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Biomedical subjects

A Stokes

Publications and source records attributed to A Stokes.

At least 37 records · Page 2Linked to original sources
PubMed1993

The complete nucleotide sequence of two cold-adapted, temperature-sensitive attenuated mutant vaccine viruses (cp12 and cp45) derived from the JS strain of human parainfluenza virus type 3 (PIV3).

Two cold-passaged mutant vaccine viruses (cp12 and cp45) derived from the JS wild-type (wt) strain of human parainfluenza virus type 3 (PIV3) have been sequenced. These mutant viruses display the cold-adapted (ca), temperature-sensitive (ts), and attenuation (att) phenotypes. Sequence data indicate that both cp12 and cp45 sustained nucleotide substitutions during cold passage and subsequent cloning. Fifteen nucleotide changes were present in cp12 and 18 in cp45. Of these changes, some were present in the sequence of the prototype wt strain (Wash/47885/57) or were non-coding changes present in the open reading frames (ORFs). These were considered unlikely to be of significance in contributing to phenotypic differences between the mutants and the JS wt. There were nine remaining changes in cp12 and eight in cp45 that would most likely contribute to their phenotypes. For cp12, two were non-coding changes in regulatory regions, one in the 3' genome leader and one in the NP gene transcription start signal. The remaining seven changes resulted in amino acid substitutions in NP, F, HN, and L. For cp45, two mutations were in a non-coding regulatory region, the 3' genome leader. The remaining six changes resulted in amino acid substitutions in F, HN, and L. Only one amino acid substitution was conserved between cp12 and cp45 (a valine to alanine change at position 384 of the HN gene). These results should prove useful in the future in understanding the genetic basis of attenuation of the cold-passaged PIV3 candidate vaccine viruses.

Adaptation, Physiological↗
PubMed1992

The complete nucleotide sequence of the JS strain of human parainfluenza virus type 3: comparison with the Wash/47885/57 prototype strain.

The nucleotide sequence of the JS strain of human parainfluenza virus type 3 (PIV3) was determined from a series of 14 overlapping cDNA clones and was compared to that of the previously sequenced prototype PIV3 strain, Wash/47885/57 (Galinski, 1991). Overall, there were 630 (4%) nucleotide differences between the two viruses. 15462 nucleotides comprised the JS genome in contrast to 15463 which constituted the genome of the prototype virus. This was accounted for by a single nucleotide deletion in the 5' non-coding region of the JS phosphoprotein gene. Four nucleotide substitutions were found in the leader region at the 3' end of the viral genome at positions 24, 28, 42 and 45, whereas no differences were found in the 44 base trailer region. All of the transcription start and stop signals and intergenic sequences were conserved between the two viruses with the exception of the transcription stop signal of the matrix (M) gene where there was a nucleotide transposition between bases 7 and 8. A comparison of all of the nucleotide differences in the 3' and 5' non-coding regions of each gene showed a variability of 9.8% and 10.5%, respectively. The 3' non-coding regions of the nucleocapsid (NP) and M genes were completely conserved in contrast to the polymerase (L) gene in which 25% of the nucleotides were different. Differences were observed in the 5' non-coding regions of each gene and ranged from 5.9% for the hemagglutinin neuraminidase (HN) gene to 14.6% for the M gene. An analysis of the amino acid differences in each open reading frame revealed that of all the genes, the coding region of the M gene was the most highly conserved (1.1% amino acid variability), while the phosphoprotein (P) gene was the most variable (5.8% amino acid variability). As these two viruses are wild type strains, these differences in nucleotide and amino acid sequence are compatible with efficient replication in vivo.

Base Sequence↗
PubMed1992

Cold-passaged human parainfluenza type 3 viruses contain ts and non-ts mutations leading to attenuation in rhesus monkeys.

