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PubMed1983

Neuraminidase activity and syncytial formation in variants of parainfluenza 3 virus.

By a sensitive fluorometric assay method, we could definitely demonstrate neuraminidase activity for two variants of parainfluenza 3 virus, M and SC, which were previously shown to have no detectable neuraminidase activity. The enzyme activities of these viruses were very similar to each other, showing a much lower catalytic rate, a much higher Km value, and a more acidic pH optimum than those of the virus variants of high neuraminidase activity, 910N, LT, and MR. M and SC viruses eluted from guinea pig erythrocytes very poorly, whereas 910N and LT viruses eluted readily. M virus required the aid of a bacterial neuraminidase for effective growth and plaque formation in MDBK cells, but the virus grew well and formed plaques in R66 and Vero cells without the enzyme. SC virus required no exogenous neuraminidase for growth in all of these cell types. Depending on cell type, SC virus induced slight to extensive syncytial formation which was greatly inhibited by exogenous neuraminidase. In contrast, M virus induced extensive syncytial formation in all these cells regardless of the presence or absence of exogenous neuraminidase, although development and disintegration of the syncytia were more or less retarded by the enzyme, especially in MDBK cells. These results indicate that M virus possesses highly potent inducibility of syncytial formation which is further fortified by being low in viral neuraminidase activity.

Adsorption↗
PubMed1977

Galactosyltransferase activity of the microvillous surface of human placental syncytial trophoblast.

The syncytial trophoblast has previously been shown to have minimal intrasyncytial galactosyltransferase activity at term. The biochemical and autoradiographic study reported here shows that the microvillous surface of term human placental syncytial trophoblast has a galactosyltransferase activity capable of transferring 3H-galactose from uridine diphosphate-D-galactose-1-3H to trichloroacetic-acid precipitable, endogenous acceptors. This capability of resynthesizing cleaved galactose moieties in the glycocalyx, without dependence on cytoplasmically located galactosyltransferases, would allow for reinstatement of the original surface molecular configuration without requiring synthesis and insertion of a completely new membrane molecule. It is suggested that the surface galactosyltransferase might function to repair damage to syncytial trophoblast glycocalyx induced by the enzymes in maternal blood.

Autoradiography↗
PubMed2004

Syncytial giant cell component. Review of 55 renal cell carcinomas.

Different types of multinucleated giant cells (MGC) have been documented in tumors with osteoclast-like appearance, with trophoblastic differentiation or as tumoral malignant giant cells. A new variety of MGC has been described in renal cell carcinoma. In order to study the frequency, nature and significance of this cellular type, we have reviewed our files. To assess the presence, nature and significance of these MGC in renal cell carcinomas and associated histologic subtype. To review all malignant renal tumors diagnosed in the last 5 years in our hospital and to carry out a morphologic and immunohistochemical study in renal cell carcinomas with syncytial type MGC. 55 renal cell carcinomas were reviewed. Clear cell (conventional) renal cell carcinoma was the most common type encountered (40 cases); two of these cases showed syncytial type MGC and low grade malignancy. Microscopically the MGC contained from 5 to 40 nuclei. Immunohistochemically, mononucleated and multinucleated cells were positive for cytokeratin CAM 5.2, cytokeratin AE1/AE3 and weakly positive for vimentin. Histiocytic, muscular, neural markers, beta-HCG and alpha-fetoprotein were negative. The presence of syncytial type MGC in renal cell carcinomas is an exceptional event. Among 55 renal cell carcinomas we found two cases, both of which were of clear cell subtype and low grade malignancy. The MGC proved positive for epithelial markers and probably are the result of mononucleated tumoral cell fusion. We are unaware of the impact of this MGC in the outcome of patients; such cells appear in low grade carcinomas and do not seem to be of dismal prognosis.

Biomarkers↗
PubMed1990

Pulmonary lesions induced by 3-methylindole and bovine respiratory syncytial virus in calves.

