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At least 1,405 records · Page 78Linked to original sources
PubMed2005

Recombinant Sendai virus vector induces complete remission of established brain tumors through efficient interleukin-2 gene transfer in vaccinated rats.

PURPOSE: Sendai virus (SeV), a murine parainfluenza virus type I, replicates independent of cellular genome and directs high-level gene expressions when used as a viral vector. We constructed a nontransmissible recombinant SeV vector by deleting the matrix (M) and fusion (F) genes from its genome (SeV/DeltaMDeltaF) to enhance its safety. We also estimated the therapeutic efficacy of the novel vector system against a rat glioblastoma model. EXPERIMENTAL DESIGN: We administered the recombinant SeV vector carrying the lacZ gene or the human interleukin-2 (hIL-2) gene into established 9L brain tumors in vivo simultaneous with peripheral vaccination using irradiated 9L cells. Sequential monitoring with magnetic resonance imaging was used to evaluate the therapeutic efficacy. RESULTS: We found extensive transduction of the lacZ gene into the brain tumors and confirmed sufficient amounts of interleukin 2 (IL-2) production by hIL2-SeV/DeltaMDeltaF both in vitro and in vivo. The magnetic resonance imaging study showed that the intracerebral injection of hIL2-SeV/DeltaMDeltaF brought about significant reduction of the tumor growth, including complete elimination of the established brain tumors. The (51)Cr release assay showed that significant amounts of 9L-specific cytotoxic T cells were induced by the peripheral vaccination. Immunohistochemical analysis revealed that CD4(+) T cells and CD8(+) T cells were abundantly infiltrated in the target tumors. CONCLUSION: The present results show that the recombinant nontransmissible SeV vector provides efficient in vivo gene transfer that induces significant regression of the established brain tumors and suggest that it will be a safe and useful viral vector for the clinical practice of glioma gene therapy.

Animals↗
PubMed2006

Effects of heptad repeat regions of f protein on the specific membrane fusion in paramyxoviruses.

OBJECTIVES: To identify the effects of heptad repeat regions (HR1 and HR2) of F on the specific membrane fusion in paramyxoviruses. METHODS: Site-directed mutagenesis was used to create same enzyme sites on the F genes of Newcastle disease virus (NDV) and human parainfluenza virus (hPIV). Gene recombination was used to get chimeric F proteins NDV C-HR1 and hPIV C-HR1 by exchanging HR1 fragments each other; NDV C-HR2 and hPIV C-HR2 were also obtained by the same way. All the chimeric F proteins were co-expressed with their homologous or heterogeneous HN in eukaryocytes. Cell fusion functions were assayed by Giemsa staining and reporter gene method. The expression efficiencies of F proteins were assayed with fluorescence-activated cell sorter (FACS). RESULTS: NDV C-HR1 and hPIV C-HR1 had 53.91 and 83.15% of fusion activities, and NDV C-HR2 and hPIV C-HR2 had 107.23 and 12.01% of fusion activities, respectively, as compared with their relevant wild types. The analysis of FACS indicated that the expression efficiencies of all the chimeric F proteins except NDV C-HR2 were lower than those of their relevant wild types. CONCLUSIONS: HR1 of NDV F might be important for its specific membrane fusion, but HR2 of NDV F may not; both HR1 and HR2 of hPIV F may be important for its specific membrane fusion.

Animals↗
PubMed2006

Effects of ectodomain sequences between HR1 and HR2 of F1 protein on the specific membrane fusion in paramyxoviruses.

