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E N Janoff

Publications and source records attributed to E N Janoff.

72 records · Page 4Linked to original sources

Humoral recall responses in HIV infection. Levels, specificity, and affinity of antigen-specific IgG.

To evaluate the integrity of humoral immunologic memory among persons with HIV infection, we measured the levels, specificity, and functional affinity of circulating antibodies to vaccine-related recall Ag, tetanus (TT) and diphtheria toxoids (DT), and to naturally acquired measles virus, in sera from 17 HIV-seronegative control subjects, 17 asymptomatic HIV-seropositive patients, and 10 patients with AIDS. Preimmunization levels of TT- and measles-specific IgG were similar in all groups, although DT-specific IgG was lower in AIDS patients. Four wk after immunization with TT3 and DT, all groups showed significantly increased specific antibody levels (p less than 0.02). The asymptomatic HIV+ patients and control subjects achieved similar peak serum levels of TT-specific IgG (102 +/- 32 and 169 +/- 36 micrograms/ml, respectively). In contrast, the AIDS patients had lower peak values of both TT- and DT- specific IgG (p less than 0.05). Peak levels correlated directly with the number of CD4+ T cells (p less than 0.05). However, 80 to 100% of all participants tested, independent of HIV status, showed higher levels of TT- and DT-specific IgG 6 mo after immunization compared with preimmunization levels. The antitoxoid antibodies were specific as they did not cross-react with other Ag in competitive inhibition experiments. In addition, all groups exhibited antibodies to TT and DT both pre- and postimmunization of equivalent functional affinity (avidity) (Kd = 10(-10)-10(-11) mol/liter). We conclude that, in contrast to the profoundly depressed humoral responses to new Ag, persons with asymptomatic HIV infection retain humoral immunity to certain recall Ag. These levels of specific IgG to three recall Ag are not proportional to elevated levels of total serum IgG in HIV-infected patients. In addition, many patients with HIV respond to challenge with recall Ag by producing significant amounts of high affinity IgG that may persist over time.

Antibody Affinity↗

Adenovirus colitis in the acquired immunodeficiency syndrome.

Adenovirus was identified in colonic tissue by transmission electron microscopy or culture in 5 of 67 (7.4%) homosexual men seropositive for human immunodeficiency virus (51 with the acquired immunodeficiency syndrome) with diarrhea. Colonoscopy showed the mucosa to be normal in 3 cases and mildly inflamed in 2. Light microscopy showed foci of mucosal necrosis that contained chronic inflammatory cells and degenerating and necrotic epithelial cells with amphophilic nuclear inclusions. By transmission electron microscopy, hexagonal viral particles characteristic of adenovirus were identified within the inclusions. Only 1 patient was concomitantly infected by a second potential enteric pathogen. It was concluded that adenovirus, an uncommon enteric pathogen in immunocompetent adults, causes intestinal pathology and may be associated with diarrheal illness in persons with the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is an idiopathic illness associated with a variety of immunologic abnormalities. To investigate potential pathogenetic mechanisms, we evaluated serum levels and peripheral blood mononuclear cell (PBMC) production of selected cytokines and immunoglobulins. Serum bioactive transforming growth factor beta (TGF-beta) levels were higher (P less than 0.01) in patients with CFS (290 +/- 46 pg/mL) than in control subjects (104 +/- 18 pg/mL), but levels of other cytokines tested were not different. Lipopolysaccharide-stimulated release of interleukin 1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha was increased (P less than 0.05) in PBMC cultures from patients with CFS versus control subjects; enhanced (P less than 0.01) IL-6 release to phytohemagglutinin was also observed. In contrast, TGF-beta release in response to lipopolysaccharide was depressed (P less than 0.01) in PBMC cultures derived from patients with CFS. No differences in IL-2 and IL-4 or immunoglobulin production were observed. The enhanced release of inflammatory cytokines by stimulated PBMC from patients with CFS suggests that these cells are primed for an increased response to immune stimuli. These data also suggest an association between abnormal regulation of TGF-beta production in vivo and in vitro with the immunologic consequence of CFS.

Cytokines↗

DNA fingerprinting by pulsed field gel electrophoresis and ribotyping to distinguish Pseudomonas cepacia isolates from a nosocomial outbreak.

We typed 40 isolates of Pseudomonas cepacia obtained from patients involved in a single outbreak using pulsed field gel electrophoresis and ribotyping. All isolates from the majority of the patients, 16 of 18 (89%), were included in a single group. These typing methods should aid in the clarification of the epidemiology of infection with P. cepacia.

