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Biomedical subjects

J McQueen

Publications and source records attributed to J McQueen.

At least 19 recordsLinked to original sources
PubMed1992

Angiotensin II increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells via the angiotensin II AT1 receptor.

OBJECTIVES: The aim of this study was to determine which angiotensin II receptor (AT receptor) mediates proto-oncogene expression and phosphoinositide metabolism in vascular smooth muscle cells in vitro. DESIGN: The AT receptor antagonists DuP753 (losartan), an AT1 antagonist, and PD 123319, an AT2 antagonist, were used to characterize AT receptors on cultured vascular smooth muscle cells derived from the rat mesenteric artery and to identify which receptor subtype mediates the angiotensin II-induced increase in proto-oncogene expression and phosphoinositide metabolism. METHODS: Rat mesenteric artery vascular smooth muscle cells were grown using standard cell culture methods. Proto-oncogene induction was measured using Northern blotting. Phosphoinositide breakdown was assessed by measuring [3H]-inositol phosphates released from prelabelled cells. RESULTS: Receptor-binding studies revealed that the AT1 receptor predominated on vascular smooth muscle cells. Incubation of quiescent cells with 0.1 mumol/l angiotensin II resulted in a 65% increase in total [3H]-inositol phosphates released compared with unstimulated cells and in a rapid accumulation of c-fos messenger RNA (mRNA). Pre-incubation of the cells with 10(-5) mol/l PD 123319 had no effect on either total inositol phosphates release or c-fos mRNA induction. Both responses, however, were totally abolished by pre-incubation of the cells with 10(-5) mol/l losartan or saralasin. CONCLUSIONS: Angiotensin II acts through the AT1 receptor to increase c-fos expression and phosphoinositide turnover in vascular smooth muscle cells. These mechanisms may be important in angiotensin II-induced smooth muscle hypertrophy.

Angiotensin II↗
PubMed1992

Maternal and fetal atrial natriuretic peptide levels at delivery from normal and growth retarded pregnancies.

OBJECTIVE: To determine whether circulating fetal levels of the vasodilator atrial natriuretic peptide (ANP) are reduced in pregnancies complicated by intrauterine growth retardation (IUGR). DESIGN: Prospective observational study. SETTING: University teaching hospital and research laboratory. SUBJECTS: 25 normal singleton pregnancies delivered at term by spontaneous vertex delivery (n = 16) or by elective caesarean section (n = 9), and a series of 14 singleton pregnancies complicated by IUGR. INTERVENTION: Measurement of ANP by radio-immunoassay in maternal venous, umbilical artery, and umbilical vein plasma from a series of normal, and IUGR pregnancies. MAIN OUTCOME MEASURES: Comparison of plasma ANP levels between the three groups; relation between fetal ANP, PO2 and pH. RESULTS: Mode of delivery did not influence either maternal, umbilical artery or umbilical vein plasma ANP levels in normal term singleton pregnancies. Umbilical vein ANP levels were significantly higher in the IUGR group when compared with normal pregnancies at term (mean 66 95%, CI 36-122 vs mean 37, 95% CI 29-47 pg/ml, P = 0.03) and were inversely related to umbilical artery pH (R2 = 65%; P = 0.003). CONCLUSIONS: These data suggest that umbilical vein ANP levels are elevated in pregnancies complicated by IUGR, and rise appropriately in response to the stress of acidosis. In the absence of any receptor or second messenger defect within feto-placental vascular smooth muscle, these data suggest that ANP is not directly implicated in the vascular pathophysiology of IUGR.

Atrial Natriuretic Factor↗
PubMed1990

Interaction of angiotensin II and atrial natriuretic peptide in the human fetoplacental unit.

We have identified two classes of membrane receptor for atrial natriuretic peptide (KD (dissociation constant) 0.2, 70.1 nmol/L) and angiotensin II (KD 1.7 nmol/L, 15.2 nmol/L) in human fetoplacental vasculature. In addition, in the isolated perfused placenta atrial natriuretic peptide inhibited the vasoconstrictor action of angiotensin II. These findings suggest that atrial natriuretic factor may regulate fetoplacental blood flow.

