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Biomedical subjects

J T Wilson

Publications and source records attributed to J T Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1978

Death in an adolescent following an overdose of acetaminophen and phenobarbital.

A 13-year-old epileptic girl took an overdose of acetaminophen (Tylenol) and phenobarbital. Hepatic encephalopathy developed and the patient died eight days later. Necropsy revealed extensive centrilobular necrosis of the liver, degeneration of the renal distal tubules, and infarcted and demyelinated foci throughout the white matter of the cerebral cortex. Electron microscopy of intact hepatocytes showed a proliferation of both smooth and rough endoplasmic reticulum consistent with enzyme induction from phenobarbital. To our knowledge, this is the first reported death in a child in the United States as a result of acetaminophen and should alert physicians to an expected increase in acetaminophen toxicity as the drug becomes more widely available.

Acetaminophen↗
PubMed1978

Gentisuric acid: metabolic formation in animals and identification as a metabolite of aspirin in man.

Gentisuric acid was synthesized from gentisic acid and glycine ethyl ester. NMR, mass spectrometric and elemental analysis confirmed the product as GU, and physicochemical characteristics were determined. A TLC-densitometric technique was developed to estimate GU and other metabolites of aspirin. Conjugation of gentisic acid with glycine to form GU was catalyzed by a mitochondrial fraction of rat and beef liver. GU was also formed by the rat liver microsomal hydroxylation of salicyluric acid, and phenobarbital pretreatment increased this formation. A random survey showed GU in 76% of SA-positive urines from aspirin-treated patients. Identity of GU in urine from two aspirin-treated patients was confirmed by TLC and mass spectrometric analysis, and hydrolysis of the compound from one patient yielded glycine and gentisic acid. Urine from controls or post-aspirin treatment patients did not show GU by TLC analysis. These results demonstrate for the first time the metabolic formation of GU in animals and its occurrence as a metabolite of aspirin in man.

Acyltransferases↗
PubMed1978

Insertion of synthetic copies of human globin genes into bacterial plasmids.

Double stranded human globin cDNA was synthesized by use of viral reverse transcriptase from globin mRNA of cord blood of premature infants requiring exchange transfusions. The cDNA was introduced into plasmids and the recombinant DNA plasmids used to transform E. coli X1776. A number of transformants were obtained. Plasmid DNA from selected colonies was isolated and characterized for the type of globin cDNA it contained by three types of procedures: 1) hybridization to previously characterized 3H-labeled alpha,beta and gamma cDNA; 2) analysis of the size and nature of fragments produced by digestion of the plasma DNA by different restriction endonucleases; and 3) by rapid DNA sequence analysis of selected DNA fragments produced by restriction endonuclease digestion. Analysis by these techniques of plasmid DNA from different colonies has definitively identified the presence of human alpha, beta or gamma cDNA sequences in different plasmids.

Base Sequence↗
PubMed1978

Designing a comprehensive service for a health care group: a framework for planning.

This article describes an exercise which was designed by a multidisciplinary group, including a community physician, health economist, clinician and operational research practitioner, to explore the essential nature of planning services for a particular health care group. The first programme, described in the article, was concerned with psychogeriatric services, including both community and hospital provision, but it is indicated that the exercise can be adapted to all other services, and has already been used to evolve a comprehensive accident and emergency service in a particular health area. Participants came from a wide variety of disciplines, including community medicine, psychiatry, geriatrics, hospital and community nursing and non-medical administration. The tutors to the course were those who had been involved in its planning and they spent the time working with the participants to explore the concepts involved and to produce some practical solutions that could be used in the field.

Decision Making↗
PubMed1977

Human beta-globin messenger RNA. III. Nucleotide sequences derived from complementary DNA.

