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Biomedical subjects

J A Clements

Publications and source records attributed to J A Clements.

At least 19 recordsLinked to original sources
PubMed1992

The Anagen system for automated fluorometric immunoassay.

We describe a new discrete microprocessor-controlled analyzer, the AN2000, which fully automates fluorometric immunoassays by using a magnetic separation of the solid phase and an alkaline phosphatase label. It can operate in random-access or batch mode with a dwell time typically less than 20 min. The analysis rate is 75 samples per hour and the system can hold refrigerated reagents for as many as 20 different analytes. The substrate and wash buffer are common to all analytes. The system can hold as many as 80 samples at once. The operator can select from the menu-driven operator interface any combination of the available analytes to be run for each sample, using either the touch screen or the keyboard. Results are calculated from a stored calibration curve that is stable for greater than or equal to 1 month. The AN2000 is capable of automating most assay formats because the available timings, volumes, incubations, and wash cycles can be used in any combination.

Alkaline Phosphatase↗
PubMed1991

Localization of immunoreactive beta-endorphin and adrenocorticotropic hormone and pro-opiomelanocortin mRNA to rat testicular interstitial tissue macrophages.

Pro-opiomelanocortin (POMC) gene expression and POMC peptides have been demonstrated in the Leydig cells of the testis, although selective removal of the Leydig cells with the cytotoxic drug ethane dimethane sulfonate did not significantly reduce levels of testicular POMC mRNA or peptides in adult rats. Since macrophages in the rat spleen synthesize POMC peptides, we investigated whether isolated macrophages from the adult rat testis may be an additional source of POMC-derived peptides. Testicular macrophages were isolated by collagenase treatment of adult rat testes and adherence to siliconized glass coverslips; the biological, cytochemical and immunological characteristics of the attached cells were compared with those of Leydig cells purified by Percoll gradient centrifugation. Macrophages in the cell preparations were identified by positive esterase cytochemical staining, latex bead ingestion, and immunocytochemical staining with ED2 (a macrophage-specific monoclonal antibody), and an absence of 3 beta-hydroxysteroid dehydrogenase cytochemical staining. Leydig cells in the purified preparations were positive for 3 beta-hydroxysteroid dehydrogenase and esterase staining but negative with ED2, and were not phagocytic. Based on these criteria, the purities of the macrophage and Leydig cell preparations employed in this study were estimated to be 87 +/- 4% and 91 +/- 3%, respectively. Cytoplasmic beta-endorphin (beta EP) immunoreactivity (ir) was present in 62 +/- 9% of cells in the purified Leydig cell preparations--confirming these cells as a source of POMC-derived peptides. In addition, ir-beta EP and ir-ACTH were localized to the cytoplasm of a similar proportion of cells (beta EP, 62.5 +/- 5%; ACTH, 64 +/- 5%) in macrophage preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1979

Antenatal prediction of graduated risk of hyaline membrane disease by amniotic fluid foam test for surfactant.

We measured amniotic fluid surfactant by the semiquantitative foam stability test within 24 hours before delivery of 410 infants, 64 of whom developed HMD diagnosed by standard criteria. When surfactant titers were ranked in eight categories, they predicted graded risks of HMD. On this basis we defined five "risk groups" with significantly different incidences of HMD (I = 0.5%; II = 10%; III = 25%; IV = 41%; V = 79%). Infants in Groups I and II were heavier and more mature than those in Groups III to V. However, among infants of equivalent GA or birth weight, the incidence of HMD still correlated significantly with the foam test results. Within each risk group the incidence of HMD was equal among infants delivered by vagina and by cesarean section, slightly greater among males than females, and inversely proportional to GA. In Group V the incidence of HMD was 100% among infants at less than 33 weeks' GA. We used this relationship to devise a system that improved prediction of HMD by combining the foam test results with GA.

Amniocentesis↗
PubMed1979

The disposition of intravenous doxapram in man.

