Search PubMed⌕ Search

Biomedical subjects

J Patrick

Publications and source records attributed to J Patrick.

At least 145 records · Page 8Linked to original sources
PubMed1986

Expression of a novel high-affinity purine nucleobase transport function in mutant mammalian T lymphoblasts.

The single nucleoside transport function of mouse S49 lymphoblasts also transports purine bases (B. Aronow and B. Ullman, J. Biol. Chem. 261:2014-2019, 1986). This transport of purine bases by S49 cells is sensitive to inhibition by dipyridamole (DPA) and 4-nitrobenzylthioinosine, two potent inhibitors of nucleoside transport. Therefore, wild-type S49 cells cannot salvage low hypoxanthine concentrations in the presence of 10 microM DPA and 11 microM azaserine; the latter is a potent inhibitor of purine biosynthesis. Among a mutagenized wild-type population, a cell line, JPA2, was isolated which could proliferate in 50 microM hypoxanthine-11 microM azaserine-10 microM DPA. The basis for the survival of JPA2 cells under these selective conditions was expression of a unique, high-affinity purine nucleobase transport function not present in wild-type cells. JPA2 cells could transport 5 microM concentrations of hypoxanthine, guanine, and adenine 15- to 30-fold more efficiently than parental cells did. Kinetic analyses revealed that the affinity of the JPA2 transporter for all three purine bases was much greater than that of the wild-type nucleobase transport system. Moreover, nucleobase transport in JPA2 cells, unlike that in parental cells, was insensitive to inhibition by DPA, 4-nitrobenzylthioinosine, sulfhydryl reagents, and nucleosides. No alterations in nucleoside transport capability, phosphoribosylpyrophosphate levels, or purine phosphoribosyltransferase enzymes were detected in JPA2 cells. Thus, JPA2 cells express a novel nucleobase transport capability which can be distinguished from the nucleoside transport function by multiple biochemical parameters.

Adenine↗
PubMed1985

Disposition of ethanol in maternal blood, fetal blood, and amniotic fluid of third-trimester pregnant ewes.

The disposition of ethanol in maternal arterial blood, fetal arterial blood, and amniotic fluid of nine conscious, cannulated pregnant ewes (128 to 137 days' gestation) was determined for 1-hour maternal intravenous infusion of ethanol, 1 gm/kg maternal body weight. The maternal arterial blood and fetal arterial blood ethanol concentration-time curves were virtually superimposable up to 14 hours. The apparent zero-order ethanol elimination rates for maternal arterial blood and fetal arterial blood were similar. There was a time lag in the transfer of ethanol into amniotic fluid relative to fetal arterial blood, and the peak ethanol concentration in amniotic fluid was significantly lower than the concentrations in maternal arterial blood and fetal arterial blood. The apparent zero-order ethanol elimination rate for amniotic fluid was slower, but not significantly so, compared with the ethanol elimination rates for maternal arterial blood and fetal arterial blood. Ethanol-derived acetaldehyde was found in maternal arterial blood, fetal arterial blood, and amniotic fluid at concentrations at least 1000-fold lower than the respective ethanol concentrations. The data indicate that, for administration of this ethanol dosage regimen to the third-trimester pregnant ewe, there is rapid, bidirectional placental transfer of ethanol; elimination of ethanol from the fetus is regulated primarily by maternal elimination of ethanol; the amniotic fluid may serve as a reservoir for ethanol in utero; and there is appreciable acetaldehyde-metabolizing capacity.

Acetaldehyde↗
PubMed1985

Altered nucleoside transporters in mammalian cells selected for resistance to the physiological effects of inhibitors of nucleoside transport.

From a mutagenized population of wild type S49 T lymphoma cells, clones were generated that were resistant to the physiological effects of the potent inhibitor of nucleoside transport, 4-nitrobenzyl-6-thioinosine (NBMPR). These cells were selected for their ability to survive in semisolid medium containing 0.5 mM hypoxanthine, 0.4 microM methotrexate, 30 microM thymidine, 30 microM deoxycytidine, in the presence of 30 microM NBMPR. NBMPR protected wild type cells from the effects of a spectrum of cytotoxic nucleosides, whereas two mutant clones, KAB1 and KAB5, were still sensitive to nucleoside-mediated cytotoxicity in the presence of NBMPR. Comparisons of the abilities of wild type cells and mutant cells to incorporate exogenous nucleoside to the corresponding nucleoside triphosphate indicated that the KAB1 and KAB5 mutant cells were refractory to normal inhibition by NBMPR. Moreover, rapid transport studies indicated that mutant cells, unlike wild type parental cells, had acquired a substantial NBMPR-insensitive nucleoside transport component. Binding studies with [3H]NBMPR indicated that KAB5 cells were 70-75% deficient in the number of NBMPR binding sites, whereas KAB1 cells possessed a wild type complement of NBMPR binding sites. These data suggest that the NBMPR binding site in wild type S49 cells is genetically distinguishable from the nucleoside carrier site.

