bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibodies to single‐stranded DNA: An aid in diagnosis of viral hepatitis
Authors: Villarejos Victor M. , Arquembourg Pierre C. , Visoná Kirsten A. , Gutiérrez D. Alvaro
Published: March 2007

In clinical and subclinical viral hepatitis a significant increase of antibodies to single‐stranded DNA revealed the prepatent stage of the disease before any elevation of serum transaminases. In type A hepatitis, a rise in anti‐DNA titers was detectable one to two weeks before onset of clinical and biochemical signs; in type B hepatitis, the rise of anti‐DNA coincided with or preceded the appearance of HBsAg, several weeks before the onset of clinical illness. In both hepatitis types anti‐DNA titers reached a peak (640–2,560) at onset and dropped shortly after serum transaminases returned to normal at the end of acute illness. The anti‐DNA response in non‐A/non‐B hepatitis was of similar magnitude. Anti‐DNA elevation was the only positive sign found in most silent infections of either type that later showed specific seroconversion. Anti‐DNA levels in noninfected contacts were in the same range as those found in a group of healthy individuals.

The anti‐DNA test is useful for early diagnosis of viral hepatitis and should be a valuable addition to current epidemiological and clinical procedures.
Developments in viral hepatitis
Authors: Zuckerman Arie J.
Published: March 2007

Viral hepatitis is a major public health problem occurring endemically in all parts of the world. The general term viral hepatitis refers to infections caused by hepatitis virus type A, type B and a more recently identified infection referred to as “non‐A:non‐B” hepatitis. These clinically and pathologically similar forms of hepatitis have been studied intensively following the discovery of a specific antigen, Australia antigen, one of the markers of infection with hepatitis B virus.
Potentiation of coxsackievirus B3 infection in adult mice pretreated with a gold salt
Authors: Kabiri M. , Basiri E. , Kadivar D.
Published: March 2007

In mice treated with sodium aurothiomalate (myocrisin), prior to infection with Coxsackievirus B3, 90% of the animals died by the 11 th day postinfection (p.i.) A mortality of 10% was noted in mice receiving myocrisin only, and no deaths occurred in animals infected with virus alone.

The highest amount of virus was recovered from the pancreas of myocrisin‐treated mice on day 3 p.i. This was over 500‐fold higher than the virus titer found in the pancreas of mice infected with virus only. Generally the titer of virus present in different organs was higher at every point in drug‐treated animals as compared to intact mice infected with the virus. A high and persistent viremia was present in myocrisin‐treated mice; in contrast a low viremia followed by virus clearance from the blood was observed in intact mice infected with the virus.

The antibody response was studied in intact and myocrisin‐treated mice infected with the virus. In both groups, no neutralizing antibodies were detected on days 1, 2, and 3 p.i. On day 7 after infection, the titers of antibodies were 1:16 and 1:12 in intact and myocrisin‐treated mice, respectively.

Administration of hyperimmune anti‐Coxsackievirus B3 serum 6 hours after infection protrected the myocrisin‐treated group of mice against lethal disease.

The results of these studies suggest that (1) antibodies alone may not be sufficient to limit the spread and persistence of virus in natural infections and (2) in the absence of any apparent histopathological differences the increased multiplication of Coxsackievirus B3 could be the cause of death in myocrisintreated mice.
Cross‐reactive and type‐specific complement‐fixing structures of oriboca virions
Authors: Karabatsos Nick , Shope Robert E.
Published: March 2007

Characteristics of two components of Oriboca virus were studied after they were separated and semipurified by velocity centrifugation. A component of low infectivity and broad cross‐reactivity in the complement‐fixation (CF) test had a sedimentation coefficient of 6–7S. Infectious Oriboca virions with hemagglutinating (HA) activity had a sedimentation coefficient of 457S. These virions cross‐reacted broadly with Murutucu viral antibody. The crossreactive, virion‐associated component and a type‐specific CF fragment were released from virions by disruption with Nonidet P‐40. These CF fragments separated by sucrose gradient equilibrium centrifugation had densities of 1.245 gm/ml and 1.181 gm/ml, respectively, and were both interpreted to be envelope structures. The type‐specific CF antigen appeared to be related to the viral hemagglutinin in that it blocked hemagglutination‐in‐hibiting (HI) antibody, whereas the cross‐reactive CF fragment did not.
Clinical evaluation of a rubella passive hemagglutination test system
Authors: Kilgore James M.
Published: March 2007

A recently marketed passive hemagglutination (PHA) test (Rubacell, Abbott Laboratories) was compared to the hemagglutination inhibition (HI) test for the detection of antibody to rubella virus. The performance of the PHA system in determining immunity to rubella was evaluated by comparing the PHA results and HI results on 1,086 randomly selected sera submitted for routine premarital and prenatal testing. Of the 1,079 specimens assayable by both procedures, 1,053 of the results (97.6%) were in agreement on initial testing. When the 26 initially discrepant specimens were retested for clarification, there was final agreement in 1,067 of the specimens (98.9%). Twelve specimens were classified as persistently discrepant (five were not retested by PHA) and seven were unassayable by HI. Seven of the specimens with discrepant results were PHA positive and HI negative, and five were PHA negative and HI positive. Discussion of the two tests with respect to technical difficulty, cost, and controls is also included.
Solid‐phase radioimmunoassay of IgA, IgG, and IgM antibodies to human rotavirus
Authors: Sarkkinen Hannu K. , Meurman Olli H. , Halonen Pekka E.
Published: March 2007

