Biomedical subjects

M A Dominick

Publications and source records attributed to M A Dominick.

25 records · Page 2Linked to original sources

PubMed1986

Intracellular location of unoccupied 1,25-dihydroxyvitamin D receptors: a nuclear-cytoplasmic equilibrium.

In order to investigate the subcellular distribution of unoccupied 1,25-dihydroxyvitamin D3 receptors, highly purified cytoplasts and nucleoplasts were prepared from two kidney cell lines (PK1 and MDBK). This was accomplished utilizing the technique of enucleation by cytochalasin B and density gradient centrifugation. Unoccupied 1,25-dihydroxyvitamin D3 receptors were found in both the nuclear and cytosolic compartments, with approximately 70% of the receptors localized in the cytoplasm. When cells were pretreated with 1,25-[3H]dihydroxyvitamin D, prior to enucleation, it was found that 90% of the receptor-hormone complex was associated with nucleoplasts, thus demonstrating that cytochalasin B treatment does not alter the high-affinity association of the receptor-hormone complex with the nucleus. The ratio of unoccupied receptor/protein was found to be the same in whole cells, cytoplasts, and nucleoplasts for both cell types. The ratio of unoccupied receptor/DNA was highest in cytoplasts and lowest in nucleoplasts. Taken together, these data indicate that the unoccupied 1,25-dihydroxyvitamin D receptor is generally associated with cell proteins and not specifically associated with cell DNA. We therefore propose, at least for these cells, that the unoccupied 1,25-dihydroxyvitamin D receptor exists in equilibrium between the nuclear and cytosolic compartments of the whole cell, and receptor-hormone binding shifts this equilibrium to favor nuclear localization.

Animals↗

PubMed1986

Turbinate atrophy in gnotobiotic pigs intranasally inoculated with protein toxin isolated from type D Pasteurella multocida.

Three doses (75 micrograms, 25 micrograms, and 25 micrograms) of purified toxin isolated from a toxigenic strain of type D Pasteurella multocida were given (by atomizer) into the right nasal cavities of each of 10 gnotobiotic pigs on the 21st, 24th, and 27th days of age, respectively. Inoculated pigs (usually 2) and 1 noninoculated control pig each were necropsied on 3, 6, 9, 12, and 15 days after inoculations were given. Severe bilateral atrophy of turbinates occurred in all toxin challenge-exposed pigs. Atrophy was more severe in the inoculated nasal cavity than that in the noninoculated side in 2 of the 10 pigs. Microscopic changes in turbinates of toxin challenge-exposed pigs were more severe in pigs killed at later dates. Dominant changes included degeneration and necrosis of osteoblasts, markedly accelerated osteoclastic osteolysis, replacement of the osseous core by a highly cellular mesenchymal stroma, and multifocal atrophy of submucosal glands. Seemingly, a protein toxin isolated from toxigenic type D strains of P multocida produced rapid atrophy of turbinates and may be a contributing factor in development of clinical progressive atrophic rhinitis in swine.

Animals↗

PubMed1985

Pathology of cloacal bursae of gnotobiotic turkeys orally inoculated with Escherichia coli.

Cloacal bursae from three-week-old gnotobiotic turkeys were examined by light and electron microscopy and bacteriologic techniques at 1, 2, 5, 8, 12, and 16 days after oral inoculation of highly virulent (group 1) and weakly virulent (group 2) Escherichia coli. In both groups a significant decrease in follicular volume and increase in interstitial volume were associated with infection. Follicular cortical, follicular medullary and total follicular transectional areas increased with time in inoculated and control turkeys. In group 1, granulocytic inflammation developed in bursae on day 1 and diminished by day 8 after inoculation. Microabscesses were present on days 5 and 8 after inoculation in less than 1% of follicles. Bacteria were seen in few follicular medullae on days 5 and 8 after inoculation; bacteremia was detected on days 1, 2, and 5 after inoculation. In group 2, pyogranulomatous bursitis was first seen at five days after inoculation and became progressively more severe with time. Follicular alterations in group 2 included abscessation, lymphocyte necrosis, reticuloepithelial hyperplasia and perifollicular fibroplasia. Ultrastructurally, follicular pads had degenerate and necrotic epithelial cells, intercellular edema, and cystic spaces that contained acidic mucosubstances and laminar deposits of calcium salts. Bacteria were seen within necrotic centers of follicular abscesses, in phagosomes of macrophages and multinucleate giant cells and within extracellular spaces of follicular pads and follicular medullae from day 5 to day 16 after inoculation; no bacteremia was detected. We conclude that E. coli passes through the bursal follicle-associated epithelium and replicates within follicular medullae, that extensive follicular necrosis is associated with persistence of E. coli in follicular medullae, and that E. coli of low virulence may cause severe pyogranulomatous bursitis in young turkeys without causing the respiratory or systemic diseases which are commonly associated with organisms of high virulence.

Animals↗

PubMed1985

Expression of type 1 pili by Escherichia coli strains of high and low virulence in the intestinal tract of gnotobiotic turkeys.

