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Biomedical subjects

C V Sumaya

Publications and source records attributed to C V Sumaya.

At least 37 records · Page 2Linked to original sources

Cerebrospinal fluid abnormalities in patients without AIDS who are seropositive for the human immunodeficiency virus.

Lumbar punctures were done on 114 consecutive active duty patients referred for evaluation of positive tests for antibodies to the human immunodeficiency virus (HIV). Eighty-eight percent of these patients appeared to have early HIV infections, as evidenced by intact delayed hypersensitivity, T helper lymphocyte counts greater than 400/mm3, and lack of constitutional symptoms. Forty-four (38.6%) of the patients met our criteria for abnormal cerebrospinal fluid (CSF); another 13 (11.4%) had borderline elevations of nucleated cells or protein and could not be definitely classified as having normal or abnormal CSF. No significant differences existed between the patients with normal and abnormal CSF with regard to age; sex; race; serum FTA-Abs; clinical staging; absolute T helper lymphocyte counts; or cytomegalovirus, Toxoplasma, or Epstein-Barr virus serologies. Seventy-two percent of the patients with abnormal CSF had evidence of possible viral infection of the central nervous system (CNS), as evidenced by increased CSF IgG, increased IgG synthesis rates, or the presence of oligoclonal bands. We found that a significant percentage of asymptomatic patients with apparent early HIV infections have abnormal CSF that is possibly due to CNS involvement by HIV.

Central Nervous System Diseases↗

Epstein-Barr virus infections in families: the role of children with infectious mononucleosis.

We performed a prospective evaluation of Epstein-Barr virus (EBV) infections in 78 families with a childhood index case of EBV-infectious mononucleosis (EBV-IM). During the acute index episode, adult family (household) contacts, compared with control adults, had a greater rate of oropharyngeal EBV excretion and high serum antibody responses, which suggested a recent antecedent reactivation of an old EBV infection. The increased prevalence of oropharyngeal EBV and acute serological responses found in sibling family contacts during the early surveillance period suggested that these contacts had experienced an increased rate of primary-type EBV infections shortly before or concurrent with the index case. Although nonimmune sibling contacts seroconverted at a slow rate, five of nine manifested IM with their eventual documented primary EBV infection. This study noted significant intrafamilial EBV activity surrounding an episode of childhood EBV-IM. Reactivation of an old EBV infection in adults may be an important source of virus for susceptible children within these families. Siblings of a childhood case of EBV-IM appear to be at increased risk for manifesting IM with their primary EBV infection.

Adult↗

Enhanced serological and virological findings of Epstein-Barr virus in patients with AIDS and AIDS-related complex.

The potential involvement of Epstein-Barr virus (EBV) in AIDS was examined by determining the type of EBV-specific antibody responses and the EBV content or lymphoproliferative ability present in selected body fluids of patients with AIDS or AIDS-related complex. The results were compared with two control groups. An enhanced antibody response to a broad spectrum of EBV antigens was found in patients with AIDS or AIDS-related complex. The pattern of virus-specific antibody responses resembled that associated with a persistent or reactivated infection. The content of EBV in oropharyngeal secretions and the lymphoproliferative ability in peripheral blood from patients with AIDS or AIDS-related complex was significantly greater than that from healthy controls and approached levels detected in the control group with infectious mononucleosis. These findings, together with recent reports of cellular-level interaction between EBV and human T lymphotropic virus type III, suggest that EBV may have a contributory role in these disorders.

AIDS-Related Complex↗

Epstein-Barr virus-associated B-cell proliferations of diverse clonal origins after bone marrow transplantation in a 12-year-old patient with severe combined immunodeficiency.

A 12-year-old boy with severe combined immunodeficiency who had been kept in a gnotobiotic environment since birth received bone marrow from a histoincompatible sibling in an attempt to reconstitute immunologic function. To prevent graft versus host disease, the donor's marrow was treated in vitro with monoclonal antibody and complement to remove alloreactive T cells. Eighty days after transplantation, the patient had a systemic illness characterized by fever, thrombocytopenia, gastrointestinal pain, and bleeding; he died on the 124th post-transplantation day. Postmortem examination revealed multiple tumor-like B-cell proliferations, recipient in origin, in numerous organs. Epstein-Barr virus (EBV) was isolated from the patient's pharyngeal secretions; EBV nuclear antigen was found in spontaneously transformed peripheral-blood lymphocytes, inflammatory cells from peritoneal fluid, and bone marrow cells; and EBV genomes were discovered in all tumor tissues. The donor's serum showed evidence of past EBV infection. Analysis of cellular immunoglobulin and immunoglobulin gene DNA from the tumors indicated both monoclonal and oligoclonal B-cell proliferations. These findings provide evidence for the evolution of EBV-induced polyclonal activation of B cells to oligoclonal B-cell proliferation and finally to monoclonal B-cell lymphoma.

