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PubMed1980

Non-A/non-B hepatitis in experimentally infected chimpanzees: cross-challenge and electron microscopic studies.

Inoculation of eight chimpanzees with factor VIII, factor IX, or "H" strain plasma resulted in enzymatic and histopathologic evidence of non-A/non-B hepatitis in all eight animals. Challenge of two chimpanzees convalescent from factor VIII-induced disease with either factor IX or "H" strain plasma resulted in non-A/non-B hepatitis only in the animal inoculated with factor IX materials. Reciprocal cross-challenge of a chimpanzee convalescent from factor IX-induced disease with factor VIII also produced unequivocal enzymatic and histopathologic evidence of non-A/non-B hepatitis. Cross-challenge of a chimpanzee convalescent from "H" strain-induced non-A/non-B hepatitis with factor VII did not cause a second bout of non-A/non-B hepatitis. These findings suggest the factor VIII materials and "H" strain plasma used in these studies share a common etiologic agent (or agents), but that factor VIII and factor IX may contain two distinct agents. Electron microscopic (EM) examination of thin-sectioned, acute-phase liver biopsies from all but one of the chimpanzees receiving the primary inocula revealed the presence of abnormal hepatocyte cytoplasmic structures previously shown to be associated with non-A/non-B hepatitis. Crystalline structure containing 25 to 30 nm particles were visualized by EM in the cytoplasm of endothelial or Kupffer cells in acute-phase liver biopsies obtained from three chimpanzees inoculated with either factor VIII materials or "H" strain plasma.

Animals↗
PubMed1981

Development of serum and intestinal antibody response to rotavirus after naturally acquired rotavirus infection in man.

The temporal characteristics of the response of rotavirus specific IgM, IgG, IgA in serum and secretory antibody in feces to rotavirus were studied in 77 hospitalized patients with rotavirus induced gastroenteritis. The response in serum was characterized by the sequential appearance of rotavirus specific IgM, IgG, and IgA antibody. The IgM antibody appeared to be higher in the acute phase of the disease and was subsequently replaced by the IgG and IgA antibodies. However, the titers of IgG rotavirus antibody in convalescent specimens of serum were found to be statistically significantly lower in patients with severe or prolonged rotavirus infection than in specimens from subjects with mild or moderate disease. Most fecal specimens collected during both the acute and convalescent phase of illness contained virus specific secretory IgA. Higher concentrations of antibody were measured in convalescent samples from patients with prolonged diarrhea and virus shedding. These observations suggest a possible relationship between the severity of rotavirus infection and the nature of systemic and secretory antibody response.

Antibodies, Viral↗
PubMed1985

Neutralizing antibody and interferon-alpha in cerebrospinal fluids and sera of acute aseptic meningitis.

Cerebrospinal fluids (CSFs) and sera from 20 patients with echovirus 30 (E 30) meningitis, 4 patients with enterovirus 71 (EV 71) meningitis, and 5 patients with acute aseptic meningitis (AM) of unknown etiology were investigated at the acute and the convalescent phases of the disease to elucidate the roles of neutralizing antibody (NT) and interferon-alpha (IFN-alpha) in the central nervous system (CNS) in cases of AM in humans. Viruses were isolated from the CSFs at the acute phase of AM, but not at the convalescent phase. There was a fourfold or greater rise in NT titer between paired sera to E 30 or EV 71 but only a slight rise between paired CSFs. IFN-alpha was detected in the CSFs ranging from less than 10 to 25.5 IU/ml but not in the sera, and the IFN-alpha level in the CSF was significantly higher in the acute phase than in the convalescent phase. These results suggest that in cases of acute enteroviral infections in the CNS, NT plays only a small role in the recovery from AM, and IFN-alpha plays a direct or indirect role in curbing the local spread of the virus and eliminating the virus from the CNS at the acute phase of AM.

Antibodies↗
PubMed1985

AN6520 Ag: an antigen purified from liver with non-A, non-B hepatitis.

