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Biomedical subjects

J Patrick

Publications and source records attributed to J Patrick.

At least 127 records · Page 7Linked to original sources

The role of fetal urinary excretion in the transfer of ethanol into amniotic fluid after maternal administration of ethanol to the near-term pregnant ewe.

The objective of this study was to determine whether fetal urinary excretion is a major route of ethanol transfer into the amniotic fluid surrounding the fetus following maternal administration of ethanol. Conscious instrumented pregnant ewes between 130 and 137 days' gestation (term, 147 days) with (n = 3) or without (n = 3) a catheter in the fetal bladder were administered 1 g ethanol/kg maternal body weight as a 1-h maternal intravenous infusion. Maternal blood, fetal blood, and amniotic fluid samples were collected at selected times, and fetal urine was collected continuously from the bladder-cannulated fetus during the 14-h study for the determination of ethanol concentrations. Fetal urinary excretion of ethanol occurred, and the total amount of ethanol excreted represented 0.30 +/- 0.07 (SD)% of the maternal ethanol dose. The renal clearance of ethanol by the fetus was 0.43 +/- 0.06 mL/min. The pharmacokinetics of ethanol in the maternal-fetal unit and the amniotic fluid for the bladder-cannulated fetal preparation were similar to the data for the nonbladder-cannulated preparation. The data indicate that fetal urinary excretion of ethanol is a secondary route of ethanol transfer into the amniotic fluid. It would appear that diffusion of ethanol across membranes from the maternal and fetal circulations is a major route of ethanol transfer into this intrauterine compartment.

Amniotic Fluid↗

The relationship between fetal breathing movements and prostaglandin E2 during ACTH-induced labour in sheep.

We measured fetal breathing movements and fetal carotid arterial prostaglandin E concentrations during adrenocorticotrophin-induced labour in 6 pregnant sheep and in 6 control animals starting at day 127. The 6 ACTH-treated animals went into labour on average 97 h after the onset of infusion and the incidence of fetal breathing movements diminished during the last 12h before the onset of labour. There was a significant negative relationship between the incidence of fetal breathing movements and fetal carotid arterial prostaglandin E concentrations (r = -0.88; P less than 0.001) in ACTH treated animals. These data suggest a role for prostaglandin E in the diminution of fetal breathing movements prior to the onset of labour.

Adrenocorticotropic Hormone↗

Effects of maternal indomethacin administration on fetal breathing movements in sheep.

To determine the role of prostaglandins in the control of fetal breathing movements, we infused indomethacin (5 mg/ml; 25 mg/kg per day) into the maternal femoral vein for 70 h in 5 pregnant ewes. There was a significant increase in the incidence and amplitude of fetal breathing movements beginning within 2 h reaching a peak at 8-10 h. It then diminished and was no longer present by 20-70 h despite continued indomethacin infusion. Maternal glucose concentrations were increased at 8 and 16 h following the initiation of indomethacin infusion. The data suggested that the previously reported effects of cyclo-oxygenase inhibitor on fetal breathing movements are transient and do not continue beyond 20 h.

Animals↗

Antibiotic treatment of pelvic inflammatory disease. Trends among private physicians in the United States, 1966 through 1983.

Although pelvic inflammatory disease is the most common serious infection among young women of reproductive age in the United States, no nationwide data are available on the patterns of antibiotic treatment of this disease. To examine these patterns we analyzed over 25 million antibiotic prescriptions for treatment of pelvic inflammatory disease from 1966 through 1983, using the National Disease and Therapeutic Index. Most patients received a single antibiotic on an outpatient basis. Overall, use of natural penicillins declined markedly, and use of aminopenicillins more than doubled. Cephalosporins emerged as the most frequently prescribed antibiotic for hospitalized patients. Nationwide surveillance of treatment patterns may help to identify areas needing improvement through continuing education.

Anti-Bacterial Agents↗

Dipyridamole-insensitive nucleoside transport in mutant murine T lymphoma cells.

