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J McQueen

Publications and source records attributed to J McQueen.

At least 19 recordsLinked to original sources

Different forms of LTD in the CA1 region of the hippocampus: role of age and stimulus protocol.

In this study, we have investigated the developmental range over which different stimulus protocols induce long-term depression (LTD). Low-frequency stimulation (LFS; 900 stimuli, 1 Hz) produced LTD in hippocampal slices from rats younger than approximately 40 days old, but not in animals aged between approximately 40 days and 16 weeks. We demonstrate, however, that different stimulus protocols can result in LTD in the adult hippocampus. Whilst one paired-pulse low-frequency stimulus protocol [PP-LFS; 50 ms paired-pulse interval (PPI), 900 pairs of stimuli] produced N-methyl-D-aspartate (NMDA) receptor-independent LTD, another PP-LFS protocol (200 ms PPI; 900 pairs) produced NMDA receptor-dependent LTD. Furthermore, the saturation of NMDA receptor-dependent LTD did not prevent the induction of further NMDA receptor-independent LTD. This lack of occlusion suggests that different mechanisms of expression may underlie each of the above forms of LTD in the adult hippocampus. In contrast to the adult hippocampus, NMDA receptor-dependent LTD was induced by both LFS and PP-LFS (50 ms PPI) in slices from young animals (12-20 days). Although they share a common induction mechanism, LTD induced by PP-LFS may be expressed through other mechanisms in addition to those underlying LFS-induced LTD in the young hippocampus. In conclusion, the results in this study demonstrate that mechanisms of long-term synaptic depression within the hippocampus can alter radically with development of the central nervous system and with the use of different induction protocols.

2-Amino-5-phosphonovalerate↗

Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory.

Sex steroids exert potent effects on mood and mental state in the human. Our previous experimental findings in female rats suggest that these effects may be mediated, in part, by the action of estrogen on the 5-hydroxytryptamine2A receptor (5-HT(2A)R) and serotonin transporter (SERT) in brain. Here we review our recent findings on the effect of acute (approximately 32 h) testosterone manipulation on central 5-HT(2A)R and SERT in male rats. Castration decreased while testosterone or estrogen, but not 5alpha-dihydrotestosterone (5alpha-DHT), increased significantly the content of 5-HT(2A)R mRNA and SERT mRNA in the dorsal raphe nucleus (DR) and the density of 5-HT(2A)R and SERT binding sites in higher centers of the brain. The lack of effect of 5alpha-DHT, a potent androgen which cannot be converted to estrogen, suggests that the action of testosterone depends upon its conversion to estrogen by aromatase. This may also explain why estrogen, but not testosterone or 5alpha-DHT, increased the density of 5-HT(2A)R binding sites in the caudate-putamen, a brain region where aromatase is scarce. The estrogen induction of SERT mRNA is most prominent in the rostral DR and this together with the correlation between sensitivity of DR serotonin neurons to estrogen and neurotoxic amphetamine derivatives provides a potential topochemical handle with which to investigate testosterone/estrogen regulation of SERT gene expression. These findings are discussed in relation to the possible role of interactions between sex steroids and serotonin mechanisms in mood disorders, schizophrenia and Alzheimer's disease.

Affect↗

Intrauterine growth restriction is associated with persistent juxtamedullary expression of renin in the fetal kidney.

BACKGROUND: Intrauterine growth restriction (IUGR) has been linked to impaired renal function and hypertension, suggesting that an adverse prenatal environment could alter kidney development and renin production. METHODS: Immunohistochemistry and in situ hybridization were employed to localize renin-containing cells (RCCs) in the deep, middle, and superficial zones of autopsy kidney sections, in parallel with histologic maturation, from unexplained stillborn fetuses of normal weight (N = 26) and stillborn fetuses with IUGR (N = 17). RESULTS: In the control group, the number of RCC per 100 glomeruli in the deep zone decreased with advancing gestation from 40 at 20 weeks gestation to five at term (P < 0.001), whereas the opposite change was found in the superficial zone (increase from 5 per 100 to 55 per 100; P < 0.001). In the IUGR group, the density of RCCs in both the superficial and deep zones was similar to the control group at 20 weeks, and no shift in renin gene expression was observed as gestation advanced. Histologic maturation was unaltered. CONCLUSIONS: Renin gene expression persists and predominates in the deep renal cortex of the stillborn IUGR fetus, and could contribute to the pathogenesis of neonatal oliguria and/or hypertension during postnatal life.

Embryonic and Fetal Development↗

Care of the woman with hypertension in pregnancy: the viewpoint of the midwife.

