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Since the presence of anti-p53 antibody has been correlated with the mutation and accumulation of p53, the aim of this study was to detect anti-p53 antibody and understand its correlations with anti-Tof, -Rex, or -Tax antibody reactivity in HTLV-I infected people differing in their clinical status. A plasmid (pGEX-Tof) was constructed to express Tof recombinant protein (RP) in Escherichia coli. Serum samples from 50 asymptomatic carriers (ACs), 50 adult T-cell leukemia (ATL) and 50 HTLV-I-associated myelopathyltropical spastic paraparesis (HAM/TSP) patients were assayed for reactivity with different RPs by Western immunoblotting. The results showed that 2% of ACs, 4% of ATL patients and 6% of HAM/TSP patients had anti-p53 antibody. Therefore, anti-p53 antibody is not a useful serological marker for clinical management of HTLV-I infected people. Only 1 HAM/TSP patient had anti-Tof antibody whose specificity was further confirmed by antibody competition enzyme immunoassay. This study demonstrates that Tof protein is immunogenic in vivo, suggesting that it plays a role in the life cycle and pathogenesis of HTLV-I. The rate of anti-Rex antibody among HAM/TSP patients was significantly higher than that of ACs or ATL patients. In addition, 50% of ACs, 42% of ATL and 98% of HAM/TSP patients had anti-Tax antibody. McNemar's test showed that the presence of anti-p53 antibody did not have any correlation with the anti-Tax antibody in HTLV-I-infected people, while the correlation between anti-p53 and anti-Rex antibodies or anti-p53 and anti-Tof antibodies cannot be ruled out in this study.

The complete human T-cell leukemia virus type I (HTLV-I) env gene was inserted into an expression cassette containing the adenovirus 5 major late promoter (Ad5-MLP). Recombinant Ad5-HTLV-I-env was obtained by homologous recombination in 293 cells simultaneously transfected by the expression cassette and the genomic DNA of Ad5. In vitro expression of the HTLV-I-env gene in the recombinant vector was detected by immunofluorescence and Western blotting. Functional expression of HTLV-I-env was confirmed by syncitium formation specifically in HeLa cells infected with Ad5-HTLV-I-env. Two immunization regimens against HTLV-I were tested in WKY and Fischer F-344 rats. The first involved WKY rats primed with Ad5-HTLV-I-env or naked DNA plasmids containing the HTLV-I-env gene and boosted with Ad5 containing the HTLV-I-env gp46 gene or with baculovirus-derived recombinant gp46. No antibody against HTLV-I was detected, while HTLV-I-specific cytotoxic T lymphocytes were recovered from all immunized groups but not from controls. The second approach involved Fischer F-344 rats primed and boosted with recombinant vaccinia virus containing the HTLV-I-env gene. Such rats developed antibodies against the HTLV-I env gp21 and gp46 (non-neutralizing). After challenge with human HTLV-I-producing cells (MT-2), both immunization regimens were found to induce partial protection.

We investigated clinical features and immunological parameters in 40 patients with slowly progressive spastic paraparesis including 13 cases (4 men and 9 women, aged 43 to 71, mean 61 years) with positive antibody to hepatitis B virus (HBV), 13 (6 men and 7 women, aged 39 to 75, mean 63 years) with positive antibody to HBV and HTLV-I, and 14 (3 men and 11 women, aged 33 to 71, mean 55 years) with positive antibody to HTLV-I (HAM). None showed obviously organic changes of the spine on magnetic resonance image. Patients with positive antibody to HBV (hepatitis B virus associated myelopathy, HBM) were significantly lower in disability grade and had a fewer incidence of micturition than in the HAM. Furthermore, natural killer (NK) activities were in normal range and peripheral blood lymphocytes did not show autologous proliferation response (APR). Patients with positive antibody to both HBV and HTLV-I showed APR similar to HAM, but in most patients NK activities were within normal range. These results suggest that the mechanism of myelopathy in HBM may be different from that in HAM, and HBV infection may play a role as a cofactor in HAM.

Background: We investigated behavioural and environmental risk factors for seropositivity to human T-lymphotropic virus type I (HTLV-I)., Methods: A nested case-control study of 201 HTLV-I seropositive subjects and 225 age- and sex-matched seronegative controls was performed using questionnaire data from the enrollment visit of a cohort study in 1987-1988. HTLV-I serostatus was confirmed using enzyme-linked immunosorbent assay (ELISA) and Western blot., Results: Among women, the number of lifetime sexual partners (P < 0.05, chi 2 trend) and the number of different men fathering a child by the woman (P < 0.06, chi 2 trend) were associated with HTLV-I seropositivity. Use by the female subject of an intrauterine device (IUD) was associated with an increased risk of seropositivity (odds ratio (OR) = 2.67, 95% confidence interval (CI): 1.13-6.23); condom use was rare in this population. Among male subjects, a larger number of lifetime sexual partners was also associated with HTLV-I seropositivity (P < 0.05, chi 2 trend). No association was found between HTLV-I seropositivity and educational attainment, income, or occupation. Having been breastfed as a child or receipt of a blood transfusion had elevated but imprecise OR due to very high and low prevalence of the risk factors, respectively. Several variables relating to insect or animal exposure showed no association with HTLV-I seropositivity., Conclusions: These data confirm that heterosexual intercourse is a major route of HTLV-I transmission, but do not support suggestions of insect or environmental vectors.