From a mutagenized population of S49 murine T lymphoma cells, a mutant cell line, JPA4, was selected that expressed an altered nucleoside transport capability. JPA4 cells transported low concentrations of purine nucleosides and uridine more rapidly than the parental S49 cell line. The transport of these nucleosides by mutant cells was insensitive to inhibition by either dipyridamole (DPA) or 4-nitrobenzylthioinosine (NBMPR), two potent inhibitors of nucleoside transport in mammalian cells. Kinetic analyses revealed that the apparent Km values for the transport of uridine, adenosine, and inosine were 3-4-fold lower in JPA4 cells compared to wild type cells. In contrast, the transport of both thymidine and cytidine by JPA4 cells was similar to that of parental cells, and transport of these pyrimidine nucleosides remained sensitive to inhibition by both NBMPR and DPA. Furthermore, thymidine was a 10-12-fold weaker inhibitor of inosine transport in JPA4 cells than in wild type cells. Thus, JPA4 cells appeared to express two types of nucleoside transport activities; a novel (mutant) type that was insensitive to inhibition by DPA and NBMPR and transported purine nucleosides and uridine, and a parental type that retained sensitivity to inhibitors and transported cytidine and thymidine. The phenotype of the JPA4 cell line suggests that the sensitivity of mammalian nucleoside transporters to both NBMPR and DPA can be genetically uncoupled from its ability to transport certain nucleoside substrates and that the determinants on the nucleoside transporter that interact with each nucleoside are not necessarily identical.

Animals↗

Chronic jejunostomy feeding with a non-elemental formula in undernourished patients with cystic fibrosis.

Ten patients with cystic fibrosis, moderate to severe lung disease (forced expiratory flow % predicted 26.0, 15.7 [SD]), and undernutrition resistant to oral supplementation have been treated for 10 to 36 months with night-time feeds of a non-elemental formula given via a jejunostomy. All patients gained some weight and showed a significant increase in weight for height (change % wt/ht 8.1, 6.0 [SD] and mid-arm muscle circumference (change MAMC % standard 6.2, 5.7 [SD]). Although the forced expiratory flow indicated progression of the small airways disease during the period of feeding, the forced vital capacity did not significantly decline. In nine patients improvement in % wt/ht was maintained. One patient tolerated the feeding poorly and died of severe pulmonary disease after 10 months. The non-elemental formula used cost less than half that of an elemental formula. The jejunostomy tubes were unobtrusive and secured with only a small transparent dressing, which facilitated replacement. No serious complications resulted from jejunostomy feeding.

Adolescent↗

Isolation and sequence of cDNA clones coding for the precursor to the gamma subunit of mouse muscle nicotinic acetylcholine receptor.

cDNA libraries have been constructed in plasmid (pBR322) and bacteriophage lambda gammagt10) vectors with poly (A+) RNA isolated from the nonfusing mouse muscle cell line BC3H-1. The libraries were screened with a restriction fragment derived from a genomic clone coding for a human acetylcholine receptor gamma subunit. Several clones were obtained whose cDNA inserts possessed nucleotide and deduced amino acid sequence homology with acetylcholine receptor gamma subunits from Torpedo californica, chick, calf, and human. One isolate, lambda BMG419, has 88 nucleotides of 5'-untranslated sequence, an open reading frame of 1,557 nucleotides coding for the precursor to the mouse acetylcholine receptor gamma subunit, and 144 nucleotides of 3'-untranslated sequence. Alignment of the lambda BMG419-deduced amino acid sequence with homologs from other species predicts a precursor peptide of 519 amino acids and a mature protein of 497 amino acids, with nonglycosylated molecular weights of 58,744 and 56,424 daltons, respectively. Comparison of the deduced amino acid sequence of the mouse gamma subunit with Torpedo, chick, calf, and human sequences showed overall homologies of 54%, 67%, 90%, and 90%, respectively; however, significantly higher homologies were found in several putative functional domains. Radiolabeled lambda BMG419 has been used to identify homologous RNA species, one of approximately 2 kb and one of about 3.5 kb, in poly (A+) RNA prepared from BC3H-1 cells and denervated mouse limb muscle. gamma Subunit-coding RNA species are considerably more abundant in denervated than in innervated muscle, suggesting that neural regulation of the abundance of the gamma subunit is exerted through regulation of the amount of its mRNA.