OBJECTIVES: To explore the effects of ectodomain sequences between HR1 and HR2 of F1 protein on the specific interaction with its homologous hemagglutinin-neuraminidase (HN) in paramyxoviruses. METHODS: Site-directed mutagenesis was used to obtain mutants containing new enzyme sites on the F genes of Newcastle disease virus (NDV) and human parainfluenza virus (hPIV), and four DNA segments located between the HR1 and HR2 (NDV F-1, hPIV F-1, NDV F-2 and hPIV F-2) were obtained by cutting mutant F genes with specific endonucleases. Gene recombination was used to get chimeric F proteins NDV-C1 and hPIV-C1 by exchanging NDV F-1 and hPIV F-1 each other, and NDV-C2 and hPIV-C2 were also obtained by the same way. All the mutants and chimeric F proteins were co-expressed with their homologous or heterologous HN proteins in eukaryocytes. The fusion functions were assayed with Giemsa staining and reporter gene method for qualitative and quantitative analyses, respectively. The cell surface expression of F proteins was assayed with fluorescence-activated cell sorter (FACS) for quantitative analysis. RESULTS: All the mutants of F proteins had the same functions as their relevant wild types. Chimeric F proteins NDV-C1 and hPIV-C1 had 76.34 and 65.82% of fusion activities, and NDV-C2 and hPIV-C2 had 96.25 and 93.78% of fusion activities, respectively, as compared with their relevant wild types. The analysis of FACS indicated that all the mutants and chimeric F proteins had almost the same expression efficiencies as their relevant wild types. CONCLUSIONS: The segments of NDV F-1 and hPIV F-1 were important for their specific membrane fusion, but NDV F-2 and hPIV F-2 were not.

Flow Cytometry↗
PubMed2000

Outcomes after judicious antibiotic use for respiratory tract infections seen in a private pediatric practice.

BACKGROUND: Most respiratory tract infections (RTIs) in children have a viral cause, they resolve on their own, and antibiotics need not be prescribed. OBJECTIVE: We sought to provide evidence that judicious antibiotic use can be accomplished in private pediatric practice without observing an increase in return office visits or in the rate of bacterial infections that may follow. STUDY DESIGN: This was a prospective 12-month study from July 1, 1996 through June 30, 1997. On the same 1 day each week, a representative convenience sample of acute respiratory tract illness patients was enrolled, and laboratory studies performed as appropriate, including viral cultures on all. Children were then followed for 30 days to ascertain the outcomes of not prescribing antibiotics except when specific bacterial infections were present at the initial visit. RESULTS: Three hundred eighty-three children were enrolled; 293 (77%) did not receive antibiotics at the enrollment visit. Ninety children (23%) received antibiotics based on a diagnosis of acute otitis media (n = 53), acute streptococcal tonsillopharyngitis (n = 18), or other presumed or documented bacterial infections (n = 19). An unscheduled return visit related to the initial visit occurred for 86 (29%) of the 293 children not receiving antibiotics initially and in 40 (44%) of 90 children receiving antibiotics initially. Eighty-seven children (23%) had positive viral culture results. The most frequently isolated viruses were adenovirus, enterovirus, parainfluenzae virus, and influenza virus. CONCLUSION: Children with RTIs without a concomitant presumed or proven bacterial infection do not require antibiotics. In this busy office practice, >75% of the children presenting with an RTI did not have a presumed or proven bacterial infection. These children did not have a higher rate of return office visits or an increase in bacterial infections. This reinforces the judicious use of antibiotics in managing children with RTIs.outcomes, antibiotic, respiratory infections.

Agglutination Tests↗
PubMed1999

Health evaluation of a pronghorn antelope population in Oregon.

