Multiple sites of recombination within the RNA genome of foot-and-mouth disease virus.

Recombinant foot-and-mouth disease viruses were isolated from cells infected with a mixture of temperature-sensitive (ts) mutants belonging to different subtype strains. In order to select for recombination events in many different regions of the genome, crosses were performed between various pairs of mutants, with ts mutations in different regions of the genome. ts+ progeny were analysed by electrofocusing virus-induced proteins and RNase T1 fingerprinting of their RNA. All but 5 out of 43 independent isolates, from nine crosses, proved to have recombinant RNA genomes. Maps of these genomes, based on a knowledge of the locations of the unique oligonucleotides, were constructed. Most could be interpreted as being the products of single genetic cross-overs, although three recombinants were formed by two cross-overs each. Cross-overs in at least twelve distinct regions of the genome were identified. This evidence of a large number of recombination sites suggests that RNA recombination in picornaviruses is a general, as opposed to a site-specific, phenomenon.

Isolation and biochemical characterization of intertypic recombinants of foot-and-mouth disease virus.

Recombinants were isolated between two European serotypes (O and A) and between two of the most distantly related serotypes (O from Europe and SAT2 from Africa) using appropriate ts mutants in an infectious centre assay. The recombinants were characterised by electrofocusing of their induced proteins and by RNase-T1 fingerprinting of their RNA. The approximate location of the cross-over event in each recombinant was determined by sequencing the unique distinguishable O or A oligonucleotides and locating them within the known genome sequence. Nine different types of recombinant were identified from the two types of cross (O X A and O X SAT) and all had a single cross-over in the middle or 3' half of the genome, i.e. in the nonstructural coding region. Recombination between the most distantly related viruses (O X SAT2) appeared to occur at a lower frequency than recombination between serotypes of the same group (O X A). A higher incidence of recombinant proteins with unique pI was also observed in the O X SAT2 crosses.

Prosopo-affective agnosia and computerized tomography findings in patients with cerebral disorders.

Thirty-nine male patients (median age 61, range 19-92) from a neurologic ward were examined by a test for prosopo-affective agnosia (PAA), i.e., impairment in the recognition of facial affect (emotions) with no impairment in the recognition of facial features (PA, prosopo-agnosia). The scores for patients without hemispheric damage were close to those of normal subjects; the scores for patients with right and left hemispheric disease were lower; and the worst performers were patients with diffuse bilateral disease. The relative independence of PAA from PA was re-affirmed. The neurologic findings on 21 patients were confirmed by computerized tomography (CT). On the PAA test, patients with negative CT results had scores close to those of normal subjects; patients with right or left hemispheric disease had lower scores; and the worst performers were patients with diffuse cortical atrophy. All patients who scored 87.5 percent or lower showed positive results with the CT scan, indicating that the PAA test may have some value in predicting positive CT findings. A significant deterioration in the ability to recognize facial affect was evident in the group of 15 patients aged 65 or older.

The underlying problems resulting in controversies in the clinical management of transient ischemic attacks: an overview.

Of all the controversial topics in the management of cerebrovascular diseases the subject of transient ischemic attacks is perhaps the most controversial. A preponderance of literature related to the subject, reflecting a remarkable degree of interest in the topic, is a result of this controversy. Each conclusion serves to stimulate more interest, more evaluation, and more controversy. We will attempt to give an overview of the controversies in the management of transient ischemic attacks.

T.I.A. revisited: new wine--old bottle.

TIA has been accepted as a concept of transient cerebral ischemia. There is an ever enlarging body of literature sparking controversies considering its natural history, prognosis, outcomes of clinical trials and usefulness of the concept. Much of the controversy is related to the diverse pathophysiology of TIAs, the selection of patients for clinical trials and the associated risk factor in the studied population. The advantages of the concept are a warning of the possibility of future irreversible pathology an opportunity to treat and/or remove risk factors an opportunity to establish a basis for monitoring the patient and making interim decisions concerning intervention. The risks of the concept are: administering a specific therapy to all patients, failure to fully evaluate the patient once the diagnosis is made, tendency to rely on "experts" for guidance. TIA is a useful concept if one recognizes: the pathophysiology is polymorphous and multiplex, the concept is a signal for diligent search for the underlying cause or causes, it is more important to treat the risk factors than to give a specific therapy.

Neurologic complications of the acquired immune deficiency syndrome.

The acquired immune deficiency syndrome (AIDS) is a syndrome requiring unique knowledge of its versatile manifestations for accurate diagnosis and skillfull management of its numerous complications for successful treatment. The human T-cell lymphotropic virus type III (HTLV-III), a replication-complete virus, is now reported as the etiologic agent. The neurologic complications of AIDS cover the spectrum of neurologic diseases and usually have multiple causative factors, all of which should be appropriately managed. These complications can be successfully treated, although constant monitoring is required because recurrence is frequent. The neurologic complications are the second most frequent cause of death in AIDS patients.Tests that are usually reliable in diagnosing neurologic diseases may not be reliable in patients with AIDS. The management of AIDS is a multidisciplinary effort, and the neurologist should fulfill a role in the management team.