An extract prepared from the liver of patient with chronic non-A, non-B (NANB) hepatitis was found to produce a precipitin line in immunodiffusion with a serum from a multiply transfused patient and those from patients convalescent from NANB hepatitis. The antigen was purified by gel filtration and density gradient centrifugation. The antigen had a buoyant density of 1.16-1.20 g/cm3 in cesium chloride, a sedimentation coefficient (S20,w) of 51.5, and a molecular weight of larger than 1.5 X 10(6) daltons. Electron microscopic examination revealed particles 29-34 nm in diameter (average 31.5 nm), which could be agglutinated by the specific antiserum. We developed a reverse passive hemagglutination (R-PHA) and a passive hemagglutination (PHA) technique for detection of the new antigen and antibody, respectively, and applied these to human sera. Antibody to the antigen was detected in 19/28 (67.9%) convalescent sera of NANB hepatitis. This prevalence was significantly higher than those found in convalescent sera of type A hepatitis patients (2/17 = 11.8%), type B hepatitis patients (2/15 = 13.3%), and normal blood donors (9/129 = 7.0%) (p less than 0.01); and the prevalence in hepatitis A and B patients did not differ significantly from that of normal donors. Furthermore, most (66.7%) of the cases of NANB hepatitis endemic in Shimizu City, Japan, showed clear seroconversion with respect to this antibody. These results suggest that the new antigen/antibody system is associated with NANB hepatitis.

Adult↗
PubMed1992

Serum antibodies to structural proteins of Hantavirus arise at different times after infection.

An enzyme-linked immunosorbent assay (ELISA) was developed for the quantification of serum antibodies against group-specific epitopes of the glycoproteins (G1, G2) and nucleoprotein (NP) of the genus Hantavirus. This assay was used to study the kinetics of the development of serum antibodies after natural infection with Puumala-like virus in humans. To this end a panel of 34 serum samples collected from individuals at different times after natural infection was tested by the ELISA. The samples were also tested for specific IgM and IgG levels against Puumala-like virus, which provided confirmatory data about the presumed timing of infection. It was shown that serum antibodies against the G1 epitope were present in the acute and early convalescent period just before antibodies to the NP epitope could be demonstrated. In contrast, antibodies to two G2 epitopes were present not earlier than in the convalescent and late convalescent period. Since all these categories of antibodies seem to persist for long periods, antibodies against the G1 epitope and the NP epitope may be of specific diagnostic value. Furthermore, levels of G1-specific antibodies and antibodies to either NP or G2 may allow estimation of the time elapsed following initial infection.

Antibodies, Viral↗
PubMed1995

Detection of acute measles infections by indirect and mu-capture enzyme immunoassays for immunoglobulin M antibodies and measles immunoglobulin G antibody avidity enzyme immunoassay.

An avidity test for measles IgG was developed and applied to the study of IgG immunoglobulin maturation kinetics in follow-up sera from 12 patients with known acute primary and convalescent measles and sera from blood donors. The avidity of the IgG anti-measles responses was measured using the 8 M urea elution technique, the results being expressed as the percentage ratio between the test readings for eluted and noneluted samples. The IgG avidity results were compared with those of indirect and mu-capture IgM enzyme immunoassays. This test was capable of detecting low-avidity antibodies at the acute phase of measles up to 7 weeks, and increasing avidity through immunosaturation during the convalescent phase. The avidity in these samples did not reach the level found in the samples of the blood donors under the follow-up time. Although a limited number of serum samples was examined, the results suggest that the measles IgG avidity test is a powerful tool for differentiating primary measles infection from the convalescent phase.

Acute Disease↗
PubMed1987

Reduction of the number of immunocompetent cells in the acute stage of herpes zoster.