An extensive collaboration of laboratories and investigators has been developed to define the seroprevalence of human T-cell leukaemia/ lymphoma virus type I and II (HTLV-I and -II) infection in Europe. An algorithm for serological screening for HTLV-I and -II infection has been established by consensus. Data from screening almost 4 million subjects, including many unpublished studies, which conform to this algorithm are presented. In extensive studies the seroprevalence of HTL.V-I/II in blood donors is low, ranging from < 1 in 100,000 to 30 in 100,000 donors and is due predominantly to HTLV-I. In antenatal clinics in France and the United Kingdom the seroprevalence of HTLV-I is > 0.2%, but surveillance in this setting has been limited and extensive study of the seroprevalence of HTLV-I/II infection in pregnant women in Europe is urgently required to determine the need for HTLV-I/II antenatal screening. HTLV-I is present in populations who have immigrated to Europe from endemic areas and is spreading into indigenous European populations, particularly through sexual transmission to females. HTLV-II infection is present predominantly amongst IVDU and is usually a coinfection with HIV-I. There are considerable regional differences in HTLV-II seroprevalence.

Two middle-aged patients with T cell lymphoma, both natives of Bucharest, Romania, tested positive for HTLV-I antibodies. Malignant cells had the typical phenotype and morphology of adult T cell leukemia/lymphoma (ATL). Both cases presented with extranodal manifestation, hypercalcemia, early recurrence after initial responses to therapy, and subsequent resistance to conventional and intensified chemotherapy. Infection with HTLV-I was confirmed by PCR analyses of serial biopsies. Neither patient reported known risk factors for HTLV-I infection. This report points to the possibility that Romania may represent an endemic area for HTLV-I and should heighten the awareness towards HTLV-I infections in Romanian patients.

Varicella (chicken pox) is a common viral infection in children and generally runs a benign course. However, in adults, and especially in immunocompromised subjects such as those on immunosuppressant therapy or with AIDS, varicella infection is particularly severe and is associated with the formation of hemorrhagic skin lesions and visceral involvement. These patients are at an increased risk of developing varicella hepatitis, which frequently results in fulminant hepatic failure and death. In the present report, we describe for the first time the course of disease and the histological appearance of varicella hepatitis in a patient infected with the human T cell lymphotropic viruses (HTLV) I and II; these viruses have many characteristics in common with the human immunodeficiency virus (HIV). Our patient had a relatively benign illness, suggesting that varicella infection in the presence of HTLVI and II may not run as severe a course as it does in patients with HIV infection.

A 63-year-old woman had Pneumocystis carinii pneumonia without any apparent underlying disease such as cancers or HIV infection. Although she reacted positively for HTLV-I antibody, hematological findings and clinical symptoms did not suggest that this patient had an ATL. Southern blot analysis revealed that HTLV-I infected lymphocytes had already proliferated monoclonally. The development of overt ATL should be carefully monitored in this type of patient as Pneumocystis carinii infection in HTLV-I carriers were reported to be a predictive sign of ATL and the monoclonal integration of a HTLV-I genome in the lymphocytes in this patient also suggests the presence of neoplastic clone.

Kinmen is a group of small islands located between Taiwan and Fu-Kien Province of mainland China. The general population in Kinmen are descendants of immigrants from mainland China who began arriving around 317 A.D. Since it has been reported that 0.48% of adults in Taiwan have HTLV-I infection, the decision was made to conduct a community-based epidemiological study in Kinmen to understand the origin and dissemination of HTLV-I in north-east Asia. Over 68% of residents of Kin-Hu township in Kinmen over 30 years of age participated in this study. Eight of 1,425 males and 14 of 1,595 females had HTLV-I infection. Antibody reactivities were further tested by Western blot assays with HTLV-I or HTLV-II type-specific recombinant envelope glycoproteins, and it was determined that all of those infected had HTLV-I and none had HTLV-II. Logistic regression was used for multivariate analysis. The final model indicated that the significant factors associated with HTLV-I infection in Kinmen were age and coastal residency. Age was positively correlated with HTLV-I infection. The eastern coastal area had a rate of HTLV-I infection 3.1 times higher than other areas in Kin-Hu. Further genetic analysis in Kinmen is needed to elucidate a relationship with other HTLV-I isolates in the world.

Sera from 653 female prostitutes and 153 male sexual clients living in the city of Santos, São Paulo, Brazil, were tested for the presence of antibodies to human T cell lymphotropic virus types I and II. Seroprevalence for HTLV-I in the females was 2.8% and in the males 2.0%. Infection by HTLV-II could not be demonstrated. Seropositivity to HTLV-I was not associated with intravenous drug use, modality of sexual behaviour or a history of sexually transmitted disease. Among the prostitutes, the prevalence of anti-HTLV-I antibodies was 3 times higher in those with a history of blood transfusion (P = 0.01).

The relationship between acute myeloid leukemia (AML), acute lymphocytic leukemia, chronic myeloid leukemia (CML), and refractory anemia with excess of blasts (RAEB) and antibodies to human T-cell lymphotropic virus types I and II (HTLV-I and HTLV-II), and hepatitis B virus and hepatitis C virus (HCV) was investigated in a multicenter case-control study. There were 431 cases enrolled in the study at the time of diagnosis of hematological malignancies, and 862 controls ages 15 years or older were recruited in three hospitals. Antibodies to HTLV-I and HTLV-II, antibody to HCV, hepatitis B surface antigen, and antibody to hepatitis B core antigen were assayed. All cases and controls were negative for HTLV-1 antibodies; one case (1 of 431; 0.2%), and one control (1 of 862; 0.1%) were found positive for HTLV-II antibodies. A nonsignificant excess of risk for hepatitis B surface antigen was present among RAEB cases (odds ratio, 2.40; 95% confidence interval, 0.46--12) CML, (odds ratio, 2.70; 95% CI, 0.86--8.43), and between antibody of hepatitis B core antigen and AML (odds ratio, 1.40; 95% CI, 0.93-2.10). A weak, nonsignificant association was present between AML, acute lymphocytic leukemia, RAEB, and antibody to HCV. These preliminary results suggest a possible association (elevated odds ratios) between hepatitis B virus, AML, RAEB, and CML. However, because all confidence intervals overlapped the null value, these findings need to be confirmed in larger case-control studies.