B-Lymphocytes↗

Increased prevalence and titer of Epstein-Barr virus antibodies in patients with multiple sclerosis.

The prevalence and titer of serum antibodies to several Epstein-Barr virus (EBV) antigens were compared among patients with multiple sclerosis, healthy siblings of multiple sclerosis patients, patients with other neurological diseases, and healthy non-blood-related subjects. Serum-cerebrospinal fluid (serum-CSF) pairs were available on a selected number of multiple sclerosis and control subjects. An increased antibody response to EBV antigens was noted rather consistently in the sera of the multiple sclerosis group in comparison with the control groups. A greater number of reduced ratios of serum:CSF IgG antibody to EBV-capsid antigen and antibody to EBV-early antigen components than to adenovirus, a reference or control virus, were found in the multiple sclerosis group. Reduced ratios of these EBV antibodies were detected more frequently or showed a trend in this direction in multiple sclerosis patients compared with the group with other neurological diseases. Our findings extend the results of an earlier report and strengthen the association between EBV and multiple sclerosis.

Adenoviruses, Human↗

Epstein-Barr virus infectious mononucleosis in children. I. Clinical and general laboratory findings.

Between 1976 and 1982, 113 children aged 6 months to 16 years with documented Epstein-Barr virus-induced infectious mononucleosis were studied prospectively, and in most instances serially. An unexpected finding was the large number of young children, less than 4 years old, with this disease. Children with infectious mononucleosis, in particular the very young, tended to have more rashes, significant neutropenia, abdominal pain (older children only), and possible hepatosplenomegaly than have been reported in adult patients. The intensity of the characteristic relative atypical lymphocytosis found in peripheral blood was age-related; it was less in the very young. Findings of failure to thrive, otitis media, and episodes of recurrent tonsillopharyngitis appeared to be unique or more closely associated with childhood disease. Complications such as thrombocytopenia with hemorrhagic manifestations, significant airway obstruction, and neurologic problems occurred more frequently whereas jaundice occurred less frequently than noted in adult patients. Six children, all less than 4 years old, developed pneumonia during the disease course. The increased availability of Epstein-Barr virus-specific testing should continue to expand our knowledge of this disease in children of all ages.

Adolescent↗

Epstein-Barr virus infectious mononucleosis in children. II. Heterophil antibody and viral-specific responses.

An investigation was performed to address the need to establish the rate of positive heterophil antibody responses, oropharyngeal isolation of Epstein-Barr virus (EBV), and the evolving pattern of EBV-specific antibody responses among children with documented EBV-infectious mononucleosis. Findings showed that the rate of heterophil antibody responses appeared to increase progressively with advancing age from infancy up to 4 years, after which the rates approached values similar to that reported in young adult patients. The rapid slide test detected a heterophil antibody response as frequently as the Paul-Bunnell-Davidsohn horse cell test, except in children less than 4 years old. The decreased sensitivity found with the rapid slide test in the very young was associated with their less intense heterophil response. The younger group of children also developed a lower acute mean titer and, as a result, a decreased persistence of immunoglobulin M antibody to EBV-capsid antigen, whereas they had more frequent responses to EBV-early antigen directed to restricted component than both the older subjects and adults reported elsewhere. Antibodies to EBV-nuclear antigen, characteristically a late-onset antibody, tended to develop earlier than noted in adult patients. In contrast, the prevalence and continued excretion of EBV from oropharyngeal secretions was similar to that reported in adult patients. It is speculated that these age-related differences in host responses are associated with the ontogeny of the immunologic system.

Adolescent↗

Human peripheral blood monocytes release a 30,000 dalton factor (30 KD MF) that stimulates immunoglobulin production by activated B cells.

Supernatants (SN) of well-washed adherent human monocytes, obtained from T cell-depleted peripheral blood mononuclear cells, contain a 30,000 dalton protein (30 KD MF) that increases immunoglobulin (Ig) synthesis by EBV-activated B cells two- to fourfold. This factor is released spontaneously during the first 20 hr after monocytes are placed in culture. SN containing 30 KD MF are inactive in the thymocyte co-stimulator assay, under conditions that will detect as little as 0.5 U of purified IL 1. The addition of autologous T cells to isolated adherent monocytes, previously depleted of T cells, suppresses the release or activity of this B cell stimulator in a dose-dependent manner. In addition, 30 KD MF stimulates a two- to fourfold increase in IgA production by cells of an EBV-transformed B cell line (JB/FF line) without increasing incorporation of [3H]thymidine. In contrast, stimulation of this B cell line with up to 10 U of purified IL 1 increases IgA synthesis by less than 50%, and addition of up to 100 U of recombinant IL 2 causes no change whatsoever in IgA production. However, co-stimulation with 30 KD MF and recombinant IL 2 or recombinant gamma-interferon induces more Ig production than is caused by the monocyte factor alone. These observations suggest that the monocyte, in addition to acting as an antigen-presenting cell and source of IL 1, facilitates B cell differentiation by producing a factor which acts both independently and in synergy with cytokines produced by T cells to stimulate Ig production by B lymphocytes.

