Rho and omega production in pi+p interactions at 15.7 GeV/c.
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Journal Article↗
Biomedical subjects
M Ferguson
Publications and source records attributed to M Ferguson.
The effect of strain differences on the assay of rabies virus glycoprotein by single radial immunodiffusion.
Antigenic differences between rabies virus strains used for vaccine manufacture can be demonstrated using monoclonal antibodies. We have shown that these differences are sufficiently large to affect the potency values of vaccines measured in single radial immunodiffusion (SRD) assays if the reference and test vaccines are antigenically heterologous. The production of reagents for use in SRD assays for each strain of rabies virus should be considered.
Animals↗
Evolution of poliovirus during an outbreak: sequential type 3 poliovirus isolates from several persons show shifts of neutralization determinants.
An outbreak of poliomyelitis in Finland resulted in the widespread circulation of wild-type 3 poliovirus strains that had antigenic properties distinct from the strains used to produce the attenuated and inactivated vaccines. Considerable variation was observed in the ability of broadly reacting monoclonal antibodies directed against type 3 poliovirus to neutralize the 54 strains examined. Sequential isolates from several persons showed an antigenic drift with these monoclonal antibodies and selected human sera. In addition, some faecal specimens were found to contain more than one antigenic variant. Primer extension sequencing of genomic RNAs of three plaque-purified antigenic variants isolated from one patient showed base substitutions in the region coding for the major antigenic site of poliovirus type 3. The resulting difference in the amino acid sequence in the virion protein VP1 could explain the differences observed in the neutralization of these strains by the monoclonal antibodies. Whether the observed changes in the antigenic characteristics of the sequential isolates represent true antigenic drift under immunological pressure or whether the emergence of the new variants is based on other modes of selection during replication is not known.
Antibodies, Monoclonal↗
Conservation in vivo of protease cleavage sites in antigenic sites of poliovirus.
Polioviruses possess three major antigenic sites which have been located chemically and structurally on the particle. One of these sites, designated site 1, is strongly immunodominant for serotype 3, but highly immunorecessive for type 1. We report that monoclonal antibodies directed against site 1 of type 1 poliovirus may be isolated by an altered route of immunization of the donor mice. Site 1 is shown to be highly variable for type 1, but highly conserved for type 3 poliovirus, although the converse would be predicted from their immunodominance. The evidence presented suggests that the antigenic conservation is associated with a strong selective pressure for a proteolytic cleavage site within site 1 of type 3. As proteolytic cleavage results in the loss of the antigenicity of site 1 the presence of the cleavage site in a virus replicating in the gut in the presence of proteases would protect the virus from neutralizing antibodies directed against uncleaved site 1. The conservation of the site in type 3 is thus consistent with the view that site 1 is a significant target of a human as well as a murine immune response against type 3.
Animals↗
Reverse Southern hybridization.
A DNA oligomer 25 nucleotides long which contained an HMT (4'-hydroxymethyl-4,5', 8-trimethylpsoralen) furan side monoadduct to thymidine at a 5'-TpA-3' site was used as a probe for the polylinker sequence present in single-stranded M13 mp19 DNA and in double-stranded pUC 19 DNA. Hybridization and photofixation were carried out simultaneously in solution under conditions approximating the melting temperature of the probe-target hybrid. Use of probe concentrations greater than 10(-8) M permitted hybridization times of a few minutes. Irradiation with near ultraviolet light converted the HMT monoadduct present in hybrid complexes into an interstrand crosslink. Efficient photofixation removed hybrid from the equilibrium distribution and resulted in the formation of additional probe-target complex. After removal of excess probe by centrifugation through a semi-permeable membrane (Centricon-30), samples were electrophoresed through an alkaline agarose gel which was analyzed by autoradiography. When using an HMT-modified 25-mer probe end-labeled with 3,000 Ci/mmole 32P, 0.015 ng (3.8 X 10(6) copies) of M13 DNA could be detected. With this same probe 10 micrograms of denatured human DNA (corresponding to 3.0 X 10(6) copies) did not give a signal.