Animals↗
PubMed1985

Effects of maternal ethanol infusion on fetal cardiovascular and brain activity in lambs.

Ethanol (1 gm/kg of maternal body weight administered over 1 hour) was infused intravenously into 11 chronically prepared pregnant ewes between 128 to 137 days' gestation. Fetal breathing movements were suppressed for 9 hours following ethanol administration, and both high- and low-voltage fetal electrocortical activity were suppressed for 3 hours and replaced by intermediate-voltage electrocortical activity. Fetal blood gases and pH were not altered. These data support the hypothesis that ethanol suppresses fetal breathing movements by a direct central mechanism rather than indirectly by alteration of electrocortical activity.

Animals↗
PubMed1985

The distribution of accelerations of the human fetal heart rate at 38 to 40 weeks' gestational age.

In order to further understand the use of antepartum fetal heart rate monitoring we measured the distribution, in time, of two, three, or five fetal heart rate accelerations of greater than or equal to 15 bpm for greater than or equal to 15 seconds and of greater than or equal to 10 bpm for greater than or equal to 6 seconds in 12 healthy pregnant women at 38 to 40 weeks' gestation. The length of time necessary to measure 50% or 95% of intervals containing five accelerations would be substantially reduced by changing to a definition of two or three accelerations. However, an observation interval of at least 80 minutes is required to include the longest time interval of two, three, or five accelerations. These data may suggest new strategies for decreasing time and expense of fetal heart rate testing.

Female↗
PubMed1985

The relationship between the Wiggins' PSY scale and length of hospitalization: a re-examination.

Peteroy, Pirrello, and Adams' (1982) findings on two Wiggins content scales, DEP and PSY, were re-examined. In contrast to Peteroy et al.'s results, both scales were found to relate significantly to length of psychiatric hospitalization (LOH) when a larger, more heterogeneous sampling (N = 362) was employed, together with a wider range of LOH values. This study demonstrates how attention to relevant sampling parameters in predictive validity studies can help to ensure that the utility of measures such as PSY is not misjudged.

Adolescent↗
PubMed1985

Regulation of purine biosynthesis in G1 phase-arrested mammalian cells.

The effects of G1 phase growth arrest on purine biosynthesis were studied in cultured S49 T lymphoma cells. Incubations of wildtype S49 cells for 18 hr with dibutyryl cyclic AMP or forskolin, two agents which induced G1 arrest, reduced the rates of purine biosynthesis by 95%. Time course and concentration dependence studies indicated that the decrease in rates of purine biosynthesis correlated with the extent of G1 phase arrest. Similar studies with somatic cell mutants deficient in some component of cyclic AMP action or metabolism indicated that the depression in purine synthetic rates required G1 arrest and did not result from cell death. Rates of RNA and DNA synthesis were also markedly diminished in the growth arrested cells. Measurements of purine rates in the presence of azaserine indicated that the block in purine biosynthesis was prior to the formation of phosphoribosylformylglycinamide. Additionally, the activities of adenylosuccinate synthetase and IMP dehydrogenase were diminished in G1 arrested cells. The levels of all controlling enzymes, substrates, and cofactors, however, were not diminished in G1 arrested cells. Despite diminished rates of purine biosynthesis, the amounts of intracellular nucleotides in G1 cells were equivalent to those in exponentially growing cells. However, the concentrations of intracellular nucleotides were 30-50% higher in the growth arrested cells. These results suggested that perturbations in the consumption of nucleotides via inhibition of nucleic acid synthesis have profound effects on the purine pathway and indicated the importance of feedback inhibition by nucleotides in the regulation of purine synthesis in situ.

Animals↗
PubMed1985

Isolation of a clone coding for the alpha-subunit of a mouse acetylcholine receptor.

