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Biomedical subjects

H W Smith

Publications and source records attributed to H W Smith.

At least 37 records · Page 2Linked to original sources
PubMed1986

Effect of Piriprost, a 5-lipoxygenase inhibitor, on leukocyte accumulation during thioglycollate-induced acute inflammation.

We evaluated the effect of a prototype 5-lipoxygenase enzyme inhibitor, Piriprost [6,9-deepoxy-6,9-(phenylimino-)delta 6,8-prostaglandin I1], on the leukocyte accumulation induced by intraperitoneal injection of thioglycollate in rats. Piriprost, at 40 mg/kg, i.p., inhibited leukocyte accumulation by 34 +/- 12% (mean +/- S.D., n = 9). With experimental groups containing small numbers of rats (6 to 9) inhibition was statistically significant in 7 of 9 cases. Piriprost shared this property with dexamethasone; however, dexamethasone at 5 mg/kg, p.o., inhibited leukocyte accumulation to a greater extent, 61 +/- 6% (mean +/- S.D., n = 5) and the inhibition was statistically significant in 5 of 5 cases. Conventional non-steroidal antiinflammatory agents including aspirin and phenylbutazone were ineffective in our model. Our results suggest that certain compounds that inhibit the 5-lipoxygenase enzyme, without inhibiting the cyclooxygenase enzyme, can reduce the leukocyte accumulation associated with acute inflammation.

Animals↗
PubMed1986

Crystal structure of quinespar, a quinazoline analogue of methotrexate.

The molecular structure of quinespar, a quinazoline analogue of methotrexate and aminopterin, has been determined by X-ray crystallography. The molecule displays an extended conformation with the p-aminobenzoyl plane rotated 66 degrees from the plane of the quinazoline. The orientation of the quinazoline ring relative to the rest of the molecule is intermediate between the orientations of the comparable pteridine rings in folic acid and in DHFR-bound methotrexate. Evidence is presented to suggest that 2,4-diaminoquinazolines bind to DHFR in the same manner as do 2,4-diaminopteridines.

Folic Acid↗
PubMed1986

Infectious bronchitis immunity: its study in chickens experimentally infected with mixtures of infectious bronchitis virus and Escherichia coli.

The live infectious bronchitis (IB) vaccine, H120, protected chickens against intranasal challenge with a mixture of Escherichia coli strains (E. coli Pool) and IB virus (IBV) strains of the same (Massachusetts) serotype as H120; it usually also protected against challenge with the E. coli Pool and IBV strains of other serological types. When these challenge strains were themselves used as vaccines they usually protected against challenge with a mixture of the E. coli Pool and an IBV strain of the Massachusetts serotype (VF69-149) or an IBV strain not of the Massachusetts serotype (HVI-116). Poor protection, when observed, was most common in those experiments involving a minority of the IBV strains that had been incriminated in recent outbreaks of disease in vaccinated flocks of chickens. Much lower concentrations of IBV strain VF69-149 and E. coli O18 were found in the nose, trachea and spleen of H120-vaccinated chickens killed at different times after they were given a mixture of these organisms than were found in these sites in similarly challenged unvaccinated chickens. Some protection against challenge with IBV and the E. coli Pool was also observed in chickens vaccinated with an inactivated IBV strain; it was much less effective than that obtained following vaccination with the corresponding live IBV strain.

Administration, Intranasal↗
PubMed1986

Two toxin-converting phages from Escherichia coli O157:H7 strain 933 encode antigenically distinct toxins with similar biologic activities.

Escherichia coli O157:H7 strain 933 contains two distinct toxin-converting phages (933J and 933W). The biologic activities and antigenic relationship between the toxins produced by 933J and 933W lysogens of E. coli K-12, as well as the homology of the genes that encode the two toxins, were examined in this study. The 933J and 933W toxins, like Shiga toxin produced by Shigella dysenteriae type 1, were cytotoxic for the same cell lines, caused paralysis and death in mice, and caused fluid accumulation in rabbit ileal segments. The cytotoxic activity of 933J toxin for HeLa cells was neutralized by anti-Shiga toxin, whereas the activity of 933W toxin was not neutralized by this antiserum. In contrast, an antiserum prepared against E. coli K-12(933W) neutralized 933W toxin but not 933J toxin or Shiga toxin. For E. coli 933, most of the cell-associated cytotoxin was neutralized by anti-Shiga toxin, whereas most of the extracellular cytotoxin was neutralized by anti-933W toxin. However, a mixture of these antisera indicated the presence of both toxins in cell lysates and culture supernatants. Among 50 elevated cytotoxin-producing strains of E. coli, we identified 11 strains isolated from cases of diarrhea, hemorrhagic colitis, or hemolytic uremic syndrome that produced cell-associated cytotoxins which were neutralized by the 933W antitoxin. Southern hybridization studies showed that the cloned toxin structural genes from phage 933J hybridized with DNA from phage 933W under conditions estimated to allow no more than 26% base-pair mismatch. These findings indicate that E. coli produces two genetically related but antigenically distinct cytotoxins with similar biologic activities which we propose to name Shiga-like toxins I and II. Strains of E. coli that produce elevated levels of Shiga-like toxin I or Shiga-like toxin II, or both, have been associated with the clinical syndromes of diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome.

