Search PubMed⌕ Search

Biomedical subjects

H Boyd

Publications and source records attributed to H Boyd.

At least 19 recordsLinked to original sources
PubMed2001

Urinary cytokines for assessing inflammation in HIV-associated wasting.

The relationship between cytokines and HIV-related weight loss has not been well established. Unlike most cytokines that are secreted in a paracrine manner, IL-6, sTNFR-II, and IL-1ra are readily detected in the systemic circulation and serve as markers of the inflammatory response. Twenty-four-hour urine concentrations of these proteins are believed to provide an integrative assessment of their systemic levels over the preceding hours. We sought to determine whether spot measurements of IL-6, sTNFR-II, and IL-1ra could be related to subsequent 24 h concentrations and prior weight loss. Eighteen subjects with severe wasting (average BMI=18+/-3 kg/m2with 19+/-13 kg of weight loss) and six HIV-negative healthy subjects were tested. Compared to values in controls, 24-h urinary concentrations of the three proteins adjusted for creatinine excreted were elevated in 44%, 89%, and 72% of patients, respectively. Twenty-four-hour concentrations were highly correlated with the spot concentrations (r=0.80, 0.87, 0.84, respectively, P<0.001). IL-1ra concentrations (24 h and spot) were correlated with weight loss in the previous 6 months, lifetime rate of weight loss and the 6 month rate of weight loss (spot: r=0.66, 0.73, 0.68, respectively, P< or =0.001). These data suggest that spot urinary collections can be used to estimate 24 h excretion rates. This strategy may be useful in assessing the inflammatory response in HIV-associated wasting.

Adult↗
PubMed2000

SB-253514 and analogues; novel inhibitors of lipoprotein-associated phospholipase A2 produced by Pseudomonas fluorescens DSM 11579. I. Fermentation of producing strain, isolation and biological activity.

Two new classes of inhibitors of LpPLA2 have been identified in fermentations of Pseudomonas fluorescens. The two structurally isomeric series differ in the geometry of closure of the bicyclic carbamate and comprise a range of compounds varying only in length of their lipophilic sidechain. The most abundant species were extracted from the cells and purified by silica and C18 chromatography. Members of the more stable class were shown to be potent and selective competitive inhibitors of LpPLA2.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1999

Transmural myocardial blood flow distribution in hypertrophic cardiomyopathy and effect of treatment.

Verapamil alleviates symptoms in patients with hypertrophic cardiomyopathy (HCM), but the underlying mechanism of improvement remains speculative. Baseline and dipyridamole myocardial blood flow (MBF) were measured in 15 HCM patients (14 men, 42 +/- 10 years), before and after 4 weeks of verapamil SR 480 mg daily, using 15O labelled water the positron emission tomography (PET). Subendocardial (endo) and subepicardial (epi) MBF was measured in the septum (thickness 25.4 +/- 5.8 mm). Pre-treatment baseline whole heart MBF was 1.02 +/- 0.28 ml/min/g and 1.01 +/- 0.30 ml/min/g on treatment (p = ns). Dipyridamole MBF was 1.39 +/- 0.31 ml/min/g off treatment and 1.23 +/- 0.34 ml/min/g on treatment (p = ns). Coronary flow reserve (dipyridamole/resting MBF) was 1.45 +/- 0.52 and 1.30 +/- 0.51, respectively (p = ns). At baseline, the septal endo/epi MBF ratio was uniform off and on treatment (1.13 +/- 0.18 vs 1.18 +/- 0.21, p = ns). Before treatment, the endo/epi ratio following dipyridamole decreased to 0.93 +/- 0.24 (p < 0.01 vs baseline) and 5/15 (33%) patients had a ratio < 0.8 which would suggest subendocardial underperfusion. During treatment, the endo/epi ratio following dipyridamole was no more different from baseline (1.06 +/- 0.24, p = ns vs baseline) and 2/14 (14%) patients had an endo/epi < 0.8. PET can be successfully used to determine transmural MBF in vivo in patients with hypertrophied ventricles. Despite symptomatic improvement, high dose verapamil therapy does not increase total MBF in patients with HCM but may improve septal transmural MBF distribution during dipyridamole in some patients.