Sarcoid of the nervous system.

Sarcoid is a granulomatous disease of undetermined etiology characterized by the presence of epithelioid cell aggregates without caseation which proceeds to conversion to hyaline fibrous tissue or resolution. The sites of nervous system involvement include the meninges, cranial, and peripheral nerves, hypothalamus and pituitary gland, muscles, and, more rarely, brain and spinal cord parenchyma. In nervous system involvement there is usually cerebrospinal fluid lymphocytic pleocytosis and elevated protein but these findings are not specific. When other systems are involved with sarcoid the diagnosis of neurosarcoidosis is obvious. When an unusual neurological symptom complex presents, sarcoid should be considered. The author reviews the literature and presents 22 cases of sarcoid involvement of the nervous system.

Acute spinal epidural abscess.

Acute spinal epidural abscess is an uncommon disease. Recommended management has been mainly surgical. We recently treated three cases within 4 weeks. Lowered immune resistance played a role in two of the cases. We suggest that acquired immunodeficiency syndrome will increase the incidence of this uncommon entity and advise that acute spinal epidural abscess can be successfully treated by nonsurgical means in some cases.

Neurologic complications of cardiovascular diseases.

Neurocardiology considers the interrelationships between the circulatory and nervous systems. An appreciation of the anatomic relationship preceded the concept of the clinical relationship of the two systems. Epidemiologic studies link risk factors of the cardiovascular and nervous systems. Neurologic signs and symptoms are often the presenting indication of cardiovascular disease. Neurologic complications occur during the natural history of cardiovascular disease, during diagnostic evaluation, and in the treatment process. A knowledge of potential complications as well as their frequency will help the physician make ethical and valid recommendations to patients concerning their management. This article highlights some of the potential complications that may be encountered in the management of patients with cardiovascular diseases.

Evidence for recombination between two different immunological types of foot-and-mouth disease virus.

Recombination was observed between temperature-sensitive (ts) mutants of two immunological types of foot-and-mouth disease virus which were distinguishable by two marker characteristics in addition to their antigenic type. Putative ts+ recombinants were isolated and the segregation patterns of their marker characteristics examined. The results are discussed in terms of the origin of new sub-type strains.

A sensitive method for the detection and isolation of recombinants of foot-and-mouth disease virus.

Recombination between temperature-sensitive (ts) mutants of foot-and-mouth disease (FMD) virus was examined, using an infectious centre technique that was more sensitive (approx. 30-fold) than the conventional virus yield test. The test involved a brief incubation of the mixedly infected cells at the permissive temperature to allow recombination to occur followed by assay at the restrictive temperature to select for those cells in which recombination had occurred. With crosses involving widely separated mutations, as many as 28% of the infected cells produced presumptive recombinant plaques. Since each plaque was the result of an independent event, large numbers of different presumptive recombinants could be isolated for further study. Analysis of presumptive recombinant plaques from a variety of crosses showed that, in general, the virus produced had the properties expected of recombinants. An approximate correlation was found between genetic distance, as determined in the yield recombination test, and the percentage of recombinant infectious centres observed. The phenomenon was very sensitive to the balance between the input multiplicities of the two parent viruses and occurred very early in virus replication. The test has considerable potential for the study of genetic interactions in FMD virus, but it would be surprising if this potential was limited to picornaviruses.

A genetic recombination map of foot-and-mouth disease virus.

Sixty ts mutants were isolated from the Pacheco strain of type O foot-and-mouth disease virus after treatment with either 5-fluorouracil or hydroxylamine. The conditions affecting recombination and assay of the ts+ recombinants were standardized. Using two ts mutants resistant to guanidine, three-factor crosses, supported by two-factor crosses, located 34 of the mutations in a linear arrangement. The recombination frequencies between certain pairs of mutations were additive. The guanidine character of the two resistant mutants mapped as a single site mutation and was located near the middle of the map.

The potential of recombination for the production of foot-and-mouth disease virus vaccine strains.

Biological proof of recombination in foot-and-mouth disease virus has been provided by studies on a large suite of conditional lethal mutants and a recombination map of approximately 70 mutations has been produced. However, recombination is a highly variable phenomenon and this has cast doubt on its validity and certainly on its applicability to such practical purposes as the production of good vaccine strains. Evidence is presented to demonstrate (1) that the genetic map has a good correlation with the biochemical map of polypeptide coding sequence for the genome and (2) that recombinants can be isolated bearing biochemical and biological markers from both parents. Finally, the analysis of 36 recombinants from a cross involving a cattle-attenuated and a cattle-virulent virus is described. These results have enabled us to identify the location of biological properties such as a mouse virulence and good growth in BHK cells on the genome of these two parent viruses.