Key principles underpin good midwifery care of every pregnant woman, including a sound knowledge base, meeting the woman's needs and enhancing care. Normal antenatal care, with regular measurement of blood pressure, remains the mainstay of screening for hypertension in pregnancy. The midwife's role is that of accurate assessment and communication when detecting the first signs of hypertension. The midwife will then play a major role in the ongoing monitoring of the condition, liaison with the medical team and education of the woman and her family. Continuity of care is an important principle in avoiding errors in recording blood pressure between care givers; familiarity of a known midwife may reduce the likelihood of white coat hypertension. Advocacy should be employed by the midwife as a key link between the woman, her family and the obstetric team. Every woman who has experienced pre-eclampsia should be given the opportunity to talk through her care at a later date. This may be at the postnatal appointment or through a debriefing service.

Blood Pressure↗

Introduction: evolution of patient-focused care within the contextural framework of an integrated delivery system (IDS).

Whatever the specific actions taken to move toward a truly integrated delivery system, the most critical success factor may be the "rate of integration." (See Figure 2 below). The IDS that achieves the most rapid rate of integration (A) may not initially be the market leader. However, the ability to integrate will have a major impact on how well an organization manages managed care and subsequently the long-term growth and profitability of the system. Many thanks are extended to the authors of the following articles. I believe you will find the articles helpful in developing a deeper understanding of patient-focused care in general and in understanding strengths, areas of needed improvement, and application of the model in an IDS environment.

Continuity of Patient Care↗

Fetal vascular atrial natriuretic peptide receptors in human placenta: alteration in intrauterine growth retardation and preeclampsia.

OBJECTIVE: Our purpose was to quantify fetoplacental vascular atrial natriuretic peptide receptor subtypes in human pregnancies complicated by intrauterine growth retardation or preeclampsia and to relate these parameters to the fetoplacental vascular impedance as assessed by Doppler velocimetry. STUDY DESIGN: Guanylate cyclase-coupled and uncoupled receptors were quantified by radioligand-binding methods in membrane fractions prepared from primary and secondary stem villous vessels. Data for 16 abnormal pregnancies delivered preterm were compared with that for six gestationally matched preterm controls. RESULTS: The number of guanylate cyclase-coupled receptors was significantly (p < 0.001) greater in pregnancies complicated by intrauterine growth retardation or preeclampsia irrespective of normal or abnormal umbilical artery Doppler blood flow velocity pattern. The number of guanylate cyclase-uncoupled receptors was unaltered. CONCLUSIONS: Because fetal plasma atrial natriuretic peptide concentration is normal or elevated in intrauterine growth retardation and preeclampsia, these data suggest that atrial natriuretic peptide-mediated fetoplacental vasodilation is augmented in these disorders even in the presence of increased vascular resistance within the fetoplacental unit.

Atrial Natriuretic Factor↗

Renal and hormonal effects of chronic inhibition of neutral endopeptidase (EC 3.4.24.11) in normal man.

1. Acute pharmacological inhibition of the enzyme neutral endopeptidase (EC 3.4.24.11), which cleaves the cardiac hormone atrial natriuretic peptide, raises endogenous levels of the hormone. Short-term administration of inhibitors causes natriuresis and diuresis in normal and hypertensive subjects; we report here the effects of an orally active neutral endopeptidase inhibitor (candoxatril, 200 mg) given twice daily for 10 days to normal salt-replete male subjects (n = 12) in a placebo-controlled cross-over study. 2. Candoxatril administration caused a transient natriuresis on day 1 of treatment, but this was not sustained, and cumulative sodium excretion at the end of the study was not altered by active therapy [1720 +/- 40 versus 1734 +/- 57 (placebo) mmol; means +/- SEM]; exchangeable body sodium content was similarly unchanged. However, urinary cyclic GMP excretion was elevated throughout the active treatment phase when compared with placebo. 3. Although a change in plasma levels of atrial natriuretic peptide could not be demonstrated, platelet atrial natriuretic peptide binding sites were reduced by active treatment [23 +/- 3 versus 39 +/- 4 (placebo) fmol/10(9); P < 0.001]. 4. Basal blood pressure and heart rate were not affected by candoxatril treatment. After 10 days of therapy subjects were given incremental infusions of angiotensin II (2, 4 and 8 ng min-1 kg-1) followed by phenylephrine. Although active therapy had not altered basal plasma concentrations of active renin and angiotensin II, levels of angiotensin II during infusion of the octapeptide were higher during the active phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Fetal angiotensin II levels and vascular (type I) angiotensin receptors in pregnancies complicated by intrauterine growth retardation.