Circulating and in situ mononuclear cell subsets were phenotypically characterized during both the acute and convalescent phase of herpes zoster infections in 14 patients. In peripheral blood a significant reduction in the absolute number of Leu 4+ T cells, Leu 2a+ suppressor/cytotoxic T cells, Leu 3a+ helper/inducer T cells, Leu 7+ killer cells, and B1+ B cells were found during the acute stage compared to convalescents and normal controls. In contrast no change in the absolute number of MO2+ monocytes was seen in the acute stage of the disease. During convalescence a return to normal values in the lymphocyte subsets and killer cells was seen within 1-2 months after the initial disease presentation. In skin biopsy specimens from 4 of the 14 patients with active herpes zoster lesions the cellular infiltrate consisted of T cells (Leu 4+) the majority being helper/inducer T cells (Leu 3a+). Most of the cells expressed HLA-DR (Ia) antigens and were according to this in an activated state. The observed changes in effector and regulatory cell numbers may have implications for the acquisition of Varicella-zoster virus infections, the immune deficiency state associated with the disease, and/or the immune response to resolve the infection.

Aged↗
PubMed1989

Ia-expressing microglial cells in experimental allergic encephalomyelitis in rats.

Monoclonal antibodies (MRC OX-6 and OX-17) recognized three types of cells expressing Ia antigen during the course of acute experimental allergic encephalomyelitis (EAE) in rats. In earlier stages of the disease, in animals with or without paralysis, Ia antigens were mostly localized to subarachnoidal and perivascular lymphocytic and histiocytic cell infiltrates, possibly serving as antigen-presenting cells. On the other hand, in convalescent rats, Ia antigens were expressed in a large number of cells with dendritic processes heavily populating the spinal gray matter. The appearance of these Ia-expressing cells in the convalescent stage coincided with the development of degenerating axon terminals in the spinal gray matter. These Ia-expressing cells possessed morphological features characteristic of microglia and were positive for ML-1 lectin but did not express glial fibrillary acidic protein. Immune electron microscopy disclosed the presence of Ia reaction products in the Golgi apparatus, endoplasmic reticulum and plasma membrane of these cells with dendritic processes, indicating active synthesis of Ia molecules in microglia. In addition, Ia antigens were localized to the cells with ultrastructural features of macrophages. Thus, Ia-expressing cells in EAE seems to play dual roles: the induction of immunological reactions during earlier stages and the participation in reparative processes during convalescence.

Animals↗
PubMed1980

Sero-diagnosis of invasive aspergillosis: attempts to determine antigen and antibody relevance to infection.

Attempt was made to define antigens and antisera which might prove useful in diagnosis of invasive aspergillosis in man. A convalescent antiserum (serum from rabbits after liver infection with Aspergillus fumigatus conidia) which might be more representative of immunological reaction to fungal growth in vivo, did not react in enzyme-linked immunosorbent assay with commerical antigens which are used at present in attempts to detect antibody response in systemic infections in man. However, this convalescent antiserum reacted with antigens from a range of fungal extracts. Antigens from young culture filtrates in particular the 24th culture filtrate are advocated as the standard antigens for antibody detection using conventional immunoprecipitation techniques. For the detection of circulating antigens, the use of convalescent antiserum in enzyme-linked immunosorbent assay might be promising in the early diagnosis of invasive aspergillosis.

Antibodies, Fungal↗
PubMed1995

Validation of an enzyme immunoassay for serodiagnosis of acute Q fever.

An enzyme immunoassay was validated for the serodiagnosis of acute Q fever. Minimum positive tests were determined for both serial dilutions and a single dilution of patient sera. To establish the specificity of the test, 152 serum samples were tested from individuals with no evidence of past Coxiella burnetii infection. Diagnostic titers were set at > or = 128 for the IgM and IgG responses to phase I, at > or = 512 for the IgM response to phase II and at > or = 1,024 for the IgG response to phase II Coxiella burnetii. These titers gave a false-positive rate of < or = 1%. Alternatively, testing a single dilution of sera (1:128) gave specificities ranging from 97.3 to 98.7%. Tests with the greatest sensitivities, using serially diluted early convalescent-phase sera, were the IgM (84%) and IgG (80%) responses to phase II Coxiella burnetii. At a single serum dilution, 92% of early convalescent sera had a positive IgG response to phase II Coxiella burnetii. With a high specificity and good sensitivity, the EIA can be used to diagnose acute Q fever with a single convalescent serum specimen. The duration of a positive response was greater than five years.