Bacterial Typing Techniques↗

Endemic Cryptosporidium and Giardia lamblia infections in a Thai orphanage.

We conducted a point prevalence survey for enteric protozoa in 205 institutionalized orphans 1-61 months of age in Bangkok, Thailand. Cryptosporidium was identified in 17 children (8%), Giardia lamblia in 42 (20%), and 3 children (1%) had both parasites. At the time of diagnosis, diarrheal symptoms were present in a minority of subjects: 36% of children with Cryptosporidium alone, 10% with G. lamblia alone, and in 20% of those with neither parasite. Although chronic nutritional status (height/age) was similar in all groups, acute nutritional status (weight/height) was lower only in children with Cryptosporidium (Z score = -1.39 +/- 0.13) compared with children with G. lamblia (mean Z score +/- SEM = -0.56 +/- 0.26) or neither parasite (Z score = -0.78 +/- 0.13; P = 0.05). Detectable levels of Cryptosporidium-specific IgG antibodies by ELISA were identified in 15 of 16 Thai children with Cryptosporidium and in 17 of 19 Thai children without Cryptosporidium (mean OD +/- SEM = 1.27 +/- 0.18 vs. 1.06 +/- 0.13, respectively), but in only 1 of 18 sera from toddlers in day-care centers in Denver, CO (OD = 0.128 +/- 0.03). Although neither infection with Cryptosporidium nor G. lamblia was consistently associated with acute diarrheal symptoms, Cryptosporidium was more often associated with depressed acute nutritional status than G. lamblia. The high prevalence of specific antibodies to Cryptosporidium in Thai orphans suggests an association between high rates of exposure with asymptomatic excretion of the parasites.

Animals↗

Serum antibodies to Giardia lamblia by age in populations in Colorado and Thailand.

We measured levels of antibodies to Giardia lamblia by age in serum specimens from persons in Denver, Colorado, and Soongnern, Thailand. Serum levels of immunoglobulin (Ig) G, IgM, and IgA G lamblia-specific antibodies measured by enzyme-linked immunosorbent assay increased substantially during childhood in both geographic areas, although children in Soongnern showed significantly higher mean levels of each antibody class (P less than .05). After adolescence, levels of G lamblia-specific IgM fell steadily with age in both populations. In contrast, specific IgA levels remained elevated throughout life among the Thai but decreased to low levels among adults in Denver. Similarly, rates of carriage of G lamblia were high among children aged 1 to 4 years in Denver and Soongnern (14.3% versus 26.5%, respectively) but were much lower among adults in Denver (0% versus 14%; P less than .01). These data suggest that levels of G lamblia-specific IgM may reflect exposure to the parasite early in life in both areas. Levels of parasite-specific IgA may reflect recurrent exposure to G lamblia in Soongnern, where G lamblia is endemic, but less frequent exposure to the parasite in Denver, where exposure is often episodic.

Adolescent↗

Rapid detection of giardia antigen in stool with the use of enzyme immunoassays.

Enzyme-linked immunosorbent assays (ELISAs) using sera from rabbits and goats immunized with Giardia trophozoites were compared for detection of Giardia antigen in 300 stool specimens, 80 of which had positive results for Giardia by microscopic examination. The diagnostic accuracy of the two assays was similar, with sensitivities of 92% and 87% and specificities of 87% and 91% with the use of rabbit and goat antisera, respectively. Both ELISAs detected Giardia antigen in stool samples from asymptomatic as well as symptomatic excretors and from treated patients after organisms were no longer visualized by microscopic examination. The specificity of the assays was confirmed by consistently negative results on stool specimens from 10 neonates and 27 patients with enteric parasitic infections other than Giardia. Negative results also occurred when stool specimens containing 21 bacterial enteropathogens were tested. Potential confounding variables including multiple freezing and thawing episodes, prolonged storage, and stool filtration did not affect test results from clinical specimens. Antidiarrheal compounds did not interfere with assay results. Preservation of specimens in formalin did interfere with the assay, even if formalinized stool specimens were dialyzed before testing. For diagnosis of giardiasis, the ELISA is a sensitive and specific test that is not influenced by many environmental factors or by other enteropathogens. This test provides a practical and reliable method for evaluating large numbers of specimens in a variety of clinical and epidemiologic settings.

Animals↗

Blastocystis hominis gastroenteritis in a hemophiliac with acquired immune deficiency syndrome.

