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Biomedical subjects

J Sever

Publications and source records attributed to J Sever.

At least 37 records · Page 2Linked to original sources

A long-term follow-up study of patients with post-poliomyelitis neuromuscular symptoms.

A "post-polio" syndrome characterized by new neuromuscular symptoms, including muscle weakness, may develop years after recovery from acute paralytic poliomyelitis. We studied 27 patients (mean age, 50.6 years) in whom new muscle weakness developed a mean of 28.8 years after recovery from acute polio. We reevaluated these patients during a mean follow-up period of 8.2 years (range, 4.5 to 20) after they were originally studied at the National Institutes of Health. The total mean follow-up period after the onset of new weakness was 12.2 years (range, 6 to 29). The patients were assessed with quantitative muscle testing, muscle biopsy, electromyography, and virologic and immunologic examination of the cerebrospinal fluid. Muscle strength had declined in all patients. The rate of decline averaged 1 percent per year. The decrease was irregular, with subjective plateau periods that ranged from 1 to 10 years. None of the patients had amyotrophic lateral sclerosis. Oligoclonal bands (IgG) were found in the cerebrospinal fluid of 7 of 13 patients studied, but no specific elevation of antibodies to poliovirus was observed in the cerebrospinal fluid. The newly affected muscles that were evaluated longitudinally with follow-up muscle biopsies and electromyography showed signs of chronic and new denervation. Groups of atrophic muscle fibers (group atrophy) and "neurogenic jitter" were not present. New post-polio muscle weakness is not a life-threatening form of motor-neuron deterioration. It appears that this weakness is not due to a loss of whole motor neurons, as in amyotrophic lateral sclerosis, but that it is due to a dysfunction of the surviving motor neurons that causes a slow disintegration of the terminals of individual nerve axons.

Adult↗

Establishment of a line of human fetal glial cells that supports JC virus multiplication.

Primary cultures of human fetal brain cells were transfected with plasmid DNA pMK16, containing an origin-defective mutant of simian virus 40 (SV40). Several weeks after DNA treatment, proliferation of glial cells was evident in the culture, allowing passage of the cells at low split ratios. Initially, only 10% of the cells demonstrated nuclear fluorescence staining using a hamster tumor antibody to the SV40 T protein. By the sixth passage, however, 100% of the cells reacted positively to the same antibody. During these early passages, the cells designated SVG began growing very rapidly and acquired a homogeneous morphology. Cell division required only low serum concentrations, was not contact-inhibited, and remained anchorage dependent. These characteristics of the SVG cells have been stable through 25 passages or approximately equal to 80 cell generations. The SV40 T protein is continuously produced in the cells and can direct the replication of DNA inserts in the pSV2 vector, determined by in situ hybridization using biotin-labeled DNA probes, which contains the SV40 replication origin. More importantly, SVG cells support the multiplication of the human papovavirus JCV at levels comparable to primary cultures of human fetal glial cells, producing infectious virus as early as 1 week after viral adsorption. Their brain-cell derivation has been established as astroglial, based on their reactivity with a monoclonal antibody to glial fibrillary acid protein and lack of activity with an anti-galactocerebroside antibody, which identifies oligodendroglial cells. The SVG cells represent a unique line of continuous rapidly growing human fetal astroglial cells that synthesizes a replication-proficient SV40 T protein. Their susceptibility to JC virus (JCV) infection obviates a host restriction barrier that limited JCV studies to primary cultures of human fetal brain and thus should allow for more detailed molecular studies of human brain cells and JCV that infects them.

Antigens, Polyomavirus Transforming↗

Viral antibodies in twins with multiple sclerosis.

Viral antibodies to measles, rubella, corona, vaccinia, and mumps viruses in serum and CSF (and to Epstein-Barr virus in serum only) were studied in 24 twin pairs, both discordant and concordant for clinical MS. In pairs, CSF antibody titers for rubella in MS monozygotic and dizygotic twins and for vaccinia in dizygotic twins were higher than for unaffected twins. Increased CSF titers among MS twins existed for measles, rubella, and vaccinia when pairing was ignored. Among MS twins, serum rubella and measles and CSF measles antibody titers, and CSF:serum ratios for measles virus, were higher in those who were DW2 positive.

Antibodies, Viral↗

CSF oligoclonal bands, immunoglobulins, and viral antibodies in progressive myoclonus epilepsy.

We studied CSF and serum samples from 16 patients with progressive myoclonus epilepsy (PME). These patients had juvenile-onset PME with evidence of autosomal recessive inheritance and no Lafora bodies. Twelve of the 16 patients with PME had immunologic abnormalities. Oligoclonal gamma bands were seen in six of the eight patients from whom sufficient CSF was available. The CSF albumin and serum/CSF albumin ratios were normal in all 16 patients, indicating the presence of intact blood-brain barriers. Six of the 16 patients showed increased CSF IgG levels and five had an increased CNS IgG synthesis. All patients had normal serum and CSF IgM and IgA levels. Three patients, all with bands, had reduced measles and/or vaccinia serum/CSF antibody ratios. The findings suggest altered immune response of the CNS of some patients with PME apparently caused by nonspecific immunostimulation.

