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K Hoover

Publications and source records attributed to K Hoover.

At least 19 recordsLinked to original sources
PubMed2001

Altered expression and localization of the tight junction protein ZO-1 in primary and metastatic pancreatic cancer.

INTRODUCTION: ZO-1 is a tight junction membrane protein that plays a critical role in cell-cell interaction, proliferation, and differ entiation. AIM: To localize and evaluate the expression of ZO-1 in the normal human pancreas, in pancreatic ductal adenocarcinoma (PDAC), and in chronic pancreatitis (CP). METHODOLOGY AND RESULTS: Northern and Western blot analysis revealed ZO-1 expression in all six tested pancreatic cancer cell lines. Expression of ZO-1 mRNA was increased sixfold in PDAC samples in comparison with normal samples (p = 0.04). Confocal microscopy revealed the presence of ZO-1 in the apical and apicolateral areas of ductular cells in the normal pancreas. Similarly, in CP, ZO-1 was localized at apical and apicolateral areas of small proliferating ductular cells and large metaplastic ducts. In PDAC, however, ZO-1 expression was observed irrespective of whether the cancer cells formed duct-like structures or exhibited a diffuse infiltrating pattern. Metastatic pancreatic cancer cells within lymph nodes displayed variable staining patterns, ranging from apical and apicolateral to a diffuse membranous staining. CONCLUSION: These observations suggest that ZO-1 is overexpressed in PDAC and raise the possibility that this overexpression may confer a metastatic advantage to pancreatic cancer cells.

Adult↗
PubMed2000

Midgut-based resistance of Heliothis virescens to baculovirus infection mediated by phytochemicals in cotton.

The decrease in susceptibility to polyhedrosis disease when Heliothis virescens larvae feed on cotton is profound, limiting the utility of baculoviruses for controlling noctuids on this important crop. We observed that the mortalities of H. virescens larvae challenged with a reporter-gene construct of Autographa californica M nucleopolyhedrovirus (AcMNPV-hsp70/lacZ) and fed either lettuce or artificial diet were approximately 2.5-fold higher than that of cotton-fed insects. This decrease in susceptibility on cotton was observed following oral but not intrahemocoelic inoculation of virus, and it was negatively correlated with levels of foliar peroxidase. The rates of development of both infected and uninfected larvae also were correlated negatively with levels of foliar peroxidase, and hence, were significantly lower for insects fed cotton. When Calcofluor White M2R, an optical brightener reported to enhance the retention of AcMNPV-infected midgut cells, was included in inoculum administered orally to larvae, mortality levels were equivalent regardless of diet. These results suggest that sloughing of infected midgut cells occurred at a higher rate in insects that fed on cotton compared to the other two diets, and that midgut cell sloughing is the mechanism whereby susceptibility to mortal infection by AcMNPV-hsp70/lacZ is decreased on cotton. This conclusion is consistent with previous reports that ingestion of cotton can generate reactive oxygen species within the midgut lumen that may damage midgut epithelial cells. As far as we know, this is the first study to link resistance intrinsic to the physiology of the insect (e.g., developmental resistance) and resistance conferred by host plant chemistry to a single mechanism, i.e., midgut cell sloughing.

Journal Article↗
PubMed1999

Selective type III phosphodiesterase inhibition prevents elevated compartment pressure after ischemia/reperfusion injury.

BACKGROUND: A new synthetic cyclic adenosine monophosphate phosphodiesterase inhibitor, cilostazol, has been shown to inhibit platelet aggregation and act synergistically with endogenous prostaglandin I2 to enhance smooth-muscle cell vasodilitation. The effect of cilostazol in ischemia/reperfusion injury-induced compartment syndrome was investigated. METHODS: Sixteen rabbits underwent femoral artery occlusion after ligation of branches from the terminal aorta to the femoral artery. After 7 hours of ischemia, reperfusion was established with heparinized polyethylene shunts. Experimental animals (n = 8) received cilostazol (3.0 mg/kg) and control animals (n = 8) received normal saline as an intravenous infusion 10 minutes before shunt placement. During reperfusion, anterior compartment pressure was continuously monitored in the left lower extremity, and femoral artery blood flow was measured by laser Doppler fluorometry. To quantitate skeletal muscle oxidative metabolism and viability, triphenyltetrazolium chloride (TTC) reduction (micrograms of TTC per milligram of protein) of tibialis anterior muscle from the right lower extremity was measured at femoral artery occlusion, 7 hours of ischemia, and 2 hours of reperfusion. To assess tissue edema, dry/wet weight ratios were also determined at these intervals. Data were expressed as means +/- SE. Comparisons within groups were performed by analysis of variance, and comparisons between groups with two-tailed unpaired t tests. RESULTS: At 2 hours of reperfusion, the difference between controls and cilostazol-treated animals was extremely significant (p = 0.0008). Preischemia and 2-hour reperfusion TTC and dry/wet weight ratios were not significantly different within or between experimental groups, nor was femoral artery blood flow during reperfusion. CONCLUSION: Cilostazol inhibits the increase in compartment pressure central to the development of the compartment syndrome. The mechanism appears to be independent of altered tissue permeability or oxidative metabolism.