Our objectives were to describe the ultrastructural morphogenesis of pulmonary lesions induced by 3-methylindole in 30- to 45-day-old Holstein calves and to determine whether toxic exposure to 3-methylindole exacerbates pulmonary lesions induced by bovine respiratory syncytial virus. Administration of 3-methylindole (0.25 g/kg) to calves resulted in interstitial edema and ultrastructural swelling of type-I alveolar epithelial cells and nonciliated bronchiolar epithelial cells as early as 4 to 6 hours after intraruminal administration. More severe alveolar edema containing protein was associated with swelling of capillary endothelial cells at 2 days after administration. Proliferation of type-II alveolar epithelial cells was first observed at 2 days after 3-methylindole administration, and marked hyperplasia of type-II epithelial cells and nonciliated bronchiolar epithelial cells was evident by 4 days after administration. Pulmonary cytochrome P-450 monooxygenase concentrations decreased significantly (P less than 0.001) by 12 hours after administration and did not increase significantly again by 8 days after administration. Calves were inoculated with bovine respiratory syncytial virus 3 days after administration of 3-methylindole, and pulmonary lesions were assessed 5 days after viral inoculation. Viral replication was demonstrated by fluorescence microscopy for viral antigen or by transmission electron microscopy in ciliated and nonciliated airway epithelial cells. Viral antigen was identified infrequently in alveolar macrophages and in type-II alveolar epithelial cells. 3-Methylindole exposure in calves did not result in more widespread distribution of viral antigen in alveolar tissue of respiratory syncytial virus-inoculated calves or in significant enhancement of viral pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Spread of bovine syncytial virus in a dairy herd over a two year period.

During a two year period the spread of bovine syncytial virus was monitored in a closed herd of 50 to 100 milking cows. Out of a nucleus of 49 nonpregnant and pregnant heifers, six were found to be infected with bovine syncytial virus. Virus was detected only in the progeny of infected cows and not in the progeny of uninfected animals. Nineteen progeny of the bovine syncytial virus infected cows were studied in detail and virus was isolated from only four. Horizontal spread of the virus did not occur.

Animals↗
PubMed1986

Intervillous connections in the mature human placenta: instances of syncytial fusion or section artifacts?

In order to investigate the nature of apparent intervillous syncytial connections in the normal mature human placenta, 250 examples were followed through plastic serial sections at 2 micron intervals. It was possible to classify them into four types according to their origin. Type 1 (20%): section through an area of syncytial fusion or genuine bridge; Type 2 (53%): tangential section through the syncytium filling the crotch of a villus branching point; Type 3 (4%): tangential section through the syncytium lining the internal angle of a tight 'U' bend of a villus; Type 4 (23%): tangential section through the syncytium of a sinuous villus. It is clear, therefore, that whilst areas of syncytial fusion do occur between adjacent villi, the majority of supposed intervillous connections seen in sections are artifacts.

Cell Fusion↗
PubMed1998

Pancreatic adenocarcinomas with DNA replication errors (RER+) are associated with wild-type K-ras and characteristic histopathology. Poor differentiation, a syncytial growth pattern, and pushing borders suggest RER+.

The clinical and pathological features of carcinomas of the pancreas with DNA replication errors (RER+) have not been characterized. Eighty-two xenografted carcinomas of the pancreas were screened for DNA replication errors using polymerase chain reaction amplification of microsatellite markers. Cases with microsatellite instability in at least two markers of a minimum of five tested were considered RER+. RER status was correlated with histological appearance, karyotype of the carcinomas when available, K-ras mutational status, and patient outcome. Three (3.7%) of the eighty-two carcinomas were RER+. In contrast to typical gland-forming adenocarcinomas of the pancreas, all three RER+ carcinomas were poorly differentiated and had expanding borders and a prominent syncytial growth pattern. Neither a Crohn's-like lymphoid infiltrate nor extracellular mucin production were prominent. Ductal adenocarcinomas of the pancreas typically contain a mutant K-ras gene, yet all three RER+ carcinomas had wild-type K-ras. One of the three RER+ carcinomas was karyotyped and showed a near diploid pattern. All three of the RER+ tumors were removed via Whipple resection. One of the three patients is free of disease 16 months after pancreaticoduodenectomy, one is alive and free of tumor at 52 months but developed two colon carcinomas during this period, and the third died of pancreatic cancer at 4 months. None of the three patients had a family history of colorectal carcinoma. A review of the K-ras wild-type carcinomas in a previously characterized series of pancreatic carcinomas with known K-ras mutational status identified two additional cancers with poor differentiation, a syncytial growth pattern, and pushing borders. Both of the cancers were diploid and both patients were longterm survivors (over 5 years). The inclusion of such patients in previous prognostic studies of pancreas cancer may explain the failure of histological grade to be a predictor of prognosis. These data suggest that DNA replication errors occur in a small percentage of resected carcinomas of the pancreas and that wild-type K-ras gene status and a medullary phenotype characterized by poor differentiation, and expanding pattern of invasion, and syncytial growth should suggest the possibility of DNA replication errors in carcinomas of the pancreas.

Adenocarcinoma↗
PubMed1998

Respiratory syncytial virus and human bronchial epithelium.

