bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions between polymerized human albumin, hepatitis B surface antigen, and complement: II. involvement of Clq in or near the hepatitis B surface antigen receptor for polyalbumin
Authors: Milich D. R. , Bhatnagar P. K. , Papas Ellece D. , Vyas G. N.
Published: March 2007

A species‐specific receptor for polymerized human albumin (PHALB) has been reported on hepatitis B surface antigen (HBsAg)‐carrying particles. Our previous observations that human Clq also binds PHALB in a species‐restricted manner led us to investigate the possibility that HBsAg‐associated Clq is involved in the PHALB receptor on HBsAg particles. The temperature, ionic strength, and pH requirements necessary for binding of PHALB to both Clq and HBsAg were compared and found to be similar. Normal human serum and purified Clq inhibited the PHABL‐HBsAg interaction; the inhibition was markedly reduced in heat‐inactivated and Clq‐depleted serum. Heat‐denatured or reduced and alky‐lated Clq failed to inhibit the PHALB‐HBsAg binding. Moreover, human Clq was found to be present in purified preparations of HBsAg and the quantity detected paralleled the degree of PHALB‐HBsAg binding. While anti‐Clq inhibited the PHALB‐HBsAg interaction, anti‐Clr, ‐Cls, ‐C3, and ‐Ig were not inhibitory. Collagenase treatment of purified HBsAg reduced both PHALB‐binding activity and the degree of HBsAg‐associated Clq. These observations provide evidence that HBsAg‐associated Clq is involved in or near the HBsAg‐binding site for PHALB.
Propagation of hepatitis A virus in human embryo fibroblasts
Authors: Gauss‐Müller Verena , Friösner Gert G. , Deinhardt Friedrich
Published: March 2007

Human diploid fibroblasts and human primary liver cell carcinoma cells (PLC/PRF/5) were infected with hepatitis A virus (HAV) adapted to growth in cell culture or derived directly from human stool. Viral antigen was expressed in PLC/PRF/5 cells 28 days after infection with cell culture‐adapted HAV, and 50 days after infection with virus from human stool. In human fibroblasts the periods until first expression of viral antigen were 90 and 210 days, respectively. During further passages of HAV in fibroblasts the time of first appearance of antigen decreased to about 28 days. Biophysical properties of HAV extracted from infected fibroblasts were comparable to those of HAV derived directly from human stool. Immunofluorescence studies showed that the antigen was located exclusively within the cytoplasm of the infected fibroblasts. Kinetics of antigen production indicated that an equilibrium between virus multiplication and cell metabolism was reached in persistently infected fibroblasts.
Demonstration and partial characterization of an intermediate HBcAg (dane particle) population
Authors: Hess Georg , Arnold Wolfgang , Buschenfelde Karl‐Hermann Meyer Zum
Published: March 2007

Hepatitis‐B core antigen (HBcAg) was released from Dane particles previously separated from anti‐HBc by repeated pelleting through sucrose gradients separated into three HBcAg populations when analysed by cesium chloride density gradient centrifugation. Heavy HBcAg particles banded at a density of 1.355 gm/ml, intermediate HBcAg particles at a density of 1.33 gm/ml, and light HBcAg particles at a density of 1.30 gm/ml. Like heavy HBcAg particles, intermediate HBcAg particles contained DNA polymerase activity, but the ratio of HBcAg to DNA polymerase activity was significantly different in both populations. Intermediate HBcAg particles could not be separated from heavy HBcAg particles by rate sedimentation centrifugation. The size of the HBV‐DNA and the size of its single‐stranded gaps were not significantly different in heavy and and intermediate HBcAg populations. Data accumulated in this paper suggest that the intermediate HBcAg particle differs from the heavy HBcAg particle by the amount of HBcAg polypeptides and the number of HBcAg determinants exhibited.
Precipitin system detected in sera from patients with non‐A, non‐B hepatitis
Authors: Hoofnagle Jay H.
Published: March 2007

A precipitin system detected by immunodiffusion was identified using sera from patients with non‐A, non‐B hepatitis. This system resembled those described by other authors as serological tests for non‐A, non‐B antigens and antibodies. However, testing of sera from a large number of patients with acute and chronic liver diseases revealed that this precipitin system was not specific for non‐A, non‐B hepatitis. Further characterization of the precipitin system demonstrated that it did not represent a true antigen‐antibody reaction. Precipitin lines detected by immunodiffusion during the course of acute and chronic non‐A, non‐B hepatitis may not represent reactions specific for this disease.
Detection of antibody to varicella‐zoster virus by competitive and IgM‐antibody capture immunoassay
Authors: Tedder R. S. , Lord R. Bridget , Mortimer P. P.
Published: March 2007

A simple, sensitive, and specific competitive solid phase immunoassay for antibody to varicella‐zoster virus (anti‐VZV) is described. The assay uses reagents that can easily be prepared and is sparing of viral antigen. Using a solid phase coated with sheep IgG from a serum raised against human μ‐Fc, the same reagents will accurately detect anti‐VZV IgM.

