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Biomedical subjects

S Sonoda

Publications and source records attributed to S Sonoda.

At least 19 recordsLinked to original sources

A new genotype of TT virus (TTV) infection among Colombian native Indians.

Serum TTV DNA was assayed in 140 native Indians and 40 members of the general population in Colombia to determine the prevalence of TT virus (TTV) infection among Colombian native Indians. Of the 140 native Indians, 23 (16.4%) were positive for TTV DNA, compared to 4 (10.0%) of 40 from the general population (P = not significant). The prevalence of TTV DNA among native Indians was much higher than that of HBsAg and anti-HCV. Comparison of subjects with and without TTV DNA revealed no significant differences in all characteristics between the two groups. A phylogenetic tree, using the open reading frame 1 sequence (222 bp), indicated that the virus could be classified into four different genotypes, including three previously reported ones. The results show that TTV infection is common in Colombian native Indians without liver disease and also indicate the existence of a novel genotype of TTV.

Adolescent

Clonal expansion within CD4+ and CD8+ T cell subsets in human T lymphotropic virus type I-infected individuals.

To investigate the diversity of the T cell repertoire involved in human T lymphotropic virus type I (HTLV-I) infections, peripheral blood T cell subsets were analyzed by using a PCR-based assay that permits determination of complementarity-determining region 3 (CDR3) length variation in TCR Vbeta transcripts. In two of four asymptomatic HTLV-I carriers and in four of five patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), mono- or oligoclonal expansions were detected in the CD4+ T cell subset. In one patient with adult T cell leukemia, a specific clone bearing Vbeta7 was detected in the CD4+ T cell subset. In contrast, clonal expansion was not observed in the CD4 T cell subsets of three individuals with asymptomatic HTLV-II infection or in our previous studies of a large number of uninfected individuals. Oligoclonal expansions in the CD8+ T cell subset were detected in all subjects, including the patient with adult T cell leukemia. No differences in the number of expanded clones were noted between asymptomatic carriers and in patients with HAM/TSP and there was no obvious restriction in the TCR V region usage. Direct sequencing revealed no significant bias in the CDR3 motifs utilized by the predominant clones. This report is the first direct demonstration of clonal expansions within fractionated T cell subsets (CD4+ and CD8+) in HTLV-I infections and suggests that 1) clonal expansion of CD4+ T lymphocytes likely occurs as a direct result of infection and 2) polyclonal CD8+ T cell expansion occurs frequently and independently of disease association.

Adult

Human leukocyte antigen class II alleles associated with human T-cell lymphotropic virus type I infection and adult T-cell leukemia/lymphoma in a Black population.

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) is linked to adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy (HAM; also known as tropical spastic paraparesis [TSP]), a chronic neurodegenerative disorder. Worldwide, several million HTLV-I carriers are at risk for disease, with an estimated lifetime cumulative risk of 1%-5%. However, the determinants of disease progression are relatively unknown. We studied human leukocyte antigens (HLA class II) that have been implicated in the pathogenesis of HTLV-I-related diseases. METHODS: We analyzed HLA class II alleles among asymptomatic HTLV-I carriers (n = 45), patients with ATL (n = 49) or HAM/TSP (n = 54), and HTLV-I seronegative control subjects (n = 51). All participants were of African descent and were enrolled in epidemiologic studies conducted at the University of the West Indies, Kingston, Jamaica. We used standard microlymphocytotoxicity assays for HLA antigen serotyping and polymerase chain reaction-based methods to examine HLA class II DRB1 and DQB1 alleles. RESULTS: Two antigens determined by serotyping, DR15 and DQ1, occurred at significantly increased frequency among HTLV-I carriers compared with seronegative control subjects (42% versus 22% for DR15 [odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.0-7.2] and 78% versus 53% for DQ1 [OR = 3.1; 95% CI = 1.2-8.5]). Asymptomatic carriers were shown to have an HLA class II allele distribution similar to that of patients with ATL, and the frequencies of the alleles DRB1*1501, DRB1*1101, and DQB1*0602 were significantly greater in patients with ATL and asymptomatic carriers than in patients with HAM/TSP. In addition, haplotypes DRB1*1101-DQB1*0301 and DRB1*1501-DQB1*0602 were significantly increased among patients with ATL compared with patients with HAM/TSP. CONCLUSIONS: These data suggest that host genetic background is an important factor in determining whether HTLV-I carriers develop either ATL or HAM/TSP.

