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Biomedical subjects

F E Jones

Publications and source records attributed to F E Jones.

At least 19 recordsLinked to original sources
PubMed2001

Herpes simplex virus virion host shutoff protein requires a mammalian factor for efficient in vitro endoribonuclease activity.

The virion host shutoff protein (vhs) of herpes simplex virus (HSV) triggers global shutoff of host protein synthesis and accelerated mRNA turnover during virus infection and induces endoribonucleolytic cleavage of exogenous RNA substrates when it is produced in a rabbit reticulocyte (RRL) in vitro translation system. Although vhs induces RNA turnover in the absence of other HSV gene products, it is not yet known whether cellular factors are required for its activity. As one approach to addressing this question, we expressed vhs in the budding yeast Saccharomyces cerevisiae. Expression of vhs inhibited colony formation, and the severity of this effect varied with the carbon source. The biological relevance of this effect was assessed by examining the activity of five mutant forms of vhs bearing previously characterized in-frame linker insertions. The results indicated a complete concordance between the growth inhibition phenotype in yeast and mammalian host cell shutoff. Despite these results, expression of vhs did not trigger global mRNA turnover in vivo, and cell extracts of yeast expressing vhs displayed little if any vhs-dependent endoribonuclease activity. However, activity was readily detected when such extracts were mixed with RRL. These data suggest that the vhs-dependent endoribonuclease requires one or more mammalian macromolecular factors for efficient activity.

Animals↗
PubMed1999

ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation.

Signaling by members of the epidermal growth factor receptor family plays an important role in breast development and breast cancer. Earlier work suggested that one of these receptors, ErbB4, is coupled to unique responses in this tissue. To determine the function of ErbB4 signaling in the normal mouse mammary gland, we inactivated ErbB4 signaling by expressing a COOH terminally deleted dominant-negative allele of ErbB4 (ErbB4DeltaIC) as a transgene in the mammary gland. Despite the expression of ErbB4DeltaIC from puberty through later stages of mammary development, an ErbB4DeltaIC-specific phenotype was not observed until mid-lactation. At 12-d postpartum, lobuloalveoli expressing ErbB4DeltaIC protein were condensed and lacked normal lumenal lactation products. In these lobuloalveoli, beta-casein mRNA, detected by in situ hybridization, was normal. However, whey acidic protein mRNA was reduced, and alpha-lactalbumin mRNA was undetectable. Stat5 expression was detected by immunohistochemistry in ErbB4DeltaIC-expressing tissue. However, Stat5 was not phosphorylated at Y694 and was, therefore, probably inactive. When expressed transiently in 293T cells, ErbB4 induced phosphorylation of Stat5. This phosphorylation required an intact Stat5 SH2 domain. In summary, our results demonstrate that ErbB4 signaling is necessary for mammary terminal differentiation and Stat5 activation at mid-lactation.

Animals↗
PubMed1999

Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation.

Overexpression of the receptor tyrosine kinase ErbB2/HER2/Neu (ErbB2) occurs in 15-40% of human breast cancers. To determine the function of ErbB2 signaling during normal mouse mammary gland development, we expressed a carboxyl-terminal truncated dominant negative allele of ErbB2 (ErbB2deltaIC) in the developing mouse mammary gland. Despite ErbB2deltaIC expression within mammary glands of pubescent virgin and pregnant mice, a phenotype was not observed until late in pregnancy. At 1 day post-partum, lactationally active, distended lobuloalveoli failed to form. This phenotype was exaggerated in multiparous females expressing ErbB2deltaIC. Immunohistochemical staining for ErbB2deltaIC revealed a concordance between high levels of ErbB2deltaIC protein expression and the absence of lactational products within the lumens of ErbB2deltaIC stained lobuloalveoli. These results demonstrate that ErbB2 signaling is required for proper mammary development and lactation at parturition.

3T3 Cells↗
PubMed1996

Heregulin induces in vivo proliferation and differentiation of mammary epithelium into secretory lobuloalveoli.

Mammary gland development and differentiation is mediated through the combined activities of systemic hormones and locally synthesized growth factors. To determine the in vivo response of mammary epithelium to heregulin (HRG), we implanted Elvax pellets containing HRG alpha or HRG beta within the mammary glands of prepubescent female mice in the presence or absence of exogenous estradiol and progesterone (E/ P). Mice treated in the same way with transforming growth factor alpha (TGF-alpha) were included as a positive control. Each growth factor treatment induced epithelial ductal branching in the presence or absence of E/P. In the absence of E/P, HRG beta did not effect terminal end bud formation, mammary epitheilum branching, or ductal migration. In contrast, TGF-alpha and HRG alpha induced ductal branching and HRG alpha induced ductal migration in the absence of E/P. The overall mammary response to growth factors was potentiated by the concomitant presence of E/P. In every case, the in vivo mammary epithelial responses to HRG alpha were more robust than TGF-alpha. Limited lobuloalveolar development was also observed in growth factor-treated mammary glands when E/P was present. Histological examination of growth factor-induced lobuloalveoli revealed secretory products within the lumen of HRG alpha and HRG beta lobuloalveoli. TGF-alpha-induced lobuloalveoli lacked similar secretory products.