Animals↗
PubMed1997

Effects of diet-age and streptomycin on virulence of Autographa californica M nucleopolyhedrovirus against the tobacco budworm.

Addition of the antibiotic streptomycin to two artificial diets routinely used in bioassays of neonate lar vae of Heliothis virescens (tobacco budworm) infected with Autographa californica M nucleopolyhedrovirus (AcMNPV) increased lethal times of the virus. After storage of diets for 3 weeks at 4 degrees C, lethal times of infected larvae were significantly slower compared to those for larvae bioassayed using diets stored for 2 weeks or less. The effect of diet-age on rate of mortality was not the result of a change in total protein content or pH of the diet, but was apparently the result of some other alteration in the quality of the diet (e.g. microbial spoilage, palatibility, and/or nutritional value unrelated to total protein). Although we did not determine why lethal times were slower in response to streptomycin concentration or diet-age, we did find that slower lethal times were correlated with slower relative growth rates (RGR) of infected larvae. In addition, RGR of infected larvae decreased as a function of increasing streptomycin concentration, diet-age, and the interaction of the two factors. These results demonstrate that it is difficult to obtain consistent and comparable bioassay results if antibiotic composition and diet-age are not controlled. We suggest a standardized diet or highly standardized procedures for a given diet be developed that permits comparison of bioassays among and within laboratories.

Animals↗
PubMed1997

Interactions of recombinant and wild-type baculoviruses with classical insecticides and pyrethroid-resistant tobacco budworm (Lepidoptera: Noctuidae).

In tests with neonate Heliothis virescens (F.), we characterized interactions of all combinations of a recombinant Autographa californica (Speyer) nuclear polyhedrosis virus (AcAaIT) that expresses an insect-selective neurotoxin (AaIT) and wild-type AcNPV when combined with low concentrations of several conventional insecticides. All combinations of the recombinant virus AcAaIT and insecticides showed a positive interaction (decrease in the median lethal time (LT50) compared with the LT50 for either component alone). A type II pyrethroid (cypermethrin, which modifies currents of sodium channels) and a carbamate (methomyl, an inhibitor of acetylcholinesterase) were synergistic in combination with AcAaIT. Other insecticides also showed a positive interaction when tested in combination with the recombinant virus, but joint activity was slightly antagonistic (i.e., less than predicted activity when combined) with wild-type AcNPV. We also characterized the effectiveness of AcAaIT against pyrethroid-resistant H. virescens larvae. Our results show that a resistant strain of H. virescens is more sensitive to the recombinant virus compared with a susceptible strain. Results of these studies should be useful in planning of future field trials to increase the effectiveness of nuclear polyhedrosis viruses and to manage resistance to pyrethroids and other insecticides.

Animals↗
PubMed1995

Production of polyhedra of the Autographa californica nuclear polyhedrosis virus using the Sf21 and Tn5B1-4 cell lines and comparison with host-derived polyhedra by bioassay.

Both wild-type and recombinant baculoviruses are becoming more attractive for the control of insect pests. Thus, there is an increased incentive to address and resolve logistical problems associated with large-scale production of these viruses. In this study, we have compared the potential of two insect cell lines, Tn5B1-4 and Sf21, for the production of polyhedra and compared the efficacy of both cell culture-derived and host-derived viruses by bioassay. The efficacy of both wild-type AcMNPV and AcAaIT, a recombinant baculovirus expressing an insect-specific scorpion toxin, were compared. Yields of polyhedra from Tn5B1-4 were sixfold higher than those from the cell line Sf21. Morphological analysis of polyhedra derived from cell culture showed greater variability in size relative to host-derived polyhedra. The maximum size of cell culture-derived polyhedra was over 1.5 times larger than that of insect-derived polyhedra. The efficacy of AcMNPV and AcAaIT derived from cell culture, or from amplification in larvae of Trichoplusia ni or Heliothis virescens, was compared by bioassay in H. virescens. There was a significant difference between the slopes for lethal time data for host-derived and cell culture-derived wild-type virus. Mortality occurred at a faster rate following infection with host-derived virus. No significant difference was seen for the recombinant virus AcAaIT. Lethal doses of cell- and host-derived polyhedra were not significantly different. The reasons for and implications of this for pest control are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Production of functional human hemoglobin in transgenic swine.