Angiotensin II↗
PubMed1990

Vascular angiotensin II and atrial natriuretic peptide receptors in normal and growth-retarded human placentae.

Receptors for angiotensin II (AII) and atrial natriuretic peptide (ANP) were characterized in a membrane fraction from resistance-type artery from human placentae. Placentae from normal pregnancies and pregnancies complicated by intrauterine growth retardation (IUGR) were studied. High- and low-affinity receptors for AII (dissociation equilibrium constant (Kd) 1.7 and 15.7 nmol/l respectively) and ANP (Kd 0.2 and 55.5 nmol/l respectively) were identified; these parameters were unchanged in IUGR, but there was a reduction in high-affinity receptor number by approximately 50% for AII and 80% for ANP in this condition. Both peptides may have a role in the regulation of fetoplacental blood flow. The alterations in IUGR are consistent with sustained activation of the fetal renin-angiotensin system and suggest altered vascular responsiveness to ANP.

Angiotensin II↗
PubMed1989

Divalent cation-induced interconversion of hepatic angiotensin receptor subtypes.

The effects of divalent cations on the hepatic angiotensin receptor have been investigated using radioligand binding methods. With a plasma membrane-enriched fraction from rat liver, a total binding capacity for angiotensin peptides of 0.5 pmol/mg of membrane protein was observed. In the absence of divalent cations, almost all of these sites showed low affinity (KD, 11.25 nM) for angiotensin II. In the presence of Ca2+, there was a concentration-dependent increase in the proportion of sites with high affinity (KD, 0.94 nM) for angiotensin II. Mg2+, Sr2+, and Ba2+ were less effective in this respect, although Mg2+ also modified affinity of the high affinity subtype. Monovalent cations (Na+, Cs+, and K+) had little effect on angiotensin binding. Both receptor subtypes showed high and approximately equal affinity for sarcosine1-analogues of angiotensin II and 10-fold lower and equal affinity or Ile7-angiotensin III. The low affinity subtype appeared to be more sensitive to N-terminal deletions in the peptide. Interconversion of receptor subtypes could be prevented by 5'-guanylylimidodiphosphate, La3+, diltiazem, and verapamil. The results show that the hepatic angiotensin receptor can exist in high and low affinity states in vitro and that the proportion in each state can be modified by divalent cations, guanine nucleotides, and some Ca2+ antagonist drugs.

Angiotensin II↗
PubMed1988

Temporary A-V sequential pacing using transluminal pacing electrodes.

A case is presented which describes the initiation of atrial-ventricular (A-V) sequential pacing using atrial epicardial wires and an in-situ transluminal ventricular pacing probe. A 68-year-old female with a permanent A-V sequential pacemaker was scheduled for elective aortocoronary bypass. Following sternotomy, pacing function was converted to ventricular pacing (VVI) with the use of electrocautery. A Chandler V-pacing probe was introduced through a Paceport (American Edwards) pulmonary artery catheter and with a paced increase in ventricular rate, the cardiac output increased from 2.8 to 3.2 L.min-1. At the conclusion of cardiopulmonary bypass the patient was in sinus rhythm at a rate of 67.min-1 and was paced to a faster rate using bipolar atrial epicardial wires. The patient subsequently developed intermittent heart block so temporary A-V sequential pacing was established using atrial epicardial wires and the in situ ventricular pacing probe. Pacing was achieved at routine generator output settings of seven milliamps (mA) for both atrium and ventricle and at an A-V interval of 0.120 sec. This resulted in an immediate increase in cardiac output from 3.3 to 4.1 L.min-1. The compatibility of these two pacing systems offers an increased margin of safety in cardiac surgery patients requiring atrial pacing, who are at risk for developing postoperative heart block.

