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Biomedical subjects

W C Mitchell

Publications and source records attributed to W C Mitchell.

16 recordsLinked to original sources

Efficacy of a commercial bacterin in protecting strain 13 guineapigs against Bordetella bronchiseptica pneumonia.

Bordetella bronchiseptica is known to be endemic in many guineapig (Cavia porcellus) colonies, and periodically is the aetiological agent of fatal epizootics of bronchopneumonia. A commercial, non-adjuvant B. bronchiseptica bacterin, which is approved for use in canines, was evaluated for induction of a protective immune response in Strain 13/N guineapigs against an airborne challenge of virulent B. bronchispeptica in small-particle aerosol. Seronegative animals were vaccinated on days 0 and 21 with intramuscular injections of 0.2 ml of bacterin. Humoral antibody titres of the vaccinated animals, as determined by ELISA, ranged from 128-1024 on day 49. On day 30 following the second dose of bacterin (study day 51), 12 vaccinated and 12 PBS sham-vaccinated animals were exposed to an inhaled dose of 4.3 x 10(5) CFU of B. bronchiseptica (325 LD50). Vaccinated, challenged animals remained clinically normal, although each guineapig did develop a localized upper respiratory infection. The rate of weight gain as well as rectal temperature of these animals were analogous to those exhibited by the control groups. Examination of 4 of the vaccinated, challenged animals on day 7 after exposure showed bacteria present in moderate to high numbers in the larynx and trachea but only minimally detectable in the lungs; by 30 days after exposure, the numbers of bacteria in the larynx and trachea were diminished, with none being detected in the lungs. Pathological alterations induced by B. bronchiseptica were not detected at either day 7 or day 30 after challenge in any of the vaccinated, challenged animals. Protection induced in Strain 13/N guineapigs by the commercial canine bacterin was sufficient to preclude the development of pulmonary disease, even in animals presented with a massive challenge of virulent bacteria in a small-particle aerosol.

Animals↗

Triphenylethylene antiestrogen binding sites (TABS) specificity.

The relative binding affinities (RBA) of various compounds for the triphenylethylene antiestrogen binding sites (TABS) were examined. The ability of tamoxifen to inhibit the binding of [3H]tamoxifen to salt extracted (0.4 M KCl) TABS from rat liver nuclei was used as a standard by which other compounds were compared (tamoxifen RBA, 100; Kd approximately 1 nM). Nafoxidine was the most effective triphenylethylene compound used (RBA 333; Kd approximately 0.3 nM) whereas the RBA of zuclomiphene and enclomiphene was not different from tamoxifen. MER-29 was the weakest inhibitor of the triphenylethylene derivatives (RBA 10; Kd approximately 10 nM). Trifluoperazine, chlorpromazine and the anti-calmodulin drugs W-13 and W-12 had RBA's of 25, 1, 1 and 0.1 respectively. The binding affinities of cholesterol and 7-ketocholesterol were significant (Kd approximately 22 nM) while the steroid hormones, estradiol, testosterone, progesterone and corticosterone displayed not observable affinity. Various compounds obtained from Merrill Dow Pharmaceuticals and the Eli Lilly Company which contained alklaminoethoxy side chains linked to aromatic ring structures had RBA's ranging from 1-0.3. We conclude, as other investigators have also concluded, that the similar binding affinities of various triphenylethylene antiestrogens for TABS and their divergent activities as antiestrogens makes it unlikely that TABS are directly involved in estrogen antagonism. The moderate but significant affinity of TABS for trifluoperazine and other drugs thought to be involved in calmodulin regulation indicates that TABS may be a linked in some way to calmodulin function. The binding of cholesterol and 7-ketocholesterol is also significant and may indicate that TABS are involved in cholesterol metabolism.

Animals↗

Airborne-induced experimental Bordetella bronchiseptica pneumonia in strain 13 guineapigs.

