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PubMed2000

Evaluation of three 'ready to formulate' oil adjuvants for foot-and-mouth disease vaccine production.

Foot-and-mouth disease virus (FMDV) type OR(2)/75, grown on BHK 21 clone 13 cell monolayers, was inactivated with formalin. The virus was clarified and was either concentrated with 8% polyethylene glycol 6000 (PEG) or used in its untreated form for the preparation of oil adjuvant vaccines. The oil adjuvants used in this study were Montanide ISA 206 (which renders a water-in-oil-in-water (w/o/w) type of emulsion), Montanide ISA 57 and Montanide ISA 50V (both of which render water-in-oil (w/o) type of emulsions). The vaccines were tested on guinea pigs and calves. The results indicated that vaccines emulsified using Montanide ISA 57 elicited the best protective immune response in the animals, followed by those emulsified with Montanide ISA 50V and Montanide ISA 206. It was also found that vaccines formulated with virus concentrated using 8% polyethylene glycol (PEG) were more immunogenic than the vaccines formulated with the untreated harvest virus.

Adjuvants, Immunologic↗
PubMed1975

The sub-type classification of strains of foot-and-mouth disease virus.

Sixteen foot-and-mouth disease virus (FMDV) strains of type SAT 1 were compared in complement-fixation tests. With the test used, the range of antigenic variation within a type appeared to be greater than previously described. The concept of a sub-type group within which all strains are more closely related to each other than to any strain outside the group was not supported. Considering the group of strains studied, it is suggested that the classification of strains is best achieved by moninating a reference strain for each sub-type. Others are classified as related strains in one or more sub-type groups according to their relationships with the reference strains.

Animals↗
PubMed1996

Recognition of the initiation codon for protein synthesis in foot-and-mouth disease virus RNA.

Foot-and-mouth disease virus (FMDV) RNA utilizes two in-frame initiation codons to produce two precursor proteins with identical carboxy termini. The 5' untranslated region (5'UTR) directs the ribosome to internal sequences without the need for a cap structure as used in host mRNAs. The FMDV 5'UTR was cloned upstream of the reporter gene chloramphenicol acetyltransferase (CAT) in order to study the selection of initiation site and to facilitate quantification of the translation products. After in vitro transcription with T7 RNA polymerase and translation in rabbit reticulocyte lysate, the two CAT products, resulting from initiation from the two initiation codons, were quantified. The downstream initiator AUG (AUGLb) was selected more efficiently in the wild-type 5'UTR. In truncated RNA, the upstream initiation site (AUGLab) was more efficiently utilized than in the wild-type 5'UTR. Protein synthesis initiation factors were added to translation assays to determine whether these factors influenced initiation site selection. Addition of eIF-2 and of eIF-2B changed the selection process for both types of RNA. These factors induced a 2.5-fold higher usage of the upstream AUGLab for wild-type and 5'UTR-truncated RNA. A change in mRNA concentration also induced a change in the usage of initiation codons; however, the effect of eIF-2 was measured over a broad range of mRNA concentrations. In conclusion, eIF-2 mediates the recognition of the initiation codon during both cap-dependent and internal ribosome entry site-dependent initiation.

Animals↗
PubMed1999

Evidence for the role of His-142 of protein 1C in the acid-induced disassembly of foot-and-mouth disease virus capsids.

Foot-and-mouth disease virus (FMDV) capsids are inherently labile under mildly acidic conditions, dissociating to pentamers at pH values in the region of 6.5, with the release of protein 1A and the viral RNA. This acid-induced disassembly is thought to be required for the entry of the virus genome into the host cell. Previous work has highlighted a histidine-alpha-helix charge-dipole interaction at the twofold axes of symmetry between pentamers and has suggested that this interaction plays a role in acid-induced disassembly. The validity of this theory has now been tested by converting the implicated residue, His-142 of protein 1C, to Arg, Phe and Asp. The effects of such changes were studied by using a previously described vaccinia virus expression system, in which synthesis and processing of FMDV capsid proteins results in the self-assembly of capsids. In agreement with the histidine-alpha-helix charge-dipole theory, assembly in the arginine mutant was found to be greatly reduced, while capsids of the aspartic acid mutant were considerably more stable under acidic conditions than the wild-type. Aberrant but acid-stable complexes were obtained in the phenylalanine mutant.