Coxiella burnetii↗
PubMed1989

Kinetics of C-reactive protein in acute viral hepatitis.

The significance of C-reactive protein (CRP) in acute viral hepatitis was studied by measuring the serum CRP level in patients with acute hepatitis type A (AHA), B (AHB), and non-A, non-B (AHNANB) and examining its localization in liver biopsy specimens by the immunohistochemical method. The mean value of the serum CRP level determined by enzyme immunoassay (EIA), was markedly increased in the acute phase of AHA and AHB, particularly the former. It decreased rapidly in both AHA and AHB during the convalescent phase, but was generally low in AHNANB with no marked difference between the acute phase and the convalescent phase. Under light microscopy, CRP was stained in the cytoplasm of hepatocytes, and immuno-reactive products were observed in the rough endoplasmic reticulum (RER) by electron microscopy. In the acute phase, the intensity of staining was slightly greater in AHA, decreasing during the convalescent phase in AHA and AHB, but only weak staining was observed in all patients with AHNANB. Evaluation of CRP may be useful for clarification of differences in clinical manifestations and the mechanisms of inflammation among different types of hepatitis.

Acute Disease↗
PubMed1988

Computerized morphometry of liver cells in diffuse hepatic diseases.

Computerized morphometrical measurements were made of liver cells and their nuclei taken from livers of healthy persons and from patients with acute hepatitis (AH), chronic hepatitis (CH), and liver cirrhosis (LC). Liver biopsies were performed on 127 people (24 convalescing from acute hepatitis, 20 with chronic inactive hepatitis (CIH), 24 with chronic active hepatitis (CAH), 38 with liver cirrhosis (LC) and 21 who were healthy controls (HC]. The specimens were stained with hematoxylin-eosin, then light microscopic pictures were obtained. The original cells were magnified 1000 times. The sizes of the cells and of their nuclei were calculated using a computer. Correlative variation was noted in cell and nuclear sizes resulting in an consistently constant nucleus-cytoplasm ratio. Average sizes of both cells and nuclei were maximal in livers with LC, followed in decreasing order by those in livers with CAH, CIH, HC and convalescent AH. The smallest cells and nuclei were found in convalescent AH cases. It might be possible to some degree to obtain gross impressions of the histopathological type of the liver lesion by measuring the sizes of cells and nuclei of the liver.

Biopsy↗
PubMed2003

Type 1 diabetes islet associated antibodies in subjects infected by echovirus 16.

AIMS/HYPOTHESIS: To determine whether the emergent infection by echovirus 16 that occurred in Cuba during the year 2000 was related to the presence of Type 1 diabetes associated autoantibodies. METHODS: The presence of ICA, IAA, GADA, IA2 antibodies and neutralizing antibodies (NtAb) to echovirus 16 were determined in sera from 38 infected children and adolescents and 80 control subjects, matched in sex, age, local residence and time of sample collection. RESULTS: The occurrence of a large-scale echovirus 16 epidemic was associated with the appearance of humoral autoimmune markers of Type 1 diabetes, especially for ICA, IAA and GADA. In the convalescent stage, ICA, IAA and GADA seroconversion was shown in 92.1%, 44.7% and 28.9% of echovirus 16 infected subjects. None of the 80 uninfected subjects had ICA or IAA, while one was GADA positive. ICA, IAA and GADA frequency was higher in the convalescent than in the acute stage (p<0.0005). A strong positive correlation was found between the NtAb to echovirus 16 and ICA titres in both acute and convalescent stage (r=0.91; p<0.0001, r=0.55; p=0.0003 respectively). CONCLUSION/INTERPRETATION: This work provides evidence of an association between echovirus 16 infection and the presence of Type 1 diabetes related antibodies (ICA, IAA and GADA). Our data show that the echovirus 16 infection might be capable of inducing a process of autoimmune beta-cell damage and support the hypothesis that enterovirus infections are important risk factors for the development of Type 1 diabetes.