Adolescent↗

Familial multiple sclerosis: clinical, histocompatibility, and viral serological studies.

Evaluation of presumed "multiple sclerosis families" and comparison with recently reported families has led us to the following observations: (1) Seven of our original fourteen presumptive multiple sclerosis families had to be eliminated after personal clinical evaluation of family members failed to confirm the diagnosis in a second close relative. (2) No segregation of HLA type was noted between affected and unaffected individuals in our seven bona fide multiple sclerosis families, and no consistent segregation was noted in the twenty-eight families reported elsewhere. This supports other genetic evidence that there is not a single, major gene mapping in the HLA complex which predisposes to multiple sclerosis. (3) The DW2 antigen was increased in frequency among affected members of our families, and the A3 B7 haplotype was more frequent among affected members of other families reported. But unaffected members also tended to have an increased frequency of these same antigens. (4) No relationship was noted between HLA type and antimeasles antibody titer within our families.

Antibodies, Viral↗

Colposcopic examination of the cervix of cebus monkeys.

A total of 410 colposcopic examinations were performed on 188 female cebus monkeys that were under study to determine the oncogenic potential of herpes simplex virus type 2 in this genus. A split-cone vaginal speculum was developed that permitted good observation of the vaginal cervix in the cebus monkey. The cervical anatomy of cebus monkeys was found to differ from that of humans in that the surface of the animal cervix was more papilliform, with thinner squamous epithelium, and the squamocolumnar junction lay within the endocervical canal. Therefore, the ability to detect abnormalities in the cervical epithelium by colposcopic examination in the cebus monkey was restricted to vascular changes in the squamous epithelium. After 100 examinations, several vascular patterns were distinguishable and interpretations of these patterns were compared with cytologic findings on the same animals. Findings by both cytology and colposcopy were mild in nature; no carcinoma was detected. Colposcopic and cytologic findings correlated at a level of 84%. More abnormalities were detected with colposcopy than with use of cytologic techniques.

Animals↗

Swine influenza virus vaccination in patients with multiple sclerosis.

A double-blind, placebo-controlled study was conducted to evaluate the safety and efficacy of inactivated influenza virus vaccines in patients with multiple sclerosis. The vaccine used contained 200 chick cell-agglutinating (CCA) units of influenza A/New Jersey/76 and 200 CCA units of influenza A/Victoria/75 whole viruses (Merrell-National Laboratories, Cincinnati, Ohio). The frequency of clinical relapses of multiple sclerosis was the same in the vaccine-treated (four of 33 patients) and placebo-treated (four of 33) groups. An untreated control group had a slightly higher rate of relapses (four of 22). Toxic reactions to the vaccine were not a significant problem. The efficacy of the vaccination as measured by titers of hemagglutination-inhibiting antibody was comparable to that reported for the general population. However, patients with preexisting antibody were less responsive to the vaccine than normal controls studied previously. The patients who did not respond to the vaccine tended to be older and more disabled. There were no changes in titers of antibody to rubeola or rubella virus after vaccination or in relation to change in clinical course. It is concluded that the vaccine is safe and effective in patients with multiple sclerosis.

Antibodies, Viral↗

Crystals, paracrystals, and rigid tubules in multiple sclerotic brain and spinal fluid.

Brain and spinal fluid were obtained post mortem from an individual with multiple sclerosis who died following carbon monoxide inhalation. Electron microscopic examination of the plaque region revealed a crystalline structure (repeat unit 380 to 410 A) within rough endoplasmic reticulum of astrocytes, a paracrystal (160 to 220 A) within the cytoplasm of astrocytes, and rigid tubules (outer diameter 320 to 450 A) within a cell in the lumen of a capillary. The paracrystal was enclosed by the glial fibrils. A second crystalline material was observed within cells in the 15,000 X g pellet from spinal fluid. The ultrastructural pattern of this second crystal was generated by three sets of parallel lines; a given set was intersected by the other two sets. The crystal had only two different repeat units (410 to 450 A; 310 to 350 A) since the smaller dimension was common for two sets of lines. The two crystals were large; the one in astrocytes had a length of 52,000 A and that in spinal fluid sediment was 62,000 A. These structures were observed in the one multiple sclerotic brain obtained at autopsy but were not detected in multiple sclerotic brains that had been frozen for extended periods. Plaque regions and grossly normal white matter were homogenized and the 1000 X g supernatant of this material was fractionated in a continuous CsCl-sucrose density gradient. Long tubules (320 to 500 A diameter) were observed in the 1.24 to 1.26 density region. The major proteins of the 1.24 to 1.26 fraction had molecular weights clustered at 40,000 to 45,000, 88,000 to 130,000, and 300,000.

Astrocytes↗

Fatty alcohols (normal and isoprenoid) in sediments.

Normal long-chain alcohols were isolated from Recent marine sediments from several environments. The isoprenoid alcohol dihydrophytol, which is thought to originate from phytol, the side chain of chlorophyll, by hydrogenation in the reducing environment of the sediment, was also present in most of the samples. Both the normal and isoprenoid alcohols were found in the Green River shale (Eocene). Geochemical implications are considered.

Alcohols↗