Synthesis and evaluation of 5-aminosalicyl-glycine as a potential colon-specific prodrug of 5-aminosalicylic acid

OBJECTIVE: To estimate more precisely the risk of fetal loss and congenital abnormalities after maternal parvovirus B19 infection, and to assess the long term outcome for surviving infants. DESIGN: Prospective cohort study of pregnant women with confirmed B19 infection with follow up of the surviving infants. The rate of fetal loss in the study cohort was compared with that in pregnant women with varicella. SETTING: Cases reported by laboratories in England and Wales between 1985-1988 and 1992-1995. SAMPLE: Four hundred and twenty-seven pregnant women with B19 infection and 367 surviving infants of whom 129 were followed up at 7-10 years of age. METHODS: Questionnaires to obstetricians and general practitioners on outcome of pregnancy and health of surviving infants. Maternal infection confirmed by B19-specific IgM assay and/or IgG seroconversion. RESULTS: The excess rate of fetal loss in women with B19 infection was confined to the first 20 weeks of gestation and averaged 9%. Seven cases of fetal hydrops followed maternal infections between 9 and 20 weeks of gestation (observed risk 2.9%, 95% CI 1.2-5.9). No abnormalities attributable to B19 infection were found at birth in surviving infants (observed risk 0%, upper 95% CI 0.86%). No late effects were found at 7-10 years. CONCLUSIONS: Around 1 in 10 women infected before 20 weeks of gestation will suffer a fetal loss due to B19. The risk of an adverse outcome of pregnancy after this stage is remote. Infected women can be reassured that the maximum possible risk of a congenital abnormality due to B19 is under 1% and that long term development will be normal.     

Sex-associated differences in cold-induced UCP1 synthesis in rodent brown adipose tissue

OBJECTIVE: To evaluate the usefulness of new ELISA for human parvovirus B19 (B19) antibodies and PCR for the diagnosis of acute onset of B19 polyarthritis. METHODS: We evaluated the reproducibility and sensitivity on the detection of anti-B19 antibody by ELISA using recombinant VP-1 and VP-2 (empty particle), and then studied for the prevalence of IgM and IgG B19 antibody in 125 samples for anti-B19 tests. The random study on anti-B19 antibody assay as well as PCR for B19-DNA was also performed in 130 cases with acute onset of arthritis excluding those with known origins, 224 with rheumatoid arthritis and 149 with other categories. RESULTS: The results by using B19-empty particle ELISA were reproducible and showed the assay was a sensitive way for clinical use. IgM anti-B19 antibodies were positive not only in all samples from erythema infectiosum, but also often in those from hemolytic anemia, pure red cell aplasia, fetal hydrops, hepatic injury, fever of unknown origin. Among 130 with acute onset of arthritis, 21 showed positive tests for IgM anti-B19 antibody and/or B19 DNA. On the other hand, 4 among 224 patients with rheumatoid arthritis were positive for IgM anti-B19 antibody, but all of 149 in control group were negative for IgM anti-B19 antibodies and for B19 DNA. CONCLUSION AND DISCUSSION: Anti-B19 ELISA using B19-empty particle which has been introduced as a routine test system, is a useful tool for the diagnosis of acute onset of B19 arthritis. An additional examination using PCR for B19 DNA may contribute for understanding persistent B19 polyarthritis or reactivation of B19 infection.     

The reinforced laryngeal mask airway (LMA) as an alternative airway device to manage the difficult airway

