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Biomedical subjects

N Tachibana

Publications and source records attributed to N Tachibana.

At least 19 recordsLinked to original sources

High HTLV-I proviral DNA level associated with abnormal lymphocytes in peripheral blood from asymptomatic carriers.

The level of proviral DNA in peripheral blood mononuclear cells from a representative group of asymptomatic HTLV-I carriers in Miyazaki district, an HTLV-I endemic area in Japan, was determined by a single-cycle polymerase chain reaction method (PCR). Of 217 subjects, 26% had a high level of proviral DNA, 43% a medium level, 18% a low level, and 13% an undetectable level. In the high-DNA group, 60% had at least 0.6% abnormal lymphocytes on peripheral blood smears, significantly higher than in those with low DNA levels (19%). This association was present for men of all ages and for women under 55. Men were more than twice as likely to have abnormal lymphocytes as well as high levels of proviral DNA. These differences may reflect different host responses to the virus by sex or by the time or route of infection. This study supports the utility of PCR for molecular screening in epidemiologic studies of the natural history of HTLV-I, and may lead to the identification of those carriers who are at greatest risk of developing HTLV-I-induced malignancy.

Age Factors

Case-control study of factors associated with human T-cell leukemia virus type I infection in southern Miyazaki, Japan.

BACKGROUND: An unusual age- and sex-specific distribution and a remarkably restricted geographic seroprevalence characterize human T-cell leukemia virus type I (HTLV-I) infection. Although the transmission routes of HTLV-I are known, these seroepidemiologic features cannot be fully explained. PURPOSE: This study was designed to identify potential characteristics associated with HTLV-I infection in a highly endemic Japanese community. METHODS: We evaluated occupational, residential, dietary, and medical histories in a case-control study conducted in two neighboring villages in southeastern Miyazaki Prefecture. One hundred forty-four case subjects and 276 control subjects, frequency matched by age, sex, and village, were interviewed. Village-specific profiles of demographic determinants of HTLV-I seroprevalence were generated using multiple logistic regression. RESULTS: Although a different pattern of factors was found for each village, occupations of the subjects and their fathers were associated with HTLV-I infection in both communities--farming in village A and fishing and farming in village B. For village A, there was more than a twofold association both with residence in the township for 55 years or more and with living in a particular area within the village. In addition, case subjects were more likely to have a mother who was deceased (odds ratio = 1.7; 95% confidence interval = 0.96-2.9). CONCLUSIONS: HTLV-I infection is characterized by a high degree of microepidemicity in this population, with seroprevalence related to both sociologic and geographic determinants. Moreover, as carriers' mothers themselves have a higher probability of being HTLV-I positive, an increased mortality among those infected with the virus is suggested.

Adult

Sensitivity of polymerase chain reaction assay for Rickettsia tsutsugamushi in patients' blood samples.

We developed a nested polymerase chain reaction (PCR) method to detect Rickettsia tsutsugamushi (R. tsutsugamushi) DNA and determined its sensitivity. Primers were selected from the DNA sequence of the 58-kDa group-specific antigen gene of the Karp strain. The target sequence of rickettsial DNA was detectable as the band corresponding to 88 bp in 1.0 microgram of the DNA extracted from BS-C-1 cells infected with R. tsutsugamushi. Rickettsia-specific bands were observed not only for the homologous Karp strain, but also for four heterologous strains: two other reference strains (Gilliam and Kato) and two prototype strains prevalent in Miyazaki district (Irie and Hirano). The minimum copy number detectable by this method was estimated to be five rickettsiae. All of nine peripheral blood mononuclear cell samples from patients with tsutsugamushi disease who were seen 2-11 days after disease onset tested positive for rickettsial DNA. The PCR assay method presented here could be a specific diagnostic tool for tsutsugamushi disease, especially in its early acute stage.

Adult

Successful graft of HTLV-I-transformed human T-cells (MT-2) in severe combined immunodeficiency mice treated with anti-asialo GM-1 antibody.

