bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary hepatocellular carcinoma and hepatitis B virus infection in korea
Authors: Chung Whan Kook , Sun Hee Sik , Park Doo Ho , Minuk Gerald Y. , Hoofnagle Jay H.
Published: March 2007

Serological evidence of hepatitis B virus (HBV) infection and serum alphafetoprotein (AFP) were assayed in sera from 112 Korean patients with primary hepatocellular carcinoma (PHC) and from 63 age‐ and sex‐matched controls. Serological evidence of HBV infection was found in 100% of PHC patients and in 97% of controls. The majority of PHC patients (87%) were positive for hepatitis B surface antigen (HBsAg). In contrast, only 14% of control individuals were positive for HBsAg, but 82% were positive for antibody to HBsAg (anti‐HBs). Hepatitis B e antigen (HBeAg) was detected in a high percentage (38%) of HBsAg‐positive PHC patients, but in none of the nine HBsAg‐positive control individuals. Serum AFP was detectable in 83% of PHC patients but in only one of 63 controls (1.5%). These results document that HBV infection may be the mjor factor in the development of PHC in this country.
The detection of antibodies to cytomegalovirus in the sera of renal transplant patients by an igm antibody capture assay
Authors: Sutherland Sheena , Briggs J. Douglas
Published: March 2007

An IgM antibody capture assay for detection of cytomegalovirus (CMV) IgM antibody (MACRIA) was developed. It was shown to be of similar sensitivity to the indirect immunofluorescence test but has the advantage that rheumatoid factor does not react in it and pretest fractionation of serum is not required. It does, however, give false results with some Paul Bunnell‐positive sera.

The assay was used to measure the IgM response in 28 renal transplant patients followed prospectively. Seven patients (100%) with primary infections and six of 13 (46%) patients with secondary infections developed IgM by MACRIA. Nine of 13 (69%) patients with CMV IgM‐positive sera had symptoms other than pyrexia associated with CMV infections, while only one of seven (14%) IgM‐negative infections were symptomatic. Four of seven irreversible rejection episodes were associated with CMV IgM. The possible significance of CMV IgM production is discussed.
Congenital and perinatal infection with junin virus in guinea pigs
Authors: Sangiorgio Patricia , Weissenbacher Mercedes C.
Published: March 2007

Junin virus infection in guinea pigs is known to be similar to human Argentine hemorrhagic fever (AHF). The guinea pig was chosen as a model for transplacental transmission of Junin virus, as both guinea pig and man have a similar placental structure. Pregnant guinea pigs were infected with the pathogenic XJ strain of Junin virus intramuscularly route at different stages of pregnancy. The group infected during the last third of pregnancy produced 16 newborn, but mortality reached 100%: 18% were born with typical AHF hemorrhagic signs, 54% without signs, and the remainder were stillborn.

Virus was recovered from organs of newborns, as well as placental tissues. A second group, infected in the second third of pregnancy, died with intrauterine fetuses, all of which showed hemorrhagic signs and virus present. In a last group, infected in the first third of pregnancy, fetuses were free from macroscopic lesions. In order to determine whether lactation may be an alternative infection route in guinea pigs, mother guinea pigs were infected with Junin virus at different times postparturition. The 84% noninfected newborn housed together with their infected mothers died during the suckling period, half with typical AHF signs.

Junin virus transmission from mother to fetus was thus proved, and lactation may be considered as an alternative perinatal infection route.
Candidate adenoviruses 40 and 41: Fastidious adenoviruses from human infant stool
Authors: De Jong J. C. , Kapsenberg Jacoba G. , Muzerie C. J. , Wermenbol A. G. , Kidd A. H. , Wadell G. , Firtzlaff R.‐G. , Wigand R.
Published: March 2007

About 200 antigenically related adenovimses were isolated from cases of infantile diarrhoea in the Netherlands and North‐West Germany. The viruses were fastidious and failed to replicate serially in human diploid fibroblasts and in primary human embryonic kidney cells. A number of strains were established in HeLa, HEp‐2, Graham (293), cynomolgus monkey kidney, and Chang conjunctival cells. The viruses were mammalian adenoviruses by the usual criteria. No relationship to the 39 known human adenovirus species was found, either by neutralization tests or by haemagglutination inhibition tests. Neutralization tests showed two distinct variants, represented by strains Tak and Dugan. The variants were identical in haemagglutination inhibition tests. DNA restriction enzyme analysis showed Tak and Dugan to have considerably different genomcs, indicating that these variants should be classified as different species (Wadell et al, 1983). It is proposed that the variants should be called Mastadenovirus h 40 (with reference strains Dugan and Hovi X) and Mastadenovirus h 41 (with reference strain Tak). Neutralization and haemagglutination inhibition tests demonstrated that the viruses from Glasgow and Helsinki (Hovi X) described by Johansson ct al [1980] and by Kidd and Madeley [1981] belong to these two adenovirus species.
Replication of encephalomyocarditis virus in various mammalian cell types
Authors: Kelly Pamela M. , Shanley John D. , Sears Joel
Published: March 2007