BACKGROUND: A suitable model for respiratory syncytial virus (RSV) infection has yet to be developed. OBJECTIVE: To describe an in vitro model of human respiratory epithelium in primary cell culture linked with a computer microscope interface that allows evaluation and imaging of living RSV-infected respiratory epithelium. DESIGN: A descriptive, controlled study. Human bronchial cells were obtained from surgical samples by elastase dissociation and replated on collagen gel membranes. After 7 to 10 days, cells were brought to air interface. Baseline sampling of cell fluid for cytokine production by enzyme-linked immunosorbent assay (interleukin [IL] 1beta, IL-6, IL-8, and RANTES) and leukotriene C4 by radioimmunoassay was taken before treatment with RSV (n=30) or HEp-2 (human laryngeal carcinoma cells) control (n=25). Sampling was done at 4, 24, 72, and 120 hours thereafter. The infectious process was monitored with a microscope (Zeiss UEM, Carl Zeiss Inc, Thornwood, NY) equipped with a camera (Newvicon, Dage Corporation, Stamford, Conn). Images were either digitized using a computer (Macintosh Quadra 950, Apple Computers Inc, Cupertino, Calif) equipped with a digitizing board (Perceptics Corporation, Knoxville, Tenn) or were recorded on an SVHS videotape using a videocassette recorder (JVC, Elmwood Park, NJ). RESULTS: Respiratory syncytial virus induced profound effects on the ciliated cells: ciliostasis, clumping, and loss of cilia from live cells and sloughing of cells. Significant differences in the release of IL-6, IL-8, and RANTES (P<.03 for each cytokine) were noted in RSV-infected bronchial cultures by 24 hours with a peak at 72 hours. The IL-beta and leukotriene C4 were not altered by RSV infection in bronchial cells. CONCLUSIONS: This model closely mirrors human RSV disease and affords a unique opportunity to study interepithelial cell interactions, cytokine responses from cells of different donors, and ciliary activity of live cells undergoing RSV infection.

Bronchi↗
PubMed2001

Persistent infection of B lymphocytes by bovine respiratory syncytial virus.

Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in young cattle. Here we demonstrate BRSV persistence at low levels in tracheobronchial and mediastinal lymph nodes up to 71 days after the experimental infection of calves. Positive results were obtained on viral genomic RNA and messenger RNA coding for the nucleoprotein, glycoprotein (G), and fusion protein (F). G and F proteins were also detected in the pulmonary lymph nodes by immunohistochemistry. Double-staining experiments revealed that viral antigen was present in B-lymphocytes. Coculture experiments with the lymph node cells showed that the virus was still able to infect permissive target cells, even though no cytopathic effect was recorded. In vitro studies indicate that BRSV was still able to replicate in bovine B-lymphocyte cell lines 6 months after infection. These results may also be relevant to the understanding not only of the epidemiology and the peculiarities of the immune response of BRSV infections but also of human respiratory syncytial virus infections.

Animals↗
PubMed1996

Respiratory syncytial virus infection in the elderly.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in infants and children throughout the world. Respiratory syncytial virus infections in the elderly represent reinfections in the hosts who have had many prior episodes. Thus, RSV infections are usually not considered serious in adults, since reinfections are generally known to result in mild disease. Nevertheless, in adults, as in children, the infection has been reported to cause altered airway resistance and exacerbation of chronic obstructive lung disease. In people over 60 years of age, RSV usually causes mild nasal congestion, but can also result in fever, anorexia, pneumonia, bronchitis, and even death. Diagnosis of RSV infection in the elderly by the standard methods used in children is not as successful as in the latter group. This may be due to a combination of factors such as shorter shedding phase, lower viral titers, and dry mucosa. An alternative, rapid, and direct viral diagnostic method, the polymerase chain reaction, has recently been introduced in the diagnosis of RSV infections.

Aged↗
PubMed2001

Community and nosocomially acquired respiratory syncytial virus infection in a German paediatric hospital from 1988 to 1999.

