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J A Clements

Publications and source records attributed to J A Clements.

At least 109 records · Page 6Linked to original sources
PubMed1985

Vasopressin-neurophysin II gene expression in the ovary: studies in Sprague-Dawley, Long-Evans and Brattleboro rats.

The neurohypophysial hormones oxytocin and arginine vasopressin (AVP) have been identified on immunological criteria in the ovary. Confirmation of extraneuronal synthesis requires the demonstration in the tissue of the specific messenger RNA (mRNA) for the preprohormone. Using a synthetic pentadecamer nucleotide probe, highly specific for the 5' region of rat neurophysin II (NP II), we have demonstrated the presence of AVP-NP II mRNA in the ovary of Sprague-Dawley, Long-Evans and Brattleboro rats, with an apparent molecular weight identical to that seen for hypothalamus. These findings, together with the presence of immunoreactive AVP in the ovaries but not hypothalami of Brattleboro rats, suggest that tissue-specific differences in AVP-NP II gene expression occur at the translational as well as transcriptional level.

Animals↗
PubMed1984

Protein composition of rabbit alveolar surfactant subfractions.

The goal of this investigation was to characterize the proteins in subfractions of alveolar surfactant obtained by lung lavage and separated by differential centrifugation. It was previously demonstrated that the material in the more sedimentable fraction, which was enriched in tubular-myelin and was surface-active may be a precursor to the less sedimentable, vesicular, inactive material [1]. Separation of the proteins by polyacrylamide gel electrophoresis showed that the more sedimentable subfractions and rabbit surfactant isolated by conventional methods contained proteins with molecular weights comparable to those previously reported for alveolar surface active material (approximately 36 000 and 10 000). The less sedimentable subfractions contained less of these proteins. Immunoblots with anti-dog surfactant apoprotein antibodies, which cross-react with rabbit proteins, supported these observations. Immunoblots also showed that all of the subfractions contained serum proteins and secretory IgA, with the less sedimentable subfractions containing more secretory IgA. These results suggested that changes in protein composition may accompany functional changes in surfactant in the alveoli.

Animals↗
PubMed1984

Oral ketamine.

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Administration, Oral↗
PubMed1984

The role of sulphate conjugation in the metabolism and disposition of oral and intravenous paracetamol in man.

The effects of paracetamol dose (5 and 20 mg/kg) and route of administration (intravenous and oral) on the urinary excretion of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates were studied in five healthy subjects. The fractional urinary excretion of unchanged paracetamol and its conjugates was independent of the route of administration at both dose levels, suggesting that the gastrointestinal tract is not an important site for paracetamol metabolism. The percentage of the dose excreted as the sulphate conjugate was significantly higher after 5 than after 20 mg/kg (37.7% and 33.3% respectively) and this is consistent with saturation of sulphate conjugation. No significant effect of paracetamol dose upon the area under the plasma concentration-time curve (AUC), corrected for dose, was found for the sulphate or glucuronide conjugates. The total plasma clearance of paracetamol and the renal clearance of the sulphate conjugate were significantly higher after the 5 than the 20 mg/kg dose (331 +/- 42 ml/min and 295 +/- 48 ml/min; 273 +/- 74 ml/min and 205 +/- 46 ml/min respectively). The oral systemic availability of paracetamol was 80% and independent of dose.

Acetaminophen↗
PubMed1984

Effects of ascorbic acid and disodium edetate on the stability of isoprenaline hydrochloride injection.

Disodium edetate (0.01%), either alone or in combination with ascorbic acid (0.1%) was an effective stabilizer for isoprenaline injection B.P. but adjustment to pH 2.8 was necessary. The bubbling of nitrogen through the solution in the ampoule before sealing did not prevent degradation in unprotected solutions. Solutions sterilized by filtration or by autoclaving for 30 min at 116 degrees C were stable for at least 1 year at 5 degrees C or 25 degrees C.

Ascorbic Acid↗
PubMed1984

Relationship between endogenous opioids and the oestrous cycle in the rat.