Recently, the biological and biochemical characteristics of EMC virus have received considerable attention, but little is known concerning the relative susceptibility of various mammalian cells to EMC virus. In this study, a variety of mammalian cell types was evaluated for susceptibility to the M strain of EMC virus by comparing peak viral titers, time course of infection, plaquing efficiency, and formation of viral antigens. Infection of all murine and guinea pig cell types resulted in substantial virus replication and induction of viral antigens in greater than 95% of cells. Human cell lines supported replication with a slower time course, but significant increases in viral yield and plaquing efficiency occurred with viral adaptation following successive replication cycles in human cells. All rat cell lines were relatively resistant to EMC virus infection and replication, and less than 1% of rat cells expressed viral antigens. Attempts were unsuccessful to adapt virus by successive replication cycles in rat cells. The possible reasons for the relative resistance of rat cells are currently under investigation.
Antibodies to fastidious faecal adenoviruses (species 40 and 41) in sera from children
Authors: Kidd A. H. , Banatvala J. E. , de Jong J. C.
Published: March 2007

Three hundred and seventy‐seven single sera from children in the United Kingdom, Hong Kong, New Zealand, Gambia, Guatemala, and Kuwait were tested for antibodies to fastidious fecal adenoviruses (species 40 and 41) by neutralisation test using a variant of Ad41 (Ad4la). All children were less than 12 years of age, and at least 41.1% of the total tested had antibodies. One hundred and fifty‐four of these sera were collected during the 1960s from London children attending day nurseries, and 54.5% had antibodies to Ad40 or Ad41. The proportion of seropositive children from an isolated Gambian village community in 1979 was similar to the proportion of seropositives in London children bled in 1979–1980.
Relationship between type specific antibodies to herpes simplex virus and type specificity in human sera
Authors: Ozaki Yoshikatsu , Ishiguro Tatsuya
Published: March 2007

A quantitative analysis was carried out on the relationship between type specific neutralizing antibodies to herpes simplex virus and the type specificity, using a mutual absorbing procedure. Forty‐two samples were selected among human sera, on the basis of type specificity expressed by the value of II/I index. All sera with values of less than 90 of II/I index contained only type 1 specific antibody, while those with values over 111 contained only type 2 specific antibody. When the values were between 90 and 110, type 1 specific antibody was present in all, and type 2 specific antibody was present in some serum samples.
Subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection
Authors: Lemon Stanley M. , Scott Robert Mcnair , Bancroft William H.
Published: March 2007

To assess the feasibility of jet injection for mass immunization against hepatitis B virus, inactivated, alum‐adsorbed hepatitis B vaccine (Merck, Sharp, and Dohme Research Laboratories, West Point, PA) was administered subcutaneously by automatic jet injection to 19 volunteers lacking antibody to hepatitis B surface antigen (anti‐HBs). Three 20‐μg doses were given at 0, 1, and 6 months. Of 19 volunteers, 5 (26%) developed anti‐HBs by 1 month after the first injection, and 15 of 19 (79%) were anti‐HBs‐positive 6 to 8 weeks after the first booster administration. Following the second booster, 16 of 19 (84%) recipients had detectable anti‐HBs. Possible systemic reactions were limited to low‐grade fever (37.8°C) in one volunteer following one injection, and mild lethargy in a second recipient. Local reactions to jet injection of vaccine occurred more frequently, with indurated, nodular lesions 3–10 mm in diameter developing at the site of 19 of 57 (33%) vaccine injections, compared with 2 of 57 (3%) saline placebo injections. Such nodules were generally painless. Sore arms were noted in 11 of 57 (19%) vaccine injections.

With the exception of frequent but minor local reactions, subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection is safe, and results in vaccine immunogenicity approximating that associated with intramuscular needle injection.
Combined chemotherapy of cutaneous herpes simplex infection of the guinea pig
Authors: Burkhardt U. , Wigand R.
Published: March 2007

Cutaneous infection of guinea pigs with HSV1 was topically treated from 2 to 6 days post infection with 7 antiherpetic substances. Phosphonoformic acid and acyclovir were found to be highly effective; trifluorothymidine, thymine arabinoside, ethyldeoxyuridine, and adenine arabinoside monophosphate all had some therapeutic effect in decreasing order, whereas iododeoxyuridine was ineffective. The efficacy of treatment was evaluated from cutaneous lesion scores by the Wilcoxon rank test. The substances were combined in marginally effective concentrations. From the 21 combinations, acyclovir + phosphonoformic acid, acyclovir + thymine arabinoside, and phosphonoformic acid + thymine arabinoside suggested a synergistic interaction, which appeared significant for acyclovir + phosphonoformic acid.
Alteration of blood coagulation and complement system in neotropical primates infected with Junin virus
Authors: Molinas Felisa C. , Giavedoni Elda , Frigerio Marcelo J. , Calello Miguel A. , Barcat Juan A. , Weissenbacher Mercedes C.
Published: March 2007

The neotropical primate Callithrix jacchus infected with Junin virus presented an acute disease with hematological and neurological manifestations and died 17 to 24 days after infection. This picture is similar to that of human Argentine hemorrhagic fever (AHF). Blood coagulation and complement studies were performed in ten C jacchus animals inoculated with 103 TCID50 of Junin virus, the prototype pathogenic XJ strain. Four monkeys were used as normal controls. Infected monkeys and normal controls were bled to death on days 7, 14, 17, and 21. A progressive decrease in the number of platelets was found after day 7 of infection. On day 21, the last monkey had a value of 24,000/μl. The levels of blood clotting factors did not change until day 17, when a shortened partial thromboplastin time activated with Kaolin (PTTK) (36 sec) and increased factors VIII (192.2%) and VII‐X (266.6%) were found. On day 21, the PTTK was prolonged (50.7 sec) and factors II, V, and VIII, were decreased. Thrombin time was found prolonged from day 14 onward. Fibrinogen and fibrin degradation products (FDPs) were increased on days 17 (754 mg/dl and 9.2 μg/ml) and 21 (457 mg/dl and 29.4 μg/ml). No changes in the levels of α2 macroglobulin were observed. Complement hemolytic levels were found to be low on day 7 (58.3 UCH50, increased on day 14 (165.1), and within normal range at the end of infection (107.2). C3 levels showed a similar pattern. The bone marrow was active and hypercellular, and the number and morphology of megakaryocytes were normal in all but one of infected animals. The results of blood clotting suggest a limited activation. The complement system presented a profile of activation followed by a rebound phenomenon. The activation of complement appeared ten days before the alteration of the clotting system was evident.
Class‐specific antibody responses to early and late antigens of varicella and herpes simplex viruses
Authors: Schmidt Nathalie J. , Gallo Dana
Published: March 2007

