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L M Burrell

Publications and source records attributed to L M Burrell.

72 records · Page 4Linked to original sources
PubMed1994

Inhibitory effects of HIV-1-infected stromal cell layers on the production of myeloid progenitor cells in human long-term bone marrow cultures.

This report presents the results of studies using long-term bone marrow cultures (LTBMC) of human bone marrow cells to investigate the effect of HIV-1 on in vitro hematopoiesis. Confluent stromal cell layers established from human bone marrow cells were irradiated to eliminate residual hematopoietic progenitor cells and exposed to HIV-1ADA or to HIV-1IIIB, monocytotropic and lymphocytotropic strains of HIV-1, respectively. A productive infection did not develop in cultures exposed to HIV-1IIIB but did for cultures exposed to HIV-1ADA as there was a progressive increase in HIV-1 p24 antigen. Stromal cell layers infected with HIV-1ADA were also cocultured with autologous CD34+ bone marrow cells. Four days, 1, 2, and 3 weeks later, the number of colony-forming units granulocyte/macrophage (CFU-GM) in non- and HIV-infected LTBMC was determined. The number of CFU-GM increased during the first week in both non- and HIV-infected LTBMC. One week after the coculture of CD34+ cells with stromal cell layers infected with HIV-1ADA, the number of CFU-GM in six out of eight experiments was reduced compared to noninfected control LTBMC. In those six experiments, the number of CFU-GM was 53 +/- 6% standard error of the mean (SEM) of the number in noninfected LTBMC. A reduced number of CFU-GM was observed in the nonadherent fraction of HIV-infected LTBMC for at least 2 weeks. These results demonstrate that some cells in the stromal cell layers of LTBMC were targets for HIV-1 and that HIV-infected stromal cell layers suppressed or delayed the production of CFU-GM.

Antigens, CD↗
PubMed1993

Effects of an orally active vasopressin V1 receptor antagonist.

1. This paper reports on the in vitro and in vivo characteristics of a non-peptide vasopressin V1 receptor antagonist 1-(1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl)-3,4-dihydro-2( 1H)- quinolinone (OPC-21268). 2. OPC-21268 caused a concentration-dependent displacement of the selective V1 receptor antagonist radioligand, [125I]-[d(CH2)5, sarcosine7]AVP from vasopressin V1 receptors in rat liver and kidney membranes, inhibitory concentration of 50% (IC50) 4 x 10(-8), 0.3 mol/L liver and 1.5 x 10(-8), 0.2 mol/L kidney. OPC-21268 had little effect on the selective V2 antagonist radioligand [3H]desGly-NH2(9)-d(CH2)5[D-Ileu2, Ileu4]AVP binding to V2 receptors in renal membranes (IC50 > 10(-4) mol/L). 3. After oral administration to rats, OPC-21268 was an effective V1 antagonist to both liver and kidney V1 receptors, in a dose-dependent manner. 4. These studies confirm that OPC-21268 is a potent non-peptide, orally effective V1 vasopressin receptor antagonist.

Administration, Oral↗
PubMed1993

Characterization of a novel non-peptide vasopressin V1 receptor antagonist (OPC-21268) in the rat.

A non-peptide, orally effective, vasopressin (AVP) V1 receptor antagonist 1-(1-[4-(3-acetylaminopropoxy) benzoyl]-4-piperidyl)-3,4-dihydro-2(1H)-quinolinone (OPC-21268) has recently been described. This paper reports the in-vitro and in-vivo characterization of OPC-21268 binding to vasopressin receptors in rat liver and kidney. OPC-21268 caused a concentration-dependent displacement of the selective V1 receptor antagonist radioligand, 125I-labelled [d(CH2)5,sarcosine7]AVP to V1 receptors in both rat liver and kidney medulla membranes. The concentration of OPC-21268 that displaced 50% of specific AVP binding (IC50) was 40 +/- 3 nmol/l for liver V1 and 15 +/- 2 nmol/l for kidney V1 receptors (mean +/- S.E.M.; n = 3). OPC-21268 had little effect on the selective V2 antagonist radioligand [3H]desGly-NH2(9)]d(CH2)5,D-Ile2,Ile4] AVP binding to V2 receptors in renal medulla membranes (IC50 > 0.1 mmol/l). After oral administration to rats, OPC-21268 was an effective V1 antagonist in a time- and dose-dependent manner. Binding kinetic studies showed that OPC-21268 acted as a competitive antagonist at the liver V1 receptor in vitro and in vivo, in addition to its in-vitro competitive effects at the renal V1 receptor. OPC-21268 shows promise as an orally active V1 antagonist.