A solid‐phase radioimmunoassay (RIA) has been developed for the detection of human rotavirus‐specific IgA, IgG, and IgM antibodies. Nebraska calf diarrhea virus grown in LLC‐MK2 cell cultures in the presence of trypsin was directly adsorbed onto polystyrene balls, and antibodies that attached to the virus‐coated balls were detected by subsequent binding of 125I‐labeled antibodies specific to human alpha, gamma or mu chains of human IgA, IgG, or IgM immunoglobulins. A total of 116 serum specimens from 58 adult patients were tested. Binding ratios between the positive and the negative serum varied between 5 and 15, occasionally being 20 or more in the IgA and IgG assays, but rarely exceeding 3 in the IgM assay. The RIA was found to be more sensitive in detecting antibodies to rotavirus than the complement fixation (CF) test, the RIA titers obtained being 50–100 times as high as the CF titers. The method described offers a possibility of evaluating the immune response to human rotavirus and of detecting recent infection.
ECHOvirus 33 replication in human peripheral white blood cells
Authors: Gnann John W. , Hayes Edward C. , Smith Joan Z. , Wilfert Catherine M.
Published: March 2007

ECHOvirus 33 isolated from the cerebrospinal fluid of a patient with agammaglobulinemia was shown to replicate in vitro in peripheral leukocyte suspensions from a normal antibody negative donor. Replication was demonstrated by use of sequential dilution experiments. Washed glass adherent mononuclear cell cultures from a normal antibody negative donor were also capable of supporting ECHOvirus 33 replication in vitro. Leukocyte suspensions from the infected agammaglobulinemic patient extinguished detectable infectious virus in vitro.
OC43 strain‐related coronavirus antibodies in different age groups
Authors: Hovi Tapani , Kainulainen Helena , Ziola Barry , Salmi Aimo
Published: March 2007

Serum antibodies against human coronavirus OC43 in different age groups were measured by complement fixation (CF), haemagglutination inhibition (HI), radial diffusion haemolysis‐in‐gel (HIG), and solid‐phase radioimmunoassay (RIA) methods. Antigen grown in suckling mouse brain was used in all tests. Results obtained by the CF and HIG tests, and the RIA, were in good agreement with regard to the presence or absence of antibodies. Similar results were also obtained with the HI test if nonspecific haemagglutination inhibitors were first removed by treatment with phospholipase C and only titers of 1:20 or greater were considered positive.

Children 6–23 months of age (n = 45) were without measurable coronavirus antibodies in all four assays. A rapid increase in the prevalence of antibodies then occurred in subsequent age groups, and practically all persons 6 years of age or older were found to have OC43 antibodies as measured by the HIG test or the RIA. The mean antibody levels determined by these two methods continued to increase, however, up to the age group of 10–14 years. This increase in antibody levels after the initial antibody incidence plateau may be due to boosting effects caused by related coronavirus strains, since OC43 antigens are known to cross‐react with antibodies induced by other human coronaviruses. Taken together, these data suggest that OC43 virus, or an antigenically related coronavirus strain, is very common in Finland.
Cell‐mediated cytotoxicity following influenza infection and vaccination in humans
Authors: Reichman Richard C. , Pons Vincent G. , Murphy Brian R. , Caplan Ellis A. , Dolin Raphael
Published: March 2007

Cell‐mediated cytotoxic activity in circulating mononuclear cells from 31 volunteers challenged with live influenza A/Victoria virus, and 22 volunteers vaccinated with inactivated influenza vaccine, was examined employing target cells infected with several viruses by means of a 51 Cr release assay. Effectors from infected volunteers, and from volunteers who manifested four‐fold rises in serum HAI antibody after vaccination, demonstrated significantly elevated levels of cytotoxicity against targets infected with the homologous virus. Elevated cytotoxicity was seen by days 3 and 4 after challenge or vaccination and returned to baseline levels by day 9 to 10. In infected volunteers, cytotoxic activity was broadly directed, rising against targets infected with an antigenically distinct virus within the same influenza type (A), against targets infected with a serologically unrelated virus of a different influenza type (B), and also against cells infected with Newcastle disease virus, a paramyxovirus from another species. However, elevated levels of cytotoxicity were not observed when targets infected with herpes simplex virus, a member of an entirely different virus group, or when uninfected target cells were employed. In vaccinated volunteers, the rise in cytotoxicity was more restricted than after infection, since elevated cytotoxic activity was seen only against cells infected with the homologous virus and not against influenza B‐infected cells. Fractionation of mononuclear cell populations indicated that effector cell activity is associated with T‐cell depleted fractions and can only partially be reduced by depletion of adherent cells. The rapid development, short duration, and broadly directed specificity of this cytotoxic response suggest that it may be involved in early events following acute influenza infection in humans.
Physicochemical heterogeneity of hepatitis B e antigen detected in asymptomatic carriers and carriers in a hemodialysis unit
Authors: Yamada Ei , Ohori Hitoshi , Ishida Nakao
Published: March 2007

Physicochemical studies of hepatitis B e antigen (HBeAg)

Both e1 and e2 antigens were included in the terminology of HBeAg or e antigen in the article for easy understanding. The e2 antigen corresponds to Magnius and Espmark's original e antigen and this should be called HBe antigen in the future (authors' opinion).

revealed a clear cut difference between e1 and e2 antigen. The e1 antigen was found to have a MW of Ca 150,000 and a pI of 6.4–7.2, whereas both the MW and pI of the e2 antigen were heterogeneous depending upon the source of serum.