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 x 10(7) 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.

Animals

Determinants of HTLV-1 seroprevalence in Miyazaki Prefecture, Japan: a cross-sectional study.

To evaluate determinants of the prevalence of human T-cell leukemia virus type I (HTLV-I) antibody positivity in an endemic region, Miyazaki Prefecture, Japan, demographic and serologic data were collected on 7,055 individuals consecutively seen at Miyazaki City Health Promotion Center between September 1983 and December 1984. The overall HTLV-I seroprevalence was 8.5%; age and gender distributions of HTLV-1 antibody positivity were consistent with previous findings for endemic populations. The prefecture could be divided into two geographic areas based on seroprevalence: high prevalence (12.1%) in the southwest and medium prevalence (6.6%) for the rest of the prefecture. Current occupation in fishing, forestry, or livestock raising significantly correlated with HTLV-1 seropositivity [relative risk (RR) = 3.0, 2.5, 2.0, respectively]; farming also was associated but only in the medium prevalence region (RR = 1.3; p = 0.06). For a subset of 157 HTLV-I-positives and 175 negative controls screened for antibodies to the toxoplasmosis organisms, toxoplasma exposure was not significantly associated with HTLV-I infection. In this endemic Japanese population, both geographic and sociologic factors characterized the distribution of HTLV-I seroprevalence, reflecting transmission patterns and historical duration of the infection.

Adolescent

Unusual pattern of antibodies to human T-cell leukemia virus type-I in family members of adult T-cell leukemia patients.

Detection methods for the human T-cell leukemia virus type-I (HTLV-I) for blood screening and diagnosis generally rely on antibody tests that use the structural proteins of HTLV-I as antigen. We have found an unusual pattern of antibody reactivity among people who are at high risk of HTLV infection due to being a family member of an adult T-cell leukemia (ATL) patient: a specific antibody reaction exclusively directed to the HTLV regulatory protein tax, and not to the HTLV-I structural proteins. Sera from 7 of 82 (8.5%) structural antibody-undetectable family members of ATL patients had the anti-tax reactivity. Two seroconverters were observed. One seroconverter a healthy resident of Miyazaki, tested negative for structural antibody, but positive for tax antibody. Two years later she tested positive for both. The other seroconverter, an Israeli hemophiliac, tested negative for both antibodies, but converted to tax antibody-positive/structural antibody-negative. The HTLV-I tax-only antibody profile was also observed in sera sets from two other populations at risk for HTLV infection, human immunodeficiency virus-1-infected patients at the Bronx-Lebanon Hospital in New York and Israeli hemophiliacs. DNA samples from lymphocytes of four individuals with antibody reactivity only to HTLV-I tax were tested in polymerase chain reaction experiments; no HTLV-I or -II DNA was detected.

Animals

Polysomnographic characteristics of healthy elderly subjects with somnambulism-like behaviors.

We compared the sleep characteristics of seven healthy elderly people complaining of nocturnal somnambulism-like behaviors with those of 14 age-matched healthy elderly people who had never shown such behavior. Polysomnographic data revealed the appearance of "Stage 1-REM with tonic electromyographic (EMG) activity" sometimes accompanied by abnormal behavior in the first group, but the sleep architecture and parameters showed no significant difference between the two groups except for higher REM density in the first group. "Stage 1-REM with tonic EMG," observed in the first group was considered equivalent to REM sleep without muscle atonia. It is suggested that both reduced activity of tonic phenomena (muscle atonia) and increased activity of phasic phenomena (higher REM density) of REM sleep are essential for the induction of somnambulism-like behaviors during sleep in healthy elderly subjects.

Aged

Sexual transmission of human T-cell leukemia virus type I associated with the presence of anti-Tax antibody.

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 differences 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.

Agglutination Tests

Ultrastructural evidence for the origin of mast cells in normal human bone marrow.

