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Biomedical subjects

J McDonald

Publications and source records attributed to J McDonald.

At least 163 records · Page 9Linked to original sources
PubMed1988

Non-isotopic immunoassay drug tests in racing horses: a review of their application to pre- and post-race testing, drug quantitation, and human drug testing.

We have introduced large scale non-isotopic immunoassay testing into pre- and post-race drug testing in racehorses. The technologies utilized are Particle Concentration Fluorescence Immuno Assay (PCFIA) and the one-step Enzyme Linked Immuno Sorbent Assay (ELISA). These technologies are rapid, inexpensive, and highly effective. On introduction into post-race testing in the Western United States, these ELISA tests exposed several previously undetected patterns of drug abuse. The drugs detected were buprenorphine, oxymorphone, mazindol, sufentanil and cocaine. This led to the suspension of a large number of trainers and exposed the high false negative rate of thin layer chromatography (TLC) based testing. More recently, we have introduced both PCFIA and ELISA assays into pre- and post-race testing in Illinois. Within days, our pre-race PCFIA tests detected signs of acepromazine abuse. Directed searches of post-race urines from these horses showed evidence for acepromazine metabolites in the urine of these horses. Examination of frozen samples from associated horses yielded about 70 ELISA "positives" for acepromazine. To date, about 25 of these ELISA "positives" have been confirmed by mass spectrometry. We have also raised antibodies to phenylbutazone and furosemide to enable rapid and inexpensive quantitation of these permitted medications. Furosemide is a particular problem since its use requires a pre-race detention barn. For furosemide, we have developed a regulatory schedule based on our immunoassay test that allows elimination of the detention barn. For phenylbutazone, we have developed a similar immunoassay that allows rapid and inexpensive quantitation of this drug in blood. To enable racing authorities to test jockeys and other racetrack personnel, we have adapted PCFIA technology to human drug testing, and a full range of very sensitive tests for human drugs of abuse is available. These immunoassays are sufficiently sensitive to control abuse of the most potent drugs available to horsemen. In principle, an immunoassay can be raised to any drug within about six months, and made available worldwide at competitive rates. It appears clear that these non-isotopic immunoassays provide racing with the only technological basis that is sufficiently sensitive to detect the most potent abused drugs pre- and post-race, and has the flexibility to be readily adaptable to different drugs. Because of the high false negative rate generated by TLC, credible pre- and post-race testing programs cannot be based on TLC alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Acepromazine↗
PubMed1988

Allopurinol hypersensitivity in a patient with coexistent systemic lupus erythematosus and tophaceous gout.

A patient with coexistent Klinefelter's syndrome, systemic lupus erythematosus (SLE) and chronic tophaceous gouty arthritis developed allopurinol hypersensitivity. The drug was reinstituted by a schedule of gradually increasing doses. Gout should be considered in the differential diagnosis of patients with SLE who present with acute arthritis and/or subcutaneous nodules particularly in those with longstanding stable nephritis who are receiving diuretics for concomitant hypertension.

Adult↗
PubMed1988

Immunoassay detection of drugs in racing horses. III. Detection of morphine in equine blood and urine by a one step ELISA assay.

A one step enzyme-linked immunosorbent assay (ELISA) test for morphine was evaluated as part of a panel of pre- and post-race tests for narcotic analgesics in racing horses. This ELISA test is very sensitive to morphine with an I-50 for morphine of about 400 pg/ml. The test is also rapid, and ten samples, a normal pre-race complement, can be analyzed in about thirty minutes. The test can be read with an inexpensive spectrophotometer, or even by eye. The test readily detects the presence of morphine or its metabolites in equine blood for up to six hours after administration of sub-therapeutic doses. The antibody also cross-reacts with hydromorphone, orymorphone, nalorphine, levorphanol, and codeine, and the test either can detect or is likely to detect these drugs in blood or urine shortly after their administration to horses. As such this test is capable of dramatically improving the speed and efficacy of both pre-race and post-race testing for morphine and its congeners in racing horses. On initial introduction into post-race urine screening this test flagged 18 of 166 samples positive for opiates, and 13 of these samples were confirmed positive for opiates by mass spectrometry.

Animals↗
PubMed1987

Structural elements and organization of the ancestral translational machinery.