Sera obtained from asymptomatic carriers were characterized by low titers of HBs antigen, HBc antigen and DNA polymerase and contained e2 antigen of larger molecular weight (200,000–300,000) with a narrow distribution range and a pI of 4.8 to 5.2 (type 1). On the other hand, the sera from patients in a hemodialysis unit who were HBs antigen carriers and had high titers of HBs antigen, HBc antigen and DNA polymerase contained e2 antigen of heterogeneous distribution in MW (from 300,000 to 70,000) and pI (type 2 and 3). The e2 antigen obtained from the higher MW type 3 serum had lower isoelectric points (pI 4.5 to 5.2) as was the case with e2 antigen obtained from asymptomatic carriers whereas a relatively wide range of isoelectric points (pI 5.1 to 8.2) was found with the lower molecular weight e2 antigen.
Adenine arabinoside inhibition of adenovirus replication enhanced by an adenosine deaminase inhibitor
Authors: Wigand R.
Published: March 2007

The inhibition of adenovirus multiplication by adenine arabinoside was determined by yield reduction in one‐step multiplication cycle. Inhibition was greatly enhanced by an adenosine deaminase inhibitor (2‐deoxycoformycin) in concentrations down to 10 ng/ml. Adenovirus types from four subgroups showed similar results. However, the enhancing effect of adenosine deaminase inhibitor was great in HeLa cells, moderate in human fibroblasts, and negligible in Vero cells. This difference could be explained by different concentrations of adenosine deaminase found in cell homogenates.
Antibodies to single stranded DNA: A diagnostic aid in chronic hepatitis b virus infections
Authors: Villarejos Victor M. , Serra C. Jaime , Visoná Kirsten A. , Eduarte Carlos E.
Published: March 2007

Serial determinations of titers of binding antibodies to single stranded DNA were performed over a period of three years in 43 type B hepatitis patients with persisting HBsAg who had either developed chronic hepatitis or were asymptomatic carriers. Patients with histopathological diagnosis of chronic active or chronic persistent hepatitis, with or without clinical symptoms, showed high titers of anti‐DNA throughout the course of the disease, whereas in most of these patients the serum alanine transaminase and bilirubin levels fluctuated widely and were often normal; in such cases the elevation of anti‐DNA was frequently the only positive sign present. On the other hand anti‐DNA titers were within the normal range in chronic asymptomatic HBsAg carriers who showed no histopathological or biochemical changes.

Anti‐DNA determinations are proposed as a reliable diagnostic aid to supplement current procedures for assessment of the disease status during the course of chronic hepatitis B virus infections.
Rhinovirus type 14 persistence in hela cells studied by use of guanidine
Authors: Gauntt Charles J.
Published: March 2007

Guanidine at 2 mM completely prevents replication of rhinovirus type 14 (RV14) in HeLa cells and spares these cells from RV14‐induced cytopathic effects. Three serial subcultivations of these cells in the continued presence of guanidine reduced infectious virus titers in cell lysates to undetectable levels. However, the capacity of RV14‐infected guanidine‐cultured cells to form infectious centers when cultured in the absence of guanidine was not completely abolished until the fifth serial subcultivation (14 days post‐inoculation). Production of defective‐interfering particles of RV 14 in HeLa cells was not observed. Thermal stability and transmission of uncoated RV 14 to daughter cells in the presence of guanidine can account for the persistence. Cells inoculated with RV14 and cultured in the presence of guanidine synthesized genomic RNA associated with a structure of 1.394 gm/ml density in CsCI, and these structures exhibited low infectivity by standard plaque assay. Nascent RV14 RNA did not appear in virions in cells treated with guanidine. HeLa cell lines (HeLaV+G), established following six serial subcultures of cells initially infected with RV 14 and continuously cultured in the presence of guanidine, were negative for RV 14 antigens by specific immunofluorescence tests. HeLaV+G cells were as efficient as normal HeLa cells in production of interferon; replication of RV 14 and mengovirus; and plaque assay of RV 14, rhinovirus type 2, and coxsackievirus B3.
Deeper insight into HBsAg — anti‐albumin antibody correlations
Authors: Lenkei R. , Babe¸ V. T. , Mustea A. , Dobre I.
Published: March 2007

The presence and titers of anti‐albumin antibodies (AAA) — ie, precipitins (AA‐IP) and agglutinins (AA‐Aggl) — and the serum concentrations of immunoglobulins and albumin were determined in 210 asymptomatic carriers of HBsAg grouped according to HBsAg titer and subtype. A different immunologic pattern was observed in the HBsAg/ad and HBsAg/ay carriers, the results suggesting an increased aggressivity for the HBsAg/ay subtype which was more evident in subjects with lower HBs antigenemia and characterized by higher concentrations of IgG and IgM and rises in AA‐P titers. A positive linear correlation was found between HBsAg and AA‐Aggl titers; the carriage of HBsAg/ad was associated with significant higher values of AA‐Aggl than of HBsAg/ay. These subtle correlations between HBsAg titer and subtype and AAA suggest that the human serum albumin (HSA) known to exist on the HBsAg particles may be similar in a modified form, to that representing AAA specificity.
Labeling of hepatitis B virus surface antigen (HBsAg) synthesized in a HBsAg‐producing hepatoma cell line
Authors: Hofschneider Peter Hans , Zaslavsky Vladimir , Deinhardt Friedrich , Frösner Gert G. , Alexander Jennifer J.
Published: March 2007