DNA↗
Localization of sympathetic and sensory neurons innervating the rat kidney.
Following injection of horseradish peroxidase (HRP) into the hilar region of the left kidney of the rat, 66% of labeled sympathetic neurons were located in the ipsilateral paravertebral ganglia, with most cells in T13 and L1, and 14% were located in equivalent segments of the contralateral chain. A similar distribution of sympathetic neurons projected to the right kidney, with most cells in T12 and T13 paravertebral ganglia. Only 20% of the total sympathetic supply to either kidney arose from the prevertebral ganglia. The renal sensory innervation was also bilateral in origin, with about 80% of the neurons arising from ipsilateral dorsal root ganglia. Injection of HRP into the caudal and rostral poles of the left kidney labeled paravertebral neurons which were concentrated in ganglia L1 and T13, respectively, but did not label any sensory neurons. We conclude that most of the renal sympathetic innervation is paravertebral in origin, and that a substantial bilateral component exists for both sympathetic and sensory supplies. Neurons arising from the contralateral side have their cell bodies in segments that provide the main ipsilateral innervation to the same kidney. The majority of sensory axons appear to be restricted to subcortical areas.
Adrenergic Fibers↗
Reactivity of anti-peptide and anti-poliovirus type 3 monoclonal antibodies with synthetic peptides.
Monoclonal antibodies were prepared from mice immunized with an 18-residue synthetic peptide with an amino acid sequence from a major antigenic sequence involved in the neutralization of type 3 poliovirus. Approximately 250 hybridomas secreted antibodies that reacted with the peptide but not the virus, two antibodies reacted with the virus but not the peptide and no antibody reacted with both. Conversely 26 monoclonal antibodies prepared from mice immunized with type 3 poliovirus and known to be directed against the appropriate sequence on the virus, generally failed to react with the peptide. These results might be expected if only a small proportion of the free or coupled peptide molecules adopt molecular conformations which resemble that of the homologous antigenic site in the virus. Antibodies specific for other antigens occasionally reacted well with the synthetic peptides, indicating that antibodies may bind to peptides of inappropriate sequence. The identification of antigenic sites by the use of synthetic peptides therefore requires considerable caution.
Animals↗
Antigenic and molecular evolution of the vaccine strain of type 3 poliovirus during the period of excretion by a primary vaccinee.
A 4 month old child was immunized with a vaccine containing the Sabin live attenuated vaccine strains of all three serotypes of poliovirus. The antigenic and molecular evolution of the Sabin strain of poliovirus type 3 was then followed throughout the entire period of virus excretion. Novel strains appeared at 8, 42 and 52 days post-vaccination and were the products of both intertypic recombination between type 2 and type 3 poliovirus in regions of the genome coding for non-structural proteins and of point mutations in the region coding for the structural proteins. Excretion of virus continued for 73 days. All strains examined reacted with all monoclonal antibodies specific for the main immunodominant antigenic site of type 3 poliovirus, but variation was observed at other, immunorecessive sites. These findings have possible implications for the evolution of the virus in vaccinees or in epidemics and are consistent with the known antigenic stability of the virus.
Antibodies, Monoclonal↗
Antigenic and molecular properties of type 3 poliovirus responsible for an outbreak of poliomyelitis in a vaccinated population.
Virus isolated from an outbreak of poliomyelitis in Finland has been examined serologically and at the molecular level. The causative agent was an antigenically unusual strain of type 3 poliovirus, which was unrelated to the strains used to manufacture either live or killed poliovaccines. It is likely that the antigenic properties of the virus played a part in establishing a limited outbreak of poliomyelitis in a vaccinated population.
Amino Acid Sequence↗
Antigenic structure of polioviruses of serotypes 1, 2 and 3.
