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Biomedical subjects

N E Cremer

Publications and source records attributed to N E Cremer.

At least 37 records · Page 2Linked to original sources

Viral antibodies in cerebrospinal fluid of multiple sclerosis and control patients: comparison between radioimmunoassay and conventional techniques.

Cerebrospinal fluid antibodies to measles, rubella, vaccinia, herpes simplex, and varicella-zoster viruses in four patient study groups (clinically definite multiple sclerosis [MS], early probable MS, optic neuritis, and control patients with other neurological diseases) were assayed by radioimmunoassay, complement fixation, hemagglutination-inhibition, or complement-enhanced plaque reduction methods. Antibodies were more frequently found and at higher dilutions by radioimmunoassay than by other techniques. Measles virus antibody, the most frequently found antibody, was present in the cerebrospinal fluid of 72% of MS patients and 5% of control patients. The differences between the numbers of MS patients and control patients with antibodies to other viruses were not as marked. Thus, 58% of MS patients versus 21% of control patients had antibody to rubella virus, 20 versus 3% had antibody to vaccinia virus, 50 versus 33% had antibody to herpes simplex virus, and 25 versus 8% had antibody to varicella virus. Sixty-seven percent of MS patients and 26% of control patients had antibodies to two or more viruses in their cerebrospinal fluid.

Adolescent↗

Analysis of antibody assay methods and classes of viral antibodies in serodiagnosis of cytomegalovirus infection.

Forty-nine serum pairs with antibody to cytomegalovirus (CMV) were evaluated for rises in antibody titer (greater than or equal to fourfold) by indirect hemagglutination (IHA) and complement fixation (CF), using a freeze-thaw antigen (FT) and a glycine extract antigen (GE). In this sample CF-FT detected more rises in antibody titer than did CF-GE. IHA detected the least number. The apparent reason for stationary antibody titers with CF-GE and IHA was the presence of high antibody titers in the first serum specimen. Separation of immunoglobulin classes of 20 serum pairs by sucrose gradient centrifugation indicated that these antibodies with IHA were of the immunoglobulin M (IgM) class and those with CF-GE were of the IgG class. By separation of immunoglobulin classes, rises in IgG CMV antibody titers were seen with IHA, rises not observed in the whole serum because of high IgM antibody titers in the first serum specimen. Absence of rises in antibody titers with CF-FT was due in part to too early sampling of the second serum specimen (less than 21 days) and in part to an apparent inability of some individuals to respond with antibody reactive with FT antigen. CF-GE and CF-FT antibodies of the IgM class were detected in some sera, usually in specimens collected more than 10 days after the onset of symptoms. Although reactive with CMV antigen, the specificity of these IgM antibodies in relation to rheumatoid factor requires clarification.

Adult↗

Role of rheumatoid factor in complement fixation and indirect hemagglutination tests for immunoglobulin M antibody to cytomegalovirus.

Absorption of immunoglobulin M (IgM)-rheumatoid factor (RF) from serum samples by reaction with insolubilized gamma globulin reduced the complement-fixing (CF) antibody titer to cytomegalovirus (CMV) antigen to less than 1:2 in the IgM fraction of some, but not all, sera. Thus, IgM-CF activity in some sera appeared to be due to specific IgM anti-CMV antibody and in other sera to complexes of IgM-RF with antiviral IgG antibody. Prozones were present in the CF tests on IgM fractions. Increasing the concentration of antigen from 2 to 4 U reduced the prozone titer by one or two double dilutions. This observation suggested that a competition for antigen may be operating at low dilutions of IgM antibody fractions. Removal of RF had little or no effect on the reaction of the IgM fraction of sera with CMV by the indirect hemagglutination test.

Absorption↗

Acute optic neuritis: a virological study in relation to multiple sclerosis.

Previous ultrastructural examination of peripheral blood lymphocytes revealed the presence of intranuclear filamentous structures in multiple sclerosis (MS) and in some optic neuritis (ON) patients. The present investigation was undertaken in the attempt to correlate the presence of such structures with the etiology of ON and MS and possibly to demonstrate the viral origin of the filaments. Suitable virological and serological techniques were used to detect and isolate infectious agents from peripheral blood samples and body excretions of 12 monosymptomatic ON patients at their first acute attack. Nevertheless, any efforts to demonstrate the presence of a virus in these patients have been unsuccessful: no evidence of active viral infection was obtained by serological studies of serum and cerebrospinal fluid samples, nor could viral antigens or inclusions be observed by immunofluorescence and cytochemical analysis. Negative results were also obtained from studies performed in parallel on MS patients and various controls. The significance of the failure to isolate infectious agents from either ON and MS patients is discussed.

Acute Disease↗

Complications and immunological studies of measles virus infection in antithymocyte-treated hamsters.