Antibody responses to early antigens of varicella‐zoster virus (VZV), simian varicella virus, and herpes simplex virus types 1 and 2 (HSV‐1 and HSV‐2) were studied in primary, secondary, and latent infections. IgG antibody responses to the early antigens occurred in primary and secondary VZV and HSV infections, and antibodies to early antigens were also demonstrable in healthy individuals with latent VZV and HSV infections, indicating that the presence of antibodies to early antigens cannot be taken as evidence of active infection with the viruses. Patients with current VZV or HSV infections showed heterotypic IgG antibody responses to early antigens of VZV and HSV to the same extent as to late antigens. In all groups of patients, IgG antibody titers to early antigens were similar to those against the corresponding late antigens, and no difference was seen in the reactivity of early antigens produced with four different blocking agents (cytosine arabinoside, bromodeoxyuridine, trisodium phosphonoformate, and cycloheximide). Antibodies of the IgM and IgA classes reacted with both early and late antigens of HSV, but only with late antigens of VZV and simian varicella virus, suggesting that these antibodies may be directed against late proteins that are expressed to a greater extent in HSV‐infected cells treated with blocking agents than they are expressed in treated VZV‐infected cells. Homologous IgM antibody responses occurred in both primary and secondary VZV infections, but only in primary HSV infections. Heterotypic IgM responses to HSV‐2 antigen were noted in a few VZV patients who did not have demonstrable IgG antibody to HSV, suggesting that even in patients without prior experience with HSV, a VZV infection may stimulate the production of IgM antibodies that react with antigens that are shared by VZV and HSV‐2. IgA antibodies to late antigens of VZV and HSV were demonstrable in latent, as well as active, infections with these viruses.
Three different serotypes of human rotavirus determined using an interference test with coxsackievirus B 1
Authors: Suzuki Hiroshi , Konno Tasuke , Numazaki Yoshio , Kitaoka Setsuko , Sato Tetsuo , Imai Aki , Tazawa Fumiyo , Nakagomi Toyoko , Nakagomi Osamu , Ishida Nakao
Published: March 2007

MA104 cells were used to titrate human rotavirus, and its capacity to render the cells resistant to coxsackievirus B 1 infection enabled us to determine easily the infectious titer of three prototype human rotaviruses. When rabbit antisera prepared against these prototype viruses were used for the neutralization test, the viruses could be discriminated from each other by a specific neutralization test.
Sensitive enzyme immunoassay for the detection of delta antigen and anti‐delta, Using serum as the delta antigen source
Authors: Shattock Alan G. , Morgan Bridget M.
Published: March 2007

A sensitive enzyme‐linked immunosorbent assay (ELISA, EIA) was developed for the detection of delta antigen in serum treated with Tween 20. The serum delta antigen so derived was used in an ELISA for anti‐delta. Both tests were specific and more sensitive than radioimmunoassay (RIA) when applied to testing parenteral drug abusers. It is concluded that the different sources of delta‐antigen used may account for the different sensitivities noted, and that delta antigenaemia in acute infection may be more frequently detectable than was first thought, amounting to 71% of those with delta infection in this study and that these sera are a convenient alternative source of antigen.
The use of IgM tests for analysis of the causes of measles vaccine failures: Experience gained in an epidemic in hungary in 1980 and 1981
Authors: Nagy G. , Kósa Susanna , Takátsy Susanna , Koller M.
Published: March 2007

Following a period of 6 years of low measles incidence, an epidemic occurred in Hungary with more than 11,000 reported cases between September 1980 and August 1981. About 60% of the cases had a documented history of previous measles vaccination. Serum samples obtained from 7815 patients were examined for measles antibody by haemagglutination inhibition (HI). In addition to conventional antibody titration, most of the sera or their IgM fraction obtained by a simple ion exchange chromatography were tested for the presence of measles‐specific IgM antibodies by 2‐mercaptoethanol (2‐ME) treatment, and in 300 patients also by the fluorescent antibody (FA) technique. Laboratory results confirmed the diagnosis of measles in 5356 patients and supported it in 685 cases. Primary antibody response was found in 96.1% of unvaccinated and in 77.4% of previously vaccinated patients. The percentage of secondary antibody responses increased with increasing time from vaccination only in patients vaccinated before their first birthday, whereas in those who were immunized when over 12 months old, the distribution of primary and secondary antibody responses was independent from the time that had elapsed since vaccination. Therefore, secondary vaccine failure due to waning immunity account for only 6.2% of previously vaccinated patients, whereas in 93.8% of patients, including the majority of those with secondary antibody response, a primary failure of vaccination due to unsuccessful immunization was incriminated.
Incidence of herpes simplex virus types 1 and 2 in penile lesions of college men
Authors: Docherty John J. , Lohse Megan A. , Dellaria Marco F. , Naugle Floyd P. , Mason Charles W. , Knerr Richard A. , McDermott Harry M. , Mundon Francis K. , Zimmerman Daniel H.
Published: March 2007