UNLABELLED: Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants. Since epidemiological data from Germany are scarce, a large retrospective hospital based analysis was performed. In the first part of the study, laboratory records were checked for RSV positive specimens from January 1988 to December 1997. A total of 1664 specimens were positive corresponding to 1171 episodes in 1064 patients; 88% were up to 4 years old and 47% up to 3 months old. The percentage of premature newborns from all patients 0-4 years old was 24%. The rate of nosocomial infection was 38%. The core RSV season began in December, lasted until April, and peaked in January and February. In the second part of the study, from April 1, 1997 to March 31, 1999, which encompassed two RSV winter seasons, patients with the ICD-9 coded discharge diagnoses of lower respiratory tract infections, bronchopulmonary dysplasia (BPD) and prematurity were analysed. Of the premature newborns, 25% were tested RSV positive at least once up to the age of 1 year, as were 52% of those with BPD. The rehospitalisation rate due to RSV infection was 22% in patients with BPD, and 8.9% in all premature newborns. Of patients with community acquired RSV infection, 12% required intensive care and 6% had to be ventilated mechanically. The mortality rates in both parts of the study were 0.8% and 0.7%, respectively. CONCLUSION: Respiratory syncytial virus infection in young children is also of major importance in Germany. Although the mortality rate is low, the high incidence and the severity of the disease in the particular risk group of premature infants with chronic lung disease contribute to a very high disease burden.

Child, Preschool↗
PubMed1995

Respiratory syncytial virus--is it preventable?

Respiratory syncytial virus infection spreads readily among hospital wards, nurseries and intensive care units. Careful handwashing is the cornerstone in the prevention of nosocomial transmission. Use of rapid diagnostic tests permits the cohorting of patients and staff which has been shown to limit the spread in hospital wards. In addition, the use of gowns and gloves and limiting visitors have been recommended. In the future passive immunization with respiratory syncytial virus (RSV) immune globulin or RSV vaccination may be helpful in high risk patients.

Adult↗
PubMed2004

Reduced clearance of respiratory syncytial virus infection in a preterm lamb model.

Respiratory syncytial virus (RSV) causes significant respiratory disease in children worldwide. For the study of severe RSV disease seen in preterm infants, a suitable animal model is lacking. The novel hypothesis of this study was that preterm lambs are susceptible to bovine RSV (bRSV) infection, an analogous pneumovirus with ruminant host specificity, and that there would be age-dependent differences in select RSV disease parameters. During RSV infection, preterm lambs had elevated temperatures and respiration rates with mild anorexia and cough compared to controls. Gross lesions included multifocal consolidation and atelectasis with foci of hyperinflation. Microscopic lesions included multifocal alveolar septal thickening and bronchiolitis. Immunohistochemistry localized the RSV antigen to all layers of bronchiolar epithelium from a few basal cells to numerous sloughing epithelia. A few mononuclear cells were also immunoreactive. To assess for age-dependent differences in RSV infection, neonatal lambs were infected similarly to the preterm lambs or with a high-titer viral inoculum. Using morphometry at day 7 of infection, preterm lambs had significantly more cellular immunoreactivity for RSV antigen (P <0.05) and syncytial cell formation (P <0.05) than either group of neonatal lambs. This work suggests that perinatal RSV clearance is age-dependent, which may explain the severity of RSV infection in preterm infants. The preterm lamb model is useful for assessing age-dependent mechanisms of severe RSV infection.

Aging↗
PubMed1995

Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) prospective study of risk factors and outcomes in patients hospitalized with respiratory syncytial viral lower respiratory tract infection.

OBJECTIVE: To provide information on disease attributable to respiratory syncytial viral lower respiratory tract infection (RSV LRI) and to quantify the morbidity associated with various risk factors. DESIGN: Prospective cohort study. SUBJECTS: Patients hospitalized with RSV LRIs at seven centers were eligible for study if they were younger than 2 years of age, or hospitalized patients of any age if they had underlying cardiac or pulmonary disease or immunosuppression. MEASUREMENTS AND RESULTS: Enrolled (n = 689) and eligible but not enrolled (n = 191) patients were similar in age, duration of illness and proportion with underlying illness, use of intensive care, and ventilation. Of the enrolled patients, 156 had underlying illness. The isolates from 353 patients were typeable: 102 isolates were subgroup A, 250 were subgroup B, and one isolated grouped with both antisera. The mean hospital stay attributable to respiratory syncytial virus (RSV) was 7 days; 110 patients were admitted to intensive care units, 63 were supported by mechanical ventilation, and 6 patients died. Regression models were developed for the prediction of three outcomes: RSV-associated hospital duration, intensive care unit admission, and ventilation treatment. In addition to previously described risk factors for an increased morbidity, such as underlying illness, hypoxia, prematurity and young age, three other factors were found to be significantly associated with complicated hospitalization: aboriginal race (defined by maternal race), a history of apnea or respiratory arrest during the acute illness before hospitalization, and pulmonary consolidation as shown on the chest radiograph obtained at admission. The RSV subgroup, family income, and day care attendance were not significantly associated with these outcomes. CONCLUSIONS: Hypoxia on admission, a history of apnea or respiratory arrest, and pulmonary consolidation should be considered in the management of children with RSV LRIs. Vaccine trials should target patients with underlying heart or lung disease or of aboriginal race.