Hepatitis B virus surface antigen (HBsAg) could be studied until recently only by isolating it from the blood of carriers, thus making incorporation of radioactive precursors into this protein(s) impossible. The isolation of a cell line producing HBsAg [Alexander et al, 1978] has eliminated this obstacle. The cell line was therefore used for labeling HBsAg either with 35 S‐methionine or with 35 S‐cystine. HBsAg was purified by pelleting the component and by isopycnic centrifugation in CsCI gradients. HBsAg‐positive fractions (as determined by solid‐phase radioimmunoassay) were isolated from the gradients and analyzed in sodium dodecyl sulfate‐containing polyacrylamide gels. It was found that although HBsAg contains substantial amounts of35 S‐cystine, very little 35 S‐methionine was incorporated into this protein. In contrast, both labels were found in other structures having a buoyant density of about 1.3 gm/cm3 in CsCI. It was concluded that HBsAg is very low in methionine, and therefore this amino acid should not be used for labeling HBsAg in cells or in a cell‐free system. Analysis of 35 S‐cystine‐labeled HBsAg‐positive material (buoyant density about 1.2 gm/cm3 in CsCI) revealed five proteins with molecular weights in the range of 48,000–82,000.
Comparison of four‐layer radioimmunoassay and electron microscopy for detection of human rotavirus
Authors: Sarkkinen Hannu K. , Halonen Pekka E. , Arstila Pertti P.
Published: March 2007

A four‐layer radioimmunoassay (RIA) using polystyrene beads as the solid phase, anti‐rota guinea pig IgG as primary antibody, anti‐rota rabbit IgG as secondary antibody, and 125I‐labelled sheep anti‐rabbit immunoglobulin as indicator antibody has been developed for the detection of human rotavirus in stool specimens. A comparison was made of the developed RIA, routine electron microscopy, and research electron microscopy of 147 unconcentrated stool specimens from patients with infantile gastroenteritis. In routine electron microscopy 17 (11.6%) false‐positive or false‐negative results were obtained when compared with research electron microscopy. Each specimen positive in research electron microscopy was positive in RIA, and six additional RIA positives were found from 58 electron microscopy negative specimens. A confirmatory test was necessary to find out marginally positive but nonspecific reactions in RIA. The developed radioimmunoassay is slightly more sensitive than research electron microscopy of unconcentrated stool specimens and considerably more sensitive and more specific than routine electron microscopy.
Replication of murine cytomegalovirus in murine Y‐1 cells
Authors: Shanley John D. , Lutwick Larry I. , Donta Sam T.
Published: March 2007

Murine Y‐1 cells, a continuous epithelial cell line derived from an adrenal adenocarcinoma, are highly susceptible to murine cytomegalovirus (MCMV) infection. Inoculation of these cells with MCMV results in production of infectious virus and is associated with development of both cytopathic changes and the expression of viral‐specific nuclear and cytoplasmic antigens. Examination of the ultrastructure of infected Y‐1 cells reveals MCMV in various stages of replication. Cytomegalovirus replication in this hormone‐responsive epithelial cell line should provide a model system in which virus‐host cell interactions and their effects on cellular metabolism can be studied.
The effect of sodium thiocyanate on virus structure
Authors: Almeida June D. , Bradburne Anthony F. , Wreghitt Timothy G.
Published: March 2007

A study of two different virus types after elution from immunosorbent columns by sodium thiocyanate has shown that virus degradation occurs. The two virus types studied were hepatitis B and rotavirus. Hepatitis B antigen (HBAg) was only slowly degraded and retained many of its morphological features, although in an altered form; rotavirus was highly sensitive to the chaotropic agent, losing both its viability and its morphological integrity. During the process of disassembly a previously undetected inner component of rotavirus could be visualised, which was termed the “core”.
Purification of adenovirus 4 type‐specific hemagglutinins for use in diagnostic counterelectrophoresis tests
Authors: Hierholzer John C. , Tannock Gregory A.
Published: March 2007

Three type‐specific hemagglutinins of adenovirus (AV) 4 were purified, tested for various activities, and used as immunogens in rabbits. The components were purified by anion exchange and exclusion chromatographies to purification factors of 33, 20, and 37, respectively, and were identified as fiber (polypeptide, mol wt 70,000; incomplete hemagglutinin), penton (mol wt >400,000; incomplete hemagglutinin; possession of cytotoxic activity), and dodecon (mol wt ≫ 400,000; complete hemagglutinin; appearance by electron microscopy), Rabbit antisera to these hemagglutinating components possessed type‐specific hemagglutination‐inhibition and serum neutralization antibodies and were thoroughly evaluated for potency and specificity in immunodiffusion (ID), immunoelectrophoresis, and counterelectrophoresis (CE) tests. The anti‐fiber and anti‐dodecon sera were highly type‐specific in ID and CE tests with a battery of commonly isolated AV serotypes; the anti‐penton serum was similarly specific after it was absorbed with AV 2 hexons. These sera were thus proved to be suitable reagents for use in both the routine diagnostic ID test and the more rapid CE test.
The separation and analysis of hepatitis B e antigen
Authors: Howard C. R. , Zuckerman A. J.
Published: March 2007