Animals↗
PubMed1967

Detergent-solubilized RNA polymerase from cells infected with foot-and-mouth disease virus.

The foot-and-mouth disease virus RNA polymerase complex was dissociated from cellular membranes with deoxycholate in the presence of dextran sulfate. The soluble polymerase complex was active in the cell-free synthesis of virus-specific RNA; solubilization of the complex permitted direct analysis of the cell-free reaction mixtures without recourse to RNA extraction. A major RNA-containing component found early during cell-free incubation ranged from approximately 140 to 300S. The final major products of the cell-free system were 37S virus RNA, 20S ribonuclease-resistant RNA, and a 50S component containing RNA.

Aphthovirus↗
PubMed1995

Viral RNA modulates the acid sensitivity of foot-and-mouth disease virus capsids.

Foot-and-mouth disease virus (FMDV) manifests an extreme sensitivity to acid, which is thought to be important for entry of the RNA genome into the cell. We have compared the low-pH-induced disassembly in vitro of virions and natural empty capsids of three subtypes of serotype A FMDV by enzyme-linked immunosorbent assay and sucrose gradient sedimentation analysis. For all three subtypes (A22 Iraq 24/64, A10(61), and A24 Cruzeiro), the empty capsid was more stable by 0.5 pH unit on average than the corresponding virion. Unexpectedly, in the natural empty capsids used in this study, the precursor capsid protein VP0 was found largely to be cleaved into VP2 and VP4. For picornaviruses the processing of VP0 is closely associated with encapsidation of viral RNA, which is considered likely to play a catalytic role in the cleavage. Investigation of the cleavage of VP0 in natural empty capsids failed to implicate the viral RNA. However, it remains possible that these particles arise from abortive attempts to encapsidate RNA. Empty capsids expressed from a vaccinia virus recombinant showed essentially the same acid lability as natural empty capsids, despite differing considerably in the extent of VP0 processing, with the synthetic particles containing almost exclusively uncleaved VP0. These results indicate that it is the viral RNA that modulates acid lability in FMDV. In all cases the capsids dissociate at low pH directly into pentameric subunits. Comparison of the three viruses indicates that FMDV A22 Iraq is about 0.5 pH unit more sensitive to low pH than types A10(61) and A24 Cruzeiro. Sequence analysis of the three subtypes identified several differences at the interface between pentamers and highlighted a His-alpha-helix dipole interaction which spans the pentamer interface and appears likely to influence the acid lability of the virus.

Amino Acid Sequence↗
PubMed1995

Identification of the active-site residues of the L proteinase of foot-and-mouth disease virus.

The foot-and-mouth disease virus (FMDV) leader (L) protein is involved in autocatalytic cleavage at the L/P1 junction and in the cleavage of translation initiation factor p220, a subunit of the cap-binding protein complex. It has been suggested that this proteinase has homology to the papain-like family of cysteine proteinases, and from this information, we have investigated the active-site residues by introducing specific mutations into the L gene. Mutations of Cys-23 to Ala or His-120 to Leu resulted in enzymes that lacked cis activity at the L/VP4 cleavage site, trans activity on a truncated L-P1 substrate, and p220 cleavage activity. Mutations of Cys-23 to ser or His-110 to Leu resulted in enzymes that retained some or all cis activity and had reduced p220 cleavage. These mutations were introduced separately into a full-length FMDV cDNA, and RNA transcripts derived from these cDNAs were translated in a cell-free system and transfected into cells. The C23S mutant inefficiently cleaved at the L/P1 junction and within P1, and virus obtained from transfected cells reverted to wild type. The H110L mutant cleaved the L/P1 junction almost as well as the wild-type enzyme, and virus recovered from transfected cells retained the mutation and displayed wild-type viral protein synthesis and host shut-off kinetics.

