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Biomedical subjects

M Wainwright

Publications and source records attributed to M Wainwright.

14 recordsLinked to original sources

Conditioned withdrawal in environments associated with the presence or absence of morphine.

An experiment designed to compare conditioned withdrawal in environments associated with the presence or absence of morphine was conducted in hamsters. For some animals, morphine administration was paired with distinctive environmental cues. For other animals, naloxone-precipitated withdrawal was paired with the distinctive environmental cues. For still other animals, naloxone-precipitated withdrawal and the distinctive environmental cues were unpaired. Following 12 days of training, animals were observed for signs of withdrawal (e.g., wet-dog shakes, etc.) in the distinctive environment following vehicle injections. Results indicated that more conditioned withdrawal responses occurred in the environment paired with the absence of morphine (naloxone-precipitated withdrawal) than in the environment paired with morphine administration.

Animals

Blocking naloxone-precipitated withdrawal in rats and hamsters.

Three experiments studied the effects of putative antagonists of opiate withdrawal in hamsters and rats. In Experiment 1, the calcium channel antagonists verapamil (20 mg/kg) and nifedipine (20 mg/kg) failed to antagonize naloxone (1 mg/kg)-precipitated withdrawal in hamsters implanted with two 75-mg morphine pellets, whereas clonidine (0.4 mg/kg), the alpha 2-adrenergic agonist, blocked most withdrawal signs. In Experiment 2, clonidine (0.4 mg/kg) and verapamil (20 mg/kg) were tested against naloxone-precipitated withdrawal in hamsters made acutely dependent by a single injection of morphine (15 mg/kg). As in Experiment 1, clonidine but not verapamil was effective. In Experiment 3, the effects of verapamil on naloxone-precipitated withdrawal were studied in morphine-pelleted rats and hamsters. In rats implanted with two morphine pellets, verapamil (20 mg/kg) reversed naloxone-precipitated withdrawal. By contrast, in hamsters implanted with either one or two morphine pellets neither of two doses of verapamil (20 and 30 mg/kg) was effective. These results are discussed in terms of species' differences in sensitivity to calcium channel blockers.

Animals

Oligotrophic micro-organisms in industry, medicine and the environment.

Micro-organisms are generally grown in the laboratory in nutrient-rich medium containing large amounts of sugars, nitrogen, phosphorus and other nutrients which are considered essential for their growth. Modification of these conditions on an industrial scale provides an ideal environment in which micro-organisms can produce large quantities of useful products such as antibiotics, biochemicals, and enzymes. Natural environments, in contrast, contain only trace amounts of nutrients. Micro-organisms which are adapted for growth under these conditions are called oligotrophs. Many bacteria and fungi can grow as oligotrophs by scavenging traces of nutrients from solution or from the atmosphere. The ability of micro-organisms to grow in this way has a number of important biotechnological, medical and environmental implications.

Anti-Bacterial Agents

Streptomycin: discovery and resultant controversy.

The antibiotic streptomycin was discovered soon after penicillin was introduced into medicine. Selman Waksman, who was awarded the Nobel Prize for the discovery, has since generally been credited as streptomycin's sole discoverer. However, one of Waksman's graduate students, Albert Schatz, was legally recognized as streptomycin's co-discoverer and received a share of the royalties from the drug. The aim of this essay is to discuss the streptomycin story, largely using previously unquoted archival material, and in particular to provide further evidence for the important role which Schatz played in the discovery.

History, 20th Century

Autistic children and their first-degree relatives: relationships between serotonin and norepinephrine levels and intelligence.

Whole-blood serotonin (5-HT) and plasma norepinephrine (NE) were studied in 16 autistic children, 21 siblings of autistic children, and 53 parents of autistic children. Both plasma NE and whole-blood 5-HT were negatively correlated with vocabulary performance. Whole-blood 5-HT and plasma NE did not differ between autistic children with or without histories of self-injurious behavior or decreased pain sensitivity. Eighteen subjects were hyperserotonemic (whole-blood 5-HT greater than 270 ng/ml). For these subjects, plasma NE was significantly higher than for subjects without hyperserotonemia. Seven of 10 families with one hyperserotonemic member had two or more hyperserotonemic members. Observations of familiarity of whole-blood 5-HT suggest that larger-scale and more focused study of whole-blood 5-HT as a possible genetic marker may be productive.

Adolescent

Hypoalbuminemia in energy-malnourished rats infected with Nippostrongylus brasiliensis (Nematoda).