Animals↗
PubMed1985

Acquisition of genes from an O18:K1:H7 ColV+ strain of Escherichia coli renders intracranially-inoculated E. coli K12 highly virulent for chickens, ducks and guinea-pigs but not mice.

The virulence of intracranially-inoculated mutant forms of an O18ac:K1:H7 ColV+ strain of Escherichia coli (designated MW) that lacked different combinations of its O and K antigens and ColV, and of an E. coli K12 strain to which these characters had been transmitted was studied in mice, chickens, ducks and guinea-pigs. The O18+K1+ColV+ form of MW was highly virulent for chickens and mice but the corresponding form of K12 was only highly virulent for chickens; the O18-K1-ColV- forms of both strains were of low virulence for chickens and mice. K1 was more important than O18 or ColV in determining virulence for both animal species. Ducks and guinea-pigs resembled chickens, not mice, in their response to infection with the O18+K1+ColV+form of K12. Pathogenesis studies revealed that the virulence of the forms of MW and K12 was associated with their ability to proliferate in the central nervous system; only low numbers of organisms were found in the blood and spleen of inoculated animals. The O18+K1+ColV+ form of K12 multiplied in mouse brain and in mouse blood in vitro; its multiplication in chicken blood was partially inhibited. Agglutinins to this and other forms of K12 were found in chicken serum but not in mouse serum. Large doses of mouse serum given to chickens and large doses of chicken serum given to mice did not alter the manner in which these animals responded to K12 O18+K1+ColV+ infection. Vaccination protected chickens and mice against lethal intracranial infection with the O18+K1+ColV+ forms of K12 or MW; it produced a much stronger immunity in mice against intraperitoneal challenge than against intracranial challenge.

Animals↗
PubMed1985

The experimental infection of chickens with mixtures of infectious bronchitis virus and Escherichia coli.

By inoculating chickens intranasally with a collection of strains of infectious bronchitis virus (IBV) of the Massachusetts serotype and of Escherichia coli of different serotypes, a pool of viral and bacterial strains was selected which, on inoculation, consistently produced a highly lethal disease closely resembling the natural disease produced by these two organisms. The conditions for reproducing the experimental disease were not rigorous in that, within broad limits, the size of the viral and bacterial inocula were not important; neither were the times at which both organisms were administered in relation to each other. The breed or strain of chicken used was important and the resistance of chickens to fatal infection increased with age. When the E. coli strains of the pool were inoculated intranasally without the IBV component, the chickens remained well; bacteriological examination of chickens inoculated with one of the E. coli strains, O18, revealed little evidence of invasion of the tissues or even of persistence of the inoculated E. coli strain in the upper respiratory tract. A minority of the IBV strains examined were lethal for chickens when inoculated without E. coli but many of them only produced a substantial mortality when the E. coli were included in the inoculum; IBV strains in this latter category included the vaccine strains H52 and H120. High concentrations of IBV strain M41 and E. coli O18 persisted in the upper respiratory tract for a number of days after they had been inoculated together. Much lower concentrations of IBV M41 were found in the internal organs, such as the spleen; E. coli O18 was only found in these sites in some of the inoculated chickens. Coliform organisms proliferated in the upper respiratory tract of chickens inoculated with IBV alone; they were rarely found in their internal organs.

Animals↗
PubMed1985

The toxic role of alpha-haemolysin in the pathogenesis of experimental Escherichia coli infection in mice.

Filtrates from strains of Escherichia coli possessing plasmid-cloned haemolysin (Hly) genes and from strains possessing 'wild' Hly plasmids were lethal for mice on intravenous inoculation; similar doses of preparations from derivatives of these strains in which the Hly genes had been rendered non-functional or which did not possess the 'wild' plasmids were not. Live cultures of both kinds of Hly+ strain usually had a lower lethal dose for mice on intraperitoneal inoculation than the corresponding Hly- forms. Mice that had been inoculated with Hly+ forms had shorter survival times and lower numbers of organisms in peritoneal washings, lungs and blood at point of death than mice that had been inoculated with the corresponding Hly- forms; this was also so for mice pre-treated with FeSO4, a procedure which rendered mice equally susceptible to the lethal effects of the Hly+ and Hly- forms of a strain. In FeSO4-treated mice the numbers of organisms in the tissues of those dying from infection with Hly+ organisms were no higher than they were at the same time after inoculation in others given the corresponding Hly- forms; before mice of the latter category died the numbers of organisms in their tissues increased greatly. The clinical and pathological signs exhibited by mice inoculated with Hly+ organisms, but not with Hly- organisms, resembled those exhibited by mice inoculated with bacteria-free haemolysin preparations. These results suggest that haemolysin played a significant role in the pathogenesis of the disease produced by the Hly+ organisms by having a direct toxic action on the host.

