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Biomedical subjects

R Edelman

Publications and source records attributed to R Edelman.

At least 55 records · Page 3Linked to original sources

Evaluation in humans of a new, inactivated vaccine for Venezuelan equine encephalitis virus (C-84).

A new, formalin-inactivated vaccine for Venezuelan equine encephalitis (VEE) virus (C-84), prepared from an attenuated vaccine strain of virus (TC-83), was tested in humans. Only occasional, mild, local and systemic reactions were noted in 28 volunteers; no meaningful changes in clinical laboratory values occurred. The vaccine augmented preexisting titers of serum neutralizing antibody to VEE virus in seropositive recipients of TC-83 vaccine, and it induced high titers of neutralizing antibody in nonimmune subjects after one primary and two booster vaccinations. Circulating antibody persisted for at least 14 months in these persons. The neutralizing antibody produced after one dose of C-84 vaccine in immune subjects and after booster doses in nonimmune subjects had broad cross-reactivity within the VEE virus complex. The C-84 vaccine induced a VEE virus-specific lymphocyte transformation response. The vaccine was safe, and immunologic results showed it to be highly antigenic in healthy immune and nomimmune adults.

Adolescent

Interaction of alphaviruses with human peripheral leukocytes: in vitro replication of Venezuelan equine encephalomyelitis virus in monocyte cultures.

Human peripheral blood leukocytes (PBL) were examined for their ability to support growth of several group A arboviruses in vitro. Cells were refractory to infection with eastern (EEE) and western (WEE) equine encephalitis viruses, whereas Venezuelan equine encephalomyelitis (VEE) virus was shown to infect and replicate to a substantially high titer. When PBL were fractionated into purified subpopulations, only the monocytes were susceptible to predictive VEE virus infection. Lymphocytes treated 24 h before virus inoculation with phytohemagglutinin (10 microgram/ml) were capable of propagating significant amounts of VEE virus. A monocytic cell line, J-111, was also susceptible to infection with VEE, EEE, and WEE viruses, whereas a lymphocytic cell line, Raji, was refractory. Additional information on the participation of PBL during human infection with these viruses may add considerably to our understanding of their differing pathogenicities and clinical pictures.

Arboviruses

Plasma kallikrein activation and inhibition during typhoid fever.

As an ancillary part of a typhoid fever vaccine study, 10 healthy adult male volunteers (nonimmunized controls) were serially bled 6 days before to 30 days after ingesting 10(5)Salmonella typhi organisms. Five persons developed typhoid fever 6-10 days after challenge, while five remained well. During the febrile illness, significant changes (P < 0.05) in the following hematological parameters were measured: a rise in alpha(1)-antitrypsin antigen concentration and high molecular weight kininogen clotting activity; a progressive decrease of platelet count (to 60% of the predisease state), functional prekallikrein (55%) and kallikrein inhibitor (47%) with a nadir reached on day 5 of the fever and a subsequent overshoot during convalescence. Despite the drop in functional prekallikrein and kallikrein inhibitor, there was no change in factor XII clotting activity or antigenic concentrations of prekallikrein and the kallikrein inhibitors, C1 esterase inhibitor (C1-INH) and alpha(2)-macroglobulin. Plasma from febrile patients subjected to immunoelectrophoresis and crossed immunoelectrophoresis contained a new complex displaying antigenic characteristics of both prekallikrein and C1-INH; the alpha(2)-macroglobulin, antithrombin III, and alpha(1)-antitrypsin immunoprecipitates were unchanged. Plasma drawn from infected-well subjects showed no significant change in these components of the kinin generating system. The finding of a reduction in functional prekallikrein and kallikrein inhibitor (C1-INH) and the formation of a kallikrein C1-INH complex is consistent with prekallikrein activation in typhoid fever. The correlation of these changes with the drop in platelet count suggests that a common mechanism may be responsible.

Adult

Defective local leukocyte mobilization in children with kwashiorkor.