A 57-year-old woman was admitted to our hospital complaining of left exophthalmos in July, 1991. Biopsy specimen of a tumor in the left orbit suggested an inflammatory pseudotumor. The orbit was irradiated and the exophthalmos disappeared. During admission, an erythema was noted on her anterior chest wall. After discharge, right exophthalmos and generalized skin eruptions developed. The skin eruption on her anterior chest wall was histopathologically diagnosed as angiocentric lymphoma and she was readmitted. Since her serum was positive for anti-HTLV-I antibody, adult T-cell leukemia/lymphoma was suspected. Chemotherapy yielded limited relief of the right exophthalmos and transient fading of the skin eruptions. She died due to progression of the disease. Close examination of the skin eruption on the calf revealed that the lymphoma cells were CD56-positive immunohistochemically and electron microscopy revealed that they had large membrane-bound granules. Rearrangement of the T-cell receptor beta chain gene was observed. Incorporation of HTLV-I proviral DNA was not observed. Re-examination of the left orbital tumor confirmed the infiltration of these lymphoma cells. This is a rare case of T-cell lymphoma with NK cell phenotype involving orbits and skin, and showing a rapid clinical course.

Human T-cell lymphotropic virus type I is an oncogenic retrovirus, endemic in Southwestern Japan, the Caribbean, some parts of Africa and Central and South America. The virus is etiologically associated with adult T-cell leukemia/lymphoma and a myelopathy called tropical spastic paraparesis or HTLV-I associated myelopathy. Transmission of the virus is almost identical to that of HIV. The latency period before onset of clinical symptoms can last from a few years (tropical spastic paraparesis) up to several decades (adult T-cell leukemia/lymphoma). Four different clinicopathological subtypes of the T-cell neoplasia are known, and in this article we describe two patients with the subtype lymphoma.

A review of 100 patients with HTLV-I associated myelopathy revealed 9 cases of retinochoroidal degeneration. The ocular disease was characterized by late onset, usually bilateral, progressive degenerative changes of the retina and choroid, which were preceded by, concurrent with, or followed by HTLV-I associated myelopathy. Ophthalmoscopic features were consistent with diffuse or localized retinochoroidal degeneration, the resultant functional disturbance being dependent on the extent of disease. It is noteworthy that the clinical picture in 3 cases was indistinguishable from primary retinitis pigmentosa. However, based on the prevalence of primary retinitis pigmentosa in the general population estimated from a questionnaire to ophthalmologists in the area, it was plausible that retinitis pigmentosa in HTLV-I associated myelopathy does not represent a coincidence of primary retinitis pigmentosa but a meaningful association with the neurological disease. Hence, we propose the existence of HTLV-I associated retinochoroidal degeneration (HARD) as a distinct disease. An additional study revealed that 21 (17.8%) of 118 patients with isolated, retinitis pigmentosa were seropositive for HTLV-I, the ratio being not significantly different from that in the general population. Therefore, the hypothesis that HTLV-I also contributes to an isolated form of retinochoroidal degenerative disease is not readily acceptable.

The purpose of this study was to confirm that ophthalmological features seen in patients in Martinique, French West Indies, could be linked to infection by HTLV-I. The authors studied 93 HTLV-I infected patients divided into 70 patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 23 asymptomatic HTLV-I carriers. They did a complete ophthalmological examination with an assessment of lacrymal secretion by means of three tests: Shirmer 1, break-up time and rose Bengal. Some patients had a biopsy of secondary salivary glands. When possible, detection of HTLV-I antibodies was carried out in the aqueous humor. In 45 of the 93 patients (48.4%) the presence of dry keratoconjunctivitis was recorded. In 22 of these 45 cases, a biopsy of the secondary salivary glands showed the presence of lymphoplasmocytoid infiltrations comparable to the glandular changes that occur with Gougerot-Sjögren syndrome. Among the 93 patients, 15 cases of uveitis were noted (16.1%) with 13 cases of anterior uveitis and 11 cases of vitritis. The inflammation was bilateral in 9 cases (9/15 = 60%). Two cases of cotton wool spots, 3 cases of abnormalities in the distribution of the retinal pigment and 7 cases of corneal lesions were also noted. Higher levels of anti-HTLV-I antibodies were detected in the aqueous humor of 3 patients with uveitis. The coexistence of dry eye (keratoconjunctivitis), uveitis and retinal microangiopathy in patients who are suffering from HAM/TSP could suggest the involvement of an autoimmune or immunological mechanism in the physiopathology of the illness.

Background: Adult T-cell leukemia/lymphoma (ATL) is associated with infection with human T-cell lymphotropic virus type I (HTLV-I)., Objective: The objective was to describe the clinical, histopathologic, and immunologic features in three patients with ATL involving the skin., Methods: Clinical histories and skin biopsy specimens were reviewed. Immunophenotypic studies were performed on peripheral blood lymphocytes (three patients) and on skin biopsy specimens (one patient)., Results: Serologic testing in each patient was positive for HTLV-I. Specific cutaneous lesions of ATL were diverse. Histologic features included markedly epidermotropic lymphoid infiltrates and dermal aggregates of lymphocytes and macrophages resembling granulomas. One patient died 3 months after diagnosis; the other two are alive with residual lymphoma., Conclusion: A spectrum of clinical, histologic, and immunophenotypic features are seen in ATL involving skin. Those cases with a chronic course may resemble mycosis fungoides clinically and histologically. Serologic testing for HTLV-I is recommended in all patients with cutaneous lymphoma from endemic areas and in those with other risk factors for HTLV-I infection.