Adolescent↗
PubMed2003

Hemodynamic profiles of patients with dengue hemorrhagic fever during toxic stage: an echocardiographic study.

OBJECTIVE: To study left ventricular performance and hemodynamic abnormalities during different stages of dengue hemorrhagic fever (DHF). DESIGN AND SETTING: Observational study in a tertiary medical school hospital. PATIENTS: Twenty-four patients with serologically confirmed diagnosis of dengue virus infection and DHF according to the WHO criteria. METHODS: Echocardiography was performed during toxic, convalescent stages and at least 2 weeks after discharge (recovery). Left ventricular ejection fraction, rate-corrected velocity of circumferential fiber shortening adjusted for end-systolic meridional wall stress (VCFC/ESS) Z score, end-diastolic volume Z score, cardiac index, heart rate, mean arterial pressure, and total systemic vascular resistance (SVR) were compared between different stages of DHF. RESULTS: Ejection fraction and VCFC/ESS were significantly lower during the toxic stage than after recovery. End-diastolic volume was low during toxic stage and returned to normal during convalescence and recovery. Cardiac index was low during the toxic stage due to decreased preload (low end-diastolic volume) and depressed left ventricular ejection fraction. Cardiac index remained subnormal during convalescence due to sinus bradycardia. Wide variation in heart rate during toxic stage resulted in a small, nonsignificant increase compared to recovery. With treatment, heightened SVR resulted in relatively normal mean arterial pressure throughout the course of the illness. CONCLUSIONS: The mechanism of decreased cardiac output during toxic stage of DHF is complex. Decreased preload is accompanied by decreased left ventricular performance, and possibly a subnormal heart rate response in some patients.

Analysis of Variance↗
PubMed2000

Diagnostic laparoscopy for the acute abdomen and trauma.

BACKGROUND: We set out to investigate the potential benefits of routine diagnostic laparoscopy (DL) in cases of acute abdomen. METHODS: A prospective study of 120 DL in acute abdominal cases was performed in comparison with 310 similar acute abdominal cases treated without DL. The diagnostic accuracy, hospital stay, therapeutic delay, and convalescence time were then evaluated. RESULTS: DL established the indications for intervention in 96% of cases, yielded a diagnosis in 90%, and changed the treatment in 14%. The sensitivity achieved was 99.3%, specificity was 83.3%, and accuracy was 88.6%. There were two false positives, one false negative, and three results insufficient to make a diagnosis. Morbidity was one (0.8%), and mortality was one (0.8%). Seventy-nine patients (66%) were managed by laparoscopy and 24 by open interventions. The hospital stay in DL groups was shorter (median, 5 days vs 6 days in controls, p<0.0003), as was the effective treatment time (median, 5 days vs 6 days, p<0.0012). The convalescence time was also shorter in DL groups (median, 14 days vs 14 days, p<0.04). Therapeutic delay occurred in 16% of the control group cases, doubling the morbidity rate, increasing mortality by 50%, and prolonging hospital stay (median, 9 days vs 6 days, p>0.3 (NS). CONCLUSIONS: DL in the acute abdomen is a safe and accurate procedure that enables laparoscopic interventions and helps avoid nontherapeutic surgery. DL and appropriate treatment reduces hospital stay, therapeutic delay, and convalescence time.

Abdomen, Acute↗
PubMed1992

Fibrin (ogen)-derived peptide B beta 30-43 is a sensitive marker of activated neutrophils during fibrinolytic-treated acute myocardial infarction in man.