Sequences of human beta-globin mRNA were determined by analysis of complementary DNA. beta-mRNA was transcribed into double-stranded cDNA by RNA-dependent DNA polymerase. cDNA was cut by restriction endonucleases and the fragments were terminally labeled by means of polynucleotide kinase and [gamma-32P]ATP. After purification, fragments were degraded by snake venom phosphodiesterase. Alternatively single-stranded [32P]cDNA was prepared by transcription in the presence of [alpha-32P]dCTP and actinomycin D; the product was digested by endonuclease IV and degraded by snake venom phosphodiesterase. cDNA tracts obtained by both labeling methods enabled us to construct a sequence for the translated and 3'-terminal untranslated regions of human beta-mRNA.

Anemia, Sickle Cell↗
PubMed1977

Human beta-globin messenger RNA. I. Nucleotide sequences derived from complementary RNA.

Sequence analysis studies were carried out on human beta-globin mRNA (beta-mRNA) prepared from alpha-thalassemic, sickle cell, and Hb A reticulocytes. Highly purified beta-mRNA served as substrate for the preparation of cDNA by RNA-dependent DNA polymerase. The cDNA was transcribed by Escherichia coli RNA polymerase and the resulting cRNA was analyzed. Over 300 nucleotides were assigned to the beta-mRNA coding region and 37 nucleotides were assigned to the 3'-terminal noncoding region. The normal termination codon is UAA which is separated by 28 nucleotides from an out of phase UAA triplet. The origin of each of the abnormally long beta-globin variants Tak and Cranston is consistent with reduplication of dinucleotides prior to the normal termination codon, and both globin variants can terminate at the out of phase UAA.

Anemia, Sickle Cell↗
PubMed1977

Human globin messenger RNA: importance of cloning for structural analysis.

The sequence of most of the human beta globin messenger RNA and large sections of the alpha globin messenger RNA has been determined. Partly because of genetic polymorphism, it was necessary to clone globin complementary DNA in order to extend the analysis. Purified human fetal globin messenger RNA was isolated and used as a template by reverse transcriptase to produce duplex complementary DNA molecules. These molecules were linked in vitro to plasmid DNA by use of T4 ligase in the presence of Escherichia coli Pol 1. Several colonies transformed by these molecules have been shown to hybridize with labeled human globin complementary RNA.

Base Sequence↗
PubMed1977

Nucleotide sequence of 3' untranslated portion of human alpha globin mRNA.

We have determined the nucleotide sequence of 75 nucleotides of the 3'-untranslated portion of normal human alpha globin mRNA which corresponds to the elongated amino acid sequence of the chain termination mutant Hb Constant Spring. This was accomplished by sequence analysis of cDNA fragments obtained by restriction endonuclease or T4 endonuclease IV cleavage of human globin cDNA synthesized from globin mRNA by use of viral reverse transcriptase. Analysis of cRNA synthesized from cDNA by use of RNA polymerase provided additional confirmatory sequence information. Possible polymorphism has been identified at one site of the sequence. Our sequence overlaps with, and extends the sequence of 43 nucleotides determined by Proudfood and coworkers for the very 3'-terminal portion of human alpha globin mRNA. The complete 3'-untranslated sequence of human alpha globin mRNA (112 nucleotides including termination codon) shows little homology to that of the human or rabbit beta globin mRNAs except for the presence of the hexanucleotide sequence AAUAAA which is found in most eukaryotic mRNAs near the 3'-terminal poly (A).

Anemia, Sickle Cell↗
PubMed1977

Structure of human hemoglobin messenger RNA and its relation to hemoglobinopathies.

1. One-fifth to 1/4 of globin mRNA is untranslated sequence other than polyadenylic acid. 2. The untranslated sequences of mRNA vary markedly in their sequence and in their length. 3. Globin mRNAs demonstrate a marked bias in codon selection. 4. Viral mRNA shows a quite different pattern of codon selection; therefore, the selection of codons is not uniform for all mRNAs functioning in animal cells. 5. Elongated hemoglobin chains can be accounted for by frame-shift mutations, or point mutations within the normal termination codon. The additional amino acids are then coded for by sequences that are normally untranslated. 6. Certain hemoglobin deletion mutants occur at sites where there are partially reiterated sequences within the heomoglobin messenger RNA.