Adult↗
PubMed1999

A report system for PET assessment of myocardial viability.

Coronary bypass surgery can improve the prognosis of patients with heart failure due to coronary artery disease. However, these patients have a high operative risk and should be operated on only if they have a sizeable amount of viable tissue (i.e. asynergic myocardium) that can recover contractile function following coronary revascularization. In the clinical setting, regional wall motion is usually evaluated by two-dimensional echocardiography, whereas retained metabolic activity assessed by positron emission tomography (PET) and 18F-fluorodeoxyglucose is a well-established means for the evaluation of myocardial viability. Unfortunately, the two-dimensional echocardiography and PET reports are often different, and this renders the matching of information difficult and the estimation of the risk-benefit ratio of the operation unreliable. In this paper, we present a report system for the evaluation of myocardial viability with PET. We divided the left ventricle into 16 segments following the proposal of the American Society of Echocardiography for wall motion analysis by two-dimensional echocardiography. Following this partition, three portions of the left ventricle are identified along the long axis: basal, mid and apical. Each plane of the basal and mid portions is automatically divided into six segments with the super-imposition of a radial divider over the short-axis images. Similarly, each plane of the apical portion is automatically divided, but into four segments. This partition of the left ventricle permits a precise match between the information on wall motion obtained with two-dimensional echocardiography and that on viability obtained with PET.

Coronary Artery Bypass↗
PubMed1998

ATP-Citrate lyase as a target for hypolipidemic intervention. 2. Synthesis and evaluation of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids and their gamma-lactone prodrugs as inhibitors of the enzyme in vitro and in vivo.

A series of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids have been synthesized and evaluated as inhibitors of the recombinant human form of ATP-citrate lyase. The best of these have Ki's in the 200-1000 nM range. As the corresponding thermodynamically favored gamma-lactone prodrugs, a number of compounds are able to inhibit cholesterol and fatty acid synthesis in HepG2 cells and reduce plasma triglyceride levels in vivo. The best of these, compound 77, is able to induce clear hypocholesterolemic and hypotriglyceridaemic responses when administered orally to rat and dog. These results provide evidence to support the hypothesis that compounds which inhibit ATP-citrate lyase have the potential to be a novel class of hypolipidemic agent, which possess combined hypocholesterolemic and hypotriglyceridemic activities.

ATP Citrate (pro-S)-Lyase↗
PubMed1998

The role of ATP citrate-lyase in the metabolic regulation of plasma lipids. Hypolipidaemic effects of SB-204990, a lactone prodrug of the potent ATP citrate-lyase inhibitor SB-201076.

ATP citrate (pro-S)-lyase (EC 4.1.3.8), a cytosolic enzyme that generates acetyl-CoA for cholesterol and fatty acid synthesis de novo, is a potential target for hypolipidaemic intervention. Here we describe the biological effects of the inhibition of ATP citrate-lyase on lipid metabolism in Hep G2 cells, and plasma lipids in rats and dogs, by using SB-204990, the cell-penetrant gamma-lactone prodrug of the potent ATP citrate-lyase inhibitor SB-201076 (Ki=1 microM). Consistent with an important role of ATP citrate-lyase in the supply of acetyl-CoA units for lipid synthesis de novo, SB-204990 inhibited cholesterol synthesis and fatty acid synthesis in Hep G2 cells (dose-related inhibition of up to 91% and 82% respectively) and rats (76% and 39% respectively). SB-204990, when administered orally to rats, was absorbed into the systemic circulation; pharmacologically relevant concentrations of SB-201076 were recovered in the liver. When administered in the diet (0.05-0. 25%, w/w) for 1 week, SB-204990 caused a dose-related decrease in plasma cholesterol (by up to 46%) and triglyceride levels (by up to 80%) in rats. This hypolipidaemic effect could be explained, at least in part, by a decrease (up to 48%) in hepatic very-low-density lipoprotein (VLDL) production as measured by the accumulation of VLDL in plasma after injection of Triton WR-1339. SB-204990 (25 mg/kg per day) also decreased plasma cholesterol levels (by up to 23%) and triglyceride levels (by up to 38%) in the dog, preferentially decreasing low-density lipoprotein compared with high-density lipoprotein cholesterol levels. Overall these results are consistent with the concept that ATP citrate-lyase is an important enzyme in controlling substrate supply for lipid synthesis de novo and a potential enzyme target for hypolipidaemic intervention.