The mouse cell line BC3H-I synthesizes an acetylcholine receptor (AChR) with the pharmacological properties of a muscle nicotinic cholinergic receptor. We have purified mRNA from this cell line and used the size-fractionated poly(A)+RNA to produce a cDNA library of approximately 50,000 clones. The library was screened with a subclone containing genomic sequences coding for the putative acetylcholine-binding site of the alpha-subunit of chicken AChR. We obtained a plasmid, pMAR alpha 15, with a 1,717-base pair insert. The insert cDNA has 26 nucleotides at the 5'-end which code for a portion of the signal peptide followed by a single open reading frame of 1,311 nucleotides which code for a protein of 49,896 daltons. The insert has 377 bases of 3'-untranslated sequence with 3 polyadenylation sites. Radiolabeled plasmid DNA has been used to identify homologous RNA species of about 2 kilobases in Northern blot analyses of poly(A)+ selected RNA from BC3H-I cells. A similar size mRNA is seen in innervated mouse diaphragm and leg muscle, and both mouse and rat brain. Comparisons of the deduced amino acid sequence of the mouse AChR alpha-subunit with Torpedo marmorata, T. californica, chicken, human, and calf sequences show overall homologies of 80%, 80%, 86%, 96%, and 95%, respectively. More detailed analyses reveal a non-random distribution of amino acid substitutions in several structural domains. Based on the absolute conservation of cysteine residues, a new model for the arrangement of the disulfide bonds in the extracellular portion of the alpha-subunit is proposed.

Amino Acid Sequence↗
PubMed1985

Muscle denervation increases the levels of two mRNAs coding for the acetylcholine receptor alpha-subunit.

The mRNA coding for the alpha-subunit of the acetylcholine receptor was studied in mouse leg and rat diaphragm muscle. We find that denervation of rat diaphragm results in a 7-fold increase in mRNA coding for the alpha-subunit, whereas denervation of mouse leg muscle results in approximately a 50-fold increase in alpha-subunit-specific mRNA. The relationship of the mRNAs purified from innervated and denervated muscle was investigated by SI nuclease mapping. Two mRNA species were found in both innervated and denervated muscle which differ in their 3'-untranslated region. The levels of both these mRNA species increase upon denervation of mouse leg muscle.

Animals↗
PubMed1984

High-performance liquid chromatographic assay for labetalol in human plasma using a PRP-1 column and fluorometric detection.

A high-performance liquid chromatographic assay for the determination of labetalol, a novel antihypertensive agent, in human plasma was developed. Reversed-phase separation of labetalol and the internal standard was accomplished on a 150 X 4.1 mm column commercially packed with a spherical (8-12 micron particle size) macroporous co-polymer (PRP-1). Unlike silica-based columns, the unique properties of PRP-1 permit operation at pH extremes. Based on this advantage, a mobile phase which was sufficiently basic (pH 9.5) to optimize the fluorescent yield of analyte and provide the necessary specificity was selected. Detector response (peak area ratio) was linear from 4 to 500 ng/nl. Following a simple extraction procedure, samples were automatically injected and analyzed using micro-processor-controlled equipment. No interferences were observed in the extracts obtained from drug-free plasma which were processed under the conditions described for unchanged drug. The limit of quantitation using 0.5 ml of plasma was validated to 4 ng/ml. The inter-assay precision (coefficient of variation) was less than 4.6% at all concentrations evaluated from 4 to 300 ng/ml. This method is suitable for the routine quantitation of labetalol or its RR isomer (dilevalol) in plasma (0-24 h) following the administration of therapeutically effective doses to man.

Chromatography, High Pressure Liquid↗
PubMed1984

The effects of maternal hyperoxia on fetal breathing movements in third-trimester pregnancies.

Fetal breathing movements and gross fetal body movements were observed before, during, and after maternal hyperoxia induced by inhalation of 50% oxygen in 14 women with normal term pregnancies. Studies were performed with real-time B-scan linear-array ultrasound and were standardized for time of day, maternal nutritional status, postprandial interval, and length of observation. Each study included a 30-minute baseline, followed by 15 minutes of hyperoxia, and 45 minutes of continued monitoring. No significant changes occurred in the mean incidences of fetal breathing movements, gross fetal body movements, the mean breathing rate, or breath interval variability, as analyzed in 5-minute epochs. Maternal PO2, as measured by transcutaneous electrodes, increased to the maximum level after 5 minutes of hyperoxia (155% over control levels). The breathing activity of normal third-trimester fetuses appears to be stimulated maximally in the second and third postprandial hours and cannot be further increased by maternal hyperoxia. This protocol represents a possible clinical strategy for investigating fetuses at risk for intrauterine hypoxia, provided that similar experimental conditions are maintained.

Female↗
PubMed1984

Maternal glucose injections do not alter the suppression of fetal breathing following maternal ethanol ingestion.

