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Biomedical subjects

H W Smith

Publications and source records attributed to H W Smith.

At least 55 records · Page 3Linked to original sources
PubMed1983

Activated cyclophosphamide anticancer drugs: molecular structures of cis- and trans-4-hydroperoxyisophosphamides.

Molecular structures of two stereoisomers of 4-hydroperoxyisophosphamide (HPIPA) have been determined by single-crystal X-ray diffraction. These isomers are active cytostatic agents closely related to an active metabolite of the antitumor drug isophosphamide, an analogue of cyclophosphamide. Both isomers crystallize in monoclinic space group P21/c with cell dimensions for cis-HPIPA of a = 8.999 (2), b = 8.743 (2), c = 17.078 (4) A; beta = 107.91 (2) degrees, and Z = 4 molecules per unit cell, and cell dimensions for trans-HPIPA of a = 15.184 (3), b = 10.345 (3), c = 18.205 (3) A, beta = 114.15 (1) degrees, and Z = 8. The structures were solved by direct methods and refined by anisotropic least squares to a discrepancy index R = 0.048 for cis-HPIPA and R = 0.065 for trans-HPIPA. In both isomers the 4-hydroperoxy group is situated axial to the ring. The phosphoryl oxygen atom is situated axial to the ring and, thus, cis to the C(4) oxygen in the cis-HPIPA isomer. In the trans-HPIPA isomer, the phosphoryl oxygen is equatorial to the ring and trans to the C(4) oxygen.

Chemical Phenomena↗
PubMed1983

Vero cell toxins in Escherichia coli and related bacteria: transfer by phage and conjugation and toxic action in laboratory animals, chickens and pigs.

Sixty-eight of 519 strains of Escherichia coli and six of 10 strains of Pseudomonas aeruginosa produced toxins acting on Vero cells (VT+); all of 63 Salmonella, Shigella, Klebsiella, Enterobacter and Proteus strains were VT-. Most of the VT+ E. coli strains were from weaned pigs suffering from oedema disease and/or diarrhoea and belonged to serogroups O141:K85,88, O141:K85, O138:K81, and O139:K82; six VT+ E. coli strains were from diarrhoeic human babies, four of serogroup O26 and two of serogroup O128. The VT genes in two of the O26 strains and in the O128 strains were located in the genome of the phages with which they were lysogenized. One O141:K85,88 pig E. coli strain transferred its VT genes, probably by conjugation, to E. coli K12. The VTs of the human E. coli strains, the pig E. coli strains and the P. aeruginosa strains were antigenically different from each other; unlike the others, the P. aeruginosa VT was heat-resistant. Cell-free preparations of cultures of E. coli K12 to which the VT genes of the four human E. coli strains had been transferred caused fluid accumulation in ligated segments of rabbit intestine. Inoculated intravenously, they were lethal for mice and rabbits; similar preparations of E. coli K12 to which the VT genes of the pig E. coli strain had been transferred produced a disease in pigs that clinically and pathologically resembled oedema disease.

Animals↗
PubMed1983

Effectiveness of phages in treating experimental Escherichia coli diarrhoea in calves, piglets and lambs.

A mixture of two phages, B44/1 and B44/2, protected calves against a potentially lethal oral infection with an O9:K30,99 enteropathogenic strain of Escherichia coli, called B44, when given before, but not after, the onset of diarrhoea; a mixture in which phage B44/3 was replaced by phage B44/3 was effective after the onset of diarrhoea. Calves that responded to phage treatment had much lower numbers of E. coli B44 in their alimentary tract than untreated calves. Usually, high numbers of phage B44/1 and rather lower numbers of phage B44/2 or B44/3 were present in the alimentary tract of these animals. At death, most calves that had not responded to treatment with phages B44/1 and B44/2 had high numbers of mutants of E. coli B44 resistant to phage B44/1 in their small intestine. Phage-treated calves that survived E. coli infection continued to excrete phage in their faeces, at least until the numbers of E. coli B44 also excreted were low. The phages survived longer than E. coli B44 in faecal samples taken from phage-treated calves and exposed to the atmosphere in an unheated animal house. Calves inoculated orally with faecal samples from phage-treated calves that contained sufficient E. coli B44 to cause a lethal infection remained healthy. A mixture of two phages, P433/1 and P433/2, and phage P433/1 alone cured diarrhoea in piglets caused by an O20:K101,987P strain of E. coli called P433. The numbers of the infecting bacteria and phages in the alimentary tract of the piglets resembled those in the calves. Another phage given to lambs 8 h after they were infected with an O8:K85,99 enteropathogenic strain of E. coli, called S13, reduced the numbers of these organisms in the alimentary tract and had an ameliorating effect on the course of the disease. No phage-resistant mutants of E. coli S13 were isolated from the lambs. The only mutants of E. coli B44 and P433 that emerged in the calves and piglets were K30- or K101- and resistant to phage B44/1 or P433/1 respectively; those tested were much less virulent than their parent strains.