Whether the origin of the progenitor of mast cells occurs in the basophil/mast cell system or the myeloid cell system of neutrophils and monocytes/macrophages remains controversial. Lactoferrin or lysozyme is known to be present in the myeloid cell system. By electron microscopy, antibodies against lactoferrin and lysozyme were observed to stain the granules of normal bone marrow mast cells. This supports the proposal that the precursor cell of bone marrow mast cells is nearer to the myeloid cell system than the basophil/mast cell system.

Adult

High incidence of antibodies to HTLV-I tax in blood relatives of adult T cell leukemia patients.

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-I and ATL, members of ATL families were examined for antibodies to the tax protein and compared with matched HTLV-I-positive blood donors. To investigate 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-I antibody-positive control blood donors (P less than .05). The difference between direct offspring of ATL patients and matched HTLV-I blood donors was even greater (84.2% [16/91] vs. 44.2% [42/95]; P less than .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.

Adolescent

Polymerase chain reaction analysis of defective human T-cell leukemia virus type I proviral genomes in leukemic cells of patients with adult T-cell leukemia.

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia, and the clonally derived leukemic cells all contain proviral genomes. Polymerase chain reaction with a variety of primers which span the HTLV-I genome was used to determine that a significant fraction of patients (at least 32%) carry deleted viral genomes in their leukemic cells. The pX region of the HTLV-I genome encoding the regulatory genes tax and rex was preferentially retained. The fact that the tax coding region was retained provides supporting evidence that the tax protein contributes to leukemogenesis in vivo. The reasonably high fraction of patients with adult T-cell leukemia carrying deleted genomes in their tumor cells suggests that the deletions have a role in leukemogenesis.

Adult

Antibody profile of early HTLV-I infection.

To define the antibody profile of early seroconversion in infection with human T-cell lymphotropic virus type I (HTLV-I), consecutive serum samples from 10 subjects presumed to have seroconverted on the basis of the particle agglutination test were studied by three enzyme immunoassays and two confirmatory tests (radioimmunoprecipitation and western blot). 3 samples positive and 1 sample indeterminate in the confirmatory tests were reactive in one enzyme immunoassay, which used recombinant envelope antigen, but not in the other two enzyme immunoassays. 2 of 38 particle-agglutination-negative samples had a prozone effect. The confirmatory tests identified 8 seroconverters (7 women, 1 man); their serum samples were used to study the antibody reactivity by western blot assays to HTLV-I specific antigens (three recombinant proteins spanning the N-terminal, middle, and C-terminal env glycoprotein gp46; a recombinant transmembrane protein gp21; a recombinant tax protein; and three gag proteins [p28, p24, and p19]). All 8 seroconverters had antibody reactivities to the C-terminal region (aminoacid residues 229-308) of gp46 and to gag p19 and p24 when their seroconversion was detected.

Adult

[Seroepidemiological analysis of the age specific prevalence of anti HTLV-I in Miyazaki Prefecture].

Antibody for HTLV-I in sera from 11,224 residents in Miyazaki Prefecture, Japan, was determined by indirect immunofluorescent antibody method to compare age- and sex-specific antibody prevalence among three geographically divided areas of the prefecture. There was a significant difference in the positive rate of older age groups among three areas, 9.0% for the northern part, 14.5% for the southern part and 8.4% for Miyazaki City, in spite of little variation in younger age groups. A marked rise of positive rate in the southern part at the age of 40th was observed, which suggests that changes of some conditions for mother-to-child transmission happened in the time of their birth. Six seroconversions were observed by the follow-up study for five years of the 971 residents. They were between 28 and 38 years of age, four men and two women. This may provide another reason for the increase in antibody positive rate by age in the adult. However, it could not be investigated if the seroconversion was caused by a horizontal transmission from their spouse. The possibility of the long latency of the virus in man as in the experimental animal may also have to be considered.

Adolescent