BACKGROUND: Infection with human parvovirus B19 (B19) has been reported in a few patients with various vasculitis syndromes. Mixed cryoglobulinaemia (MC), a model of small vessel size vasculitis, may result from numerous infectious diseases, particularly hepatitis C virus (HCV) infection. AIM: To assess the prevalence of seric B19 infection markers in a large series of patients with MC, with or without HCV infection. PATIENTS AND METHODS: Sixty-four patients were studied: essential MC (EMC, n = 19), MC associated with non-infectious diseases (non-essential MC, n = 9), and patients with HCV infection with (HCV-MC, n = 18) or without MC (HCV-no-MC, n = 18). Patients were considered to have MC if two successive determinations of their serum cryoglobulin concentration were above 0.05 g/l. Serum samples were analysed for specific IgG and IgM antibodies to B19 by enzyme immunoassay. B19 DNA detection was performed by polymerase chain reaction using a set of primers located in the VP1 gene, separately in serum and in cryoprecipitates to investigate a possible capture of B19 DNA in cryoprecipitate. The study also looked for a possible enrichment for of IgG antibodies to B19 in MC. RESULTS: The presence of specific IgG antibodies to B19 was found in 68% EMC, 56% non-essential MC, 78% HCV-MC, and 78% HCV-no-MC. No patient of either group had specific IgM antibodies to B19, or B19 DNA in serum or in cryoprecipitate. Overall, IgG antibodies to B19 were found in 46 of 64 (72%) serum samples, a prevalence quite similar to the prevalence in general adult population (> 60%). A specific enrichment of IgG antibodies to B19 in the MC was not found. CONCLUSION: These results suggest that B19 infection is neither an aetiological factor of EMC, nor a cofactor that may lead to MC production in patients with chronic HCV infection.     

Rhabdomyolysis after infection and taking a cold medicine in a patient who was susceptible to malignant hyperthermia

OBJECTIVE: To investigate the role of human parvovirus B19 (Parvo B19), cytomegalovirus (CMV) and human papilloma virus (HPV) viruses in the aetiopathogenesis of spontaneous abortions. STUDY DESIGN: Abortion material from 102 cases of women with spontaneous abortions were analysed for the presence of Parvo B19, CMV and HPV DNA using the polymerase chain reaction (PCR) technique. Serological assays were used for the detection of specific IgM and IgG antibodies against Parvo B19 virus and CMV in the maternal sera. RESULTS: Parvo B19 virus genome was detected in two cases of spontaneous abortion, by PCR amplification, while CMV and HPV genomes were not observed. Serological markers were indicative for Parvo B19 virus and CMV infection in ten and four cases, respectively. CONCLUSIONS: PCR is a useful method for investigating the viral contribution to the aetiopathogenesis of spontaneous abortions and for detecting the viral genome in the abortion material. This study of 102 cases of spontaneous abortion does not implicate CMV and HPV in the aetiopathogenesis of spontaneous abortion, although it indicates a possible abortional role for Parvo B19 virus.     

Stepwise analysis of cerebral blood flow SPECT imaging on standard brain atlas in patients with dementia of Alzheimer''s type

In 1994 the first human parvovirus B19 (B19) epidemic to be documented in Denmark was recorded from February 2 to September 30. In total, 10,333 serum samples were tested for specific B19 IgM and IgG antibodies, using IDEIA Parvovirus B19 IgM and IgG kits. The prevalence of B19 IgM positivity was 11% for the whole period and 29% at the peak of the epidemic in week 14, declining from week 39 and onwards to 1-3%. The prevalence of B19 IgG (IgM-negative samples) was 60%, indicating an earlier infection, and the same for men and women. The gender distribution of tested patients was the same at the beginning of the epidemic as at the end of the epidemic and a year after its peak, i.e. 86% of samples were from women and only 14% from men. Age distribution for women was the same for the three periods (median age 34 years). For men the median age was 32 years, 39 years and 31 years, respectively. Only a few samples from children were tested. No change in test pattern was observed during the three periods. Approximately 75% of all samples tested were from women of childbearing age (18-45 years old), suggesting a fear of fetal complications in an actual or future pregnancy, rather than a serological verification of clinical symptoms. From the sparse clinical information that accompanied the serum sample we were not able to demonstrate that women were more likely than men to have a symptomatic B19 infection. With reservations we estimate that 14% of adverse pregnancy outcome is correlated with a B19 infection.     