Antigens, Viral↗
PubMed1998

Respiratory syncytial virus RNA in cells from the peripheral blood during acute infection.

It is not known whether respiratory syncytial virus spreads beyond the respiratory tract. With the use of reverse transcriptase polymerase chain reaction, we found viral and transcribed RNA in cells from the arterial blood of four children with bronchiolitis but none in serum or cerebrospinal fluid. Respiratory syncytial virus might therefore spread outside the respiratory tract.

Bronchiolitis, Viral↗
PubMed2001

Monophosphoryl lipid A adjuvant reverses a principal histologic parameter of formalin-inactivated respiratory syncytial virus vaccine-induced disease.

The mechanisms by which administration of a formalin-inactivated respiratory syncytial virus vaccine resulted in enhanced disease among children after they later became naturally infected with the virus remains largely undefined. After immunization and live virus challenge, the cotton rat demonstrated the histopathologic marker of the enhanced disease, polymorphonuclear leukocyte infiltration of lung alveolar spaces. We now report that immunization with formalin-inactivated vaccine formulated with the adjuvant, 3-deacylated monophosphoryl lipid A, dramatically reduces or eliminates the polymorphonuclear leukocyte infiltration within the alveoli of cotton rats post-challenge. We suggest, that this or similar adjuvants may be beneficial components of candidate non-replicating respiratory syncytial virus vaccines, whose development has been hampered by safety concerns.

Adjuvants, Immunologic↗
PubMedDate not supplied

Detection of influenza, parainfluenza, adenovirus and respiratory syncytial virus during asthma attacks in children older than 2 years old.

BACKGROUND: Viral upper respiratory tract infections (URTI) have been correlated with the onset of asthma attacks in children and viral identification was reported in 14-49 % of nasal samples. The aim of the present study was to detect influenza, parainfluenza, adenovirus and respiratory syncytial virus (RSV) in older children during acute asthma attacks. METHODS: A total of 104 children (2-14 years) were included in four groups: group I: asthmatics with acute attack and URTI; group II: asthmatics without URTI (group I children, 30 days later); group III: non-asthmatics with URTI; group IV: non-asthmatic, asymptomatic children. A diagnosis of URTI was considered when (3 symptoms (cough and/or sneeze, nasal obstruction, hypertrophy of turbinates, pain and/or retropharynx hyperemia, headache and fever) in asthmatics and at least 2 symptoms in non-asthmatics were present, starting within 7 days. Samples of nasal mucosa cells (n = 123) were collected, and culture and indirect immunofluorescence were carried out to identify respiratory syncytial virus, adenovirus, influenza A and B, parainfluenza 1,2 and 3 and rhinovirus. RESULTS: Viral identification rates were higher in the asthmatic groups: 13.9 % in group I, 11.1 % in group II; 2.8 % in group III and 0 in group IV. The following viruses were identified: RSV 2/36, rhinovirus 1/36, adenovirus 1/36 and parainfluenzae 1/36 in group I; adenovirus 2/18 in group II; RSV 1/36 in group III. CONCLUSIONS: The rate of viral identification was higher in asthmatic children, whether symptomatic or not, suggesting a possible susceptibility to viral infections. Virus could also be a triggering factor in attacks, although it is not the most preponderant in older children.

Adenovirus Infections, Human↗
PubMed1997

Analysis of the bovine respiratory syncytial virus fusion protein (F) using monoclonal antibodies.

Seven monoclonal antibodies (MAbs) directed against bovine respiratory syncytial virus (BRSV) fusion (F) protein were produced and characterized by radioimmunoprecipitation and immunofluorescence assays. These seven MAbs together with the previously described MAbs (Beeler and Van Wyke Coelingh, 1989) to the F protein of human respiratory syncytial virus (HRSV) were used to study the antigenic variation of 12 strains of ungulate RSV. All except one MAbs specific for the HRSV-F protein reacted with ungulate RSV strains less efficiently, indicating that some epitopes are conserved, and others are not conserved on the F proteins of HRSV and BRSV strains. Three MAbs specific to the BRSV-F protein neutralized virus infectivity and reacted with all the ungulate RSV strains, suggesting that these epitopes are well conserved. Based on the reactivity of three other MAbs specific to the BRSV-F protein, ungulate RSVs could be grouped into two subgroups. The results indicated that there are antigenic variations in the F protein among ungulate RSV strains.

Animals↗