Herpes simplex virus (HSV) was isolated from penile lesions of 15 college men. Using (E)‐5‐(2‐bromovinyl)‐2'‐deoxyuridine sensitivity, monoclonal antibody immunofluorescence, and restriction endonuclease EcoRI digestion of viral DNA, 4 of 15 (26%) isolates were found to be HSV‐1, and 11 of 15 (74%) isolates were found to be HSV‐2. It is likely that some of the genital HSV‐1 infections are related to oral genital contact, but this fact could not be established for all cases, since the females in this group had previously been shown to have a high incidence of genital HSV‐1.
Hepatitis B surface antigen (HBsAg) subtype‐specific antibodies in persons vaccinated against hepatitis B
Authors: Jilg Wolfgang , Delhoune Corinne , Deinhardt Friedrich , Roumeliotou‐Karayannis Anastasia J. , Papaevangelou George J. , Mushahwar Isa K. , Overby Lacy R.
Published: March 2007

One hundred sixty‐three persons immunised against hepatitis B with a vaccine containing HBsAg either of adw or ayw subtype were examined for antibodies against the a, d, and y determinants of HBsAg. Sera were tested for antibodies against HBsAg adw and HBsAg ayw separately by a solid‐phase radioimmunoassay using polystyrene beads coated with HBsAg of either adw or ayw subtype, and the relative amounts of antibodies against the single determinants were calculated. After the third immunisation, all vaccinees had antibodies against the common determinant a. A quantitative evaluation showed that on average about 50% of HBsAg‐specific antibodies were directed against the a determinant, and about 50% against d or y, respectively. However, as only anti‐a is protective against cross‐infection with other HBsAg subtypes, the degree of immunity of a person vaccinated against hepatitis B should be evaluated by the determination of antibodies to a rather than antibodies against total HBsAg.
The use of monoclonal antibodies to differentiate isolates of herpes simplex types 1 and 2 by neutralisation and reverse passive haemagglutination tests
Authors: Buckmaster E. A. , Cranage M. P. , McLean C. S. , Coombs R. R. A. , Minson A.
Published: March 2007

Monoclonal antibodies specific for herpes simplex type 1 or type 2 were used in reverse passive haemagglutination tests or infectivity neutralisation tests to serotype 100 isolates of herpes simplex virus (HSV). All isolates were independently serotyped by measuring their sensitivity to bromovinyl deoxyuridine. Reverse passive haemagglutination tests with type‐specific antibodies directed against the HSV glycoprotein D and major DNA binding protein gave results in perfect agreement with the results of drug‐sensitivity measurement. A single isolate behaved anomalously in the neutralisation test with a type 1‐specific antibody directed against glycoprotein A/B. Restriction‐enzyme analysis of virus DNA suggests that this isolate contains a variant glycoprotein A/B.

The two methods used for serotyping proved very sensitive, giving adequate results with samples containing as little as 100 plaque forming units (pfu) of HSV. The reverse passive haemagglutination test has the additional advantages of speed and simplicity.
In vitro neutralization of HSV‐2: Inhibition by binding of normal IgG and purified Fc to virion Fc receptor (FcR)
Authors: Dowler Kenneth W. , Veltri Robert W.
Published: March 2007

We designed experiments to assess the effects of binding of the HSV‐2 Fc receptor (FcR) to purified rabbit nonimmune IgG and purified Fc. Purified Fc (75 μg) or nonimmune IgG (100 μg) when bound to HSV‐2 did not reduce infectivity but did protect the virions against thermal inactivation at 37°C. However, preincubation of these two reagents with HSV‐2 virions significantly protected against neutralization by specific anti‐HSV‐2, F(ab')2 purified rabbit antiserum. The blockage of neutralization and protection against thermal inactivation afforded by FcR‐Fc interaction on HSV‐2 virions provide a tenable mechanism to explain viral persistence in an immune host.
Polymorphonuclear leukocyte‐associated antigenemia in measles: Demonstration and significance
Authors: Abramowitz Aron , Tamir Israel , Livni Nelly , Lotan Chaim , Morag Abraham
Published: March 2007

An indirect immunoperoxidase technique was used for the identification of measles virus (MeV) antigen in routinely prepared peripheral blood smears. Characteristic brown immunoperoxidase staining was present in the polymorphonuclear (PMN) leukocytes in 25 of 31 children during the exanthematous stage of measles. No peroxidase staining was seen on peripheral blood smears in any of 9 children convalescing from measles or in 9 children with upper respiratory tract infections (URTI) without exanthema. These findings were confirmed by control studies and were reproduced by immunofluorescent staining. The data suggest that MeV antigen is localized in the PMN leukocytes during the acute stage of measles infection, and may be connected to phagocytosis of viral antigenic material by PMN leukocytes. The technique described has potential for rapid laboratory diagnosis of measles and, possibly, of other viral infections during the acute stage and before measurable amounts of antibodies are produced.
An electron microscope study of three‐component immune complexes
Authors: Almeida June D. , Bradburne A. F.
Published: March 2007