Blastocystis hominis is an enteric protozoan that has occasionally been associated with gastrointestinal illness in man but is not considered an opportunistic pathogen. We describe a 16-year-old hemophiliac with acquired immune deficiency-related complex in whom upper gastrointestinal symptoms in conjunction with high densities of B. hominis in duodenal secretions and stool developed. Furazolidone treatment was associated with eradication of the organism and improvement in clinical symptoms. One month later, the patient had invasive Candida albicans esophagitis and died 2 weeks later of complications of acute pancreatitis. In immunocompetent individuals surveyed in Colorado the frequency of identification of B. hominis in stool concentrates was not different between asymptomatic and symptomatic persons. We suggest that B. hominis may be an opportunistic pathogen in immunocompromised patients and should be sought in duodenal secretions and feces when gastrointestinal symptoms are present.

Acquired Immunodeficiency Syndrome↗

Diagnosis of Giardia lamblia infections by detection of parasite-specific antigens.

Antigen detection methods may facilitate diagnosis of Giardia lamblia in stool specimens. As determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and immunoblotting, G. lamblia cysts and trophozoites share several antigens, especially in the 65-kilodalton and 30- to 34-kilodalton regions. By using blind methods, we compared results obtained by counterimmunoelectrophoresis using cyst-immune rabbit serum and by enzyme-linked immunosorbent assay (ELISA) using trophozoite-immune rabbit serum with results obtained by microscopic examination of a preserved, concentrated, and permanently stained stool specimen. Results were similar when these three methods were used to examine 118 stool specimens from clinical microbiology laboratories (53 specimens with G. lamblia) and specimens from 239 day-care-center toddlers (39 specimens with G. lamblia). Compared with microscopy, we found, for counterimmunoelectrophoresis and ELISA, respectively: sensitivity, 88 versus 94%; specificity, 97 versus 95%; positive predictive value, 86 versus 76%; negative predictive value, 98 versus 97%; and concordance, 89%. The false-positive rate by ELISA was 24% (10 of 42) in day-care-center toddlers but only 3% (1 of 32) in healthy adults (P less than 0.04) as corroborated by microscopy. This discrepancy suggests that the ELISA may be more sensitive than microscopy, which is considered the reference standard, and that results may be dependent, in part, on the epidemiology of the infection in the study subjects.

Animals↗

Elevated levels of immunoglobulin A to Giardia lamblia during a waterborne outbreak of gastroenteritis.

During an outbreak of diarrheal illness among residents of a trailer park in rural Vermont, 37 (30%) of 122 residents met the case definition of outbreak-related giardiasis. Convalescent-phase sera from 24 residents and 20 nonresident control subjects were tested by enzyme-linked immunosorbent assay for immunoglobulin G (IgG), IgM, and IgA antibodies to Giardia lamblia. Residents showed higher levels of parasite-specific antibody than did nonresident controls for IgG and IgA but not IgM. Nine residents with giardiasis had a higher median level of G. lamblia-specific IgA but not IgG or IgM than 15 healthy residents (0.61 versus 0.16 optical density units; P = 0.004). Moreover, parasite-specific IgA levels were higher in those consuming tap water than in those who did not (0.31 versus 0.08 optical density units; P = 0.03) and increased with increasing water consumption. Levels of serum antibody to G. lamblia, particularly IgA, may be useful in determining exposure to G. lamblia-contaminated water and illness from G. lamblia during waterborne outbreaks of diarrheal illness.

Adult↗

Acute antibody responses to Giardia lamblia are depressed in patients with AIDS.

We investigated the ability of patients with AIDS to develop antibody responses to a naturally encountered antigenic stimulus, Giardia lamblia. Using an enzyme-linked immunosorbent assay to detect IgG, IgM, and IgA to G. lamblia trophozoites, we tested sera from 29 patients with AIDS (15 without and 14 with G. lamblia infection); 20 healthy homosexual men; and 91 immunocompetent heterosexual subjects, 25 of whom were infected with G. lamblia. Heterosexual subjects infected with G. lamblia had significantly higher levels of all three classes of specific antibody than did the uninfected subjects (P less than .0001). Patients with AIDS who had acute symptomatic giardiasis had significantly lower levels of all antibodies than did the heterosexual subjects who had giardiasis; specific IgM was absent in all but one patient with AIDS. The symptomatically infected patients with AIDS had low levels of G. lamblia-specific antibodies that were similar to those of the uninfected patients with AIDS. Patients with AIDS do not have to suffer from prolonged symptomatic G. lamblia infections, however, because available therapy is effective against the parasite, independent of a patient's immune status.