Base Sequence↗
PubMed1977

Biphasic kinetic profile for carbamazepine epoxide formation.

The formation of the stable 10,11-epoxide from carbamazepine by rat liver microsomes was studied. A biphasic activity-substrate profile was consistently found with microsomes from both control and phenobarbital pretreated rats. These data could either indicate epoxide formation by multiple catalytic sites with differential substrate affinity or a solvent effect on the enzyme or its environment.

Animals↗
PubMed1976

Growth hormone and drug metabolism. Acute effects on microsomal mixed-function oxidase activities in rat liver.

Adult male rats were subjected either to sham operation or to hypophysectomy and adrenalectomy and maintained for a total of 10 days before treatment with growth hormone. Results of the early effects of growth hormone on the activities of the mixed-function oxidases in rat liver over a 96h period after growth-hormone treatment are presented. 2. Hypophysectomy and adrenalectomy result in decreased body and liver weight and decreased drug metabolism (mixed-function oxidases). Concentrations of electron-transport-system components are also decreased. 3. In the hypophysectomized/adrenalectomized rats, growth hormone decreases the activities of the liver mixed-function oxidases and the cytochrome P-450 and cytochrome c reductases, as well as decreasing the concentration of cytochrome P-450 compared with that of control rats. Similar but less dramatic results are obtained with sham-operated rats. 4. It is concluded that whereas growth hormone enhances liver growth, including induction of many enzyme activities, it results in a decrease in mixed-function oxidase activity. Apparently, mixed-function oxidase activity decreases in liver when growth (mitogenesis) increases.

Adrenalectomy↗
PubMed1976

Growth hormone and drug metabolism. Acute effects on nuclear ribonucleic acid polymerase activity and chromatin.

Adult male rats, subjected either to sham operation or to hypophysectomy and adrenalectomy were maintained for 10 days before treatment with growth hormone. Results of the acute effects of growth hormone on the rat liver nuclear RNA polymerase I (nucleolar) and II (nucleoplasmic) activities as well as the chromatin template capacity were then studied and compared with the growth-hormone effects on the drug metabolism described in the preceding paper (Wilson & Spelsberg, 1976). 2. Conditions for isolation and storage of nuclei for maintenance of optimal polymerase activities are described. It is verified that the assays for polymerase activities require a DNA template, all four nucleoside triphosphates, and a bivalent cation, and that the acid-insoluble radioactive product represents RNA. Proof is presented that under high-salt conditions DNA-like RNA (polymerase II) is synthesized, and that under low-salt conditions in the presence of alpha-amanitin, rRNA (polymerase I) is synthesized. 3. In the livers of hypophysectomized/adrenalectomized rats, growth hormone increases the activity of both RNA polymerase enzymes and the chromatin template capacity within 1h after treatment. The effects last for 12h in the case of polymerase II but for only 6h in the case of polymerase I. Sham-operated rats respond to growth hormone in a manner somewhat similar to that shown by hypophysectomized/adrenalectomized rats. These results, which demonstrate an enhancement of RNA polymerase I activity in response to growth hormone, support those from other laboratories. 4. Growth-hormone enhancement of the chromatin template capacity in the liver of hypophysectomized/adrenalectomized rats contrasts with previous reports. The growth-hormone-induced de-repression of the chromatin DNA could represent the basis of the growth-hormone-induced enhancement of RNA polymerase II activity in the hypophysectomized/adrenalectomized rats, although some effect of growth-hormone on the polymerase enzymes is still suggested.

Adrenalectomy↗
PubMed1976

Comparison of the half-life of antipyrine in plasma, whole blood and saliva of man.