Animals↗
PubMed1983

The activity of a new, novel inhibitor of leukotriene synthesis in rhesus monkey Ascaris reactors.

The IgE-mediated hypersensitivity to Ascaris antigen in reactor rhesus primates was used to assess the pharmacologic profile of U-60,257, a pyrrole analog of prostacyclin. Whether the compound was given by aerosol or intravenously, it effectively inhibited the bronchopulmonary effects of antigen challenge. Dose responses by the aerosol route showed a dose-dependent inhibition of resistance (RL) and compliance (Cdyn) changes (100% +/- 0 to 10.2% +/- 14.5 for RL and 79.9% +/- 20 to 0% for Cdyn after 15 breaths of 1.0-0.01% solutions delivered into the lungs; n = 16). When administered at 1.0% by aerosol the duration of the inhibitory effect was 6 h (n = 3). Dose-dependent inhibition in both RL (93.3% +/- 5.6 to 69.4% +/- 34.8) and Cdyn (51.4 +/- 40.4 to 47.0% +/- 28.5) was also seen when the compound was given intravenously (5.0-0.01 mg/kg; n = 16). U-60,257 is a selective inhibitor of leukotriene synthesis in in vitro systems. Therefore, the finding of synergism in the inhibition of response of primates to Ascaris between this compound and the H1 histamine blocker diphenhydramine suggests that the leukotrienes may play an etiologic role in this response.

Aerosols↗
PubMed1982

The synthesis of 6,9-deepoxy-6,9-N-phenylimino-delta 6,8-prostaglandin I1. A novel inhibitor of leukotriene C and D synthesis.

The pyrrole analog of prostacyclin, 6,9-deepoxy-6,9-N-phenylimino-delta 6,8-prostaglandin I1 was synthesized from PGF2 alpha methyl ester. This pyrroloprostacyclin (U-60,257) and its methyl ester (U-56,467) have been shown to inhibit leukotriene C/D biosynthesis and antagonize leukotriene C/D contractions in vitro. Antigen induced bronchopulmonary changes in monkeys and guinea pigs are inhibited by U-60,257 in vivo.

Animals↗
PubMed1982

Salmonella organisms in garden fertilizers of animal origin.

Of 120 specimens of garden fertilizers of animal origin purchased in retail shops, 40 (33.3%) were found to be contaminated with salmonella organisms. Untreated bone meal (53.1%) was the most heavily contaminated but 25% of specimens of this product classed as heat-treated or sterilized were positive. In all, 32 serotypes were identified.

Animals↗
PubMed1982

Successful treatment of experimental Escherichia coli infections in mice using phage: its general superiority over antibiotics.

Anti-K 1 phages were more active in vitro and in vivo against an 018:K1:H7 ColV+ Escherichia coli strain, designated MW, than were other phages. A single intramuscular dose of one anti-K1 phage was more effective than multiple intramuscular does of tetracycline, ampicillin, chloramphenicol, or trimethoprim plus sulphafurazole in curing mice of a potentially lethal intramuscularly or intracerebrally induced infection of MW; it was at least as effective as multiple intramuscular doses of streptomycin. When MW and the phage were inoculated into different gastrocnemius muscles of the same mice, a rapid reduction in numbers of MW organisms occurred in the MW-inoculated muscle and in other tissues; the numbers of phage particles in the MW-inoculated muscle increased rapidly and greatly. MW failed to proliferate in the brains of intracerebrally infected mice that had been inoculated intramuscularly with the phage at the same time; many more phage particles were found in the brains of these mice than in other sites. The few phage-resistant mutants of MW found in the phage-treated mich were K1-; previous studies had shown such mutants to be of greatly reduced virulence. The phage administered intramuscularly 3-5 d before challenge with a potentially lethal intramuscularly induced infection of MW was protective, the protective effect varying between phage propagated on different bacterial strains.

Animals↗
PubMed1982

6,9-deepoxy-6,9,-(phenylimino)-delta 6,8-prostaglandin I1, (U-60,257), a new inhibitor of leukotriene C and D synthesis: in vitro studies.