UDP-glucuronosyltransferase in Gilbert''s syndrome

BACKGROUND: The long-term consequences of parvovirus B19 infection in transfusion recipients are not known, and thus the value of B19 screening of blood donors remains unresolved. Hemophiliacs, at risk for B19 through their chronic exposure to clotting factor concentrates, have frequent, close medical follow-up and thereby constitute an ideal group in which to study the hematologic sequelae of B19 infection. STUDY DESIGN AND METHODS: An enzyme-linked immunosorbent assay was used to detect B19 IgG and IgM and the polymerase chain reaction was used to detect B19 DNA in frozen, stored plasma samples, obtained between 1987 and 1994, from 136 subjects with hemophilia, including 71 who were human immunodeficiency virus (HIV)-positive and 65 who were HIV-negative. Then the results of the tests were compared with clinical hematological data and blood product usage data. RESULTS: B19 seroprevalence in the hemophilic cohort was 81.6 percent (111/136), including 74.6 percent (53/71) of HIV-positive and 89.2 percent (58/65) of HIV-negative hemophiliacs. It was not affected by age, type or severity of hemophilia, HIV status, CD4 number, or yearly blood product usage. Only 1 (0.7%) of the 136 samples was positive for B19 IgM and none was positive in polymerase chain reaction for B19 DNA. After adjusting for HIV status, there were no differences between B19-positive and B19-negative hemophiliacs in hematologic values, CD4 counts, or blood product use. CONCLUSION: Although B19 IgG seroprevalence in this hemophilic cohort is high and indicative of past B19 infection, there is no detectable B19 viral activity or any associated long-term clinical or hematologic sequelae.     

Thrombolytic therapy with tissue plasminogen activator for prevention of vasospasm in experimental subarachnoid hemorrhage: its efficacy and problems

Parvovirus B19 infection has been associated with fetal anaemia, hydrops, and in some cases demise. Most of the reported cases of fetal hydrops were detected in second-trimester fetuses. We report a series of three cases in which human parvovirus infection was associated with hydropic changes at an earlier gestational age. Spontaneous resolution of hydrops occurred in all fetuses. A greater understanding of the natural history of human parvovirus infection is needed prior to deciding on the mode of therapy (conservative management versus in utero fetal therapy).     

Imaging fistula-in-ano

Intrauterine viral infection commonly presents as nonimmune hydrops fetalis or intrauterine growth restriction. Cytomegalovirus (CMV) and parvovirus are commonly recognized causes of fetal infection using serology and cultures. We used the polymerase chain reaction (PCR) to evaluate the frequency of fetal viral infection and the associated clinical course and outcome. Specimens (amniotic fluid, fetal blood, pleural fluid, tissue) from 303 abnormal pregnancies at risk for viral infection and 154 controls were analyzed using primers for CMV, herpes simplex virus, parvovirus B19, adenovirus, enterovirus, Epstein-Barr virus, and respiratory syncytial virus. Viral genome was detected in 144/371 samples (39%) or 124/303 patients (41%), with adenovirus (n = 74 patients; 24%), CMV (n = 30 patients; 10%), and enterovirus (n = 22 patients; 7%) most common. Only 4/154 (2.6%), unaffected control patients' samples were PCR positive. We conclude that diagnosis of fetal viral infection by PCR is common in abnormal pregnancies. Adenovirus and enterovirus may cause fetal infection that have been previously unrecognized.     

Hemolytic reaction due to graft-versus-host (GVH) antibody production after liver transplantation from living donors: report of two cases

Among 27 patients who received minor ABO-incompatible partial liver transplantations and 19 who received major ABO-incompatible partial liver transplantations from living donors, 2 developed hemolytic anemia within 2 weeks after transplantation. These 2 patients had received livers from their living fathers whose blood type was ABO-incompatible. B-to-A transplantation was performed in patient 1 and O-to-B transplantation was performed in patient 2. Anti-A IgM and IgG were detected in the serum of patient 1, and anti-B IgM and IgG were detected in the serum of patient 2. These antibodies were eluted from the red blood cells of the patients. The coexistence of donor-specific DNA in the peripheral blood of the patients proved that they had chimerism, and graft-versus-host antibody production due to passenger B lymphocytes in the donor's liver was subsequently confirmed.     