The aim of this study was twofold: (1) to document changes in levels of immunoreactive beta-endorphin (Ir-beta-EP) in the hypothalamus, anterior pituitary gland, neurointermediate lobe and plasma during the oestrous cycle of the rat and (2) to investigate stress-induced changes in plasma Ir-beta-EP at different stages of the oestrous cycle. Evidence was found that Ir-beta-EP levels in the hypothalamus, anterior pituitary gland and plasma are not constant during the oestrous cycle and that the Ir-beta-EP response to stress is a function of the phase of the oestrous cycle at which stress is applied. It is suggested that fluctuations in ovarian hormones may influence oestrous Ir-beta-EP levels both under normal conditions and after exposure to stress.

Animals↗
PubMed1984

Expression of the gene for arginine vasopressin in Brattleboro rats.

There is now overwhelming evidence--radio-immunoassay, immunofluorescence, Northern blot analysis with highly specific cDNA probes--for the production of vasopressin and its congeners in the rat ovary as well as the hypothalamus. Ontogeny studies and studies over the oestrous cycle suggest that such production is controlled by different mechanisms in the two tissues. Studies in Brattleboro rats suggest that the production of vasopressin and its congeners involves different post-transcriptional mechanisms in these tissues. In Brattleboro rats hypothalamic mRNA is either not translated, or yields a very short-lived product, whereas ovarian levels of immunoreactive vasopressin are indistinguishable from those in control animals. The mechanism of this tissue specificity, and its implications in terms of potential paracrine roles for vasopressin and, or its congeners awaits explanation.

Animals↗
PubMed1983

Changes in phospholipid composition of lung surfactant during development in the fetal lamb.

The lung surfactant isolated from pulmonary fluid of fetal sheep changes both in amount and composition during gestation. Total phosphatidylcholine (PC) and its most surface-active components, disaturated PC, are present at very low levels 3-4 weeks prior to term and rise to adult levels 3-4 days before birth. The acidic phospholipids appear with a different time course. Phosphatidylserine reaches elevated levels about 21 days before birth. Phosphatidylinositol begins to increase at about 130 days of gestation. Phosphatidylglycerol is not a component (less than 1%) of the surfactant in this fetal lung fluid. At term, phosphatidylinositol is the major acidic phospholipid found in these fluids.

Acid Phosphatase↗
PubMed1983

Coffee contains potent opiate receptor binding activity.

Opiate receptor-active peptide fragments (exorphins) have been identified recently in casein and gluten hydrolysates, and morphine has been found in bovine and human milk. To determine whether similar peptides or alkaloids occur in other foodstuffs, we have screened potential sources using a rat brain homogenate assay to detect opiate receptor activity. We report here that instant coffee powders from a variety of manufacturers compete with tritiated naloxone for binding to opiate receptors in the rat brain membrane preparations, with no significant difference between normal and decaffeinated coffee. The receptor binding activity resembles that seen with opiate antagonists, in that there was no change in the half-maximal effective dose (ED50) in the presence of 100 mM Na+; on bioassay, the activity was similarly shown to be antagonistic and specific for opiate-induced inhibition of twitch. Preliminary characterization of the activity reveals that it has a molecular weight (MW) in the range 1,000-3,500, is heat-stable, ether-extractable, not modified by enzymatic digestion with papain, and clearly separable from caffeine and morphine on TLC. As its concentration in an average cup of coffee is five times the ED50, these data suggest that drinking coffee may be followed by effects mediated via opiate receptors, as well as effects of caffeine.

Animals↗
PubMed1983

Subfractionation of lung surfactant. Implications for metabolism and surface activity.

Because previous studies have suggested that lung surfactant is not a simple compartment of homogeneous material, we subfractionated lamellar bodies and components of alveolar lavage from male New Zealand white rabbits, according to differences in sedimentability. We recovered two lamellar body populations at different densities in discontinuous sucrose density gradients; we separated six subfractions of alveolar lavage by differential centrifugation. To determine whether or not precursor-product relationships existed among the subfractions, we injected radioactive palmitate intravenously, killed the rabbits 1-72 h later, and measured phospholipid specific activities. The two populations of lamellar bodies had similar phospholipid composition, fatty acyl composition of phosphatidylcholine and phosphatidylglycerol, and surface activity. Light lamellar bodies had a higher ratio of phospholipid to protein, and labelled with tracer later in time than dense ones. For alveolar lavage subfractions, later labelling with tracer, lower adsorption rate and lower total protein and phosphatidylglycerol content seemed to correlate with decreasing average density and particle size as well as with the disappearance of tubular myelin structure and appearance of predominantly vesicular structure. The subfractions appear to be in a metabolic sequence in which heavier, more dense material is a precursor to lighter, less dense material. The results suggest that subfractions of surfactant are extensively recycled.