Animals↗
PubMed1993

Blockade of the renin-angiotensin system at different sites: effect on renin, angiotensin and aldosterone.

INHIBITION OF RENIN-ANGIOTENSIN SYSTEM: It is now possible to effectively block the renin-angiotensin system at several steps by orally active inhibitors. Blockade of renin, the angiotensin coverting enzyme (ACE) or the angiotensin II (Ang II) type 1 (AT1) receptor leads to different hormonal changes. All three modes of blockade reduce aldosterone and all cause a reactive rise in plasma renin due to removal of angiotensin II tonic inhibition on renal renin release. ASSOCIATED CHANGES IN ANG I AND ANG II: AT1 blockade by losartan is followed by rises in plasma Ang I and Ang II; ACE inhibitors are associated with an increase in plasma Ang I but a fall in Ang II, whereas both plasma Ang I and Ang II fall with renin inhibition. DIFFERENCES IN MODE OF INHIBITION: Potential differences between the mode of blockade of the renin-angiotensin system include differences in the bioavailability of compounds, the effect of ACE on other peptide substrates, particularly bradykinin, the possibility of other actions or unknown substrates for renin and the presence of unblocked AT2 angiotensin receptors in the presence of high levels of Ang II. Whether these will result in clinically important differences remains to be determined.

Angiotensin II↗
PubMed1993

Angiotensin converting enzyme inhibitors in perspective: an update.

Orally active inhibitors of angiotensin converting enzyme (ACE) have made a major impact on the clinical therapy of hypertension, congestive cardiac failure and ventricular remodelling after myocardial infarction. The ACE inhibitors combine the advantages of efficacy and low incidence of side effects, with the promise of cardio-, vasculo- and reno- protection.

Age Factors↗
PubMed1992

Atrial natriuretic peptide inhibits fluid intake in hyperosmolar subjects.

1. The effect of atrial natriuretic peptide on osmotically stimulated thirst appreciation and consequent fluid intake was investigated in healthy man. 2. Six seated male subjects were studied on two occasions: synthetic alpha-human atrial natriuretic peptide (99-126) (2 pmol min-1 kg-1) or placebo (saline, 150 mmol/l NaCl) was infused intravenously for 105 min; 30 min after the start of atrial natriuretic peptide/placebo infusion, hypertonic saline (855 mmol/l NaCl) was infused (0.06 ml min-1 kg-1) for 60 min. Subjects were then allowed free access to water for the next 2 h; infusion of atrial natriuretic peptide/placebo continued for the first 15 min of the drinking period. 3. The plasma atrial natriuretic peptide concentration did not alter significantly during infusion of hypertonic saline and placebo; it rose to a steady state of 12.7 +/- 1.1 pmol/l (mean +/- SEM) during the infusion of atrial natriuretic peptide and hypertonic saline, and remained at this level during the first 15 min of the drinking period. During infusion of hypertonic saline and atrial natriuretic peptide or placebo, similar increases in plasma osmolality (P less than 0.001) and plasma vasopressin concentration (P less than 0.005) occurred. During infusion of hypertonic saline and atrial natriuretic peptide or placebo, thirst increased significantly over the time course of both studies (P less than 0.01), but the effect of atrial natriuretic peptide infusion compared with placebo infusion was to significantly decrease thirst at 60 min. 4. Drinking rapidly abolished thirst and vasopressin secretion before changes in plasma osmolality occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The tissue renin-angiotensin system and its functional role.

1. The components of the renin-angiotensin system exist in many cardiovascular tissues (heart vessels, kidneys, adrenal glands). 2. Angiotensin-converting enzyme (ACE) is similar in somatic cells from all these sites. 3. ACE contains two catalytic sites that have different conformation requirements. This suggests that each site may have different substrates and that specific inhibitors could be developed for each site. 4. The cardiovascular functions of tissue ACE may include the regulation of regional blood flow, modulation of local sympathetic activity, stimulation of hyperplasia and hypertrophy and the mediation of inflammation.

