Explore the vast range of titles available.

The progression from chronic hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) has been reported. We evaluated whether co‐infection with the human T‐lymphotropic virus type I (HTLV‐I) might be associated with this transition in a cross‐sectional analysis of 127 patients with HCV‐chronic hepatitis (mean age=51.7) and 43 patients with HCV‐associated HCC (mean age=62.4); the seroprevalence of anti‐HTLV‐I was 9.5% and 30.2%, respectively. For subjects 50 years or older, the seroprevalence of anti‐HTLV‐I in HCC patients was 13/41 (31.7%) which was significantly higher than that in chronic hepatitis patients (6/82, 7.3%) (P=0.001). The relative risk (RR) of association was 12.8 (P=0.0004) among the males, however, no association was evident among the females, RR=1.3 (P=0.80). The increased prevalence of HTLV‐I positivity among the HCC cases could not be attributed to a higher rate of prior transfusion. These data suggest that co‐infection with HTLV‐I may contribute to the development of HCC among patients with HCV‐induced chronic liver diseases in a highly HTLV‐I‐endemic area.

Sexual transmission of human T cell lymphotropic virus type 1 (HTLV-1) is considered to be an important route of infection in adults. However, no direct evidence has been reported that supports this observation. To address this issue, sequence variations of the gp46 (envelope)-coding region of HTLV-1 were determined in 13 patients infected with HTLV-1 who experienced seroconversion and in their spouses. Twenty-two nucleotide changes that were different from the reference sequence of λATK-1 were identified. However, the gp46 sequences found were identical within each married couple. HTLV-1 proviral DNA loads measured in 11 of these couples varied from 10 to 3430 copies per 105 PBMC, and the proviral DNA loads of spouses often differed. This study provides the first genetic confirmation of the transmission of HTLV-1 from a carrier spouse to his/her partner. The findings also suggest that host-related factors play a more important role than do virus-specific factors in determining HTLV-1 proviral DNA load.

To identify factors that may modify the heterosexual transmission of human T cell leukemia/lymphoma virus type 1 (HTLV-I), 534 married couples enrolled in the Miyazaki Cohort Study between November 1984 and April 1989 were studied: 95 husband HTLV-I-seropositive (H+)/wife seropositive (W+), 33 H+/W−, 64 H−/W+, and 342 H−/W−. After 5 years of follow-up, seven seroconversions occurred and clustered significantly among serodiscordant pairs (relative risk [RR] = 41.2); the rate oftransmission was 3.9 times higher if the carrier spouse was male (P = .19). Among H+/W− couples, husband's age ⩾60 years strongly predicted seroconversion in the WIves (RR = 11.5). All 4 carrier husbands whosewivesseroconverted had HTLV-I titers ⩾1:1024 (P = .04) and were anti-tax antibody positive (P = .06). In cross-sectional analysis, total parity also was independently associated with wife's serostatus but only length of marriage with husband's. Overall, sexual transmission of HTLV-I was primarily from older infected husbands to their wives, with husbands' viral status being an important factor.

Twenty-three human T lymphotropic virus type I (HTLV-I) seroconverters were identified among 1120 HTLV-I–seronegative adults followed up for 11 years in an area of Japan endemic for HTLV-I. The geometric mean titer of anti–HTLV-I was 1:453 in the first year after seroconversion; the titer of each subject did not change significantly during 2–10 years of follow-up. HTLV-I proviral DNA load was quantified in 15 seroconverters, and a broad range of levels was observed—from <10 to >1000 copies/105 peripheral blood mononuclear cells. However, there was no obvious change in HTLV-I proviral DNA load over several years within individual subjects. Therefore, both proviral DNA load and humoral response in adult HTLV-I seroconverters were shown to stabilize within a few years after initial infection. In addition, 1 subject tested positive for HTLV-I proviral DNA before antibody seroconversion, which suggests the existence of a window period in community-acquired infection

Morbidity associated with human T lymphotropic virus type I (HTLV-I) infection was investigated in a Japanese population within an area in which HTLV-I infection is endemic. Of 1824 subjects enrolled in the Miyazaki Cohort Study between November 1984 and May 1991, 500 (27.4%) were seropositive for HTLV-I antibodies. As expected from previous studies, HTLV-I positivity appeared to be associated with baseline history of anemia (adjusted odds ratio [OR] = 1.3; 95% confidence interval [CI] = 0.99–1.7) and kidney disease (OR = 1.6; 95% CI = 0.91–2.9); a positive association also was noted for asthma in men (OR = 3.4; 95% CI = 1.2–9.8). Unanticipated findings included a relationship between HTLV-I infection and cardiac disease history (OR = 1.4; 95% CI = 0.94–2.2); HTLV-I carriers also were more likely to have an abnormal electrocardiogram at baseline (OR = 1.5; 95% CI = 1.2–1.9). Furthermore, an apparent protective effect for ulcers (OR = 0.62; 95% CI = 0.40–0.95) and diabetes (OR = 0.49; 95% CI = 0.22–1.1) was observed. HTLV-I infection may modify the risk of specific disease outcomes by altering host immune function.