To evaluate the efficacy of a commercial bacterial vaccine in protecting Strain 13 guineapigs against fatal Bordetella bronchiseptica pneumonia, it was necessary to establish the infectivity and disease pathogenesis induced by virulent organisms. When guineapigs were exposed to small-particle aerosols of varying concentrations of virulent B. bronchiseptica, a spectrum of disease was produced that ranged from inapparent illness to fulminant bronchopneumonia. Clinical signs began by day 4 after exposure, and were evidenced by anorexia, weight loss, respiratory distress and serous to purulent nasal discharge. Pathological alterations were limited to the respiratory system. Moribund animals exhibited a suppurative necrotizing bronchopneumonia and necrotizing tracheitis. In animals that survived the challenge, the bacteria were eliminated from the lungs by day 28 but continued to persist in the laryngeal area and the trachea. The median infectious dose and the median lethal dose were estimated to be 4 colony-forming units (CFU) and 1314 CFU respectively. These data suggest that the guineapig will be a valuable model system in which to study interactions between Bordetella species and host cells as well as to evaluate potential B. bronchiseptica immunogens.

Air Microbiology↗

Benzyl acetates as attractants for the male oriental fruit fly, Dacus dorsalis, and the male melon fly, Dacus cucurbitae.

Fifty compounds related to benzyl acetate were evaluated quantitatively as attractants to the male oriental fruit fly (Dacus dorsalis) and the male melon fly (Dacus cucurbitae). Thienylmethyl acetate was nearly as attractive as benzyl acetate to both species, but cyclohexylmethyl acetate was completely unattractive, emphasizing the role of the planar aromatic ring in receptor interaction. Although benzyl acetate was equally attractive to both species, para substituents invariably reduced attraction to the oriental fruit fly. A number of derivatives, including p-hydroxy-, p-methoxy-, p-acetoxy-, and p-cyanobenzyl acetates were highly attractive to the melon fly. Selective fluorination indicated that the polarizability of the carbonyl carbon is important in receptor interaction with the melon fly but is not specifically involved in the oriental fruit fly. Attraction to the melon fly was lost with ortho, meta, or dimethoxy substitution of benzyl acetate, but the 3,4- and 2,5-dimethoxybenzyl acetates were attractive to the oriental fruit fly. These results are interpreted in terms of specific olfactory receptor interactions for the two species of fruit flies.

Journal Article↗

Effects of metoclopramide on detrusor function.

Metoclopramide (Reglan) has been widely used as a motility agent because of its contractile effects on gastrointestinal smooth muscle. This agent also may demonstrate significant effects in the urinary system; however, controlled studies of possible effects on bladder function have not been previously reported. Metoclopramide effects on the detrusor smooth muscle were studied using a canine model system. Metoclopramide was compared with bethanechol chloride and a control substance in a random double blind study. Preliminary data from this animal model suggests that metoclopramide significantly increased detrusor contractility as manifested by a decrease in bladder capacity, an increase in detrusor peak voiding pressure and a decrease in post-void residual volume. These effects were similar to those manifested by parenteral bethanechol chloride.

Animals↗

Olfactory receptors in the melon fly Dacus cucurbitae and the oriental fruit fly Dacus dorsalis.

Male melon flies (Dacus cucurbitae) from a colony in Hawaii were evaluated for limit of response to the olfactory stimulant raspberry ketone and to more than 40 related molecules. The results were compared with the limits of response of oriental fruit flies (Dacus dorsalis) under identical conditions. The nature of the response of the two species to attractive compounds appeared to be identical with regard to orientation, searching, pulsating mouthparts, and compulsive feeding. However, there was very little overlap in the response of the two species to phenylpropanoid-type compounds. D. cucurbitae responded most strongly to p-hydroxyphenylpropanoids while D. dorsalis responded most strongly to 3,4-dimethoxyphenylpropanoids. The results are discussed in terms of antennal receptor site geometry and with regard to the coevolution of two major groups of Dacini with plant kairomones.

