bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody responses in recipients of varicella vaccine assayed by immunoblotting
Authors: Harper David R. , Kangro Hillar O. , Heath Raymond B. 
Published: March 2007

AbstractSera taken from 35 children with cancer who had been vaccinated with live varicella vaccine were assayed using immunoblotting for the presence of IgG class antibodies to proteins present in varicella‐zoster virus (VZV)‐infected cells. Sera from 23 of these patients were also assayed for IgM class antibodies.The patterns of immunoreactivity observed for these patients following vaccination were substantially weaker and more variable than those detected following natural VZV infection in otherwise healthy individuals. The IgG responses detected following vaccination involved up to 10 protein bands between 28 and 188 kDa. Bands were particularly frequent in the 78–96 kDa region. IgM responses involved up to 10 bands between 28 and 114 kDa, with the bands in the 78–96 kDa region and at 32–36 kDa being detected most frequently.Repeated vaccination generally produced a stronger IgG antibody response than did single vaccination, and subsequent exposure of vaccinees to natural VZV infection resulted in an increased level of reactivity for IgG antibodies, but not for IgM. Similar reaction patterns were obtained with sera from vaccinees when the vaccine virus and wild‐type VZV were used as antigens.Immunoblotting showed good correlation with indirect radioimmunoassay for the detection of a vaccine‐induced IgG response.
Mother to infant transmission of hepatitis C virus infection
Authors: Wejstål R. , Hermodsson S. , Iwarson S. , Norkrans G. 
Published: March 2007

AbstractEight women with chronic hepatitis C virus (HCV) infection during pregnancy gave birth to 11 children. Five of these children had elevated ALT, but only two had increased levels in more than one sample. All children tested before 6 months of age were positive for anti‐HCV at most up to 7 months of age and then became negative. One child with a maximum ALT level of 8.4 μkat/I however, regained anti‐HCV positivity at 12 months of age, and a liver biopsy at 21 months of age showed resolving hepatitis. Passively acquired HCV antibodies are obviously found in newborns of anti‐HCV‐positive mothers with chronic hepatitis. In 1 of 11 children, active anti‐HCV production and concomitant liver disease suggested mother to infant transmission of hepatitis C virus infection.
Junin virus‐induced suppressor cells are effective only on the efferent limb of the delayed‐type hypersensitivity response
Authors: Campetella Oscar E. , Galassi Nora V. , Barrios Hebe A. 
Published: March 2007

AbstractJunin virus (JV), the etiological agent of Argentinian hemorrhagic fever, induces high mortality in the suckling BALB/c mouse, which correlates with delayed‐type hypersensitivity (DTH)‐like immune response. In contrast, the adult mouse is resistant to infection, and no DTH response can be detected. An antigen‐nonspecific DTH suppressor T‐cell activity induced by JV has been described that may be related to adult mouse survival. In this report, we present evidence supporting the inability of such cells, identified here as bearing the L3T4 marker, to affect the normal establishment of a DTH reaction. In the same form, virus‐induced suppressor cells were unable to alter the expression of DTH effector cells in the absence of antigen‐specific DTH suppressor cells. Besides, we found that a single high dose (200 mg/kg) of cyclophosphamide before or after JV inoculation was unable to alter the activity of virus‐induced suppressor cells.
Natural killer (NK) cell response after vaccination of volunteers with killed influenza vaccine
Authors: Schapiro J. M. , Segev Y. , Rannon L. , Alkan M. , Rager‐Zisman B. 
Published: March 2007

AbstractMany experiments have shown convincingly that natural killer (NK) cell activity against viral infections is an important early defence mechanism in mice. Since the NK response occurs soon after infection, often long before clinical signs of disease become manifest, it has been difficult to design studies to monitor accurately NK cell kinetics following infection, without actually administering pathogens to volunteers. There is therefore little data pertaining to the role of NK cells in humans. Nevertheless, a number of studies have shown elevated NK activity in response to herpes simplex and influenza virus infections in humans. Our study was designed to show that NK activity could be provoked in humans by exposure to viral particles without actual live viral infection. The development of NK cell response in the peripheral blood of volunteers shortly after vaccination with killed influenza trivalent vaccine was studied. The results demonstrate that killed virus vaccine induces and augments NK cell activity for relatively long periods. Such data may prove valuable for designing possible modes of augmenting NK activity as a therapeutic tool.
Comparison of enzyme immunoassay with radioimmunoassay for the detection of antibody to hepatitis B core antigen as the only marker of hepatitis b infection in a population with a high prevalence of hepatitis B
Authors: Parkinson Alan J. , McMahon Brian J. , Hall David , Ritter Donald , Fitzgerald Mary Anne 
Published: March 2007