Acquired Immunodeficiency Syndrome↗

Class-specific antibody response to pneumococcal capsular polysaccharides in men infected with human immunodeficiency virus type 1.

We characterized the effect of infection with human immunodeficiency virus type 1 (HIV) on levels of total immunoglobulins and pneumococcal vaccine-specific immunoglobulins in 28 heterosexual and 25 homosexual men seronegative for HIV; 27 asymptomatic, seropositive homosexual men; and 21 patients with AIDS. Total serum IgG levels were increased in both HIV-seropositive groups compared with the HIV-seronegative men (P less than .001). Total IgM levels, however, were elevated only in the asymptomatic, HIV-seropositive men (P less than .08); total IgA levels were elevated only in the patients with AIDS (P less than .05). Vaccine-specific serum IgG, IgM, and IgA significantly increased over baseline three and six weeks after immunization in all groups (P less than .05). Responses to vaccine among the HIV-seronegative groups were similar but were greater for all antibody classes than were responses among the HIV-seropositive groups (P less than .05).

Acquired Immunodeficiency Syndrome↗

Perspectives on gastrointestinal infections in AIDS.

Gastrointestinal illnesses are among the most common and debilitating complication of infections with HIV, affecting 50 per cent to almost 100 per cent of AIDS patients in developed and developing countries, respectively. A number of factors including relevant modes of transmission, the environment, and immunosuppression conspire to determine which enteric infectious agents HIV-infected persons acquire. In developed countries, transmission of a diverse spectrum of bacteria, viruses, and protozoa is facilitated by unprotected receptive anal intercourse and anal-lingual contact among homosexual men with multiple partners. In developing countries, where most HIV infections occur among heterosexual persons, waterborne and foodborne transmission are the principal modes of transmission of enteric organisms. The severity and duration of symptoms associated with enteric pathogens are determined by the host's immunologic response to the organism. Candida albicans often causes local mucosal disease but less often causes systemic infections in HIV-infected persons, likely because polymorphonuclear cell function is intact. The ability of AIDS patients to control infections with G. lamblia and C. jejuni is related to their ability to mount an antibody response to these organisms during infection. The virulence of the organism may also affect the clinical response to infection. Cryptosporidium causes diarrheal symptoms in both immunocompetent and AIDS patients, but illness is more severe and prolonged in the latter. Giardia lamblia and C. jejuni infections are associated with a range of clinical manifestations in both AIDS patients and HIV-seronegative persons, whereas CMV and possibly adenovirus appear to cause significant disease only among immunocompromised subjects. The availability of effective therapy is among the most decisive factors in determining the duration of enteric infections in AIDS patients. For example, Giardia lamblia may cause acute abdominal pain and diarrhea in HIV-infected subjects but prolonged infections with the parasite are uncommon because effective therapy is available. In contrast, infections with CMV and Cryptosporidium may be severe and chronic as available therapy is generally ineffective or only transiently effective. Awareness of these clinical, epidemiologic, immunologic, and therapeutic aspects of gastrointestinal illness in HIV-infected subjects should help to direct the diagnostic evaluation of these patients and to direct areas of research.

Acquired Immunodeficiency Syndrome↗

Infectious diarrhea in human immunodeficiency virus infection.

Gastrointestinal symptoms, particularly diarrhea, are common in patients with AIDS. Recent evidence indicates that enteric pathogens can be identified in most of these cases. Appreciating the clinical features caused by protozoal, fungal, bacterial, and viral pathogens will assist the clinician in effectively evaluating the gastrointestinal symptoms. Antimicrobial agents now are available for many of these pathogens.

Acquired Immunodeficiency Syndrome↗

Prevalence of Giardia lamblia and risk factors for infection among children attending day-care facilities in Denver.

A sample of children in the toddler age group was surveyed in Denver, CO, to determine the prevalence of Giardia lamblia and to identify risk factors for the intestinal disease. The sample consisted of 236 children attending day-care centers (DCC) and 79 who were not attending. Thirty-eight children (16 percent) attending DCCs and 7 (9 percent) who had not were positive for G. lamblia in stool samples. Risk factors for those attending DCC facilities included increasing duration of attendance, time per week attending DCCs, low family income, and large family size. The only risk factor for those not attending DCC facilities was travel to Colorado mountains. Multivariate analysis showed that risk factors for all children in the sample included travel to Colorado mountains, large family size, and attending DCC facilities. Infection was not associated with symptoms.

Animals↗