The antigenic sites recognized by monoclonal antibodies with neutralizing activity for the Sabin vaccine strains of poliovirus of serotypes 1, 2 and 3 have been studied by the isolation and characterization of mutants resistant to neutralization by antibody. Three distinct sites have been identified which are designated site 1, site 2 and site 3. Site 1 includes a region of 12 amino acids of VP1, from residues 89 to 100, and a corresponding region of VP1 has been identified as an antigenic site for poliovirus 2. This site was strongly immunodominant in type 2 and type 3 but was not detected for poliovirus 1. Site 2 is a complex site including residues 220 to 222 from VP1 (site 2a) with residues including 169 and 170 and others of VP2 (site 2b). Both site 2a and site 2b have been detected in type 1 poliovirus, while as yet only site 2b has been detected in type 3 poliovirus. Site 3 is a complex site including residues 286 to 290 from VP1 (site 3a) with residues including 58 and 59 and others of VP3 (site 3b). Both sites 3a and 3b have been detected in type 3 poliovirus, while as yet only site 3b has been detected in type 1 poliovirus.
Amino Acid Sequence↗
Modulation of humoral response to a 12-amino-acid site on the poliovirus virion.
Most monoclonal antibodies to poliovirus 3 but not poliovirus 1 require a single 12-amino-acid sequence in virion protein VP1 for neutralization (site 1). None of the available monoclonal antibodies requiring this site bound virions after tryptic cleavage of site 1. This result allowed the amount of site 1-specific antibodies to be determined in an antiserum by comparing its reactivity with virus and trypsin-cleaved virus. Antisera to poliovirus 3 Sabin strain (PS3) but not poliovirus 1 Sabin showed site 1 immunodominance, consistent with the frequency of isolation of site 1-specific monoclonal antibodies to these viruses. Cleavage of site 1 prior to immunization dramatically reduced the immunogenicity of this site in PS3. However, the antiserum against trypsin-cleaved PS3 still had a high neutralization titer, demonstrating that sites other than site 1 can elicit a neutralizing response to PS3. Other antisera to PS3 showed significant variability in the response to site 1, indicating that other factors, such as the genetic background of inbred mouse strains, the species immunized, and the immunization protocol, also affect immunodominance. In particular, a serum from a human infant recently immunized with oral trivalent vaccine had little response to site 1.
Amino Acid Sequence↗
Avidin-biotin-immunoglucose oxidase: use in single and double labeling procedures.
We have investigated the use of an avidin-biotin-immunoglucose oxidase (AB-GO) technique for single and double antigen localization in conjunction with the avidin-biotin-immunoperoxidase (AB-P) technique in fixed, embedded specimens, using sequential monoclonal and polyclonal antibodies of the same species. The optimal technique for double labeling requires the first antibody to be applied and localized with the AB-P technique using 3,3'-diaminobenzidine (DAB) as the chromogen, followed by an optional elution step and/or incubation with mild detergent (0.01% Triton). The second antigen is localized with the AB-GO technique with nitro blue tetrazolium (NBT) as a chromogen. Effects of antigen concentration, intermediate elution steps, and the relative efficiency of the two methodologies are described.
Avidin↗
Postoperative recurrence of lung cancer: detection by whole-body gallium scintigraphy.
The records were reviewed of 111 consecutive patients who had lung cancer resected and who were followed with serial postoperative whole-body gallium scans. Scans were obtained preoperatively at intervals of 3-6 months for about 1 year after surgery and subsequently at yearly intervals. The period of follow-up varied from 1 1/2 to 8 years. Of 55 patients who developed tumor recurrence, a gallium scan was the first indicator of recurrence in 11 (20%) and was judged helpful in confirming or localizing a recurrence in another 14 patients (25%). False-positive rates were determined from 175 postoperative scans in the other 56 patients who did not suffer recurrence. Of these 175 scans, 15 (9%) demonstrated abnormalities that were sufficiently suspicious that an additional diagnostic procedure, other than chest radiography, was performed for clarification. However, in no case did the gallium scan result adversely affect the management of the patient. Our data demonstrate that routine postoperative whole-body gallium scanning can facilitate early detection of recurrence in some cases. Judicious use of gallium scanning in cases with clinically suspected recurrence can enable prompt localization, diagnosis, and treatment of recurrent tumor.