AbstractEnzyme immunoassay (EIA) and radioimmunoassay (RIA) for the detection of antibody to hepatitis B core antigen (anti‐HBc) were compared using serum specimens from Alaska Natives screened during a hepatitis B control program that were initially positive by EIA for only anti‐HBc. Of 36 specimens from persons previously HBsAg positive but who were now only anti‐HBc positive by EIA, 94.4% were anti‐HBc positive by both assays, with anti‐HBc levels exceeding 93% inhibition. Low‐level antibody to hepatitis B surface antigen (anti‐HBs) (<10 SRU) and antibody to hepatitis Be (anti‐HBe) were also present in 50% and 48% of specimens positive for anti‐HBc, respectively. Of 148 specimens from persons initially positive for only anti‐HBc by EIA who had no previous documentation of any hepatitis B virus (HBV) infection, 64.5% were positive by repeat testing for anti‐HBc by both assays, and anti‐HBc levels in this sample exceeded 70% in 91.6% and 80.2% of specimens by EIA and RIA, respectively. Low‐level anti‐HBs and anti‐HBe were present in 45.8% and 15.6%, respectively. EIA detection of anti‐HBc was found to be less specific than RIA. Of specimens positive for anti‐HBc by EIA, 14.8% were negative by RIA. The specificity of the EIA could be improved with respect to RIA by increasing the cut‐off from 48% to 68%. In samples with lowlevel anti‐HBc (≧70% inhibition) as measured by either method, the anti‐HBc results was less likely to persist upon retesting, whereas sample with anti‐HBc levels of >70% inhibition the anti‐HBc was a reproducible finding frequently accompanied by either low‐level anti‐HBs or anti‐HBe.
History, precedent, and progress in the development of mammalian cell culture systems for preparing vaccines: Safety considerations revisited
Authors: Hilleman Maurice R. 
Published: March 2007

AbstractThe use of cell substrates to propagate viruses or recombinant plasmids for vaccine productions has been the subject of long evolutionary conflict, primarily from the standpoint of product safety, and especially from the viewpoint of cancer induction.The present concern is for safety of vaccines made using transformed or neoplastic mammalian cells that may contain endogenous contaminating viruses or integrated gene sequences from oncogenic viruses. There is also concern for use of plasmid vectors employing promoter elements from oncogenic viruses. The principal concern for safety lies with retention of residual DNA in the vaccine, especially since induction of cancer is a single‐cell phenomenon, and a single functional unit of foreign DNA integrated into the host cell genome might serve to induce cell transformation as a single event or part of a series of multifactorial events.Current proposed standards for vaccines would permit contamination with up to 100 pg of heterologous DNA per dose. This is equivalent to about 108 “functional lengths” of DNA. Total safety would seem to require complete absence of DNA from the product.While preparation of biologicals used to treat serious disease might demand the use of mammalian cells, this is not the situation with vaccines that are given prophylactically to persons who might be given equally efficacious vaccines produced in bacterial cells or in yeast that have attributes for greater safety. Careful assessment of safety and risk vs. benefit of continuous mammalian cell‐produced vaccines should be made by technically expert scientists in the relevant disciplines and a consensus needs to be evolved in the scientific community at large.
Hepadnaviruses in cirrhotic liver and hepatocellular carcinoma
Authors: Robinson William S. , Klote Linda , Aoki Naoto 
Published: March 2007