The Rebuck window technique was used to determine the functional integrity of the inflammatory response in nine children with kwashiorkor. The total numbers of leukocytes mobilized into skin abrasions were similar between kwashiorkor and control patients. However, children with kwashiorkor showed significantly delayed and decreased macrophage migration and increased polymorphonuclear leukocyte migration. These defects of leukocyte mobilization were corrected with nutritional repair.

Anti-Bacterial Agents

Persistence in humans of antibody to subtypes of Venezuelan equine encephalomyelitis (VEE) virus after immunization with attenuated (TC-83) VEE virus vaccine.

We studied the persistence of antibody to Venezuelan equine encephalomyelitis (VEE) virus subtypes in sera of 20 volunteers inoculated seven or nine years previously with attenuated TC-83 VEE virus vaccine. Serological patterns were compared with those of 10 other persons from whom samples of serum were obtained 28 days after vaccination with TC-83 virus. Vaccines had no other known exposure to a group A arbovirus. Titers of neutralizing antibody of greater than or equal to 1:10 were measured against the homologous TC-83 strain of virus in all long- and short-term vaccinees. In both groups of vaccinees the percentage of antibody-positive persons and their geometric mean titers of antibody to the epizootic subtypes I-A, I-B, and I-C were higher than titers to the enzootic subtypes I-D, I-E, II, III, and IV. However, proportionally fewer long-term vaccinees than short-term vaccinees had detectable neutralizing antibody reactive with enzootic strains. These results reveal long-lasting circulation of neutralizing antibody to TC-83 virus and closely related epizootic variants in 95%-100% of vaccinees. The relatively lower rate of antibody conversion and the loss of antibody to more antigenically remote enzootic subtypes of VEE virus suggest that vaccinees may be less well protected against infection by these strains.

Antibodies, Viral

Sequential immunization of laboratory personnel with influenza A/New Jersey/76 split- and whole-virus vaccines.

One hundred thirty-three healthy, at-risk Fort Detrick laboratory workers were inoculated with 400 chick cell-agglutinating (CCA) units of influenza A/New Jersey/76 split-virus vaccine (Wyeth Laboratories, Philadelphia, Pa.). Systemic and local reactions were infrequent, mild, and comparable to those of a sham-vaccinated group of volunteers. Only 28% of subjects 19-24 years old developed titers of hemagglutination-inhibiting (HAI) antibody of greater than or equal to 1:20, whereas titers of 91%-100% of subjects 25-62 years old reached this level. Thirty-one vaccinated subjects with no or low titers of antibody were given a booster dose (400 CCA units) of Wyeth vaccine six weeks after the first inoculation. Only 58%-67% of these vaccinees achieved HAI titers of greater than or equal to 1:20 after the booster. Fourteen persons required a second booster dose for protection; after vaccination with 400 CCA units of whole-virus vaccine from Merck Sharp and Dohme (West Point, Pa.), 89%-100% of the 14 vaccinees finally achieved HAI titers of greater than or equal to 1:20. The split-virus vaccine was safe, but it was poorly antigenic as a primary vaccine in persons 19-24 years old and as a booster in persons of all ages who have poor antibody responses in general.

Adult

Serologic responses and systemic reactions in adults after vaccination with bivalent A/Victoria/75-A/New Jersey/76 and monovalent B/Hong Kong/72 influenza vaccines.

Bivalent A/Victoria/75-A/New Jersey/76 and monovalent B/Hong Kong/72 influenza vaccines were given alone or together to adutls, and systemic reactions and antibody responses were determined. The rates of systemic reactivity observed varied among vaccine groups. Disrupted vaccines and whole-virus vaccines containing type B antigen only did not cause significant reactivity. Systemic reactions were observed after administration of the bivalent A whole-virus vaccines, and this reactivity was increased if the B vaccine was also administered. Reactions to the more reactive vaccines were less frequent in older subjects or in younger individuals with evidence of previous exposure to influenza antigens in the vaccine. Antibody responses in this study indicated that individuals older than 25 years responded better to A/New Jersey antigens than did younger subjects. The A/Victoria antigen produced lower antibody levels in older individuals than in younger subjects. The B/Hong Kong antibody responses were similar in all vaccine groups.