A construct containing the locus control region (LCR) from the human beta globin locus together with two copies of the human alpha 1 gene and a single copy of the human beta A gene was used to obtain three transgenic pigs. The transgenic pigs are healthy, not anemic, and grow at a rate comparable to non-transgenic littermates. All animals expressed the human genes. However, alpha globin was consistently expressed at higher levels than beta globin. Isolation of the human hemoglobin from both porcine hemoglobin and other non-hemoglobin proteins was accomplished by ion exchange chromatography. The purified porcine derived human hemoglobin exhibited an oxygen affinity similar to that of human derived human hemoglobin.

Animals↗
PubMed1990

The inhibition by methionine and choline of liver carcinoma formation in male C3H mice dosed with diethylnitrosamine and fed phenobarbital.

The ability of the dietary methyl donors methionine and choline to inhibit the carcinogenic and tumor-promoting effects of phenobarbital (PB) in the livers of male weanling C3H mice was examined. The mice were fed a commercial rodent diet with or without 0.05% PB. Thirty animals from each set received the diet with either: (1) no dietary supplementation, (2) an additional 1.0% choline chloride, (3) 1.5% DL-methionine or (4) both 1.5% DL-methionine and 1.0% choline chloride. Additional groups of 30 animals with the same eight dietary and PB-treatment regimens described above were given a single initiating dose of 150 mg diethylnitrosamine (DENA)/kg body wt dissolved in saline, or the saline solution only, 1 week prior to the start of PB feeding. The 16 treatment groups were fed their respective diets for 12 months. Statistical trend analysis showed that increasing levels of supplemental methyl donors gave highly significant protection in PB-treated mice (P less than 0.01). The incidence of liver carcinomas in the four dietary groups not receiving PB or DENA varied from 0 to 7%. The PB-treated animals not receiving an initiating dose of DENA developed hepatocellular carcinomas (HCCs) at incidences of 79% in group 1 animals, 74% in group 2 animals, 60% in group 3 animals, and 31% in group 2 animals respectively. Thus, incidence of HCCs in group 4 was significantly lower than in groups 1, 2 or 3 (P less than 0.01). However, the total incidence of liver tumors (adenomas plus carcinomas) was about the same in all DENA or PB-treated groups. Thus, dietary supplementation with methyl donors increased the proportion of animals bearing liver adenomas as their most advanced hepatic lesion in PB-treated mice. In DENA-treated mice fed PB, dietary supplementation with methionine and choline protected against the formation of liver carcinomas (P less than 0.02); however, methionine and choline had no significant effect on liver tumor formation in mice fed the PB-free diets. Methionine and choline supplementation gave significant protection against HCC metastases in the lungs of the tumor-bearing mice in groups initiated with DENA followed by PB promotion. These results support the hypothesis that PB exerts it tumorigenic activity in mice at least in part through a physiological insufficiency of labile methyl groups.

Animals↗
PubMedDate not supplied

Reanalysis of the Harvard Six Cities Study, part I: validation and replication.

Because the results of the Harvard Six Cities Study played a critical role in the establishment of the current U.S. ambient air quality objective for fine particles (PM(2.5)), the U.S. Environmental Protection Agency, industry, and nongovernmental organizations called for an independent reanalysis of this study to validate the original findings reported by Dockery and colleagues in the New England Journal of Medicine (vol. 329, pp. 1753-1759) in 1993. Validation of the original findings was accomplished by a detailed statistical audit and replication of original results. With the exception of occupational exposure to dust (14 discrepancies of 249 questionnaires located for evaluation) and fumes (15/249), date of death (2/250), and cause of death (2/250), the audit identified no discrepancies between the original questionnaires and death certificates in the audit sample and the analytic file used by the original investigators. The data quality audit identified a computer programming problem that had resulted in early censorship in 5 of the 6 cities, which resulted in the loss of approximately 1% of the reported person-years of follow-up; the reanalysis team updated the Six Cities cohort to include the missing person-years of observation, resulting in the addition of 928 person-years of observation and 14 deaths. The reanalysis team was able to reproduce virtually all of the original numerical results, including the 26% increase in all-cause mortality in the most polluted city (Stubenville, OH) as compared to the least polluted city (Portage, WI). The audit and validation of the Harvard Six Cities Study conducted by the reanalysis team generally confirmed the quality of the data and the numerical results reported by the original investigators. The discrepancies noted during the audit were not of epidemiologic importance, and did not substantively alter the original risk estimates associated with particulate air pollution, nor the main conclusions reached by the original investigators.

Air Pollutants↗