ATP Citrate (pro-S)-Lyase↗
PubMed1996

Myocardial beta-adrenoceptor density and plasma catecholamines in syndrome X.

Recent research has cast doubt on the ischemic hypothesis of etiology of syndrome X (anginal pain, ischemic-like changes in the stress electrocardiogram, but normal coronary arteriogram). Abnormalities of pain perception have been shown and abnormal sympathetic nervous system activation has also been implicated. The aim of this study was to test the hypothesis that downregulation of myocardial beta adrenoceptors is demonstrable in patients with syndrome X. Such downregulation would be consistent with raised myocardial catecholamine concentrations. We performed positron emission tomography with (11)C-CGP-12177 to measure beta-adrenoceptor density. Plasma catecholamines were sampled simultaneously and assayed using high-performance liquid chromatography. Twenty syndrome X patients (11 female, age 57 +/- 9 SD years, range 33 to 69) and 18 matched controls (9 women, age 50 +/- 13 years, range 25 to 65; p = NS vs patients) were studied. Myocardial beta-adrenoceptor density did not differ between syndrome X patients and controls: 8.0 (1.9) pmol/g for patients versus 8.3 (2.1) pmol/g for controls; p = 0.62. No differences were found between patients and controls for plasma norepinephrine (2.82 [1.07] and 2.76 [1.18] nM, respectively; p = 0.89) or for epinephrine (0.29 [0.14] and 0.30 [0.20] nM, respectively; p = 0.84). In patients with syndrome X, beta-adrenoceptor density is normal and, by inference, myocardial catecholamines would also be normal. This weakens the case for a generalized enhancement of sympathetic activation in this disorder, although increased sympathetic reactivity during actual episodes of chest pain remains a possibility.

Adrenergic beta-Antagonists↗
PubMed1996

Health-related quality of life of adults surviving malignancies in childhood.

While sophisticated data on specific problems are available, very little is known about the overall quality of life of long-term survivors of malignancies in childhood. We used a previously validated 15-dimensional questionnaire to examine the perceived health-related quality of life of 168 survivors, currently aged 16-35 years, who had been treated for a malignancy at a single institution between 1961 and 1993. All had been off therapy for at least 1 year (median, 12 years). In statistical terms, the quality of life score of the survivors was significantly better than that of 129 normal controls [0.966 versus 0.941 (theoretical maximum 1), respectively; P < 0.001]; however, a difference of this magnitude is most likely not clinically significant. There were no associations between original diagnosis and present quality of life, but the numbers in each diagnostic group were small. The survivors reported significantly better levels of vitality, distress, depression, discomfort, elimination and sleeping dimensions than the controls. Although we are presently not able to identify all the contributing factors, we speculate that the high perceived quality of life of long-term survivors of childhood malignancies is at least in part a consequence of denial mechanisms which compensate or even overcompensate the objectively measurable late effects of childhood cancer.

Adolescent↗
PubMed1996

Characterization of pituitary adenylate cyclase-activating polypeptide 38 (PACAP38)-, PACAP27-, and vasoactive intestinal peptide-stimulated responses in N1E-115 neuroblastoma cells.