AbstractHepadnaviruses share properties of virion structure, genome structure and replication, epidemiologic behavior, and pathogenic effects, including an association with hepatocellular carcinoma (HCC). Epidemiologic evidence implicating hepadnavirus infection in HCC includes the observation that the geographic distributions of HBV infection and HCC are similar, that the incidence of HCC is much higher in hepadnavirus infected than uninfected hosts, and that viral DNA sequences are integrated in the cellular DNA of most (e.g., 80–90%) but not all hepadnavirus‐associated HCC. Cirrhosis further increases the risk of HCC in HBV infected humans. The precise role of hepadnaviruses in development of most HCC is unclear, although the finding of viral integrations within or near protooncogenes in a few cases suggests the possibility that these integrations may play a direct role in these HCC. However, in the great majority of HCC associated with HBV infections, viral integrations are in different cellular DNA sites in different HCC, integrations are not within domains of known protooncogenes, and integrations are not found in some 10–15% hepadnavirus‐associated HCC, suggesting that persisting viral sequences are not directly involved in the development of these HCC as viral sequences are for tumors caused by viruses with oncogenes or viruses that act by a “promoter‐insertion” mechanism. It is possible, however, that oncogenic mutations could arise via other mutagenic mechanisms that may operate in chronic hepatitis B and/or cirrhosis and which do not involve persisting viral integrations. For example, liver regeeration, which is a feature of the cirrhosis associated with chronic HBV infection (and sometimes with chronic hepatitis B) involves proliferation of many cells with HBV integrations, and such integrations have been shown to be unstable and may lead to mutations through post‐integration rearrangements of cellular sequences at sites of viral integrations. Viral sequences appear to be lost or deleted at some such sites of rearranged cell DNA. Chronic HBV infection shares pathologic features of liver cell injury and reactive inflammation, liver regeneration, and in man sometimes cirrhosis with other important risk factors for HCC including chronic alcoholic liver disease, chronic non‐A, non‐B hepatitis, hemochromatosis, and crypogenic cirrhosis, suggesting that this common pathologic process may be carcinogenic by a mechanism that does not depend specifically on the factor which initiates liver cell injury. The pathogenetic role of chronic hepadnavirus infection in such a process would be in causing liver cell injury with reactive infammation and hepatocyte proliferation (regeneration). It is important to investigate mutagenic mechanisms in such liver disease, to search for one or a few common oncogenic mutations in hepadnavirus‐associated HCC, and to determine how these viruses may play a role in the carcinogenic process.
Molecular mechanisms of nucleic acid integration
Authors: Coffin John M. 
Published: March 2007

AbstractThere are three known mechanisms by which foreign DNA can be made a permanent part of the genome of an animal cell, and their properties are summarized in this report. Naked DNA introduced into cells is usually rapidly lost, but a small fraction can be integrated by illegitimate recombination, usually accompanied by major and unpredictable rearrangements in both inserted DNA and target. This mechanism, although inefficient and disruptive, accounts for virtually all integrated DNA seen in virus infections, and is often used for making cell lines carrying specific genes as well as transgenic mice. Homologous recombination between inserted and resident DNA is much rarer but can be detected and put to use. The best understood mechanism is that employed by retroviruses and related elements. In contrast to the other mechanisms, retroviral integration results in a predictable, stable association between virus and cell DNA with only minor sequence changes. However, it occurs only when the DNA is derived by reverse transcription of the RNA in an incoming viral particle and contains the correct sequences at its ends. Thus, from a standpoint of vaccine safety, only the first of the three mechanisms is at all relevant. Based on some prior experimentation in animals, the risk of introduction of activated oncogenes or other dangerous sequences by this means is extremely small.
Risk of tumor induction in vivo by residual cellular DNA: Quantitative considerations
Authors: Löwer Johannes 
Published: March 2007

AbstractCertain genes, termed oncogenes, have the ability to transmit the transformed phenotype from tumor cells to hitherto normal cells in vitro and in vivo. This observation is the basis for the concern that medicinal products derived from tumor cell lines could contain possibly tumorigenic contaminating cellular DNA. A comparison between the number of oncogenes necessary for the induction of tumors in a suitable animal model and the quantity in 100 pg residual cellular DNA was carried out. It is shown that the latter contains less than a billionth of the number needed to induce tumors in half of the animals tested. Some factors implicit to this calculation such as the validity of the model system, the linearity of the dose response curve, the concept of multistep carcinogenesis, the amplification of oncogenes, and the transfection enhancing effect of other constituents of the drug are discussed. In summary, 100 pg residual cellular DNA per dose seems to be a safe and, therefore, an acceptable upper limit provided that some factors such as excessive amplification of oncogenes, co‐purification of oncogenic DNA with the product or some transfection mediating activity can be excluded.
Genome and antigenic analysis of influenza A (H3N2) viruses isolated from an epidemic in a closed community of Carmelite nuns
Authors: Donatelli I. , Takhonova A. M. , Klimov A. I. , Ghendon Y. Z. , Oxford J. S. 
Published: March 2007

