bluuebunny/crossref_metadata_2025 huggingface dataset:
Tolerance of one‐month intranasal interferon
Authors: Scott G. M. , Onwubalili J. K. , Robinson J. A. , Doré C. , Secher D. S. , Cantell K.
Published: March 2007

Under double‐blind conditions, groups of volunteers (68 in total) were allocated at random to take intranasal solutions of placebo or one of three doses of highly purified leucocyte interferon by intranasal spray twice a day for 28 days. The highest dose would have been expected to protect against experimental colds. Treatment was discontinued because of upper respiratory symptoms as often in each of the interferon groups as in the placebo group. However, it was possible to distinguish clinically between “colds” on placebo and low‐dose interferon and “reactions to treatment” on high‐dose interferon. The features of the reactions to treatment were a protracted build‐up of local symptoms and minor epistaxis. None of the volunteers on the high‐dose interferon were thought to have a definite cold, but viruses were isolated from four out of six volunteers on low‐dose interferon who had definite colds. Previous experiments had also shown this dose to be insufficient to protect against experimental rhinovirus challenge.

The dose of interferon that appeared to protect against virus infection caused significant unwanted effects. It is essential to find interferon preparations with less inflammatory activity before interferon can be considered for use as a long‐term prophylactic against the common cold.
Hantaan virus infection in suckling mice: Virologic and pathologic correlates
Authors: McKee Kelly T. , Kim Gum Ryong , Green David E. , Peters C. J.
Published: March 2007

The Hantaan virus suckling mouse model was examined to delineate virologic and histopathologic characteristics of infection at the organ level. Viral antigen and infectious virus were detected in all organs examined, with highest titers achieved in brain, lung, and kidney. A constellation of histologic lesions was identified in brain (diffuse meningoencephalitis with bilaterally symmetrical thalamic necrosis), liver (pericholangiohepatitis), lung (pneumonitis), and spleen (lymphoid hyperplasia); this tetrad is apparently unique to this model system. The chronology of clinical, virologic, serologic, and pathologic findings in Hantaan‐infected newborn mice suggests an immune‐mediated mechanism in disease pathogenesis.
Humoral immune response to HSV‐1 and HSV‐2 viral proteins in patients with primary genital herpes
Authors: Ashley Rhoda , Benedetti Jacqueline , Corey Lawrence
Published: March 2007

The humoral immune response to HSV‐1 and HSV‐2 proteins was examined in patients with primary first‐episode genital herpes. Ten patients had culture‐proven HSV‐1 infections, 37 had HSV‐2 infections, and all were seronegative to HSV proteins before developing their infections. Development of serum antibodies to individual HSV proteins and glycoproteins was determined by immunoprecipitation of radiolabeled HSV‐1‐ and HSV‐2‐ infected cell proteins and subsequent gel electrophoresis. In HSV‐1 patients, a sequential development of antibodies to HSV‐1 proteins was observed with early appearance of antibodies to the nucleocapsid protein p148 and to glycoproteins gB and gC. Seroconversion to gD and to a polypeptide of 88,000 molecular weight (p88) occurred next, and, finally, seroconversion to gE and to a nonglycosylated 66,000 dalton protein p66. In HSV‐2 patients, antibodies to HSV‐2 proteins p148, gB, and p88 appeared within 1 week of onset of symptoms. Seroconversion to p66, gD, and to a complex of glycoproteins gC and gE (g80) occurred later, at a mean time of approximately 3 weeks. Seroconversion to HSV‐1 gB, p88, and p66 occurred significantly later than seroconversion to the homologous counterparts. Seroconversion within 21 days of onset to HSV‐2 gD, g80, and p66 was associated with a longer time to the first recurrence in HSV‐2 patients, suggesting a possible role of these antibodies, alone or in combination, in the maintenance of HSV‐2 latency in humans.
An outbreak of hepatitis A on a hospital ward
Authors: Skidmore S. J. , Gully P. R. , Middleton J. D. , Hassam Z. A. , Singal G. M.
Published: March 2007

An outbreak of hepatitis A has been recognised on a medical ward of a district general hospital. Eleven nurses and one patient were reported to have hepatitis over a period of 18 days in October, 1984. Specific tests for hepatitis A IgM were positive in all cases. Following extensive investigations, the outbreak was traced to a female patient who had recently returned from India and who was incontinent. Her serum, when tested subsequently, showed evidence of recent hepatitis A infection. The implications of this outbreak are discussed.
Human immune response to cytomegalovirus structural polypeptides studied by immunoblotting
Authors: Landini M. P. , Re M. C. , Mirolo G. , Baldassarri B. , La Placa M.
Published: March 2007

To define better the human immune response to individual structural proteins of human cytomegalovirus (HCMV), 55 human sera with different IgG and IgM titres were studied for their reactivity with HCMV structural polypeptides separated by SDS‐PAGE and electrotransferred to nitrocellulose paper. The results obtained showed that antibody titres detected by immunoassay correlate with the intensity and the number of polypeptides reacting by immunoblotting (IB). The IB profiles of HCMV polypeptides reacting with different sera having the same antibody titres show considerable variation. Sera with high levels of IgG antibody and that are IgM‐positive frequently react with 155, 149, 82.5, 74.5, 67, 57, 55, 38.5, and 28 kD polypeptides; all these sera react with 155, 67, 57, 55, 38.5 kD polypeptides. Sera with high levels of IgG antibody but that are IgM negative frequently react with all these polypeptides, with the exception of 149 and 74.5. Only 155 and 28 kD polypeptides were recognized by all sera of this group. The sera with moderate levels of IgG antibody preferentially recognize 155, 110, 82.5, 62, 55, 38.5 and 28 kD polypeptides. The sera with low levels of antibody reacted especially with 155 and 62 kD polypeptides. IgM antibody seems to recognize preferentially 155, 110, 67, 57, 55, 38.5 kD polypeptides.
A survey of respiratory syncytial virus and parainfluenza virus type 3 neutralising and immunoprecipitating antibodies in relation to paget disease
Authors: Pringle C. R. , Wilkie M. L. , Elliott R. M.
Published: March 2007