The anti-HTLV-I prevalence was studied by particle agglutination technique (PA) in 2,609 samples including: 403 antenatal care women from Srinagarind Hospital, Faculty of Medicine, 342 high-risk sexually transmitted disease blood donors and 1,864 randomly selected blood donors from the Blood Transfusion Centre, Faculty of Medicine, Khon Kaen University. All of the 2,609 samples gave negative anti-HTLV-I. The result revealed that HTLV-I infection is not common in northeast-Thailand. However, as the sample size from this study may be too small, further study should be carried out.

Human T-cell lymphotropic virus type I (HTLV-I) is endemic in the Caribbean basin and in Japan. HTLV-II, a closely related virus, is endemic in several groups of native Americans, including Panamanian Guaymi. In Panama, a nationwide HTLV-I/II seroprevalence of 1-2% has been reported. We evaluated the frequency of HTLV-I/II infection in patients with neurologic diseases admitted to state tertiary hospitals in Panama City between 1985 and 1990. Nineteen of 322 patients with eligible diagnoses had antibodies to HTLV-I/II, 17 with HTLV-I and 2 with HTLV-II. HTLV-I was associated with spastic paraparesis (13 of 23, 56.5% versus 4 of 299, 1.3%, p < 0.001) and with cerebellar syndrome (2 of 13, 15.4%) and multiple sclerosis (2 of 54, 3.7%) (p < 0.05 for both diseases compared with subject with none of these diagnoses). The two HTLV-I infected patients with cerebellar syndrome later developed spastic paraparesis. HTLV-II infection was noted in one patient with cerebellar syndrome and one with amyotrophic lateral sclerosis. All patients with other diagnoses were seronegative. Among patients with spastic paraparesis, HTLV-I-infected patients were clinically indistinguishable from seronegative subjects. There is apparently an overlapping clinical spectrum of neurologic diseases associated with HTLV-I and HTLV-II infection.

The HTLV-I seroprevalence rate among the patients with Sjögren's syndrome (SjS, 23.0%) was significantly higher than that among blood donors (3.4%). The age-adjusted summary odds ratio of HTLV-I infection among SjS patients as compared with blood donors was 3.1. The etiologic fraction, i.e., the proportion of SjS in the study population that are attributable to HTLV-I infection, was estimated to be 17.6%. Titers of serum antibodies to HTLV-I in the seropositive SjS patients were significantly higher than those among healthy carriers. IgM class antibodies were commonly detected in sera of SjS patients. Salivary IgA class antibodies were common among seropositive SjS patients, but not in HAM patients or in healthy subjects. The findings strongly suggest that HTLV-I is involved in the pathogenesis of the disease in a subset of patients with SjS in endemic areas.

Recently human T-cell lymphotropic virus type I (HTLV-I) has been shown to be responsible for a kind of uveitis in southwestern Japan, where HTLV-I infection is highly endemic. To investigate further the association of HTLV-I with various ocular diseases, we studied HTLV-I seroprevalence in 1,350 patients in central Japan, where HTLV-I infection is not endemic. Of 1,350 patients with various ocular diseases, 40 (2.96%) were seropositive for the retrovirus. There was no statistically significant difference in HTLV-I seroprevalence among various ocular diseases. Four of 9 (44.4%) seropositive cases from southwestern Japan developed HTLV-I associated uveitis (HAU), whereas only 2 of 26 (7.7%) seropositive cases from central Japan developed HAU. The difference was statistically significant (p < 0.05). This suggests that the incidence of HAU could be influenced by environmental or hereditary factors. On the other hand, 3 of 7 (42.9%) patients with episcleritis showed HTLV-I infection.

A fully automated ELISA system was constructed using a pipette tip as a solid phase, urease as a detecting enzyme, and a pH-FET as a detector of urease activity. The inner wall of the end part of a pipette tip was used as a solid phase, and the urease activity of the conjugate, captured after a two-step immunoreaction, was measured by coupling the pipette tip with the pH-FET in a pH-measuring cell. Full automation of the ELISA system was achieved by using a disposable reagent cartridge and three pipetters for all mechanical operations, including sample dilution and B/F separation. This system can treat 60 samples per hour with an assay time of 21 min for all assay configurations. The system was applied to two-step sandwich assays for AFP, CEA, HBsAg, and HBsAb, a two-step competition assay for HBcAb, and a second antibody assay for HTLV-I Ab.

Neurolathyrism is a form of human spastic paraparesis related to the overconsumption of the legume Lathyrus sativus or grass pea (Khesari in Bangladesh) containing the neurotoxin 3-N-oxalyl-2,3-diaminopropanoic acid (beta-ODAP). The clinical symptoms of neurolathyrism are similar to those of Tropical Spastic Paraparesis. In order to eliminate the proposed causative agent of TSP (HTLV-I) as a potential cause of the symptoms ascribed to neurolathyrism, a total of 444 diagnosed lathyrism patients were screened for HTLV-I antibodies. 50 CSF and 394 serum samples were collected from male (415) and female (29) patients. Only 4 serum samples were found sero-positive for HTLV-I. This agrees with the assumption that overconsumption of beta-ODAP containing Lathyrus seeds, and not HTLV infection, is the causative agent for neurolathyrism.