A previously described GLC method has been modified and applied to measurement of antipyrine levels in plasma, blood and saliva of man following administration of a single oral dose (10 mg/kg). Tery time studied. The half-life of antipyrine determined in blood, plasma or saliva in any given individual was similar. The intersubject variation in half-life was about two-fold (n = 5). Antipyrine levels in saliva were not affected by the rate of saliva flow when collections were made continuously for 20 minutes. This study has demonstrated that kinetic data about antipyrine comparable to that from plasma may also be obtained from readily accessible tissue fluids, such as saliva and capillary blood.

Adult↗
PubMed1976

Disposition of propoxyphene and propranolol in children.

The disposition of propoxyphene and propranolol was studied in children by means of two protocols which minimized the number of blood samples taken from each child. Propoxyphene and its metabolite, norpropoxyphene, were measured in two plasma samples obtained from different children at various times after a single oral dose. These data were pooled and a plasma concentration/time curve was obtained which was consistent with an average T 1/2 of 3.5 hr in this population. The bioavailability of tablets and a solution of propranolol was compared with a crossover design by obtaining plasma samples at the end of the dosage interval during chronic oral administration of various doses. No clear differences in the bioavailability of the two formulations could be detected. Both drugs showed marked interindividual differences in plasma concentrations following oral administration. These findings are consistent with the high hepatic extraction ratio and large presystemic (first pass) effect previously described in adults. The large individual variability supports the concept of monitoring plasma levels as an aid to therapy and demonstrates that the use of a weight-adjusted dose in children can be only an approximation for initial treatment.

Adolescent↗
PubMed1976

Kinetics of carbamazepine and its 10,11-epoxide metabolite in children.

The plasma steady-state concentration of carbamazepine (CBZ) and its metabolite (carbamazepine-10,11-epoxide, CBZ-epoxide) was assessed in 43 children (2-15 yr) on CBZ (Tegretol) treatment. Twenty of the children received combined treatment with other anticonvulsant drugs simultaneously. The plasma concentrations were in the same range as had been found in adult patients on corresponding doses. Only a weak correlation was noted between dose and plasma CBZ concentration in the group of children on single-drug treatment, and there was no correlation in the group of children on combined drug regimen. Plasma levels of CBZ correlated with those of the metabolite. Children on combined treatment had lower CBZ concentration and, expressed as percent of the parent drug, the metabolite concentration was significantly higher than in children treated only with CBZ. In 2 children the plasma half-life of CBZ was estimated and found to be slightly shorter than has previously been reported in adults. In evaluating the plasma level-effect relationship of CBZ, the plasma concentration of the CBZ-epoxide should be measured simultaneously because of its anticonvulsant effect and interindividual variability.

Adolescent↗
PubMed1976

Loading and conventional dose therapy with phenytoin in children: kinetic profile of parent drug and main metabolite in plasma.

Epileptic children were given phenytoin (DPH) in loading (four doses of 4.4 to 6.3 mg/kg/dose given 8-hourly and then 6 mg/kg/day) or conventional (5 to 9 mg/kg/day) doses. Plasma levels of DPH and its main metabolite (p-OH-DPH) were measured by a mass fragmentographic technique. Plasma DPH levels of more than 10 mug/ml were achieved within 16 to 38 hr in the children given loading doses and within 5 days in the conventionally dosed children. No immediate side effects were noted, but within 8 to 10 days 9 of 13 children developed a generalized skin rash. Plasma p-OH-DPH (free or conjugated) paralleled DPH during the accumulation phase but not during DPH elimination. The ratio of metabolite to DPH in plasma showed both an interindividual variation and an inverse relation to the level of DPH. Identical twins in the study had a similar ratio and plasma level-time course profile. It is concluded that the loading dose regiment achieves an appropriate plasma level of DPH rapidly, that saturation kinetics are operative for p-OH-DPH formation, that the ratio of metabolite to DPH in plasma is an individual characteristic in children, and that further studies on the delayed toxicity are needed before the loading dose regimen can be recommended.

Adolescent↗