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M J Griffiths

Publications and source records attributed to M J Griffiths.

At least 19 recordsLinked to original sources
PubMed1997

Endothelin-1 in rat endotoxemia: mRNA expression and vasoreactivity in pulmonary and systemic circulations.

Endothelin-1 (ET-1) is a vasoconstrictor and proinflammatory peptide, but its role in the vascular response to sepsis is unknown. After intraperitoneal injection of male Wistar rats (300 g) with 20 mg/kg of Salmonella enteritidis lipopolysaccharide (LPS), the expression of ET-1 mRNA was significantly increased in pulmonary artery and aorta within 1 h and arterial ET-1 concentration was elevated. Despite this increase in ET-1 production, there was no difference in baseline systemic or pulmonary arterial pressures between control and endotoxin-treated rats, and, furthermore, combined ETA/ETB receptor antagonism using bosentan produced reductions in systemic and pulmonary arterial pressures that were not greater than the modest fall seen in controls. However, bosentan completely antagonized the hemodynamic effects of exogenous ET-1 in controls but only weakly antagonized its effects in LPS animals. After LPS the initial (ETB-mediated) systemic hypotensive responses to ET-1 were attenuated, but the subsequent systemic pressor responses were not. By contrast, the increases in pulmonary arterial pressure in response to ET-1 and the ETB receptor agonist sarafotoxin S6c were significantly reduced in LPS animals. Vascular ET-1 mRNA expression and arterial ET-1 concentration are elevated after LPS treatment in rats, but the functional activity of ET-1 cannot be exposed by combined ETA/ETB receptor antagonism, possibly because of an alteration in the functional status of ET receptors.

Animals↗
PubMed1997

In vivo treatment with endotoxin increases rat pulmonary vascular contractility despite NOS induction.

Pulmonary hypertension is a feature of clinical and experimental acute lung injury. Nitric oxide (NO) synthesis is increased in hyporesponsive systemic and pulmonary conductance arteries after endotoxin (LPS) injection in the rat. We examined the effects of NO synthase (NOS) induction by LPS on vascular reactivity of the isolated perfused rat lung (IPL) using the selective inducible (iNOS) inhibitor aminoguanidine (AG). Baseline pulmonary artery pressures (Ppa) were higher in the LPS compared with the sham-treated rats and were further increased only in the LPS-treated group by AG. Increased NOS activity in whole lung and the vasopressor effect of AG suggested that iNOS was active in pulmonary resistance vessels after LPS treatment. Vasoconstriction to hypoxia, angiotensin II (AII), and prostaglandin F2 alpha (PGF2 alpha) was enhanced or unchanged in LPS-treated rats despite NOS induction. Hence, iNOS activity counterbalances increased pulmonary vascular contractility in this model.

Angiotensin II↗
PubMed1996

A false-positive diagnosis of Turner syndrome by amniocentesis.

A 45,X karyotype was observed in all cells examined from an amniotic fluid sample taken at 16 weeks' gestation from a 37-year-old patient referred because of her age. Following termination of the pregnancy, all cells examined from fetal tissues (cardiac blood, skin, and muscle) showed a 46,XX karyotype. The most likely explanation for the discordant results is thought to be a dizygotic twin pregnancy with a normal fetus and an empty sac, the latter being sampled at amniocentesis resulting in a 45,X karyotype.

Adult↗
PubMed1996

Bilateral metastatic spread of testicular teratoma to mandibular condyles.

The clinical and radiological features of a patient with metastatic spread of testicular teratoma to both mandibular condyles are presented. It is suggested that in patients with known systemic malignancy, a local metastatic deposit should be considered as a possible cause of unexplained pain in the temporomandibular joints.

Adult↗
PubMed1996

Ischaemia--reperfusion injury in the rat is modulated by superoxide generation and leads to an augmentation of the hypoxic pulmonary vascular response.

