. The present review summarizes the current knowledge of the properties of the two channels, as well as their relationship. Because the gene encoding the ORCC has not been identified, a discussion as to possible candidates for this chloride channel is included.
Molecular Characteristics And Functional Diversity Of Clca Family Members
Authors: Pauli Bendicht U , Abdel‐Ghany Mossaad , Cheng Hung‐Chi , Gruber Achim D , Archibald Heather A , Elble Randolph C 
Published: March 2003

SUMMARY1. In the present brief review, we describe some of the molecular and functional characteristics of a novel mammalian family of putative Ca2+‐activated chloride channels (CLCA).2. So far, two bovine (bCLC1; bCLCA2 (Lu‐ECAM‐1)), three mouse (mCLCA1; mCLCA2; mCLCA3) and four human (hCLCA1; hCLCA2; hCLCA3; hCLCA4) CLCA family members have been cloned. Each CLCA exhibits a distinct, often overlapping, tissue expression pattern.3. With the exception of the truncated secreted hCLCA3, all CLCA proteins are synthesized as an approximately 125 kDa precursor transmembrane glycoprotein that is rapidly cleaved into 90 and 35 kDa subunits.4. The CLCA proteins expressed on the luminal surface of lung vascular endothelia (bCLCA2; mCLCA1; hCLCA2) serve as adhesion molecules for lung metastatic cancer cells, mediating vascular arrest and lung colonization.5. Expression of hCLCA2 in normal mammary epithelium is consistently lost in human breast cancer and in all tumorigenic breast cancer cell lines. Re‐expression of hCLCA2 in human breast cancer cells abrogates invasiveness of Matrigel (BD Biosciences‐Labware, Bedford, MA, USA) in vitro and tumorigenicity in nude mice, implying that hCLCA2 acts as a tumour suppressor in breast cancer.
Bufokinin: Actions And Distribution In The Toad Cardiovascular System
Authors: Liu Lu , Shang Fei , Comis Alfio , Burcher Elizabeth 
Published: March 2003

SUMMARY1. Bufokinin is a substance P‐like neuropeptide and potent spasmogen isolated from the intestine of the cane toad Bufo marinus. In the present study, we investigated the effects of bufokinin on systemic blood pressure and heart rate in the anaesthetized toad and the distribution of bufokinin‐like immunoreactivity in the toad vasculature.2. Intravenous bufokinin caused a dose‐dependent fall in systemic blood pressure (maximum fall 20 mmHg) with an ED50 of 2.9 pmol. At higher doses, the effect was prolonged and blood pressure did not return to baseline within 60 min. There was no significant change in heart rate associated with hypotension.3. Bufokinin‐like immunoreactivity was mapped in whole mounts of toad blood vessels and organs using a mouse polyclonal antibody BK3 (at 1 : 5000) and the avidin–biotin method. Bufokinin‐immunoreactive fibres were associated with most blood vessels examined: a moderately dense perivascular network of varicose fibres was present around renal arteries, with sparser immunoreactive fibres in the ventral aorta, sciatic artery, anterior abdominal vein and hepatic portal vein.4. Bufokinin‐immunoreactive fibres, mainly following blood vessels, were seen in whole mounts of the urinary bladder and tongue, but not in the air sac. In the heart ventricle, varicose fibres were found in the valve cusps, intracardiac ganglia, epicardium and myocardium close to the endocardium, but not in the rest of the myocardium.5. The vasodepressor action of bufokinin and the presence of bufokinin‐like immunoreactivity in varicose fibres in various vessels suggest a role for bufokinin in haemodynamic regulation and/or sensory nerve function in the toad. The lack of any reflex tachycardia in response to the falls in blood pressure was of note.
Proceedings of the Australian Neuroscience Society Symposium: Schizophrenia A PROPOSED PATHOLOGICAL MODEL IN THE HIPPOCAMPUS OF SUBJECTS WITH SCHIZOPHRENIA
Authors: Scarr E , Dean B 
Published: March 2003

SUMMARY1. The hippocampal formation plays an important role in the normal functioning of the brain, being implicated in cognition and sensory gating, both of which are affected in schizophrenia. The hippocampal formation receives information from the association cortices, which is processed by glutamatergic transmission within the hippocampus. Dopamine, noradrenaline, 5‐hydroxytryptamine (5‐HT), acetylcholine and GABA, all of which have been proposed to play a role in the neurobiology of schizophrenia, can affect this transmission.2. The advent of the ‘atypical’ antipsychotics, with their broad pharmacological spectra and improved therapeutic outcome, has revitalized research into neurotransmitter dysfunction other than that of dopamine. In particular, there has been interest in the serotonergic and cholinergic systems within the hippocampal formation because these are two of the transmitter systems targeted by clozapine and olanzapine.3. From the study of these systems, using tissue obtained post‐mortem from subjects with schizophrenia, we propose that there is a hyperserotonergic state in the hippocampal formation of some subjects with schizophrenia caused by a conformational change in the 5‐HT transporter. The model we propose allows us to construct further studies that will test the consequences of such a hyperserotonergic state in the hippocampal formation. This model has the potential to open new avenues in schizophrenia research.
Effects Of Ageing On The Activation Metabolism Of Rat Papillary Muscles
Authors: Kiriazis Helen , Gibbs Colin L 
Published: March 2003