A solid‐phase radioimmunoassay has been used successfully for detecting hepatitis B e antigen in fractionated hepatitis B virus‐containing serum. Ammonium sulphate precipitation followed by gel filtration through a column of Sepharose CL‐6B resulted in two fractions of antigen‐containing material with molecular weights of 220,000 and 130,000. The smaller of these two fractions was found to possess an average isoelectric point of 4.9 and consisted of two major polypeptide species with estimated molecular weights of 66,000 and 17,000 respectively. Affinity chromatography on Blue Sepharose showed that e antigen was not retained under conditions which bound serum albumin. These results are discussed in relation to the immunopathogenesis of hepatitis B.
Large‐scale efficacy trials of hepatitis B vaccines in the USA: Baseline data and protocols
Authors: Szmuness Wolf
Published: March 2007

The protocols of three placebo‐controlled, randomized, double‐blind clinical trials to assess the efficacy of an inactivated hepatitis B vaccine in dialysis patients and staff, and in male homosexuals are described. Based on the projected attack rates of HBV in the controls, the vaccine efficacy and rates of loss to follow‐up, over three thousand participants followed for at least twelve months are required to prove the efficacy of the vaccine. The results of longterm baseline studies in these populations are also reviewed.
Mitogen responses and interferon production after exposure of human macrophages to infectious and inactivated influenza viruses
Authors: Roberts Norbert J. , Diamond Margaret E. , Douglas R. Gordon , Simons Ruth L. , Steigbigel Roy T.
Published: March 2007

Human macrophages were exposed to two influenza A viruses representing different subtypes. The donors were likely to have been exposed to one subtype (H3N2) but not to the other (H0N1). Similar effects upon the macrophages were observed for both subtypes: macrophage enhancement of mitogen‐stimulated lymphocyte transformation responses was depressed, and the macrophages produced interferon. In contrast, macrophages exposed to inactivated virus exhibited normal enhancement of lymphocyte transformation response, yet produced interferon, although in lower titers than did macrophages exposed to infectious virus.
Two low molecular weight peptides as common determinants to different molecular forms and specificities of hepatitis b e antigen (hbeag)
Authors: Blanchy B. , Hantz O. , Vitvitski L. , Trépo C.
Published: March 2007

Two fractions, I and II, corresponding to heavy and light molecular forms of HBeAg and respectively associated with the (HBe/1 + HBe/2) and (HBe/3) specificities, were separated by ammonium sulfate precipitation in HBeAg‐positive chimpanzee plasma. I 125‐labeling of fractions I and II and immune precipitation by anti‐HBe and anti‐Human IgG were followed by autoradiographic analysis after SDS polyacrylamide gel electrophoresis:

This revealed that two small peptides (a major 17,000 MW and minor 21,000 MW) seem common to the various molecular forms and specificities of HBeAg. Both peptides were found tightly linked to IgG in fraction I, associated with HBe/1 and HBe/2 and precipitated by 1.33 M (NH4)2SO4. In the HBe/3‐positive fraction II these peptides seemed attached to IgG light chains only.
Further evidence of cellular changes associated with non‐a, non‐b hepatitis
Authors: Tsiquaye Kwesi N. , Bird Richard G. , Tovey George , John Wyke R. , Williams Roger , Zuckerman Arie J.
Published: March 2007

Two distinct types of ultrastructural changes were found in the hepatocytes of chimpanzees infected with two forms of non‐A, non‐B hepatitis. In the type of infection that was of long incubation, there was a marked cytoplasmic derangement of the endoplasmic reticulum, with the formation of tubules, but no pathological changes in the nuclei. In the short‐incubation type of non‐A, non‐B hepatitis, induced experimentally in a chimpanzee that had recovered from the long‐incubation type of infection, nuclear alterations were found together with the presence of aggregates of particles measuring 15–27 nm in diameter. Cytoplasmic tubules were not seen in this type of non‐A, non‐B infection.
Characterization of hbeag by physicochemical and immunochemical methods
Authors: Katz David , Melnick Joseph L. , Blaine Hollinger F.
Published: March 2007

HBeAg, which is a hepatitis B‐associated antigen, was purified and characterized. The end product from ion exchange, gel filtration and immunoadsorbent columns consisted mainly of immunoglobulin G (IgG) molecules, identified by immunoelectrophoresis and polyacrylamide gel electrophoresis. At least four polypeptides with molecular weights of 55,000, 38,000, 25,000 and 20,000 daltons were detected in four different preparations of HBeAg. Two of these have molecular weights similar to the heavy and light chains of IgG (55,000 and 25,000 daltons). It is postulated that HBeAg may be a small ligand of 20,000 daltons with an affinity for IgG. This affinity, especially if it involves the light chain of IgG, could account for the 38,000 or 42,000 molecular weight polypeptides seen by autoradiography.
Further studies on subacute encephalitis and hydrocephalus in hamsters caused by measles virus from persistently infected cell cultures
Authors: Norrby Erling , Swoveland Peggy , Johnson Kenneth P. , Kristensson Krister
Published: March 2007

Newborn hamsters were inoculated intracerebrally (IC) with disrupted measles carrier Lu 106 cells. No acute neurological disease developed, but limited, persistent neural infection was identified by immune fluorescence and by virus isolation. By ten days after inoculation, virus could be recovered only by co cultivation of explant cultures of central nervous system (CNS) tissue and Vero cells. Virus was still demonstrable in CNS by both techniques 50 days after inoculation, the latest sample collected. Animals inoculated as newborns developed a poor hem agglutination‐inhibiting (HI) antibody response.