Animals↗

Effects of vibratory acoustic stimulation on human fetal breathing and gross fetal body movements near term.

Twenty-five pregnant women between 36 and 40 weeks' gestational age were studied to examine effects of a 5-second external vibratory acoustic stimulus on fetal breathing and gross fetal body movement patterns. When the study period was compared with the control period, there was an immediate significant decrease in the incidence of fetal breathing movements that persisted for 1 hour after the stimulus. Moreover the fetal breathing pattern was more irregular for the hour after the stimulus. There was also a significant but delayed increase in the incidence of gross fetal body movements that persisted for 1 hour after the stimulus. We hypothesize that an external vibratory acoustic stimulus causes a change from a state of sleep to a state of wakefulness in near-term healthy fetuses.

Acoustic Stimulation↗

Stimulation of human fetuses with sound and vibration.

Forty pregnant women between 30 and 42 weeks' gestational age were studied to examine the effects of external sound and vibration on the fetal heart rate. A significant increase in the mean duration and amplitude of the first acceleration after sound stimulus was found when these values were compared with the control values. Conversely the mean time to the first acceleration in the control period was greater than that in the stimulated period. There was a significant increase in the mean duration of fetal heart rate accelerations, the mean amplitude of fetal heart rate accelerations, and the total time spent in accelerations up to 15 minutes after the sound stimulus as compared with the control period. There was no change in the number of accelerations following the sound stimulus compared to control. These data suggest that vibratory acoustic stimuli may influence patterns of fetal heart rate during human pregnancy.

Acoustic Stimulation↗

Analysis of fetal activity and maternal and fetal heart rate using a laboratory minicomputer.

Using a PDP-11 minicomputer, a system was developed for real-time acquisition of fetal breathing, body movement, and heart rate data. Analogue event pulses were input electronically to a DR-11 16 channel A/D, D/A interface and the event times were measured using an AR-11 real-time clock. Event times were stored for comprehensive off-line analysis and useful data summaries were also provided on-line. The on-line printouts enabled investigators to examine the quality of the data at the time of the study. The system has resulted in faster data acquisition and analysis and greater accuracy of measurement.

Computers↗

Mapping of brain areas expressing RNA homologous to two different acetylcholine receptor alpha-subunit cDNAs.

We have used an in situ RNA X RNA hybridization technique to determine, in the central nervous systems of the mouse and rat, the distribution of RNA homologous to cDNA clones encoding the alpha subunit of a putative neural nicotinic acetylcholine receptor and the alpha subunit of the muscle nicotinic acetylcholine receptor. Hybridization of the neural alpha-subunit probe was strongest in the medial habenula but was also detected consistently in the compact part of the substantia nigra and ventral tegmental area, in the neocortex, and in certain parts of the thalamus and hypothalamus. The in situ hybridization technique makes it possible to compile a map of brain regions containing cell bodies expressing RNA coding for a specific receptor type and subsequently to apply the techniques of molecular biology to study these brain receptors.

Animals↗

The effect of dietary polyunsaturated fat on cation transport and hypertension in the rat.

1. Essential hypertension is associated with increased intracellular sodium in both erythrocytes and leucocytes. Reports in the literature indicate that increasing the level of polyunsaturated fat in the diet reduces hypertension. In the present study, spontaneously hypertensive rats (Wistar-Kyoto, which develop systolic blood pressures in excess of 140 mmHg by 8 weeks of age) were fed on high-fat diets (40% energy derived from fat), the fat being maize oil (high in polyunsaturated fatty acids, PUFA) and coconut oil (low in PUFA). 2. Significantly higher blood pressures developed by 110 d of age in the rats fed on a high-PUFA diet, compared with those fed on the low-PUFA diet. 3. In thymocytes, ouabain-sensitive efflux rate constants were significantly lower in the group fed on the high-PUFA diet. Ouabain-insensitive efflux rate constants were unaffected by diet.

Animals↗

Transitory stimulation of human platelet 12-lipooxygenase by vitamin E supplementation.