The aetiology of Paget disease of bone has not been established but certain features have suggested involvement of a parainfluenzalike virus. To seek further evidence of the possible role of paramyxoviruses in Paget disease we have surveyed the presence of neutralising and immunoprecipitating antibodies to both respiratory syncytial virus and parainfluenza virus type 3 in the sera of patients attending a bone disease clinic. These two viruses were implicated by the sporadic observation of viral antigen in individual nuclei of osteoclasts in Paget disease bone lesions. A total of 315 samples were obtained from 177 patients attending the clinic during 1 year. Thirty‐six of the patients had confirmed Paget disease and the remainder other conditions. All sera possessed neutralising activity to both viruses. The mean titres for each virus were similar in patients with Paget disease and those with other conditions whether matched or not. In the case of respiratory syncytial virus the neutralising titres were distributed closer to the mean in the Paget group and showed little variation in repeat samples taken over periods of up to 1 year in contrast to the greater variability of the control group.

The antigenic specificity of 20 age‐ and sex‐matched sera from each group was examined by immunoprecipitation. No significant differences were observed between Paget and non‐Paget patients. These results do not provide confirmation of involvement of either virus in Paget disease, but the serological data suggest that persistent infection with respiratory syncytial virus can occur.
Molecular epidemiology of rotavirus infections in Uppsala, Sweden, 1981: Disappearance of a predominant electropherotype
Authors: Svensson Lennart , Uhnoo Ingrid , Grandien Monica , Wadell Göran
Published: March 2007

The molecular epidemiology of rotavirus infections was studied in children with acute gastroenteritis in Uppsala, Sweden, during 1981. Altogether 118 virus strains were investigated by analysis of the RNA migration pattern in silver‐stained polyacrylamide gels. Six different electropherotypes were seen: two with “short” and four with “long” RNA migration patterns. Forty‐two strains (36%) exhibited “short” patterns. The seasonal distribution showed that strains with “long” and “short” RNA patterns cocirculated in equal frequency during the first seven months of the year, until the predominant “short” RNA electropherotype suddenly disappeared. More than 11 RNA segments were seen in two stool specimens. A complete correlation was found between the electrophoretic migration of segments 10 and 11 and the serological defined subgroup specificity.
Detection by ELISA of immunoglobulin G subclass‐specific antibody responses in rotavirus infections in children
Authors: Grauballe Per C. , Hornsleth Allan , Hjelt Karsten , Krasilnikoff Peter Andreas
Published: March 2007

IgG subclass‐specific antibody responses to a human subgroup 2 rotavirus were studied in 26 children by ELISA by use of monoclonal antibodies specific to the four human IgG subclasses. One hundred twenty‐nine serum samples were obtained before, during, and after an episode of rotavirus‐induced diarrhoea in these patients. When these sera were investigated, an increase in IgG1 and IgG3 subclass‐specific antibodies was detected in all 26 patients. IgG3 antibodies reached a peak concentration 1 week after rotavirus was detected in faecal samples and then progressively declined over the following months, whereas the peak concentration of IgG1 subclass antibodies was found 2 months later and seemed to persist thereafter. IgG2 rotavirus‐specific subclass antibodies were never found and IgG4 subclass antibodies were detected only in sera from seven of the 26 patients.
Involvement of infants, children, and adults in a rotavirus gastroenteritis outbreak in a kibbutz in southern Israel
Authors: Galil A. , Antverg R. , Katzir G. , Zentner B. , Margalith M. , Friedman M. G. , Sarov B. , Sarov I.
Published: March 2007

An outbreak of acute gastroenteritis in a kibbutz in southern Israel, characterized by diarrhea, fever, vomiting, and abdominal pain, involved 32 kibbutz members of all ages. Nineteen percent of the children and 3.5% of the adults were ill. Transmission of the illness occurred in direct proportion to the degree of close contact, involving first infants, then mothers and nursery staff, and only later youngsters, adolescents, and fathers. Stool samples obtained from 32 kibbutz members with clinical illness and from 44 asymptomatic close contacts were examined for the presence of rotavirus antigen. Fifty‐six percent of symptomatic members were positive for rotavirus antigen as compared with 4.5% of asymptomatic close contacts. Positivity of stool samples correlated inversely with the number of days elapsed after onset of illness until the sample was obtained. Serologic studies carried out on acute and convalescent sera of symptomatic and asymptomatic subjects further supported a rotavirus etiology for the outbreak. RNA profiles of stool sample extracts obtained by polyacrylamide gel electrophoresis and silver staining indicate that one electropherotype may have been responsible for the outbreak.
Response to hepatitis B vaccine in family members of HBsAg carriers
Authors: Lok Anna Suk‐Fong , Ng Matthew Mai‐Tai , Lal Ching‐Lung , Wu Pul‐Chee
Published: March 2007

The family members of HBsAg carriers have an increased risk of hepatitis B virus (HBV) infection. 214 subjects from 98 families with no HBV markers were randomized to receive hepatitis B vaccine: HEVAC B (Institute Pasteur) or GCC VAC (Green Cross Corporation) at 0, 1, and 5 months. Of those who completed the course, 87.8% had an anti‐HBs response of > 10 mIU/ml at 6 months. The response rate was similar for both sexes. There was a decrease in response rate and anti‐HBs titre with age. The response rate for HEVAC B was 92.5% and GCC VAC 84.3%. The offspring had comparable response to the spouses who were not blood relatives of the index carriers, but this could be related to their younger age. Discriminant analysis showed that a higher anti‐HBs titre was associated with HEVAC B, younger age, and less direct relationship with the index carrier.
Identification of a dominant immunogenic epitope of the nucleocapsid (HBc) of the hepatitis B virus
Authors: Waters J. A. , Jowett T. P. , Thomas H. C.
Published: March 2007