Bone Neoplasms↗
WHO collaborative study on the use of monoclonal antibodies for the intratypic differentiation of poliovirus strains.
An international collaborative study was carried out to identify monoclonal antibodies that could reliably discriminate between wild polioviruses and strains derived from Sabin vaccine viruses. For poliovirus types 2 and 3, monoclonal antibodies were identified that reacted specifically with type 2 or type 3 strains which gave T1-oligonucleotide maps similar to or indistinguishable from that of Sabin vaccine virus, thus indicating their vaccine origin. These monoclonal antibodies failed to react with strains which gave T1 maps unrelated to that of Sabin vaccine virus. However for type 1, five of the six antibodies examined in the study reacted only with strains with a T1 map indistinguishable from that of type 1 Sabin vaccine virus. In contrast, other monoclonal antibodies against poliovirus types 1, 2 and 3 reacted broadly within a serotype.
Antibodies, Monoclonal↗
Single radial immunodiffusion assays for the standardization of the antigenic content of rabies vaccines.
The method currently recommended for the assay of rabies vaccine potency is a mouse protection test, the NIH test. It is widely accepted that the estimates of potency obtained in such tests are imprecise. We have applied the single radial immunodiffusion (SRD) technique to the assay of the glycoprotein antigen, the major protective antigen of the rabies virion. In this paper we have summarized the results of an international collaborative study, in which SRD was shown to give reproducible estimates of glycoprotein content. In addition the use of SRD in assessing the stability of rabies vaccines is discussed.
Animal Testing Alternatives↗
Substance P-immunoreactive nerves in the rat kidney.
Previously published data have indicated that in the rat, unlike other species examined, the kidney is not supplied by sensory nerves containing substance P (SP). As part of a study of reflex control of renal function in the rat, we have now reassessed this situation. Many fine, varicose, SP-immunoreactive nerve fibers were found in the wall of the proximal ureter and the renal pelvis, and around the larger renal blood vessels. Sparser populations of similar nerves were also seen running close to proximal and distal tubules in the renal cortex. Occasional fibers were seen at the margins of the glomeruli. Our findings suggest that sensory nerves containing SP may carry sensory information of several types from the rat kidney.
Animals↗
Triggered-bubble-chamber study of the reaction pi +p--> Delta ++ pi 0 pi 0 at 16 GeV/c.
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Journal Article↗
Induction by synthetic peptides of broadly reactive, type-specific neutralizing antibody to poliovirus type 3.
A region of virus capsid protein VP1 located 89-100 amino acids from the N-terminus has been proposed to comprise a major antigenic site involved in the neutralization of poliovirus type 3. Synthetic peptides 10-18 amino acids in length, containing all or part of this sequence, were tested for their ability to induce antiviral antibodies. Rabbits, but not guinea pigs or mice, immunized with the most active peptide, developed hightitered, type-specific, neutralizing antibodies for a wide range of poliovirus type 3 strains. Consistent with the broad type specificity of the antibody response was the observation that amino acids 89-100 of VP1 are highly conserved among different poliovirus type 3 strains. This sequence thus appears to provide, at least in part, a molecular basis for serotype antigenic specificity. Individual amino acids from 93 to 98 within this sequence were shown to be important for the neutralization of virus by antipeptide sera by examination of the ability of the sera to neutralize laboratory-derived poliovirus type 3 mutants with known single amino acid substitutions in the proposed antigenic site.
Amino Acid Sequence↗