Immune electron microscopy has been used to examine the appearance of three‐component complexes. The three components are antigen, supplied by two dissimilar viruses, antibody, and a secondary immune reactant. Secondary reagents used in the study are antispecies immunoglobulin (anti‐IgG), rheumatoid factor (RF), and complement. Each of these secondary reagents produced cross‐linking between antigenically unrelated immune complexes, and it was found possible to distinguish visually the mixed complexes produced by each of them. The significance of the appearance of these mixed complexes is discussed and related to the neutralisation enhancement that can occur in the presence of secondary immune reactants. The appearance of the complexes is also related to the false positive results that can be obtained in carrying out solid phase immunoassays.
Evaluation of the effectiveness of 2H‐1, 3‐Oxazine‐2,6(3H)‐dione (Oxauracil) in the treatment of herpes simplex virus (HSV)‐Induced acute encephalitis in mice
Authors: Seal Lawton A. , Jamison Richard M.
Published: March 2007

Treatment of suckling mice with the pyrimidine analogue 2H‐1,3‐oxazine‐2,6(3H)‐dione (oxauracil) proved successful in reducing mortality associated with HSV‐2‐induced encephalitis. Oxauracil did not decrease mortality associated with HSV‐1 infection; however, there was an increased survival time and a decrease in the amount of infectious virus recovered from the brains of HSV‐1‐infected animals.
Cultivation of human rotaviruses in cell culture
Authors: Albert M. John , Bishop Ruth F.
Published: March 2007

Sixteen specimens of faeces from children with acute diarrhoea due to rotavirus were inoculated into MA‐104 cells. Rotaviruses present in six of the specimens were successfully adapted to growth after serial passage. Two of these strains had “short RNA” patterns and had caused epidemics of diarrhoea in children in Melbourne, Australia from 1977 to 1979, or in children in the Highlands of Papua New Guinea in 1979. The remaining four strains had “long RNA” patterns. One of these four strains was of major epidemiological importance as a cause of childhood diarrhoea in Melbourne during 1981. The other three strains appeared identical and were isolated from babies born in a Melbourne obstetric hospital during 1977. All six strains were successfully adapted to stationary culture, but only four strains could be plaqued. Selection of strains of rotavirus for culture on the basis of their known epidemiological importance in different communities will increase information about clinically important strains throughout the world.
Acquisition of antibodies to various coxsackie and echo viruses and hepatitis A virus in agricultural communal settlements in Israel
Authors: Morag Abraham , Margalith Miriam , Shuval Hillel I. , Fattal Badri
Published: March 2007

A seroepidemiological study was conducted to measure the antibody prevalence for eight different enteric viruses. These include seven “classical” enteroviruses, ie, Coxsackie virus types A9, B1, B3, B4 and three ECHO virus types 4, 7, and 9, as well as hepatitis A virus (HAV), recently classified as enterovirus 72. Sera samples were obtained from 791 residents living in 29 agricultural settlements (kibbutzim) with a total population of 15,950. The results indicated that the acquisition of antibodies to Coxsackie and ECHO viruses occurred at a significantly earlier age than to HAV. Prevalence of antibodies to Coxsackie and ECHO viruses at two to four years of age was 40%–69%, in contrast to 4% for HAV. At age 5–17 years, 85% had antibodies to five or more of the seven “classical” enteroviruses, as compared with 10% to HAV. The latter steeply increased to 63% for age group 18–24 years and reached a peak of 95% for age group 50 years and older. Prevalence of antibodies to ECHO and Coxsackie viruses were often found to be higher in females than in males, within the age group of 18 years and older, but not in age groups 18 years and younger. Prevalence of antibodies to HAV was observed to be much higher in males than in females 18–24 years of age. No significant difference was found in the prevalence of individuals harboring antibodies to three or more and even up to five or more Coxsackie and ECHO viruses between those HAV‐negative versus those HAV positive. This suggests that in addition to the well‐known fecal‐oral mode of transmission in these agents, other factors are involved that are responsible for the significantly different mode of aquisition of infection and immunity to classical enteroviruses and HAV in the community of the kibbutz.
Measurement of BK papovavirus IgG and IgM by radioimmunoassay (RIA)
Authors: Zapata M. , Mahony J. B. , Chernesky M. A.
Published: March 2007

Current techniques for the measurement of BK papovavirus (BKV) specific IgM include sucrose density gradient centrifugation followed by hemagglutination inhibition (HAI) or indirect immunofluorescent (IF) staining of BKV infected cells using a fluorescein conjugated anti‐human IgM antibody. These techniques are cumbersome and labor intensive and do not lend themselves to testing large numbers of sera.

A solid phase radioimmunoassay (RIA) was developed to facilitate the measurement of BKV IgG and IgM in large numbers of sera. Solid phase antigen was prepared by adsorbing CsCl purified BKV antigen to polyvinyl chloride microtiter plates. Following reaction with serum, bound immunoglobulin was detected with iodinated goat anti‐human IgG or IgM. RIA for the measurement of BKV IgG was sensitive with titers approaching 10−6. Determination of IgG titers by RIA and HAI showed good agreement (P < 0.01, correlation coefficient = 0.74). Measurement of BKV IgM was not affected by the presence of BKV IgG as evidenced by sucrose density gradient fractionation of IgM positive sera, removal of IgG by treatment with S. aureus protein A, and addition of BKV IgG to BKV IgM. Rheumatoid factor (RF) gave false positive IgM titers in the presence of BKV IgG when RF titers were ≥ 1:640 by latex agglutination testing and BKV IgG levels exceed 1:256 by HAI. False positives due to RF could be eliminated by treatment of sera with sheep anti—human IgG antisera. RIA for BKV IgM was specific as sera containing JCV‐, cytomegalovirus (CMV)‐, rubella‐, or hepatitis B core antibody (anti HBc)—IgM were negative by RIA. RIA detected BKV IgM in several sera from renal dialysis or allograft palienls with titers ranging from 1:400 to 1:128,000 and demonstrated that BKV IgM persisted in sera of renal allograft patients for as long as 343 days post transplantation.
IgM antibodies in sera from patients with chronic active hepatitis reacting with the measles virus matrix protein and nucleoprotein
Authors: Christie K. E. , Endresen C. , Haukenes G.
Published: March 2007

The antigenic specificity of measles virus IgM antibodies in sera from patients with chronic active hepatitis not caused by hepatitis B virus has been examined. An immunosorbent column containing antihuman IgM covalently bound to Sepharose was used to pick up IgM from the sera. Radiolabelled measles virus antigens were then allowed to react with the IgM antibodies. The immune complexes were eluted and analysed by sodium dodecyl sulfate [SDS]‐polyacrylamide gel electrophoresis.

