Search PubMed⌕ Search

Biomedical subjects

F G Hayden

Publications and source records attributed to F G Hayden.

At least 109 records · Page 6Linked to original sources
PubMed1992

In vitro studies of the antirhinovirus activity of soluble intercellular adhesion molecule-1.

We studied the in vitro antirhinovirus activity of a soluble form of intercellular adhesion molecule-1 (sICAM-1). sICAM-1 inhibited the cytopathic effect of 10 representative human rhinovirus (HRV) serotypes of the major receptor group with, 50% effective concentrations (EC50s) of 0.1 to 7.9 micrograms/ml. Cell type-dependent variation in the inhibitory activity of sICAM-1 was observed for two major receptor group serotypes in HeLa cells (EC50, greater than 32 micrograms/ml), and no inhibitory effect was observed for two serotypes which use different cell receptors. Yield reduction assays showed that sICAM-1 inhibited the replication of HRV serotype 39 (HRV-39) in human adenoid explants in a concentration-dependent manner. No direct inactivation of infectivity of HRV-39 (EC50, 0.5 microgram/ml) was observed after incubation with sICAM-1 (32 micrograms/ml) for up to 24 h. Single-cycle-of-replication experiments with the addition of sICAM-1 at 10 micrograms/ml at different times showed that the inhibitory effect occurs only when sICAM-1 is added within 30 min after infection. In experiments in which absorption was carried out at 4 degrees C and then a single cycle of replication incubation was carried out at 33 degrees C, it was found that sICAM-1 at 10 micrograms/ml was inhibitory only when it was present during the absorption period. Our data show that sICAM-1 is inhibitory for representative major receptor group serotypes of HRV in two cell lines and human respiratory epithelium, that the interaction of sICAM-1 with HRV is readily reversible by dilution, and that the inhibitory effect of sICAM-1 on virus replication is present early in the infection cycle.

Cell Adhesion Molecules↗
PubMed1991

Localization of rhinovirus replication in vitro with in situ hybridization.

To facilitate understanding of human rhinovirus (HRV) pathogenesis, methods were developed for detection of HRV infection in vitro using in situ hybridization (ISH). HRV-14 RNA probes and oligonucleotide probes representing conserved sequences in the 5'-non-translated region were labeled with 35S and used to detect infected HeLa or WI-38 strain human embryonic lung cells in cytological preparations. ISH was shown to be specific for detection of HRV on a single-cell basis. Subsequently, in human nasal polyps infected in vitro, both oligonucleotide- and ribo-probes produced a strong signal in association with ciliated epithelial cells. In human adenoids infected in vitro, a signal was observed in non-ciliated epithelial cells. This study shows that HRV replicates in ciliated cells in the epithelium of human nasal polyps infected in vitro, and the presence of viral RNA in non-ciliated cells of the human adenoid infected in vitro suggests that other cell types may also support rhinovirus replication.

Adenoids↗
PubMed1991

Acute respiratory viral infections in ambulatory children of urban northeast Brazil.

The morbidity of acute respiratory infections in young children and the role of respiratory viruses were evaluated in a 29-month household-based study in an impoverished urban population in Fortaleza, Brazil; subjects were 175 children less than 5 years of age in 63 families. Home visits were conducted three times weekly during which staff recorded the presence of respiratory and systemic symptoms and collected upper respiratory tract samples for viral isolation. A large and sustained burden of respiratory illness was observed, and respiratory viruses were isolated in 35% of the samples collected. Of the isolates, 45.6% were rhinoviruses, 16% parainfluenza viruses, 15.8% enteroviruses, 9.9% adenoviruses, 7.0% herpes simplex viruses, and 5.7% influenza viruses. The results indicate that poor children in northeast Brazil have a high prevalence of respiratory illness and that rhinovirus is the most frequent respiratory virus.

Acute Disease↗
PubMed1991

Virulence of rimantadine-resistant human influenza A (H3N2) viruses in ferrets.

The influence of rimantadine-resistance mutations on the virulence of human H3N2 viruses in ferrets was examined. The similarities in virulence of the drug-resistant mutants with single amino acid substitutions at three different locations, 27, 30, and 31, within the M2 sequence and their corresponding sensitive wild-type isolates contrasted with differences in virulence between the three pairs of viruses. These data provide further evidence that rimantadine-resistant viruses that emerge during treatment of patients with the drug are unaltered both in their growth characteristics and virulence.

Animals↗
PubMed1991

Recovery of drug-resistant influenza A virus during therapeutic use of rimantadine.