The competitive assay divided sera from children and adults into immune and nonimmune groups that closely correlated with a history of previous VZV illness. It was not affected by the presence or absence of antibody to other herpes viruses. The IgM antibody capture assay demonstrated the presence of anti‐VZV IgM in sera from patients with both varicella and zoster and gave negative results in patients with infections unrelated to VZV and in healthy blood donors.
Antibody‐mediated infection of macrophages and macrophage‐like cell lines with 17D‐yellow fever virus
Authors: Schlesinger Jacob J. , Brandriss Michael W.
Published: March 2007

The 17D vaccine strain of yellow fever virus (17D‐YF) produces a safe human arboviral infection that can provide antisera of well‐defined specificity under chronologically defined conditions. We studied 17D‐YF growth in human peripheral blood macrophages and in two continuous Fc receptor‐bearing, macrophage‐like cell lines, P388D of mouse origin and U937 of human origin. Cells were infected with virus in the presence or absence of antibody to 17D‐YF and to two related flaviviruses, St. Louis encephalitis (SLE) and dengue 2 (D2V). The virus 17D‐YF grew in the three cell types when infection was established without antibody; viral yields were increased by addition of antibody to 17D‐YF, SLE, and D2V. Increased titers of virus were accompanied by an increased number of infected cells by immunofluorescent assay. Enhancing activity was present in the IgG but not the IgM fractions of immune sera. Infection without cytopathic effect was observed in U937.
Comparison of different methods for the detection of rubella‐specific IGM antibodies
Authors: Braun R. , Doerr H.W. , Geisen H.P. , Hornig C. , Huschka U. , Munk K.
Published: March 2007

The rubella specific IgM titer in the serum specimens originating from healthy persons and from patients with clinical signs of rubella infection was determined by hemagglutination inhibition or hemagglutination reduction after IgM separation with the following methods: (a) density gradient centrifugation; (b) Polyacrylamide agarose gel chromatography; (c) ion exchange chromatography with diethylaminoethyl cellulose columns; (d) solid‐phase immunosorbent technique using micro‐plates; (e) solid‐phase immunosorbent technique using Polyacrylamide microimmunobeads. Alternatively, we removed IgG and IgA by the use of protein A, anti‐IgG, and anti‐IgA, covalently coupled to controlled‐pore glass (f). The titers obtained by the different methods showed qualitatively good correlations when combined with mercaptoethanol reduction. The quantitative measurement of specific IgM titers, however, revealed a lower sensitivity of column chromatography and methods of removal of IgG/IgA.
Effect of centrifugation on herpes simplex virus isolation
Authors: Darougar S. , Gibson J. A. , Thaker U.
Published: March 2007

The effects of high‐speed centrifugation on the isolation of herpes simplex virus (HSV) were studied. Aliquots of laboratory or clinical specimens were inoculated into test tubes and flat‐bottomed tubes containing HEp2 monolayers. Test tubes were incubated at 35°C on roller drums (standard method), and flat‐bottomed tubes were centrifuged at 15,000g at 35°C for 1 hr, before being incubated at 35°C without rolling (centrifuged method).

Centrifugation of clinical and laboratory specimens of HSV type 1 and HSV type 2 produced significantly increased isolation rates compared with the standard method. When clinical and laboratory specimens were diluted, the centrifuged method was more sensitive at all dilutions. When 20 specimens were used for end‐point titrations, the centrifuged method was 10 times more sensitive for 15 specimens and 100 times more sensitive for five specimens. There was no difference in the time taken for the appearance of cytopathic effect (CPE) between the standard and centrifuged methods.
Radioimmunoassay detection of igm antibodies to the hbv‐associated delta (δ) antigen: Clinical significance in δ infection
Authors: Smedile Antonina , Lavarini Carla , Crivelli Osvaldo , Raimondo Giovanni , Fassone Maurizio , Rizzetto Mario
Published: March 2007

A sensitive radioimmunoassay was developed for specific detection of IgM antibodies to the hepatitis B virus‐associated δ antigen. The test is based on the selective absorption of IgM by anti–IgM fixed on a solid phase.

Transient primary IgM anti4 responses with no conversion to a secondary IgG response were observed in acute self–limited δ infection. IgM anti‐δ was invariably found in hepatitis B surface antigen (HBsAg) carriers with active δ infection and liver disease, while it was absent in HBsAg‐positive or negative individuals with anti‐δ of IgG class but without liver damage or intrahepatic δ antigen.

IgM anti‐δ appears useful in defining the epidemiology of acute δ infection and in the serological diagnosis of active δ disease from nonpathogenic or past δ infection.
Perinatal transmission of the hepatitis b virus and of the hbv‐associated delta agent from mothers to offspring in northern italy
Authors: Zanetti A.R. , Ferroni P. , Magliano E.M. , Pirovano P. , Lavarini Carla , Rizzetto M. , Massaro Anna L. , Gavinelli R. , Fabris C.
Published: March 2007

We report a prospective study on infants born to hepatitis B surface antigen (HBsAg) carrier mothers to estimate the incidence of perinatal transmission of HBV and HBV‐associated delta agent in Northern Italy. The risk of infection to the infant was related to the presence of the HBe antigen‐antibody system, HBV‐specific DNA polymerase activity and antibody to delta in maternal sera, and to the titer of anti‐HBe in babies at birth. The data of this study indicate:

1. Babies born to HBsAg carrier mothers with HBeAg in serum are at extremely high risk of acquiring HBV infection and of developing a chronic carrier state, whereas those born to anti‐HBe‐positive mothers are at a lower (P <.01) yet consistent risk of infection.

2. HBs antigenernia is usually prolonged and symptomatic in babies born to HBeAg–positive mothers while being self‐limited and asymptomatic in babies born to anti‐HBe‐positive mothers.

3. DNA polymerase activity in maternal serum appears to be the most sensitive marker predicting HBV transmission to the infant since it was detected in all the HBeAg‐positive mothers and also in two anti‐HBe‐positive mothers and in one HBeAg/anti‐HBe‐negative mother who transmitted infection to their babies.