1. The effects of the scavengers of reactive oxygen species superoxide dismutase and catalase, the iron chelator desferrioxamine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester and saline (control vehicle) on hypoxic pulmonary vasoconstriction, a measure of albumin flux and an index of lipid peroxidation (palmitic:linoleic acid ratio) were investigated after ischaemia-reperfusion in an isolated, blood-perfused rat lung model. 2. Lungs treated immediately before reperfusion with catalase (5,000 units), desferrioxamine (2 mg/kg), NG-nitro-L-arginine methyl ester (5 mmol/l) or saline showed a significant augmentation in pre-ischaemia-reperfusion hypoxic pulmonary vasoconstriction (57.7 +/- 6.0%, 82.7 +/- 28.8%, 95.2 +/- 36.6% and 45.95 +/- 10.53% respectively), an increase in albumin flux (0.35 +/- 0.04, 0.31 +/- 0.06, 0.29 +/- 0.04 and 0.33 +/- 0.02) and an increase in pre-ischaemia-reperfusion palmitic:linoleic acid ratio (0.64 +/- 0.08, 0.51 +/- 0.19, 0.5 +/- 0.04 and 0.17 +/- 0.07). Superoxide dismutase (2,750 i.u.) administered immediately before reperfusion prevented completely the changes in hypoxic pulmonary vasoconstriction (-0.3 +/- 5.4%), albumin flux (0.09 +/- 0.11) and palmitic:linoleic acid ratio (-0.06 +/- 0.12). In control lungs (2h of continuous perfusion), superoxide dismutase, catalase, desferrioxamine and saline did not affect hypoxic pulmonary vasoconstriction (5.5 +/- 4.9%, 1.0 +/- 3.1%, -5.1 +/- 1.8% and 3.0 +/- 6.6%). However, NG-nitro-L-arginine methyl ester significantly augmented hypoxic pulmonary vasoconstriction (275.1 +/- 39.3%). There was no effect of superoxide dismutase, catalase, desferrioxamine, NG-nitro-L-arginine methyl ester or saline in control lungs on albumin flux (0.10 +/- 0.04, 0.11 +/- 0.01, 0.1 +/- 0.01, 0.12 +/- 0.01 and 0.11 +/- 0.01 respectively) or palmitic:linoleic acid ratio (-0.08 +/- 0.08, 0.73 +/- 0.76, -0.03 +/- 0.12, 0.01 +/- 0.17 and 0.00 +/- 0.0 respectively). 3. We conclude that superoxide dismutase attenuates ischaemia-reperfusion-induced increases in albumin flux and hypoxic pulmonary vasoconstriction, and prevents consumption of linoleic acid in the isolated, blood-perfused rat lung.

Animals↗
PubMed1996

Endothelin-1-induced contraction of pulmonary arteries from endotoxemic rats is attenuated by the endothelin-A receptor antagonist, BQ123.