Four monoclonal antibodies to hepatitis B core antigen are described. The antibodies bind to the same or a very closely related epitope. Antibodies to this dominant epitope are present in the sera of patients with either acute or chronic hepatitis B virus (HBV) infection. A high percentage of inhibition of the binding of these antibodies to the core antigen by these four monoclonal antibodies suggests that the core antigen has a restricted antigenicity in man. Radiolabeled or peroxidase labeled forms of these monoclonal antibodies can be used to assay IgM and total anticore in serum.
Serum HBsAg, HBeAg, anti‐HBe, and hepatitis B viral DNA in asymptomatic carriers in Taiwan
Authors: Chen Ding‐Shinn , Lai Ming‐Yang , Lee Sheng‐Chung , Sheu Jin‐Chuan , Yang Pel‐Ming , Sung Juei‐Low
Published: March 2007

Plasma samples from 89 asymptomatic hepatitis B surface antigen (HBsAg) positive volunteer blood donors were titrated for HBsAg by radioimmunoassay using the parallel line method. HBsAg titers ranged widely from 0.01 to 325 μg/ml. The titers correlated well with hepatitis B viral DNA (HBV DNA) and hepatitis B e antigen (HBeAg) in the serum. The HBsAg titers in 55 HBV DNA positive carriers were 90.7 ± 61.7 μg/ml (Mean ± SD) vs. 6.3 ± 12.2 μg/ml in the 34 carriers without HBV DNA in the serum. The titers were 93.9 ± 59.1 μg/ml in 56 carriers with HBeAg, 6.4 ± 10.1 μg/ml in 24 anti‐HBe‐positive carriers, and 4.9 ± 4.6 μg/ml in 9 HBeAg/anti‐HBe‐negative carriers. 50 (89.3%) of the 56 HBeAg‐positive carriers had HBV DNA, in contrast to four (16.7%) of 24 anti‐HBe‐positive carriers. The study indicated that high‐titered HBsAg carriers were much more likely to be infectious, and confirmed that HBeAg is a practical marker of infectivity. Absence of HBeAg, however, did not exclude infectivity in asymptomatic HBsAg carriers, inasmuch as one‐sixth of the carriers had HBV DNA.
Perinatal transmission of hepatitis B virus in Kenya: Its relation to the presence of serum HBV‐DNA and Anti‐HBe in the mother
Authors: Greenfield C. , Osidiana V. , Karayiannis P. , Galpin S. , Musoke R. , Jowett T. P. , Mati P. , Tukei P. M. , Thomas H. C.
Published: March 2007

In Kenya hepatitis B virus (HBV) infection and its sequelae are common. We followed up 49 hepatitis B surface antigen (HBsAg)‐ positive mothers and their newborn infants for 9 months to determine the importance of perinatal transmission in the African and to relate this to the HBe and HBV‐DNA status of the mother. Our study shows that perinatal transmission is relatively unimportant in Kenya and that this may be a consequence of the low levels of circulating HBVDNA in the maternal plasma. These results imply that vaccination without hyperimmune globulin may be adequate to control HBV infection in Kenya.
The association of rhinoviruses with lower respiratory tract disease in hospitalized patients
Authors: Krilov Leonard , Pierik Lauren , Keller Evelyn , Mahan Kevin , Watson David , Hirsch Martin , Hamparian Vincent , McIntosh Kenneth
Published: March 2007

An analysis of 32 hospitalized infants and children from whom rhinoviruses were isolated in our diagnostic laboratories in 1982–83 suggests that these agents are associated with lower respiratory tract disease with focal findings in susceptible patients. In 23 cases, an acute lower respiratory disease was the cause for admission, while nine patients were cultured after new respiratory symptoms developed during hospitalization. Presenting signs and symptoms included cough (23), fever (19), rhinorrhea (19), respiratory distress (14), and decreased feeding (15). Seventeen of 25 chest x‐rays showed new focal abnormalities. Twenty‐five patients had a significant underlying disease including seven with malignancies, six with respiratory tract abnormalities, and four with congenital heart lesions. Six of the remaining seven patients were less than 2% months of age. In no cases were significant bacterial or fungal pathogens isolated; two did have concomitant viral isolates. Rhinoviruses in the appropriate clinical setting are associated with significant pulmonary disease.
An immunoglobulin G capture assay (GACRIA) for anti‐HTLV III/LAV and its use as a confirmatory test
Authors: Parry John V.
Published: March 2007

An immunoglobulin G (IgG) antibody capture assay (GACRIA) methodologically distinct from other assays for the detection of antibodies to human T‐lymphotropic virus type III/lymphadenopathy‐associated virus (anti‐HTLV III/LAV) was developed and used to test 1,055 serum samples previously screened by a competitive assay (COMPRIA). Eight hundred and twenty‐three (78%) sera were positive and 129 (12.2%) negative in both assays. The coefficient of correlation between the two assays was 0.87, and COMPRIA appeared more sensitive than GACRIA. On retesting 103 sera that gave initially conflicting results, 81 discrepancies were resolved, 77 because of a change in the COMPRIA result. The 22 persistently discrepant samples gave an equivocal or positive result by COMPRIA and were negative by GACRIA. Thirteen of these 22 were positive in a commercial ELISA (ELAVIA). Twenty of them were also tested by Western blot; all were reactive with at least two HTLV III/LAV protein bands. The persistently discrepant samples were of four types: 1) laboratory control sera (n = 2); 2) naturally occurring weakly reactive samples (n = 5); 3) samples that were anti‐HTLV IU/ LAV IgG negative but IgM positive (n = 5; all five individuals from whom these samples were drawn were symptomatic); 4) samples from one laboratory that were probably accidentally contaminated with anti‐HTLV III/LAV‐positive serum (n = 10).