The pharmacokinetics of intravenous doxapram in healthy individuals is consistent with a three-compartment open model. Doxapram was administered by bolus injection (1.5 mg . kg-1) and by intravenous infusion (6.5 mg . kg-1 for 2 h) to 5 subjects on separate occasions. There was no significant difference in mean terminal plasma half-lives (355 and 448 min) or in mean total body clearances 5.9 and 5.6 ml . min-1 . kg-1) following i.v. bolus injection or infusion respectively. In 3 subjects plasma doxapram concentrations during and after i. v. infusion agreed with those predicted from pharmacokinetic values obtained from the bolus injection study. Since mean steady-state concentrations (9.9 microgram . ml-1) would be reached only after an extended interval (mean 15.2 h), a variable-rate infusion regimen was calculated to produce and maintain a concentration of 2 microgram . ml-1 from 15--25 min onwards. A regimen in which the infusion rate is reduced step-wise is recommended to achieve early near-constant plasma doxapram concentrations.

Adult↗
PubMed1979

Pulmonary surface film stability and composition.

Stability of pulmonary alveoli at end expiration requires a very low air-water surface tension (e.g., less than 10 mN.m-1). Another important requirement is that the surface film maintain this low surface tension for a sufficiently long time at fixed lung volume. We measured monolayer collapse rates at 37 degrees C of lung surface-active material (SAM) and certain lipids found in this material and compared them with alveolar monolayer collapse rates calculated from published lung compliance changes. We found collapse rates for purified SAM or a mixture of dipalmitoyl lecithin (DPPC):monoenoic lecithin (PC):cholesterol (CHOL) (3.03:1.65:1 molar ratios) to be much greater than collapse rates of alveolar films estimated from indirect measurements. Monolayers of pure DPPC or DPPC with 10 mol% monoenoic PC and/or CHOL had collapse rates equal to or less than those estimated from lungs. We conclude that the alveolar monolayer is enriched in DPPC to the extent of 90 mol% or greater. Enrichment may exclude more mobile components from the monolayer during expiration when surface tension reaches verry low values.

Animals↗
PubMed1979

Tracheal fluid in fetal lambs: spontaneous decrease prior to birth.

We studied tracheal fluid (TF) production in 14 fetal lambs: 6 controls, 6 receiving atropine on 1 or more of the last 7 days before birth, and 2 with bilateral section of the cervical vagosympathetic trunk. A cannula diverted all TF into an intrauterine bag; we collected TF intermittently and measured its volume. All ewes delivered spontaneously at 128-150 days' gestation. TF production decreased before birth in all fetuses except one control. TF production decreased before birth in all fetuses except one control. TF production did not correlate with fetal arterial blood gas tensions, hematocrit, or plasma proteins. In controls only, TF production correlated with fetal arterial pH (P less than 0.02); however, the pH range was small and the correlation has questionable physiological significance. For all fetuses, TF production during the 7 days before birth correlated inversely with the plasma cortisol concentration of 48 h previously (n = 36; r = -0.603; P less than 0.001). We conclude a) TF production in fetal lambs decreases before spontaneous term or preterm labor; b) this decrease is not affected by atropine or by section of the cervical vagosympathetic trunk; and c) the decrease in TF production may be related to increased secretion of cortisol.

Animals↗
PubMed1979

Stimulation of breathing movements in fetal sheep by inhibitors of prostaglandin synthesis.

We studied the effects of inhibitors of prostaglandin synthesis on fetal breathing movements on 17 occasions in 11 lambs (gestational age 125-141 days). We gave 12 h infusions of sodium mechlofenamate (8.6-22.2 mg.kg-1) in 13 studies and indomethacin (21.8-38.8 mg.kg-1) in four studies. Results were similar with both agents and did not correlate with drug dosage. There were no changes in fetal arterial blood pressure, pH or blood gas tensions. We assessed fetal breathing movements by measurements of tracheal pressure for a control period of 224 h prior to and 208 h during the infusion of inhibitors of prostaglandin synthesis; their administration caused a marked stimulation of fetal breathing movements judged from the following four variables: (1) incidence of fetal breathing movements increased from 38.4 to 69.2% of the time (P < 0.001); (2) average amplitude of change in tracheal pressure during fetal breathing movements increased from 4.1 to 6.0 torr (P < 0.01); (3) maximal amplitude of change in tracheal pressure during fetal breathing movements increased from 8.8 to 13.4 torr (P < 0.01); and (4) the duration of the longest continuous episode of fetal breathing movements increased from 37 to 229 min (P < 0.05). Two fetuses had electrocorticogram (ECoG) recordings. In control periods, fetal breathing movements occurred only during low voltage, high frequency ECoG activity; however, during infusions of inhibitors of prostaglandin synthesis, fetal breathing movements occurred also during high voltage, low frequency ECoG activity. We conclude that inhibitors of prostaglandin synthesis stimulate fetal breathing movement in fetal sheep. These results suggest that a component of the prostaglandin system is a factor which inhibits breathing movements during fetal life.