Cold-passaged (CP) mutants derived from the JS strain of wild type wt parainfluenza type 3 virus (PIV3) are being evaluated as candidate live virus vaccines. The wt virus was serially passaged 45 times at low temperature and mutant clones with the cold-adapted (CA), temperature-sensitive (ts), and attenuation (ATT) phenotypes were selected following passage levels 12, 18 and 45 (cp12, cp18, and cp45). The cp45 virus was more ts than the cp12 or cp18 mutants, although all 3 mutant viruses were clearly attenuated in rhesus monkeys compared to wild type virus. The mean peak titers of the cp12 and cp18 viruses administered by the intratracheal route were at least 6000-fold lower than JSwt in both the upper and lower respiratory tracts. The cp45 virus was not recovered from monkeys administered virus by the i.t. route alone; however, when the cp45 virus was administered by the intranasal route, it replicated in the upper respiratory tract to a level comparable to that of the cp12 and cp18 viruses, but continued to be markedly restricted in the lower respiratory tract. These data indicate that the cp12 and cp18 viruses contain predominantly non-ts attenuating mutations whereas the cp45 mutant has both non-ts and ts attenuating mutations. Each of the CP mutants induced a high level of resistance to wild type virus challenge. Also, the ATT phenotype of the cp12 and cp18 viruses as measured in rhesus monkeys was stable after replication in chimpanzees or humans, respectively, although the ts phenotype was not. Based on its greater level of temperature sensitivity in vitro and its greater degree of attenuation in rhesus monkeys, the cp45 virus appears to be the most promising vaccine candidate for humans.

Animals↗
PubMed1991

Clinical signs and humoral immune response in horses following equine herpesvirus type-1 infection and their susceptibility to equine herpesvirus type-4 challenge.

A group of three horses was experimentally infected with equine herpesvirus type 1 (EHV-1) and showed clinical signs characterised by a biphasic febrile response, leucopenia and cell associated viraemia accompanied by virus shedding from the nasopharynx. A second exposure to the virus 18 days later resulted in the isolation of virus from the nasopharynx of one horse. This and a further group of three EHV-1 seropositive horses were subsequently infected with equine herpesvirus type 4 (EHV-4) 147 days after the initial EHV-1 infection and virus was shed from the nasopharynx in the absence of clinical disease. Following the first EHV-1 infection, virus specific immunoglobulin M (IgM) was present by day 5 and remained high until the second exposure at day 18 at which point levels decreased. In contrast, EHV-1 specific IgG, detected at day 6 peaked at day 18, after which time levels remained high. Virus neutralising antibodies and antibodies able to mediate antibody-dependent cellular cytotoxicity were present by day 10. The immune response to EHV-1 is discussed with reference to the disease.

Animals↗
PubMed1991

Studies on glycoprotein 13 (gp13) of equid herpesvirus 1 using affinity-purified gp13, glycoprotein-specific monoclonal antibodies and synthetic peptides in a hamster model.

Hamsters were immunized with either an affinity-purified preparation of equid herpesvirus 1 (EHV-1) glycoprotein 13 (gp13) or synthetic peptides representing three sequences within the homologous glycoprotein of EHV-4, resulting in the production of anti-peptide (in the case of peptide-immunized animals) or antivirus antibodies. The sera from gp13-immunized hamsters contained antibodies which showed virus-neutralizing activity and complement-mediated antibody lysis of EHV-1-infected target cells. These hamsters were protected from EHV-1 challenge. The characteristics of a panel of anti-gp13 monoclonal antibodies (P28, P17, 14H7, 16E4 and 16H9) were assessed both in vivo and in vitro. 16E4 and P28 showed high levels of complement-mediated neutralization of virus, complement-mediated lysis of virus-infected target cells and passive protection of hamsters. Furthermore, epitope mapping studies demonstrated that this glycoprotein contains a neutralizing epitope recognized by EHV-1-immune horse serum. The data imply that gp13 has potential as a candidate antigen for a molecular vaccine.

Amino Acid Sequence↗
PubMed1991

Peer problems in Tourette's disorder.