The molecular mechanisms underlying the primitive translational apparatus have been studied in light of present day protein biosynthesis. Using the structural information available from the contemporary system as a key to its function, both the structural necessities for an early adaptor and the multipoint recognition properties of such adaptors have been investigated. This was done by first critically examining the potential feasibility of right- and left-handed hairpin adaptor models. Second, a molecular model of the contemporary transpeptidation complex has been constructed in order to ascertain the structural requirements of the adaptor molecule needed for peptidyl transfer. Third, a model of the tRNATyr-tyrosyl tRNA synthetase complex including the positioning of the disordered region is proposed. This model is used to illustrate those required recognition properties of aminoacyl synthetase which lead to a perspective on the structure of the ancestor synthetase.

Amino Acyl-tRNA Synthetases↗
PubMed1987

A rehabilitation response to the call for asylum.

Recently, the Schizophrenia Bulletin published an article on the concept of "asylum" for the mentally ill (Wasow 1986). This concept of asylum, while based on a desire to protect people with psychiatric disabilities is too vague to be useful and is politically dangerous. As a response to currently inadequate community service systems, it fails to take into account the empirical evidence of effectiveness of community support and rehabilitation programs and ignores the larger social responsibility to provide stable housing, employment, and other necessities to these individuals. Finally, it conflicts with the desires of psychiatrically disabled persons themselves. There is a need for aggressive development of community support and rehabilitation services, greater attention to the stated desires of mental health consumers, and continuing research into program effectiveness.

Chronic Disease↗
PubMed1987

Rearrangement and expression of erythropoietin genes in transformed mouse cells.

The erythroleukemia cell line IW32, derived by transformation with the Friend murine leukemia virus, has been shown previously to produce erythropoietin (EPO) constitutively. Here we demonstrate that, in addition to the normal mouse EPO locus, this cell line has another EPO locus which has undergone rearrangement and amplification. Both loci were cloned, and the rearrangement breakpoint of the second EPO locus was located within a 1.1-kilobase region upstream of an otherwise apparently normal EPO gene. There are no viral sequences present in the immediate vicinity of the rearranged EPO gene. DNase I digestion studies suggest that the rearranged gene is in a region where the chromatin is more sensitive to DNase hydrolysis than is the site of the normal gene. We conclude, tentatively, that the rearranged EPO locus is probably the transcriptionally active one and that either proviral sequences are acting at a distance to activate the EPO gene or the rearrangement itself has served to activate the gene.

Animals↗
PubMed1987

Expression of the erythropoietin gene.

Comparison of maps of the human and mouse erythropoietin (EPO) genes shows overall general conservation. A cloned mouse EPO gene was used to study EPO gene expression by the Northern blot method. Ten hours after bleeding to induce stress erythropoiesis in the rat, the only tissue to show detectable message was the kidney. Other preliminary studies on EPO expression in cells transformed by FMuLV that secrete EPO constitutively showed no detectable viral sequences close to the gene regardless of high levels of EPO expression. Further studies on regulation of EPO gene expression are now possible with the probes developed from the cloned gene.

Animals↗
PubMed1987

Immunoassay detection of drugs in horses. I. Particle concentration fluoroimmunoassay detection of fentanyl and its congeners.

We investigated the use of particle concentration fluorescence immunoassay (PCFIA) as a technique for drug detection in racing horses. The test was constructed from an antiserum to a carboxyfentanyl-BSA conjugate and carboxyfentanyl linked to b-Phycoerythrin. Using these reagents and a PCFIA apparatus levels of fentanyl as low as 0.1 ng/ml could be detected by the assay. In addition, cross-reactivity studies on this assay showed that the anti-serum cross-reacted well with carfentanil, sufentanil and the methylated analogs of fentanyl. We therefore evaluated the ability of these agents to produce pharmacological effects in the horse and the ability of this test to detect pharmacologically significant doses of this drug in racing horses. All of these agents produced good locomotor responses in horses at doses of between 0.1 and 10 micrograms/kg. Of these agents, carfentanyl was the most potent followed by 3-methylfentanyl, sufentanyl, alpha-methylfentanyl, and fentanyl. Similarly, when these agents were administered to horses at doses sufficient to produce a pharmacological response, all produced sufficient inhibition of fluorescence in the PCFIA system to enable their detection in post-race urines from these horses. Since PCFIA is a much faster technique than radioimmunoassay, is of approximately similar sensitivity, and requires much less instrumentation we concluded that this technique holds considerable promise as an equine drug testing technique.

Animals↗
PubMed1986

Potent vasopressin antagonists lacking the proline residue at position 7.