Animals↗
PubMed1991

Osmoregulation of thirst and vasopressin release in severe chronic renal failure.

Subjects with severe chronic renal failure (CRF) have higher plasma concentrations of arginine vasopressin (AVP) than normal subjects, and some develop severe thirst. Eight patients with CRF and seven matched controls underwent hypertonic saline infusion to explore the relationship of thirst and plasma AVP with plasma osmolality. Differences in urea concentration between the two groups were controlled for by correcting measured osmolality to a urea of zero. Linear regression analysis of the relationships between plasma AVP and thirst with plasma osmolality (corrected for urea) was performed. Mean results were: control, pAVP = 0.26 (pOsmc - 283.7) versus CRF, pAVP = 0.72 (pOsmc - 282.0); and control, thirst = 4.0 (pOsmc - 279.4) versus CRF, thirst = 3.5 (pOsmc - 281.8). The apparent sensitivity (slope) of AVP release was greater in severe CRF than in normal controls (P = 0.04). There was no significant difference between the groups in thirst sensitivity, threshold for thirst onset and threshold for AVP release. Osmoregulated thirst was normal in severe CRF, but increasing osmolality leads to higher concentrations of AVP than would be expected.

Adult↗
PubMed1991

The effect of drinking on atrial natriuretic peptide, vasopressin and thirst appreciation in hyperosmolar man.

OBJECTIVES: To assess whether drinking and oropharyngeal stimuli mediate the release of plasma atrial natriuretic peptide (ANP) in man. DESIGN: Hypertonic saline was infused into male volunteers to stimulate thirst. In order to avoid any effect of volume change on ANP release, the studies were performed with the subject in the seated position. SUBJECTS: Seated normal male volunteers (n = 6) were infused with hypertonic saline at a rate of 0.06 ml/kg/min for 90 min on two separate occasions. After a 15-min equilibrium period, subjects were allowed to drink for the following 45-min period on one occasion, but no drinking was permitted on the other occasion. MEASUREMENTS: Aliquots of blood were withdrawn at 30-min intervals for 90 min during hypertonic saline infusion, and +3, 6, 9, 12, 15, 30 and 45 min during the drinking/control period for the measurement of plasma ANP, plasma vasopressin, plasma osmolality, serum sodium and haematocrit; thirst was assessed at the same time points using a visual analogue scale. Blood pressure was measured at 15-min intervals. RESULTS: Hypertonic saline infusion induces increases in plasma vasopressin, plasma osmolality, serum sodium and thirst appreciation (P less than 0.005), and blood volume (P less than 0.05) on both study days; there was no increase in plasma ANP during hypertonic saline infusion. During the drinking period there was the expected decrease in plasma vasopressin (P less than 0.01), plasma osmolality (P less than 0.05), serum sodium (P less than 0.05) and thirst appreciation (P less than 0.01); no significant changes occurred in plasma atrial natriuretic peptide, mean arterial blood pressure or haematocrit during either the drinking or the control period. CONCLUSIONS: The drinking-mediated inhibition of thirst appreciation and plasma vasopressin is not associated with any change in plasma ANP concentrations; it does not appear that oropharyngeal stimuli contribute to the release of ANP in man.

Adult↗
PubMed1991

Effect of atrial natriuretic peptide on thirst and arginine vasopressin release in humans.

We investigated the effect of human alpha-atrial natriuretic peptide (alpha-hANP) on osmotically stimulated arginine vasopressin (AVP) secretion and thirst appreciation. Seven normal male volunteers were studied on two occasions: synthetic alpha-hANP-(99-126) (2 pmol.kg-1.min-1) or control was infused intravenously for 30 min before and for the first 60 min of a 120-min hypertonic saline (855 mmol/l) infusion (0.06 ml.kg-1.min-1). Plasma ANP did not alter significantly during infusion of control and hypertonic saline (C+HS) but rose to steady-state concentrations of 17.4 +/- 3.2 pmol/l during infusion of ANP and hypertonic saline (ANP+HS). Plasma osmolality increased on both study days [ANP+HS: 284.4 +/- 0.6 to 299.7 +/- 1.1 mosmol/kgH2O (P less than 0.01)], C+HS: 283.6 +/- 1.2 to 299.1 +/- 1.6 mosmol/kgH2O (P less than 0.01)], as did plasma sodium [ANP+HS: 139.0 +/- 0.6 to 148.0 +/- 0.4 mmol/l (P less than 0.01), C+HS: 137.6 +/- 0.75 to 145.8 +/- 0.7 mmol/l (P less than 0.01)] and blood volume (ANP+HS: 7.7 +/- 0.6%, C+HS: 9.4 +/- 1.0%). The increase in plasma osmolality was accompanied by an increase in plasma AVP [ANP+HS: 1.4 +/- 0.3 to 8.3 +/- 1.2 pmol/l (P less than 0.01), C+HS: 1.6 +/- 0.4 to 7.8 +/- 1.5 pmol/l (P less than 0.01)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Is the fluorescein dilaurate test suitable for monitoring the effectiveness of pancreatic enzyme replacement therapy?