Rats fed a restricted amount (60% of ad libitum intake) of a well-balanced diet (protein energy:total energy ratio of 0.20) had a reduced growth rate but maintained near-normal plasma albumin concentrations. However, when such animals were infected with Nippostrongylus brasiliensis (a hookwormlike intestinal parasite), plasma albumin values fell precipitously, from a preinfection value of 34.7 g/L to 21.3 g/L on d 10 postinfection (p.i.). The hypoalbuminemia developed rapidly, without changes in body weight and despite an adequate amount of dietary protein. Similarly infected well-nourished animals showed a much less severe effect, plasma albumin values falling from 34.8 to only 31.3 g/L by d 10 p.i. Two measurements of gastrointestinal integrity, [51Cr]albumin leakage from the plasma and intestinal permeability to mono- and disaccharide sugars, suggested that the alterations in plasma albumin values could be explained on the basis of protein leakage into the gastrointestinal tract through parasite-induced lesions. Much greater changes in the indices of mucosal integrity were observed in the undernourished animals and overall it was clear that the energy-restricted animals had been far more severely affected by the parasite than their well-fed counterparts. The results are discussed with reference to the etiology of kwashiorkor in humans.

Animals

Plasma albumin concentrations and intestinal permeability in Bangladeshi children infected with Ascaris lumbricoides.

Plasma albumin concentration and intestinal permeability have been investigated in Bangladeshi children before and 9-14 d after successful treatment for ascariasis. Children infected with A. lumbricoides had lower plasma albumin concentrations than counterparts not harbouring this worm and values increased with successful treatment. Intestinal permeability tests indicated that the children had impaired gastrointestinal function and some loss of mucosal integrity; these factors had not improved 9-14 d after A. lumbricoides expulsion. The lowered nitrogen nutritional status implied by the reduced plasma albumin values in infected children, and the improvement following treatment, are in keeping with previous reports that A. lumbricoides impairs protein digestion or absorption. This may be the basis of the better growth rates of dewormed children in this area.

Anthelmintics

Protein losing enteropathy associated with Nippostrongylus brasiliensis infestation and its impact on albumin homoeostasis in rats fed two levels of dietary protein.

Alterations in plasma albumin concentration and gastrointestinal permeability have been investigated in rats infected with the nematode Nippostrongylus brasiliensis and fed adequate or low protein diets. Infection caused only minor changes in growth and food consumption of well nourished rats but resulted in significant reductions in those fed the low protein diet. Animals in both dietary groups were able to mount an immune response beyond day 10 post-infection (p.i.) which caused expulsion of the parasites, but this was less effective in rats fed the low protein food. Uninfected rats fed the low protein diet had significantly lower plasma albumin concentrations than their well nourished counterparts. Animals of both dietary groups showed a progressive reduction in plasma albumin concentration as the infection developed but values returned towards normal as the parasites were expelled. The reduction in plasma albumin concentration was closely associated with increases in gastrointestinal leakage of plasma protein but losses were far greater in the protein deficiency animals. Beyond day 10 p.i. protein loss decreased in both dietary groups and by day 21 p.i. had returned to normal in well nourished animals but not those fed the low protein diet. Intestinal permeability measured by the lactulose:mannitol ratio technique gave similar results to the protein loss data. Permeability increased as the infection progressed then fell as the worms were expelled but remained above control values in infected protein deficient animals. Overall, animals fed the low protein diet were more severely affected by the parasite than were their well fed counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The effect of translation and transcription inhibitors on the synthesis of periplasmic phosphatases in E. coli.

Previous studies by others have indicated that the synthesis of secreted enzymes is unusually sensitive to many translation inhibitors and resistant, for about 30 min, to rifampicin. We have studied the sensitivity of secreted (periplasmic) phosphatases to such inhibitors. Alkaline phosphatase synthesis is more sensitive than total protein synthesis to tetracyclin and spectinomycin, but not to sparsomycin, streptomycin, chloramphenicol, kasugamycin, blasticidin S or thiostrepton; it is slightly more resistant than total protein synthesis to the latter two antibiotics. Acid hexose-phosphatase was also preferentially sensitive to tetracyclin and spectinomycin and also to kasugamycin. beta-galactosidase was also included in the study, as an intracellular enzyme, and was found to be preferentially inhibited ("repressed"), sometimes transiently, by all eight translation inhibitors. This effect did not seem to be mediated through cyclic AMP or guanosine tetraphosphate; the "repression" was still evident in mutants with altered rho factor indicating that it may also not be related to artificial polarity. Synthesis of both periplasmic phosphatases was immediately inhibited by rifampicin. These results differ from those found in previous studies with other organisms and suggest a reappraisal of the usual interpretation of these phenomena.

Acid Phosphatase