OBJECTIVE: Sepsis is characterized by systemic vasodilation and hyporesponsiveness to constrictor agents, at a time when the pulmonary circulation exhibits varying degrees of vasoconstriction. Plasma endothelin-1 concentrations are increased, but the role of this potent vasoconstrictor peptide in modulating the vascular response to sepsis is unknown. Therefore, we assessed the effect of endothelin-A receptor antagonism in the response of pulmonary arteries from rats treated with lipopolysaccharide to endothelin-1, and determined the vasomotor role of the endothelin-B receptors that are known to be located on rat pulmonary artery smooth muscle and endothelium. DESIGN: Prospective, controlled study. SETTING: Animal research laboratory. SUBJECTS: Male Wistar rats (275 to 300 g). INTERVENTIONS: Animals were injected with either lipopolysaccharide (20 mg/kg i.p.) or saline (1 mL i.p.) 4 hrs before being killed. The main pulmonary arteries were cut into 2-mm rings, and suspended in an organ bath. In the first set of experiments, half of the rings underwent a procedure that removed the endothelium, and the contractile response to cumulative doses of endothelin-1 (10(-11) to 10(-6) M) was measured. Half of the rings were pretreated with the endothelin-A receptor antagonist, BQ123 (10(-5) M or 10(-6) M), and the other half of the rings were treated with vehicle. In a separate group of experiments, the contractile response to cumulative concentrations of the selective endothelin-B agonist, sarafotoxin S6c (10(-11) to 10(-6) M), was measured in rings at baseline tension. Second, the possible dilator effect of endothelin-B receptor activation was tested by the administration of sarafotoxin S6c (10(-7) to 10(-6) M) to rings preconstricted by 10(-6) M of U46619, a thromboxane receptor agonist, either in the presence or absence of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine-methylester (10(-4) M). Acetylcholine-induced (10(-4) M), endothelium-dependent vasodilation was also measured. MEASUREMENTS AND MAIN RESULTS: BQ123 (10(-5) or 10(-6) M) caused consecutive rightward shifts in the endothelin-1 concentration-contraction curves for all ring types, including the intact rings from endotoxemic animals. Sarafotoxin S6c failed to induce any direct constriction in rings from sham-treated or lipopolysaccharide-treated rats. However, sarafotoxin S6c induced transient vasodilation at the initial dose in rings from sham-treated rats but not lipopolysaccharide-treated rats-an effect that was attenuated by N omega-nitro-L-arginine-methylester. Acetylcholine induced an N omega-nitro-L-arginine-methylester-sensitive vasodilation that was reduced in rings from endotoxin-treated rats. CONCLUSIONS: Endothelin-A receptor blockade is an effective means of attenuating endothelin-1-induced contraction of isolated pulmonary artery rings, even from rats rendered endotoxemic. Endothelin-B receptors on the pulmonary artery cause vasodilation via the release of nitric oxide, and have no constrictor component. The functional effects of endothelin-B receptors on tone are lost after lipopolysaccharide treatment. The endothelium is involved in both the constrictor and dilator effects of endothelin in rat pulmonary artery, confirming a pivotal role for endothelial cells in the vascular response to sepsis.

Animals↗
PubMed1995

Contraction to endothelin-1 in pulmonary arteries from endotoxin-treated rats is modulated by endothelium.

Sepsis is characterized by hyporesponsiveness of vascular smooth muscle to pressor agents. Levels of the potent vasoconstrictor, endothelin-1 (ET-1), are elevated in animal models of sepsis and in patients. This study assesses the contractile response of pulmonary artery from endotoxin-pretreated rats to ET-1 to determine whether this contraction is modified by the endothelium. Both intact and denuded rings from endotoxin-pretreated rats exhibited hyporesponsiveness to ET-1, but the endothelium was found to be essential for maximal ET-1-induced contraction. Upon pretreatment of vessels with the cyclooxygenase inhibitor, indomethacin (10(-5) M), the novel ETB-receptor antagonist, BQ-788 (10(-8) and 10(-6) M), and the thromboxane A2-receptor antagonist, ICI-192605 (10(-5) M), each of these agents caused a reduction in the ET-1-induced contraction of endotoxin-pretreated rat pulmonary artery only in the presence of the endothelium but had no effect in endothelium-denuded vessels or in sham-treated groups. These findings demonstrate that ET-1-induced contraction in pulmonary arteries from septic rats is partially dependent upon an endothelially derived cyclooxygenase product, the release of which appears to involve ETB-receptor stimulation.

Animals↗
PubMed1995

In vivo treatment with endotoxin induces nitric oxide synthase in rat main pulmonary artery.