Aged↗
PubMed1987

Immunocytochemical localization of prolactin in carcinoma of the cervix.

Immunocytochemical methods were used to demonstrate prolactin in both normal and malignant human cervices. Four of five cervices with epidermoid carcinoma and three of four cervices with adenocarcinoma demonstrated prolactin. One of four normal cervices stained positive for prolactin in the endocervical glands. Four cervices from pregnant patients were positive for prolactin. The results of this study show prolactin in human cervical carcinomas. The role and source of cervical prolactin is unknown.

Adenocarcinoma↗
PubMed1987

Cation-dependent and cation-independent stages in regulation of the vascular angiotensin receptor after alteration of sodium balance in the rat.

The role of cations in vascular angiotensin receptor regulation has been investigated by radioligand receptor assay using a cell membrane fraction derived from mesenteric arterial muscle of the rat. In arterial membrane fractions from normal rats, the apparent receptor density varied with the ambient [Ca++] over the range, 0-10 mM. Receptor densities of 50 +/- 4, 102 +/- 4, and 156 +/- 5 fmol/mg membrane protein were obtained in low (0 mM), normal (4.8 mM), and high (25 mM) [Ca++], respectively. After 2 days of sodium loading, sodium depletion, and converting enzyme blockade altered receptor densities were detected in normal assay but not in high [Ca++] or low [Ca++], indicating changes in the relationship between [Ca++] and apparent receptor density. Similar results were obtained after 12 days of sodium loading or converting enzyme blockade. After 12 days of sodium depletion, there was no difference in receptor density between normal and high [Ca++] (44 +/- 5 fmol/mg protein) and the value obtained in low [Ca++] (27 +/- 2 fmol/mg protein) was significantly below that for all other groups. No change in receptor affinity was observed. These results suggest that there are two stages in vascular angiotensin receptor regulation; an initial masking-unmasking process which involves Ca++, and with prolonged agonist occupancy, an actual loss of receptors.

Angiotensin II↗
PubMed1978

The modifying effect of progestogen on the response of the post-menopausal endometrium to exogenous oestrogens.

Cyclical regimes of unopposed oestrogens are associated with the development of both cystic glandular and atypical hyperplasia, and the incidence of hyperplasia is related to the dose of oestrogen prescribed. Atypical hyperplasia develops later than, and perhaps from, cystic glandular hyperplasia. With sequential oestrogen/progestogen therapy the incidence of this condition was greatly reduced, and therefore, progestogens appear to protect against the development of this condition. In all cases but one, sequential regimes also reversed both spontaneously-arising and oestrogen-induced hyperplasia to a normal endometrium. Cyclical high-dose unopposed oestrogen therapy may not be capable of reversing spontaneously-arising hyperplasia, and this condition may progress to endometrial adenocarcinoma. Spontaneously-arising hyperplasia can be present before therapy commences, but may be unsuspected, as it can occur in the absence of abnormal vaginal bleeding. Therefore, cyclical oestrogen therapy should not be prescribed unless pre-treatment curettage has been performed and spontaneously-arising hyperplasia has been excluded; and unless subsequent monitoring of the endometrial response is being performed by serial biopsy.

Endometrial Hyperplasia↗
PubMed1978

Clinical considerations in the management of the menopause: the endometrium.

Exogenous oestrogens prescribed for the relief of menopausal symptoms are being given in pharmacological doses and the term 'hormone replacement therapy' is inappropriate. The frequent development of endometrial hyperplasia during unopposed cyclical oestrogen therapy is therefore to be expected, but no single pattern of vaginal bleeding accurately reflected the histology of the endometrium. As such doses of oestrogens are required for effective relief of symptoms, progestogens must be given to protect against endometrial hyperstimulation. Patient acceptability of sequential oestrogen/progestogen therapy is high (90%) and with such therapy breakthrough bleeding may subsequently be shown to be a reliable indicator of underlying endometrial pathology.

Endometrial Hyperplasia↗