As part of a program to design potent antidiuretic vasopressin antagonists and to define the minimum effective pharmacophore requirements for vasopressin (VP) antagonist activity, we studied the importance of the C-terminal tripeptide of a previously reported peptide antagonist of arginine-vasopressin (AVP,1). The proline residue at position 7 in AVP is proposed to impart a conformational constraint to the peptide backbone that is essential for V2-receptor agonist activity. Since the structure-activity relationships for VP agonists and antagonists are different, we investigated the effect of proline on antagonist activity, by synthesizing analogue 3 lacking this residue. This analogue was found to retain a high degree of antidiuretic antagonist activity. Since deletion of the Gly residue at position 9 of the antagonist did not adversely affect VP antagonist potency, several vasopressin antagonist analogues (4-7 and 9) that lacked both the Pro and Gly residues were also studied. These, too, were found to block vasopressin V2-receptor activity. Our results indicate that neither the proline nor glycine residues are essential for antagonism of the V2 receptor.

Animals↗
PubMed1986

Herpes simplex type II encephalitis in infancy presenting with focal encephalitis.

Herpes virus was recovered from a throat swab, nasopharyngeal washings as well as from brain tissue from a six-month-old infant, who presented with fever, left focal seizures and an enhancing right frontal CT-scan lesion. Cytopathic effect (CPE) as seen with genital herpetic infection was seen, suggesting HSV-2. Immunofluorescent typing of the virus isolate confirmed HSV-2. Early IgM positivity preceding a CF and SN titer rise was observed. The patient received a course of ARA-A and recovered with a left sided hemiparesis. HSV-2 encephalitis occurs beyond the newborn period as a primary infection. In adults however HSV-2 encephalitis occurs predominantly in the immunocompromised host. HSV-1 encephalitis probably is due to reactivation of a latent herpetic infection in previous virus exposed juvenile or adult immunocompetent hosts.

Antibodies, Viral↗
PubMed1986

Discovery and therapeutic utility of vasopressin antagonists in rats.

Vasopressin is the primary physiological factor regulating renal water reabsorption in mammals. Inhibitors of vasopressin-stimulated water reabsorption have previously been used as water diuretic agents in both experimental animals and man. The present studies describe and characterize the pharmacological effects of the potent vasopressin antagonist desGly d(CH2)5D-Tyr(Et)VAVP (SK&F 101926) and related analogs on renal water and solute excretion in conscious rats. Administration of SK&F 101926 was associated with dose-dependent increases in renal water excretion in conscious hydropenic rats. A selective vasopressin pressor (V1) antagonist (SK&F 100273) was inactive as a diuretic agent in these tests. SK&F 101926 antagonized, in a competitive fashion, exogenous vasopressin-stimulated antidiuresis in conscious water-loaded rats. Only modest increases in renal excretion of Na+, K+, and urea were observed when SK&F 101926 was administered. No changes in endogenous creatinine excretion were associated with the administration of SK&F 101926, suggesting that this drug does not affect glomerular filtration rate. The rank order of bioequivalency of alternative routes of administration of SK&F 101926 was intraperitoneal = intravenous = intramuscular = subcutaneous greater than intranasal much greater than rectal, ocular, and oral. SK&F 101926 (20 micrograms/kg/day) was effective in blocking the development of hyponatremia in a rat model of the syndrome of inappropriate antidiuretic hormone (SIADH). SK&F 100273 (100 micrograms/kg) hastened the onset of endotoxin-associated shock in rats. We conclude that SK&F 101926 is a potent water diuretic (aquaretic) agent in rats. The mechanism of action is most probably antagonism of vasopressin at renal epithelial (V2) receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Vasopressin antagonist analogs modified at position 7.

Vasopressin antagonist analogs having alanine or glycine at position 7 were essentially equipotent with analogs with proline, N-methylalanine or sarcosine at position 7. This demonstrates that the conformational constraint imposed by an N-alkyl residue at position 7 is not necessary for binding of antagonist to the receptor, the exact opposite of what is seen in agonists. This suggests that antagonists bind to the receptor in a manner which is very different from that of agonists.

Animals↗
PubMed1986

Expression of the erythropoietin gene.

Injection of cobalt into rats resulted in erythropoietin (EPO) mRNA accumulation in the kidney. The same response was obtained upon bleeding. No EPO mRNA was detected in the spleen, salivary gland, or thymus following cobalt injection or bleeding. In some animals, but not in others, EPO mRNA was also expressed in the liver in response to cobalt injection. Time course studies showed that message appearance begins sometime between 3 and 6 h after cobalt injection. This correlated very well with the EPO concentration in the circulation; EPO levels in the circulation were the same as those of controls at 3 h but increased to six- to sevenfold that of controls by 6 h after cobalt injection. The mature EPO mRNA in the rat and mouse comigrated with the 18S rRNA, indicating that it is about 1,850 nucleotides in length.

Animals↗