In order to determine whether intravenous injections of glucose could reverse the effects of maternal ingestion of ethanol (0.25 gm/kg), glucose (25 gm intravenously) or an equal volume of saline solution was administered to eight pregnant women at 37 to 40 weeks' gestation after ingestion of ethanol. Fetal breathing movements were abolished within 30 minutes after ingestion of ethanol and were not increased by maternal intravenous injections of glucose. Maternal heart rate was increased by ethanol. The disposition of ethanol in maternal blood was not altered by injection of glucose, and fetal gross body movements were not influenced by maternal ingestion of ethanol or by injections of glucose after ethanol.

Blood Glucose↗
PubMed1984

Fetal breathing, gross fetal body movements, and maternal and fetal heart rates before spontaneous labor at term.

In order to examine patterns of fetal breathing and body movements and fetal and maternal heart rates near term, we studied 28 healthy pregnant women over 24-hour observation intervals at 38 to 40 weeks' gestation. There was a significant decrease in the incidence of fetal breathing movements during the last 3 days before spontaneous parturition at term, but there was no significant difference in the patterns of gross body movements or fetal and maternal heart rates. We concluded that, prior to spontaneous labor at term, there is a normal decrease in the incidence of fetal breathing movements but no similar change in the incidence of gross fetal body movements. This study suggested that the presence of gross fetal body movements is a more consistent index of fetal health before spontaneous labor at term.

Female↗
PubMed1984

Effect of intravenous glucose injection on human maternal and fetal heart rate at term.

The effects of maternal intravenous glucose administration (25 gm) on maternal heart rate, fetal heart rate, gross fetal body movements, and fetal heart rate accelerations was measured in 11 healthy pregnant women at 38 to 40 weeks' gestational age. Mean maternal heart rate increased from 78.3 +/- 0.8 bpm during the control period to 82.7 +/- 0.5 bpm at 30 to 85 minutes following glucose injections (p less than 0.01). Mean fetal heart rate rose from 137.8 +/- 0.4 bpm to 142.4 +/- 0.3 bpm at 50 to 95 minutes following injections (p less than 0.001). The incidence of gross fetal body movements and the number, duration, and amplitude of fetal heart rate accelerations did not change following glucose injection. We conclude that maternal glucose administration near term results in a small but significant increase in the mean maternal heart rate and fetal heart rate and no change in the incidence of gross fetal body movements or in fetal heart rate accelerations.

Blood Glucose↗
PubMed1984

Accelerations of the human fetal heart rate at 38 to 40 weeks' gestational age.

In order to document the normal structure and pattern of fetal heart rate accelerations near term, we measured fetal heart rate and fetal movements for 24-hour observation intervals in 12 healthy pregnant women at 38 to 40 weeks' gestation. There were 34 accelerations per hour on the average with a mean amplitude of 22.8 bpm and a mean duration of 40.7 seconds. The longest time between successive accelerations was 37 minutes. There was a significant negative correlation between the mean daily maximum amplitude of accelerations and the mean daily fetal heart rate (r = -0.84). Fetal heart rate acceleration patterns suggested a prolonged period of fetal wakefulness during the late evening.

Electrocardiography↗
PubMed1984

The effect of sex differences and nondefensiveness on the predictive validity of Barron's Es scale.

Extended research reported by Clayton and Graham (1979) on the relationship between Es scores and nondefensiveness with respect to prognosis for positive change in treatment (N = 103). Sex differences and the effect of restricting the F-K index as a measure of defensiveness to the normal range (+1 to +9) were investigated. Results indicated that for females only low Es scores and nondefensiveness (as measured by patients' willingness to admit to having problems and by an F-K index in the normal range) were to a limited degree significantly related to positive outcome. Implications of these findings in terms of the validity of Barron's Es scale for an inpatient psychiatric population were discussed.

Adolescent↗
PubMed1984

Predicting outcome of psychiatric hospitalization: a comparison of attitudinal and psychopathological measures.

Demonstrated that a generalized measure of locus of control (the Rotter I-E Scale) is not as effective in predicting outcome of hospitalization as a direct assessment of psychiatric patients' (N = 103) willingness to admit to having problems. The addition of diagnostic classification to patients' acknowledgment of problems did not improve the discriminative capacity of the latter with regard to length of hospitalization or readmission within 1 year. Patients' acceptance of responsibility for their problems was not related significantly to length of stay or readmission, except in the presence of severe pathology (as indicated by diagnostic classification). Implications for therapeutic strategies based on these findings were presented.

Adolescent↗