Adult↗

Changes in T-lymphocyte subsets during childhood Epstein-Barr virus infectious mononucleosis.

Lymphocyte subsets were measured using monoclonal antibodies in 11 children with Epstein-Barr virus-induced infectious mononucleosis and compared with those of 10 normal children. In acute infectious mononucleosis the percentage of T8+ lymphocytes was greater while the percentage of T4+ lymphocytes and the T4+ to T8+ ratio were less than those measured in normal children. The percentage and absolute number of T lymphocytes, as enumerated by E rosetting, did not differ from the values for normal children. The children with acute infectious mononucleosis had a somewhat lower T8+ response than that observed in four adult infectious mononucleosis patients. With clinical recovery, the T lymphocyte-subset values returned toward normal. T8+ lymphocytes, a phenotype subset with predominantly suppressor activity, presumably reduce normal cellular immune functions transiently and may limit the continued proliferation of Epstein-Barr virus-infected B lymphocytes.

Adult↗

The role of antibody in host defense against the agent of mouse pneumonitis.

Athymic nude (nu/nu) mice, which are more susceptible to the agent of mouse pneumonitis (MoPn) (murine Chlamydia trachomatis) than are their heterozygous littermates (nu/+), do not develop significant IgG or IgA antibody to the MoPn agent. Nu/+ mice develop significant titers of both specific IgG or IgA antibodies after either intranasal or intrauterine challenge. Prior intranasal or intrauterine immunization protects nu/+ but not nu/nu mice against subsequent intranasal challenge with the MoPn agent. Resistance to pneumonia due to the MoPn agent can be transferred to nu/nu mice by nu/+ mouse immune serum (with high titers of IgG and IgA antibodies to the MoPn agent) but not by nu/+ mouse normal serum (with undetectable titers of IgG and IgA antibodies to the MoPn agent). Serum components, probably specific antibodies, are important in host defense against the MoPn agent.

Animals↗

Improved test for IgM antibody to Epstein-Barr virus using an absorption step with Staphylococcus aureus.

The determination of levels of IgM antibody to Epstein-Barr virus (EBV) capsid antigen was improved by absorbing unfractionated test serum with Staphylococcus aureus cells containing protein A. Nonspecific background fluorescence was significantly decreased, thus facilitating the reading of slides and the detection of specific fluorescent reactions in serum with low levels of this IgM antibody. Moreover, the inclusion of the absorption step eliminated false-positive reactions caused by the presence of rheumatoid factor in serum and shortened the time needed for the incubation of test serum with the EBV-infected cell smear. This improved antibody test should facilitate the laboratory diagnosis of acute EBV infections, including unaccompanied by a heterophil antibody response.

Antibodies, Viral↗

Persistence of antibody after the administration of influenza vaccine to children with cancer.

Children with cancer who received an intramuscular injection of inactivated split or whole bivalent (A/New Jersey/76-A/Victoria/75) influenza virus vaccine during the fall of 1976 were tested up to 18 months later for the persistence of antibody. Titers of antibody greater than of equal to 10 to influenza A/New Jersey/76 virus were present in the sera of 34 children two weeks after immunization. The geometric mean titer was 40.0. Eighteen months later a titer greater than or equal to 10 was present in 13 (38%) children; the geometric mean titer was 8.5. Of 36 children with a titer of antibody greater than or equal to 10 to A/Victoria/75 virus two weeks after immunization, 34 still had a detectable titer in the later examination. The geometric mean titer declined from 65.3 to 25.6. Titers of antibody to B/Hong Kong/72 virus (not included in the vaccine) remained relatively stable. In 11 children the usual chemotherapy was discontinued during the study. The shorter persistence of antibody to A/New Jersey/76 virus, in contrast to that of the other two influenza viruses tested, was associated with a lack of prior exposure to the virus and the absence of subsequent natural infection with this virus or an antigenically related subtype. The potential effect of cancer chemotherapy on the persistence of antibody levels is unclear.

Antibodies, Viral↗

Pneumococcal vaccine failures. Two case reports and review.

In six patients (four described previously) who received the currently licensed pneumococcal vaccine (Pneumovax), severe pneumococcal disease developed from a type contained in the vaccine. All exhibited a poor or inconsistent antibody response to the vaccine. Immunosuppressive drugs and radiation used to treat existing disorders, predominantly Hodgkin's disease, appeared to be major factors responsible for the poor immune response. None were receiving antimicrobial prophylaxis at the time of the pneumococcal infection. We suggest that type-specific antibody at a level below 215 ng of antibody nitrogen per milliliter of serum may not be protective. More extensive vaccine trials in persons, particularly children, at high risk of severe pneumococcal disease are needed. The optimal time to immunize persons receiving radiation or immunosuppressive drugs remains to be established.

Adolescent↗