We have employed an oral test of pancreatic digestive function using fluorescein dilaurate (a substrate for pancreatic cholesterol ester hydrolase), administered together with pancreatic enzyme supplements, in order to test the hypothesis that urinary excretion of fluorescein provides a simple method for determining the optimal dose of oral pancreatic enzymes. Commercially available pancreatic enzyme supplements had negligible cholesterol hydrolase activity in vitro, and did not increase the urinary excretion of fluorescein when administered together with fluorescein dilaurate in 16 patients with pancreatic exocrine insufficiency. Inhibition of gastric secretion by ranitidine resulted in a statistically significant increase in urinary fluorescein excretion during the fluorescein dilaurate test. The fluorescein dilaurate test is not, therefore, suitable for determining the effectiveness of oral pancreatic enzyme replacement therapy. Moreover, the manufacturer's advice to stop oral pancreatic enzyme therapy for 5 days before performing the fluorescein dilaurate test appears unnecessary, since oral pancreatic enzymes do not alter test results.

Amylases↗
PubMed1990

A new radioimmunoassay for human alpha atrial natriuretic peptide and its physiological validation.

A new sensitive, specific radioimmunoassay for human alpha atrial natriuretic peptide (hANP) and a novel extraction method for hANP have been developed. Antiserum to hANP (Keq = 1.923 x 10(11) l/mol) showed no cross-reactivity with related analogues. Displacement of 50% bound 125I-hANP occurred at 4.7 +/- 0.1 fmol/tube (n = 15). The limit of detection of plasma hANP after extraction of 2 ml plasma with Florisil was 1.2 pmol hANP/litre plasma. The recovery of synthetic hANP from plasma over the range 6.5-162.5 pmol/l was 71.2 +/- 1.9%. Inter- and intra-assay coefficients of variation were 13.1% and 10.1% respectively. Extracted plasma was stored at -80 degrees C without loss in immunoreactivity. The radioimmunoassay was physiologically validated in man by measuring plasma hANP following central volume expansion - (a) plasma hANP rose from 2.5 +/- 0.5 to 4.1 +/- 0.6 pmol/l in 9 normal volunteers after postural change from seated to lying (b) infusion of normal saline (2 litre/2 hour) increased hANP from 1.6 to 4.3 pmol/l (n = 2). Infusion of hANP (2 pmol/kg/min) increased plasma hANP to 19.9 +/- 3.4 pmol/l (n = 6).

Animals↗
PubMed1990

Release of atrial natriuretic peptide during hypertonic saline infusion: the importance of posture.

It is well known that atrial distension is an important stimulus for atrial natriuretic peptide (ANP) release, but conflicting evidence exists as to whether hyperosmolality also stimulates the release of atrial natriuretic peptide (ANP) in man. As infusion of hypertonic saline causes an increase in both blood volume and plasma osmolality, we have employed this stimulus to investigate: (i) whether hyperosmolality increases plasma ANP concentrations; (ii) the importance of posture in ANP release. Normal male volunteers (n = 6) were infused with hypertonic saline at a rate of 0.06 ml/kg/min for 2 h on two different occasions separated by 1 month. Infusion was performed with subjects in the seated and supine positions in random order. Hypertonic saline infusion induced increases in plasma osmolality (P less than 0.001), plasma sodium (P less than 0.01) and blood volume (P less than 0.001) in both seated and supine position. The increase in plasma osmolality was accompanied by an increase in plasma ANP during the supine infusion (2.7 +/- 1.0 to 9.0 +/- 2.4 pmol/l (mean +/- SEM; P less than 0.01] but no significant change in plasma ANP concentration occurred during the seated infusion. A positive linear correlation was obtained between increase in plasma osmolality and plasma ANP in the supine but not in the seated hypertonic saline infusion. There was a positive linear correlation between estimated increase in blood volume and plasma ANP in the supine but not the seated infusion of hypertonic saline. We suggest that the increase in ANP during hypertonic saline infusion reported by some workers was due to atrial distension, secondary to increased blood volume and is dependent on the position in which the subjects were studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Small cell lung cancer: staging with MR imaging.