4. High titers of anti‐HBe (up to 1:103) do not prevent HBV infection.

5. Vertical transmission of delta infection seems to occur only in circumstances that permit perinatal transmission of HBV infection.
An electron microscopic demonstration of immune complexes of hepatitis b e‐antigen using colloidal gold as a marker
Authors: Stannard Linda M. , Lemon Margaret , Hodgkiss Margaret , Smuts Heidi
Published: March 2007

Immune complexes of the hepatitis B e‐antigen (HBeAg) could be labeled and thus visually identified in the electron microscope by using antibody to HBeAg (anti‐HBe) tagged with colloidal gold particles. Circulating immune complexes of HBeAg were detected in sera from patients with acute hepatitis B infections as well as from asymptomatic carriers of hepatitis B surface antigens (HBsAg). Sera positive for rheumatoid factor frequently contained mixed aggregates in which immune complexes of HBsAg were closely bound to immune complexes of HBeAg.
Examination of crystalline arrays in non‐a, non‐b hepatitis
Authors: McCaul T.F. , Tsiquaye K.N. , Tovey G. , Duermeyer W. , Zuckerman A.J.
Published: March 2007

Individual particles within crystalline arrays found in the endothelial cells of hepatic sinusoids in experimental non‐A, non‐B hepatitis were examined by the Markham rotation technique. The particles appeared to possess an outer structure with 16–18 divisions. The presence of the crystalline structures is probably a reflection of host cell response to infection.
Prevalence of human coronavirus antibody in the population of southern iraq
Authors: Hasony Hassan J. , Macnaughton Malcolm R.
Published: March 2007

Sera from adults in Southern Iraq were collected during winter and screened by an enzyme–linked immunosorbent assay for the presence of antibodies to the two antigenic groups of human coronaviruses, the 229E and the OC43 groups: 91% of the sera had antibodies to at least one of the groups, whereas 4 and 5% of the sera had antibodies to only the 229E or OC43 groups, respectively. There was significant correlation between the levels of antibody to the 229E and OC43 group coronaviruses in these sera.
Antibody class capture assay (ACCA) for rubella‐specific IgM antibody
Authors: Isaac M. , Payne R. A.
Published: March 2007

Enzyme‐linked immunosorbent assays for IgM antirubella were carried out on 1,546 sera, using an IgM capture method with a F (ab/)2 conjugate (ACCA). Under the conditions described, sera containing IgM antirubella bound up to 15 times as much enzyme activity as negative specimens.

Paired serum specimens from 27 patients, serial serum specimens from 6 patients, and single serum specimens from 15 patients who had had recent rubella were examined by the haemagglutination inhibition test (HAI) in the presence and absence of 2‐mercaptoethanol following sucrose density gradient centrifugation (SDGC). ACCA confirmed all the results found with HAI following SDGC. Specimens were examined from ten patients with congenital rubella; ACCA confirmed the results found with both immunofluorescence following SDGC and radioimmunoassay. Pre‐ and post‐vaccination specimens from 123 patients who had been vaccinated against rubella were examined. An IgM response could only be demonstrated in the 57 cases when IgG was absent in the first specimen.

The specificity of the assay was confirmed by testing 31 serum specimens from rubella immune patients that also contained rheumatoid factor, 163 serum specimem from patients with acute infections other than rubella, and 12 serum specimens from infants with miscellaneous neonatal abnormalities other than congenital rubella. The ACCA proved a simple, sensitive, and specific test for IgM antirubella and the results compared favourably with those obtained by the SDGC technique.
Low molecular weight IgM in cytomegalovirus infections and cardiac patients
Authors: Nagington J. , Smith D. J. , Cranage M. P.
Published: March 2007

When 71 ischaemic heart disease and cardiomyopathy patients' sera were examined by the IFA (indirect fluorescent antibody) test, 18 of the 49 (36%) with CMV (cytomegalovirus) CF antibody appeared to contain a specific LMW (7S approx) IGM.

This IgM was unrelated to the presence of RF (rheumatoid factor) demonstrable by agglutination of IgG‐coated latex and by an immunofluorescence test, was not absorbed by heat‐aggregated IgG and latex, nor did its demonstration appear to be complement dependent. It was demonstrable in acute CMV infection and in some cardiac patients, binds to HSV (herpes simplex virus) and CMV‐infected cells.
Virus receptors for polymerized human albumin: A prognostic marker in HBeAg‐positive chronic hepatitis type B?
Authors: Alberti A. , Pontisso P. , Realdi G.
Published: March 2007

Seventeen out of 30 patients with chronic hepatitis type B with hepatitis B e antigen (HBeAg) in serum remained persistently positive for e antigen, while 13 seroconverted to antibody (anti‐HBe) when followed over a period of one to five years. Initial levels of serum hepatitis B virus (HBV) markers, such as the hepatitis B surface antigen (HBsAg), HBeAg, and HBV‐DNA polymerase (HBV‐DNAP) were similar in the two groups of patients, while initial titres of the HBsAg‐associated receptor for polymerized human serum albumin (pHSA), recently identified on HBV particles, were significantly higher in the patients who remained HBeAg positive (mean titre ± SD = 2−7.00 ± 2 −3.2) compared to the cases who eventually seroconverted to anti‐HBe during the follow‐up (2−2.54 ± 2−2.14 P < 0.001). A receptor titre above 1:64 by haemagglutination was highly predictive of persistence of HBeAg, suggesting that in patients with HBeAg‐positive chronic hepatitis testing for the HBsAg‐associated pHSA receptor may be useful in predicting the duration of HBe antigenaemia, with relevant clinical and prognostic implications.
Isolation and characterization of midway virus: A new tick‐borne virus related to nyamanini
Authors: Takahashi Mitsuo , Yunker C. E. , Clifford C. M. , Nakano Wataru , Fujino Norio , Tanifuji Katsuo , Thomas L. A.
Published: March 2007