Animals↗
PubMed1983

Ketamine disposition in children and adults.

The pharmacokinetics of ketamine 2 mg kg-1 i.v. and 6 mg kg-1 i.m. were investigated in nine children undergoing minor surgery. After either route of administration plasma ketamine concentrations were similar to those found in adult patients receiving the same dose, except at later times after i.v. injection, when concentrations were smaller in children. Also, absorption after i.m. injection appeared to be more rapid in children. Substantially larger concentrations of the metabolite norketamine were found in children than in adults after the injection of ketamine. Concentrations of ketamine upon awakening in a further group of nine children receiving ketamine as the sole anaesthetic showed large inter-individual variation. The concentrations were greater than those previously reported for adults. The greater dose requirements in children, compared with adults, are probably attributable to pharmacodynamic rather than pharmacokinetic factors.

Adult↗
PubMed1983

Mexiletine disposition: individual variation in response to urine acidification and alkalinisation.

The disposition of mexiletine has been studied in five subjects on two occasions with urine pH controlled at 5.0 and at 8.0. With acid urine total plasma clearance was similar in all subjects (462 to 497 ml min-1) and the plasma half-life ranged from 3.8 to 9.2 h (mean 6.7 h). With alkaline urine the total plasma clearance varied considerably (239 to 441 ml min-1); the mean half-life, 9.7 h, (range 7.6 to 12.7 h) was not significantly different from that in the acid urine study. Renal clearance fell greatly in every subject on alkalinisation of the urine. The total plasma clearance fell by a similar amount in two. In the remaining three the fall in total clearance was much smaller because of an increase in non-renal clearance. The reduction in total plasma clearance only just achieved statistical significance. The increase in predicted steady-state plasma mexiletine concentrations during infusion with change in urine pH from 5 to 8 varied between +5% and +95% (mean +39%). Changes in urine pH have a predictable effect upon renal clearance of mexiletine. However, disposition is changed in an unpredictable manner and inter-subject variation in distribution volume and non-renal clearance are important factors.

Adult↗
PubMed1983

Phosphatidylglycerol-deficient lung surfactant has normal properties.

We have investigated the effects of substituting phosphatidylinositol (PI) for phosphatidylglycerol (PG) on the functional properties of rabbit lung surfactant. We gave oral 10% glucose solution for 3 days to 11 rabbits and 10% inositol to 12 others. Lung lavage surfactant phospholipids were normal in both groups, except that PG was low and PI was high in the inositol group. Fatty acyl group distributions did not differ, except for a slight decrease of oleic acid in the inositol group. Electron microscopic examination showed normal surfactant structure in both. The time course of surfactant adsorption to an air-water interface was similar in both groups. Minimum surface tension after film compression was 4.0 +/- 0.8 mN . m-1 in the glucose group and 2.9 +/- 1.3 mN . m-1 in the inositol group (mean +/- SE). Surface potential-surface pressure isotherms were identical to within 12 mV. Arterial blood gases breathing air and 100% O2 were the same in both groups, as were pressure-volume curves of excised lungs, with both air and saline filling. The results suggest that, if acidic phospholipids are necessary for maintaining normal surfactant structure and surface properties, normal pressure-volume relationships, and normal gas exchange, then PI may substitute for PG.

Animals↗
PubMed1983

Opiate binding sites in bovine adrenal medulla.

Previous studies using a variety of opiate ligands have suggested the existence of several subclasses of opiate receptors in crude membrane fractions of rat brain, and a similar diversity in bovine adrenal medulla. To examine the receptor profile of bovine adrenal medulla in detail we have studied the binding of classical ligands for mu (mu), delta (delta) and kappa (kappa) opiate receptors. [3H]naloxone ([3H]NAL), [3H]morphine ([3H]MOR), [3H]D-Ala2-D-Leu5-enkephalin ([3H]DAL) and [3H]ethyl-ketocyclazocine ([3H]EKCZ) were used as tracers; unlabeled competitors were NAL, MOR, DAL and ketocyclazocine (KCZ). In adrenal medulla [3H]NAL was specifically bound with a hierarchy of displacement NAL greater than MOR greater than KCZ much greater than DAL. No specific binding of [3H]DAL or [3H]EKCZ was found; for [3H]MOR very low levels of binding were seen, with no displacement by NAL or DAL, inconsistent displacement by KCZ and substantial displacement by MOR with an ED50 of 1.5 nM. In parallel studies rat brain membranes bound each labeled ligand with affinity and specificity consistent with previously published reports. Identical results were obtained in membranes from both tissues prepared with a preincubation step including 100 mM Na+, suggesting that the results were not influenced by occupation of binding sites by endogenous ligands. We interpret these data as supporting the existence of opiate receptors of the mu subtype in bovine adrenal medulla. We find, however, no evidence of delta or kappa sites in this tissue.