Animals↗
PubMed1993

Cross-reactive idiotopes among anti-foot and mouth disease virus neutralizing antibodies.

Foot and mouth disease virus (FMDV) viral protein 1 is the only one of the four viral proteins (VP) that induces neutralizing antibodies as an isolated protein. A 32 amino acid (AA) residue (32dimer) of FMDV subtype A12 Lp ab VP1 (AA 137-168) was immunogenic against the A12 subtype. Three antibody populations each recognizing different epitopes on 32dimer were isolated by affinity chromatography (AFC) from the serum of a steer which had been immunized with the 32dimer. The 32dimer contains an AA sequence that is recognized by a protective paratope carried on a murine monoclonal antibody (mAb) (7SF-3.H3.1). Polyclonal anti-7SF-3 idiotype antibodies specifically inhibited the binding activity of one of these anti-32dimer antibody populations suggesting the existence of cross-reactive paratopic-related idiotopes between mAb 7SF-3 and antibodies elicited by the 32dimer. These anti-idiotypic antibodies were used in AFC to purify antibodies from the anti-32dimer serum. The purified antibody population has characteristics that resemble those of the mAb 7SF-3, i.e. its reactivity with FMDV A subtypes in ELISA, radioimmunoassay (RIA), mouse neutralization and its lack of reactivity with a mAb 7SF-3 neutralizing escape virus variant. Furthermore, these antibodies were specifically inhibited by either anti-mAb 7SF-3 idiotypic antibodies or peptides containing the mAb 7SF-3 epitope. Using the same experimental approach, mAb 7SF-3 idiotope-bearing antibodies were shown to be present in serum from bovine and swine convalescent from FMDV A12 Lp ab infection. Thus, the highly immunogenic area between residues 137 and 168 of FMDV VP1 elicited a cross-reactive neutralizing idiotope response conserved amongst several animal species.

Animals↗
PubMedDate not supplied

Epidemiology of tinea pedis in marathon runners: prevalence of occult athlete's foot.

Studies on the prevalence of tinea pedis, a frequently encountered dermatophytic infection, have been conducted mostly in swimmers although people who regularly practise other types of physical activities may also have a high rate of clinical or subclinical infection. This investigation was undertaken to establish the rate of infection in marathon runners, and to determine the incidence of occult athlete's foot disease in this population. Among samples obtained from 405 individuals, 22% were positive. The rate of infection was highest in the older age groups. The prevalence of infection was 24.2% in men and 6.1% in women. Trichophyton rubrum and Trichophyton mentagrophytes were the two species of dermatophytes most commonly isolated on culture. Occult athlete's foot disease represented 48% of cases with a positive culture. Finally, routine sampling of both feet was confirmed necessary to adequately establish the rate of infection: 26.9% of cases with a positive culture would have been missed by unilateral sampling. Other epidemiological factors were not clearly linked to the prevalence of disease in marathon runners: weight; presence of pet animals; practice of other sports; race and country of origin. In conclusion, we establish that marathon runners represent a population at risk for the occurrence of both clinical and subclinical tinea pedis infection.

Adolescent↗
PubMed2003

The pathogenesis and diagnosis of foot-and-mouth disease.

The pathogenesis of foot-and-mouth disease (FMD) is reviewed, taking account of knowledge gained from field and experimental studies and embracing investigations at the level of the virus, the cell, the organ, the whole animal and the herd or flock. The review also addresses the immune response and the carrier state in FMD. Progress made in understanding the pathogenesis of the disease is highlighted in relation to developments in diagnosis and methods of control.

Animals↗
PubMedDate not supplied

Local treatment for neuropathic foot ulceration and osteoarthropathy.