Midway virus, a new tick‐borne virus isolated from two species of Ornithodoros (Alectorobius) ticks of the capensis group (O capensis, O denmarki), is described from Midway, Kure, and Manana islands in the Central Pacific (Hawaiian Archipelago) and from norther Honshu (Japan). Midway virion is enveloped, unusually large, acid and temperature sensitive, and its type of nucleic acid is RNA. Complement‐fixation (CF) tests show a close relation of Midway to Nyamanini virus, which has been isolated from ardeid birds and Argas ticks in Africa, the Indian subcontinent, and Southeastern Asia. However, cross‐box tests (CF, mouse and tissue culture neutralization, immunofluorescence) show that these two viruses are quite distinct. Midway virus is lethal for newborn Swiss mice inoculated by intracerebral, but not intraperitoneal route. It fails to kill four‐week‐old mice by either route. Midway virus causes cytopathic effects in BHK‐21 cells and titerable plaques in Vero cells. Antibodies to it were prevalent among nestlings of Larus crassirostris (Black‐tailed Gull) on Aomatsushima I., but were scarce among those of Nycticorax nycticorax (Black‐crowned Night Heron) of the same island.
Diversity within a human isolate of coxsackie B4: Relationship to viral‐induced diabetes
Authors: Hartig Phillip C. , Madge Gordon E. , Webb Stanley R.
Published: March 2007

The ability of different strains of a single virus type to produce different pathogenic expressions is well documented within the picornavirus group. Coxsackievirus, group B, type 4 (CB4) has been associated with viral‐induced diabetes in man, but expression of its potential to induce diabetes in experimental animals is variable. Evidence is presented here for one of the primary sources of this variability that could explain resulting contradictory reports offered in support or rejection of its diabetogenic potential. C57B1/6 and SWR mice were infected with the Edwards isolate of CB4 (CB4‐Edw) and three of its plaque‐purified virion “strains.” These were designated Edwards isolate‐1 (E1), E2, and E3. CB4‐Edw, E1, E2, and E3 were serologically similar by infectivity neutralization tests, had identical plaque morphology, and replicated to a similar level in the pancreas. The most profound difference was the level of virus antigen accumulation in the islet cells as determined by immunoperoxidase localization. CB4‐Edw had moderate antigen accumulation in most islet cells of SWR mice but was restricted to only a few specific cells within the periphery islets of C57B1/6 mice. Unlike CB4‐Edw all three new isolates accumulated antigen in most islet cells of both mouse strains. Virus isolate (strain) E2 showed the most intense accumulation in islet cells. These observations suggest that the Edwards isolate of CB4, like other human isolates of CB4 virus, probably exists as a heterogenous population of virion strains. The pathogenic consequences and expression of any diabetogenic potential is, therefore, dependent on virus strain selection. This diversity must be considered when evaluating the pathogenic nature of CB4 viruses in experimental animals and the possible role of the viruses in diabetes of man.
Characterization of a precipitating antigen detected in the serum of patients with viral hepatitis
Authors: Zhuang Hui , Coulepis Anthony G. , Locarnini Stephen A. , Marshall John A. , Gust Ian D. , Kaldor Jakov
Published: March 2007

During a search for the aetiological agent of non‐A non‐B hepatitis, a precipitating antigen was detected in the sera of some patients during the acute phase of their illness. The antigen was detected by agar gel diffusion using antibody from convalcscent sera obtained from patients with non‐A non‐B hepatitis, and from haemophiliac sera. The antigen was usually detected early in the patient's illness, disappearing as liver function tests returned to normal. In some patients specific antibody appeared during the convalescent phase of the disease. The antigen does not appear to be specific for non‐A non‐B hepatitis, as it could be detected with similar frequency in patients with hepatitis A or hepatitis B and some patients with other liver disorders. Biochemical and biophysical studies suggest that the antigen is probably an abnormal lipoprotein produced as a result of acute liver damage.
Detection and persistence of specific iga antibodies in serum of patients with hepatitis A by capture radioimmunoassay
Authors: Sikuler Emanuel , Keynan Arieh , Hanuka Negba , Friedman Maureen G. , Sarov Israel
Published: March 2007

The serum immunoglobulin A (IgA) response to hepatitis A virus (HAV) was investigated with a sensitive capture radioimmunoassay. In serial serum samples drawn from 15 patients with viral hepatitis A, IgA anti‐HAV antibodies reached their highest titer between 1–2 weeks after onset and peak titers ranged from 10,000–20,000. Serum samples were available from six patients 30–32 months after onset of illness. These samples were all positive for IgA anti‐HAV and some had titers similar to peak titers during illness. However, the height of the titration curves, expressed as the binding ratio (BR) at a dilution of 1/1000, was in all cases significantly lower at 30–32 months than during acute illness and early convalescence. The significance of the persistence of the IgA anti‐HAV and possible reasons for the change in the BR are discussed.
Progressive multifocal leucoencephalopathy: Detection of papovavirus jc in kidney tissue
Authors: Dörries K. , Meulen V. Ter
Published: March 2007