Animals↗
PubMed1995

Mutational analysis of the herpes simplex virus virion host shutoff protein: evidence that vhs functions in the absence of other viral proteins.

Herpes simplex virus (HSV) virions contain one or more factors that trigger rapid shutoff of host protein synthesis and accelerated decay of cellular and viral mRNAs in infected cells. HSV isolates bearing mutations at the virion host shutoff (vhs) locus (gene UL41) are defective for both processes, indicating that the vhs protein is required; however, it is not clear whether the role of vhs in shutoff is direct or indirect and if other virion components are also necessary. We therefore used a transient-cotransfection assay to determine if the vhs protein displays activity in the absence of other viral gene products. We found that a vhs expression vector strongly suppressed expression of a cotransfected lacZ reporter gene and that this effect was eliminated by the vhs1 point mutation that abolishes virion-induced host shutoff during HSV infection. Further evidence for the biological relevance of the transfection assay came from the demonstration that five vhs in-frame linker insertion mutations yielded concordant results when assayed in cotransfected cells and following transfer into the viral genome: three mutations eliminated activity in both assays, while two had no effect. On the basis of these results, we conclude that the vhs protein can trigger host shutoff in the absence of other HSV proteins. The cotransfection assay was used to rapidly assess the activities of a panel of linker insertion mutants spanning the vhs polypeptide. All mutations that mapped to regions conserved among the vhs homologs of alphaherpesvirus inactivated function; in contrast, four of five mutations that mapped to regions that are absent from several vhs homologs had no effect. These results further support the biological relevance of the transfection assay and begin to delineate functional domains of the vhs polypeptide.

Amino Acid Sequence↗
PubMed1987

Age at immigration and education: further explorations.

Trends in the relationship between age at immigration and educational attainment are examined using age- and sex-specific data for Canada, 1881-1973. "Although initial analyses of data, collected for the [1973] Canadian Mobility Study, reveal a weak relationship between age at immigration and educational attainment, inclusion of a measure of periodicity in educational attainment models reveals age at immigration to have an effect comparable to that of family size on educational attainment. Given the strong periodicity effect, when age at immigration is excluded from the analysis, it is argued that the status attainment model, which best accounts for the educational attainment of native-born Canadians, also accounts best for the educational attainment of the foreign-born."

Age Factors↗
PubMed1986

Calcification simulating infection in congenital brachydactyly.

Two cases of idiopathic soft tissue calcification occurring in the vestigial fingers of infants with congenital brachydactyly are reported. Both patients presented with acute local inflammation simulating infection and responded well to simple excision of the calcium deposits.

Bacterial Infections↗
PubMed1984

The effects of ascorbic acid and butylated hydroxyanisole in the chemoprevention of 1,2-dimethylhydrazine-induced large bowel neoplasms.

Human large bowel neoplasia seems to be caused by environmental carcinogens. The experimental carcinogen, 1,2-dimethylhydrazine (DMH), must be oxidized in the body to have effect. The antioxidants, butylated hydroxyanisole (BHA) and ascorbic acid, were tested for efficacy in prevention of experimental large bowel neoplasia. Carcinogenesis was induced in female CF-1 mice by administering DMH, 20 mg/kg, sq for 24 weekly doses. Test animals received varying doses of ascorbic acid, BHA, or both agents together. Animals were sacrificed when moribund or at 35 weeks. All colons were totally embedded and analyzed histologically. Ascorbic acid demonstrated no effects on incidence or density of large bowel tumors. Ascorbic acid did increase the ratio of adenomas to adenocarcinomas. BHA decreased the incidence and density of large bowel tumors. The lowest incidence was obtained in the group receiving both agents combined. It is concluded that BHA is effective in the chemoprevention of DMH-induced large bowel neoplasms. Ascorbic acid demonstrates only modest effect. The greatest effect on tumor incidence is seen when ascorbic acid and BHA are administered together.

1,2-Dimethylhydrazine↗
PubMed1982

Altered hepatic disposition of doxorubicin in the perfused rat liver at hyperthermic temperatures.