In three‐week‐old hamsters inoculated IC no detectable replication of carrier virus occurred. The serum HI antibody response was more than 20 times higher than that in animals inoculated as newborns.

Hydrocephalus developed in a fraction of animals inoculated at birth or at the age of three weeks. Both infectious and heat‐inactivated disrupted virus carrier material, but not control material of Lu 106 cells, gave hydrocephalus. The precise mechanism leading to hydrocephalus is unclear. Carrier virus material may produce a meningeal irritation causing disturbances of the extraventricular flow or resorption of cerebrospinal fluid, leading to communicating hydrocephalus. Infectious carrier virus may replicate in and destroy ependymal cells, further contributing to hydrocephalus.
Tubular structures in the cervix of mice experimentally infected with herpes simplex virus type 2
Authors: Iwasaka Tsuyoshi , Oda Hiroshi , Hino Yuwao , Mori Ryoichi
Published: March 2007

Experimental infection of the C3H/N mouse genital tract was demonstrated after intravaginal inoculation with herpes simplex virus type 2 (HSV‐2). About 75% of the infected animals died by Day 7, and 75% of the surviving animals had severe vaginitis or neurological signs on Day 7. Titers of the virus recovered from vaginal secretions of infected animals reached a maximum on Day 2 and gradually decreased until Day 7. On the other hand, under the electron microscope, virus particles and tubular structures could be found in the nuclei of infected cells of the cervix in the 1st, 2nd and 4th days after infection. All cases in which virus particles could be found in the nuclei of infected cells were also positive for tubular structures and vice versa. These observations indicate that in situ diagnosis of HSV‐2 infection can be made in the mouse model. The same method would be applicable for the diagnosis of human HSV‐2 infection.
An outbreak of hepatitis a in an institution for the mentally retarded
Authors: Helmsing Pieter J. , Duermeyer Willem , Wielaard Frits , van Hattem Gerard C.A.M.
Published: March 2007

From December 1977 until April 1978 a hepatitis A outbreak occurred in an institution for the mentally retarded. The institution housed 311 residents and had a staff of 308. The outbreak was studied by enzyme‐linked immunosorbent assays for hepatitis A antigen and antibodies, and by liver function tests in serum.

When the investigations started, 13 residents and one staff member were ill and already seropositive; 34 of the 182 residents that were seronegative at that time and 1 2 of the 223 seronegative staff members subsequently developed disease. Out of the 60 eases 32 were asymptomatic; 19 cases with jaundice were seen.

Normal human immunoglobulin was administered to a large part of the seronegative group, but the effect is difficult to interpret as the immunoglobulin was often given after the presumed time of infection and failed to protect. Elevated liver enzyme levels were demonstrated in 38 of 60 patients.
Evaluation of solid‐phase enzyme‐lmmunoassay procedure in immunity surveys and diagnosis of rubella
Authors: Vaheri Antti , Salonen Eeva‐Marjatta
Published: March 2007

In the development of optimized micro‐ and macromethods for solid‐phase rubella enzyme‐immunoassay (EIA), the effect of various technical parameters was studied. Special emphasis was placed on elimination of defective polystyrene material, purity and quantity of immobilized antigen, use of reference sera in each microplate or macroprocedure, use of nonionic detergent in washing and diluent buffers, and use of a colourless enzyme substrate. A single serum dilution, analysed in duplicate, was sufficient provided the procedure was standardized. In quantitation of serum rubella antibodies, EIA gave values correlating well with those obtained with the single radial haemolysis test but not with low haemagglutination inhibition titres. The EIA procedure proved to be a useful and reliable serological tool in immunity surveys. When complemented by a rubella IgM test, EIA could also be used in diagnosis of recent rubella infections as a convenient primary serological test.
Relationship between antigenic type of virus and antibody response in female patients with herpes genitalis
Authors: Ozaki Yoshikatsu , Ohashi Masami , Kimura Edna Matiko , Ishiguro Tatsuya
Published: March 2007

The antigenic types of virus recovered from genital sites in cases of adult female genital herpes and antibody response in these patients were investigated. Twelve strains were isolated from 23 clinical specimens, and half the number of the isolates was classified as type 1 virus and the remaining half as type 2 virus. The results of serological typing corresponded well to biological differentiation by plaque‐forming ability on chick embryo cultures. The patients with type 1 virus infection had only the complement requiring neutralizing antibody, thus indicating a fresh infection. On the other hand, the noncomplement requiring neutralizing antibody was found in the patients with type 2 virus infection, indicating a later phase of infection.
Detection of antibodies to single‐stranded dna in naturally acquired and experimentally induced viral hepatitis
Authors: Gust Ian D. , Feinstone Stephen M. , Purcell Robert H. , Alter Harvey J.
Published: March 2007

A sensitive “Farr” assay, utilizing 125 I‐labelled DNA was developed for detecting antibody to single‐stranded DNA (anti‐ssDNA). The test was shown to be specific and as sensitive as assays using 14C‐labelled DNA, for the detection of antibody in patients with connective tissue diseases.