Our aim was to demonstrate increased NO activity from inducible NO synthase (iNOS) in pulmonary arteries (PA) from rats treated with endotoxin [lipopolysaccharide (LPS), 20 mg/kg ip]. LPS treatment diminished the contractile response of PA to potassium chloride (KCl) and phenylephrine (PE) and increased levels of guanosine 3',5'-cyclic monophosphate (cGMP) in endothelium-denuded vessels. Both the NO synthase (NOS) antagonists NG-monomethyl-L-arginine (L-NMMA; nonselective) and aminoguanidine (selective for iNOS) enhanced PE-induced contraction in endothelium-denuded vessels from LPS-treated rats. Furthermore, L-NMMA-induced contraction of endothelium-denuded vessels from LPS-treated rats was stereospecifically antagonized by L-arginine and associated with decreased cGMP levels. These data suggest that NO is produced in increased amounts from PA smooth muscle after LPS treatment. LPS treatment caused increased expression of mRNA for iNOS in PA. This effect of LPS was attenuated by pretreatment with dexamethasone, suggesting that induction of NOS in PA smooth muscle underlies the increased NO activity associated with LPS administration.

Amino Acid Oxidoreductases↗
PubMed1995

Aminoguanidine selectively decreases cyclic GMP levels produced by inducible nitric oxide synthase.

Overproduction of nitric oxide (NO) following induction of NO synthase in vascular smooth muscle by endotoxin and certain cytokines contributes to the vasodilation and hyporesponsiveness to vasopressors that characterize the septic circulation. Guanosine 3',5'-cyclic monophosphate (cGMP) mediates the effects of NO in vascular smooth muscle. Vessels from animals treated with endotoxin have elevated cGMP levels compared with control animals. Aminoguanidine has been proposed as a selective inhibitor of the inducible form of NO synthase. This study compares the effects of aminoguanidine on phenylephrine-induced contractions and cGMP levels in thoracic aortic rings from endotoxin treated (20 mg/kg intraperitoneally) with sham-treated (1 ml saline intraperitoneally) rats. Endotoxin-treatment depressed phenylephrine-induced contraction and raised tissue levels of cGMP. Aminoguanidine (100 microM and 1 mM) increased phenylephrine-induced tension and decreased cGMP levels in a dose-dependent manner in intact and endothelium-denuded aortas from endotoxin-treated rats but had no effect on vessels from sham-treated rats. These findings are consistent with the hypothesis that endotoxin treatment causes increased vascular production of endothelium-independent NO, which is associated with a diminished response to vasoconstrictors. Aminoguanidine decreases indices of NO production only after endotoxin treatment, providing further evidence that it is a selective inhibitor of inducible NO synthase.

Animals↗
PubMed1995

Anatomy and physiology as a predictor of success in baccalaureate nursing students.

The purpose of this two-part study was to identify early indicators of students' success (N = 98) in a baccalaureate nursing program. Part I determined how well six variables predicted competence on a criterion-referenced anatomy and physiology (A/P) examination. A multiple regression model was used to analyze the relationships among the predictor and the criterion variables. Data analyses show that only two predictors, grade point average and type of college in which the A/P course was taken, were significantly related (p = 0.0001) to A/P test scores. Part II used students' A/P score to predict success in the didactic component of clinical nursing coursework. In part II, a simple regression model was used to predict the relationship between A/P test score and success in the second clinical nursing course. These results indicated that A/P test score was significantly related (p = 0.003) to success in the second clinical nursing course.

Anatomy↗
PubMed1994

Chromosome preparations of both direct and long-term cultures from the same fragment of chorionic villi.

A simplified method is described for processing both direct preparations and long-term cultures from the same fragment of chorionic villi. Enzyme separation of the outer trophoblast layers (used for direct preparations) from the inner mesenchymal core (used to initiate long-term cultures) facilitates the utilization of the same fragments for the two procedures, without jeopardizing the success of either method. This has proved useful in cases where the sample was so small that only one method of chromosome preparation may have been possible using other techniques.

Cells, Cultured↗
PubMed1994

Oral melanotic macules that develop after radiation therapy.

External beam radiotherapy treatment of malignant conditions in the head and neck can give rise to several adverse oral effects if the oral or salivary tissues are within the field of beam. We report on a patient with widespread oral melanotic hyperpigmentation that developed after a course of radiotherapy for metastatic carcinoma in the cervical lymph nodes. As no other local or systemic cause was evident it is possible this abnormal hyperpigmentation was a result of the radiotherapy. The development of oral melanotic macules as a consequence of radiotherapy has not been previously described.