SUMMARY1. A myothermic technique has been used to investigate the mechanics and energetics of left ventricular papillary muscles from 6‐, 15‐, 22‐ and 27–32‐month‐old Sprague‐Dawley rats.2. There was a significant increase in the left ventricular mass to body mass (LVM:BM) ratio in the senescent, 27–32‐month‐old group of animals compared with the younger animals (P < 0.05).3. The maximum stress developed in the senescent groups was reduced by almost 40% in comparison with the stress developed by the 6‐, 15‐ and 22‐month‐old groups (P < 0.001). The mean rise time, half relaxation time and half width were increased significantly (P < 0.05) in the 22‐month‐old group but, unexpectedly, this effect was not seen in the senescent group.4. Heat production per beat versus total stress relationships were obtained in two different ways to determine the magnitude of the activation heat and the isometric economy (given by the slope of the relationship). The activation heat was not significantly different between groups with either method, but there was a significant increase (P < 0.001) in the economy with which stress was developed in the senescent group in comparison with the 6‐ and 15‐month‐old groups.5. A combination of forskolin (2.5–6.5 μmol/L) and high Ca2+ (7.5 mmol/L) was used to increase the energy usage per beat. In the 6‐ and 15‐month‐old groups, these agents caused a four‐fold increase in the activation heat magnitude compared with a less than two‐fold increase in the 22‐month‐old and senescent groups (P < 0.001). There was no effect of forskolin/high calcium on the slope of the heat : total stress relationship.6. The data suggest that, under conditions known to increase cardiac contractility, there is a reduced ability to cycle calcium in the 22‐month‐old and senescent groups relative to the young adult 6‐month‐old and adult 15‐month‐old groups.
Two Possible Mechanisms Underlying Nitrate Tolerance In Monkey Coronary Arteries
Authors: Omura Tomoko , Matsumoto Tetsuya , Nakae Ichiro , Takahashi Masayuki , Kinoshita Masahiko 
Published: March 2003

SUMMARY1. Previous studies using isolated arteries have demonstrated cross‐tolerance between nitric oxide (NO) donors such as nitroglycerin (NTG) and sodium nitroprusside (SNP). However, it remains unclear whether the vasorelaxing effect of atrial natriuretic peptide (ANP), an activator of particulate guanylate cyclase, is affected by treatment with NO donors. To investigate the cross‐tolerance and interactions between NTG and ANP in coronary vasorelaxant responses, we used two models of monkey coronary arterial strips (Macaca fuscata).2. In one model, which was induced by a 1 h treatment with 4.4 × 10–4 mol/L NTG followed by washout of the agent for 1 h, the vasorelaxing effects of subsequent NTG were markedly attenuated, whereas those of ANP and NO were not affected. These findings suggest that the development of NTG tolerance is associated with a biotransformation process from NTG to NO. In the other model, which did not include washout after exposure to 3 × 10–6 mol/L NTG, the vasorelaxant responses to 10–8 mol/L ANP (31.1±5.4 vs 5.1±2.1%, respectively; P < 0.001), 10–6 mol/L NO (61.5±2.4 vs 29.5±8.5%, respectively; P < 0.001) and 10–8 mol/L SNP (49.4±6.4 vs 8.0±2.0%, respectively; P < 0.001) were significantly attenuated. The concentration– response curve for 8‐bromo‐cGMP (8‐Br‐cGMP) was shifted to the right, whereas responses to papaverine and forskolin were unchanged. These findings suggest that an intracellular process that occurs after the synthesis of cGMP is responsible for this interaction.3. As a mechanism of NTG tolerance, two possible processes may be impaired: (i) biotransformation from NTG to NO; and (ii) an intracellular process that occurs after the synthesis of cGMP.
Gene Expression Studies Using Microarrays
Authors: Burgess Janette K 
Published: March 2003