Cellular DNA of the kidney from a patient with PML was analyzed by reassociation kinetics for the presence of JC virus DNA. Various amounts of viral DNA sequences were detected in different areas of the kidney. The highest concentration (175 genome equivalents/cell) was found in the renal medulla and there were almost none in the renal cortex. Differentiation from the closely related BK virus was carried out by reassociation kinetics and restriction enzyme cleavage with subsequent Southern blot analysis. The enzyme Hind II, which does not cleave within the BK virus genome, generated four restriction enzyme fragments in the cellular DNA from the kidney, thus documenting the presence of JC virus DNA. By examination of the renal DNA with the “no‐cut” restriction enzyme XHO I and the “one‐cut” enzymes Eco RI and BAM HI it was possible to show that free and not integrated viral DNA was present in these cells. Nonhomogeneous defective DNA bands were not detectable. By in situ hybridization the epithelial cells lining the collecting tubules were found as predominant site of the viral infection in the kidney.
Opsonization of alphaviruses in hamsters
Authors: Jahrling Peter B. , Hesse Richard A. , Anderson Arthur O. , Gangemi J. David
Published: March 2007

Immune elimination of alphaviruses in immunized hamsters appears to involve formation of virus/antibody aggregates which are subsequently cleared from the circulation by cells of the reticuloendothelial system (RES). Virulent strains of Venezuelan (VEE) and Western equine encephalitis (WEE) viruses which were cleared slowly from the circulation of nonimmune hamsters, were cleared rapidly when inoculated into the blood of immunized hamsters. Likewise, when these viruses were mixed with specific hamster immune serum prior to inoculation, they were efficiently cleared from the circulation of nonimmune hamsters. Virus, mixed with specific immune serum, or inoculated into immunized hamsters, formed virus/antibody aggregates, as demonstrated by density gradient centrifugation, filtration through polycarbonate membranes, precipitation with Staphylococcus protein A, and electron microscopy. Cleared virus was concentrated primarily in liver and spleen, as confirmed by autoradiography. Immune clearance of virulent VEE was demonstrable within 5 to 6 days following immunization of hamsters with live attenuated VEE vaccine, strain TC‐83. In these hamsters, a close association was established between formation of virus/antibody aggregates, rapid clearance, and survival of challenged hamsters. Adsorption of virus to hamster macrophages in culture was enhanced by immune serum in the presence of complement. These results are compatible with the hypothesis that immune clearance of virus in the intact hamster involves a complement‐dependent interaction of virus/antibody complexes with cells which possess Fc and complement receptors. The clearance of immune complexes by the RES serves to amplify the protective effect of neutralizing antibody alone.
Protection of lassa virus‐infected guinea pigs with lassa‐immune plasma of guinea pig, primate, and human origin
Authors: Jahrling P. B.
Published: March 2007

Lassa virus‐immune plasma has been used to treat human Lassa fever patients; however, criteria for plasma selection were based arbitrarily on available serologic tools and protective efficacy was never directly assessed. To test the validity of plasma therapy for Lassa virus infections in an animal model, and to develop biologically relevant criteria for selection of protective immune plasma, inbred, strain 13 guinea pigs were infected with a lethal dose of Lassa virus and treated with various Lassa‐immune plasmas obtained from guinea pigs, primates, and convalescent human patients. Neutralizing antibody titers were determined in a virus dilution, plaque reduction test, and were expressed as a log10 plaque‐forming units (PFU) neutralization index (LNI). All guinea pigs treated with immune plasma 6 ml/kg/treatment on days 0, 3, and 6 after virus inoculation were protected, provided the LNI exceeded 2.0. Plasmas obtained from donors in early convalescence (32–45 days) had low titers of N‐antibody (LNI < 2) and failed to confer protection, despite high titers of Lassa antibody measured in the indirect fluorescent antibody (IFA) test. Higher doses of marginally titered plasma conferred increased protection. The degree of protection and suppression of viremia was closely associated with LNI and not IFA titers. Administration of low‐titered plasma did not result in immune enhancement. A high dose of human plasma from Liberia (12 ml/kg/treatment) was required to confer complete protection to guinea pigs infected with a Lassa virus strain from Sierra Leone (LNI = 1.6), while a lower dose (3 ml/kg/treatment) was sufficient for protection against a Liberian strain (LNI = 2.8), suggesting that a geographic matching of immune plasma and Lassa virus strain origin may increase treatment success. These studies support the concept of plasma therapy for Lassa infection and suggest that the plaque reduction neutralization test is more appropriate than the IFA test for predicting protective efficacy of passively administered plasma.
Preliminary observations on unidentified particles in mouse “L” cells found by electron microscopy
Authors: Ellis D. S. , Lloyd G. , Stamford Susan , Stagg Gillian
Published: March 2007

Long particles, 75 nm in diameter, some branching and some curled at their ends, were found within vacuoles in “L” cells. These could be easily transmitted to Vero cells, which like the “L” cells were killed. The particles were up to 20 μm in length with hollow cores 37 nm in diameter surrounded by a smooth unit membrane from which no spikes protruded. The particles could not be assigned to any known taxon.
Age‐specific prevalence of complement‐fixing antibodies to sixteen viral antigens: A computer analysis of 58,500 patients covering a period of eight years
Authors: Ukkonen Pentti , Hovi Tapani , Bonsdorff Carl‐Henrik Von , Saikku Pekka , Penttinen Kari
Published: March 2007