The perfused rat liver was used to study the effects of heat on hepatic functions and on the metabolism and biliary excretion of doxorubicin (Ad). Livers were perfused for 1 hour at 37 degrees C and 42 degrees C in the presence of biosynthetic substrates with or without Ad. Gluconeogenesis was decreased at both temperatures in the presence of Ad. Bile flow and excretion of Ad ceased at 42 degrees C. Perfusate levels of Ad were not significantly different in the 1-hour perfusions. Livers were then perfused at 37 degrees C and 41 degrees C for 3 hours in the presence of 10 mM glucose and amino acids. The beta half-life of Ad measured as total fluorescence and as parent drug was prolonged at 41 degrees C. The area under the plasma concentration-time curve was unchanged for parent drug but increased from 2010 micrograms/ml . min at 37 degrees C to 4477 micrograms/ml . min at 41 degrees C for total drug equivalents. Biliary excretion of total Ad equivalents was 7.39% +/- 1.35% of the total dose at 37 degrees C and 2.56% +/- 2.08% of the total dose at 41 degrees C (P less than 0.05). Biliary excretion of Ad was 2.07% +/- 0.37% of the total dose at 37 degrees C and 1.31% +/- 0.84% of the total dose at 41 degrees C (P less than 0.05). Hepatic tissue levels of total Ad equivalents were 288.7 +/- 21.2 micrograms/g at 37 degrees C and 322.7 +/- 10.6 micrograms/g at 41 degrees C (P less than 0.05). Tissue levels of Ad were 57.5 +/- 14 micrograms/g at 37 degrees C and 23.0 +/- 10.7 micrograms/g at 41 degrees C (P less than 0.05). Bile flow at the two temperatures decreased after 2 hours of perfusion. The greatest decrease in bile flow occurred during the third hour of perfusion at 41 degrees C. The data indicate that at elevated temperatures there was a significant alteration in the pharmacokinetics of Ad in the perfused rat liver system. Since the liver plays a primary role in the metabolism and elimination of Ad, the observed changes might also occur during wholebody hyperthermia.

Animals↗
PubMed1977

Current sociological research in Canada: views of a journal editor.

On the basis of submissions to the Canadian Review of Sociology and Anthropology and to the Annual Meetings of the Canadian Sociological and Anthropological Association, sociology in Canada may be described as social problem oriented, empirical, and atheoretical. There is a strong interest in research on ethnicity and on immigrant adjustment, reflecting a continuity with earlier periods of sociology in Canada, and on deviance and social control. Research on stratification, social mobility, and the family has been relatively neglected. As sociology in Canada shares the interest of "mainline" sociology, it has not escaped criticism or attempts to change its direction. A general model, identifying influences on the formulation of investigative issues in sociology, is used to interpret these criticisms and responses to them.

Canada↗
PubMed1977

H. influenzae meningitis treated with ampicillin or chloramphenicol, and subsequent hearing loss.

Sensori-neural hearing loss after H. influenzae meningitis in children has been reported to occur more frequently after treatment with ampicillin than with chloramphenicol. In the present survey, hearing was assessed clinically and, in most cases, audiometrically in 47 children seen after H. influenzae meningitis. Three children were found to have some sensori-neural hearing loss. In no case was this severe or suspected prior to examination. One was among 27 children treated with ampicillin; one was among eight treated with ampicillin and chloramphenicol; and one was treated with chloramphenicol and streptomycin. Most of the children received ampicillin in a dose of 250mg/kg/day or less, but the two who were treated with ampicillin and developed hearing loss were among five children who received higher doses, suggesting that ampicillin may be ototoxic when given in very high doses.

Ampicillin↗
PubMed1976

Evaluation of "instant" preparation of the colon with povidone-iodine.

The antimicrobial effect of 20 minutes exposure to 10% povidone-iodine solution and to 5% neomycin-erythromycin solution was evaluated in vitro in 6 suspensions of dog feces. Povidone-iodine eliminated aerobic growth (P less than 0.001) and reduced anaerobes 4.01 +/- 1.06 (P less than 0.02); C. perfringens was the only anaerobic organism grown. Forty unprepared dogs underwent resection of the sigmoid colon and primary anastomosis. Twenty received normal saline and 20 povidone-iodine injected intraluminally immediately before resection. The colon contents of povidone-iodine treated dogs grew only 0.07 +/- 0.07 aerobes and 3.74 +/- 0.49 anaerobes (all Clostridia) (log10/ml colon contents) (P less than 0.001). All povidone-iodine dogs survived 3 weeks with no anastomotic leaks; three controls died from anastomotic leak within the first week (P = 0.12). Reexploration of survivors revealed less perianastomotic reaction in the povidone-iodine group. Twenty minutes exposure to povidone-iodine produced a significant decrease in bacterial counts in vitro and in unprepared sigmoid colon. No adverse effects were demonstrated.

Animals↗
PubMed1975

Local infusion of urokinase and heparin into renal arteries in impending renal cortical necrosis.

Two patients with presumed impending cortical necrosis, after haemolytic uraemic syndrome in one and after concealed accidental haemorrhage in the other, were treated by local infusion of urokinase and heparin into the renal artery. Both recovered and one regained normal renal function. Local infusion of anticoagulants or thrombolytic drugs into one renal artery offers the possibility of a controlled examination of the efficacy of this treatment in preventing cortical necrosis.

Adult↗