SUMMARY1. The rapid progression of the collaborative sequencing programmes that are unravelling the complete genome sequences of many organisms are opening pathways for new approaches to gene analysis. As the sequence data become available, the bottleneck in biological research will shift to understanding the role of each of these genes. Techniques that enable the analysis of large sets of genes in one experiment will elucidate the interactions of genes in diverse biological systems.2. Microarrays, which consist of large numbers of cDNA or oligonucleotides spotted onto a glass microscope slide, are one such technology. RNA isolated from two populations of cells, one control and one altered by experimental treatment or disease, is labelled with two different fluorochromes before being hybridized to the microarray. After a standard hybridization reaction, a scanner records the intensity of the two fluorochromes. The data can be analysed using special software that enables clustering of genes that have similar expression patterns.3. Such powerful analysis techniques will provide information about genes whose functions are currently unknown and enhance our understanding of how genes interact to provide molecular control. This increase in knowledge about gene function will allow new targeted approaches for the development of drugs and/or gene therapies.
Extracellular ATP and cAMP as Paracrine and Interorgan Regulators of Renal Function P2Y Receptors of MDCK Cells: Epithelial Cell Regulation by Extracellular Nucleotides
Authors: Insel Paul A , Ostrom Rennolds S , Zambon Alexander C , Hughes Richard J , Balboa Maria A , Shehnaz Darakhshanda , Gregorian Caroline , Torres Brian , Firestein Bonnie L , Xing Mingzhao , Post¥ Steven R 
Published: March 2003

SUMMARY1. Madin–Darby canine kidney (MDCK) cells, a well‐ differentiated renal epithelial cell line derived from distal tubule/collecting duct, respond to extracellular nucleotides by altering ion flux and the production of arachidonic acid‐derived products, in particular prostaglandin E2 (PGE2). Our work has defined the receptors and signalling events involved in such responses.2. We have found evidence for expression of at least three P2Y receptor subtypes (P2Y1, P2Y2 and P2Y11) in MDCK‐D1 cells, a subclone from parental MDCK.3. These receptors appear to couple to increases in calcium and protein kinase C activity, probably via a Gq/G11‐mediated activation of phospholipase C.4. In addition, P2Y receptor activation can promote a prominent increase in cAMP. This includes both a P2Y2 receptor‐mediated cyclo‐oxygenase (COX)‐dependent component and another COX‐independent component mediated by other P2Y receptors.5. We have documented that changing media in which cells are grown releases ATP and, in turn, activates P2Y receptors. Such release of ATP contributes in a major way to basal cAMP levels in these cells.6. The data indicate that MDCK cells are a useful model to define the regulation of epithelial cells by extracellular nucleotides. Of particular note, spontaneous or stretch‐induced release of ATP and subsequent activation of one or more P2Y receptors contributes to establishing the basal activity of signalling pathways.
John Ludbrook APPS Symposium Statistics In Physiology And Pharmacology: A Slow And Erratic Learning Curve
Authors: Ludbrook John 
Published: March 2003

SUMMARY1. Learning how to apply statistical analyses to the results of experimental or clinical studies may take a lifetime of trial (and sometimes error), as it has done in the author’s case. There is no evidence that biomedical investigators of the present generation are on a steeper learning curve. Gross misunderstandings of the purpose and functions of statistical analysis are apparent in applications to research grant‐giving bodies and ethics committees, in manuscripts submitted to journals and sometimes in published papers.2. Although estimation of minimal group (sample) size for a given power is an essential step in planning clinical studies, it seems to be used rarely in laboratory experimental work. This is despite exhortations to restrict the number of animals used to a minimum.3. Most investigators use hypothesis testing to analyse their results, but their understanding of the meaning of the resultant P‐values is slight.4. A flaw found almost universally in biomedical manuscripts is to make multiple inferences from the results of a single study. The goal of statistical analysis is to maintain the familywise type I error rate (risk of false‐positive inference) at a predetermined level (usually 5%). But, when multiple inferences are made from the same experiment, the risk of false‐positive error is inflated. There are two solutions to this problem: (i) use a multiple comparison procedure to control the familywise type I error rate; and (ii) test a single, global hypothesis.5. Biomedical investigators have been quick to acquire computer statistics software and to use it to analyse their experiments. However, they have been slow to recognize the limitations of this software. These include: (i) inadequate documentation of routines, so that neither the user nor the reader of published papers can be sure how the tests have been executed; (ii) flawed algorithms for the execution of statistical procedures; and (iii) failure to recognize that the best software for their purposes is that which takes them just beyond their statistical horizons.6. The obvious solution to these difficulties is to recruit a biomedical statistician into every research group, at a relatively trivial cost. However, properly qualified biostatisticians are in desperately short supply in Australia. It follows that research groups, national grant‐giving agencies and academic institutions must make provision for the proper training and subsequent employment of biostatisticians.
Circumventricular Organs: Gateways to the Brain Axonal Projections From The Organum Vasculosum Lamina Terminalis To The Supraoptic Nucleus: Functional Analysis And Presynaptic Modulation
Authors: Bourque Charles W , Richard Dominique 
Published: March 2003