A 70-year-old man was admitted to our hospital because of a 15-year history of walking difficulty, disturbance of sensation in the palm for 2 years and hand tremor for 6 months. On admission, the scapulohumeral muscles showed fasciculation and atrophy. There was action tremor in the upper limb, and the proximal lower limb showed atrophy and weakness. Standing and walking were impossible. Deep tendon reflexes were decreased in lower limbs. Pathologic reflexes were not found. There was distal dominant sensory disturbance, and urination was difficult. Needle EMG showed a neurogenic pattern in 4 all limbs. MCV and F-latency were delayed. SCV in the median nerve and the amplitude in the sural nerve were decreased. Biopsy of the sural nerve revealed both axonal change and demyelination. Biopsy of the quadriceps femoris muscle showed neurogenic change with helper T-cell infiltration. Anti-HTLV-I antibody and ATL-like cells in both blood and CSF were positive. There were HTLV-I provirus DNA with a polyclonal pattern and the type of HLA as HAM. The HTLV-I infection was of the HAM type. As the present patient showed mainly neuropathy without pyramidal signs, was not considered to have HAM.

The aim of this study was to compare rates of human T-cell lymphotropic virus type I (HTLV-I) seroprevalence in pregnant women belonging to different ethnic groups in French Guiana and to determine the risk factors associated with HTLV-I seropositivity. All 1,873 deliveries between 1 July 1991 and 30 June 1993 in the only gynecologic and obstetric unit at Saint Laurent du Maroni were enrolled. Serologic status could be established for 1,727 women, with 75 (4.3%) being HTLV-I seropositive. The HTLV-I seroprevalence rate differed significantly between ethnic groups: 5.7% for Noir-Marron (70/1,302), 6.3% for Haitian (3/50), and 0% for Creole (126), Amerindians (166), and Hmong (64). In Noir-Marron pregnant women, HTLV-I seropositivity was associated with a maternal age of > 35 years [odds ratio (OR), 3.3; 95% confidence interval (CI), 1.4-7.6], prior miscarriage (OR, 1.7; CI, 1-2.8), prior cesarean section (OR, 2.1; CI, 1.1-4.0), a parity > 4 (OR, 4.0; CI, 1.8-8.8), a gravidity > 6 (OR, 4.2; CI, 2.0-7.2), and a negative Rhesus factor (OR, 2.2; CI, 1.1-4.5). Two separate stepwise logistic regressions were done because gravidity and parity were highly correlated. HTLV-I seropositivity remained associated with a gravidity > 6 (OR, 3.9; CI, 2.1-7.4) and a negative Rhesus factor (OR, 2.6; CI, 1.2-5.3) for the first model and with a parity > 4 (OR, 4.1; CI, 1.9-9.0) and a negative Rhesus factor (OR, 2.5; CI, 1.2-5.1) for the second model.(ABSTRACT TRUNCATED AT 250 WORDS)

A new artificial carrier particle agglutination test using polyamino acid (polyamino PA) was developed for anti HTLV-I assay. We carried out the comparative study on anti-HTLV-I among polyamino PA, gelatin PA, EIA and WB methods. All of 76 ATL, 20 HAM/TSP, 53 patients with uveitis and 50 HTLV-I carriers were seropositive and 50 HTLV-I non carriers were seronegative with four methods. Eighteen of 503 patients include autoimmune diseases showed seropositive by polyamino PA and gelatin PA. One of 19 seropositives by EIA was false positive. All of 25 sera showed non-specific reaction by the gelatin PA were clearly negative by the polyamino PA. This is due to the fact that the polyamino acid particle has a greater specific gravity as carrier. The final judgement was got within 45 minutes. It was earlier more 30 minutes than the gelatin PA. The polyamino PA is a simple, rapid, sensitive and specific method. Therefore, it is useful for mass screening and clinical diagnosis.

Human T-cell lymphotropic virus type I (HTLV-I) was associated with carcinoma of the cervix in Japan in a recent study that compared hospital cases with healthy population-based controls. To test this relationship in women more alike for cervical neoplasia risk factors (including sexual behavior and human papilloma virus; HPV), we enrolled consecutive patients from a colposcopy clinic in Kingston, Jamaica (an HTLV-I endemic area). Patients underwent Pap smear, colposcopy, biopsy and cervical swab for detection of HPV by polymerase chain reaction. Cases were defined as women with CIN-3 or invasive cancer (CIN-3/CA). Controls included all patients with either CIN-I or koilocytotic atypia, atypical squamous cells of undetermined significance or benign cervical pathology (all but one had at least inflammatory changes). Patients with CIN-2 were excluded to minimize risk of case-control misclassification. Cases were much more likely to be HTLV-I seropositive than controls. Although mean age differed significantly between cases (mean age = 39 years) and controls (mean age = 33 years), control for age did not explain the relation of CIN-3/CA with HTLV-I. Among HPV DNA positive subjects the age-adjusted association was not diminished but lost statistical significance. HTLV-I seroprevalence may be independently associated with progression to severe neoplasia of the cervix.