The therapeutic activity of rimantadine and its relationship to the shedding of drug-resistant influenza A virus were assessed in two randomized, double-blind, placebo-controlled trials involving patients with laboratory-documented influenza A virus (H3N2 subtype) illness of 2 days' duration or less. In a family-based study, rimantadine treatment for 10 days (24 children and adults) was associated with significant decreases in the number of days to a 50% reduction in symptoms (mean difference, 2.5 days), days of fever (1.6 days), and days of restricted activity (1.5 days) compared with the results obtained with placebo-treated patients (32 children and adults). Drug-resistant virus was recovered from eight (33%) of the rimantadine recipients on day 5. No differences in patient demographics or illness severity at the time of enrollment in the study were apparent between those who shed resistant virus and those who did not. Illness resolution tended to be slower in those who shed resistant virus compared with that in those who did not. In a study of adults treated for 5 days (six treated with rimantadine, six treated with placebo), resistant virus was recovered in three rimantadine recipients by day 3 of treatment. The results indicate that drug-resistant influenza A virus (H3N2) can be recovered from rimantadine-treated children and adults as early as 2 days after starting treatment, but that rimantadine retains a net therapeutic benefit compared with that of placebo.

Adolescent↗
PubMed1991

Immunoblot studies to analyze antibody to the Rickettsia typhi group antigen in sera from patients with acute febrile cerebrovasculitis.

In 1986, an unusual syndrome of acute febrile cerebrovasculitis in the Piedmont Region of Virginia was reported. All patients had encephalopathy and prior exposure to both a sylvan environment and flea-infested animals. The initial serological studies suggested a rickettsial origin, corroborating clinical, epidemiological, and histopathological findings. Sera from four of five patients were subsequently studied by immunoblotting. Unabsorbed and absorbed sera were tested with electrophoresed and electroblotted Rickettsia typhi, Legionella bozemanii, and Proteus vulgaris OX19 antigens. The unabsorbed sera reacted with all three antigens. The P. vulgaris- and L. bozemanii-absorbed sera reacted with R. typhi only and without significantly less intensity. In contrast, the reactivity of R. typhi-absorbed sera was significantly lower with all three antigens. These results indicate that these patients had specific antibodies to a typhus group antigen. Although our findings suggest that a rickettsia of the typhus group may have caused this syndrome, no definitive diagnosis could be achieved because a rickettsial organism was not isolated.

Acute Disease↗
PubMed1990

Anti-influenza virus activity of the compound LY253963.

The compound LY253963 (1,3,4-thiadiazol-2-ylcyanamide) inhibited the in vitro replication of representative influenza A and B viruses in Madin-Darby canine kidney (MDCK) cells at concentrations of 1-3.2 micrograms/ml. The yield of an influenza A (H3N2) virus in primary rhesus monkey kidney (RMK) cells was inhibited at 0.1-0.3 micrograms/ml. However, similar concentrations were inhibitory for the growth of uninfected MCDK or RMK cells. Combination drug studies generally found indifferent interactions between LY253963 and ribavirin or rimantadine. In timing of additional studies, hemagglutinin expression was inhibited to the greatest extent when LY253963 exposure was begun at least 8 h before viral infection, which suggested either slow uptake or intracellular metabolism of LY253963 to an active form. Virus-specific protein synthesis was inhibited to a greater extent by ribavirin 10 micrograms/ml or rimantadine 1 microgram/ml than by LY253963 10 micrograms/ml. No drug-resistant mutants were detected during serial passage of an influenza A (H3N2) virus in the presence of LY253963 1-16 micrograms/ml. In summary, we found that LY253963 inhibited influenza A and B virus replication in several cell types, but that it was associated with cytostatic effects at low concentrations. These studies failed to identify a selective anti-influenza action.

Antiviral Agents↗
PubMed1990

Peripheral blood mononuclear cell interleukin-2 and interferon-gamma production, cytotoxicity, and antigen-stimulated blastogenesis during experimental rhinovirus infection.