Groups of sera from patients with naturally acquired viral hepatitis and experimentally infected chimpanzees were tested for anti‐ssDNA by the 125I assay and by counterimmunoelectrophoresis (CIEP). No consistent pattern was observed with either technique, indicating that elevated levels of this antibody are not as reliable markers of parenchymal liver damage as had been previously suggested.
Hepatitis b e antigen and antibody: detection by radioimmunoassay in chimpanzees during experimental hepatitis b
Authors: Tabor Edward , Frösner Gert , Deinhardt Friedrich , Gerety Robert J.
Published: March 2007

Hepatitis B e antigen (HBeAg) and its antibody (anti‐HBe) were evaluated using a sensitive radioimmunoassay (RIA) in weekly serum samples obtained from nine chimpanzees experimentally infected with hepatitis B virus (HBV). In two chimpanzees with HBV infection with detectable hepatitis B surface antigen (HBsAg) for less than five weeks, and in one chimpanzee with documented HBV infection with no detectable HBsAg, HBeAg was not detected; in all three, anti‐HBe became detectable early in the infection. In six chimpanzees in which HBsAg was detected for 16 weeks or longer, HBeAg was detected early in the infection; in five, anti‐HBe became detectable and HBeAg unde‐tectable prior to the clearance of HBsAg. The sixth remained HBsAg‐positive and HBeAg‐positive for more than two years and never developed anti‐HBe. These results confirm the sensitivity of this RIA and its value in predicting the course of HBV infections.
Immunogenicity and reactogenicity of a highly purified vaccine against tick‐borne encephalitis
Authors: Kunz Christian , Heinz Franz X. , Hofmann Hanns
Published: March 2007

Immunogenicity and reactogenicity of a vaccine containing inactivated tick‐borne encephalitis vims prepared by continuous flow zonal ultracentrifugation were compared with those of a previously used, less purified vaccine. Antibody response as measured by hemagglutination inhibition (HI) and enzyme‐linked immunosorbent assay (ELISA) was 93% after two vaccinations and 100% after a third dose. The zonally purified vaccine impressively reduced the incidence of side reactions. Pyrexia (> 37.3°C) was recorded in only 4–10% of the vaccinees almost exclusively after first vaccinations compared to 17–68% with the old type of vaccine. When these results are evaluated according to criteria commonly used in the United States (ie, pyrexia> 100°F = 37.8°C), almost no fever would be recorded. The frequency of systemic side reactions was even lower (statistically significant) after second and third vaccinations. This highly purified vaccine therefore represents an effective and well‐tolerated means for the immunoprophylaxis of TBE.
Post‐Transfusion hepatitis: antigen/antibody systems correlated with non‐a, non‐b hepatitis
Authors: Chircu L.V. , Pezzella M. , Lacava V. , Ricci G.
Published: March 2007

In seven patients post‐transfusion hepatitis (PTH) was due to non‐A, non‐B virus(es) (38.9% of all PTH, while 61.1% were due to hepatitis B virus (HBV). No clinical or biochemical differences were observed in non‐A, non‐B PTH when compared with PTH due to HBV, while incubation period was very ample, from 15 days to nine months (generally 45 days to two months). An antigen/antibody system was shared by five of our patients (their sera showed precipitin lines when assayed by immunodiffusion with known sources of antigen or antibody), while in one patient an antigen/antibody system was detected when onset serum was assayed with self‐recovery serum but not when assayed with known sources of antigen and antibodies, nor with sera of the other five patients. Antigen was detected during the first weeks of illness, antibody at recovery, for both systems. The results suggest that there may be at least two antigen/antibody systems correlated to non‐A, non‐B hepatitis, not necessarily linked to incubation period.
Non‐A/Non‐B hepatitis in experimentally infected chimpanzees: cross‐challenge and electron microscopic studies
Authors: Bradley Daniel W. , Maynard James E. , Cook E. H. , Ebert James W. , Grave Me Clifton R. , Tsiquaye Kwesi N. , Kessler Harold , Zuckerman Arie J. , Miller Mahlon F. , Ling Chung‐Mei , Overby Lacy R.
Published: March 2007

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 VIII 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 structures 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.
Tubular forms of hepatitis b surface antigen bind with the nucleus of 22‐nm spherical hbsag particles
Authors: Mishiro S. , Imai M. , Gotanda T. , Takahashi K. , Sano T. , Yoshizawa H. , Miyakawa Y. , Mayumi M.
Published: March 2007

Spherical hepatitis B surface antigen particles (HbsAg) of 22‐nm diameter were treated with sodium dodecylsulphate in the absence of reducing agents, and their nuclei were exposed. Factors that interact with the nucleus of HbsAg were detected in the serum of HBsAg carriers who were seropositive for hepatitis B e antigen and identified as tubular forms of HBsAg. The other categories of hepatitis B antigen, Dane particles, and 22‐nm spherical HBsAg did not bind with the nucleus of HBsAg. When tubular forms of HBsAg had been treated with a proteolytic enzyme, they lost the reactivity to bind with the nucleus of HBsAg. On the basis of the results obtained, tubular forms of HBsAg bear the receptor of protein nature for the nucleus of 22‐nm spherical HBsAg. The receptor allows rapid determination of tubular forms by a haemagglutination method for the evaluation of their clinical and epidemiological implications.
Antibodies as immunological probes for studying the denaturation of hbsag
Authors: Neurath A. R. , Strick N.
Published: March 2007

