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Biomedical subjects

J M Ellis

Publications and source records attributed to J M Ellis.

53 records · Page 3Linked to original sources
PubMed1983

Selective acylation of lyso platelet activating factor by arachidonate in human neutrophils.

Human polymorphonuclear leukocytes (PMN) incubated with 1-O-[3H]alkyl-2-acetyl-sn-glycero-3-phosphocholine (1-[3H]alkyl-2-acetyl-GPC; platelet activating factor) inactivated the compound by removing the acetyl group and replacing it with a long chain acyl residue. The nature of the acyl group added at the 2-position of the 1-O-[3H]alkyl-2-acyl-GPC formed was examined by argentation chromatography and by reverse phase high performance liquid chromatography. A striking selectivity for arachidonate was observed in the acylation reaction. The major labeled component of the starting material was the 1-O-hexadecyl-linked species; high performance liquid chromatography analysis revealed that 75 to 80% of this component was acylated by arachidonate. Similarly, based on argentation thin layer chromatography, approximately 80% of the total starting material was acylated by tetraenoic acyl residues. The incorporation of 1-O-[3H]alkyl-2-lyso-GPC into 1-O-alkyl-2-acyl-GPC by the PMN was compared; no difference in the acylation pattern was observed with the 2-acetyl and 2-lyso precursors. Thus, activation of the PMN does not appear to be required to elicit the selectivity for arachidonate. When labeled 1-palmitoyl-2-lyso-GPC was compared in the system under the same conditions, it was also preferentially acylated by arachidonate; thus, it is not clear at this time whether or not the selectivity for arachidonate is physiologically limited to platelet activating factor. Our findings suggest a close relationship exists between the metabolism of platelet activating factor and arachidonate in human PMN.

Acylation↗
PubMed1983

1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine: a novel source of arachidonic acid in neutrophils stimulated by the calcium ionophore A23187.

Rabbit peritoneal neutrophils incorporated [14C]arachidonic acid into seven molecular species of choline-containing phosphoglycerides. These 2-[14C]arachidonoyl species differed with respect to the alkyl ether or acyl residue bound at the sn-1 position; four of the seven were ether-linked. Stimulation with calcium ionophore A23187 induced a proportionate release of arachidonate from all seven molecular species: 40% of the released arachidonate came from alkyl ether species. Thus, 1-O-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine (GPC) is a significant source of metabolizable arachidonic acid. Since 1-O-alkyl-2-lyso-GPC is the metabolic precursor of platelet activating factor, these results further interrelate pathways forming arachidonate metabolites and platelet activating factor; they also supply a rationale for the observation that both classes of stimuli form concomitantly during cell activation.

Animals↗
PubMed1983

Metabolic fate of platelet-activating factor in neutrophils.

1-O-[3H]Alkyl-2-acetyl-sn-glycero-3-phosphocholine (1-O-[3H]alkyl-2-acetyl-GPC) incubated with rabbit polymorphonuclear leukocytes was metabolized to 1-O-alkyl-2-acyl-GPC containing long chain groups at the 2 position. Within 5 min, 60% of the total label added to the cell suspension was found in the 1-O-[3H]alkyl-2-acyl-GPC. At earlier time points, 1-O-[3H]alkyl-2-lyso-GPC was present. No metabolites were detected that would indicate the ether bond had been cleaved or the polar head group had been altered by the cells. At subaggregating and subdegranulating concentrations of labeled 1-O-[3H]alkyl-2-acyl-GPC, the same pattern of product formation was observed. Furthermore, when 1-O-[3H]alkyl-2-lyso-GPC was added to the cells, it was taken up and acylated in the same manner as that from 1-O-alkyl-2-acetyl-GPC. The nature of the long chain acyl residues incorporated into the 2 position was then examined by argentation chromatography and high performance liquid chromatography. Argentation chromatography of 1-O-[3H]alkyl-2-acyl-3-acetylglycerols obtained from 1-O-[3H]alkyl-2-acyl-GPC after acetolysis indicated that mono-, di-, and tetraenoic fatty acids were the predominant molecular species being incorporated into the 2 position of the molecule (18, 55, and 18%, respectively). Furthermore, high performance liquid chromatographic analysis using synthetic 1-O-alkyl-2-acyl-GPC standards indicated that three fatty acids, linoleic, arachidonic, and oleic (50, 15, and 12%, respectively), were the major chains being incorporated into the 1-O-hexadecyl-linked species. Analysis of 1-O-[3H]alkyl-2-acyl-GPC derived from exogenously added 1-O-[3H]alkyl-2-lyso-GPC revealed the same distribution of acyl groups linked to the 2 position. The findings are consistent with a pathway in which two enzymatic activities are responsible for the metabolism of exogenous platelet-activating factor in the rabbit neutrophils: one that hydrolyzes the acetyl residue (acetylhydrolase) and another that transfers a fatty acyl chain to the 1-O-alkyl-2-lyso-GPC formed (possibly acyl-CoA:1-O-alkyl-2-lyso-GPC acyltransferase). These events appear to play an important role in inactivating this potentially lethal phospholipid.

Acylation↗
PubMed1982

Response of vitamin B-6 deficiency and the carpal tunnel syndrome to pyridoxine.

