Structural polypeptides of Orthopoxvirus: their distribution in various members and location within the virion

The structural polypeptides of accepted species and recently isolated members of the genus Orthopoxvirus have been examined by SDS-polyacrylamide gel electrophoresis. The viruses shared many polypeptides but some differences were found. The viruses could be divided into a vaccinia group (including buffalopox, 'Lenny' and MK-10), an ectromelia group (including elephant virus and Moscow virus), cowpox, camelpox and monkeypox. Minor differences were found in the polypeptides of monkeypox virus strains from human and monkey outbreaks. Controlled degradation of virions showed that the polypeptides which enabled the viruses to be differentiated were located in the surface and sub-surface layers. The cores of the viruses all gave the same complex polypeptide pattern.     

Genomic instability in scleroderma

Scleroderma is an enigmatic rheumatic disorder of uncertain etio-pathogenesis. Cancer has an approximately two-fold higher incidence in scleroderma patients than in the general population. There are preliminary data of acquired genetic damage in scleroderma but the significance of these observations are uncertain. To determine somatic mutation frequency at the glycophorin-A (GPA) locus in patients with limited and diffuse cutaneous scleroderma. The GPA assay measures the total somatic mutation frequency (Vf), composed of gene inactivating mutations (NO) and mutations arising from mitotic recombination (NN) in individuals heterozygous for the GPA MN blood group. Mutation frequency was determined using a validated GPA flow cytometric assay using fluorescent labeled monoclonal antibodies specific for the GPA blood groups M and N. This assay detects and enumerates progeny of red blood cell (rbc) precursor cells which have acquired genetic damage resulting in a loss of expression of one of the GPA alleles. It was found that patients with scleroderma (n = 23) had significantly elevated Vf as compared with young healthy controls (p < 0.001) and elderly controls (p = 0.03). Patients with diffuse scleroderma had higher mean Vf as compared with limited scleroderma (p = 0.055). In comparison with controls, patients with scleroderma exhibit a higher proportion of mitotic recombinant mutations than inactivating mutations (p < 0.002). There was no correlation between Vf and disease duration, age at onset or autoantibody status. We have documented evidence of acquired genetic damage at the GPA locus in scleroderma. Evidence of acquired genetic damage in this disorder may be importance in explaining both the etio-pathogenesis of scleroderma and the association of scleroderma with cancer.     

Purification and characterisation of membrane-form variant surface glycoproteins of Trypanosoma brucei

Membrane-form variant surface glycoprotein of Trypanosoma brucei can be prepared in the presence of para-chloromercuriphenylsulphonic acid. The membrane-bound enzyme that usually cleaves a lipid from this glycoprotein, thus producing the soluble variant surface glycoprotein, is inhibited by a range of sulphydryl reagents. The effect of such inhibitors, both on cell lysates and on semi-purified enzyme, reveals that the enzyme may have a sulphydryl at or near its active site. Fatty acid analysis and isoelectric point measurements of membrane form and soluble form are presented.     

Interaction of mouse peritoneal macrophages with fixed rabies virus in vivo and in vitro.

The resistance of mice to intraperitoneal and intramuscular infection with fixed rabies virus increases with age. Treatment of mature animals with either silica, indian ink or antimacrophage serum, which are cytotoxic for macrophages, reduced their resistance to intraperitoneal, but not to intramuscular or intracerebral infection. Transfer of peritoneal macrophages from adults to syngeneic suckling mice delayed but did not prevent mortality from intraperitoneal infection: transfer of peritoneal macrophages to intramuscular sites of infection did not protect adult mice. Rabies virus was phagocytosed by peritoneal macrophages in culture but neither replicated nor induced interferon. Evidence of active intracellular destruction of virus was obscured by thermal inactivation at 37 degrees C. Less inactivation occurred at 33 degrees C. Infected macrophages from suckling mice, but not those from adult mice, spread infection to susceptible cells.     

Spontaneous pallidal neuronal activity in human dystonia: comparison with Parkinson's disease and normal macaque

Dystonia is a movement disorder defined by sustained muscle contractions, causing twisting and repetitive movements and abnormal postures. To understand the abnormalities in pallidal discharge in dystonia, we have analyzed the spontaneous activity of 453 neurons sampled from the internal or external pallidum (GPi or GPe) of 22 patients with dystonia, 140 neurons from 11 patients with Parkinson's disease (PD), and 157 neurons from two normal non-human primates (NHPs; Macacca mulatta). All recordings were performed without systemic sedation. Mean GPi discharge rate in dystonia was 55.3 +/- 1.3 (SE) Hz. This was significantly lower than in the normal NHPs (82.5 +/-2.5 Hz) and lower than in PD patients (95.2 +/- 2.3 Hz). Mean GPe discharge rate in dystonia (54.0 +/- 1.9 Hz) was lower than in the normal NHPs (69.7 +/- 3.3 Hz) and was indistinguishable from that in PD patients (56.6 +/- 3.5 Hz). Mean GPi discharge rate was inversely correlated with dystonia severity. GPi showed increased oscillatory activity in the 2- to 10-Hz range and increased bursting activity in both dystonia and PD as compared with the normal NHPs. Because the abnormalities in discharge patterns were similar in dystonia compared with PD, we suggest that bursting and oscillatory activity superimposed on a high background discharge rate are associated with parkinsonism, whereas similar bursting and oscillations superimposed on a lower discharge rate are associated with dystonia. Our findings are most consistent with a model of dystonia pathophysiology in which the two striatal cell populations contributing to the direct and indirect intrinsic pathways of the basal ganglia both have increased spontaneous activity.     