Highly virulent (strain 1) and weakly virulent (strain 3) Escherichia coli were examined using immunofluorescent and electron microscopic techniques to determine their ability to express type 1 pili in the intestinal tract of 3-week-old gnotobiotic turkeys. Turkeys were necropsied on postinoculation day (PID) 1, 2, 5, 8, and 12. Nonpiliated forms of strains 1 and 3 were more numerous than piliated forms in cecal and colonic contents examined by negative staining electron microscopy. A piliated form of strain 1 was seen in intestinal contents on each PID and was more numerous in cecal contents than in colonic contents. The mucus blanket of the cecum and colon contained large numbers of bacteria, although organisms were rarely intimately associated with the intestinal epithelium. Immunofluorescent staining indicated large numbers of piliated forms of strains 1 and 3 within the mucus blanket of the cecum and colon on PID 2, 5, 8, and 12. Piliated bacteria were infrequently seen in the ileal mucus blanket. Serum antibody titers to type 1 pili increased markedly by PID 5 and persisted in turkeys inoculated with strain 1. In contrast, antibody titers in turkeys exposed to strain 3 increased gradually and varied markedly among birds at each PID. Type 1 pili may not be important for adherence of pathogenic E coli to intestinal epithelium of turkeys.

Animals↗

PubMed1984

Colonization and persistence of Escherichia coli in axenic and monoxenic turkeys.

Sites of colonization and persistence of virulent (O78) and avirulent (O2) Escherichia coli were determined in 3-week-old axenic turkeys. Colonization of O78 in turkeys infected with Streptococcus faecalis was also determined. Colonization and persistence of E coli in the intestinal tract and lung were not correlated with virulence. Both serotypes persisted in high titer in crop, ileum, ceca, colon, and lung. Persistence of E coli in the liver was positively correlated with virulence, although both serotypes were recovered from the liver in the absence of bacteremia, indicating possible intestinal translocation of E coli to the liver. A reduction in intestinal colonization and translocation of O78 was determined in monoxenic turkeys infected with S faecalis. In contrast, S faecalis had no effect on lung titers of O78. Air sacculitis, pericarditis, and pneumonia were observed in axenic and monoxenic turkeys infected with O78. Bacteremia was detected in a turkey exposed to O78.

Animals↗

PubMed1983

Effects of carbon monoxide exposure on pregnant sows and their fetuses.

Miniature and domestic sows at 108 to 110 days of the gestation were exposed to atmospheric carbon monoxide (CO) concentrations of 150 to 400 ppm for 48 to 96 hours. Overall stillbirth rates were 6.7%, 34.8%, 42.3%, and 80.0% in the sows exposed to CO in concentrations of 200, 250, 300, and 350 ppm, respectively. A significant linear relationship was determined between these concentrations of CO and the resultant maternal carboxyhemoglobin (COHb) concentration (P less than 0.01). The frequency of stillbirth increased significantly when maternal COHb concentration exceeded 23% saturation of hemoglobin. The COHb concentrations in new-delivered pigs (cesarean section) were greater than maternal COHb concentrations by 3 to 22%. Common gross lesions in stillborn pigs were cherry red discoloration of the subcutaneous tissues, muscle, and viscera and accumulation of a large volume of serosanguineous pleural effusion. Hypoxic ischemic leukoencephalopathy was found in new-delivered pigs from 3 of 14 litters. Lesions included focal leukoencephalomalacia, glial-vascular proliferation, multifocal hemorrhage, and vacuolation of the neuropile. Many extramedullary hematopoietic centers were present in liver sections.

Animals↗

PubMedDate not supplied

Toxicologic effects of a novel acyl-CoA:cholesterol acyltransferase inhibitor in cynomolgus monkeys.

PD 132301-2, an acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, was administered orally to cynomolgus monkeys for 2 wk at doses of 25, 50, 100, and 200 mg/kg to assess potential subacute toxicity. Sporadic episodes of soft feces and diarrhea increased in incidence from 100 to 200 mg/kg. Histopathologic alterations in adrenocortical cells of treated monkeys consisted of a dose-related decrease in cytoplasmic fine vacuolation and an increase in cytoplasmic eosinophilia most conspicuous in the zona fasciculata and reticularis. At 50, 100, and 200 mg/kg, a narrow discontinuous zone of cytotoxic cortical cell degeneration occurred in the outer zona fasciculata. Decreased fine vacuolation of cortical cells correlated ultrastructurally with reduced size and number of intracellular lipid vacuoles and biochemically with a dose-related decrease in adrenal total cholesterol (from 56 to 13% of control) and cholesteryl ester (from 51 to 3% of control) concentrations. Other ultrastructural changes noted in zona fasciculata cortical cells at all doses were an apparent increase in both smooth endoplasmic reticulum and variably sized autophagic vacuoles. Ovarian corpora lutea in some females at all doses had increased coarse vacuolation of luteal cells, foci of cellular degeneration, increased numbers of cholesterol clefts, and slight infiltrates of mononuclear cells. Sebaceous glands were atrophic in all treated monkeys due largely to a reduction in size and number of differentiated foam cells. Sebaceous gland reserve cells were hypertrophic and hyperplastic. Toxicity data from this study indicated that PD 132301-2 at 25-200 mg/kg targeted cholesterol-rich cells of the adrenals, ovaries, and skin adnexa.

Adrenal Glands↗