The age‐specific prevalence of CF antibodies against 16 viral antigens was determined by using the computerized data registry of the routine diagnostic laboratory of the authors' department. The material consisted of data based on serum specimens from about 58,500 patients. All ages from newborn infants to 90‐year‐olds were represented. The sera had been collected and tested with a CF screening test over a period of 8 years (1971–1978). Several different antibody prevalence patterns were distinguished in regard to the rapidity and timing of the initial increase of the prevalence, as well as to the mode of later changes in prevalence. For most respiratory viruses a rapid increase of the prevalence was seen through the childhood continuing, for some of them, up to the 30s (influenza A and coronavirus), while rather variable patterns were found in the older age groups. Herpes simplex and cytomegaloviruses showed, interestingly, another type of pattern: a slow increase of prevalence continuing through the whole age range. The frequency of herpes simplex antibodies reached 90% by the age of 80 years. Antibody levels against any antigen in infants less than one‐month‐old were equal to those in 20‐ to 40‐year‐old adults, and the expected rapid decrease of antibodies took place within the first 6 months of life. Possible influences of epidemics and repeated exposures to different viruses (external boosting), and of latent or chronic infections (internal boosting), as wells as of technical variations, on the observed prevalence patterns are discussed.
Monoclonal antibodies to herpes simplex virus type 1 glycoproteins show that epitope location influences virus neutralization
Authors: La Thangue N. B. , Chan W. L. , Almeida June D.
Published: March 2007

Three monoclonal antibodies, G8D1, C2D2, and TI57, reacting with herpes simplex virus type 1 glycoproteins have been characterised according to the location of their epitope and ability to neutralize infective virus. Immune electron microscopy and a blocking radioimmunoassay were used to locate the epitopes. The results indicate that the epitope recognised by G8D1 is located on the surface of the glycoprotein fringe, whereas those recognized by C2D2 and TI57 are interior with respect to this. Only G8D1 has neutralizing activity alone, whereas C2D2 can neutralize when antiglobulin is added. Thus, epitope location and density determine the neutralizing capacity of individual antibody molecules.
Diagnosis of respiratory syncytial virus infection in children: Comparison of viral antigen detection and serology
Authors: Meurman Olli , Sarkkinen Hannu , Ruuskanen Olli , Hanninen Pentti , Halonen Pekka
Published: March 2007

Direct detection of viral antigen in nasopharyngeal secretion by radioimmunoassay was compared with serology by IgG antibody enzyme immunoassay for diagnostic efficacy in 77 children with clinically suspected respiratory syncytial virus (RSV) infections. Antigen detection gave a positive diagnosis in 26 of 33 (79%) children in whom RSV infection was diagnosed by any of the two methods. The diagnostic efficacy of antigen detection was dependent upon the interval after onset at which specimens were collected; 88% of specimens taken during the first 5 days and 50% of specimens taken 6–10 days after onset of illness were positive. It was also dependent on the age of the patients, the diagnostic efficacy being 88 and 76% in children under and over 6 months of age, respectively.
The isolation of enteroviruses from blood: A comparison of four processing methods
Authors: Prather Sandra L. , Dagan Ron , Jenista Jerri A. , Menegus Marilyn A.
Published: March 2007

Blood from 28 children hospitalized with symptomatic enterovirus infections was processed by four different methods in an effort to define optimum conditions for detecting viremia. Enteroviremia was demonstrated in 11/28 children. Virus was isolated by method 1 (serum) in 7/11 children and by method 2 (mononuclear leukocytes) in 9/11, but in only 3/10 and 3/11 children by methods 3 and 4 (granulocytes and plasma‐mixed leukocytes, respectively). In four children, the only blood isolate was from mononuclear leukocytes, and in two, serum was the only positive blood preparation. This suggests that viremia can be often detected in hospitalized children with enterovirus disease and shows that the methods used for processing blood may significantly influence the isolation rate.
Treatment of chronic non‐A, non‐B hepatitis with acyclovir: Pilot study
Authors: Pappas S. Chris , Hoofnagle Jay H. , Young Neal , Straus Stephen E. , Jones E. Anthony
Published: March 2007

Five patients with chronic non‐A, non‐B hepatitis were entered into a pilot therapeutic study of the antiviral agent acyclovir [9‐(2‐hydroxyethoxymethyl) guanine]. Each patient received acyclovir by slow intravenous infusion in a dosage of 5 mg/kg every 8 hr for 10 days. During therapy, serum aminotransferase levels decreased by more than 50% in two patients, remained unchanged in two patients, and rose (by 32%) in the final patient. The two patients whose serum aminotransferase levels decreased during acyclovir treatment subsequently received a second course of drug using a higher dose (10 mg/kg every 8 hr for 10 days). Serum aminotransferase levels rose in both patients (by 54% and 121%) during the second course of therapy. Acyclovir was well tolerated in these patients, and there were no symptoms or signs attributable to drug toxicity during or after treatment. During a subsequent 12‐month follow‐up period, none of the five patients has manifested either a clinical or serum biochemical improvement in their chronic liver disease. Spontaneous fluctuations in serum aminotransferase levels unrelated to acyclovir therapy were noted in three of the five patients. These findings suggest that a short course of acyclovir does not have any appreciable long‐term beneficial effect on the course of chronic non‐A, non‐B hepatitis.
Antiviral effect of flavonoids on human viruses
Authors: Kaul Tej N. , Middleton Elliott , Ogra Pearay L.
Published: March 2007