Animals↗
PubMed1978

Kinetics of acetaminophen absorption and gastric emptying in man.

Eight healthy male volunteers ingested an aqueous solution containing acetaminophen (20 mg/kg) and a nonabsorbable isotopic marker. The concentrations of unconjugated acetaminophen in samples of blood plasma taken at frequent intervals were measured by gas-liquid chromatography. The data points followed a smooth curve in most cases and were fitted to the classical two-compartment pharmacokinetic model to obtain KA, the apparent first-order rate constant for absorption from the gastrointestinal tract. Gastric emptying was measured simultaneously from serial scintiscans of the subject's abdomen. The subjects were also studied after intramuscular injection of meperidine (150 mg) and pentazocine (60 mg) with and without naloxone (1.2 mg). The acetaminophen absorption curves and gastric emptying patterns were consistent with negligible absorption from the stomach. A new model is proposed in which the conventional single compartment used to represent the gastrointestinal tract is replaced by two compartments: one represents the stomach and the other the small intestine, from which absorption occurs rapidly. Pharmacokinetic analysis using this model showed good agreement in all cases, and provided an estimate of KA, the first-order rate constant for drug transfer from the intestinal lumen into the systemic circulation. The mean half-time for transfer was 6.8 +/- 0.9 min. As expected, KA was greater than KG (the first-order rate constant for gastric emptying), showing that gastric emptying was rate-limiting in the absorption of acetaminophen. The value of KA was greater than KA and the two were not related. The value of KA was not equal to KG in most studies because gastric emptying was not a single exponential process.

Acetaminophen↗
PubMed1978

Direct determination of volume- and time-dependence of alveolar surface tension in excised lungs.

We measured alveolar surface tension directly by observing the spreading properties of fluid droplets placed by micropipette within individual alveoli. Alveolar surface tension in excised rat lungs at total lung capacity and 37 degrees was 29.7 +/- 1.4 mN-m-1. In lungs held at functional residual capacity, surface tension changed slowly, rising to 9 mN-m-1 at 30 min with a subsequent approximately linear rise to 16 mN-m-1 at 115 min. Thereafter it rose more rapidly (20 mN-m-1 at 140 min), suggesting that it was not asymptotically approaching an equilibrium value.

Animals↗
PubMed1978

Control of lung surfactant by ventilation, adrenergic mediators, and prostaglandins in the rabbit.

In a previous study, we showed that increasing minute ventilation (VE) in rabbit lung by adding a dead space augmented pulmonary surfactant in the airspaces by a cholinergically mediated mechanism. Using the same model in the present study of 148 rabbits, we found that increasing VE augmented airspace phospholipid, the main component of surfactant, from 2.50 +/- 0.61 (mean +/- SD) mg per g of lung during normal VE to 3.15 +/- 1.22 (mean +/- SD) mg per g of lung during increased VE (P = 0.02). Both blocking beta-adrenergic receptors with propranolol or sotalol and inhibiting prostaglandin synthetase with indomethacin or sodium meclofenamate prevented the expected increase in phospholipid during increased VE (P is less than 0.05). The beta-2 agonist, terbutaline, increased phospholipid by 43 per cent during normal VE (P is less than 0.01), and propranolol blocked this increase (P is less than 0.05). Isoproterenol, arachidonic acid, prostaglandins E1, E2, F2alpha, and a cyclic endoperoxide analog of prostaglandin H2 (U-46619) injected during normal VE failed to increase phospholipid. We concluded that acetylcholine (previous study), beta-adrenergic mediators, and prostaglandins are involved in controlling alveolar surfactant during increased VE.