Radioimmunoassays were developed for antibodies to denaturated forms of HBsAg (reduced and alkylated in an isotonic buffer (RA‐HBs) or in 8 M urea (RA‐urea‐HBs), or reduced in 8 M urea but not alkylated). These tests revealed that intact HBsAg and RA‐HBs shared common antigenic determinants, termed Re[Imai et al, 1974]. Anti‐Re is elicited in the course of immune response to intact HBsAg in humans and experimental animals. Denaturation in 8 M urea and alkylation causes the appearance of additional antigenic determinants, the specificity of which is affected by the reagent used for alkylation. Reduction in 8 M urea followed by treatment with iodoacetate reveals antigenic sites common for HBsAg and some human serum proteins. Antibodies specific for the Le Bouvier determinants of HBsAg are probably not the appropriate probe for detection of primary translational products of the hepatitis B virus genome.
Contrasting patterns and frequency of antibodies to the surface, core, and e antigens of hepatitis b virus in blood donors and in homosexual patients
Authors: Tedder R.S. , Cameron C.H. , Wilson‐Croome Ruth , Howell D.R. , Colgrove Anne , Barbara J.A.J.
Published: March 2007

An attempt was made to assess the significance of the relatively frequent low‐titre positive reactions in radioimmunoassays for antibody to hepatitis B surface antigen.

Serum specimens negative for surface antigen were assayed for antibodies to the surface, core, and e antigens of the Hepatitis B virus.

Two populations were studied—one of low hepatitis B incidence (2000 blood donors) and one of high incidence (200 male patients attending a clinic for sexually transmitted diseases).

The validity of some singly occurring low‐titre anti‐HBs and anti‐HBc reactions is questioned, and the occurrence of positive reactions unrelated to previous hepatitis B infection inferred.
Hepatitis a antibody in israel defence forces recruits
Authors: Kark Jeremy D. , Bar‐Shani Shulamit
Published: March 2007

Sera drawn from a sample of 1,147 military inductees, representative of the conscript population entering service in the Israel Defence Forces (IDF), in 1977, were examined by radioimmunoassay for hepatitis A virus (HAV) antibody. The prevalence of HAV antibody is considerably higher in males of Eastern origin (84.4%) than of Western origin (39.7%) and in females of Eastern origin (79.9%) as compared with those of Western origin (30.3%). The difference between males and females is not statistically significant when level of education is controlled. An inverse association between years of schooling and HAV antibodies is evident both for males and females, but is stronger in Westerners than Easterners. These findings have implications for HAV prevention in the IDF.
Ultrastructural Changes and Virus‐Like Particles Localized in Liver Hepatocytes of Chimpanzees Infected With Non‐A, Non‐B Hepatitis
Authors: Burk Kenneth H. , Cabral Guy A. , Dreesman Gordon R. , Peters Robert L. , Alter Harvey J.
Published: March 2007

Virus‐like particles have been visualized by electron microscopy in the liver hepatocytes of two out of four chimpanzees inoculated with two different human non‐A, non‐B hepatitis‐implicated plasmas. The first two chimpanzees, which were infected with the same inoculum (inoculum A), developed liver histological features characteristic of mild acute viral hepatitis as well as rises in their serum alanine aminotransferase levels. Clusters of intranuclear particles, 22 ± 2 nm in diameter, were visualized in one of every fifth hepatocytes in one of these two chimpanzees. Intracytoplasmic circular membrane fusions, 100 to 350 nm in diameter, were observed in the hepatocytes of the other chimpanzee receiving inoculum A.

The second two animals were infected with a different human plasma containing infectious NANB material (inoculum B). Both animals developed mild increased serum enzyme levels that were variable but generally elevated throughout the course of this study (220 days); minor, equivocal histologic changes were also observed. Intranuclear and intracytoplasmic particles, 20 ± 1 nm and 37 nm in diameter, respectively, were visualized in the liver of one of the two chimpanzees infected with inoculum B; intranuclear particles were observed in one of seventy‐five hepatocytes and intracytoplasmic particles were observed less frequently. In this same animal, intracytoplasmic circular membrane fusions, similar, if not identical to those described above, were also noted. The intranuclear particles observed in animals receiving inocula A and B were essentially identical, as were the cytoplasmic membrane fusions. Thus, both inocula produced nuclear and cytoplasmic ultrastructural changes. The intracytoplasmic particle clusters (37 nm) were seen in only one animal and demonstrated a high degree of homogeneity, as evidenced by their presence in highly ordered crystalline arrays. All chimpanzees were screened for and found to be negative for evidence of hepatitis A and B, as well as for Epstein‐Barr virus or cytomegalo‐virus‐induced hepatitis. Previous studies have suggested that nuclear and cytoplasmic ultrastructural changes, similar to those described herein, result from two distinct NANB infectious agents. In contrast, our data suggest that both morphologic changes may be caused by a single agent.