Journal Article↗

Molecular parameters and olfaction in the oriental fruit fly Dacus dorsalis.

The methyl eugenol receptor of the male oriental fruit fly (Dacus dorsalis) has been further characterized by evaluating the role of the linear free energy parameters product operator and sigma in the depolarization of the receptor by 37 substituted 3,4-dimethoxybenzenes. There was a strong positive correlation between the hydrophobic character of the primary substituent and intense odor and a positive correlation between the electron donating property of the primary substituent and intense odor. Maximum odor intensity was also associated with substituents of 3 atomic diameters and was improved by a center of unsaturation. Preference tests suggest that this simple and versatile odor receptor can serve as a model for investigation of molecular interactions between receptors and odorant molecules.

Journal Article↗

Evolution of olfactory receptor in oriental fruit fly Dacus dorsalis.

Male oriental fruit flies (Dacus dorsalis) from colonies in Taiwan and Hawaii were evaluated for limit of response to various analogues of methyl eugenol. The results are interpreted in terms of the geometry and allosteric requirements of the antennal receptor that triggers the characteristic methyl eugenol reflex. This receptor has evolved for complementarity to all portions of the methyl eugenol molecule and responds only to ortho-substituted benzenes with adjacent oxygen atoms or isoelectronic equivalents. Substantial differences in responses of Taiwan and Hawaiian D. dorsalis suggest that perceptible evolution of the receptor protein has occurred during the past 50 years. A plausible scheme for the coevolution of dacini flies with plants containing phenylpropionoid essential oils is outlined.

Journal Article↗

Attraction of the oriental fruit fly, Dacus dorsalis, to methyl eugenol and related olfactory stimulants.

The attraction of male oriental fruit flies to methyl eugenol and 34 analogues was investigated quantitatively using the characteristic feeding response. Methyl eugenol was the most active compound studied, with a feeding response to 0.01 mug, but saturation of the allyl side chain or replacement of allyl by allyloxy produced compounds almost as effective. Replacement of the methoxy groups by methylenedioxy, methyl, or chloro groups abolished all response. The ring geometry of the methoxy groups was critical, with orthodimethoxy most active and meta-dimethoxy inactive. Replacement of methoxy with hydroxy, methylthio, or amino groups did not abolish the response. The failure of the oriental fruit fly to respond to the methyl and chloro isosteres of methyl eugenol was contrasted with the response of a human odor panel which perceived these compounds as having weak floral odors.

Animals↗

Nonsurgical repair of furcal perforations: a literature review.

The important steps in the management of a furcal perforation are immediate action, adequate isolation, debridement, and sealing of the defect. Studies have shown that repair materials or underlying matrix material such as amalgam, Cavit, calcium hydroxide, glass ionomers, hydroxylapatite, tricalcium phosphate, and demineralized freeze-dried bone have not been able to produce consistent results. However, current research on new materials such as mineral trioxide aggregate may advance treatment modalities significantly for furcation repair.

Aluminum Compounds↗

Staphylococcus hyicus associated with turkey stifle joint osteomyelitis.

Essentially pure cultures of Staphylococcus hyicus were isolated in moderate to high numbers from tibia growth-plate lesions from five of nine turkey hens showing clinical signs of stifle joint osteomyelitis. Of the four other tibia growth-plate specimens examined, Salmonella sp. and Enterococcus faecalis were individually isolated from one bird each, and no bacterial pathogens were isolated from the remaining two cases. Staphylococcus aureus, considered the most common cause of osteomyelitis in turkeys, was isolated from none of the nine birds examined in this flock. These findings suggest a strong association between S. hyicus and turkey stifle joint osteomyelitis.

Animals↗

Porcelain veneer repair of prostheses.

Metal-ceramic restorations have the potential to fracture. Repairing porcelain restorations creates a serious dilemma for the restorative dentist. The most common repair technique is one using composite resin; porcelain veneer provides an alternative.

Dental Porcelain↗