Animals↗
PubMed1985

Transduction complicates the detection of conjugative ability in lysogenic salmonella strains.

When lysogenic salmonella strains were examined for conjugative ability in tri-parental crosses, false positive results were sometimes obtained because phage carried by the lysogenic strains multiplied on the intermediate salmonella recipient strain and then transduced its streptomycin/sulphonamide resistance plasmid to the final salmonella recipient strain. Back transfer of the plasmid to the lysogenic strains was also detected.

Conjugation, Genetic↗
PubMed1984

Shiga-like toxin-converting phages from Escherichia coli strains that cause hemorrhagic colitis or infantile diarrhea.

Escherichia coli K-12 acquired the ability to produce a high titer of Shiga-like toxin after lysogenization by either of two different bacteriophages isolated from a highly toxinogenic Escherichia coli O157:H7 strain that causes hemorrhagic colitis. One of these phages and another Shiga-like toxin-converting phage from an Escherichia coli O26 isolate associated with infantile diarrhea were closely related in terms of morphology, virion polypeptides, DNA restriction fragments, lysogenic immunity, and heat stability, although a difference in host range was noted. These phages are currently the best-characterized representatives from a broader family of Shiga-like toxin-converting phages.

Animals↗
PubMed1984

The effect of feeding diets containing avoparcin on the excretion of salmonellas by chickens experimentally infected with natural sources of salmonella organisms.

Chickens were readily infected with salmonella organisms when fed diets containing unsterilized bone-meal or provided with drinking water containing a suspension of natural salmonella infected chicken faeces. When fed diets containing avoparcin at concentrations of 10 or 100 mg/kg chickens infected in these ways excreted larger numbers of salmonellas for longer periods than did chickens fed a nonmedicated diet.

Animal Feed↗
PubMed1984

Antibiotic resistance in Escherichia coli causing generalized infections in chickens in the UK in 1982: the relationship between the results of in vitro and in vivo furazolidone sensitivity tests.

Compared with a similar survey conducted ten years previously, a survey conducted in 1982, eleven years after the implementation of legislation forbidding the routine use of feeds containing 'therapeutic' antibiotics, revealed a decreased incidence of resistance to tetracyclines, furazolidone and sulphonamides in Escherichia coli strains causing generalized infections in chickens in the UK; the decrease was particularly marked in the case of tetracycline resistance, 17.9% of strains in 1982 being resistant to this antibiotic compared with 31.2% in 1972. Giving furazolidone to groups of chickens inoculated intramuscularly with O2:K1 strains of E. coli of differing degrees of furazolidone sensitivity indicated that great care is required in the performance and interpretation of laboratory tests for sensitivity to this antibiotic. Infections caused by strains that required as little as 1.25 micrograms/ml of furazolidone to inhibit their multiplication in laboratory tests responded poorly to furazolidone treatment; those that were inhibited by less responded well, better than to treatment with tetracycline, chloramphenicol, ampicillin or trimethoprim.

Animals↗
PubMed1984

Biomechanics of femur fractures secondary to gunshot wounds.

Nonlethal gunshot wounds to the femur produce four classical types of fractures. The 'drill-hole,' incomplete, and 'butterfly' fractures have been described in both clinical and experimental settings. The remote spiral fracture, sometimes attributed to the fall on the femur after wounding, is unique to the weight-loaded femur. A mathematical model relying on the beam in bending and the mechanics of a cylindrical shell is offered. An experimental method utilizing an apparatus (the 'osteoclast') designed to apply torsion, bending, or combined forces to cadaveric long bones is discussed. Femur failure proximal or distal to the impact site of a projectile is a function of stress risers operating at relatively great distances. Predictable primary and secondary peak moment locations for fracture are illustrated.

Adult↗
PubMed1984

Myoglobinuria and acute renal failure associated with intravenous vasopressin infusion.

Myoglobinuria and acute renal failure were observed in two patients with vasopressin-treated gastrointestinal hemorrhage. Because there were no other obvious causes of renal failure in either patient, we propose that skeletal muscle ischemia developed during vasopressin infusion, followed by release of myoglobin and renal damage. This association should be considered in the period after vasopressin-treated gastrointestinal hemorrhage.

Acute Kidney Injury↗
PubMed1984

Steroid use in idiopathic sudden sensorineural hearing loss.

Few studies have investigated the effect of steroids on idiopathic sudden hearing loss (ISHL). Recently, Wilson, et al., reported a double blind study demonstrating a statistically significant improvement of hearing using steroids is ISHL. This report, fashioned after the Wilson study, confirms his findings and analyzes the relationship of several factors to the probability of hearing recovery.

Adult↗