Adolescent

The active E-rosette test: a sensitive in vitro correlate for human delayed-type hypersensitivity.

The "active" rosette test was adapted as an in vitro assay and correlated with human delayed cutaneous hypersensitivity (DCH) to two microbial antigens. Peripheral lymphocytes were purified from donors known to be responders or nonresponders to PPD-tuberculin or tularemia on the basis of prior DCH reactions. Skin test antigen, incubated with lymphocytes from antigen-sensitive donors, produced a significant increase (+2 S.D.) in the ability of the lymphocytes to form active rosette-forming cells (A-RFC) when compared to lymphocytes cultured without antigen. Skin test antigen incubated with lymphocytes from nonsensitive donors produced no increase in their A-RFC. The optimal dose of each antigen was approximately 100 ng/ml. The percentage of A-RFC rose to maximum levels between 3 and 4 hr after the addition of antigen to the lymphocytes incubated at 37 degrees C. The assay appears to be specific for the antigen to which the individual demonstrates DCH. This assay may provide a new in vitro method for investigating mechanisms of cell-mediated immunity and a rapid diagnostic test for sensitization to microbial antigens.

Adult

Complement activity in children with protein-calorie malnutrition.

Using the hemolytic complement (CH50) assay, we evaluated the complement system of 28 children with severe protein calorie malnutrition (PCM) during their hospital admission and recovery. The mean CH50 activity in children with kwashiorkor was significantly less on hospital days 1 and 4 than in 17 healthy control subjects. On day 8 it rose to normal, and by day 50 it was significantly higher than the controls. The mean CH50 titer of 16 well-nourished febrile children was, in contrast to that of untreated PCM, significantly greater than the healthy controls. Of the children with PCM, 11 (40%) evidenced anticomplementary (AC) activity in their serum on either day or 1 or 4, but only two (7%) had detectable serum AC activity during later convalescence. Significantly, the CH50 titer in a PCM serum correlated inversely to the amount of AC activity in that serum (P less than 0.01). These results indicate that, in children with PCM, the complement system is compromised functionally, and that its repair coincides with intake of adequate diet. The presence of AC activity provides a possible mechanism for depressed complement activity in some untreated PCM children.

Child, Preschool

Immunoglobulins and antibody response in children with protein-calorie malnutrition.

The immunoglobulin levels (IgG, IgA, IgM, IgD, and IgE) were studied in 28 Northern Thai children with protein-calorie malnutrition (PCM). Of these 14 had marasmus, 7 had marasmus-kwashiorkor, and 7 had kwashiorkor. The immunoglobulin levels were measured on admission and serially during 12 weeks of treatment leading to recovery. All immunoglobulin fractions either equalled or exceeded levels seen in well-nourished urban and rural Thai children, with or without infection. There was no difference in levels of IgG, IgM, IgA, or IgD in children with marasmus when compared with those who had marasmus-kwashiokor or kwashiorkor. IgA levels were higher in malnourished than control children and returned to normal with treatment. Eighty percent of the children with PCM had detectable IgD levels while 64% had detectable IgE levels as compared to none in the control groups. Ten additional children admitted with PCM and 10 who had recovered from PCM were immunized with intradermal typhoid antigen. Within 8 days a significant increase in typhoid H antibody appeared in the recovered group, while the malnourished group demonstrated no significant increase in H antibody titer.

Antibodies, Bacterial

Persistence of virus-specific IgM and clinical recovery after Japanese encephalitis.

We have searched for evidence of a chronic Japanese encephalitis virus (JEV) infection in six Thai patients convalescing from acute Japanese encephalitis (JE) in whom JEV-specific IgM antibody was last detected 116 to 350 days after their acute illness. These six patients were compared with 94 other JE patients matched for age, sex and serological response and in whom JEV-specific IgM was either short-lived (less than 90 days) or not tested. All patients were evaluated for the presence or absence of seven abnormal neurological signs over a 1- to 2-year period. During the first 30 days of illness the mean numbers (+/- S.E.M.) of abnormal signs per patients for the IgM and control groups were 3.8 +/- 0.3 and 2.3 +/- 0.1, respectively (P less than 0.01). After 1 year the six IgM patients still had significantly more abnormal neurological signs than controls (1.3 +/- 0.3 and 0.6 +/- 0.1, respectively [P less than 0.01]). By 2 years, the IgM group showed no neurological impairment; examination of cerebrospinal fluids revealed no evidence of subclinical viral infections. The recovery of the six IgM patients between 1 and 2 years after their relatively severe acute illness suggests that IgM antibody persistence was related to acute virulence rather than chronicity of the JEV infection.