A study was done to investigate possible late central nervous system (CNS) complications of latent measles infection in hamsters. Signs of CNS disease, consisting of myoclonus and paralysis, occurred in some weanling hamsters inoculated intraperitoneally at 3 or 9 days of age with antithymocyte serum (ATS) and measles virus, but no late complications in adult life attributable to measles virus were seen. A single series of ATS injections plus an injection of measles virus resulted in sustained antibody formation postulated due to establishment of a latent viral infection, whereas similar treatment with normal rabbit serum plus virus caused no or minimal antibody response. The majority of hamsters receiving ATS as newborns and ATS plus virus as weanlings also did not produce antibody. This differential effect of ATS may be due to combined elimination of suppressor and helper cells in the latter ATS-treated group and of suppressor cells only in the former ATS-treated group. Cellular immunity could not be evaluated since lymphocytes from inoculated and uninoculated hamsters released equal and variable amounts of 51Cr for both infected and noninfected labeled, allogeneic hamster target cells.

Animals↗

Viruslike particles in muscle from a patient with amyotrophic lateral sclerosis.

An electron microscopic study of muscle and central nervous tissue from a case of amyotrophic lateral sclerosis showed crystalline arrays of 20 to 24 nm viruslike particles in muscle. The particles were located between the myofibrils, adjacent to the Z bands, and near the perinuclear region, but were never seen within the nucleus. Cell cultures from the same muscle specimens showed no such particles. Central nervous system tissues and cultures also failed to show viruslike particles. The cultures were negative by the indirect fluorescent antibody technique with serums from patients with amyotrophic lateral sclerosis. The nature of these particles or their relationship to amyotrophic lateral sclerosis is unknown.

Amylases↗

Progressive rubella panencephalitis. Late onset after congenital rubella.

In children with congenital rubella infection the deficits remain stable; neurologic deterioration after the first few years of life is not believed to occur. We have encountered three patients with a definite or presumptive diagnosis of congenital rubella, in whom a progressive neurologic illness developed that began in the second decade and was characterized by spasticity, ataxia, intellectual deterioration, and seizures. High antibody titers to rubella virus in serum and spinal fluid were present in two, and all had increased cerebrospinal-fluid protein and gamma globulin. Extensive attempts to recover a virus from brain and body fluids were unsuccessful. The brains of two patients showed a widespread, progressive, subacute panencephalitis mainly affecting white matter. These data suggest that rubella virus may be a cause of progressive panencephalitis.

Adolescent↗

Chronic progressive panencephalitis due to rubella virus simulating subacute sclerosing panencephalitis.

Late-onset chronic progressive panencephalitis developed in a 12-year-old boy with congenital rubella syndrome from whose brain rubella virus was isolated. Progressive dementia began at eight, and ataxia, choreiform movements, myoclonic seizures, and fine perimacular pigmentation appeared at 11 years of age. The cerebrospinal fluid was minimally pleocytotic and had a total protein of 156 mg per deciliter, of which 52 per cent was gamma globulin. Electroencephalography demonstrated generalized medium and occasional high-voltage slowing without burst suppression. The antibody titer to rubella virus (hemagglutination inhibition) was 1:8192 in serum and 1:256 in cerebrospinal fluid. Antibody titer to measles virus (complement fixation) was less than 1:8 in serum. Microscopical study of biopsied brain tissue at the age of 11 disclosed panencephalitis similar to subacute sclerosing panencephalitis, but with perivascular deposits and without inclusion bodies. Rubella virus was isolated from the brain by cocultivation with CV-1 cells.

Antibodies, Viral↗

In vitro activation, infectivity, and production of endogenous type-C virus from OM rats.

T24C, a continuous cell line derived from the pooled thymic tissue of normal inbred OM rats, spontaneously produced type-C virus. The virus genome was expressed cyclically. The amount of RNA-dependent DNA polymerase (RDP) and the number of 1.14 g dense particles/ml fluctuated simultaneously with cultivation. The released virus, RPT24C, did not infect cell lines from the rat, mouse, dog, or human. T31, also a rat thymus line, during its 2.5 years of cultivation did not produce type-C virus. Cocultivation with potentially permissive lines did not rescue any virus. 5-lodo-2'-deoxyuridine treatments at earlier passages yielded negative results. Chemical treatment at passages 111, 116, 123, and 128 yielded varying amounts of 3H-uridine incorporation at a sucrose density of 1.14 g/ml. Enzyme assays on chemically treated T31 cultures tested at passage 111 showed a small but transient burst of RDP activity. T31-B, a subline of T31, which was frozen and thawed once, released rat type-C virus spontaneously at passage 56. Two additional sublines of T31 (NI-T31 and NII-T31) were maintained for 2.5 years in culture without any cell-dispersing treatment. NI-T31, but not NII-T31, spontaneously released type-C virus. Once induced, the type-C viruses from T31-B and NI-T31 were continuously produced.

Animals↗

Tubular particles in a case of recurrent lymphocytic meningitis followed by amyotrophic lateral sclerosis.