It was concluded that GACRZA for anti‐HTLV III/LAV is specific and adequately sensitive and, in conjunction with other assays, is a useful confirmatory test whose format could readily be changed to ELISA.
Seasonal Variations in Maternal Serum and Mammary Immunity to RS Virus
Authors: Nandapalan N. , Taylor C. E. , Greenwell J. , Scott M. , Scott R. , Hey E. N. , Toms G. L.
Published: March 2007

We have recorded the systemic and mammary/mucosal immune responses of women following natural infection with RS virus during the second and third trimesters of pregnancy. Anti‐RS virus IgG antibody levels in the sera of women collected in the first trimester of pregnancy showed a bimodal distribution with high and low antibody groups. Antibody levels increased after exposure to the winter RS virus epidemic in the second trimester of pregnancy, probably as a result of infection but only for women in the low antibody group. Despite the increases, antibody levels for these women remained well below those of the high antibody group. There was no rise in mean antibody levels after exposure in the third trimester, even among women with low antibody, suggesting a degree of immunosuppression in late pregnancy. There was no evidence that infection during pregnancy was associated with adverse consequences for the infant.

Exposure to RS virus in the first two trimesters, but not the third, was associated with high colostral IgA antibody levels that were maintained in the milk throughout the first 7 weeks of lactation. There was a significant correlation between colostral and maternal nasal IgA antibody levels at delivery. Levels of blood or colostral lymphocyte transformation responses at delivery were unaffected by exposure to RS virus in pregnancy.

These observations upon natural infection suggest that vaccination during pregnancy is likely to achieve only marginal effects upon serum antibody levels but boost maternal mammary/nucosal immunity.
Comparative Trial of Acyclovir and Vidarabine in Disseminated Varicella‐Zoster Virus Infections in Immunocompromised Patients
Authors: Vildé J. L. , Bricaire F. , Leport C. , Renaudie M. , Brun‐Vézinet F.
Published: March 2007

A comparative assessment of vidarabine and acyclovir in the treatment of varicella and disseminated zoster in immunosuppressed patients was undertaken. Thirty‐eight immunosuppressed patients with varicella (N = 18) or disseminated zoster (N = 20) were treated intravenously with 10 mg/kg/day of vidarabine or 30 mg/kg/day of acyclovir for 5 days according to a preestablished code within each diagnosis group–varicella and disseminated zoster. Two deaths, although not directly related to VZV infection, were observed in the vidarabine‐treated varicella group. The times to cessation of formation of new lesions and to the disappearance of fever were similar for vidarabine and acyclovir in each group. In the varicella group, VZV was isolated on day 5 in four out of five vidarabine patients versus one out of five acyclovir patients. No severe adverse effects were observed with either drug. Neutropenia present in patients of both drug groups was transitory and most often related to previous cytolytic chemotherapy.

These data suggest that either vidarabine or acyclovir could be used in the treatment of severe VZV infections in immunosuppressed patients, although a larger number of patients would be required for definitive conclusion. Because of the large amount of solute required for vidarabine administration, acyclovir may be preferred when the risk of cardiorespiratory failure is high.
New Findings in Live, Attenuated Hepatitis A Vaccine Development
Authors: Provost P. J. , Gerety R. J. , Hilleman M. R. , McAleer W. J. , Scolnick E. M. , Bishop R. P. , Stevens C. E.
Published: March 2007

Strain CR326F of hepatitis A virus, derived from a fecal specimen of Costa Rican patient 033–03, was passed 15 times in fetal rhesus monkey kidney (FRhK6) cell cultures plus eight times in human diploid lung (MRCS) cell cultures to yield variant F and 16 times in MRCS cell cultures to yield variant F'. Both variants were purified by limit dilution passages. Virulence for marmosets was assessed at six different passage levels, including variants F and F'. There was a gradual loss of virulence with in vitro passage. Variant F retained slight virulence for marmosets; variant F' showed no evidence of virulence. Both variants induced hepatitis A antibody in most marmosets that received them, and the animals were immune to infection when challenged. Variants F and F' were also assessed in chimpanzees. As in marmosets, F retained slight virulence but F' did not. Experimental vaccines made from variants F and F' were then inoculated parenterally into adult human volunteers. A portion of recipients of variant F showed brief, low‐order enzyme elevations; none was seen in recipients of F', although their occurrence could not be totally ruled out. As in the animal models, F' appeared more attenuated than F. Most persons developed hepatitis A antibody, indicating the feasibility of developing a live, attenuated hepatitis A vaccine for human beings.
Antibody Determination in an Ongoing Hepatitis B Vaccination Program
Authors: Burckhardt Johann J. , Born Pius , Pletscher Walter
Published: March 2007

In an interim analysis of our ongoing immunization program against hepatitis B (HB), started in early 1982, we tested 283 serum samples from 77 female and 110 male vaccinees for antibody to HB surface antigen (anti‐HBs). We compared two methods, Anti‐HBs EIA (ROCHE) (method 1), which is a neutralization test, and AUSABR EIA (method 2), which is a double‐antigen‐sandwich test.

The nonresponder rate (after the 12‐month booster dose of Hevac B Pasteur) was 4% in females with both methods, in males 15% measured with method 1 and 11% measured with method 2. Five healthy HBsAg carriers were detected only by method 1.