Alleles

An expression of anaplastic large cell lymphoma-associated antigens on HTLV-I-infected CD4+ T cells.

We investigated tumor-associated antigens induced by infection with human T-lymphotropic virus type I(HTLV-I). Anaplastic large cell lymphoma (APLL) antigens were found to be expressed on interleukin 2 (IL-2)-dependent, HTLV-I-infected CD4+ T-cell lines established from patients with adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. However, APLL antigens were not detected on unstimulated lymphocytes, mitogen-activated T lymphocytes, or Epstein-Barr virus-infected B cells. Furthermore, APLL antigens were not found on IL-2-independent HTLV-I-transformed cells such as MT-I or MT-2. When naive CD4+ T cells were infected with HTLV-I in vitro in the presence of IL-2, the APLL antigens were detected on them 4 weeks after infection. The expression level increased in a time-dependent fashion. These results indicate that HTLV-I infection induces a unique category of tumor-associated antigens on CD4+ T cells.

CD4-Positive T-Lymphocytes

Nucleotide sequence analysis of the 3' terminal region of a wasabi strain of crucifer tobamovirus genomic RNA: subgrouping of crucifer tobamoviruses.

The 3' terminal 2378 nucleotides of a wasabi strain of crucifer tobamovirus (CTMV-W) infectious to crucifer plants was determined. This includes the 3' non-coding region of 235 nucleotides, coat protein (CP) gene (468 nucleotides), movement protein (MP) gene (798 nucleotides) and C-terminal partial readthrough portion of 180 K protein gene (940 nucleotides). Comparison of the sequence with homologous regions of thirteen other tobamovirus genomes showed that it had much higher identity to those of four other crucifer tobamoviruses, 85.2% to cr-TMV and turnip vein-clearing virus (TVCV), 87.4% to oilseed rape mosaic virus (ORMV) and 87.1% to TMV-Cg, than to those of other tobamoviruses. Thus CTMV-W was most similar to ORMV and TMV-Cg in sequence, but only marginally so, whereas the location and size of its MP gene was the same as cr-TMV amd TVCV. These results, together with other analyses, show that CTMV-W is a new crucifer tobamovirus, that the five crucifer tobamoviruses can be classified into two subgroups based on MP gene organization, and that the rate of sequence change is not the same in all lineages.

Amino Acid Sequence

Safety and optimal dose of intracoronary adenosine 5'-triphosphate for the measurement of coronary flow reserve.

BACKGROUND: Adenosine 5'-triphosphate (ATP) has been demonstrated to have similar vasodilator potency and fewer hemodynamic or electrocardiographic derangements compared with papaverine in the measurement of coronary flow reserve. However, there is little data about its optimal dose and the effect on myocardial lactate metabolism. METHODS: Under continuous monitoring of the left anterior descending coronary flow velocity with a Doppler guide wire, we investigated the changes of hemodynamics, electrocardiogram, and myocardial lactate metabolism before and after the administration of 50 microg ATP and 10 mg papaverine into the left coronary artery in 18 patients with normal coronary arteries. To determine the optimal dose of ATP for the coronary flow reserve in the left coronary artery, we measured coronary flow velocity with five incremental doses of intracoronary ATP (0.5, 5, 15, 30, and 50 microg) and 10 mg of papaverine in another seven patients. RESULTS: In contrast to papaverine, ATP did not produce any significant changes in hemodynamics or the electrocardiogram. The increase in the coronary flow velocity of the two agents was similar. Although all patients showed lactate production after the administration of papaverine, only three patients showed lactate production after ATP (p < 0.001). The coronary flow reserve derived from > or = 215 microg of ATP was similar to that derived from papaverine. There was a significant correlation between the coronary flow reserve obtained with > or = 5 microg of ATP and that obtained with papaverine. CONCLUSIONS: These results suggest that maximal coronary vasodilation in the left coronary artery can be safely obtained with doses > or = 15 microg of intracoronary ATP in patients with normal coronary arteries.

Adenosine Triphosphate

Search for human T-lymphotropic virus type I carriers among northeastern Chinese.