Four sera from patients with hepatitis B surface antigen [HBsAg]‐negative chronic active hepatitis with high measles virus haemagglutination inhibition [HI] and complement fixation [CF] antibody titres and positive enzyme‐linked immunosorbent assay [ELISA] for measles‐virus‐specific IgM were examined. The results were compared with those obtained using sera from patients with an acute measles virus infection and from healthy controls.

In both patient groups, IgM antibodies with specificity against the matrix protein represented the major portion of the measles virus IgM. IgM antibodies against the measles virus nucleoprotein and probably against host‐cell‐derived actin were also present. The patient sera contained only traces of IgM antibodies with specificity against the measles virus haemagglutinin or fusion protein. No specific IgM antibodies were found in sera from healthy controls.
Poliovirus and vesicular stomatitis virus replication in the presence of 6‐diazo‐5‐oxo‐L‐norleucine or 2‐deoxy‐D‐glucose
Authors: Goldstein Gerald , Guskey Louis E.
Published: March 2007

The effects of 6‐diazo‐5‐oxo‐L‐norleucine (DON), 2‐deoxy‐D‐glucose (DOG), and tunicamycin (TM) on the replication of poliovirus (PV) and vesicular stomatitis virus (VSV) were examined. During a 48‐hr replication period, TM, DON, and DOG inhibit VSV plaque formation in HEp‐2 cells by 99.9%, 99.8%, and 99.9% respectively. Inhibition of VSV by DON is reversed with glutamine. Although all three agents are known to affect glycoprotein synthesis, DON and DOG also inhibit plaque formation of viruses devoid of structural glycoproteins. Thus, plaque formation of PV types 1 and 3 and Coxsackie B3 virus is delayed in HEp‐2 and Buffalo green monkey kidney cells during exposure to these agents. Since these viruses do not contain glycoproteins and since concentrations up to 10 μg TM/ml cause no significant inhibition of PV, DON and DOG are affecting another viral or cellular process. Inhibition of PV replication by DON is reversed by addition of 25 mM glutamine or marginally by exposure to a combination of 5 mM concentrations of cytidine, uridine, adenosine monophosphate, and guanosine monophosphate. Inhibition of PV replication by DOG is reversed with 5 mM uridine alone. During DON exposure of HEp‐2 cells infected with PV, the amount of 3H‐uridine incorporation at 5.5 hr postinfection (pi) is reduced to 53% of untreated controls, an amount 11% greater than incorporation in cultures infected with PV but not treated with DON. These data indicate that the inhibition of PV replication by DON or DOG occurs at the level of viral RNA synthesis, while the primary target of these agents during VSV replication is probably glycosylation.
Serological diagnosis of parainfluenza virus infections by enzyme immunoassay with special emphasis on purity of viral antigens
Authors: Julkunen Iikka
Published: March 2007

Enzyme immunoassay (EIA) for parainfluenza virus type 1,2, and 3 antibodies was compared with the complement fixation test (CF) as a diagnostic method in 180 patients with respiratory symptoms. The CF test detected rises in parainfluenza virus antibodies in 30 cases, whereas EIA detected 47 rises. Patients with antibody rises in parainfluenza or mumps virus antibodies were studied for cross‐reactions by CF, hemagglutination inhibition (HAI), and EIA using purified viral envelope glycoprotein and nucleocapsid preparations. All methods showed marked cross‐reactivity between parainfluenza virus type 1 and 3 antibodies. Mumps virus infection often raised heterologous antibodies even against purified viral antigens. Rabbit antisera produced against viral envelope glycoproteins showed heterologous antibody responses between parainfluenza 1 and 3 antibodies and between parainfluenza 1 and mumps antibodies by HAI, EIA, and immunoprecipitation. The cross‐reactive antibodies were usually directed against both of the envelope glycoproteins, HN and F proteins, of the viruses.
Genome variants of human adenovirus 40 (subgroup F)
Authors: Kidd A. H. , Berkowitz F. E. , Blaskovič P. J. , Schoub B. D.
Published: March 2007

Twenty‐six strains of faecal adenovirus from three continents (two from Europe, 16 from South Africa, and eight from Canada) were typed as Ad40 by restriction enzyme analysis of the DNA using Sma I. The DNA of the strains was further compared by digestion with six other enzymes, namely Bam HI, Eco RI, Bgl I, Xho I, Sst I, and Hind III. At least two different restriction profiles were found to exist for each enzyme. Nineteen of the 26 strains studied had the same combination of profiles for all the enzymes, within the limits of resolution of the technique. This genome type was detected from all three continents and included the Finnish reference strain Hovi‐X. The other seven strains were genome variants, representing five other genome types. Three genome types were detected only in South African specimens, whereas one genome type was detected in single specimens from both South Africa and Canada. Strain Dugan from Holland, indistinguishable from other Ad40 strains in neutralization tests using polyclonal antibody preparations [de Jong et al, 1983], deviated from the common Hovi‐X‐like genome on digestion of the DNA with any of the enzymes except Sma I.
Intracytoplasmic inclusions in human hepatocytes in non‐A, non‐B hepatitis: An ultrastructural study
Authors: McCaul Thomas F. , Tovey George , Anderson Michael G. , Murray‐Lyon Lain M. , Zuckerman Arie J.
Published: March 2007