When the samples were grouped according to their anti‐HBs titers, method 1 measured higher in samples taken after three vaccine doses and method 2 did so in samples collected after the 12‐month booster dose. This tendency was confirmed with samples from slow responders who received a 4th vaccine dose soon after the initial three doses. We therefore confirm the efficacy of the plasma‐derived HBsAg vaccine and validate the assay systems used to measure anti‐HBs, one parameter of immunity to HB virus infection.
Detection of Human Papillomavirus DNA by the Nucleic Acid Sandwich Hybridization Method From Cervical Scraping
Authors: Parkkinen Sinikka , Mantyjarvi Rauno , Syrjanen Kari , Ranki Marjut
Published: March 2007

Cervical scrapes collected from 100 consecutive patients participating in a prospective follow‐up study for cervical human papillomavirus (HPV) infections were tested for the presence of HPV 11 DNA by the nucleic acid sandwich hybridization method, which allows testing the specimens in a crude form. Part of each specimen was processed through phenol extraction and DNA purification to a dot blot hybridization assay. The dot blots were serially hybridized with HPV 6, 11, 16, and 18 probes as well as with an Alu‐repeat probe to estimate the number of cells in the specimen. In PAP smears, HPV‐infection was suspected in 63 patients whereas in 37 patients the smear was negative. In the first group, the dot blot assay revealed three cases of HPV 11, two of HPV 16, and one of HPV 18 infection. In the second group with normal PAP smear, one additional HPV 18 infection was found. The sandwich hybridization assay detected 5 HPV 11 infections, including the three mentioned above. All HPV DNA‐positive samples contained at least 1.6 × 106 cells. Since we considered this a prerequisite for successful diagnosis, only 25 specimens in the first group and 15 in the second were adequate specimens. Thus the HPV‐DNA detection rate was 32% (8/25) in the first group and 1115 in the second. This study demonstrates that sandwich hybridization, detecting 1–3 × 105 HPV 11 molecules is a reliable diagnostic method. Cervical scrape is a valuable altenative to punch biopsy, but the number of cells collected is critical for the outcome of the assay.
Detection of Human Rhinoviruses and Their Molecular Relationship Using cDNA Probes
Authors: Ai‐Nakib W. , Stanway G. , Forsyth M. , Hughes P. J. , Almond J. W. , Tyrrell D. A. J.
Published: March 2007

We describe here a cDNA: RNA hybridization system for the study of human rhinoviruses. We have constructed an M13 probe from the 5′ end of the genome of rhinovirus 14 (HRV‐14) and used this to detect directly viral RNA. Of the 56 human rhinoviruses so far investigated 54 or 96.4% gave clearly positive hybridization signals. However, the strength of this signal depended very much on the molecular relationship of these viruses. Thus, HRV‐3, 4, 17, 72, and, to a slightly lesser extent, HRV‐2, 6, 9, 13, 19, 31, 42, 49, 64, and 69 appear to be closely related to HRV‐14 whereas HRV‐5, 7, 8, 16, 32, 40, 45, 55, 56, 63, 80, 82, and 85 appear to be relatively divergent. Further, evidence is provided in this study that indicates that it would be feasible to use cDNA probes to detect human rhinoviruses in nasal washings. However, the sensitivity of detection was clearly affected by both the inclusion of inhibitors of endogenous RNase activity in the RNA extraction mixture and also in the method of extracting the viral RNA. From reconstruction experiments in nasal washings and under optimal conditions, we can detect virus at 102.8 TCID50/ml.
Rotavirus Fecal IgA Antibody Response in Adults Challenged With Human Rotavirus
Authors: Bernstein David I. , Ziegler John M. , Ward Richard L.
Published: March 2007

Our studies of rotavirus challenge in adult volunteers enabled us to evaluate the relationship of pre‐existing antirotavirus fecal IgA antibody to infection and illness and to investigate the local response to this infection. No relationship could be found between the pre‐existing levels of fecal antirotavirus IgA antibody and protection from infection or illness. A greater than six‐fold increase in the level of antibody was seen in 16/19 infected volunteers with determinable increases but in 0115 controls who received less than the minimal infectious dose of rotavirus. Antibody levels increased rapidly in infected volunteers and were consistent with an anamnestic response. Two of seven volunteers who received an infectious dose of rotavirus but were considered uninfected on the basis of other laboratory methods had greater than or equal to six‐fold increases of fecal antibody and one of these experienced symptoms compatible with a rotavirus infection. This finding indicates that an increase in fecal antibody may be a reliable indicator of rotavirus infection even in the absence of detectable shedding or seroconversion.
Visualization of Replicating Herpes Simplex Virus in Cervical Dorsal Root Ganglia of Mice Following Explant of Individual Ganglion Onto Susceptible Indicator Cells
Authors: Blondeau Joseph M. , Embil Juan A. , Sandra McFarlane E. , James Hana , Henry Marlene , Sangalang Virgilio E.
Published: March 2007

Herpes simplex virus (HSV) establishes a latent state in the sensory ganglia of the peripheral nervous system of its natural or experimental host following primary infection. At various times thereafter, the virus can be reactivated from the latent state whereby it migrates back to the periphery and sometimes initiates a clinical syndrome referred to as recurrent disease.