A patient suffered recurrent episodes of aseptic lymphocytic meningitis for many years and then developed amyotrophic lateral sclerosis (ALS). Immune-complexes were deposited in the renal glomerular basement membrane and mesangia. The necropsy study revealed both lymphocytic meningitis and ALS. Study of the motor neurons with the electron microscope revealed proliferation of endoplasmic reticulum, small cytoplasmolytic areas and focal neurofibrillar accumulations in axons. Interwoven, serpentine 10-15 nm. tubules first appeared with ER proliferation and, presumably at a later stage, were sometimes present in large masses. These tubules might be virus material but virus cultures, including tissue culture, and animal inoculations have thus far been negative.

Amyotrophic Lateral Sclerosis↗

Isolation of rubella virus from brain in chronic progressive panencephalitis.

Rubella virus was isolated from the brain of a congenitally-infected, 12-year-old child in whom progressive mental and motor deterioration became evident at age 8 and 11 years respectively. The virus was initially isolated in a co-culture of CV-I cells with the trypsinized brain tissue; subsequently the culture of the brain tissue also showed evidence of rubella virus infection recognized by indirect fluorescent antibody technique (IFA) using anti-rubella virus antibody prepared in rabbits as intermediate serum. Both isolates interfered with infection of BSC-I cell lines by echovirus type II. The interfering virus was identified as rubella virus by IFA with the specific antiserum, and it is designated as the NTr strain of rubella virus. The complement fixing antibody titre to rubella virus in serum was I:256. The spinal fluid was anticomplementary. Rubella virus haemagglutinating antibody titre (HI) in serum was I:8196 and in the spinal fluid I:128. The HI antibody was of the IgG class. The corresponding HI titres to rubeola virus in serum and spinal fluid were I:8 and less than I:2 respectively.

Antibodies, Viral↗

Complement-fixing antibody in human sera reactive with viral and soluble antigens of cytomegalovirus.

Antibody titers to cytomegalovirus were determined in 204 single-serum specimens and in 138 serum pairs, utilizing as antigen extracts of infected cells prepared by either freezing and thawing cells (FT antigen) or extracting them with a glycine buffer (GE antigen). With the serum pairs, 40% of the early sera and 44% of the late sera showed a fourfold or higher antibody titer with the GE antigen compared with those with the FT antigen, whereas 39% of the single sera had a fourfold or higher titer with the GE antigen. Sucrose density gradient centrifugation of the two antigen preparations indicated that the GE antigen contained two peaks of complement-fixing activity, one at a density of 1.18 to 1.22 g/cm3 and one at 1.06 to 1.10 g/cm3. The FT antigen had only one discernible peak of complement-fixing activity at 1.04 to 1.10 g/cm3. On electron microscopy, the more dense peak contained mainly nucleocapsids with some dense bodies and occasional enveloped virions, and the lighter peak was composed of amorphous material. Antibody titers obtained with the crude GE antigen and the more dense peak (designated viral antigen) were in agreement, whereas titers with the FT antigen agreed with those obtained with the lighter peak (soluble antigen). The antibody detected with both antigens was mainly immunoglobulin G.

Antibodies, Viral↗

Old dog encephalitis and demyelinating diseases in man.

Pathologic findings in mature dogs with old dog encephalitis were compared with the findings in multiple sclerosis, subacute sclerosing panencephalitis and neuromyelitis optica in man. Fluorescent antibody studies in animal and human tissues were compared. Optic neuritis in dogs with chronic distemper shows changes similar to those in the optic tract of human patients with severe demyelinating disease. The pathologic changes in multiple sclerosis, such as perivascular infiltration with lymphocytes, plasma cells and demyelination are similar to those seen in old dog encephalitis. Demyelination in old dog encephalitis is usually diffuse. The findings strongly support a possible relationship of old dog encephalitis to multiple sclerosis, subacute sclerosing panencephalitis, and neuromyelitis optica.

Animals↗

Atypical demyelinating disease.

A 17 year old girl died after an illness characterized by progressive mental deterioration and severe myoclonic jerks. Extensive pathological, virological, and immunological studies failed to support the diagnosis of subacute sclerosing panencephalitis but were compatible with disseminated demyelinating disease. The spinal fluid was positive for measles virus antibodies when examined by the fluorescent antibody technique, by complement fixation, and by haemagglutination inhibition tests, but the antibody titres were not high. The concentration of vaccinia antibody in the serum was consistent with that found in the general population and none was detected in the spinal fluid. Animal and tissue culture studies failed to disclose a viral agent, but pathological sections revealed perivascular cellular infiltration, demyelination, rare inclusion bodies, and multinucleated giant cells. Although these studies were not definitive, a record of procedures used and results obtained, both positive and negative, may be helpful to other investigators interested in defining more accurately the clinical features and the pathogenesis of these diseases.

Adolescent↗