To determine whether rhinovirus infection induced a systemic cellular immune response in humans, specific antigen-stimulated blastogenesis, natural killer cell activity, and mitogen-stimulated production of interleukin-2 and interferon-gamma by peripheral blood mononuclear cells (PBMC) were quantified during experimental rhinovirus infection of normal volunteers. Phytohemagglutinin-stimulated interleukin-2 production by PBMC collected on day 5 after rhinovirus inoculation was increased fourfold compared with production by PBMC collected before rhinovirus challenge (P less than .05); phytohemagglutinin-stimulated interferon-gamma production was doubled (P less than .05). An inverse relationship was observed between the increase in interleukin-2 production and both nasal mucus production (P less than .02) and the number of days virus was cultured from nasal washings (P less than .02). Natural killer cell-mediated cytotoxicity of PBMC collected on day 5 after rhinovirus challenge was also increased (P less than .01) compared with preinfection levels, as was specific antigen-stimulated blastogenesis on day 21 (P less than .05). The extent of blastogenic response correlated directly with both mucus production (P less than .05) and the number of days virus was cultured from nasal washings (P less than .05). These observations are consistent with the hypothesis that rhinovirus infection results in activation of a systemic cellular immune response.

Antibodies, Viral↗
PubMed1990

A randomized controlled trial of glucocorticoid prophylaxis against experimental rhinovirus infection.

The effects of combined intranasal and systemic glucocorticoid steroids on the local inflammatory response, and symptoms due to experimental rhinovirus infection were studied in 45 adults randomized to prophylaxis with either placebo or steroids. Intranasal beclomethasone (168 micrograms twice a day) was begun 4 days before viral challenge and continued 5 days after challenge. Oral prednisone (30 mg twice daily) was given for 3 days beginning 1 day before challenge. During the first 48 h after viral inoculation, nasal obstruction, nasal mucus weights, and kinin concentrations in nasal lavages were lower in steroid recipients, but subsequent increases in these variables in the steroid group resulted in no significant cumulative differences between treatment groups. These data suggest that steroid prophylaxis may suppress nasal inflammation and cold symptoms during the first 2 days in experimental rhinovirus colds.

Administration, Intranasal↗
PubMed1989

Emergence and apparent transmission of rimantadine-resistant influenza A virus in families.

To determine whether rimantadine can protect family members from acquiring influenza A viral illness and to assess the possible selection of drug-resistant strains of virus, we conducted a randomized, double-blind, placebo-controlled study in three communities during two influenza seasons. When influenza A occurred in a family, the members (including the index patient) were given either rimantadine (adult oral dose, 200 mg per day) or placebo for 10 days. The presence of illness was monitored by daily recording of symptoms and temperature measurements; infection was determined by isolation of the virus and by serologic studies. Among households with documented influenza A infections, symptomatic illness occurred in one or more contacts in 10 of 28 families treated with rimantadine and in 10 of 209 families treated with placebo. Asymptomatic secondary influenza A infections were found in five families assigned to receive rimantadine and in four families assigned to receive placebo. Rimantadine-resistant strains of influenza A virus (H3N2 subtype) with mutations consisting of single amino acid changes in the M2 protein (residue 27, 30, or 31) were recovered from eight index patients and five contacts treated with rimantadine. There was apparent transmission of drug-resistant strains of virus in six contacts with secondary illnesses in five families. We conclude that when index patients are treated concurrently, rimantadine is ineffective in protecting household members from influenza A infection. If rimantadine is used for both treatment and postexposure prophylaxis in families, rapid selection and apparent transmission of drug-resistant influenza A viruses can occur.

Adamantane↗
PubMed1989

Alterations of the eustachian tube, middle ear, and nose in rhinovirus infection.

This study measured the changes in 64 ears of 32 adult volunteers in eustachian tube function by the nine-step test, middle ear pressure by tympanometry, and nasal patency by active posterior rhinomanometry for 18 days following type 39 or Hanks rhinovirus infection. Abnormal measures were limited to the 75% of subjects (24) with clinical illness (colds) defined by symptom scores. Two days after infection, tubal function was present in only 50% of ears (48) and 20% of persons (5), middle ear underpressures of less than -50 mm H2O were measured in 50% of volunteers (12), and decreased nasal patency was observed in 54% of those with colds (13). These changes resolved 6 to 10 days after challenge. These results support a causal relationship between viral upper respiratory tract infection eustachian tube obstruction and abnormal middle ear pressure.

Acoustic Impedance Tests↗
PubMed1989

Protective effect of rhinovirus receptor blocking antibody in human fibroblast cells.

Infection of HeLa cells by human rhinoviruses (RV) of the major receptor group is inhibited by a HeLa-derived rhinovirus receptor murine monoclonal antibody (RRMA). In yield reduction studies in human embryonic lung fibroblast cells, pretreatment with 1.0 or 10 micrograms/ml of RRMA partially protected (greater than 90% titer reduction) against infection by RV 39 or coxsackie A21 (members of the major receptor family), but not by RV 1A (member of the minor receptor family). The protection afforded by RRMA persisted at least 72 h after a 2-h exposure. These results suggest that RV receptors can be effectively blocked for prolonged periods in cultured fibroblast cells.