Carcinoma, Squamous Cell↗
PubMed1993

Osteoarthrosis, the temporomandibular joint, and Eagle's syndrome.

Temporomandibular joint osteoarthrosis is common but typically asymptomatic. This article describes a patient with symptomatic left temporomandibular joint osteoarthrosis in whom pain in the right side of the tongue and ear, and dysphagia, subsequently developed simulating Eagle's syndrome. The concept of Eagle's syndrome is reviewed.

Adult↗
PubMed1993

Pulmonary vascular reactivity and ischaemia-reperfusion injury in the rat.

1. The endothelium has been shown to modulate the pulmonary vascular response to hypoxia in the rat. Acute lung injury is associated with loss of hypoxic pulmonary vasoconstriction and increased pulmonary vascular permeability. Similar loss of the vascular response to hypoxia is seen after ischaemia-reperfusion injury of the myocardium. 2. The effects of reperfusion injury on pulmonary endothelial integrity, as shown by the albumin escape index and hypoxic pulmonary vasoconstriction, were investigated in isolated, blood-perfused rat lungs. 3. Ischaemia for 0.5 h, which itself caused no increase in the albumin escape index, was followed by reperfusion for 0.25 h, 0.5 h and 1 h. Controls were subjected to 2 h of perfusion only (n = 5 in all groups). The pulmonary pressor response to hypoxia (fractional inspired oxygen concentration, 3%) was measured before and after ischaemia-reperfusion, and the dilator response to acetylcholine was measured after ischaemia-reperfusion in all cases. 4. Ischaemia-reperfusion significantly increased the albumin escape index after 0.5 h (mean +/- SEM, 1.40 +/- 0.27) and 1 h (2.0 +/- 0.30) compared with controls (0.54 +/- 0.30, P < 0.05 in both cases). The pulmonary pressor response to hypoxia was augmented significantly after reperfusion when compared with baseline hypoxic pulmonary vasoconstriction (change from baseline: 13.2 +/- 4.63 and 22.2 +/- 7.1% after 0.5 and 1.0 h of reperfusion, respectively, P < 0.05). Vasorelaxation of sustained hypoxic vasoconstriction using acetylcholine was similar in both control lungs and those subjected to ischaemia-reperfusion. 5. These results suggest tht the pressor response to hypoxia is augmented after damage to the pulmonary vascular endothelium induced by ischaemic-reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

Aminoguanidine selectively inhibits inducible nitric oxide synthase.

1. Endotoxin induces nitric oxide synthase in vascular tissue, including rat main pulmonary artery. Currently available agents that cause inhibition of nitric oxide synthase are relatively non-selective between the constitutive and inducible forms of the enzyme. 2. Aminoguanidine caused a dose-dependent increase in phenylephrine-induced tension in intact and endothelium-denuded pulmonary artery rings from endotoxin-treated rats, but had no effect on sham-treated controls. 3. Contraction caused by aminoguanidine in endothelium-denuded vessels from endotoxin-treated rats was unaffected by indomethacin (10 microM), and by cimetidine and mepyramine (both 10 microM), excluding an effect of aminoguanidine mediated by arachidonic acid metabolites or histamine. 4. Contraction caused by aminoguanidine in endothelium-denuded vessels from endotoxin-treated rats was abolished by L-arginine (2 mM) and L-NG-monomethyl arginine (300 microM), but unaffected by D-arginine and D-NG-monomethyl arginine, suggesting that its action is mediated by the L-arginine/nitric oxide pathway. 5. Aminoguanidine had no effect on acetylcholine-induced relaxation of intact vessels from shamtreated rats. However, relaxation of artery rings from endotoxin-treated rats by L-arginine was competitively inhibited by aminoguanidine.6. These results in isolated main pulmonary arteries of the rat confirm previous reports that aminoguanidine is a selective inhibitor of inducible nitric oxide synthase.

Acetylcholine↗