Late complications of radiotherapy. Role of the time factor

Purpose of the study was to determine the prevalence of toxoplasma infection among the pregnant women and their newborn infants in Chengdu and to identify risk factors of acquiring toxoplasma infection. The Maternal and Child Health Hospital was selected by random cluster sampling method in the study. Each pregnant women admitted to the above hospital consecutively and her surviving newborn at birth were included in this survey. History, physical examination and blood specimens were obtained from 1,211 pairs of mother-newborns. ELISA was used to detect toxoplasma IgG and IgM antibodies. Results revealed that sera prevalence of toxoplasma IgG antibodies and IgM antibodies of pregnant women were 39.14% and 4.21% respectively. Seraprevalence of toxoplasma IgM antibodies of newborn infants was 1.07%. Congenital malformation of newborn infants may be associated with congenital toxoplasma infection (P < 0.05, OR = 6.32).     

Long-term lipid-based total parenteral nutrition activates mononuclear cells and modulates membrane lipid composition in pigs

This study aims to assess the possible strain-dependent variations in detection of Toxoplasma antigens and antibodies. The virulent RH strain or avirulent Beverley strain of T. gondii were injected into mice, intraperitoneally, and their antigens, antibodies and parasites were identified from the blood or tissues; liver, brain and spleen by ELISA, Western blot and PCR. In mice infected with RH strain, circulating antigens and parasitemia were first detected from 2 days after infection, and Toxoplasma DNA were found in the blood, liver, brain and spleen from 3 days after infection. It was impossible to detect specific IgM and IgG antibodies to T. gondii, and any specific band was not found by Western blot. In mice infected with Beverley strain, circulating antigens were detected between day 10 and day 35. The Toxoplasma DNA was found in the blood and liver from day 15 until day 60, and in the brain from day 20. But Toxoplasma DNA in the spleen were mainly detected between day 10 and day 30. The IgM antibodies were first appeared on day 10 post-infection, and were noted obviously increased between day 15 and 25. The IgG antibodies were first detected on day 15, and showed progressively increased titers. The antibody binding bands were specific according to infection period. Sera from mice infected with Beverley strain reacted mainly with the antigen of 27.5-kDa and 32.5-kDa. In conclusion, mice infected with RH strain revealed Toxoplasma antigens strongly, but not antibodies. However, mice infected with Beverley strain revealed both the Toxoplasma antigens and antibodies. The present results showed that immune responses are different between avirulent and virulent T. gondii.     

Response of colony stimulating factor in cancer chemotherapy induced myelosuppression--a case report

BACKGROUND: The aim of the study was to describe the seroprevalence against Parvovirus B19 in a random sample of blood donors in the Hospital Universitario de Salamanca. METHODS: We studied the presence of IgG and IgM antibodies against Parvovirus B19 in 136 sera from asymptomatic blood donors by enzyme immunoassay methods. RESULTS: From 136 samples tested, 88 (64.7%) had positive absorbance values for IgG. Forty eight samples (35.5%) were negative. IgM was negative in all cases. We did not find indeterminate results. DISCUSSION: Parvovirus primoinfection usually happens in the childhood. Thus, we can expect a high percentage of general population to have antibodies against Parvovirus B19. Anti-Parvovirus B19 antibodies prevalence in blood donors was 64.7%. This failure is similar to data reported before (65%). Clinical importance of these viruses in currently related with hemathopoyesis diseases and with the possible role in theratogenesis. The presence of IgG seems to give protection except in some chronic infections recently described.     