AbstractEighteen influenza A (H3N2) viruses were isolated during a single outbreak in a closed community of Carmelite nuns. Serological analysis of the virus haemagglutinin (HAs), using a panel of monoclonal antibodies, demonstrated antigenic microheterogeneity. In contrast, no significant biochemical differences were detected in viral genes by RNA:RNA hybridisation or in structural or nonstructural polypeptides analysed by high‐resolution polyacrylamide gel electrophoresis (PAGE) or by limited proteolysis followed by PAGE. Influenza A (H3N2) viruses isolated in the vicinity of the convent were distinguishable from each other and from the epidemic viruses isolated in the convent both antigenically and biochemically.
Recurrent herpes simplex virus type 1 infection precipitated by the impaired production of interleukin‐2, alpha‐interferon, and cell‐mediated cytotoxicity
Authors: Kuo Yuh‐Chi , Lin Ching‐Yuang 
Published: March 2007

AbstractIn order to understand whether immunosuppression due to the primary host defense defect provokes the reactivation of herpes simplex virus type 1 (HSV‐1), 11 healthy persons were evaluated immunologically after recurrence of herpes. A decrease was found in the production of interleukin‐2 (IL‐2) and alpha‐interferon (IFN‐α) to HSV‐1 antigen stimulation in the recrudescent stage (0 to 3 days after onset of the lesion). The cell‐mediated cytotoxicity also decreased. To clarify the relationship between the immunosuppression and the occurrence of herpes recurrence, a further longitudinal study was undertaken measuring IL‐2, IFN‐α production, and cell mediated cytotoxicity every other week in 12 persons who suffered frequently from recurrent HSV‐1 infection. IL‐2 and IFN‐α production after HSV‐1 antigen stimulation and cell‐mediated cytotoxicity before recurrence of herpes were lower than those without recurrence. These defective immunologic responses were persistent and became more pronounced during the recrudescent phase. The results suggest that the defect in the immunologic responses to HSV‐1 antigen is related to the recurrence of herpes simplex.
Typing of hepatitis B virus genomes by a simplified polymerase chain reaction
Authors: Norder Helene , Hammas Berit , Magnius Lars O. 
Published: March 2007

AbstractThe amplification of hepatitis B virus (HBV) DNA sequences in sera for molecular epidemiology of HBV is an important application of the polymerase chain reaction (PCR) with regard to HBV. To simplify the PCR for this purpose, the optimal concentrations of SDS and detergents for carrying out the proteinase K digestion and the amplification of DNA by Taq polymerase were evaluated. It was found that by using 1% deoxycholic acid as detergent for the proteinase K step and diluting the digest 10 times before carrying out the PCR, the phenol extraction of DNA became superfluous. The sensitivity of this procedure equalled that of PCR after phenol extraction on comparable amounts of serum.Four pairs of oligonucleotide primers were compared for amplification of HBV DNA sequences in 48 sera previously subtyped with respect to hepatitis B surface antigen (HBsAg), and in eight sera with different genotypes of HBV, representing the subtypes of HBsAg P1 to P8, defined at an international meeting [Couroucé‐Pauty et al.: “HBs Antigen Subtypes.” Basel: Karger, 1976]. Two primer pairs, selected from conserved regions in the X and S genes of HBV, gave a positive PCR with sera harbouring all the eight different strains of HBV, resulting in DNA fragments consistent with the sizes deduced from genome sequence data. Two other primer pairs were selected in order to discriminate genotypes with regard to differences between d/y and w/r strains. With these primer sets total agreement was obtained with previous results from subtyping with regard to d/y and w/r with all 48 sera, but more complex results were obtained with P1 to P8, which partially, however, confirm a recent grouping of HBV genomes based on genetic relatedness [Okamoto et al.: Journal of General Virology 69:2575, 1988].
Relation of maternal CMV viremia and antibody response to the rate of congenital infection and intrauterine growth retardation
Authors: Harrison C. J. , Myers M. G. 
Published: March 2007