Human T-lymphotropic virus type I (HTLV-I) is thought to be the causative agent of adult T-cell leukemia/ lymphoma (ATL). This virus infection is endemic in southwestern Japan, parts of Africa and the Caribbean Islands. We examined sera of 1645 subjects of Liaoning province, northeastern China to detect HTLV-I carriers in an effort to reveal the migratory route taken by the early Japanese (Jomon people). As a result, all sera were found to be negative as tested by particle-agglutination (PA), immunofluorescence (IF), enzyme-linked immunoabsorbent (ELISA) and Western blotting methods. This suggests that the Jomon people, who are thought to have brought HTLV-I to the Japan archipelago tens of thousands of years ago, did not come from northeast China.

Adult

An epidemiologic study of herpes simplex virus type 1 and 2 infection in Japan based on type-specific serological assays.

A seroepidemiologic study of herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) was performed on Japanese adults. Serum samples collected between 1985-9 from a total of 536 healthy adults, female prostitutes, males with sexually transmitted diseases (STD), homosexual men, and pregnant women were studied by immunodot assays using HSV type-specific antigens, glycoproteins G (gG1 and gG2). HSV-1 infections correlated mostly with age and was widely prevalent among subjects < 40 years. HSV-2 prevalence varied greatly among subgroups defined by sexual activity and was associated with risk behaviours for prostitution, infection with STD, and homosexual activity. HSV-2 seroprevalence was highest among prostitutes (80%), lowest among pregnant women (7%), and intermediate in STD patients (23%) and homosexuals (24%). Because HSV-1 infection during childhood has been decreasing, primary genital HSV-2 infection, with its higher frequency of clinical manifestations, will become a greater burden to the public health in Japan.

Adult

Human CD4+ T lymphocytes recognize a highly conserved epitope of human T lymphotropic virus type 1 (HTLV-1) env gp21 restricted by HLA DRB1*0101.

HTLV-1 causes two distinct human diseases, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell leukaemia/lymphoma (ATL). Persistently infected individuals carry a risk of <1% of developing either disease. These basic epidemiological data imply that virus-host interactions, especially immunogenetic factors, influence the outcome of infection. Several studies showed that the HLA class II DR1 DQ5 haplotype is over-represented in HAM/TSP, but rare in ATL. Therefore, we selected four patients with HAM/TSP and one seronegative control who all carried the HLA DR1 DQ5 haplotype. We analysed the CD4+ T lymphocyte response against eight synthetic peptides of HTLV-1 envelope (env) glycoprotein gp21, a crucial target antigen in HAM/TSP. The first of two immunodominant epitopes corresponded to a domain of the HTLV-1 envelope protein which had previously been shown to be essential for HTLV-1 envelope function. The second immunodominant epitope overlapped a highly conserved sequence of the retroviral transmembrane envelope protein. DR1 (DRB1*0101)-restricted T lymphocytes were activated by the conserved peptide sequence in nanomolar concentrations. In contrast, this conserved sequence can also induce non-specific, cAMP-mediated immunosuppressive effects on T cells when added in micromolar concentrations to culture media, as shown by Haraguchi S, Good RA, James-Yarish M, Cianciolo GJ, Day NK, Proc Natl Acad Sci USA 1995; 92:5568-71. Hence, HTLV-1 env gp21 might exert either stimulating immunological or immunosuppressive effects in HTLV-1-infected individuals, depending on the level of its expression and the presence of HLA DRB1*0101.

Amino Acid Sequence

HLA class I and class II of the Nivkhi, an indigenous population carrying HTLV-I in Sakhalin, Far Eastern Russia.