Small cell lung cancer is an aggressive neoplasm; metastases are detected in two-thirds of patients at diagnosis with use of conventional staging, which includes bilateral bone marrow biopsy, bone scintigraphy, and computed tomography (CT) of the head and abdomen. In 25 patients, small cell lung cancer was staged prospectively with both conventional staging and a magnetic resonance (MR) imaging protocol that included 1.5-T MR imaging of the pelvis, abdomen, spine, and brain. According to conventional staging, 14 patients had extensive disease and 11 patients had limited disease; according to staging with MR, 19 patients had extensive disease and six had limited disease. All metastatic disease sites seen with conventional staging were identified on MR images. MR images showed additional metastatic involvement in bone (four patients) and liver (three patients) not detected at conventional staging. A low-attenuation hepatic lesion on a CT scan was identified as a hemangioma on MR images. These preliminary data suggest that small cell lung cancer may be accurately staged with use of a single MR imaging study.

Adrenal Glands↗
PubMedDate not supplied

Validation of an echocardiographic assessment of cardiac function following moderate size myocardial infarction in the rat.

1. The present study determined whether two dimensional guided M-mode echocardiography could assess left ventricular (LV) geometry and function following a moderate size myocardial infarction in the rat. 2. Myocardial infarction (MI) was induced by left coronary artery ligation and rats were studied 4 weeks later. Infarct rats showed increased LV internal diastolic diameter (7.33 +/- 0.8 vs 5.91 +/- 0.6 mm; P < 0.001), LV systolic diameter (3.73 +/- 1.2 vs 1.87 +/- 0.6 mm; P < 0.001) and thickening of the noninfarcted posterior wall compared with sham operated rats (1.81 +/- 0.2 vs 1.47 +/- 0.3; P < 0.001; n = 10/group; mean +/- s.d.). Systolic function was impaired in infarct rats who showed reduced fractional shortening (50 +/- 12 vs 68 +/- 9%; P < 0.001) and fractional area change (41 +/- 14 vs 78 +/- 5%; P < 0.001). Infarct size measured echocardiographically was comparable to that measured by quantitative histological examination (29 +/- 10 vs 28 +/- 5%; NS). 3. The present study indicates that postinfarction remodelling leading to LV cavity dilation, hypertrophy of surviving myocardium and impaired systolic function is apparent 4 weeks following moderate size MI in the rat. 4. Transthoracic echocardiography is a noninvasive technique that may be used to assess serially the efficacy of therapeutic interventions designed to prevent remodelling in moderate size MI in the rat.

Animals↗
PubMedDate not supplied

Chronic vasopressin antagonism in two-kidney, one-clip renovascular hypertension.

The role of vasopressin (AVP) in the maintenance of hypertension in the rat model of two-kidney, one-clip (2K1C) Goldblatt hypertension was assessed using the nonpeptide orally effective V1a receptor antagonist, OPC-21268. Rats were studied eight weeks after surgery when mean arterial pressure (MAP) was significantly increased in 2K1C rats compared to SHAM operated controls (2K1C 139 +/- 6, SHAM 106 +/- 3, P < 0.01). Neither acute (OPC-21268, 30 mg/kg) nor chronic (OPC-21268, 30 mg/kg twice daily) V1a receptor blockade reduced blood pressure in either 2K1C or SHAM rats. The results of binding kinetic studies confirmed that OPC-21268 was effective at its putative site of action, the V1a receptor in both 2K1C and SHAM rats. These results indicate AVP is not involved in the maintenance of blood pressure in the 2K1C model of renovascular hypertension.

Animals↗