SUMMARY1. The rat organum vasculosum lamina terminalis (OVLT) contains GABA‐ and glutamate‐releasing neurons that project directly to magnocellular neurosecretory cells (MNC) in the supraoptic nucleus.2. Changes in osmolality over the OVLT in hypothalamic explants cause proportional changes in firing in MNC through corresponding changes in the frequency of spontaneous glutamatergic excitatory post‐synaptic potentials without affecting GABAergic inhibitory post‐synaptic potentials.3. Exogenously applied atrial natriuretic peptide inhibits the osmotic control of MNC by causing a decrease in the amount of glutamate released provoked by action potentials originating from OVLT neurons.
Effects of dopamine d2 receptor agonists in a pituitary transplantation‐induced hyperprolactinaemia/anovulation model in rats
Authors: Moro Makoto , Inada Yoichi , Miyata Hiroshi , Komatsu Hidetada , Kojima Masami , Tsujii Hirotada 
Published: March 2003

SUMMARY1. In the present study, we investigated the effects of hyperprolactinaemia, induced by transplantation of anterior pituitary glands under the kidney capsule in female rats, on the relationship between serum and pituitary concentrations of the gonadotropins and on the oestrous cycle.2. Rats with pituitary transplants showed increased serum prolactin concentrations and decreased serum concentrations of gonadotropins and increased pituitary concentrations of gonadotropins. Moreover, these rats showed persistent dioestrous and anovulation from 3 to 6 days after transplantation.3. A single oral administration of cabergoline (at doses between 0.001 and 0.1 mg/kg) dose‐dependently inhibited the elevated serum prolactin concentrations in hyperprolactinaemic rats. At 0.1 mg/kg, cabergoline induced a continuous reduction in serum prolactin concentrations for 5 days after administration. Terguride (0.1 mg/kg) and bromocriptine (10 mg/kg) also reduced serum prolactin concentrations at 1 and 3 days after administration. All three dopamine D2 receptor agonists increased serum gonadotropin concentrations and ovarian weight at 3 days after administration.4. In rats exhibiting anovulation, a single oral administration of any one of the three dopamine D2 receptor agonists dose‐dependently restored ovulation and a normal oestrous cycle appeared. Oral administration of cabergoline (0.03 mg/kg) or terguride (0.1 mg/kg) restored ovarian function and abolished the anovulation following a reduction in serum prolactin concentrations. However, bromocriptine (10 mg/kg) did not completely abolish anovulation. Following administration of terguride (0.3 mg/kg) or bromocriptine (30 mg/kg), only one normal oestrous cycle appeared; however, following cabergoline (0.1 mg/kg), two normal oestrous cycles appeared.5. These results suggest that cabergoline has a potent and long‐lasting action as a dopamine D2 receptor agonist and, thus, should be a useful drug for the treatment of galactorrhoea and hyperprolactinaemic amenorrhoea and/or anovulation in humans.
Coronary Artery Baroreceptor‐Mediated Changes In Arterial Pressure: A Pilot Study In Conscious And Anaesthetized Sheep
Authors: Bennetts JS , Arnolda LF , Cullen HC , Knight JL , Baker RA , McKitrick DJ 
Published: March 2003

SUMMARY1. Evidence suggesting the presence of coronary artery baroreceptors on coronary arteries has existed for over 30 years.2. Evidence that activation of ventricular mechanoreceptors can elicit cardiovascular changes has been challenged, with those changes now thought to be due to coronary artery mechanoreceptors.3. Studies have suggested that coronary artery mechanoreceptors act as coronary baroreceptors with a role in cardiovascular regulation. However, all evidence to date has been obtained in anaesthetized animal models in physiologically compromised intra‐operative states.4. The purpose of the present study was to design an ovine model that would allow the discrete stretch of coronary arteries without causing ischaemia or changing flow or intra‐arterial pressure and that would confirm results seen in previous studies. In addition, the possibility that the technique could be used for studies of coronary artery baroreflexes in conscious sheep was investigated.5. Controlled stretch of the proximal left anterior descending coronary artery elicited decreases in arterial pressure without changes in heart rate or electrocardiographic activity in halothane‐anaesthetized sheep. Similar results were demonstrated in conscious sheep after surgical recovery of up to 2 weeks.6. The present study supports the possibility that coronary artery baroreceptors exist and likely have a role in cardiovascular regulation. The results of the present study in anaesthetized sheep are in agreement with previous results in anaesthetized animals, but also provide the first demonstration of coronary baroreceptor activity in a conscious animal model, underscoring the potential use of the model in the study of coronary artery baroreceptors in the intact animal.