The Nivkhi are a native people isolated in the Nogliki region of Sakhalin, Far East Russia, where our group recently recognized human T-cell lymphoma virus type I (HTLV-I) infection. In order to trace the Nivkhi's ethnic background and the HTLV-I carriers, we investigated HLA class I and II allele types of 53 Nivkhi (including four HTLV-I carriers). Major HLA class I alleles of the Nivkhi were A*24, A*02, B*40, B*48, B*27, B*35 with allele frequencies similar to the Orochon, a native people isolated in Northeast China. Major Nivkhi class II alleles were DRB1*0901, DRB1*1401, DRB1*1201, DRB1*1106 with allele frequencies similar to the Ainu in Hokkaido, Japan, but dissimilar to other Asian Mongoloids, including the general Japanese population. The same HLA class I and II allele frequencies are found in both Nivkhi HTLV-I carriers and the background population. A dendrogram of HLA class I alleles showed that the Nivkhi were closely related to the Orochon and Yakut, and remotely related to the Japanese, Ainu and other Asian Mongoloids. Interestingly, the Nivkhi were intermediately related to the Amerindians (Inuit, Tlingit and Andeans), a relationship closer than to the Japanese and Asian Mongoloids. These results suggested the Nivkhi might be related to some genetic group of Northeast Asian Mongoloids like the Orochon and Yakut, being infected with HTLV-I in the distant past before diverging into the current major Mongoloid ethnic groups.

Adult

Malignant melanoma developing from an intradermal nevus.

A 58-year-old man presented a black nodule with satellites located in the left upper region of the umbilicus. Clinical history and microscopic findings led us to diagnose it as a malignant melanoma developing from an intradermal nevus. Histopathologically, melanoma cells developed upward from the nest of the intradermal nevus and no junctional activity was shown. Cases of malignant melanoma arising from an intradermal nevus have rarely been reported. Moreover, previously reported cases showed melanoma cells beneath the intradermal nevus.

Humans

GB virus C/hepatitis G virus infection among Colombian native Indians.

To elucidate the prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) infection in Colombian native Indians, serum GBV-C/HGV RNA was assayed in 163 native Indians and 67 members of the general population in Colombia. The native Indians (males:females = 40:123) and the members of the general population (males:females = 20:47) were tested by reverse transcription-semi-nested polymerase chain reaction. Of the 163 native Indians, 10 (6.1%) were positive for GBV-C/HGV RNA, compared with one (1.5%) of 67 from the general population. All Indians were negative for hepatitis B surface antigen and antibody to hepatitis C virus. Of 10 Indians with GBV-C/HGV RNA, the genotype of nine subjects was the Asian type. These data indicated that 1) the prevalence of GBV-C/HGV RNA in Colombian native Indians is high, and 2) GBV-C/HGV was probably brought from Asia and inherited for generations in some native Indian groups.

Adolescent

Polymorphism of the HLA-DRB1 locus in Colombian, Ecuadorian, and Chilean Amerinds.

We have characterized the DRB1 genotypes in a sample of 64 South American Indians drawn from populations in Chile, Colombia, and Ecuador. No novel DRB1 alleles were found in the total of 17 different alleles characterized, indicating that rapid allelic generation does not occur at the DRB1 loci, in contrast to HLA-B. Comparison between Chilean and Colombian/Ecuadorian samples revealed no major differences in their allelic frequencies. In the combined Amerind sample the HLA-DRB1*0407 and HLA-DRB1*1402 alleles occurred in the highest frequencies (38% and 22%, respectively). Genetic distance measurement showed the HLA-DRB1 frequencies reported here to agree with findings in other Amerind groups. The high frequencies of both HLA-DRB1*0407 and HLA-DRB1*1602 alleles, in conjunction with their absence in Siberian samples, suggest that migratory groups other than Siberians may have been involved in the peopling of the Americas.

Alleles

Comparative effects of dobutamine and amrinone on coronary blood flow in patients with idiopathic dilated cardiomyopathy.

