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B Yount

Publications and source records attributed to B Yount.

12 recordsLinked to original sources
PubMed2002

A case-control study of tobacco use and other non-occupational risk factors for t(14;18) subtypes of non-Hodgkin's lymphoma (United States).

OBJECTIVE: Non-Hodgkin's lymphoma (NHL) encompasses diverse subtypes, and analyzing NHL as a single outcome may mask associations. In a new approach we evaluated associations with subtypes defined by the t(14;18) translocation, reasoning that cases within these subtypes would have more common risk factors than all NHL combined. METHODS: Archival biopsies from cases in a population-based NHL study were assayed for t(14;18) using polymerase chain reaction amplification. Exposures in 68 t(14;18)-positive and 114-negative cases were compared with 1245 controls. The expectation-maximization algorithm was used to fit polytomous regression models based on all available information, including data from 440 unclassified cases. RESULTS: Family history of hemolymphatic cancer was associated with t(14;18)-negative NHL (odds ratio (OR) 2.4, 95% confidence interval (CI) 1.4 3.9). but not t(14;18)-positive NHL. Cigarette smoking was weakly associated with t(14;18)-positive NHL (OR 1.7, CI 0.9-3.3), but ORs decreased as smoking increased. Chewing tobacco was associated with t(14;18)-positive NHL, particularly when used before age 18 (OR 2.5. CI 1.0-6.0, 13 exposed cases). Odds ratios for both case-subtypes were doubled among hair-dye users. CONCLUSIONS: Cigarette smoking was not clearly associated with t(14;18)-positive NHL. Family history may be a marker for factors that act specifically through t(14;18)-negative pathogenic mechanisms.

Adolescent↗
PubMed2001

Agricultural risk factors for t(14;18) subtypes of non-Hodgkin's lymphoma.

The t(14;18) translocation is a common somatic mutation in non-Hodgkin's lymphoma (NHL) that is associated with bcl-2 activation and inhibition of apoptosis. We hypothesized that some risk factors might act specifically along t(14;18)-dependent pathways, leading to stronger associations with t(14;18)-positive than t(14;18)-negative non-Hodgkin's lymphoma. Archival biopsies from 182 non-Hodgkin's lymphoma cases included in a case-control study of men in Iowa and Minnesota (the Factors Affecting Rural Men, or FARM study) were assayed for t(14;18) using polymerase chain reaction amplification; 68 (37%) were t(14;18)-positive. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) for various agricultural risk factors and t(14;18)-positive and -negative cases of non-Hodgkin's lymphoma, based on polytomous logistic regression models fit using the expectation-maximization (EM) algorithm. T(14;18)-positive non-Hodgkin's lymphoma was associated with farming (OR 1.4, 95% CI = 0.9-2.3), dieldrin (OR 3.7, 95% CI = 1.9-7.0), toxaphene (OR 3.0, 95% CI = 1.5-6.1), lindane (OR 2.3, 95% CI = 1.3-3.9), atrazine (OR 1.7, 95% CI = 1.0-2.8), and fungicides (OR 1.8, 95% CI = 0.9-3.6), in marked contrast to null or negative associations for the same self-reported exposures and t(14;18)-negative non-Hodgkin's lymphoma. Causal relations between agricultural exposures and t(14;18)-positive non-Hodgkin's lymphoma are plausible, but associations should be confirmed in a larger study. Results suggest that non-Hodgkin's lymphoma classification based on the t(14;18) translocation is of value in etiologic research.

Adult↗
PubMed2000

Strategy for systematic assembly of large RNA and DNA genomes: transmissible gastroenteritis virus model.

A systematic method was developed to assemble functional full-length genomes of large RNA and DNA viruses. Coronaviruses contain the largest single-stranded positive-polarity RNA genome in nature. The approximately 30-kb genome, coupled with regions of genomic instability, has hindered the development of a full-length infectious cDNA construct. We have assembled a full-length infectious construct of transmissible gastroenteritis virus (TGEV), an important pathogen in swine. Using a novel approach, six adjoining cDNA subclones that span the entire TGEV genome were isolated. Each clone was engineered with unique flanking interconnecting junctions which determine a precise systematic assembly with only the adjacent cDNA subclones, resulting in an intact TGEV cDNA construct of approximately 28.5 kb in length. Transcripts derived from the full-length TGEV construct were infectious, and progeny virions were serially passaged in permissive host cells. Viral antigen production and subgenomic mRNA synthesis were evident during infection and throughout passage. Plaque-purified virus derived from the infectious construct replicated efficiently and displayed similar plaque morphology in permissive host cells. Host range phenotypes of the molecularly cloned and wild-type viruses were similar in cells of swine and feline origin. The recombinant viruses were sequenced across the unique interconnecting junctions, conclusively demonstrating the marker mutations and restriction sites that were engineered into the component clones. Full-length infectious constructs of TGEV will permit the precise genetic modification of the coronavirus genome. The method that we have designed to generate an infectious cDNA construct of TGEV could theoretically be used to precisely reconstruct microbial or eukaryotic genomes approaching several million base pairs in length.

