[A case of HTLV-I associated myelopathy presenting with cerebellar signs as initial and principal manifestations].

We reported a 75-year-old woman with HTLV-I associated myelopathy (HAM) presenting with cerebellar signs. She was admitted to our hospital because of walking unsteadiness, which initially appeared 3 years previously with gradual worsening. Neurological examination revealed limb and truncal ataxia, cerebellar type dysfunction of eye movement, pyramidal sign, diminished vibration sense and neurogenic bladder. Anti HTLV-I antibody titers in serum and CSF were markedly elevated. MRI revealed abnormal signals in cerebral white matter, mild cerebellar atrophy and thoracic cord atrophy. Cerebellar signs and symptoms were initial and main neurological manifestations in this patient, which were improved by steroid therapy. We considered this case was unique among HAM, because cerebellum was considered her main lesions.

Epstein-Barr virus (EBV)-carrying and -expressing T-cell lines established from severe chronic active EBV infection.

Four novel Epstein-Barr virus (EBV)-carrying T-cell lines, designated SIS, AIK-T8, AIK-T4, and SKN, were established from peripheral blood lymphocytes (PBL) of patients with severe chronic active EBV infection, in the presence of interleukin-2 and 4-deoxyphorbol ester. AIK-T8 and -T4 were derived from a single patient. Cell marker and genotype analyses showed that SIS, AIK-T8, and AIK-T4 had mature T-cell phenotypes with clonally rearranged T-cell receptor (TCR) genes, whereas SKN had an immature T-cell phenotype without TCR gene rearrangement. None of the cell lines expressed B, natural killer, or myeloid antigens or had Ig gene rearrangement. All lines carried EBV genomes in a single episomal form. SIS, AIK-T8, and SKN showed the same phenotype, TCR gene configuration, and/or EBV clonotype as their source or biopsied materials; therefore, they represented EBV-infected T cells proliferating in the patients. TCR gene and EBV episomal structures similar to those of AIK-T4 were not found in its source PBL, probably due to the few parental clones in vivo. All lines expressed EBV-encoded small RNA (EBER) 1, nuclear antigen (EBNA) 1, and latent membrane protein (LMP) 1, -2A, and -2B, but not other EBNAs that could be recognized by EBV-specific immune T cells. EBV replicative antigens were rarely expressed or induced. Such EBV latency reflects the in vivo situation, in which the T cells may evade immune surveillance and be insensitive to antiherpesvirus drugs. Collectively, the data suggest that EBV can target and latently infect T cells at any stage of differentiation in vivo, thus potentially causing uncontrolled T-cell proliferation. These cell lines will facilitate further analyses of possible EBV-induced oncogenicity in T cells.

[Studies on tissue distribution and expression of Epstein-Barr virus using polymerase chain reaction].

Epstein-Barr virus (EBV), a widespread human herpesvirus, establishes a life-long carrier state after primary infection. It is known that EBV infects mainly B lymphocytes and oral epithelia in vivo. However, other potential sites of EBV latent and/or permissive infection in human body have not been fully clarified. To investigate this, systemic autopsied tissues from 18 EBV-seropositive individuals without apparent EBV-related diseases were examined for EBV genomic DNA and virus-specific mRNA, by using the polymerase chain reaction technique. EBV DNA was frequently detected in oral mucosa/tongue/salivary gland, esophagus, stomach, lymph node and spleen; less frequently in bronchi, lung, kidney, adrenal gland, bone marrow and small intestine. In contrast, liver, gall bladder, pancreas, colon, heart muscle and urinary bladder contained no detectable EBV DNA. Reverse transcription-PCR analysis revealed that the latent membrane protein (LMP) 2A gene was expressed in all lymph nodes of the three cases studied, with LMP2B and EBV-determined nuclear antigen (EBNA) 1 transcripts in the lymph node and the LMP2A transcript in the stomach of one case. EBNA2 and LMP1 mRNA were not detected in any of the tissue specimens. The immediate early Bam HI-Z open reading frame no. 1 (BZLF1) gene, a key gene for EBV replicative cycle, was also expressed in the lymph nodes, but not in the spleen nor the stomach. These results indicate that EBV preferentially resides in the upper gastrointestinal tract and lympho-hemopoietic tissues where the cells harbor functionally active viral genomes. Moreover, the selective expression of the viral latent infection genes may provide advantages for EBV persistence in the setting of a host immune response. In addition, the localized detection of BZLF1 mRNA suggests that lymph nodes are another possible site of EBV replication in the asymptomatic virus carrier state in vivo.

Prevalence of human T-cell leukemia virus type 1 (HTLV-I) in family members of adult T-cell leukemia (ATL) patients in non-ATL-endemic Hokkaido of Japan.

Family members of patients with adult T-cell leukemia (ATL) in non-ATL-endemic Hokkaido, the northernmost part of Japan, were assessed for the prevalence of HTLV-I infection. Immunofluorescence assay showed that 53 out of 133 (39.8%) healthy family members of 23 ATL patients were positive for antibodies to HTLV-I. When general inhabitants in Hokkaido were examined, 3 out of 18 (16.7%) family members of 5 seropositive healthy persons had HTLV-I antibodies. The overall seropositivity in Hokkaido was 0.7%. Of 26 family members of 6 patients with non-T-cell leukemia seroconverted by blood transfusion, none (0%) was seropositive.

Prevalence of human T-cell leukemia virus type 1 (HTLV-I) in general inhabitants in non-adult T-cell leukemia (ATL)-endemic Hokkaido, Japan.

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.

Prevalence of human T-cell leukemia virus type 1 (HTLV-I) in adult T-cell leukemia (ATL) in non-ATL-endemic Hokkaido of Japan.

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.

Comparison of eumelanogenesis and pheomelanogenesis in retinal and follicular melanocytes; role of vesiculo-globular bodies in melanosome differentiation.

Vesiculo-globular bodies, 40 nm in diameter, are present in melanosomes. The mode of their involvement in melanosomal differentiation was studied by ultrastructural comparison of eu- and pheomelanogenesis occurring in retinal and follicular melanocytes. We found that the number and distribution of these bodies differ significantly with types of melanogenesis and tissues. They were not affected by physical stimuli nor by embryonic origin of melanocytes. The earliest form of melanosomes is identical in eu- and pheomelanogenesis. The vesiculo-globular bodies are involved in organization of melanosomal constituents. In eumelanogenesis, they are more numerous in feather than in retina and hair. They are least numerous in white hair and pink eyes where melanization is blocked. During melanosomal development, they become associated with melanosomal inner lamellae and their outer surface becomes melanized, but their core is hardly melanized, thus leaving small vesicular structures. In pheomelanogenesis, their number is almost equal in feather and hair. Lamellae are not formed, but these bodies fuse with each other to form an amorphous matrix on complete differentiation of melanosomes.