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Biomedical subjects

B E Campbell

Publications and source records attributed to B E Campbell.

9 recordsLinked to original sources
PubMed2004

Hydrolysis of organophosphorus insecticides by in vitro modified carboxylesterase E3 from Lucilia cuprina.

Resistance of the blowfly, Lucilia cuprina, to organophosphorus (OP) insecticides is due to mutations in LcalphaE7, the gene encoding carboxylesterase E3, that enhance the enzyme's ability to hydrolyse insecticides. Two mutations occur naturally, G137D in the oxyanion hole of the esterase, and W251L in the acyl binding pocket. Previous in vitro mutagenesis and expression of these modifications to the cloned gene have confirmed their functional significance. G137D enhances hydrolysis of diethyl and dimethyl phosphates by 55- and 33-fold, respectively. W251L increases dimethyl phosphate hydrolysis similarly, but only 10-fold for the diethyl homolog; unlike G137D however, it also retains ability to hydrolyse carboxylesters in the leaving group of malathion (malathion carboxylesterase, MCE), conferring strong resistance to this compound. In the present work, we substituted these and nearby amino acids by others expected to affect the efficiency of the enzyme. Changing G137 to glutamate or histidine was less effective than aspartate in improving OP hydrolase activity and like G137D, it diminished MCE activity, primarily through increases in Km. Various substitutions of W251 to other smaller residues had a broadly similar effect to W251L on OP hydrolase and MCE activities, but at least two were quantitatively better in kinetic parameters relating to malathion resistance. One, W251G, which occurs naturally in a malathion resistant hymenopterous parasitoid, improved MCE activity more than 20-fold. Mutations at other sites near the bottom of the catalytic cleft generally diminished OP hydrolase and MCE activities but one, F309L, also yielded some improvements in OP hydrolase activities. The results are discussed in relation to likely steric effects on enzyme-substrate interactions and future evolution of this gene.

Acetylcholinesterase↗
PubMed1994

Paradoxical embolism and acute arterial occlusion: rare or unsuspected?

PURPOSE: The high prevalence of clinically silent venous thrombosis and the presence of a patent foramen ovale (PFO) in up to 35% of the general population suggests that paradoxical emboli may be the cause of an ischemic stroke or a peripheral thromboembolic occlusion more often than is presently considered. This study was undertaken to review our experience with presumed paradoxical embolism. METHODS: Hospital records were reviewed for all patients diagnosed with both a documented PFO and a thromboembolic event between January 1970 and June 1993. Patients with a ventricular or an atrial septal defect or a probable pulmonary arteriovenous fistula were excluded. RESULTS: The presumptive diagnosis of paradoxical embolism was made in seven patients. There were five men and two women, with a median age of 43 years. Four patients were admitted with an acute cerebral ischemic event, and in three others hospitalization was prompted by the development of an acutely ischemic limb (two upper extremity; one lower extremity). In none was there evidence of angiographically significant peripheral or extracranial atherosclerotic occlusive disease. Symptoms suggestive of pulmonary emboli were noted in two patients, and in only one patient was there evidence on physical examination of a deep venous thrombosis. Before 1988 the diagnosis of paradoxical embolism had been made in only one patient after postmortem examination. All six patients who were discharged were available for follow-up (mean 20 months; range 6 to 60 months). There was one late death from lung cancer. Recurrent paradoxical emboli have not been documented during the follow-up period. CONCLUSIONS: The incidence of presumed paradoxical embolism has increased dramatically in the recent past as a consequence of our improved ability to unequivocally detect PFO with associated physiologic shunting. The suspicion of this heretofore "rare" event should be raised, particularly in the young or middle-aged adult diagnosed with an acute thromboembolic event. Until the risk of recurrent ischemic events in the presence of a PFO is better defined, we currently recommend closure of the foramen ovale after a significant or recurrent paradoxical embolus. Otherwise, the selective use of intracaval filters, antiplatelet therapy, and oral anticoagulation remain undefined.

Acute Disease↗
PubMed1988

Bicyclic peptides. VI. Synthesis, conformation, and ion-binding of two bicyclic nonapeptides.

Two related homodetic bicyclic nonapeptides (cyclo Glu-X-Pro-Gly-Lys-X-Pro-Gly)-cyclo (l gamma----5 epsilon), X = Ala(BCP2), X = Leu(BCP3) have been synthesized using conventional solution phase methods involving mixed anhydride coupling reactions starting with appropriately protected naturally occurring amino acids. The conformation and ion binding properties of BCP2 have been studied by nuclear magnetic resonance and circular dichroism techniques. The results of these studies have been compared to those of BCP3. The presence of Ala caused both Ala-Pro bonds to be trans in free BCP2. This characteristic imparted subtle differences to the ion-binding properties of BCP2 as compared to free BCP3 which has one cis Leu-Pro bond and one trans Leu-Pro bond.

Cations, Divalent↗
PubMed1981

The sonographically solid appearing benign cystic teratoma.

The sonographic appearance of 6 solid benign cystic teratomas (in 5 patients) was reviewed. Three of these tumors were difficult to identify due to the presence of acoustical shadowing obscuring the posterior portions of the tumors. This appearance was mistaken ultrasonically for bowel gas. The tumors were diagnosed by abdominal radiographs showing calcifications, teeth and/or radiolucency due to fat. With the presence of a clinically palpable pelvic mass in a young woman, and an apparently normal sonogram, an abdominal radiograph should be considered to look for evidence of a benign cystic teratoma.

Adolescent↗