Human platelet lipooxygenase converts arachidonic acid to 12-hydroperoxy-eicosatetraenoic acid (12-HPETE), which is rapidly reduced by peroxidases to 12-hydroxy-eicosatetraenoic acid (12-HETE). This study was conducted to examine the effect of vitamin E supplementation on platelet 12-lipooxygenase activity. Sixteen healthy subjects were supplemented with 400 IU/day of either D-alpha-tocopherol (268 mg) or DL-alpha-tocopherol (364 mg) for 4 wk. Supplements elicited a transitory increase of lipooxygenase activity but a suppression of peroxidase activity, as indicated by increased 12-HETE production and 12-HPETE accumulation. Plasma-tocopherol concentration was double the presupplement value and remained stable during supplementation. Neither age, sex, nor isomeric form of tocopherol supplement significantly influenced the pattern of response. Results show that vitamin E exerts a differential effect on platelet lipooxygenase and peroxidase activities.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Effect of dietary fat on sodium transport and sodium-lithium countertransport in rat erythrocytes and thymocytes.

Two groups of normotensive Sprague-Dawley rats were fed high fat diets (40% of calories derived from fat). One group received a diet high in polyunsaturated fat (corn oil 45% polyunsaturated), and the other a diet high in saturated fat (coconut oil). Growth rates were the same in both groups. Sodium transport was measured in isolated thymocytes from both groups. The rats fed the diet high in polyunsaturated fat had lower sodium efflux rate constants than those fed the diet high in saturated fat. The reduction was almost entirely confined to the ouabain-sensitive portion of sodium efflux. Sodium-lithium countertransport in isolated thymocytes and erythrocytes was the same for both groups.

Animals↗

Rapid correction of wasting in children with cerebral palsy.

Severe cerebral palsy is often accompanied by wasting. The authors used standard methods for the correction of primary protein energy malnutrition in children with severe cerebral palsy. A randomised controlled trial was used to compare intensive nasogastric tube-feeding with the best oral feeding that could be achieved. Nasogastric feeding led to highly significant increases in weight. The changes in skinfold thickness and mid-arm muscle circumference indicated increases in both lean and fat tissue. This study indicates that wasting associated with cerebral palsy can be quickly corrected, so there is no reason why such patients should be exposed to the increased risks associated with wasting.

Adolescent↗

Incomplete nucleoside transport deficiency with increased hypoxanthine transport capability in mutant T-lymphoblastoid cells.

From a mutagenized population of wild-type mouse (S49) T-lymphoma cells, a clone, 80-5D2, was isolated in a single step by virtue of its ability to survive in 80 nM 5-fluorouridine. Unlike previously isolated nucleoside transport-deficient cell lines (A. Cohen, B. Ullman, and D. W. Martin, Jr., J. Biol. Chem. 254:112-116, 1979), 80-5D2 cells were only slightly less sensitive to growth inhibition by a variety of cytotoxic nucleosides and were capable of proliferating in hypoxanthine-amethopterin-thymidine-containing medium. The molecular basis for the phenotype of 80-5D2 cells was incomplete deficiency in the ability of the mutant cells to translocate nucleosides across the plasma membrane. Interestingly, mutant cells were more capable than wild-type cells of transporting the nucleobase hypoxanthine. Residual transport of adenosine into 80-5D2 cells was just as sensitive to inhibition by nucleosides and more sensitive to inhibition by hypoxanthine than that in wild-type cells, indicating that the phenomena of ligand binding and translocation can be uncoupled genetically. The 80-5D2 cells lacked cell surface binding sites for the potent inhibitor of nucleoside transport p-nitrobenzylthioinosine (NBMPR) and, consequently, were largely resistant to the physiological effects of NBMPR. However, the altered transporter retained its sensitivity to dipyridamole, another inhibitor of nucleoside transport. The biochemical phenotype of the 80-5D2 cell line supports the hypothesis that the determinants that comprise the nucleoside carrier site, the hypoxanthine carrier site, the NBMPR binding site, and the dipyridamole binding site of the nucleoside transport function of mouse S49 cells are genetically distinguishable.

Animals↗