The effect of several naturally occurring dietary flavonoids including quercetin, naringin, hesperetin, and catechin on the infectivity and replication of herpes simplex virus type 1 (HSV‐I), polio‐virus type 1, parainfluenza virus type 3 (Pf‐3), and respiratory syncytial virus (RSV) was studied in vitro in cell culture monolayers employing the technique of viral plaque reduction. Quercetin caused a concentration‐dependent reduction in the infectivity of each virus. In addition, it reduced intracellular replication of each virus when monolayers were infected and subsequently cultured in medium containing quercetin. Preincubation of tissue culture cell monolayers with quercetin did not affect the ability of the viruses to infect or replicate in the tissue culture monolayers. Hesperetin had no effect on infectivity but it reduced intracellular replication of each of the viruses. Catechin inhibited the infectivity but not the replication of RSV and HSV‐1 and had negligible effects on the other viruses. Naringin had no effect on either the infectivity or the replication of any of the viruses studied. Thus, naturally occurring flavonoids possess a variable spectrum of antiviral activity against certain RNA (RSV, Pf‐3, polio) and DNA (HSV‐1) viruses acting to inhibit infectivity and/or replication.
Etiopathogenetic aspects of hepatitis A. I. Excretion of hepatitis A virus, biochemistry of liver function, and humoral immune response in patients with hepatitis A on admission to hospital
Authors: Ślusarczyk J. , Hansson B. G. , Nordenfelt E. , Krawczyński K. , Karwowska S. , Knap J.
Published: March 2007

The excretion of hepatitis A virus (HAV) in stools from 30 patients with clinically overt hepatitis A infection on the day of their admission to the hospital was determined and compared with the dynamics and values of biochemical indices of hepatocyte injury as well as with the immune response to HAV. Virus was found in 16 out of 30 stools (53%) collected within 1 week after the appearance of clinical symptoms. In sera obtained on the day of hospitalization both IgM and IgA anti‐HAV were detected in all of the 30 patients, while IgG anti‐HAV were found in 20 (67%). There was a correlation between HAV excretion and increasing SGPT upon admission to hospital, while the level of SGPT or bilirubin as well as presence or absence of IgG anti‐HAV did not correlate with excretion of HAV.

HAV from stools was characterized morphologically and physicochemically. The majority of particles visualized by immune electron microscopy had electron‐dense appearance, while electron‐lucid particles were only occasionally encountered. Isopycnic banding of HAV in CsCl revealed a broad range of densities with HAV activity. Rebanding of pooled fractions containing HAV revealed peak amounts of the virus in fractions with densities 1.32–1.33 gm/cm3.
Lytic cytomegalovirus replication and the hormones of human pregnancy
Authors: Koment Roger W.
Published: March 2007

The frequency of human cytomegalovirus (CMV) excretion during pregnancy denoting active infection has been demonstrated to increase as gestation advances and at term involves a significant percentage of women. This increase enhances the risk of congenital infection of the fetus. Thus it appears that some factor(s) unique to the condition of pregnancy favors susceptibility to maternal CMV infection. We designed our studies to investigate the possible association of the continuously rising levels of selected hormones and this increased susceptibility. Progesterone, 17β‐estradiol, and cortisol were added to tissue culture media in final concentrations to match those occurring in term pregnancy serum. Two strains of human foreskin cells, one neonatal and the other fetal, were treated with either single or paired combinations of hormone‐containing media. Lytic CMV replication in neonatal foreskin cells was enhanced by a maximum of 5.7‐fold when these cells were treated with cortisol. Such enhancement did not occur in the fetal cells. No synergistic effects were seen when cortisol was used in combination with other hormones nor when neonatal foreskin cells were replicated for at least three generations in either single or paired combinations of hormones prior to use. Differential hormonal enhancement of CMV replication in vitro suggests a possible mechanism for the increased incidence of CMV infection observed during human pregnancy.
Kinetics of specific IgA, IgD, IgE, IgG, and IgM antibody responses in rubella
Authors: Salonen Eeva‐Marjatta , Hovi Tapani , Meurman Olli , Vesikari Timo , Vaheri Antti
Published: March 2007

Rubella‐specific IgD and IgE antibodies were determined with a solid‐phase enzyme immunoassay using enzyme‐labeled heavy‐chain specific anti‐immunoglobulins, and the antibody responses in rubella infection were compared to IgM, IgA, and IgG antibodies. IgD and IgE antibodies increased rapidly after the onset of infection, remained at a high level for at least 2 months, and declined slightly by 6 months. In comparison, the IgM antibodies decreased more rapidly, whereas the IgG antibodies persisted longer at a steady level. By 6 months the mean levels of the different antibodies had declined from their maximal mean levels as follows: IgM, 52%; IgA, 42%; IgE, 35%; IgD, 29%; and IgG, 8%. Thus IgD and IgE antibodies, in spite of their known short half lives, persisted longer than IgM and IgA antibodies, which limits their diagnostic value. The IgA antibody responses were found too variable to substitute for IgM antibody determination in diagnosis of a recent rubella virus infection from a single serum specimen. Comparison of maternal and cord blood sera indicated that, in addition to IgG antibodies, rubellaspecific IgD antibodies were found to cross the placenta.
The prevalence of antibodies to reovirus type 3 in adults with idiopathic cholestatic liver disease
Authors: Minuk G. Y. , Paul R. W. , Lee P. W. K.
Published: March 2007