We inoculated mice in the right ear pinna and, following recovery from primary infection, killed the mice at various intervals following either the presence or absence of peripheral stimulations. Explanted cervical dorsal root ganglia yielded HSV in culture and was positive for HSV‐like virus particles when viewed with the electron microscope. Hematoxylin and eosin staining showed neuron degeneration, and corresponding HSV‐specific immunoperoxidase stains were also positive. The data indicate that ganglionic cells are capable of supporting replicating HSV and that, in vitro, numerous ganglionic cells can be infected simultaneously.
Human Cytomegalovirus Replicates in Gamma‐Irradiated Fibroblasts
Authors: Shanley John D.
Published: March 2007

Because of the unique interdependence of human cytomegalovirus (HCMV) and the physiological state of the host cell, we evaluated the ability of human foreskin fibroblasts (HFF), exposed to gamma radiation, to support HCMV growth. Irradiation of HFF with 2,500 rADS prevented cellular proliferation and suppressed cellular DNA, but not RNA or protein synthesis. Treatment of HFF cells with 2,500 rADS 6 or 48 hours prior to infection did not alter the time course or virus yield during HCMV replication. Virus plaquing efficiency in irradiated cells was comparable to that of nonirradiated cells. As judged by thymidine incorporation and BUdR inhibition of virus replication, HCMV infection induced both thymidine kinase activity and host cell DNA synthesis in irradiated cells. In addition, virus could be recovered from HFF exposed to radiation 0–2 days after infection with HCMV. These studies indicate that the damage to cells by gamma irradiation does not alter the capacity of host cells to support HCMV replication.
Estimation of the B Lymphocyte Precursor Frequencies to Herpes Simplex Type 1 Glycoproteins by a Limiting Dilution Assay
Authors: Turtinen Lloyd W. , Lathey Janet L. , Rouse Barry T.
Published: March 2007

The precursor frequency of B lymphocytes from Balb/c mice producing HSV‐1 glycoprotein B (gB), glycoprotein C (gC), and glycoprotein D (gD) antibody was determined by limiting dilution analysis under conditions to detect antibody from the clonal progeny of a single B cell precursor. In spleens of naive mice the average gC frequency was 1/48,917 ± 550, while gD was 1/73,330 ± 15,898, and gB frequency was in excess of 1/1OO,ooO. Immunization with live HSV‐1 (KOS) increased the B cell frequencies of all three glycoproteins to approximately 1:3,000; however, the serum gB antibody ELISA titer was fivefold higher than gC or gD.
Interferon‐Mediated Self‐Limiting Growth of Respiratory Syncytial Virus in Mouse Embryo Cells
Authors: Hanada Naoki , Morishima Tsuneo , Nishikawa Kazuo , Isomu Shin , Nagai Yoshiyuki
Published: March 2007

The growth of respiratory syncytial (RS) virus in primary mouse embryo (ME) cells was investigated. The virus yields in ME cells were markedly lower if compared with those in HEp‐2 cells, which are fully permissive for RS virus, and a remarkable production of interferon (IFN) was found in the early period of infection of the former cells. The virus yields in ME cells were enhanced when antimouse IFN serum was added to the medium. Indirect immunofluorescent staining of infected ME cells showed that the infection spread in the entire monolayer in the presence of antiserum, whereas it was markedly restricted throughout in the absence of the serum. All the major viral polypeptides were synthesized in the absence of the serum. However, their synthesis rates were greatly enhanced if the antiserum was added. These results suggest that the virus growth in ME cells is self‐limiting and that this limited growth is due to auto interference by endogenously produced IFN during the course of infection. Further, this type of growth restriction of RS virus appears to be characteristic of cells of mouse origin by comparative studies that used other cells of different origin.
Controlled clinical trial of acyclovir in chronic hepatitis B virus infection
Authors: Alexander Graeme J. M. , Fagan Elizabeth A. , Hegarty John E. , Eddleston Adrian L. W. F. , Williams Roger , Yeo Jane
Published: March 2007

A randomised, controlled trial comparing acyclovir, 45 mg/kg/day as a continuous IV infusion for 28 days, with no other therapy, was carried out in 30 stable HBsAg carriers seropositive for HBeAg for more than 6 months. Twenty‐eight had hepatitis B virus DNA‐polymerase activity and/or hepatitis B virus DNA in serum at entry into the study. There were no significant adverse effects of therapy. At 12 months, seroconversion from HBeAg to anti‐HBe had occurred in four of 15 treated patients, one of whom had also developed anti‐HBs, compared with only one of 15 in the untreated group (95 % confidence limits 12 % and 51 %). Seroconversion from HBeAg to anti‐HBe was accompanied by return of serum liver function tests to normal and improved liver histology. The results of this study indicate that acyclovir is of no significant benefit in chronic HBeAg carriers with stable disease.
Suramin treatment for chronic active hepatitis B—toxic and ineffective
Authors: Loke R. H. T. , Anderson M. G. , Coleman J. C. , Murray‐Lyon I. M. , Tsiquaye K. N. , Zuckerman A. J.
Published: March 2007

Suramin has recently been shown to inhibit the activity of the duck hepatitis B virus DNA polymerase (DHBV DNAp) in vitro.

However, we found no demonstrable in vivo suppression of human hepatitis B virus DNA polymerase (HBV DNAp) activity in three male patients with severe chronic active hepatitis. Suramin treatment resulted in prolongation of the prothrombin time in all cases and a rise in bilirubin in two and it may have led to haemorrhage from oesophageal varices in one patient and to hepatic encephalopathy in another. Its use in chronic hepatitis is not recommended.
Detection of adenovirus types 40 and 41 in stool specimens by immune electron microscopy
Authors: Wood D. J. , Bailey A. S.
Published: March 2007