Animals↗
PubMed2000

Subgenomic negative-strand RNA function during mouse hepatitis virus infection.

Mouse hepatitis virus (MHV)-infected cells contain full-length and subgenomic-length positive- and negative-strand RNAs. The origin and function of the subgenomic negative-strand RNAs is controversial. In this report we demonstrate that the synthesis and molar ratios of subgenomic negative strands are similar in alternative host cells, suggesting that these RNAs function as important mediators of positive-strand synthesis. Using kinetic labeling experiments, we show that the full-length and subgenomic-length replicative form RNAs rapidly accumulate and then saturate with label, suggesting that the subgenomic-length negative strands are the principal mediators of positive-strand synthesis. Using cycloheximide, which preferentially inhibits negative-strand and to a lesser extent positive-strand synthesis, we demonstrate that cycloheximide treatment equally inhibits full-length and subgenomic-length negative-strand synthesis. Importantly, following treatment, previously transcribed negative strands remain in transcriptionally active complexes even in the absence of new negative-strand synthesis. These findings indicate that the subgenomic-length negative strands are the principal templates of positive-strand synthesis during MHV infection.

Animals↗
PubMed1999

Persistent infection promotes cross-species transmissibility of mouse hepatitis virus.

Persistent infection with mouse hepatitis virus (MHV) strain A59 in murine DBT (delayed brain tumor) cells resulted in the emergence of host range variants, designated V51A and V51B, at 210 days postinfection. These host range mutants replicated efficiently in normally nonpermissive Chinese hamster ovary (CHO), in human hepatocarcinoma (HepG2), and to a lesser extent in human breast carcinoma (MCF7) cell lines. Little if any replication was noted in baby hamster kidney (BHK), green African monkey kidney (COS-7), feline kidney (CRFK), and swine testicular (ST) cell lines. By fluorescent antibody (FA) staining, persistent viruses V10B and V30B, isolated at days 38 and 119 days postinfection, also demonstrated very low levels of replication in human HepG2 cells. These data suggest that persistence may rapidly select for host range expansion of animal viruses. Pretreatment of HepG2 cells with a polyclonal antibody directed against human carcinoembryonic antigens (CEA) or with some monoclonal antibodies (Col-1, Col-4, Col-12, and Col-14) that bind human CEA significantly inhibited V51B infection. Under identical conditions, little or no blockade was evident with other monoclonal antibodies (kat4c or Col-6) which also bind the human CEA glycoproteins. In addition, an antibody (EDDA) directed against irrelevant antigens did not block V51B replication. Pretreatment with the Col-4 and Col-14 antibodies did not block Sindbis virus replication in HepG2 cells or MHV infection in DBT cells, suggesting that one or more CEA glycoproteins likely functioned as receptors for V51B entry into human cell lines. To test this hypothesis, the human biliary glycoprotein (Bgp) and CEA genes were cloned and expressed in normally nonpermissive BHK cell lines by using noncytopathic Sindbis virus replicons (pSinRep19). By growth curves and FA staining, human CEA and to a much lesser extent human Bgp functioned as receptors for V51B entry. Furthermore, V51B replication was blocked with polyclonal antiserum directed against human CEA and Bgp. Under identical conditions, the parental MHV strain A59 failed to replicate in BHK cells expressing human Bgp or CEA. These data suggest that MHV persistence may promote virus cross-species transmissibility by selecting for virus variants that recognize phylogenetic homologues of the normal receptor.

Animals↗
PubMed1998

Receptor homologue scanning functions in the maintenance of MHV-A59 persistence in vitro.

Cell lines and viruses were isolated from mouse hepatitis virus (MHV-A59) persistently-infected DBT cells at different times postinfection. Cloned cell lines had cured virus infection, displayed low levels of MHVR receptor expression and were progressively more resistance to MHV infection. MHV persistence was likely maintained by epigenetic expression of the MHVR receptor in subsets of these resistant cells and by the emergence of persistent viruses characterized by high affinity MHVR receptor usage. Persistent viruses also displayed higher affinity for alternative biliary glycoprotein receptors suggesting that receptor homologue scanning functioned in the maintenance of persistence. Importantly, persistent viruses isolated after 210 days postinfection efficiently replicated in human HepG2 cells, a hepatocarcinoma cell line, suggesting that persistence promotes the interspecies transfer of MHV.