Adult T-cell leukemia (ATL), induced by human T- lymphotropic virus type-I (HTLV-I), is endemic in Nagasaki, Japan. To investigate the effects of atomic-bomb radiation on development of this specific type of leukemia, 6182 individuals in the Radiation Effects Research Foundation (RERF) Adult Health Study sample in Hiroshima and Nagasaki were examined for positive rate of HTLV-I antibody. Several lymphocyte parameters were also studied for 70 antibody- positive subjects in Nagasaki. The HTLV-I antibody-positive rate was higher in Nagasaki (6.36%) than in Hiroshima (0.79%) and significantly increased with increasing age, but no association was observed with radiation dose. Whether relationship existed between antibody titer levels and radiation dose among antibody-positive subjects was not The frequency of abnormal lymphocytes tended to be higher in antibody-positive subjects than in antibody-negative subjects, and higher in females than in males regardless of radiation dose. The lymphocyte count was lower in antibody-positive subjects than in antibody-negative subjects and lower in female than in male subjects. No evidence was found to suggest that atomic-bomb radiation plays an important role in HTLV-I infection.

The seroprevalence of antibodies against human T-cell leukemia virus was determined by ELISA in 68 patients with filarial infestation living in an endemic area. The total seropositivity was 2.9% and the HTLV-1-positive cases were detected in 2 microfilaremic patients 12 and 40 years old. This value is very close to that obtained for healthy individuals in the same region and age groups. This result suggests that there is no relationship between filariasis and HTLV-1 infection as previously proposed.

This retrospective study was designed to determine the relationship between human T-lymphotropic virus (HTLV) type-I/II infection and human immunodeficiency virus (HIV) infection among sexually promiscuous persons in southern India. Stored sera collected between 1986 and 1993 from 822 male and 488 female patients attending clinics for sexually transmitted diseases (STD), for the purpose of HIV serosurveillance, were used. They comprised 376 HIV-positive sera and 934 HIV-negative sera. They were screened for HTLV-I/II antibody by a particle agglutination test and repeatedly reactive sera were confirmed by an immunofluorescence test and a western blot test. Five (2.4%) of 212 HIV-seropositive men were confirmed positive for HTLV-I/II antibody, while none of the 610 HIV-seronegative men were positive; the difference in prevalence between HIV-seropositive and seronegative men was statistically significant (p < 0.001). Nine (5.5%) of 164 HIV-seropositive women and 3 (0.9%) of 324 HIV-seronegative women were positive for HLTV-I/II antibody (p < 0.005). All HIV-seropositives taken together, had a significantly higher prevalence of HTLV-I/II (3.7%; 14/376) compared with HIV seronegatives (0.3%; 3/934; p < 0.001). Thus, in southern India, HTLV infection, like HIV infection, is sexually transmitted, though less effectively.

HTLV-I and HTLV-II are two related retroviruses that are transmitted by sexual contact, breast feeding, blood transfusion and needle sharing. In this study the prevalence of HTLV-I and HTLV-II was evaluated in voluntary blood donors as a measure of the infection in the general population. Samples were tested by a gelatine particle agglutination test and repeatedly reactive samples were confirmed by Western blot tests (WBT), enriched with recombinant rgp21, rgp461 y rgp4611 proteins, which differentiates HTLV-I and HTLV-II antibodies. Of 19,426 samples, 40 were repeatedly reactive by particle agglutination (0.21%). When analyzed by WBT, 6 met the criteria for HTLV-I (0.036%), 2 for HTLV-II (0.01%) and 1 for HTLV-I/II, 13 samples were indeterminate and 18 were negative. The prevalence is low and comparable to that from non endemic countries. Screening for anti HTLV-I/II antibodies is necessary to prevent transmission through blood transfusions.

Despite the likely role of mucosae in human T cell leukemia virus type I (HTLV-I) transmission, little is known about the mucosal immune response to HTLV-I. The present study evaluated the antibody response to HTLV-I in oral mucosa and the value of crevicular fluid rich saliva (CFRS) for diagnosing HTLV-I infection. CFRS and sera from patients with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM), asymptomatic carriers, and HTLV-I seronegative individuals from Tumaco, Colombia, were analyzed for HTLV-I specific IgG, IgA, and secretory IgA (sIgA). Detection of IgG in CFRS by enzyme-linked immunosorbent assay correlated with its presence in sera for TSP/HAM patients and asymptomatic carriers. IgA and sIgA were more frequently detected in CFRS and sera from TSP/HAM patients than in those from asymptomatic carriers. An HTLV-I pol fragment could be amplified from CFRS by reverse transcriptase-PCR in 3 TSP/HAM patients and one asymptomatic carrier, all of whom had an IgA response in CFRS but not in sera. The more frequent detection of IgA and sIgA in sera and CFRS of TSP/HAM patients suggests increased viral replication. Further, the association of viral RNA in CFRS with a local IgA response may signify rounds of viral replication in the oral cavity.

