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Biomedical subjects

J Eastman

Publications and source records attributed to J Eastman.

12 recordsLinked to original sources
PubMed1995

Fasciculin 2 binds to the peripheral site on acetylcholinesterase and inhibits substrate hydrolysis by slowing a step involving proton transfer during enzyme acylation.

The acetylcholinesterase active site consists of a gorge 20 A deep that is lined with aromatic residues. A serine residue near the base of the gorge defines an acylation site where an acyl enzyme intermediate is formed during the hydrolysis of ester substrates. Residues near the entrance to the gorge comprise a peripheral site where inhibitors like propidium and fasciculin 2, a snake neurotoxin, bind and interfere with catalysis. We report here the association and dissociation rate constants for fasciculin 2 interaction with the human enzyme in the presence of ligands that bind to either the peripheral site or the acylation site. These kinetic data confirmed that propidium is strictly competitive with fasciculin 2 for binding to the peripheral site. In contrast, edrophonium, N-methylacridinium, and butyrylthiocholine bound to the acylation site and formed ternary complexes with the fasciculin 2-bound enzyme in which their affinities were reduced by about an order of magnitude from their affinities in the free enzyme. Steady state analysis of the inhibition of substrate hydrolysis by fasciculin 2 revealed that the ternary complexes had residual activity. For acetylthiocholine and phenyl acetate, saturating amounts of the toxin reduced the first-order rate constant kcat to 0.5-2% and the second-order rate constant kcat/Kapp to 0.2-2% of their values with the uninhibited enzyme. To address whether fasciculin 2 inhibition primarily involved steric blockade of the active site or conformational interaction with the acylation site, deuterium oxide isotope effects on these kinetic parameters were measured. The isotope effect on kcat/Kapp increased for both substrates when fasciculin 2 was bound to the enzyme, indicating that fasciculin 2 acts predominantly by altering the conformation of the active site in the ternary complex so that steps involving proton transfer during enzyme acylation are slowed.

Acetylcholinesterase↗
PubMed1994

Localized arteriovenous malformation of the jejunum.

Arteriovenous malformations of the small intestine are a vanishingly rare cause of hemorrhage from the gastrointestinal tract. To our knowledge, only one previous case has been reported. We describe a 41-year-old man with massive gastrointestinal bleeding as the result of a jejunal arteriovenous malformation. We discuss the histologic differentiation from angiodysplasia.

Angiography↗
PubMed1993

Detection of Hb E/beta-thalassemia versus homozygous EE using high-performance liquid chromatography results from newborns.

The influx of Southeast Asian immigrants into California over the past few years has resulted in a dramatic increase of Hb E disorders detected in newborn screening. Initial hemoglobin patterns of FE do not distinguish between homozygous EE, a benign state, and E/beta-thalassemia, a clinically significant disorder which is frequently transfusion-dependent. Since language and cultural customs frequently prevent parent testing which can rule out the thalassemic disorder, and diagnosis in the neonate is not possible by traditional red cell indices and is relatively expensive by DNA methodology, an alternate screening method is proposed. This study investigated the Hb F and Hb E relative percentages obtained in the newborn's high-performance liquid chromatography result, and found that the percentage of Hb E was markedly lower in neonates with Hb E/beta-thalassemia versus those which were homozygous EE. Likewise, the F/E ratios were different in the E/beta-thalassemia group versus the EE group. This analysis can at least minimize the number of DNA tests required, and with more E/beta-thalassemia case data, may prove to be a reliable substitute.

Chromatography, High Pressure Liquid↗
PubMed1991

Social acceptability of methylphenidate and behavior modification for treating attention deficit hyperactivity disorder.

The social acceptability of methylphenidate, behavior modification, and methylphenidate plus behavior modification was evaluated. Fifty mothers of children with attention deficit hyperactivity disorder (ADHD) and 50 control mothers, along with 21 children with ADHD and 20 control children, read a case vignette of an 8-year-old boy with ADHD and descriptions of the three treatment conditions. Subjects then rated the acceptability of each treatment. The mothers of children with ADHD were reassessed 3.5 months later, after experience with interventions for their children. Both ADHD and control families rated behavior modification as the most acceptable, methylphenidate as least acceptable, and the combined condition intermediate between the other two. At follow-up, there was a significant improvement in the acceptability of methylphenidate and the combined condition. The increased acceptability of methylphenidate at follow-up was related to increases in parents' knowledge about ADHD but not to the significant improvements that occurred in the children's hyperactive behavior.

Adult↗
PubMed1982

Lethal and mild hypophosphatasia in half-sibs.

This report concerns a family showing both the lethal and mild form of hypophosphatasia in half-sibs. In addition, several other paternal family members with the mild form are documented. The lethal form is characterized by extremely low to absent alkaline phosphatase activity in serum with hypomineralization of the skeleton, whereas mildly affected individuals have enzyme levels intermediate between normal and lethal states. On the basis of this pedigree and because the mildly affected individuals have both biochemical abnormalities and the clinical phenotype of premature tooth loss, we prefer to designate hypophosphatasia as a dominant trait affecting both osteogenesis and cementogenesis which has mild clinical expression in the heterozygote but lethality in the homozygote. This situation resembles the dominantly inherited enzymopathy acute intermittent porphyria.

Adult↗
PubMed1981

Ultramicro determination of serum triglycerides by bioluminescent assay.

The ultramicro (1-microL samples) assay of serum or plasma triglycerides that we describe here is potentially applicable to 1-nL samples and to isolated cells. This technically simple method involves only three reactions: (a) enzymic hydrolysis with lipase and alpha-chymotrypsin; (b) conversion by glycerol kinase of the liberated glycerol and of adenosine triphosphate added in excess to glycerol-1-phosphate and to adenosine diphosphate; and (c) assay of the residual adenosine triphosphate by the luciferin-luciferase reaction. The assay was optimized with respect to glycerol kinase, buffer, pH, temperature, and adenosine triphosphate. Performance characteristics compare well with those of traditional triglyceride assays.

Drug Stability↗
PubMed1979

The problem of child safety in South Africa.

In Europe and the USA accidents are regarded as a public health problem. South Africa has not kept pace with this trend, particularly in the field of child safety. The Child Safety Centre, which aims at the investigation and prevention of childhood accidents, was established in Cape Town in 1978.

Academies and Institutes↗
PubMed1977

Maxillofacial dysostosis.

Four individuals in a single family affected with maxillofacial dysostosis are reported. Maxillary hypoplasia, delayed onset of speech, and poor development of language skills without associated hearing loss are the main characteristics of the syndrome which is transmitted as an autosomal dominant. Cephalometric analysis and speech and hearing evaluation of our patients confirmed the above findings.

Adolescent↗
PubMed1976

Quantitation of circulating T and B lymphocytes in children with whooping cough.

The numbers of circulating T and B lymphocytes in seven children with whooping cough due to Bordetella pertussis and eight control subjects were determined. All the children with whooping cough had an absolute lymphocytosis (mean 29,142/mm3vs. 5,225/mm3) and by surface marker criteria both T cells and B cells were increased (mean T cells, whooping cough 15,794/mm3 vs. 3,516/mm3 controls; mean B cells, 13,393/mm3 whooping cough vs. 1,706/mm3 controls). However, the ratios of T cells to B cells in the whooping cough (1.4) and control group (1.9) did not differ significantly. This proportional increase in both T and B lymphocytes indicates that whatever mechanism are responsible for lymphocytosis in B. pertussis infection affect both populations in a similar manner.

B-Lymphocytes↗