AbstractPregnancy outcome after maternal primary CMV infection initiated at different times during gestation was investigated by using the inbred Strain‐2 guinea pig model of congenital CMV infection. The highest vertical transmission rates occurred in pups from dams that were initially viremic in late gestation presumably because delivery occurred prior to detectable maternal CMV‐specific immune response. In contrast, conceptus loss was highest with maternal CMV infection initiated at conception. Intrauterine resorptions, intrauterine growth retardation, and disseminated neonatal CMV infection with CNS involvement were more frequent in pups born to mothers that were initially viremic prior to rather than after midgestation. Maternal viremia was prolonged and antibody responses were delayed after CMV inoculation in early gestation compared to late gestation. Prolonged maternal viremia plus early gestational virus exposure/infection of the fetus appeared to be associated with the most severe outcome. These findings suggest that the timing of initial maternal viremia and immune responses, the stage of fetal development, and the length of in utero exposure to CMV are important factors in subsequent disease expression and rates of congenital infection.
5‐bromodeoxyuridine enhancement of Inoue‐Melnick virus synthesis in human colon carcinoma cell lines
Authors: Inoue Y. K. , Nishibe Y. , Kimura T. 
Published: March 2007

AbstractInoue‐Melnick virus (IMV) synthesis in naturally infected human colon carcinoma cell lines can be enhanced by 5‐bromodeoxyurdine (BUDR). The optimal conditions for BUDR enhancement differed between two cell lines, SW‐480 and DLD‐1, SW‐480 cells produced 100 times more infectious IMV than DLD‐1 cells by BUDR treatment. A clonal difference in IMV synthesis in SW‐480 cells was also observed. The highest titer of virus was found in the culture fluid of clone H (SW‐480/H) cells treated with BUDR, and a herpes‐like virus was detected by negativestaining electron microscopy of concentrates of the culture fluid. One nonproducer clone (SW‐480/B) was also activated to produce virus when treated with BUDR.
Nucleotide sequence comparison of homologous genomic regions from variola, monkeypox, and vaccinia viruses
Authors: Cowley R. , Greenaway P. J. 
Published: March 2007

AbstractThe nucleotide sequences of homologous regions from the genomes of variola major strain Harvey, variola minor strains Butler and Garcia, and monkeypox strain Denmark were determined. The nucleotide sequences were compared to the homologous region in vaccinia virus which contains part of one of the genes involved in determining host range. Two major differences were detected; these corresponded to a deletion in the promoter region and the presence of a premature stop codon. It was concluded that this region of the genome may not be actively expressed in either variola‐ or monkeypox‐virus‐infected cells. It was also concluded that diagnostic nucleic acid hybridisation probes for differentiating between these members of the Orthopoxviridae may be difficult to identify.
Recombinant proteins VP1 and VP3 of hepatitis A virus prime for neutralizing response
Authors: Gauss‐Müller Verena , Mingquan Zhou , von der Helm Klaus , Deinhardt Friedrich 
Published: March 2007

AbstractSix overlapping genomic regions of capsid proteins VP1 and VP3 of hepatitis A virus (HAV) inserted into the expression vectors pBD or pUR respectively expressed β‐galactosidase‐HAV fusion proteins. The recombinant proteins were poorly soluble so they were difficult to detect by human anti‐HAV sera in radioimmunoassay, but the fusion proteins dissolved in sodium dodecyl sulfate reacted with human and rabbit anti‐HAV‐positive sera in immunoblots. Antisera against VP1 and VP3 recombinant proteins reacted with the respective structural proteins of HAV in immunoblots. Two recombinant proteins, one including the first 120 amino acids of the N‐terminus of VP1 and the other containing all of VP1 except for the first 60 N‐terminal amino acids, induced a transient neutralizing antibody response in rabbits. Antisera directed against other regions of VP1 and VP3 neither neutralized viral infectivity nor recognized native virus in a competitive radioimmunoassay. However, when immunized animals were challenged with a subimmunogenic dose of HAV, all animals responded with stable virus‐neutralizing antibodies.