An immune electron microscope (IEM) test was developed that allowed the direct detection of adenovirus type 40 (ad 40) or ad 41 in stools specimens. The polyclonal rabbit antisera used differentiated ad 40 and 41 from other ad serotypes but not from each other. The method was evaluated in a 13 month prospective study of stools from children with gastroenteritis. Seventy‐two specimens found to contain ad by conventional electron microscope screening were retested by IEM. Results were typically obtained within 2 hr and showed that 55 (76%) viruses typed as ad 40/41. No ads were recovered from conventional virus isolation attempts on these specimens. Additionally, 39 of these 55 viruses were tested by restriction endonuclease analysis (REA) after growth in 293 cells, and results showed that all produced digest patterns typical of ad 40 (seven cases) or ad 41 (32 cases). Twenty‐four percent (17/72) of viruses could not be typed by IEM; 9/17 (53%) yielded ads [ad 1 (1), ad 2 (4), ad 5 (1), ad 6 (1), ad 7 (2)] in routine culture, whereas REA identified the other eight as ad 2 (6), ad 1 (1), and ad 41 (1). The concordance between IEM and the reference methods was therefore 100% specificity and 97.5 % sensitivity. The method described allows the clinically useful diagnosis of ad 40/41 infection to be rapidly made and will be a particularly useful technique in laboratories screening faeces by electron microscopy.
Effect of combinations of difluoromethylornithine (DFMO) and 9[(1,3‐dihydroxy‐2‐propoxy) methyl]guanine (DHPG) on human cytomegalovirus
Authors: Rush Joanne , Mills John
Published: March 2007

Both the nucleoside analog 9[(1,3‐dihydroxy‐2‐propoxy)methyl]guanine (ganciclovir; DHPG) and the polyamine synthesis inhibitor difluoromethylornithine (DFMO) have been reported to inhibit replication of cytomegalovirus (CMV) in vitro. In these studies, DHPG inhibited human CMV replication at concentrations of 0.1 μM or greater, while DFMO was active (and then only inconsistently) at 5 mM or greater. (DFMO was added to cells 3 days before virus to maximize polyamine depletion.) However, DHPG combined with DFMO synergistically inhibited the replication of CMV strain AD169 and one wild‐type CMV strain in human foreskin fibroblasts; the effect was evident on both virus yield and plaque formation. The synergistic effect of these two drugs on CMV replication could potentially be exploited clinically to limit drug toxicity or increase efficacy.
Reduced doses of hepatitis B immune globulin in the prevention of perinatal transmission of hepatitis B
Authors: Ko Tsang‐Ming , Hsieh Fon‐Jou , Yaung Chih‐Liang , Chen Ding‐Shinn , Lin Kai‐Hsin , Ho Mei‐Mei , Hwang Kung‐Chang , Hwang Muh‐Fa
Published: March 2007

From October 1982 to May 1983, newborn infants of 79 hepatitis B surface antigen (HBsAg)‐positive women were enrolled in a study of the efficacy of hepatitis B immune globulin (HBIG) in the prophylaxis of perinatal transmission of hepatitis B virus (HBV) infection. HBIG 0.5 ml or 0.25 ml was given to the newborn within 15 minutes of birth and at 3 and 6 months. The mother‐infant pairs were followed‐up every 3 months for at least 9 months. Similar observations of untreated infants were used for comparison. Among infants of hepatitis B e antigen (HBeAg)‐positive carrier mothers, the HBsAg carrier rates at 3 months were similar in the 0.5‐ml and 0.25‐ml HBIG dose groups. At 12 months the difference—17.7% of 17,40% of 15—did not reach statistical significance, but the differences between these rates and that of the untreated control—85.7% of 35—did.

Among infants of HBeAg‐negative carrier mothers, HBV infection rates in both dose groups were similar to those of untreated infants.

In the treated groups at 12 months about 45% of infants of HBeAg‐positive mothers and 90% of infants of HBeAg‐negative mothers were still negative for HBsAg and anti‐HBs. Vaccination to induce active antibody is necessary to prevent postnatal infection and chronic carriage of HBV. To reduce the cost of combined passive and active hepatitis B immunoprophylaxis in children born to HBeAg‐positive carrier mothers, 0.25 ml of HBIG could be used instead of the usually recommended 0.5 ml.
Development of a plaque assay for a cytopathic, rapidly replicating isolate of hepatitis A virus
Authors: Cromeans Theresa , Sobsey Mark D. , Fields Howard A.
Published: March 2007

Most hepatitis A virus (HAV) replication in cell culture has been reported to be nonlytic and relatively slow. A rapidly replicating isolate of strain HM‐175 from persistently infected, serially passed cell cultures (pHM‐175) was found to induce a cytopathic effect. This observation allowed the development of a classic plaque assay for pHM‐175 in FRhK‐4 cells. The plaques were neutralized by polyclonal and monoclonal antisera to HAV.
Virus‐specific factors in experimental Argentine hemorrhagic fever in rhesus macaques
Authors: McKee K. T. , Mahlandt B. G. , Maiztegui J. I. , Green D. E. , Peters C. J.
Published: March 2007

A nonhuman primate model for Argentine hemorrhagic fever has been developed that closely mimics the human clinical syndrome. Parenterat infection of adult Macaca mulatta with low‐passage isolates of two Junin viral strains resulted in distinctive hemorrhagic or neurological disease in rhesus macaques that correlated with clinical illness patterns present in the humans from whom the viral strains were obtained. Transient leukopenia, together with thrombocytopenia and secondary bacterial septicemia. were documented among animals infected with both viral strains. In contrast, differing patterns of viremia oropharyngeal viral shedding and antibody response occurred in the two virus‐infected groups. These results, together with postmortem virologic and histopathologic findings, suggest that viral‐strain‐specific factors are important determinants of clinical disease pattern in this model system.
Cellular Immunity and T‐Lymphocyte Subsets in Young Children With Acute Measles
Authors: Dagan Ron , Phillip Moshe , Sarov Israel , Skibin Agneta , Epstein Sarah , Kuperman Oded
Published: March 2007