Encephalitis, Japanese

The active E rosette test: correlation with delayed cutaneous hypersensitivity.

An active subpopulation of peripheral blood T lymphocytes, characterized by rapid (5-min) rosette formation with sheep erythrocytes (A-RFC), was measured in normal individuals after they were skin tested with microbial antigens. A significant rise in A-RFC occurred in all individuals who developed positive delayed cutaneous hypersensitivity (DCH) reactions, whereas skin test nonresponders showed no significant rise in A-RFC. No similar consistent changes occurred in populations of total T cells, characterized by longer (60-min) rosette formation with sheep erythrocytes, or in B cells, measured by immunofluorescence of surface immunoglobulin. The A-RFC response paralleled the DCH response in timing, but not in intensity. These results provide in vivo evidence for a biologically distinct T cell subpopulation, and focus attention on the A-RFC as immunologically active cells.

Adult

Evaluation of the plasma kinin system in dengue hemorrhagic fever.

The role of the plasma kinin system in the pathogenesis of dengue hemorrhagic fever (DHF) ws explored by simultaneously measuring factor XLL (Hageman), prekallikrein, kallikrein inhibitors, bradykinin, and complement (C3) in the blood of Thai children with DHF and acute febrile illnesses other than dengue. Prekallikrein, factor XII, and C3 levels were significantly lower in DHF patients compared to fever control patients with the lowest mean levels found in dengue patients with shock. However, bradykinin concentrations were not elevated and mean activity levels of kallikrein inhibitors were not depressed in dengue patients. Two dengue patients first studies at least 2 days before onset of shock had falling C3 levels which were more closely related temporally to the onset of shock than were their rising levels of prekallikrein. The results fail to provide convincing evidence ofr activation of the plasma kinin system leading to free bradykinin or a significant role for bradykinin in the immunopathogenesis of DHF. By contrast, the results refocus attention on complement as a potentially important humoral mediator of the dengue shock syndrome.

Antigens, Viral

The effect of dengue virus infection on the clinical sequelae of Japanese encephalitis: a one year follow-up study in Thailand.

In order to determine if prior dengue virus infection reduces the severity of Japanese encephalitis (JE), we examined 127 patients hospitalized during the 1970 JE epidemic in the Chiangmai and Lampang Valleys of northern Thailand. Patients were studied during the first 30 days after onset of JE; 120 of these patients were examined one year later for residual neurologic sequelae. About 21% of patients had serological evidence of a prior dengue virus infection. Morbidity and mortality in patients with and without prior dengue virus experience were compared. These comparisons were made within two age groups to exclude differences due to age alone;

Adolescent

Secretory and serum IgA in children with protein-calorie malnutrition.

The local immune system of children suffering protein-calorie malnutrition (PCM) was investigated by analyzing the amount of immunoglobulins in the nasal washing on admission, repeatedly during 84 days of hospital therapy, and on follow-up, one to two years later. Although measured concentrations of total protein, IgG, and albumin in nasal washings were reduced in children with PCM, only secretory IgA concentrations were significantly lower (P less than .01) in PCM compared to normal children. Mean secretory IgA concentrations were significantly reduced on admission through hospital day 70 and returned to near normal thereafter. At one to two years after hospital discharge, mean concentrations of secretory IgA in nasal secretions were within normal limits. The concentrations of secretory IgA in nasal washings were lowest at a time when serum IgA was markedly elevated; serum IgA concentrations fell to normal values during dietary treatment. The possible role of secretory IgA deficiency in PCM and infection is discussed.

Albumins