The prevalence of antibody to parvovirus B19 in hemophiliacs and in the general population

The prevalence of antibodies to parvovirus B19 (B19) was measured in the sera of 566 hemophiliacs and 524 individuals of the general population by immunofluorescence assays, using antigen expressed by the baculovirus system. In the general population, anti-B19 IgG seroprevalence was found to continuously decline from 64 percent at birth to 0 percent in the age of 9-11 months and thereupon to increase to 61 percent in the age of 12 years. In younger adults and older people, IgG seroprevalence only slowly increased with age, reaching 77 percent in people aged 60 and above. In contrast, in hemophilic children treated exclusively with virally inactivated clotting factor concentrates, neither decrease nor increase of B19 IgG antibody was detectable and the overall seroprevalence was 92 percent. In the group of hemophiliacs older than 12 years and treated before 1984 with non-inactivated clotting factor concentrates, 98 percent showed antibody to B19. Anti-B19 IgM seroprevalence was significantly higher in hemophilic than in non-hemophilic individuals older than 12 years. Since it seems to be unlikely that the high seroprevalence in hemophiliacs is acquired by immunization with inactivated viral antigen, the results suggest that infection with B19 is transmitted by clotting factor concentrates, even if subjected to virucidal methods.     

Arthroscopy of the upper ankle joint. List of indications from the literature--realistic expectations--complications

PROBLEM: Antiphospholipid antibodies (APLs) consist of very heterogenous autoantibodies. It has not been fully explored what kind of specificities are most relevant to recurrent pregnancy loss. Thus, we investigated the effects of specific APLs on recurrent aborters. METHOD: IgG and IgM antibodies against PE (treated with 1% acetic acid) and five negatively-charged phospholipids were measured by ELISA among 334 recurrent aborters without autoimmune disease. The relationships between APL specificities and subsequent pregnancy outcome were prospectively investigated in 38 recurrent aborters with positive APL who did not receive treatment with prednisolone and aspirin. Antibody levels exceeding the 99th percentile of 280 healthy women were considered positive. RESULTS: Positive IgG and/or IgM APLs were detected in 14%, IgG APLs in 12%, and IgG antibodies against PA, PG, PI, PS, CL and PE, respectively, in 9%, 7%, 7%, 7%, 8%, and 8%. In a prospective study of the 38 untreated patients, fetal loss recurred in 82% of the 33 IgG APL-positive patients, but in 40% of the five patients positive for only IgM APLs. The incidence of fetal loss in the next pregnancy of patients with IgG specific APL-positive against PE, PI, PS, or Cl was even higher at 90% and over, and fetal loss recurred in all of 21 patients with two or more IgG APL-positive against PE, PI, PS, or CL. CONCLUSION: These results suggest the possibility that two or more IgG APL-positive value against treated PE, PI, PS, or CL, may be more accurate as a predictive variable than that of only one IgG APL-positive in patients with recurrent pregnancy loss.     

Seroprevalence of B19 parvovirus infection in patients with acute polyarthritis

Over a period of 29 months, from January 1991 to December 1994, all cases of acute polyarthritis seen at the Rheumatology Service in our Institution were studied to determine the seroprevalence of parvovirus B19 (B19) infection. The variables studied included: age and sex of patients, presence of fever and rash, Anti-B19 IgM and IgE serological determinations (ELISA, Mardix Lab.), follow-up time and final diagnosis. The study included 36 patients (22 women and 14 men, mean age 34 +/- 19 years). Thirteen and seven patients had fever and cutaneous rash, respectively. Anti-B19 IgM serology was positive in 4 patients; in 2 of them IgG seroconversion was confirmed. The mean follow-up time was 14 +/- 9 months. Final diagnoses included undifferentiated polyarthritis, rheumatoid arthritis, B19 polyarthritis, systemic lupus erythematosus, and miscellaneous in 19, 7, 4, 2, and 4 patients, respectively. Seroprevalence of B19 infection in acute polyarthritis in our area was 11%, approximately.     