The changes occurring in the T‐cell subsets during acute symptomatic measles were examined in ten malnourished and 18 well nourished hospitalized children younger than 5 years of age (median age 14 months). A significant decrease in total lymphocyte count was observed. which was due mainly to a decrease in helper/inducer T lymphocytes, whereas the suppressor/cytotoxic T‐lymphocyte subset remained unchanged. Consequently, helpdsuppressor ratio decreased significantly during the acute phase of the disease. A reduced response to mitogens (PHA, Con A, PWM) was also observed. Malnourished infants showed a trend toward a deeper depression in both helper and suppressor T cells during the acute phase than well nourished children, whereas the helper/suppressor ratio remained similar in the two groups.
Effect of acyclovir on the uptake of 131 I‐labelled 1‐(2′fluoro‐2′‐deoxy‐βD‐D‐arabinofuranosyl)‐5‐lodouracil in herpes infected cells
Authors: Tovell Dorothy R. , Yacyshyn Harold P. , Misra Hemant K. , Knaus Edward E. , Wiebe Leonard I. , Samuel John , Gill M. John , Tyrrell D. Lorne J.
Published: March 2007

Selective uptake of nucleoside analogues by herpes simplex virus infected cells may serve as the basis for a specific non‐invasive diagnostic test for herpes simplex encephalitis. We have examined the effect of acyclovir on the selective uptake of [131I]1‐(2′‐fluoro‐2′‐deixy‐β‐D‐arabinofuranosyl)‐5‐iouracil in herpes simplex virus infected primary rabbit kidney cells. Infected cells treated with acyclovir continued to concentrate [131]1‐(2′‐fluoro‐2′‐deoxy‐β‐D‐arabinofuranosyl)‐5‐iodouracil for up to 24 h after the addition of the antiviral agent. These results indicated that therapy with acyclovir for as long as 24 h would not prevent the selective trapping of nucleoside analogues. This has important implications for the use of nucleoside analogues in diagnostic brain scans to detect herpes simplex encephalitis.
Prevalence of antibody to delta antigen among HBV carriers in Japan
Authors: Tamura Ikuo , Ichimura Hiroshi , Itoh Yoshiharu , Kurimura Osamu , Kurimura Takashi
Published: March 2007

Of 280 hepatitis B virus (HBV) carriers in Kure, Hiroshima Prefecture, Japan, 14 (5.0%) were seropositive for antibody to delta antigen (anti‐HD by radioimmunoassay. HBV carriers with chronic liver disease had a greater frequency of seropositivity of anti‐HD than asymptomatic HBV carriers (7% vs. 0%, P < 0.05). Among the various geographic regions of Kure, the east suburban area had a significantly higher prevalance of anti‐HD when compared with all other regions combined (9.8% vs. 2.7%. P < 0.025). It is suggested that hepatitis delta virus (HDV) infection exists in Japan and HDV may be an etiologic agent of chronic liver disease.
Inhibition of hepatitis B virus DNA polymerase by 3′‐azido‐3′‐deoxythymidine triphosphate but not by its threo analog
Authors: Nordenfelt E. , Löfgren Bengt , Chattopadhyaya Jyoti , Öberg Bo
Published: March 2007

An inhibitory effect of 3′‐azido‐3′‐deoxythymidine triphosphate on hepatitis B virus DNA polymerase was found. No effect was seen by itsthreoanalog. The effect was detected at and above a concentration of 0.05 μM. The inhibition of DNA polymerase activity was the same in ten different strains of HBV. The mechanism was shown to be competitive, with an inhibition constant (Ki) of ˜0.04 μM, and the Km value for dTTP was 0.1 μM.
Mammary immunity in mothers of infants with respiratory syncytial virus infection
Authors: Nandapalan N. , Taylor C. , Scott R. , Toms G. L.
Published: March 2007

Seven of 230 breast fed infants followed prospectively from birth through their first winter contracted RS virus infections. The colostra from five of the mothers of these infants contained antiviral IgA antibodies. In each case antibody levels were above the mean for a group of 36 mothers whose infants were age matched to infected infants but for whom there was no evidence of RS virus infection in their first winter. Four colostral samples from mothers of infected infants also contained antiviral IgG antibody. Colostral lymphocyte reactivity to RS virus antigen was tested in three mothers of infected infants and two showed significant proliferation. There was, therefore, no evidence that mothers of infected infants lacked mammary immunity to the virus.

Maternal mammary IgA and IgG responses following diagnosis of RS virus infection in the infant were followed for the seven cases identified prospectively and for a further 23 infants admitted to hospital with RS virus infections of varying severity. There was no evidence that the mothers of more severely affected infants were deficient in IgA or IgG milk antibody.
Effect of polymorphonuclear depletion on experimental argentine hemorrhagic fever in guinea pigs
Authors: González Pedro Horacio , Ponzinibbio Carlos , Laguens Ruben Pedro
Published: March 2007

The role that polymorphonuclear leukocytes (PMN) may play in Argentine hemorrhagic fever (AHF), an endemo‐epidemic disease caused by Junin virus (JV), was investigated in experimentally infected guinea pigs depleted of PMN by means of specific antiserum. In leucopenic animals the evolution of the infection with a highly pathogenic strain of JV was more severe, with earlier mortality and higher virus yields in blood and viscera. The pathological study showed similar lesions in both the control and PMN‐depleted animals with the exception of the lung, which showed the pathological picture of the human “pulmonary distress syndrome of the adult” in nontreated guinea pigs and appeared histologically unaltered in the PMN‐depleted animals. On the basis of these results it is suggested that in AHF, PMN play a dual role. In the first stage of infection they display a defensive antiviral action, but later on they participate in the pathogenesis of tissue damage.