To develop an experimental model of adult T‐cell leukemia/lymphoma in small animals, severe combined immunodeficiency (SCID) mice treated with anti‐asialo GM‐1 antibody were inoculated with MT‐2 cells, a cell line transformed by the human T‐cell leukemia virus (HTLV–I). Three mice injected with 4 × 107 cells subcutaneously or intramuscularly developed tumors at or near inoculation sites. Immunofluorescent antibody (IFA) staining for HTLV–I structural protein, p19, revealed the specific antigen in the cytoplasm of most cells from tumors and the DNA signals of HTLV–I proviral DNA were also positive in cellular DNA by polymerase chain reaction assay with HTLV–I tax gene primers, SK43/SK44. The MT–2 cells did not invade in mouse organs.

The tax gene product (Tax protein) of human T-cell leukemia virus type I (HTLV-I) is a specific transcriptional activator of the viral long terminal repeat sequence and is essential for the replication cycle of the virus. To elucidate the relationship between the presence of anti-Tax antibody and the transmission of the viral infection, annual consecutive serum samples from married couples serologically discordant or concordant for HTLV-I were examined. These included 5 individuals whose spouses seroconverted during this 5-year follow-up study period. The samples were tested by a Western blot assay using a recombinant Tax protein as the antigen. The results showed that 24 of 32 (75%) men in the concordant couples (both husband and wife were HTLV-I carriers) had anti-Tax antibody, while only 5 of 18 (27.8%) men in the discordant couples (husband was carrier and wife was seronegative to HTLV-I) were positive for anti-Tax antibody (P = 0.0012). Furthermore, all spouses of the 5 seroconverters (4 women and 1 man) had anti-Tax antibody, while only 23 of 46 (50%) age-matched randomly selected HTLV-I carriers from the discordant-couple group had anti-Tax antibody. When the data were analyzed by gender, all husbands of the female seroconverters had anti-Tax antibodies, which was significantly higher than the prevalence of anti-Tax antibodies in men who did not transmit the virus to their spouses during the follow-up period (P = 0.017). In addition, antibody reactivity to other HTLV-I antigens (including Env gp46, transmembrane protein gp21, and Gag p19 and p24) were examined. The results indicated no significant difference between the prevalence of antibody reactivity to any of the antigens in the spouses of the seroconverters and the reference group. We conclude that the presence of anti-Tax antibody in men may indicate a high risk of viral transmission to their wives via heterosexual routes.

Adult T cell leukemia (ATL) is caused by the human T cell leukemia virus type I (HTLV-I). Although the mechanisms of the leukemogenic process are unknown, the tax gene may have a role in this process. Because clustering occurs with HTLV-Iand ATL, members of ATLfamilies were examined for antibodies to the tax protein and compared with matched HTLV-I-positive blood donors. Toinvestigate the antibody response to this protein, a plasmid, pBHX-4, was constructed to express a recombinant tax protein (r-tax). For ATL patients and their HTLV-I antibody- positive blood relatives, the rate of seroreactivity with the r-tax protein was 67.3% (35/52), compared with 51.6%(97/188)for HTLV-Iantibody-positive control blood donors (P < .05). The difference between direct offspring of ATL patients and matched HTLV-Iblood donors was even greater (84.2% [16/19] vs. 44.2%[42/95]; P <.005). Thus, tax antibody positivity in direct offspring of ATL patients may reflect differences in time or route of HTLV-I infection. Alternatively, it might reflect genetic differences in host susceptibility or virus strain.

The discriminative power of CURB-65 for mortality in community-acquired pneumonia (CAP) is suspected to decrease with age. However, a useful prognostic prediction model for older patients with CAP has not been established. This study aimed to develop and validate a new scoring system for predicting mortality in older patients with CAP. We recruited two prospective cohorts including patients aged ≥ 65 years and hospitalized with CAP. In the derivation (n = 872) and validation cohorts (n = 1,158), the average age was 82.0 and 80.6 years and the 30-day mortality rate was 7.6% (n = 66) and 7.4% (n = 86), respectively. A new scoring system was developed based on factors associated with 30-day mortality, identified by multivariate analysis in the derivation cohort. This scoring system named CHUBA comprised five variables: confusion, hypoxemia (SpO 2  ≤ 90% or PaO 2  ≤ 60 mmHg), blood urea nitrogen ≥ 30 mg/dL, bedridden state, and serum albumin level ≤ 3.0 g/dL. With regard to 30-day mortality, the area under the receiver operating characteristic curve for CURB-65 and CHUBA was 0.672 (95% confidence interval, 0.607–0.732) and 0.809 (95% confidence interval, 0.751–0.856; P  < 0.001), respectively. The effectiveness of CHUBA was statistically confirmed in the external validation cohort. In conclusion, a simpler novel scoring system, CHUBA, was established for predicting mortality in older patients with CAP.