Follow-up in 103 patients with catecholamine-secreting tumours

BACKGROUND: It is necessary to have an easy and quickly test to distinguish "false positive" rubella IgM results and residual antibodies from the antibodies produced in the primary infection, in pregnant women. The avidity of IgG antibodies test seems to differentiate between primary rubella infection and past infections, reinfections or postvaccination, showing its utility in the diagnosis of primary infection in other infectious diseases. METHOD: For 30 months, 178 sera from 157 patients with clinical and/or epidemiological rubella suspicion or with a positive rubella IgM result as result of an accidental serological finding, were remitted to our laboratory for a serological follow up. We distinguished 3 patient groups: outbreak group, 112; pregnant women, 36, and newborn 11. Rubella IgM antibodies by indirect EIA previous the rheumatoid factor absorption; IgG antibodies of low avidity by indirect EIA previous treatment of serum with 6 M urea, were detected in the sera. It considered a positive result, a rubella avidity index (AI) < 50%. RESULTS: In the epidemic outbreak group, 90.2% of the patients were not vaccinated. 80% of cases occurred in young men between 14 an 20 years old. From 109 patients (97.3%) with rubella IgG antibodies, 92 (84.4%) showed AI-IgG lower than 50%. In this group, the mean rate of AI-IgG rubella was 29.0%. In the pregnant women group, except for two of them, rubella IgM antibodies were an accidental finding in a serological pregnancy screening. Thirty patients (83.8%) showed AI-IgG rubella > 50%. The two pregnant women who had evidence of clinical and epidemiological rubella showed AI-IgG rubella of 37.4% and 20.9%. Another four pregnant women showed AI-IgG rubella close to cut-off (44.7-49.0%). The mean AI-IgG rubella in this group was 71.8%. The mean AI-IgG Rubella between the epidemic outbreak group and the pregnant women group, 29.0 and 71.8% respectively, was statistical significance (p < 0.001). CONCLUSIONS: The avidity IgG test is simple and quickly, and it allow to exclude most of positive results because of residual IgM antibodies and false reactive.     

Comparison of cardiac findings at necropsy in octogenarians, nonagenarians, and centenarians

The Toxoplasma gondii rhoptry protein Rop2 was expressed in Escherichia coli as a fusion protein containing 44 kDa of the 55-kDa mature Rop2, supplied with six histidyl residues at the N-terminal end (Rop2196-561). Humoral response during Toxoplasma infection of humans was analyzed by immunoglobulin G (IgG), IgA, and IgM enzyme-linked immunosorbent assay with Rop2196-561 as the antigen substrate. The analyzed sera were divided according to T. gondii-specific serological tests (IgG, IgA, or IgM indirect immunofluorescence and IgA or IgM immunosorbent agglutination assay) as group A (IgG+ IgA- IgM-; n = 35), group B (IgG+ IgA+ IgM+; n = 21), group C (IgG+ IgA+ IgM-; n = 5), and group D (IgG+ IgA- IgM+; n = 16). Twenty-six T. gondii-seronegative sera from individuals with other infections were also included (group E). Anti-Rop2 IgG antibodies were detected in 82.8% of group A sera and in 97.6% of the sera with acute-phase marker immunoglobulins (groups B, C, and D). The percentage of IgA antibody reactivity against Rop2196-561 was 17.1% in group A, 50% in group D, and 80.8% in groups B and C. The percentage of IgM antibody reactivity was 0% in groups A and C and 62% in groups B and D. Sera from group E failed to show IgA, IgM, or IgG antibody reactivity. Since T. gondii Rop2 elicits a strong humoral response from an early stage of infection, it is suggested that recombinant Rop2196-561 would be suitable for use in diagnostic systems, in combination with other T. gondii antigens, to detect specific IgG, IgA, and IgM antibodies.     