An ultrastructural study was carried out on 114 liver biopsies obtained for diagnostic purposes from patients with various pathological disorders of the liver including hepatitis B‐related liver disease, non‐A, non‐B hepatitis, alcoholic liver disease, fatty change, and cryptogenic cirrhosis. The opportunity was taken to evaluate the significance of intracytoplasmic crystalline structures found in the hepatocytes of nine patients with a variety of liver disorders. The cytoplasmic inclusions varied in size up to 2 μm in length and shape and were not limited by membranes. The presence of these inclusions cannot, however, be correlated either specifically with non‐A, non‐B hepatitis or with other known nonviral liver disease. The functional, physiological, and pathological significance of the crystalline structures remain to be elucidated.
Neutralizing antibody and interferon‐α in cerebrospinal fluids and sera of acute aseptic meningitis
Authors: Ichimura Hiroshi , Shimase Kohichi , Tamura Ikuo , Kaneto Eiji , Kurimura Osamu , Aramitsu Yoshimi , Kurimura Takashi
Published: March 2007

Cerebrospinal fluids (CSFs) and sera from 20 patients with echovirus 30 (E 30) meningitis, 4 patients with enterovirus 71 (EV 71) meningitis, and 5 patients with acute aseptic meningitis (AM) of unknown etiology were investigated at the acute and the convalescent phases of the disease to elucidate the roles of neutralizing antibody (NT) and interferon‐α (IFN‐α) in the central nervous system (CNS) in cases of AM in humans. Viruses were isolated from the CSFs at the acute phase of AM, but not at the convalescent phase. There was a fourfold or greater rise in NT titer between paired sera to E 30 or EV 71 but only a slight rise between paired CSFs. IFN‐α was detected in the CSFs ranging from <10 to 25.5 IU/ml but not in the sera, and the IFN‐α level in the CSF was significantly higher in the acute phase than in the convalescent phase. These results suggest that in cases of acute enteroviral infections in the CNS, NT plays only a small role in the recovery from AM, and IFN‐α plays a direct or indirect role in curbing the local spread of the virus and eliminating the virus from the CNS at the acute phase of AM.
Absence of detectable hepatitis B virus DNA in sera and liver of chimpanzees with non‐A, non‐B hepatitis
Authors: Yap S. H. , Heilings J. A. , Rijntjes P. J. M. , van Loon A. M. , Duermeyer W. , Stute R.
Published: March 2007

The risk of hepatitis B infections has been reduced by screening of blood donors for hepatitis B surface antigen (HBsAg). However, recipients remain at significant risk of developing post‐transfusion hepatitis. Studies have shown that non‐A, non‐B hepatitis virus(es) are responsible for the majority of post‐transfusion hepatitis infections. In spite of many efforts, these non‐A, non‐B hepatitis viruses have not yet been identified. Epidemiological studies, however, suggest that non‐A, non‐B hepatitis shares many features with hepatitis B. Recently, Wands et al [1982] showed, in chimpanzees infected with non‐A, non‐B hepatitis agents, the presence of antigenemia or viremia by radioimmunoassay with monoclonal antibodies directed toward distinct determinants of HBsAg and by molecular hybridization analysis. They suggested that non‐A, non‐B hepatitis agents may be related, but distinct variant(s) of hepatitis B virus (HBV). In this study, five chimpanzees were inoculated with three different agents that have been shown to transmit non‐A, non‐B hepatitis. The following inocula were used (I) a factor VIII preparation kindly provided by D.W. Bradley, (II) acute phase serum from a chimpanzee infected with the F strain kindly provided by A.J. Zuckerman, and (III) a DS‐antigen serum previously shown by us to transmit non‐A, non‐B hepatitis [Duermeyer et al, 1983]. All chimpanzees developed a rise in transaminase levels between 8 and 10 weeks after inoculation. None of the chimpanzees was positive for any markers of HBV infection. No evidence was obtained of infection with hepatitis A, cytomegalovirus, or Epstein‐Barr virus. One chimpanzee developed chronic liver disease. The presence of HBV DNA in sera and in liver biopsies was studied. HBV DNA hybridizable sequences were not detected in any of the samples collected at different stages of the disease. These findings suggest that the non‐A, non‐B hepatitis agents in our study are not related to HBV.
Hepatitis D virus antibody in HBsAg‐positive and HBsAg‐negative substance abusers with chronic liver disease
Authors: Novick David M. , Farci Patrizia , Karayiannis Peter , Gelb Alvin M. , Stenger Richard J. , Kreek Mary Jeanne , Thomas Howard C.
Published: March 2007