In seropositive HTLV-I carrier rats of the WKAH strain inoculated with 2 x 10(7) MT-2 cells at 3-6 months of age, chronic progressive myeloneuropathy, tentatively designated as HTLV-I-associated myelopathy (HAM) rat disease, occurred when the rats were 19-23 months old. Clinical and pathological findings were basically identical to those of seronegative HAM rats of the same strain neonatally inoculated with MT-2 cells. It appears that a high dose of MT-2 cells (10(8) cells) is more effective for the induction and acceleration of HAM rat disease. Seronegative and seropositive carriers of other strains (F344, ACI, and LEW), WKAH rats inoculated with HUT-78 (a human T cell line without HTLV-I infection), and untreated WKAH rats at comparable ages did not develop HAM rat disease, thereby indicating that development of this disease is caused by HTLV-I infection and is under strict genetic restriction of the host strain. Chronological examination of HAM rat disease induced by 10(7) MT-2 inoculation into newborn rats showed that the spinal cord lesion began to develop by 12 months of age. T cells were absent in the affected spinal cord throughout the disease process. There was morphological evidence of apoptotic death of oligodendrocytes in the affected spinal cord. Apoptosis was also confirmed by the specific nick end labeling of the nuclear fragmentation in situ, and the apoptotic oligodendrocytes confined to the demyelinating foci, and the number of apoptotic cells positively correlated with severity of the spinal cord lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Human T-lymphotropic virus type 1, HTLV-I, was the first human oncogenic retrovirus to be isolated in 1978. HTLV-I has previously been called Human T-cell leukaemia virus or Human T-cell lymphoma virus type I. HTLV-I infection is endemic in southwestern Japan, the Caribbean basin, and parts of South America and Africa. HTLV-I is aetiologically associated with adult T-cell leukaemia lymphoma and tropical spastic paraparesis (TSP), also known as HTLV-I-associated myelopathy. HTLV-II was isolated in 1982 and is endemic among some north American Indians. HTLV-II has not been clearly linked to any specific disease. Both viruses are found worldwide, particularly among intravenous drug users (IVDU), and have also been found in blood donors in USA and Europe. HTLV-I/II are transmitted by the same routes as HIV-1: blood-borne via blood transfusions and among IVDUs by sharing contaminated needles, and by mother-to-child transmission, primarily through breast feeding. HTLV-I/II infections are also sexually transmitted and can be transmitted in utero, though less efficiently than HIV-1. The diagnosis of HTLV-I/II infections is based on the detection of antibody to the virus. Due to the high degree of cross reactivity between HTLV-I and HTLV-II, it is difficult by serology to discriminate between the two viruses. Less than 5% of individuals infected with HTLV-I develop symptoms after a latent period, which can last from a few years to several decades. No specific treatment of adult T-cell leukaemia or tropical spastic paraparesis is currently available and no vaccine has yet been developed.

Background: Six cases of HTLV-I/II infection were selected for isolation and characterization of these retrovirus., Methods: Detection of anti-HTLV antibodies was carried out by enzyme immunoassay (EIA), immunofluorescence (IFI), and Western blot (WB). Analysis of proviral DNA was performed by PCR. Viral culture and partial sequencing of the pol and pX genes were carried out. Electron microscopy morphologically characterized the viral particles., Results: Serologic study demonstrated four cases of HTLV-II, one of HTLV-I, and one non-typeable HTLV infections. This last case was confirmed as positive for HTLV-II by PCR. Five new HTLV-II and one HTLV-I infected cell lines have been established by co-culture. Electron microscopy allowed morphologic characterization of the viral particles found in the infected cells. The sequence of the five strains of HTLV-II was identical demonstrating a divergence of 0.49% in the pX region and of 4.5% in the pol region compared with the HTLV-II Mo prototype. Comparison of these sequences with those corresponding to different strains of HTLV-II isolates from American Indians (subtypes b) suggest that these Spanish strains are more closely related with the subtype b than with the subtype a (HTLV-II Mo). Genetic variability study did not reveal any change in the sequence of these stains suggesting that the variability of these retroviruses in very infrequent in the regions studied. The analysis of the pol region of the HTLV-I strain demonstrated a divergence of 3.4% with respect to the sequence of the ATK-1 prototype (Japan) and of 1.7% of the strain HS-35 (Caribbean) showing a greater relation with the Caribbean strains than with those from Japan., Conclusions: The presence of HTLV-II subtype has been confirmed among intravenous drug addicts in Spain. Isolation and characterization of the HTLV-I strain demonstrated that this also circulating around Spain despite its South American origin.

Human T-lymphotropic virus type I (HTLV-I) is a pathogenic retrovirus associated with a chronic progressive myelopathy, termed HTLV-I-associated myelopathy (HAM). A chronic inflammatory process has been implicated in HAM by a pathological study, but the exact mechanism still remains to be elucidated. Our quantitative polymerase chain reaction study indicated that the large increase in the HLTV-I proviral DNA in peripheral blood is associated with the development of HAM. The nucleotide sequence analysis of HTLV-I in central nervous system (CNS) tissue of HAM patients revealed that the sequences of HTLV-I genome were heterogenous in all cases, and that the pX-defective mutants were found frequently in the CNS. Thus, HTLV-I exists as quasispecies in vivo, as shown in the case of human immunodeficiency virus. It is possible that the HTLV-I pX microvariants contribute to the neural damage, since the pX gene products are essential for the transactivation of various cellular genes as well as for viral replication.

Sera and peripheral blood lymphocytes of 40 adult T-cell leukemia (ATL) patients in non-ATL-endemic Hokkaido were examined for the prevalence of human T-cell leukemia virus type 1 (HTLV-I). All patients had HTLV-I-specific antibodies. When the peripheral lymphocytes were assessed after short-term cultivation, HTLV-I antigens and virus particles were detected. The seroprevalence in 96 cases of non-T-cell leukemias and lymphomas and in 30,056 healthy individuals in Hokkaido were 3.1% and 0.7%, respectively. HTLV-I seropositive inhabitants of Hokkaido can be estimated at about 40,000, and one out of every few thousand HTLV-I carriers is likely to develop ATL.

In contrast to adult T-cell leukemia (ATL)-endemic southwestern Japan, the northernmost island Hokkaido has a small number of ATL patients annually. In this study, we surveyed 32,587 healthy inhabitants throughout Hokkaido for antibodies to human T-cell leukemia virus type 1 (HTLV-I). Only 244 individuals (0.8%) were seropositive as HTLV-I carriers; 0.6% (123 of 19,512) in males and 0.9% (121 of 13,075) in females. In some areas, however, the inhabitants had relatively high seropositivity (> 2%). The highest rate was 5.2% with a cluster of ATL patients in a certain town of the Hidaka area near the Pacific Ocean, in southeast Hokkaido.