The specific activities and percentage deficiencies of the glutamic oxaloacetic transaminase of erythrocytes (EGOT) were determined for patients with carpal tunnel syndrome (CTS) diagnosed by clinical examination and electrical conduction data; the EGOT data revealed a severe deficiency of vitamin B-6. After double-blind treatment with pyridoxine and placebo, two physicians identified those receiving pyridoxine (clinically improved) and those receiving placebo (did not improve) without error, P less than 0.0078. Correcting a deficiency of the coenzyme at receptors of existing molecules of the apoenzyme appears to take place within days; correction of the deficiency in the number of molecules of the transaminase takes place over 10-12 weeks. The clinical response, appraised by the diminution of the symptoms of CTS, was correlated only with the restored levels of the transaminase which presumably results from a translational long-term increase in the number of molecules of EGOT by a mechanism activated by correcting a deficiency of pyridoxal 5'-phosphate. Apparent Km values of EGOT were identical for groups of patients with CTS and others without CTS but with identical specific activities, indicating that CTS is a primary deficiency of vitamin B-6 rather than one of a dependency state. Clinical improvement of the syndrome with pyridoxine therapy may frequently obviate hand surgery.

Adult↗
PubMed1978

Acute prolonged confusion in later life as an ictal state.

Six patients ranging in age from 42 to 69 with no prior history of seizure disorder presented an acute prolonged or intermittent confusional state, with or without psychotic symptoms, as an ictal manifestation. The EEGs demonstrated protracted generalized spike and wave discharges, but full diagnostic evaluation disclosed no evident cause for the seizures. All promptly responded to small amounts of intravenous diazepam and subsequent oral phenytoin and phenobarbital. Three of the six patients had focal spike or sharp wave discharges on EEGs recorded subsequently, suggesting that the episodes may reflect secondary generalized seizures in some cases. These cases do not fit in the classic category of petit mal status and appear to be a distinct entity.

Adult↗
PubMed1976

Vitamin B6 deficiency in patients with a clinical syndrome including the carpal tunnel defect. Biochemical and clinical response to therapy with pyridoxine.

Ten individuals having a severe clinical status associated with the carpal tunnel syndrome were selected for treatment with pyridoxine. The status of vitamin B6, as pyridoxal phosphate, was determined by the specific activities of the glutamic oxaloacetic transaminase of the erythrocytes (EGOT). Before treatment, the patients showed a deficiency of vitamin B6 as determined by 1) a comparison of the specific activities of EGOT with those of a control group (P less than 0.001); and 2) a differential assay based upon the principle of unsaturation and saturation of a Coenzyme-Apoenzyme System (CAS), as applied to EGOT. These patients were treated with pyridoxine, and the specific activities of EGOT were determined after 2 and 4 weeks. Not only was there a disappearance of the deficiency of pyridoxal phosphate, but the level of EGOT activity increased 55-68% during 2-4 weeks, respectively. More apoenzyme was apparently biosynthesized, because the specific activities were significantly higher than before therapy (P less than 0.001/4 wks). Clinical evaluation showed a great improvement in their status, and anticipated surgery for some of the patients became unnecessary. It is concluded that patients with a severe syndrome including the carpal tunnel defect have a deficiency of vitamin B6, and that both the syndrome and the deficiency are relived by therapy with pyridoxine.

Adult↗
PubMed1975

A continuing common-source outbreak of botulism in a family.

In December, 1974, three cases of botulism occurred in a family; two were fatal. The first patient died after a 10-day illness without botulism being suspected. 4 days later, after a 2-day illness, the second patient was diagnosed as having botulism after a cardiorespiratory arrest; she died 3 days later. In the third patient, the only symptom was dysphagia. Clostridium botulinum type B was found in stool specimens from all three patients. Home-canned (bottled) mushrooms, which were found to contain C. botulinum type B and its toxin, were believed to be responsible for the outbreak; mushrooms were found at necropsy in the gastrointestinal tracts of both patients who died. Heat treatment of the mushrooms during canning had been inadequate.

Adult↗
PubMedDate not supplied

Pharmacists' liability into the year 2000.

OBJECTIVE: To educate the pharmacy community regarding areas of potential liability arising from the pharmacist's role in the changing health care delivery system. DATA SOURCES: Published cases (LEXIS and Westlaw), literature (NEXIS and Westlaw), and abstracts available through July 1998. CASE SELECTION AND DATA ABSTRACTION: Selected on the basis of the authors' objectives and the usefulness of the information for practicing pharmacists. DATA SYNTHESIS: As the pharmacist's role in the health care delivery system continues to change, so too does the pharmacist's exposure to liability. Although historically a pharmacist had no common law "duty to warn," new laws requiring a pharmacist to counsel patients, along with increased scrutiny by the media, have increased the pharmacist's potential for liability. An evaluation of recent case law indicates that state courts are increasingly willing to extend a pharmacist's duty to warn where the pharmacist has special knowledge of the patient or the patient's condition, contraindicated drug usage, where a prescription substantially exceeds the maximum safe dosage, or where a pharmacist fills or refills a prescription without physician authorization. A recent issue that may add to the list of potential liability concerns is the substitution of generically equivalent narrow therapeutic index drug products. CONCLUSION: The pharmacist's role in the ever changing health care delivery system, along with the public's increased scrutiny of pharmacists' dispensing practices, may inevitably extend a pharmacist's duty to warn a patient of potential problems related to prescription drug products. This trend is expected to continue into the new millennium.

Forecasting↗