During 1996 and 1997, the U.S. Fish and Wildlife Service conducted a study to determine the cause(s) of population decline and low survival of pronghorn antelope (Antilocapra americana) fawns on Hart Mountain National Antelope Refuge (HMNAR) located in southeastern Oregon (USA). As part of that study, blood, fecal, and tissue samples from 104 neonatal fawns, 40 adult does, and nine adult male pronghorns were collected to conduct a health evaluation of the population. Physiological parameters related to nutrition and/or disease were studied. No abnormalities were found in the complete blood cell counts of adults (n = 40) or fawns (n = 44 to 67). Serum total protein and blood urea nitrogen (BUN) levels were lower compared to other pronghorn populations. Does had mean BUN values significantly lower (P < 0.001) in December 1996 than March 1997. Serum copper (Cu) levels in does (range 0.39 to 0.74 ppm) were considered marginal when compared to domestic animals and other wild ungulates. Fawns had low (0.28 ppm) Cu levels at birth and reached the does' marginal values in about 3 days. Whole blood, serum and liver selenium (Se) levels were considered marginal to low in most segments of the pronghorn population. However, serum levels of vitamin E (range 1.98 to 3.27 microg/ml), as determined from the does captured in March, were apparently sufficient to offset any signs of Se deficiency. No clinical signs of Cu or Se deficiency were observed. Fifty-five of 87 dead fawns were necropsied. Trauma, due to predation by coyotes (Canis latrans), accounted for 62% of the mortality during mid-May to mid-July of each year. Other causes included predation by golden eagles (Aquila chrysaetos) (4%), dystocia (2%), septicemic pasteurellosis (4%), starvation (5%), and unknown (23%). Adult females were tested for serum neutralizing antibodies to Brucella spp. (n = 20, negative), Leptospira interrogans (n = 20, negative), bluetongue virus (n = 20, 35% positive), epizootic hemorrhagic disease virus (n = 20, 30% positive), respiratory syncytial virus (n = 18, negative), parainfluenza virus type 3 (n = 18, 67% positive), infectious bovine rhinotracheitis (n = 18, negative), and bovine viral diarrhea (n = 18, negative). Considering the parameters examined, we found no apparent predisposing factors to mortality including those killed by coyotes, but some nutritional parameters suggest that pronghorns on HMNAR exist on a diet low in protein and Se and marginal in Cu. The effect these factors have on the population is not known.

Age Factors↗
PubMed1999

[Influence of respiratory viruses, cold weather and air pollution in the lower respiratory tract infections in infants children].

BACKGROUND: All winters, there is an increase in the number of pediatric consultations, associated to three factors: cold weather, air pollution and respiratory virus epidemics. AIM: To study the influence of these three factors in the demand for pediatric consultations between March and September, in an area of Metropolitan Santiago. PATIENTS AND METHODS: The number of consultations between March and September 1998 in the emergency room and the number of hospital discharges due to lower respiratory tract infections, were registered in a public pediatric hospital of Santiago. A respiratory virus surveillance (respiratory syncytial virus, adenovirus, influenza and parainfluenza virus) was done among children admitted for lower respiratory infections. Atmospheric temperature values and air pollution, measured as the number of particles of 10 microns or more per m3 (MP 10), were obtained from local health services. RESULTS: Two elevation waves of outpatient consultations were detected at weeks 19 and 26, that coincided with the periods of maximal detection of influenza and syncytial respiratory virus, respectively. The epidemics of respiratory syncytial virus coincided with the maximal number of hospital admissions for lower respiratory tract infections at week 27. There was no correlation between air pollution and the number of pediatric consultations. The lower ambient temperatures coincided with the higher detection of respiratory syncytial virus at week 28, moment in which the demand for consultations or hospital admissions was descending. CONCLUSIONS: There is a direct relationship between respiratory virus epidemics and the demand for pediatric consultations. There is also a minor influence of ambient temperature.

Acute Disease↗
PubMed1992

Pandora's box and the history of the respiratory viruses: a case study of serendipity in research.

As fastidious human parasites, the respiratory viruses other than influenza viruses have been among the last of the human viruses to be isolated. Their recognition has been dependent upon the evolving technology of cell culture and equally upon a series of fortuitous observations by astute investigators. Adenoviruses were discovered independently by two different groups of scientists, one utilizing explantation of ostensibly normal human tissues and the other recovering virus directly from epidemics of acute disease. In other studies, a technique developed for detection of influenza virus in cell culture led to the discovery of other hemagglutinating viruses, now known as parainfluenza viruses. From such shreds of laboratory evidence, the structural and molecular characteristics of these diverse viruses have been defined, and each in turn has been retrospectively linked to a legacy of previously described clinical syndromes and epidemic patterns. Thus, neither technology or human imagination alone is sufficient for scientific advance, but, when combined, are the essence of scientific discovery.

Adenoviridae Infections↗