To explore the social adjustment and peer relationships of children with Tourette's disorder, 29 patients with mild to moderate Tourette's disorder were studied. Children underwent neuropsychological testing. The patients completed self-esteem scales and their parents and teachers completed behavior rating scales. Peer relationships were examined with the Pupil Evaluation Inventory, which is a sociometric questionnaire completed by the child's classmates and provides measures of aggression, withdrawal, and likability. As a group, Tourette's disorder patients were significantly more withdrawn, more aggressive, and less popular than their classmates. Thirty-five percent of the children with Tourette's disorder received the lowest rating in the class on one or more of the Pupil Evaluation Inventory factors. These social problems were not predicted by the frequency or duration of tics. A clinical diagnosis of attention-deficit hyperactivity disorder and teachers' ratings on the summary scale of the Child Behavior Checklist and the Pupil Evaluation Inventory did predict poor adjustment. It is concluded that social adjustment is a major difficulty for many children with Tourette's disorder, irrespective of tic severity.

Child↗
PubMed1989

A hamster model of equine herpesvirus type 1 (EHV-1) infection; passive protection by monoclonal antibodies to EHV-1 glycoproteins 13, 14 and 17/18.

Following intraperitoneal or intranasal inoculation of the Syrian hamster with equine herpesvirus type 1 (EHV-1), strain Kentucky D, virus replicated in the liver and lungs reaching a peak at 4 days post-infection (p.i.). By day 6 p.i. virus titres in these organs had reduced and the spleen contained virus-specific cytotoxic cells. This cytotoxicity was mediated by T cells since treatment of effector cells with a monoclonal antibody to hamster T lymphocytes inhibited the effect. An antiviral humoral immune response was present by day 4 when antibodies capable of lysing EHV-1-infected target cells in the presence of complement were detected. The transfer of serum from recovered hamsters into naive recipients 24 h before challenge prevented virus infection, whereas serum transferred 24 h after challenge reduced the titre of virus recovered from target organs. Inoculation of hamsters with monoclonal antibodies directed to glycoproteins 13, 14 and 17/18 of a subtype 1 virus (Army 183) before virus challenge protected hamsters. This hamster model will prove useful for studying the immune response to EHV-1 and evaluating the immunogenicity of individual virus components.

Animals↗
PubMed1989

Neuropsychological screening of aviators: a review.

The Federal Aviation Administration (FAA) is currently investigating the possibility of including a mini-mental status exam as part of the Aviation Medical Exam. We review evidence that if such a policy is to be implemented, present mental status tests are likely to be inadequate for the job for two reasons. First, they are likely to tap a level of cognitive ability below that required for proficient piloting and second, they may not tap some cognitive skills that are relevant to aviation. We suggest that a new mini-mental status test comprised of already existing neuropsychological tests could be devised that would overcome these difficulties.

Aviation↗
PubMed1988

ADCC and complement-dependent lysis as immune mechanisms against EHV-1 infection in the horse.

Immunity to equine herpesvirus type 1 (EHV-1) was evaluated using sera collected from yearling horses involved in a trial of a commercial vaccine. Measurement of the ability of these sera to mediate antibody-dependent cellular cytotoxicity and complement-dependent lysis revealed that these mechanisms, although potentially important in recovery from EHV-1 infection, do not play a role in protection following vaccination.

Animals↗
PubMed1987

Age differences in the speed and capacity of information processing: 1. A dual-task approach.

Sixty subjects, spanning the age range from 20 to 65, performed a series of tasks designed to evaluate the effects of aging on the speed and capacity of the human information-processing system. A tracking task was performed alone and concurrently with different versions of a Sternberg memory search task that varied the degree of resource competition with the tracking task. A dichotic-listening task, a tracking-task measure of perceptual-motor speed, and a complex transcription task were also performed. The data revealed a monotonic decrease in processing speed with age but no difference in time-sharing abilities between age groups. The latter conclusion was supported by a factor analysis of the test scores, which revealed that scores on the factor defining time-sharing did not differ with age.

Adult↗
PubMed1986

Subclass distribution of IgG and IgA responses to rubella virus in man.