Adrenal Medulla↗
PubMed1982

Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans.

The pharmacokinetics of ketamine in analgesic doses after intravenous, intramuscular, and oral administration was investigated in healthy volunteers. Plasma ketamine concentration-time curves were fitted by a two-compartment open model with a terminal half-life of 186 min. Absorption after intramuscular injection was rapid and the bioavailability was 93%. However, only 17% of an oral dose was absorbed because of extensive first-pass metabolism. Simultaneous measurements of the elevation of pain threshold in an ischemic exercise test showed a marked effect for 15-60 min after intramuscular injection, but little or no effect after the oral solution. Pain threshold elevation occurred at plasma ketamine concentrations above 160 ng/ml.

Administration, Oral↗
PubMed1982

An intercostal retractometer for estimation of intrapleural pressure changes in infants.

An intercostal retractometer was developed for estimation of intrapleural pressure changes in infants. It consists of a flat reference plate which floats over the interspace and is attached to the skin by a flexible plastic film. The pressure inside the device is measured with a strain gauge. The volume inside the device is adjusted, so that the intercostal space is brought to a condition of flatness and pressure changes in the device correlate linearly with intrapleural pressure changes. The retractometer is calibrated against overall intrapleural pressure changes by matching its output to changes in airway pressure during occlusion of the airway. The calibration factor is qualitatively proportional to the thickness of the subcutaneous tissue. Retractometer and intrapleural pressures were simultaneously measured in two infant rhesus monkeys with small pneumothoraces. Esophageal and retractometer pressures were compared in seven preterm infants with an average weight of 1345 g. The device estimated the monkeys' intrapleural pressure changes to within 1.2 cmH2O and the human preterm infants' esophageal pressure changes to within 1.3 cmH2O (95% confidence limits of a linear regression).

Animals↗
PubMed1982

Adrenocorticotropin, beta-endorphin, and beta-lipotropin in normal thyroid and lung: possible implications for ectopic hormone secretion.

The expression of the proopiomelanocortin (POMC) gene by normal lung and thyroid was examined by measurement of the content of ACTH, beta-lipotropin (beta LPH), and beta-endorphin (beta EP) in porcine lung and thyroid tissue. Acid extracts of normal porcine lung and thyroid tissue each contained appreciable amounts of immunoreactive (ir) ACTH, ir-beta LPH, and ir-beta EP. The content of ir-beta LPH in both tissues exceeded by severalfold, on a molar basis, the content of ir-ACTH and ir-beta EP, suggesting that the common precursor POMC was processed predominantly to peptides other than ir-ACTH and ir-beta EP. A porcine thyroid extract (Calcitare, porcine calcitonin, Armour) showed equivalent levels of beta EP-like immunoreactivity and bioactivity, measured by opiate radioreceptor assay; in contrast, ACTH-like bioactivity, measured by rat zona fasciculata steroidogenesis, was only 4% of ACTH-like immunoreactivity. On reversed phase high performance liquid chromatography, Calcitare showed multiple peaks of ACTH-like immunoreactivity, one of which coeluted with porcine ACTH-(1-39), and two much smaller peaks of beta EP-like immunoreactivity, of which the smaller coeluted with porcine beta EP. These data suggest that both lung and thyroid gland synthesize POMC, which in normal tissue is usually predominantly processed to species other than ACTH and beta EP. Ectopic secretion of ACTH and beta EP by lung and thyroid neoplasms may thus represent the loss of a system(s) normally responsible for processing the precursor beyond ACTH and beta EP.

Adrenocorticotropic Hormone↗