In this study, the effects of three related peptides, pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), PACAP27, and vasoactive intestinal peptide (VIP), on cyclic AMP (cAMP) accumulation and intracellular Ca2+ concentration ([Ca2+]i) were compared in N1E-115 cells. PACAP38 and PACAP27 stimulated cAMP accumulation up to 60-fold with EC50 values of 0.54 and 0.067 nM, respectively. The effect of VIP on cAMP accumulation was less potent. The binding of 125I-PACAP27 to intact cells was inhibited by PACAP38 and PACAP27 (IC50 values of 0.44 and 0.55 nM, respectively) but not by VIP. In fura-2-loaded cells, both PACAP38 and PACAP27 increased [Ca2+]i with EC50 values around 10 nM. The interactions of these three peptides with ionomycin, a Ca2+ ionophore, and 4 beta-phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, were also determined. Ionomycin increased the cAMP accumulation caused by all three peptides. With low concentrations of PACAP38 or PACAP27, the effect of PMA was inhibitory, whereas at higher concentrations of PACAP (> 1 nM), the effect of PMA was stimulatory. Similar to other agents that elevate cAMP, PACAP38 was an effective stimulator of neurite outgrowth. These results show that (a) PACAP27 and PACAP38 stimulate cAMP accumulation and increase [Ca2+]i through the type I PACAP receptors in N1E-115 cells, (b) ionomycin enhances cAMP accumulation by all three peptides, and (c) activation of protein kinase C has a dose-dependent stimulatory or inhibitory effect on the PACAP38- or PACAP27-stimulated cAMP accumulation.

Calcium↗
PubMed1996

Uptake of [N-methyl-11C]propionyl-L-carnitine (PLC) in human myocardium.

We studied the uptake of propionyl-L-carnitine from plasma by the myocardium in 10 human subjects using positron emission tomography. Propionyl-L-carnitine was labeled in the N-methyl position with carbon-11 (T1/2 = 20.4 min) and administered i.v. in trace amounts. The uptake of the radiolabel by the myocardium was then scanned over a period of 1 1/2 h. The activity-time course of the tracer in blood and plasma and the exchange of the label in plasma between propionyl carnitine, acetyl carnitine and free carnitine was followed during the scans. Myocardial blood flow was also measured in the same subjects. The results show an exchange of the tracer between the myocardium and plasma, and they show an apparently irreversible component of uptake, a result consistent with the incorporation of the label into relatively large intracellular carnitine pools.

Adult↗
PubMed1995

Dobutamine stress: effects on regional myocardial blood flow and wall motion.

OBJECTIVES: This investigation studied the relation between regional myocardial blood flow and left ventricular function during dobutamine stress in patients with coronary artery disease. BACKGROUND: Dobutamine stress is becoming more frequently used as an alternative to dynamic exercise in patients with ischemic heart disease. METHODS: We studied 12 patients with coronary artery disease. Dobutamine was infused from 5 micrograms/kg body weight per min up to 40 micrograms/kg per min or until chest pain or other intolerable side effects. Regional myocardial blood flow was measured with positron emission tomography and oxygen-15-labeled water. Regional wall motion was assessed in three short-axis slices by magnetic resonance imaging. Each slice was subdivided into four regions: septal, anterior, lateral and inferior. A total of 140 regions were suitable for comparison. RESULTS: During stress, new wall motion abnormalities developed in 27 regions. Myocardial blood flow (mean +/- SD) increased in 113 regions that did not develop wall motion abnormalities (0.98 +/- 0.26 [baseline] vs. 1.98 +/- 0.87 [dobutamine] ml/min per g, p < 0.001), whereas it did not change significantly in regions with stress-induced wall motion abnormalities (1.00 +/- 0.28 [baseline] vs. 1.30 +/- 0.62 [dobutamine] ml/min per g, p = NS). An absolute decrease in myocardial blood flow below the value at rest was observed in seven segments that developed wall motion abnormalities during stress. CONCLUSIONS: The normal functional response to dobutamine stress is paralleled by an increase in coronary flow, whereas mechanical dysfunction is accompanied by a blunted increase, or even a paradoxic decrease, in regional coronary flow.

Adult↗
PubMed1994

CRIB and SNAP: assessing the risk of death for preterm neonates.