Detection of isotype-specific autoantibodies to calpastatin in sera from patients with rheumatic diseases using heat-treated HeLa cell extract as an antigen source for immunoblotting

To detect immunoglobulin isotype-specific autoantibodies to native human calpastatin in patients with rheumatic diseases, we performed immunoblot analysis using the heated HeLa cell extracts to enrich heat-resistant calpastatin. The calpastatin molecule that was apparently migrated to 110 kD by SDS-PAGE was confirmed to react with monoclonal anti-human calpastatin antibody in immunoblotting. IgG antibodies to calpastatin were detected in 22 of 48 sera (46%) from patients with RA, whereas only 20% (5/25), 11% (2/19) and 13% (2/15) of sera from SLE, SSc and PM/DM had IgG anti-calpastatin antibodies, respectively. IgM antibodies were also found in 40% (19/48) of RA and 12% (3/25) of SLE patients but not detected in sera from patients with other rheumatic diseases. IgA antibodies were found in only one RA and one SLE serum. In RA, 7 of 48 sera (15%) had IgM antibodies alone, but all SLE sera with IgM antibodies had IgG antibodies. Thus, anti-calpastatin autoantibodies were detected by using the native human calpastatin. Although these autoantibodies were found in patients with various rheumatic diseases, they were present in RA patients at the highest frequency. In particular, the presence of IgM antibodies appeared to be more specific in RA patients.     

Mutations that extend the specificity of the endonuclease activity of lambda terminase

Fetal DNA has been detected in maternal plasma during pregnancy. We investigated the clearance of circulating fetal DNA after delivery, using quantitative PCR analysis of the sex-determining region Y gene as a marker for male fetuses. We analyzed plasma samples from 12 women 1-42 d after delivery of male babies and found that circulating fetal DNA was undetectable by day 1 after delivery. To obtain a higher time-resolution picture of fetal DNA clearance, we performed serial sampling of eight women, which indicated that most women (seven) had undetectable levels of circulating fetal DNA by 2 h postpartum. The mean half-life for circulating fetal DNA was 16.3 min (range 4-30 min). Plasma nucleases were found to account for only part of the clearance of plasma fetal DNA. The rapid turnover of circulating DNA suggests that plasma DNA analysis may be less susceptible to false-positive results, which result from carryover from previous pregnancies, than is the detection of fetal cells in maternal blood; also, rapid turnover may be useful for the monitoring of feto-maternal events with rapid dynamics. These results also may have implications for the study of other types of nonhost DNA in plasma, such as circulating tumor-derived and graft-derived DNA in oncology and transplant patients, respectively.     

T-Cell-independent immunoglobulin G responses in vivo are elicited by live-virus infection but not by immunization with viral proteins or virus-like particles

Immunoglobulin G (IgG) responses to viruses are generally assumed to be T-cell dependent (TD). Recently, however, polyomavirus (PyV) infection of T-cell-deficient (T-cell receptor beta chain [TCR-beta] -/- or TCR-betaxdelta -/-) mice was shown to elicit a protective, T-cell-independent (TI) antiviral IgM and IgG response. A repetitive, highly organized antigenic structure common to many TI antigens is postulated to be important in the induction of antibody responses in the absence of helper T cells. To test whether the repetitive structure of viral antigens is essential and/or sufficient for the induction of TI antibodies, we compared the abilities of three forms of PyV antigens to induce IgM and IgG responses in T-cell-deficient mice: soluble capsid antigens (VP1), repetitive virus-like particles (VLPs), and live PyV. Immunization with each of the viral antigens resulted in IgM production. VLPs and PyV elicited 10-fold-higher IgM titers than VP1, indicating that the highly organized, repetitive antigens are more efficient in IgM induction. Antigen-specific TI IgG responses, however, were detected only in mice infected with live PyV, not in VP1- or VLP-immunized mice. These results suggest that the highly organized, repetitive nature of the viral antigens is insufficient to account for their ability to elicit TI IgG response and that signals generated by live-virus infection may be essential for the switch to IgG production in the absence of T cells. Germinal centers were not observed in T-cell-deficient PyV-infected mice, indicating that the germinal center pathway of B-cell differentiation is TD even in the context of a virus infection.