Neutrophils, elastase, the specifically elastase-derived fibrin split product, B beta 30-43, and C-reactive protein were determined in 30 consecutive patients with acute myocardial infarction. At admission to the coronary care unit 4.2 +/- 0.8 hours after the onset of symptoms, all elements were increased above the reference levels, while compared with convalescent levels, only neutrophils and B beta 30-43 were increased. After the streptokinase treatment, neutrophils, elastase, and B beta 30-43 increased abruptly and peaked (p less than 0.0001) within 1.5 hours. Plasma creatine kinase MB and C-reactive protein reached their peak levels after about 12 and 24 hours, respectively. Peak indices of neutrophils and creatine kinase correlated (r = 0.60, p less than 0.0006). Compared with the age-matched reference range, the convalescent level of B beta 30-43 was increased (p less than 0.0001). Of the tested elements suggestive of neutrophil activation, B beta 30-43 showed signs of being the most sensitive. In keeping with animal studies, neutrophils are activated early during the course of acute myocardial infarction and their activation seems to become accelerated by fibrinolytic treatment. Neutrophils may remain activated in the convalescent phase.

Biomarkers↗
PubMed1984

Modification of the clinical and histopathologic expression of experimental allergic encephalomyelitis by the vasoactive amine antagonist cyproheptadine.

Experimental allergic encephalomyelitis (EAE) is an autoimmune syndrome that can be induced in Lewis rats by myelin basic protein (BP) in complete Freund's adjuvant (CFA). Rats that have recovered from a primary episode of EAE display paradoxical long-term resistance to EAE reinduction by BP-CFA. Previous observations indicated, however, that clinical disease could be reinduced in convalescent rats by a concomitant secondary challenge with BP-CFA + Bordetella pertussis extract (PERT). Vascular permeability changes in the central nervous system (CNS) paralleled disease reinduction. To further probe the relationship between disease reinduction and vascular permeability, convalescent rats were treated with the vasoactive amine antagonist cyproheptadine (CYP) prior to a secondary challenge with BP-CFA + PERT. Data presented here indicate that CYP treatment results in substantial protection of convalescent rats from clinical disease reinduction by BP-CFA + PERT. CYP did not, however, prevent the development of new CNS lesions. CYP therapy also altered the clinical course of EAE induced by a primary injection of BP-CFA + PERT. In these rats, there was a delay in the onset of clinical signs as well as in the appearance of CNS lesions. Nevertheless, both CYP-treated and untreated naive rats challenged with BP-CFA + PERT eventually developed severe and usually lethal EAE. The effect of CYP on EAE induced in naive rats without including PERT in the sensitization protocol was also evaluated. In contrast to the mitigating effect of CYP on EAE induced or reinduced by BP-CFA + PERT, CYP treatment did not affect the clinical course or the development of CNS lesions in rats challenged with BP-CFA alone. Likewise, the passive transfer of EAE, mediated by mitogen-stimulated cells obtained from BP-CFA-sensitized donors, was not affected by CYP treatment. Collectively, these data indicate that CYP therapy altered the expression of EAE induced by regimens that included PERT, but did not affect EAE induced without PERT. In view of the opposing effects of PERT and CYP on vascular permeability, these data are consistent with the hypothesis that alterations in vascular permeability may play a crucial role in controlling the expression of autoimmune neurological diseases.

Animals↗
PubMed1981

A simple bactericidal antibody test for sero-diagnosis of typhoid fever.

Serum samples were collected from 24 confirmed cases of typhoid fever, 15 clinically suspected cases and 23 normal healthy controls. The convalescent sera were obtained in 13 of the 24 confirmed typhoid cases. In all, 13 paired sera, 11 acute phase only, 15 clinically suspected and 23 normal serum samples were tested for eliciting bactericidal antibodies to Salmonella typhi. In addition, the Widal test was also performed for comparison. All the 24 acute phase sera as well as 13 convalescent sera were found to be positive by bactericidal antibody test (titre 1:80 or above). Of 15 clinically suspected cases, 5 were positive whereas one of the 23 normal controls sera gave a false positive reaction. In contrast, the Widal test could detect only one of the 24 cases in the acute stage, but all 13 cases showed antibodies at a diagnostic titre level during the convalescent stage. None of the 15 clinically suspected cases or 23 normal controls were positive by the Widal test. The feasibility of using a bactericidal antibody test in sero-diagnosis of typhoid fever is discussed.

Acute Disease↗