SPECT and cerebrovascular accidents.
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Cerebrovascular Disorders↗
Biomedical subjects
W R Slade
Publications and source records attributed to W R Slade.
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.
Abscess↗
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.
Aged↗
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.
Acquired Immunodeficiency Syndrome↗
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.
Anticoagulants↗
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.
Aphthovirus↗
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.
Aphthovirus↗
Recombination and oligonucleotide analysis of guanidine-resistant foot-and-mouth disease virus mutants.
Guanidine resistance (gr) mutations of foot-and-mouth disease virus were mapped by recombining pairs of temperature-sensitive mutants belonging to different subtypes. In each cross, one parent possessed a gr mutation. Recombinants were isolated by selection at the nonpermissive temperature and assayed for the ability to grow in the presence of guanidine. From the progeny of three crosses, four different types of recombinant were distinguished on the basis of protein composition and RNA fingerprint. The sequences of the RNase T1-resistant oligonucleotides were determined and located in the full-length sequence of foot-and-mouth disease virus. The resulting maps show that (i) each recombinant was generated by a single genetic crossover, and (ii) both of the gr mutations studied were located within an internal 2.9-kilobase region which spans the P34 gene. This supports our hypothesis that guanidine inhibits the growth of foot-and-mouth disease virus by acting on nonstructural polypeptide P34. Additional evidence was provided by RNA fingerprinting gr mutants. In two of four cases the gr mutation was associated with a change in an oligonucleotide located near the 3' end of the P34 gene; in one of these the nucleotide substitution was identified.
Aphthovirus↗
Effect of inhibition of purine enzymes on benzodiazepine binding in the human brain.
Since inosine is an inhibitory ligand for benzodiazepine binding, and since several of the purine enzymes have a specific localization, it was hypothesized that the unique distribution of benzodiazepine receptors may be dependent on the regional concentrations and specific actions of these enzymes in increasing or decreasing the amount of inosine. To test the above theory, the binding of 3H-flunitrazepam to receptors was studied on homogenates of various regions of autopsied human brain before and after treatment with irreversible potent inhibitors of the purine enzymes guanine deaminase and adenosine deaminase. As predicted, inhibition of guanase, which metabolizes guanine and hypoxanthine to xanthine, caused a marked inhibition of binding in the cerebral cortex and midbrain, where there is an abundance of enzyme, and only slight change in binding in the medulla, cerebellum or pons, where there is little enzyme. When adenosine deaminase, which converts adenosine to inosine, was inhibited, there was increased binding, with as much as a 4-fold increase in the frontal lobe, and very little effect in the cerebellum, medulla or temporal lobe.
Adenine↗
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.
Anticoagulants↗
Recombination in RNA.
The aphthovirus genome consists of a single molecule of single-stranded RNA that encodes all the virus-induced proteins. We isolated recombinant aphthoviruses from cells simultaneously infected with temperature-sensitive mutants of two different subtype strains. Analysis of the proteins induced by 16 independently generated recombinants revealed two types of protein pattern, which were consistent with single genetic crossovers on the 5' side and 3' side, respectively, of the central P34-coding region. Recombinants invariably inherited all four coat proteins from the same parent, and novel recombinant proteins were not observed. RNAase T1 fingerprints of virus RNA, prepared from representatives of each recombinant type, confirmed the approximate crossover sites that had been deduced from the inheritance of proteins. These fingerprints provide molecular evidence of recombination at the level of RNA and demonstrate the potential of RNA recombination for producing genetic diversity among picornaviruses.
Aphthovirus↗
Biochemical evidence of recombination within the unsegmented RNA genome of aphthovirus.
Four different pairs of temperature-sensitive mutants, derived from the same strain of aphthovirus, were crossed by using an infectious center recombination test. Each parental mutant carried an unselected marker affecting the isoelectric point of a virus-coded polypeptide; progeny of the crosses, able to grow at the nonpermissive temperature, were screened for these unselected markers. Polypeptide charge was shown to be a stable, inheritable character, and three of the four crosses yielded genetic recombinants that possessed the polypeptide marker from both parents. Peptide fingerprinting and high-resolution isoelectric focusing of the polypeptides ruled out the explantation that these viruses were generated by mutation.
Aphthovirus↗
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.
Animals↗
Effect of mutation on the virulence in mice of a strain of foot-and-mouth disease virus.
Twenty-eight mutations, representing mutation in five different polypeptide-coding regions of the foot-and-mouth disease genome, were examined for their effect on the virulence of the virus for suckling mice. Five types of mutation were examined: temperature-sensitive (ts), electrophoretic (e), co-variant temperature-sensitive and electrophoretic (ts/e), guanidine-resistant (gs+) and putative co-variant guanidine-resistant and electrophoretic (gs+/e). All the ts mutations and three out of the 11 non-ts mutations produced some reductions in virulence. In the majority of cases this reduction in virulence was shown to co-vary with the mutation. No correlation was observed between the site of a mutation or its 'cut-off' temperature and the extent of the reduction in virulence. Studies of the growth in vivo of a small selection of ts mutants suggested that for most mutants their reduced virulence was a trivial effect of their slow growth rate. With one exception they all eventually grew to parental virus levels, the resulting virus being temperature-sensitive and the disease indistinguishable from that caused by the parental virus. The one exception was an avirulent ts mutant which only grew to one-thousandth the titre of the parent virus. This mutant did not cause disease and was therefore considered to be the only avirulent mutant. Its mutation was in the coat protein-coding region of the genome, probably the region coding for VP3.
Animals↗
A simple, rapid, and sensitive method of determining CSF IgG, using latex.
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Humans↗
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.
Adult↗
Temperature-sensitive mutants of foot-and-mouth disease virus with altered structural polypeptides. II. Comparison of recombination and biochemical maps.
The structural polypeptides of foot-and-mouth disease virus were digested with Staphylococcus aureus V8 protease in the presence of sodium dodecyl sulfate. The protease-resistant peptides derived from temperature-sensitive mutants were compared with those of the wild type by electrofocusing in a polyacrylamide gel. Covariation between the charge shifts of different peptides indicated that they shared common sequences: only five independent peptides in all were derived from VP1, VP2, and VP3, accounting for approximately 50% of the polypeptide sequences. In two instances, amino acid substitutions that caused similar shifts in the isoelectric point were found to be located in different peptides. However, 15 mutants that possessed identical shifts in VP2 could not be distinguished by peptide analysis. The polypeptides of revertants able to grow at the nonpermissive temperature were compared with those of the parental mutants. By this test, 6 of the 12 distinguishable classes of coat protein mutations were found to covary with temperature sensitivity. In addition to true revertants, several phenotypic revertants which possessed a second charge change, either in a different structural polypeptide or in a different region of the same polypeptide, were isolated. The orientation of the recombination map was deduced from the loci of the coat protein mutations.
Amino Acid Sequence↗
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.
Animals↗