Although amrinone has favorable hemodynamic effects in patients with congestive heart failure, little is known about its effects on coronary blood flow (CBF). We compared the effects of intravenous low-dose dobutamine and amrinone on CBF in 10 patients with dilated cardiomyopathy using a Doppler guidewire. We infused dobutamine at a dose of 5 and 10 microg/kg/min for 5 min. After the end of each stage, coronary flow velocity (CFV) and coronary arterial diameter (CAD) in the proximal left anterior descending coronary artery, and hemodynamic variables were obtained. After the CFV and hemodynamics returned to baseline, we infused 1 mg/kg of amrinone over 5 min, and obtained these variables at 5 and 10 min after the cessation of the infusion. CAD did not increase with dobutamine, but significantly increased after amrinone (% increase: 10 +/- 7%; P < 0.001 vs. baseline). CFV progressively increased with dobutamine (5 microg/kg/min: 21 +/- 26%; P < 0.05 vs. baseline; 10 microg/kg/min: 53 +/- 42%; P < 0.005 vs. baseline and 5 microg/kg/min), but slightly decreased after amrinone (-4 +/- 17%; P = not significant vs. baseline). CBF increased during dobutamine (5 microg/kg/min: 25 +/- 29%; P < 0.05; 10 microg/kg/min: 66 +/- 55%; P < 0.005) and after amrinone (19 +/- 22%; P < 0.05) compared to that at baseline. Although there was a significant correlation between the percent increase in CFV and that in dP/dt during dobutamine infusion (r = 0.82, P < 0.001), this correlation was not observed after amrinone (r = 0.23). In conclusion, although both agents significantly increased CBF in patients with dilated cardiomyopathy, they do so by different mechanisms. Amrinone mainly increases CBF by causing dilatation of epicardial coronary arteries. These results suggest that amrinone has beneficial effects on coronary flow dynamics in dilated cardiomyopathy.

Adult

Measurement of myocardial fractional flow reserve during coronary angioplasty in patients with old myocardial infarction.

Although myocardial fractional flow reserve (FFRmyo) has been demonstrated to be a useful index for determining functional significance of coronary stenosis, the data in previous studies was derived from a highly selected group of patients. The aim of this study was to investigate the value of FFRmyo in a more clinically relevant group of patients, especially in patients who also had resistance vessel dysfunction. We measured FFRmyo in 20 consecutive patients who had undergone elective coronary angioplasty. FFRmyo was calculated by the ratio of Pc/Pa during intracoronary adenosine 5'-triphosphate (ATP; 50 micrograms in the left coronary and 20 micrograms in the right coronary artery) induced maximal hyperemia, where Pa represents mean aortic pressure obtained by the guiding catheter and Pc represents mean distal coronary pressure measured by a 2.1 F infusion catheter. In total, 21 vessels were dilated and 14 of them were infarct-related arteries. The percent diameter stenosis significantly decreased from 80 +/- 14% to 27 +/- 17%, and the FFRmyo increased significantly from 0.46 +/- 0.18 to 0.77 +/- 0.15 after angioplasty. There was no significant differences in the FFRmyo between vessels with previous myocardial infarction and those without, after angioplasty (0.78 +/- 0.18 vs. 0.76 +/- 0.08). There was a significant correlation between the percent diameter stenosis and FFRmyo before (r = 0.83, P < 0.001) and after (r = 0.64, P < 0.01) angioplasty. In conclusion, FFRmyo significantly improved immediately after angioplasty in vessels with myocardial infarction as well as those without. These results led us to suggest the usefulness of FFRmyo in patients who had both epicardial stenosis and resistance vessel dysfunction. The significant correlation between FFRmyo and quantitative coronary arterial diameter stenosis would further support the more widespread use of FFRmyo in the clinical setting.

Adult

HTLV-I-infected T cells activate autologous CD4+ T cells susceptible to HTLV-I infection in a costimulatory molecule-dependent fashion.

A vigorous production of human T lymphotropic virus type I (HTLV-I)-infected CD4+ T cells is closely associated with the development of adult T cell leukemia (ATL) and neurological disease. However, the immunological mechanisms leading to generation of the HTLV-I-infected cells are not fully clarified. The modulation of CD80 and CD86 expression on the HTLV-I-infected cells and its physiological role in the interaction of infected CD4+ T cells with uninfected CD4+ T cells was examined. The HTLV-I-infected CD4+ T cell lines established from ATL patients and normal donors by infecting their CD4+ T cells with the virus expressed CD80, CD86, and HLA-DR, and induced a proliferation of autologous and allogenic CD4+ T cells. While the CD4+ T cells stimulated with the autologous HTLV-I-infected cells for 7 days expressed CD80 and CD86 but not HTLV-I gene products, they expressed HTLV-I gag antigen after 4 weeks. The interaction of HTLV-I-infected and -uninfected CD4+ T cells was profoundly suppressed by a combination of CD80 and CD86 monoclonal antibodies. These results suggest that the induction of CD80 and CD86 on HTLV-I-infected CD4+ T cells participates actively in the generation of the virus-infected progenitor cells.

Antibodies, Monoclonal