OBJECTIVE: To investigate the status of the fetal renin-angiotensin system (RAS) in pregnancies complicated by severe intrauterine growth retardation (IUGR), and its possible relationship to elevated fetoplacental vascular resistance as indicated by abnormal umbilical artery Doppler flow velocity waveforms (FVW). DESIGN: Prospective survey of pregnancies falling into predefined categories and presenting at the Queen Mothers Hospital, Glasgow, over the study period. SUBJECTS: Effects of mode of delivery and gestational age were investigated using uncomplicated term pregnancies delivered vaginally (SVD group, n = 15) or by elective caesarean section (ECS group, n = 9), and normal pregnancies with spontaneous preterm onset of labour (PREM group, n = 6; normal birthweight for gestational age (31 weeks)). These groups were used as controls for the 13 IUGR cases delivered preterm (31 weeks) by caesarean section in the fetal interest. MAIN OUTCOMES MEASURES: Umbilical artery FVW, birthweight, cord venous angiotensin II concentration ([cv ANG II]), fetoplacental vascular ANG II receptor concentration. RESULTS: Cord venous angiotensin II concentration was similar to maternal values in the ECS group (31-101 pmol/l, 95% CI), but was elevated (81-288 pmol/l, P = 0.03) after vaginal delivery. The concentration of ANG II receptors (type AT1, dissociation equilibrium constant, 1.27 nmol/l) in placental primary/secondary stem vascular tissue was lower in the SVD group (18-44 fmol/mg membrane protein, 95% CI), compared with the ECS group (29-122 fmol/mg, P = 0.03) consistent with acute receptor down-regulation by the elevated ANG II levels. No effect of gestational age on receptor number was demonstrable (P = 0.13, PREM (premature delivery) vs ECS group). In the IUGR group, [cv ANG II] (94-378 pmol/l) was markedly elevated compared with the ECS controls (P = 0.001) but receptor concentration (28-84 fmol/mg) was not significantly altered (P = 0.13). No relationships between [cv ANG II] or receptor number and umbilical artery FVW could be identified. No changes in receptor affinity were observed. CONCLUSION: These results indicate activation of the fetal RAS in IUGR and suggest that responsiveness of the fetoplacental vasculature to the peptide is not diminished as would be expected from the elevated plasma ANG II levels. ANG II may contribute to the increased fetoplacental vascular resistance observed in this disorder, but does not apparently account for the abnormal umbilical artery FVW that is observed in a proportion of IUGR cases.

Angiotensin II↗

Characterization of atrial natriuretic peptide receptors in human fetoplacental vasculature.

Two classes of high-affinity binding sites for atrial natriuretic peptide (ANP) were identified in a microsomal fraction from human placental artery using radioligand binding methods and des[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4-2 3) (C-ANP), a partially ring-deleted analogue of ANP, consistent with the presence of ANP-A and ANP-C receptor subtypes in this tissue [dissociation equilibrium constant (Kd) 58 pM, maximum binding capacity (Bmax) 14 fmol/mg membrane protein, and Kd 82 pM, Bmax 28 fmol/mg, respectively]. ANP activated a guanylate cyclase present in a particulate fraction from placental vascular tissue with half-maximal response at 104 pM and a maximal rate of guanosine 3',5'-cyclic monophosphate production of 62 pmol.min-1 x mg protein-1. Human brain natriuretic peptide was 10-fold less effective than ANP in stimulating guanylate cyclase activity, indicating the absence of the ANP-B receptor subtype. C-ANP had no effect on basal or ANP-stimulated enzyme activity. This report demonstrates the presence of functional (guanylate cyclase-coupled) receptors for ANP in the human fetoplacental vasculature, suggesting that ANP may have a role in the regulation of fetoplacental hemodynamics.

5'-Nucleotidase↗

Overcoming the barriers to implementing patient-focused care.

Potential barriers to implementing PFC sometimes seem enormous. Instead of orienting toward problems associated with implementing PFC, we can eliminate some of the barriers simply by focusing on and pursuing the ideal, "the seamless patient care experience." Fundamentally improving our health care delivery systems is not really a strategic option. It is our responsibility. We must do things better, faster, with more compassion, and at less cost. What evidence will demonstrate that your organization is becoming more patient-focused? Patients will not be inconvenienced because of "how the system works." They will consider your organization "best in class." They will know that the hospital's medical care and services will meet or exceed their expectations. Physicians and staff will feel more highly valued by the organization. Management empowers them by improving the systems they must use, providing ongoing training, and decentralizing the authority they need to deliver excellent medical care and satisfy patients' personal needs. Communication improves vertically and horizontally throughout the organization. The hospital becomes increasingly attractive to employers and HMOs. Reengineered processes result in increases in productivity. Better patient outcomes, at less cost, can be demonstrated. Occupancy rates stabilize or grow, utilization is carefully managed, and improvements in the bottom line strengthen the organization. How do we make these visions a reality? By committing to PFC and getting started right away. Just as "quality" is multidimensional, so must be our operating strategy. Patient-focused care is the model that will redefine the future of health care.

Continuity of Patient Care↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