Antibodies, Monoclonal↗
PubMed1989

Comparative susceptibility of respiratory viruses to recombinant interferons-alpha 2b and -beta.

Intranasal recombinant interferon-alpha 2b (rIFN-alpha 2b) protects against natural colds due to rhinoviruses, but apparently not against those caused by viruses. Because rIFN-beta serine17 (rIFN-beta ser) appears less active than rIFN-alpha 2b in preventing natural rhinovirus colds, we compared the two IFNs in two in vitro assays against selected respiratory viruses. In a yield reduction assay, both IFNs had comparable activity against rhinovirus types 39 and 1A and coronavirus 229E, which were inhibited by 90% or more at IFN concentrations of 10(-11) to 10(-10) gram of protein/ml (approximately 2-20 IU/ml). Similar activities were observed with rIFN-beta ser against rhinoviruses isolated from clinical specimens. At concentrations of 10(-9) gram protein/ml, both IFNs inhibited the growth of influenza A and parainfluenza viruses, but not of adenovirus or respiratory syncytial virus in the cell culture systems tested. Thus, the different clinical protection conferred by rIFN-alpha 2b and rIFN-beta ser in studies of natural rhinovirus colds are not accounted for by differences in their in vitro activity against these viruses, and other explanations must be found.

Biological Assay↗
PubMed1989

Ineffectiveness of recombinant interferon-beta serine nasal drops for prophylaxis of natural colds.

Two randomized, double-blind, placebo-controlled trials during early autumn of 1986 and 1987 evaluated the efficacy and tolerance of recombinant interferon-beta serine (rIFN-beta ser) nasal drops for prevention of natural rhinovirus colds. In 1986, 9 X 10(6) units of rIFN-beta ser (139 subjects) or placebo (157) were administered once daily except Sundays for 4 w. Rhinovirus colds occurred in 2.8% of rIFN-beta ser recipients and 6.0% of placebo recipients during the treatment period (52% reduction, P = .3). In 1987, 24 X 10(6) units of rIFN-beta ser (186) or placebo (197) were given daily for 25 consecutive days. Rhinovirus colds developed in 6.3% of rIFN-beta ser recipients and 5.3% of placebo recipients. In each study, illness frequency and number of days with subjective colds did not differ between the groups. Recipients of nasal drops of rIFN-beta ser at either dosage did not differ in tolerance from placebo recipients. The lack of both prophylactic efficacy and nasal toxicity are in contrast to prior observations with nasal sprays of rIFN-alpha 2b.

Administration, Intranasal↗
PubMed1989

Evaluation of an alpha agonist alone and in combination with a nonsteroidal antiinflammatory agent in the treatment of experimental rhinovirus colds.

The pathogenesis of symptoms of the common cold and their optimal treatment are incompletely understood. To evaluate the role of an oral alpha agonist alone and in combination with a nonsteroidal anti-inflammatory drug in the treatment of experimental rhinovirus colds, 58 subjects were randomized to receive pseudoephedrine 60 mg alone, pseudoephedrine 60 mg plus ibuprofen 200 mg, or placebo, four times daily for 4 1/2 days beginning 30 hours after intranasal rhinovirus inoculation under double-blind conditions. The frequencies of infection, colds occurrence, and viral shedding did not differ significantly between the groups. Total symptom scores were reduced by 59% by pseudoephedrine plus ibuprofen (p less than 0.05) and 48% by pseudoephedrine alone compared with placebo. Nasal symptom scores tended to be lower in recipients of pseudoephedrine plus ibuprofen compared with pseudoephedrine alone (p = 0.09), but other parameters showed no significant treatment differences between the groups. Rhinorrhea, as determined by nasal secretion weights, was significantly reduced in both treatment groups compared to placebo. Nasal patency measurements tended to show the greatest improvement in recipients of pseudoephedrine plus ibuprofen. Therapy was clinically well tolerated. The results suggest that an oral alpha agonist is effective in modifying certain manifestations of experimental rhinovirus infection and that the addition of a nonsteroidal anti-inflammatory drug may provide additional benefit in nasal symptoms and patency. Studies involving large numbers of patients with natural colds are needed to determine the clinical significance of these findings.

Adult↗