Addition of the calcium inophore, A 23187, and cysteine to isolated mononuclear cells from rat peritoneal washings causes a marked increase in the formation of thromboxane B2 (TxB2) along with the formation of leukotrienes C and D (LT's). The formation of LT's in this system was inhibited by 6,9-deepoxy-6,9-(phenylimino)-delta 6,8-prostaglandin I1, U-60,257, or its methyl ester, U-56,467, (ID50 4.6 and 0.31 microM, respectively). There was no inhibition of TxB2 formation. By contrast, two structurally-related compounds, PGI2 and its stable analog, 6-beta-PGI1, did not affect the formation of either LT's or TxB2. The inhibition of LT formation by U-60,257 was rapidly reversed after removal of this compound from the cells. U-60,257 did not inhibit the cyclooxygenase of human polymorphonuclear leukocytes. Nor did it inhibit formation of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) in human platelets. On the other hand, U-60,257 inhibited glutathione S-transferase activity of rat basophil leukemia cells (ID50, 37 microM), suggesting that this compound may inhibit the last step in LTC biosynthesis. In addition to inhibiting LT synthesis, U-60,257 also appears to be a competitive inhibitor of the action of LT on the guinea pig ileum, although this inhibition requires a higher drug concentration than those ordinarily encountered during assay for LT's in U-60,257-treated incubations.

Animals↗
PubMed1982

Measurement of cortical thickness in a human cadaver femur. Conventional roentgenography versus computed tomography.

Mechanical testing of bone specimens provides information on the fundamental properties of bone and greater understanding of the mechanisms for specific injury patterns. Because the shaft of a long bone can be considered a cylinder, relatively simple models can be used to predict the response of bone to applied forces. However, the cortex thickness along the shaft must be known prior to stressing and fracturing the bone. Conventional roentgenograms and computed tomographic (CT) scans were used to measure at 300 points along the femoral shaft. Both roentgenograms and CT scans overestimated the measured cortical thicknesses by 6% (+/- 11.1%) and 13.4% (+/- 7.8%), respectively. While the roentgenographic method is more accurate, the CT method is technically easier to implement and more generally suitable for the purposes of most research.

Femur↗
PubMed1981

Furazolidone resistance in Salmonella gallinarum: the relationship between in vitro and in vivo determinations of resistance.

Of 22 strains of Salmonella gallinarum isolated from recent outbreaks of infection in poultry in Greece (15). Amman (3), Kenya (2), Lebanon (1) and Yemen (1), 20 were more resistant to furazolidone in vitro than 6 strains that had been isolated in the U.K. in the 1950s; the minimum inhibitory concentration of furazolidone was approximately 0.3 microgram/ml for the sensitive strains and 1.3 or 2.5 microgram/ml for the more resistant strains. Furazolidone given continuously in the food did not control experimental infections in chickens caused by most of the strains that had been classed as more resistant by the in vitro tests. Chloramphenicol, trimethoprim and sulphadiazine or mixtures of the latter two were the best antibiotics for treating these infections, but they were less satisfactory than furazolidone for treating infections caused by the furazolidone-sensitive strains. As a group, the furazolidone-resistant strains and furazolidone-resistant mutants of one of the sensitive strains were less virulent for chickens than the sensitive strains.

Animals↗
PubMed1981

Escherichia coli resistant to tetracyclines and to other antibiotics in the faeces of U.K. chickens and pigs in 1980.

A survey conducted in 1980, 9 years after the banning of the use of tetracyclines as feed additives in the U.K., indicated that table chickens and pigs were still a large reservoir of tetracycline-resistant Escherichia coli; the incidence of transferable tetracycline resistance was greater in chicken E. coli strains (68%) than in pig E. coli strains (20%). Large amounts of sulphonamide-resistant and of furazolidone-resistant E. coli were found in the faeces of chickens; E. coli resistant to both sulphonamides and streptomycin were common in the faeces of chickens and pigs. E. coli with transferable or mobilizable trimethoprim resistance were present in the faeces of most pigs and in the faeces of 10% of chickens.

Animals↗
PubMed1980

Further observations on the effect of feeding diets containing avoparcin, bacitracin and sodium arsenilate on the colonization of the alimentary tract of poultry by salmonella organisms.

The continuous administration of food containing 10 mg/kg of avoparcin to groups of 28 chickens in contact with five chickens experimentally infected with a nalidixic acid-resistant (nalr) mutant of a salmonella strain strongly favoured the colinization of their alimentary tracts with salmonella organisms. Bacitracin, 10 mg/kg, either had no effect or only slightly favoured salmonella colonization and sodium arsenilate usually hindered it. These results were obtained with four different strains of chickens, four different diets and five salmonella serotypes, including a nals form of one of them; the chickens were kept both on wire-netting and littered floors. Similar results were also obtained when turkeys were used instead of chickens. When groups of 33 chickens were inoculated orally with different doses of nalr Salmonella typhimurium organisms, smaller doses were required to infect those fed on an avoparcin-containing diet than those fed on a non-medicated diet. Infection spread more rapidly and more extensively through the avoparcin-fed groups than through the non-medicated groups.

Animal Feed↗