Monoclonal anti-subclass antibodies were used in a micro-ELISA method to determine rubella-specific IgG subclass antibodies in serum from 22 subjects who had acute rubella or had been vaccinated, from 10 infants with congenital rubella, and in serum and synovial fluid samples from 21 patients with chronic arthritis. In nearly all samples IgG1 was the only type of IgG antibody detected. In acute infections it was present within 10 days of the onset of the rash. IgG4 antibody was detected in sera from two immune individuals. Rubella-specific IgA1 subclass antibody was detected by the same technique in sera from 6 of 12 subjects with acute rubella as early as 3 days but not later than 28 days after the appearance of the rash.

Adult↗
PubMed1985

Synthesis of antibodies, including antiviral antibodies, in the knee joints of patients with arthritis.

Serum and synovial fluids from 16 patients with seronegative arthritis and eight with rheumatoid arthritis were studied for immunoglobulin levels and for antibody levels to five viruses. When allowances were made for the distribution of immunoglobulins between serum and synovial fluid there was evidence that in several patients antibody to one or more viruses was synthesised locally in the joint. IgG and especially IgM were present in greatly increased amounts in arthritic joints compared with normal joints. On the basis of serum/synovial fluid ratios inflammation and local immunoglobulin synthesis are discussed as possible causes. These results are compared with antiviral antibody and immunoglobulin ratios observed in the serum and cerebrospinal fluid of patients with multiple sclerosis.

Antibodies, Viral↗
PubMed1980

Antimicrobial effects of trimethoprim and sulphadiazine in infected urine and blood.

Sulphadiazine and trimethoprim in a wide range of concentrations were added to urine from patients with untreated urinary-tract infections. At therapeutic concentrations, the antibacterial activity of trimethoprim was not increased by the addition of sulphadiazine. Exposure of Escherichia coli to trimethoprim in urine was not associated with an increase in resistance to that agent. It was also not possible to select, in vitro, stable resistance to trimethoprim in sensitive cultures of E. coli. At therapeutic levels in blood, trimethoprim and sulphadiazine singly produced mainly a bactericidal action on pathogens responsible for urinary-tract infections. Sulphadiazine occasionally enhanced the effect of trimethoprim at subtherapeutic levels. These findings support the need for further evaluation of trimethoprim alone, rather than its use as a combination with a sulphonamide.

Bacteriuria↗
PubMed1979

Studies on recently isolated cultures of methicillin-resistant Staphylococcus aureus.

Of 19 recently isolated cultures of methicillin-resistant Staphylococcus aureus, 18 showed inducible low-level resistance to minocycline, 15 showed high-level resistance to streptomycin, and 4 showed resistance to low levels of streptomycin. Two cultures produced yellow pigment and may have been derived in vivo by loss of a gene(s) determining orange pigment. Treatment of three cultures with serial exposures to N-methyl-N'-nitro-N-nitrosoguanidine resulted in a widening of phage typing pattern that included all reactions in group I, the great majority in group III, but none in group II. The widening in phage lysis was possibly due to the elimination of defective prophages. Transfer of tetracycline resistance occurred from 12 out of the 19 cultures to a recipient in mixed culture; this transfer required either Ca2+ or Mg2+, was abolished by citrate, and enhanced by high cell density. It was probably mediated by defective bacteriophages. No evidence was obtained for the occurrence of recombination within the methicillin-resistant clone in nature. Eleven methicillin-resistant cultures stored for at least 5 years on agar slopes at 20 degrees C had all lost this resistance at high frequency.

Anti-Bacterial Agents↗
PubMed1978

Effect of thymidine on activity of trimethoprim and sulphamethoxazole.

Thymidine at levels as low as 0.05 mg/1 reduces the activities of sulphamethoxazole and trimethoprim and their combination in vitro. Using a biological assay procedure, levels of thymidine greater than this were interpreted as being present in urine. The addition of sulphamethoxazole and trimethoprim, singly or in combination, to urine obtained from patients with urinary tract infections showed that all the antibacterial effect towards sensitive organisms was due to the trimethoprim component. It is suggested that trimethoprim should replace the combination co-trimoxazole for the treatment of some lower urinary tract infections, and that laboratory media, if they are to resemble the clinical environment, should contain thymidine.

Bacteriuria↗