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Biomedical subjects

M Wainwright

Publications and source records attributed to M Wainwright.

At least 55 records · Page 3Linked to original sources

Biodistribution of a methylene blue derivative in tumor and normal tissues of rats.

By using a chemical extraction procedure and confocal laser scanning fluorescence microscopy we have investigated the kinetic patterns of uptake and biolocalization of a methylene blue derivative (MBD) in tumors and various normal tissues of Wistar rats bearing fibrosarcoma (Leeds ovarian tumor) after intravenous injection of MBD (10 mg kg-1 body weight). Similar kinetics of accumulation and elimination of MBD fluorescence were found in tumor tissue and surrounding normal skin and muscle tissues. However, the tumor:skin and tumor:muscle ratios of the MBD fluorescence intensity were found to be 9 and 4, respectively, 4 h after intravenous injection, indicating selective uptake of MBD by the tumor tissue. MBD was localized on the walls of all the vessels and extensively in the area of neoplastic cellular and tumorigenic fibrous components in the tumor tissue. Interestingly, no MBD fluorescence could be detected in the metastatic neoplastic cells in the remote lymph nodes. In the skin, MBD was mainly distributed in the keratinized epithelium of the epidermis, hair follicles and their accessories, while little was found both in the epidermis and dermis. In most other tissues, the maximal fluorescence intensity of MBD was found 1-4 h after injection, after which it decreased dramatically to almost undetectable levels 120 h postinjection. Strong fluorescence of MBD was seen in the tracheal mucosal epithelium, while little fluorescence was noted in the transitional epithelium of bladder. The kinetics of biolocalization of MBD in some other tissues (liver, spleen, kidney, brain, muscle, lung, heart) were also studied.

Animals↗

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↗

Sulphur oxidation by a Streptomyces sp. growing in a carbon-deficient medium and autoclaved soil.

Streptomyces colonies, apparently all of the same species, were isolated from a range of soils using a polysulphide medium lacking an organic carbon source. Growth on this medium, and clearing of the otherwise white, opaque overlay, suggested that the organisms were capable of growing autotrophically. However, investigation of one of these isolates showed that it was unable to fix 14CO2 and did not possess the enzyme ribulose bisphosphate carboxylase, showing that it was incapable of autotrophic growth. The isolate oxidized elemental sulphur, thiosulphate and tetrathionate to sulphate in vitro in carbon-deficient medium, and also oxidized elemental sulphur to sulphate when inoculated into autoclaved soil supplemented with sulphur. It also oxidized polysulphide when growing on Czapek Dox and plate count agars. The isolate can therefore grow heterotrophically in both carbon-rich media and in media lacking organic carbon - presumably by scavenging organic carbon from the laboratory atmosphere. The possible role of these organisms in sulphur oxidation in soils is commented upon.

Carbon↗