Adrenergic alpha-Antagonists↗
PubMed1978

Development of anti-hLH antibodies after therapy with posterior pituitary extract.

This report describes the appearance of high affinity antibodies to human LH in a girl who had been treated for diabetes insipidus with injections of pitressin tannate, plus occasional nasal insufflations of posterior pituitary powder. Immunological studies indicated that the antibody was a 7S IgG directed against the beta subunit of LH, which is not species-specific. The demonstration of immunoassayable LH in a commercially available pitressin preparation strongly suggests that this patient was immunized by bovine or porcine LH. Although studies of her urinary LH excretion and serum LH (by an interstitial cell bioassay system) suggest that at least some of her endogenous LH is not bound by the antibody, the possibility remains that this type of immunization may have important implications for the development and maintenance of normal adult pituitary-ovarian relationships.

Antibodies↗
PubMed1977

Ventilatory and cholinergic control of pulmonary surfactant in the rabbit.

Four sets of experiments on surfactant secretion were performed using New Zealand rabbits under light pentobarbital anesthesia. Pa02, Paco2, and pHa remained normal during all experiments. In controls lung lavage yielded 1.62 +/- 0.26 (SD) mg of alveolar phospholipid (PL)/g lung; disaturated phosphatidylcholine comprised 55.5% of total PL. a) Acetylcholine infusion into the left pulmonary artery for 1-4 h caused a 13% increase in alveolar PL of left as compared to right lung. b) Efferent left vagus stimulation for 1 h increased alveolar PL of right and left lungs 31% as compared to controls (P = 0.012). c) Increasing minute ventilation by 100% by augmenting dead space for periods of 1, 2, and 4 h, increased alveolar PL 45% (P = 0.001), 54%, (P = 0.002), and 25% (P = 0.004), respectively, compared to controls. d) Administration of atropine prevented the increase in alveolar PL caused by increased ventilation. These findings show that increased ventilation can stimulate surfactant release through a cholinergically mediated mechanism but do not rule out the participation of other mechanisms.

Acetylcholine↗
PubMed1977

Radioimmunoassay of pulmonary surface-active material in the tracheal fluid of the fetal lamb.

We measured pulmonary surfactant antigen by radioimmunoassay and phospholipid by lipid phosphorus assay in fluid collected during 12-hour periods from the trachea of lambs in utero between 102 and 147 days of gestation. Both phospholipid and antigen were detectable at 114 days and were present at low concentrations until 137 days. The concentrations then increased rapidly and reached 5- to 10-fold higher concentrations before parturition. The ratio of lipid phosphorus to antigen increased approximately 5-fold as the lungs passed from canalicular to alveolar architecture and approximated the adult ratio only during the alveolar stage of development.

Animals↗
PubMed1977

Isolation and properties of type II alveolar cells from rat lung.

Type II alveolar cells can be isolated and partially purified from adult rat lung by a series of steps that includes enzymatic digestion of the lung with trypsin and separation of cells on a discontinuous albumin density gradient. The yield of the isolated type II cells depends on the supplier and the housing of the rats used to prepare the cells. With specific pathogen-free rats housed in a laminar flow hood, the yield was 20.3 x 10(6) cells per rat, of which 50 per cent were type II cells. With rats from 2 other suppliers and no special housing, the yields were 8.8 and 8.3 x 10(6) cells per rat, of which 67 and 65 per cent were type II cells. The ultrastructural appearance of the isolated cells was similar to that of cells from intact lung, except for some dilatation of the endoplasmic reticulum and the perinuclear space. Most cells (92 +/- 5 per cent) excluded the vital dye, trypan blue. The cells consumed O2 at the rate of 76 +/- 12 nmole per 10(6) cells per hour and released only 5.7 +/- 2.0 per cent of their lactate dehydrogenase, a cytoplasmic enzyme, into the medium after 1 hour of incubation. The isolated type II cells contained disaturated phosphatidylcholine, a major component of purified surface-active material. The cells, however, had a low glucose utilization compared to their O2 consumption, which may indicate an abnormality in the metabolism of glucose. This population of cells could be further purified to 89 per cent type II cells by unit gravity velocity sedimentation.

Animals↗