Animals↗
PubMed1997

Episodic evolution mediates interspecies transfer of a murine coronavirus.

Molecular mechanisms permitting the establishment and dissemination of a virus within a newly adopted host species are poorly understood. Mouse hepatitis virus (MHV) strains (MHV-A59, MHV-JHM, and MHV-A59/MHV-JHM) were passaged in mixed cultures containing progressively increasing concentrations of nonpermissive Syrian baby hamster kidney (BHK) cells and decreasing concentrations of permissive murine DBT cells. From MHV-A59/MHV-JHM mixed infection, variant viruses (MHV-H1 and MHV-H2) which replicated efficiently in BHK cells were isolated. Under identical treatment conditions, the parental MHV-A59 or MHV-JHM strains failed to produce infectious virus or transcribe detectable levels of viral RNA or protein. The MHV-H isolates were polytrophic, replicating efficiently in normally nonpermissive Syrian hamster smooth muscle (DDT-1), Chinese hamster ovary (CHO), human adenocarcinoma (HRT), primate kidney (Vero), and murine 17Cl-1 cell lines. Little if any virus replication was detected in feline kidney (CRFK) and porcine testicular (ST) cell lines. The variant virus, MHV-H2, transcribed seven mRNAs equivalent in relative abundance and size to those synthesized by the parental virus strains. MHV-H2 was an RNA recombinant virus containing a crossover site in the S glycoprotein gene. At the molecular level, episodic evolution and positive Darwinian natural selection were apparent within the MHV-H2 S and HE glycoprotein genes. These findings differ from the hypothesis that neutral changes are the predominant feature of molecular evolution and argue that changing ecologies actuate episodic evolution in the MHV spike glycoprotein genes that govern interspecies transfer and spread into alternative hosts.

Animals↗
PubMed1994

A strong association between mefloquine and halofantrine resistance and amplification, overexpression, and mutation in the P-glycoprotein gene homolog (pfmdr) of Plasmodium falciparum in vitro.

Stepwise selection for increased mefloquine resistance in a line of Plasmodium falciparum in vitro resulted in increased resistance to halofantrine and quinine, increased sensitivity to chloroquine, and amplification and overexpression of the P-glycoprotein gene homolog (pfmdr1). A point mutation (tyrosine to phenylalanine) noted at amino acid 86 in pfmdr1 in the mefloquine-resistant line W2mef was amplified in more resistant lines derived from it by in vitro selection pressure with mefloquine. Conversely, lines selected for increased chloroquine resistance exhibited a revertant phenotype that was sensitive to mefloquine and halofantrine. These lines also demonstrated increased sensitivity to quinine, loss of amplification of pfmdr1, loss of the mefloquine/halofantrine phenylalanine-86 mutation, and selection for a tyrosine-86 mutation previously associated with chloroquine resistance. These findings provide strong evidence for pfmdr1 mediating cross-resistance to halofantrine and mefloquine in P. falciparum in vitro.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Electrocardiographic changes following rabbit coronavirus-induced myocarditis and dilated cardiomyopathy.

Rabbit Coronavirus (RbCV) infection was divided into two phases based upon day of death and pathologic findings. During the acute phase (days 2-5) heart weights (HW) and heart weight-to-body weight (HW/BW) ratios were increased with striking dilation of the right ventricle. These changes as well as increased dilation of the left ventricle were especially pronounced during the subacute phase (days 6-12). Myocytolysis, pulmonary edema, and degeneration and necrosis of myocytes, were seen during both phases. Myocarditis, pleural effusion, calcification of myocytes, and congestion in the liver and lungs were seen in the subacute phase. Electrocardiograms (ECGs) exhibited low voltage, nonspecific ST-T wave changes, sinus tachycardia, occasional ventricular and supraventricular premature complexes and 2(0) AV block consistent with myocarditis and heart failure. Forty-one percent of the survivors exhibited increased HW and HW/BW ratios, biventricular dilation, interstitial and replacement fibrosis, myocyte hypertrophy and myocarditis. ECGs exhibited nonspecific ST-T wave changes, sinus arrhythmia, occasional ventricular and supraventricular premature complexes and 2(0) AV block. These data suggest that RbCV infection may result in viral myocarditis and heart failure with a proportion of survivors progressing into DCM.

Acute Disease↗