Recent evidence suggests that neonatal infection with Reovirus type 3 (Reo‐3) may play an important role in the pathogenesis of certain idiopathic cholestatic liver diseases of children. Whether this virus is of pathogenetic importance in similar diseases seen in adults is unclear. In this study, sera from 22 adults with idiopathic cholestatic liver disease (16 primary biliary cirrhosis (PBC) and six primary sclerosing cholangitis (PSC)) were tested for antibody to Reo‐3 virus by a standard hemagglutination inhibition assay. The results were compared to antibody prevalence in ten adults with various other causes of chronic liver disease and 11 healthy volunteers. Although patients with idiopathic cholestatic liver disease had a high prevalence of anti Reo‐3 antibodies (20/22, 91%), similar prevalence rates were found in the two control populations (7/10, 70% in chronic liver disease controls and 11/11, 100% in healthy volunteers). Moreover, the geometric mean litres of antibody to Reo‐3 virus were similar in all study groups. While these results do not exclude a pathogenetic role for Reo‐3 viral infection, they do imply that some genetic predisposition must exist if Reo‐3 infection is truly of pathogenetic importance in idiopathic cholestatic liver disease of adults.
Production of interferon alpha and interferon gamma by peripheral blood leukocytes from patients with chronic hepatitis B virus infection
Authors: Abb Jochen , Zachoval Vera , Deinhardt Friedrich , Pape Gerd R. , Zachoval Reinhart , Eisenburg Josef
Published: March 2007

Peripheral blood leukocytes from patients with chronic hepatitis B virus (HBV) infection were studied for their capacity to produce interferon (IFN) alpha or IFN gamma. Yields of IFN alpha in leukocyte cultures stimulated with influenza A virus or human leukemic cells were significantly lower than those obtained from healthy controls. Production of IFN gamma in response to induction with protein A of Staphylococcus aureus was also significantly diminished. Defects of IFN production in leukocyte cultures showed no correlation with active viral replication or the degree of severity of HBV‐associated liver disease. The demonstration of partial defects of endogenous IFN production provides a rationale for using IFN replacement therapy in patients with chronic HBV infection.
Persistence of serum IgA antibodies to herpes simplex, varicella‐zoster, cytomegalovirus, and rubella virus detected by enzyme‐linked immunosorbent assays
Authors: Morris Gillian E. , Coleman R. Marie , Best Jennifer M. , Benetato Bonnie B. , Nahmias Andé J.
Published: March 2007

Enzyme‐linked immunosorbent assays were used to detect IgG and IgA antibodies to herpes simplex virus (HSV), varicella‐zoster virus (VZV), cytomegalovirus (CMV), and rubella virus in sera from 68 adult female gynaecological patients. Of the patients who had virus‐specific IgG antibodies, the proportion who also had virus‐specific IgA was 98% for HSV, 75% for VZV, 73% for rubella virus, and 42% for CMV. IgA antibodies to all four viruses were only found when specific IgG antibodies were also detected in the serum. These results suggest that virus‐specific IgA may persist for several years; possible explanations for this are discussed.
Virological and serological diagnosis of cytomegalovirus infection in bone marrow allograft recipients
Authors: Panjwani D. D. , Ball M. G. , Berry N. J. , Wimperis J. Z. , Blacklock H. A. , Prentice H. G. , Hoffbrand A. V. , Griffiths P. D.
Published: March 2007

To detect cytomegalovirus (CMV) infections, a total of 1,074 cultures of urine, saliva, or blood were collected weekly from 43 consecutive patients undergoing allogeneic bone marrow transplantation. Twenty‐three patients were seronegative before transplant and primary infection occurred in 2 (9%). Twenty patients were initially seropositive and recurrent infections occurred in 5 (25%). Three patients in the recurrent group had proven CMV pneumonitis; viraemia was detected in two recipients, while the third had CMV isolated only from bronchial lavage fluid.

The serological response of the 43 patients was defined by testing 559 serial sera for specific IgG and IgM antibodies by radioimmunoassay. Passive acquisition of IgG antibodies from blood products was found in 78% of initially seronegative recipients. One patient with primary infection responded in a pattern typical of immunocompetent individuals with long‐term production of specific IgG and transient production of specific IgM antibodies. The second patient also had a typical response, but this was delayed until several weeks after the start of virus excretion. In patients with recurrent infections, specific IgM production did not correlate with episodes of virus excretion. Three of five such patients failed to mount a specific IgM response, and these were the only patients in the study to develop CMV pneumonitis.

We conclude that CMV infection in bone marrow recipients can only be diagnosed by detection of virus; therefore, the ability of these patients to mount humoral immune responses should not be relied upon for diagnostic purposes.
Safety and immunogenicity of a recombinant hepatitis B vaccine
Authors: Dandolos E. , Roumeliotou‐Karayannis A. , Richardson S. C. , Papaevangelou G.
Published: March 2007

A hepatitis B vaccine produced in yeast by recombinant DNA technology was evaluated using 5‐μg and 10‐μg doses in a randomized trial lasting 7 months in 110 male armed forces recruits aged 17–19 years. Results were compared to those of an identical trial of a plasma‐derived vaccine. No allergic reactions were observed, and the rate of mild side effects was similar to the plasma‐derived vaccine. Seroconversion rates in the first month were 60% (33/55) and 67% (37/55) with the 5‐μg and 10‐μg doses of the recombinant vaccine, respectively. All participants seroconverted by 3 months, and none lost antibody. These results are very similar to those for plasma‐derived vaccine. Comparison of titres of antibody to hepatitis B surface antigen (anti‐HBs) showed a slightly higher level with the 10‐μg than with the 5‐μg dose of the recombinant vaccine. Geometric mean titres of anti‐HBs after the booster dose were similar in the 5‐μg and 10‐μg dose recombinant vaccine groups (2,620 and 2,748 IU/I, respectively) and in the 5‐μg plasma‐derived vaccine group (3,591 IU/I) but significantly higher (9,227 IU/I) with the 10‐μg dose of the plasma‐derived vaccine. These results confirm the safety and immunogenicity of the recombinant vaccine, although further study is needed on the duration of immunity.