We demonstrate a significantly high incidence of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM)-or tropical spastic paraparesis (TSP)-like symptoms in WKA rats after injection with HTLV-1-producing MT-2 cells, while no symptoms were observed in F344 rats injected with MT-2 cells or in control WKA rats. Five of the eight (63%) WKA rats injected with MT-2 cells showed HAM/TSP-like paraparesis at 105 weeks of age, but none of seven MT-2-injected F344 rats or eight control WKA rats showed symptoms. This high incidence of HAM/TSP-like symptoms in WKA rats was statistically significant (P < 0.05). Six of the eight (75%) WKA rats injected with MT-2 cells showed HAM/TSP-like paraparesis at 108 weeks of age. HAM/TSP-like symptoms were also observed in one of the two WKA rats injected with HTLV-1-producing Ra-1 cells at 128 weeks of age. HTLV-1 provirus was detected in peripheral blood mononuclear cells in both WKA and F344 rats. The provirus was detected in the spinal cords of the HAM/TSP-like WKA rats that had severe neuropathological changes. WKA and F344 rats showed no significant difference in antibody response against HTLV-1 Gag antigen. However, the antibody response against the C-terminal half of gp46 HTLV-1 envelope protein was lower in WKA rats than in F344 rats. Pathological analysis of the HAM/TSP-like rats showed degeneration of the white matter of the spinal cord and peripheral nerves. These findings suggest that both the genetic background of the host and HTLV-1 infection are important in neuropathogenesis of HAM/TSP-like paraparesis in rats.

We have developed a cell-free infection system to titrate neutralizing antibodies against human T-cell leukemia virus type 1 (HTLV-1) using the polymerase chain reaction (PCR). S+L-CCC (8C) feline kidney or U-251 MG human glioma cells were infected with a cell-free culture supernatant derived from HTLV-1-infected c77 feline cells. DNA was extracted from 8C or U-251 MG cells after incubation for 24 hr and amplified by PCR. The c77 cell supernatant gave discrete bands, whereas those of HTLV-1-positive T cells did not. When the inocula were treated with HTLV-1 antibody-positive human sera or the monoclonal or polyclonal antibody against the peptide 190-199 of HTLV-1 envelope protein gp46, the subsequent formation of HTLV-1 proviral DNA was inhibited. We determined the titers of neutralizing antibodies by densitometrically scanning the intensity of the PCR bands. These titers correlated well with those determined by the plaque assay using a pseudotype of vesicular stomatitis virus bearing the envelope antigens of HTLV-1. At high serum concentrations, many seronegative samples markedly inhibited the plating of the HTLV-1 pseudotype whereas they barely affected results obtained by PCR. Thus, the c77-PCR system can detect neutralizing antibodies against HTLV-1 even at low titers.

There is accumulating evidence that human T-lymphotropic virus-1 (HTLV-1) infection contributes to the development of various inflammatory disorders. To elucidate the relation between the infection and Sjögren's syndrome, seroepidemiological and virological studies were conducted on patients with this syndrome in Nagasaki Prefecture, Japan, an area heavily endemic for HTLV-1. The HTLV-1 seroprevalence rate among the patients with Sjögren's syndrome (17/74, 23%) was significantly higher than that among blood donors (916/27,284, 3%), whereas the difference between patients with systemic lupus erythematosus and blood donors was insignificant. Moreover, among Sjögren's syndrome patients the seroprevalence was high irrespective of age, unlike that among blood donors, which rose with age. Titres of serum antibodies in the HTLV-1 seropositive patients with Sjögren's syndrome were similar to those among patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and significantly higher than those among healthy carriers. IgM class antibodies were commonly detected in the serum of patients with Sjögren's syndrome. However, unlike that in HAM/TSP patients, the viral load in peripheral-blood mononuclear cells was not necessarily high in the seropositive Sjögren syndrome group. Salivary IgA antibodies to HTLV-1 were common among seropositive patients with Sjögren's syndrome (5/7), which might be due to increased viral activity in the salivary glands. These antibodies were barely detectable in HAM/TSP patients (prevalence 1/10) or in healthy carriers (0/11). The findings strongly suggest that HTLV-1 is involved in the pathogenesis of the disease in a subset of patients with Sjögren's syndrome in endemic areas.

We describe the clinical and laboratory features of nine patients born in Chile with HTLV-I-positive adult T-cell leukemia/lymphoma (ATLL). All were adults (median age 51 years) of Caucasian origin without evidence of Indian or foreign extraction and none had been out of the country. The main disease features were organomegaly, cutaneous lesions, hypercalcemia and leukemia with atypical polylobed lymphocytes displaying a CD2+, CD3+, CD4+, CD8-, CD7- T-cell phenotype. Eight patients presented with acute type ATLL and one had a chronic form lasting for 16 months prior to the development of the acute phase. Lymph node histology (three cases) was consistent with a T-cell non-Hodgkin's lymphoma (large and small cells). Antibodies to HTLV-I were detected by ELISA and particle agglutination in the serum from eight of nine patients. DNA analysis showed HTLV-I proviral DNA in all seven cases investigated, including the single serologically negative patient. In five cases, HTLV-I was monoclonally integrated and in one case oligoclonal. In the seventh case viral DNA clonal status was ambiguous. Response to therapy was poor and median survival was 3 months (range 2-20 months). This study provides further evidence that HTLV-I is endemic in Chile, a non-tropical country where the two main diseases associated with HTLV-I, ATLL and TSP, are found.