The hepatitis D virus (HDV; previously called the “delta agent”) is a defective organism which can replicate only in the presence of the hepatitis B virus (HBV). We tested the serum of 95 substance abusers, all of whom had sufficient evidence of chronic liver disease to warrant a liver biopsy, for hepatitis D virus antibody (anti‐HDV). Anti‐HDV was detected in five of eight hepatitis B surface antigen (HBsAg)‐positive patients and 12 of 87 (14%) HBsAg‐negative patients. Antibody to the hepatitis B core antigen (anti‐HBc) was the sole hepatitis B marker in eight of the 12 (67%) anti‐HDV‐positive, HBsAg‐negative patients but in only 14 of 75 (19%) anti‐HDV‐negative, HBsAg‐negative patients (P < 0.005). None of the anti‐HDV‐positive, HBsAg‐negative patients had detectable IgM anti‐HBc in the serum or hepatitis D antigen in liver tissue, and they had similar clinical features and liver biopsy diagnoses to HBsAg‐negative patients without anti‐HDV. We conclude that anti‐HDV in HBsAg‐negative substance abusers reflects infection with HDV and HBV in the distant past and does not indicate more severe liver disease than that seen in HBsAg‐negative patients without anti‐HDV.
Unconventional pathogens causing spongiform encephalopathies absent in blood products
Authors: Tateishi Jun , Tsuji Sadatoshi
Published: March 2007

To determine whether unconventional pathogens causing subacute spongiform encephalopathy may be present in blood products, a newly developed hepatitis B vaccine and a widely used blood product were injected into mice and rats. As only a few aged mice in the test and the control groups showed spongiform encephalopathic change of a sparse or mild degree and which differed from that seen in rodents infected with Creutzfeldt‐Jakob disease, the presence of unconventional pathogens in the tested inocula can be ruled out.
Isolation and Preliminary Characterization of Mutants of Western Equine Encephalomyelitis Virus With Altered Virulence in Chickens
Authors: Fraizer G. , Main O. , Hardy J.
Published: March 2007

A small plaque (sp) and four temperature‐sensitive (ts) mutants of western equine encephalomyelitis virus (WEEV) were obtained from a highly virulent field isolate (BFS‐1703) after mutagenesis with 5‐azacytidine or nitrosoguanidine or following undiluted passage in mosquito cell culture. Three ts mutants (158, 214, and 260) expressed stable ts phenotypes as determined both by six‐hour leak yield and efficiency of plaquing (EOP) analyses. Progeny of ts mutant 214 grown at the nonpermissive temperature lacked hemagglutinin activity. The sp mutant (148) was as highly virulent as the wild‐type virus (WTV) for newly hatched chickens (infected when 12 hours old), whereas the ts mutants were attenuated in their virulence for this host. Attentuation was correlated with lower viremia titers in 24‐hour postinfection blood samples. The WTV and those mutants able to infect 21‐day‐old chickens produced nonlethal infections but the growth of ts 158 was apparently restricted in this high‐temperature nonpermissive host. All ts mutants except ts 158 lost their ts phenotype after growth for 24 hours in newly hatched chickens and in duck embryonic cell culture (DECC) maintained at 42°C.
Detection of integration during active replication of hepatitis B virus in the liver
Authors: Boender P. J. , Schalm S. W. , Heijtink R. A.
Published: March 2007

A method is described that enables the unequivocal detection of the integration of hepatitis B virus DNA (HBV‐DNA) into the genomic DNA of the host cell, while at the same time the virus exhibits active replication. This detection was achieved by separating the low molecular weight replicating HBV‐DNA from the high molecular weight genomic DNA of the host by electrophoresis of the total undigested cellular DNA through low melting agarose. The high molecular weight DNA was isolated from this gel and electrophoresed after digestion with restriction enzyme(s) on a second agarose gel. Transfer of the DNA content of both gels and hybridization of these blots with 32P‐labelled HBV‐DNA will reveal whether any integrated and/or actively replicating DNA is present. By using this method the presence of a single copy of HBV‐DNA integrated in host DNA was demonstrated in hepatocellular carcinoma tissue of a patient with active HBV replication.
Neutralization of Hepatitis B Virus Infectivity by a Murine Monoclonal Antibody: An Experimental Study in the Chimpanzee
Authors: Iwarson Sten , Tabor Edward , Thomas Howard C. , Goodall Allison , Waters Jenny , Snoy Philip , Wai‐Kuo Shih J. , Gerety Robert J.
Published: March 2007

Two study chimpanzees were inoculated intravenously with approximately 1,000 chimpanzee infectious doses of hepatitis B virus (HBV), one with subtype adr and one with subtype ayw, each previously incubated with 0.1 ml of a murine monoclonal antibody (IgG 1(K) class) directed against a single epitope on hepatitis B surface antigen common to most or all HBV. Two control chimpanzees received identical doses of HBV not incubated with the murine anti‐HBs.

Neither study chimpanzee developed HBV infection during 12 months of follow‐up as judged by normal serum aminotransferase activity, normal liver biopsies, and negative serological tests for HBV‐associated antigens and antibodies. In contrast, both control chimpanzees became infected by HBV as evidenced by elevated serum aminotransferase activity, liver biopsy changes characteristic of viral hepatitis, and the appearance of hepatitis B surface antigen (HBsAg) in their sera. Both study chimpanzees were shown to be fully susceptible to infection with these same HBV inocula when challenged 15 months after the initial inoculations at a time when passively administered anti‐HBs was no longer detectable. Prior to challenge with HBV, one of the two study chimpanzees received a second injection of the same volume of the murine monoclonal anti‐HBs. The survival of this anti‐HBs in serum was reduced from six weeks (after the initial injection) to approximately two weeks.

This study documents the biological efficacy of a murine monoclonal antibody (anti‐HBs) directed against a single epitope on HBsAg in neutralizing the infectivity of Approximately 1,000 infectious doses of either HBV subtype adr or HBV subtype ayw.