Plasma insulin and lipid levels in untreated obstructive sleep apnoea and snoring; their comparison with matched controls and response to treatment

SUMMARY  Obstructive sleep apnoea (OSA), and snoring are associated with coronary heart disease. To assess whether OSA or snoring may contribute to this by raising fasting lipid or insulin levels, venous fasting total cholesterol, triglyceride, very-low-density lipoprotein, low-density lipoprotein, high-density lipoprotein, and insulin were measured in 15 untreated OSA patients and 18 snorers. Each of these subjects was individually matched to a control of the same sex, age ± 10%, body index ± 15%, smoking and drinking habits. This produced study groups which did not differ significantly by any of these criteria. Fasting venous blood samples were collected at 06.30 hours following polysomnography, and analysed blind of the subjects respiratory status. The OSA patients were then treated with nasal continuous positive airway pressure. In 10 of these subjects lipid and insulin levels were repeated after more than three months treatment. Lipid and insulin levels were also remeasured in the controls matched to these 10 subjects. The end points were compared with paired t -tests.
There was no difference in any of the end points when the untreated OSA patients and the snorers were compared to their matched controls ( P >0.25 for all comparisons), and none of the indices changed when OSA was corrected with nasal continuous positive airway pressure ( P > 0.25 for all comparisons).
Patients with obstructive sleep apnoea or snoring do not have significant fasting hyperlipidaemia or hyperinsulinaemia when compared to carefully matched controls. These factors are therefore unlikely to be the cause of the excess cardiovascular mortality experienced by this patient group.     

Differential diagnosis of HTLV-I-associated myelopathy and multiple sclerosis in Iranian patients

Summary Two Iranian patients with chronic progressive spastic paraparesis and urinary dysfunction were referred to our hospital with the presumptive diagnosis of multiple sclerosis (MS). Routine CSF analysis and magnetic resonance imaging of the two patients were only partially characteristic of MS. Testing for antibodies to human T-cell leukemia virus type I [HTLV-1] in serum using a radioimmune precipitation assay revealed antibodies to HTLV-I in both patients. The infection with HTLV-I was confirmed by polymerase chain reaction (PCR) and liquid hybridization analysis using primers to the tax/rex region and a corresponding probe, demonstrating proviral DNA in peripheral blood mononuclear cells of both patients. On the basis of these findings demonstrating the presence of proviral HTLV-1 DNA in the two Iranian patients, the initial diagnosis of MS was corrected to that of HTLV-I-associated myelopathy (HAM). In contrast, several patients with definite MS (nine from Germany, two from Iran) with a relapsing and remitting form of the disease were tested for HTLV-1 infection by enzyme-linked immunosorbent assay and PCR, which yielded negative results. However, the mother of one HAM patient was found to be infected with HTLV-I. To support an association between HTLV-I infection and CNS disease in the two HAM patients, we analyzed the production of specific IgG antibodies within the CNS based on a simple enzyme immunoassay for viral IgG antibodies in CSF and serum. In the two HAM patients there was significant intrathecal antibody production directed against HTLV-I, but this was not found in any of the samples from MS patients. These findings demonstrate an immune reaction to HTLV-I in the CNS of HAM patients, thus confirming the association of infection and CNS disease. The demonstration of intrathecal HTLV-I antibody production also proved useful for the differential diagnosis of MS or HAM, especially in patients from areas endemic for HTLV-I.Abbreviations DTPA diethylenetriaminepentaacetic acid - ELISA enzyme-linked immunosorbent assay - HAM HTLV-I-associated myelopathy - HTLV-I human T-cell leukemia virus type I - MRI magnetic resonance imaging - MS multiple sclerosis - PBMC peripheral blood mononuclear cells - PCR polymerase chain reaction - RIPA radioimmune precipitation assay - SDS sodium dodecyl sulfate - TSP tropical spastic paraparesis     

Relation between raised concentrations of fucose, sialic acid, and acute phase proteins in serum from patients with cancer: choosing suitable serum glycoprotein markers.

Serum concentrations of fucose, sialic acid, and eight acute phase proteins were measured in single specimens from patients with cancer in order to determine whether the raised concentrations of protein bound sugars commonly found in cancer correlate with increased concentrations of the acute phase proteins. Strong positive correlations were found only with alpha 1-acid glycoprotein, alpha 1-antitrypsin, and haptoglobins. Changes in protein bound sugars and acute phase proteins were also examined in relation to patients' disease states. Serum fucose was raised more often in patients with advanced disease than in those in whom the spread of the tumour was more restricted; increased sialic acid concentrations, however, were found with a similar frequency in both these groups. Combined use of fucose and sialic acid values gave a high degree of marker positivity which could be only slightly improved on by including measurement of acute phase proteins. The combined use of serum fucose and sialic acid concentrations may have value in monitoring patients with cancer: the sialic acid provides an index of the acute phase response and the fucose a measure of the tumour spread.     

Self-report screening measures for depression in chronic pain patients

Depression is prevalent among chronic pain patients, yet little is known about the ability of various self-report measures to detect this disorder in this population. This study investigated the relationship of several self-report depression scales (Beck Depression Inventory-standard and short forms, MMPI Depression, Depression subtle, and Depression obvious scales, and the Zung Self-Rating Depression Scale) to clinician DSM-III diagnoses of major depressive disorder in 40 chronic pain patients. Thirty percent of the Ss met criteria for major depression. Sensitivity and specificity values obtained for each scale are presented. The standard and short forms of the Beck Depression Inventory and the Zung Self-Rating Depression Scale showed good sensitivity and specificity and were comparable in detecting major depression in this sample.