AIDS and the nervous system.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Wichman.
Explore the source record for details and available documents.
3'-Azido-2',3'-dideoxythymidine (AZT) has been administered to 7 patients with human immunodeficiency virus-associated neurological disease: 3 with dementia, 2 with peripheral neuropathy, 1 with dementia and peripheral neuropathy, and 1 with T-10 paraplegia. Six of the patients showed improvement in their neurological dysfunction on being administered AZT, as assessed by clinical evaluation, neuropsychological testing, nerve conduction studies, and/or positron emission tomographic scans. Three of these 6 patients showed sustained improvement 5 to 18 months after the initiation of AZT therapy. These results suggest that certain human immunodeficiency virus-associated neurological abnormalities are at least partially reversible following the administration of antiretroviral therapy and provide a rationale for further studies using antiretroviral chemotherapy.
Four patients with human-immuno-deficiency-virus-associated neurological disease were treated with 3'-azido-3'-deoxythymidine (AZT). Three (two with chronic dementia, and one with chronic dementia and peripheral neuropathy) improved as assessed by clinical examination, psychometric tests, nerve conduction studies, and/or positron emission tomography; there was no improvement in the fourth patient who presented with paraplegia. These results support the hypothesis that certain AIDS-virus-associated neurological abnormalities are reversible by antiretroviral chemotherapy.
Explore the source record for details and available documents.
Three different high-performance liquid chromatographic (HPLC) techniques, i.e., ion-exchange, hydrophobic interaction and hydroxyapatite chromatography, have been used to purify monoclonal antibodies from ascites fluid. The monoclonal antibodies were raised against coagulation factor VIII. Precipitation of the antibodies by ammonium sulphate prior to HPLC made it possible to purify the antibody in one chromatographic step. In sodium dodecyl sulphate-polyacrylamide gel electrophoresis this highly pure preparation revealed only one extra polypeptide besides the light- and heavy-chain immunoglobulin polypeptides. Attempts were also made to purify the antibody without prior ammonium sulphate precipitation. A combination of ion-exchange and hydrophobic interaction chromatography resulted in an antibody preparation comparable in purity to the one obtained from ammonium sulphate-precipitated immunoglobulin. The rapid HPLC techniques were found to be very useful for purification of monoclonal antibodies on a preparative scale, where sample loadings of up to 25 mg of ascites protein were fully resolved in satisfactory yields.
We report three sibling pairs with congenital cerebellar hypoplasia. All six children presented in the first years of life with delays in motor and language development. All patients showed cerebellar and/or vermal dysfunction and, on formal psychometric testing, cognitive abilities ranged from normal to moderately retarded. Abnormalities on CT scan ranged from prominent valleculla to an enlarged cisterna magna with hypoplasia of the cerebellar hemispheres and vermis. The pedigrees are consistent with autosomal recessive inheritance.
We evaluated seven patients with the hypereosinophilic syndrome (HES) to define the clinicopathologic spectrum of the peripheral neuropathy. Clinically, three had evident polyneuropathy; the others were asymptomatic, although they had electrophysiologic evidence of neuropathy. Nerve conduction studies and EMG were compatible with axonal neuropathy. Morphometry of sural nerves from four patients ranged from normal to marked axonal loss, more prominent in large myelinated fibers. Demyelination was rare, and there was no evidence of vasculitis. Neuropathy may be produced by an eosinophil-derived neurotoxin.
We studied the peripheral neuropathy of three sisters with abetalipoproteinemia. Clinically, a sensory neuropathy progressively increased in severity. There was a diminution in the amplitude of sensory action potentials and a slight-to-moderate slowing in maximum sensory conduction velocity, initially most marked in distal portions of the nerves. Motor conduction was normal, although EMG indicated subclinical signs of partial chronic denervation. The sural nerves showed a decreased number of large fibers (greater than 7 micron); in the patient with the neuropathy of shortest duration, small fibers and clusters of regenerating fibers indicated regeneration. In the two patients with advanced neuropathy, one-half the segments of teased fibers showed paranodal demyelination. Also, unmyelinated fibers showed evidence of regeneration.
An 18-year-old woman with headaches and visual abnormalities was found upon biopsy to have an occipital gliosarcoma, which was treated with irradiation and chemotherapy for a year. Cells in the gliosarcoma tissue were positive for GFAP. At necropsy, only the sarcoma was evident at the site of original surgical removal. The sarcoma had spread widely along meningeal routes, causing the patient's death. The biologic behavior and histologic features of the sarcoma were clearly malignant. Cells cultured from the biopsy specimen maintained features in common with sarcoma.
Human plasma low- and high-density lipoproteins were found to bind to Sepharose gels containing coupled cholesterol or cholic acid. The lipoproteins were bound very strongly, and it was not possible to elute them under non-denaturing conditions. The detergents Triton X-100 and sodium dodecyl sulphate eluted the lipoproteins in partly denatured form. Adsorbents were used where the steroid was coupled through a spacer containing a thiol ester bond. It was thus possible to elute bound lipoproteins by selective cleavage of the bond with hydroxylamine. A small proportion of albumin was the only contaminant detected, the amounts depending on which ligand was used. Low- and high-density lipoproteins were separated by gel filtration. They behaved as did the native molecules when analysed by gel filtration, immunodiffusion, immunoelectrophoresis and electrophoresis in polyacrylamide gradient gels. The high capacity and the selectivity of the adsorbents make them suitable for the removal of lipoproteins from protein solutions.
The kinetics of refolding of completely reduced human serum albumin has been studied by various methods including immunological techniques. The decrease in thiol content is very rapid in the beginning of the reoxidation process and rather slow in the later stages. Polyacrylamide gel electrophoresis studies show that, in the earlier stages of refolding, the main part of the albumin is present as various oligomers and that a slow conversion to monomer occurs as reoxidation proceeds. Rocket immunoelectrophoresis shows that the completely reduced protein is devoid of native albumin antigenic determinants but that a rapid regain of immunoprecipitability is obtained upon reoxidation. A new 'consumption' rocket immunoelectrophoretic method has been used to estimate the total regain of antigenicity. The data obtained indicate that there is a preferential rapid folding to native structure in certain parts of the molecule but that areas with wrong or incomplete foldings exist a considerable time after the inital refolding period.
The binding of hepatitis B surface antigen (HBSAg) to various matrix bound long-chain hydrocarbon structures has been studied. It was found that HBSAg was strongly bound to straight hydrocarbon chains with more than seven carbon atoms. The adsorbents can probably be used for removal and/or detection of hepatitis B infectious material.
Explore the source record for details and available documents.
Explore the source record for details and available documents.