The performance of three scoring systems for assessing mortality risk for neonates--clinical risk index for babies (CRIB), score for neonatal acute physiology (SNAP), and SNAP's perinatal extension (SNAP-PE)--were tested in the same set of patients. In 222 neonates weighing less than 1500 g at birth, CRIB scores were significantly better for assessing mortality risk than SNAP (p = 0.017) or SNAP-PE (p < 0.001), areas under receiver operating characteristic curves being 0.89 (SE 0.02), 0.82 (0.03), and 0.79 (0.03), respectively. Male sex was independently associated with poor prognosis after taking the CRIB score into account with a risk ratio of 2.75. We conclude that CRIB is the most useful score for comparing the performance of neonatal intensive-care units. New treatment methods, however, may require modifications to the system.

Female↗
PubMed1994

Familial pericentric inversion inv(8)(p23q11).

We describe two families in whom a pericentric inversion, inv(8)(p23q11), is segregating. No examples of unbalanced karyotypes were encountered. The families originated from neighbouring parishes in western Finland. In one family a mild form of mental retardation segregated. However, this phenotype did not cosegregate with the inversion karyotype. There was no evidence of a higher than average abortion rate in the inversion carriers. Carrier matings produced 19 children with a balanced inversion and 14 children with a normal karyotype, concordant with a 1:1 segregation ratio. Of 13 karyotyped men at risk, 10 were inversion carriers. However, this difference was not statistically different from the expected 1:1 ratio. In females, the inversion carrier to normal ratio was 10:11.

Abortion, Spontaneous↗
PubMed1993

Diffuse reduction of myocardial beta-adrenoceptors in hypertrophic cardiomyopathy: a study with positron emission tomography.

OBJECTIVES: This study was conducted to determine the myocardial beta-adrenoceptor density as a marker of sympathetic function in patients with hypertrophic cardiomyopathy and normal control subjects. BACKGROUND: Although some cases of hypertrophic cardiomyopathy are familial with an autosomal dominant pattern of inheritance, there remains a substantial proportion of cases in which neither a family history nor genetic abnormalities can be demonstrated. Additional abnormalities, both genetic and acquired, may be important in the phenotypic expression of this condition. Clinical features of the disease and metabolic studies suggest an increased activity of the sympathetic nervous system. METHODS: Eleven patients with hypertrophic cardiomyopathy, none of whom had previously received beta-blocking drugs, and eight normal control subjects underwent positron emission tomography to evaluate regional left ventricular beta-adrenoceptor density and myocardial blood flow using carbon-11-labeled CGP 12177 and oxygen-15-labeled water as tracers. Plasma catecholamines were also measured. RESULTS: Mean (+/- SD) myocardial beta-adrenoceptor density was significantly less in the hypertrophic cardiomyopathy group than in the control group (7.70 +/- 1.86 vs. 11.50 +/- 2.18 pmol/g tissue, p < 0.001). Myocardial blood flow was similar in both groups (0.91 +/- 0.22 vs. 0.91 +/- 0.21 ml/min per g, p = NS). The distribution of beta-adrenoceptor density was uniform throughout the left ventricle in both groups. In the hypertrophic cardiomyopathy group, there was no correlation between regional wall thickness and myocardial beta-adrenoceptor density. There were no significant differences in either plasma norepinephrine or epinephrine concentrations between the two groups. CONCLUSIONS: There is a diffuse reduction in myocardial beta-adrenoceptor density in patients with hypertrophic cardiomyopathy in the absence of significantly elevated circulating catecholamine concentrations. This most likely reflects downregulation of myocardial beta-adrenoceptors secondary to increased myocardial concentrations of norepinephrine and is consistent with the hypothesis that cardiac sympathetic drive is increased in this condition.

Adult↗
PubMed1986

Selection of a dye for use in semen transport studies in the cow.

A series of experiments was carried out to select a dye and diluent that would facilitate identification of bovine inseminate in the uterus of the live cow when using hysteroscopic techniques. Of the dyes tested, Aniline Blue and the permitted food dye Green S as 1% solutions were the most suitable when added to semen with milk buffer diluent. Neither stained the uterine mucosa nor adversely affected the equipment, and both were visually distinctive during hysteroscopy. Using 1% concentrations of these dyes, sperm motility scores were acceptable before and after slow and fast freezing processes.

Journal Article↗