Forty-one patients with 42 involved feet received local care for neuropathic foot disease. Thirty-one patients had ulcers (nine with associated fractures), and 10 did not (eight with fracture and two with severe ligamentous injury). Patients were examined at least 1 year after initiation of treatment, and follow-up averaged 3 years (range, 1 to 9). Treatment included ulcer cleansing, debridement, local bone excision, molded plaster casts, and antibiotics for patients with significant infection. Most patients used special shoes. Of the 42 involved extremities, 39 (93%) healed with treatment, 21 extremities (50%) remained healed at follow-up examination, and 16 patients (39%) continue to have difficulty with recurrent foot ulceration or osteoarthropathy. Thirty-nine patients (95%) have avoided the need for a major amputation.

Adult↗
PubMed2005

Models of foot-and-mouth disease.

During the 2001 foot-and-mouth disease outbreak in the UK, three very different models were used in an attempt to predict the disease dynamics and inform control measures. This was one of the first times that models had been used during an epidemic to support the decision-making process. It is probable that models will play a pivotal role in any future livestock epidemics, and it is therefore important that decision makers, veterinarians and farmers understand the uses and limitations of models. This review describes the utility of models in general before focusing on the three foot-and-mouth disease models used in 2001. Finally, the future of modelling is discussed, analysing the advances needed if models are to be successfully applied during any subsequent epidemics.

Animals↗
PubMed2005

Interaction effect in bladder cancer between N-acetyltransferase 2 genotype and alcohol drinking.

Cigarette smoking, aromatic amines and ionizing radiation are known carcinogens of bladder cancer. NAT2 genotype might play a role in bladder cancer carcinogenesis. This hospital-based, case-control study was conducted in Kaohsiung, Taiwan, which neighbors the high incidence region of bladder cancer in the black-foot disease area. A total of 103 cases with diagnosed bladder cancer were collected. For each case, 1 control was selected from the same hospital. A structured questionnaire was applied for all cases and controls. DNA was extracted from peripheral blood cell. The ASO-PCR/RFLP technique was used to determine the NAT2 genotype. For bladder cancer, the significantly excessive risks were observed in regular drinkers (OR = 2.74, 95% CI = 1.28-5.87) and residents of the black-foot disease endemic area (OR = 7.53, 95% CI = 2.16-26.33), and interaction of regular drinking and slow type of NAT2 (OR = 18.04, 95% CI = 2.28-142.80). We suggested that NAT2 genotype might play a role of effect modifier in bladder cancer carcinogenesis.

Aged↗
PubMed1970

Observations on the carrier state and related antibody titres during an outbreak of foot-and-mouth disease.

An outbreak of foot-and-mouth disease in a partially immune population of cattle in Botswana is described. The results show that when cattle immunized by vaccination were presented with natural field challenge of FMD, many animals with immunity sufficient to protect them against clinical disease were, however, susceptible to pharyngeal infection and subsequently became virus carriers. The proportion of animals becoming carriers appeared to vary with the degree of severity of the challenge.Vaccination before exposure to virus appeared to have little effect on the duration of the carrier state. No evidence was obtained of the spread of carrier virus to immune herds following the outbreak.Antibody titres during the outbreak were higher in the clinically infected animals than in the carrier animals and the uninfected animals. Evidence suggested that natural challenge boosted the titres of immune animals. After the outbreak, however, it was not possible to distinguish by their antibody titres between the carrier animal and the virus-negative animal.Antigenic studies on the strains of virus isolated are described.

Animals↗
PubMed2001

[Clinical signs and differential diagnosis of foot and mouth disease in pigs].

FMD in pigs is primarily a foot disease. It is dominated by rather painful formation of vesicles in the epidermis of the feet (coronary band, interdigital clefts, bulbs) combined with severe lameness. Complications will be seen as detachment of the hoof and secondary infection of disrupted aphthae which may cause purulent arthritis of the pedal joint. Concerning differential diagnosis are to be considered all cases of acute lameness, vesicle-formation as typical lesions of exudative epidermites of pemphigus in the course of infections with S. hyicus or S. aureus as well as degenerative changes after selenium-intoxication, specially near the coronary band, sometimes linked with exungulation.

Animals↗