[Malignant proliferative disorders of the lymphatic systems and viruses].
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Burkitt Lymphoma↗
Biomedical subjects
I Miyoshi
Publications and source records attributed to I Miyoshi.
Genetic analysis and molecular phylogeny of simian T-cell lymphotropic virus type I: evidence for independent virus evolution in Asia and Africa.
Type C retroviruses, designated simian T-cell lymphotropic virus type I (STLV-I), have been isolated from several genera of Old World monkeys and apes, but not from New World monkeys and prosimians. To determine the genomic diversity and molecular evolution of STLV-I and to clarify their genetic relationship to human T-cell lymphotropic virus type I (HTLV-I), we enzymatically amplified, then directly sequenced selected regions of the gag, pol, env, and pX genes of STLV-I strains from Asia and Africa. STLV-I strains Si-2, Matsu, and JM86 from Japanese macaques, which exhibited sequence similarities ranging from 98.5 to 99.8% among themselves, diverged by 12.9 to 13.3% from STLV-I strain MM39-83 from a naturally infected rhesus macaque, by 9.7 to 11.2% from STLV-I strains from Africa, and by 8.8 to 11.2% from HTLV-I strains originating in Japan, India, Africa, the Caribbean, the Americas, Polynesia, and Melanesia. By contrast, the interspecies nucleotide sequence similarity among African STLV-I strains from green monkey, yellow baboon, sooty mangabey, and common chimpanzee was remarkably high, ranging from 96.9 to 97.4%, and these STLV-I strains diverged by only 2.2 to 2.8% from HTLV-I strain EL from equatorial Zaire. Phylogenetic trees constructed by using the neighbor-joining and maximum parsimony methods indicated that the Asian STLV-I strains diverged from the common ancestral virus prior to African STLV-I and cosmopolitan and Melanesian HTLV-I strains. Thus, our data are consistent with an archaic presence of STLV-I in Asia, probably predating macaque speciation, with subsequent independent virus evolution in Asia and Africa.
Africa↗
Targeted pituitary tumorigenesis using the human thyrotropin beta-subunit chain promoter in transgenic mice.
We have generated transgenic mice that express the simian virus 40 (SV40) large T antigen under the control of a 1109 bp 5'-flanking sequence of the human thyrotropin beta-subunit (TSH beta) gene. The hybrid gene, termed TTP-1, was microinjected into fertilized mouse eggs and 11 transgenic mice were obtained. One of the transgenic mice, a female, a phenotypical dwarf, developed a pituitary tumor and wasted away from 7 to 9 weeks after birth. To establish the transgenic mouse line, her ovaries were transferred to a normal female, whose ovaries were removed beforehand. To examine the tissue specificity of transgene expression, mRNA of SV40 large T antigen was monitored in various tissues from the transgenic mice by the reverse transcriptase-polymerase chain reaction analysis, and was detected only in the pituitary. Histological and immunohistochemical analyses showed that the pituitary tumors of the transgenic mice were composed of poorly differentiated pituitary cells expressing SV40 large T antigen. These results indicated that the 1109 bp sequence of the human TSH beta 5'-flanking region is essential for pituitary-specific expression of SV40 large T antigen in transgenic mice, which exhibited a dwarf phenotype and developed pituitary tumors. The tumors were composed of undifferentiated cells and did not produce thyrotropin. These transgenic mice should provide a valuable animal model for studying the pathogenesis of anterior pituitary tumors.
Animals↗
Spontaneous urinary calculus in young LEW rats caused by Corynebacterium renale.
Spontaneous urinary calculus was observed in only 27% of female LEW rats among nine inbred strains maintained in the Institute for Animal Experimentation. The condition occurred between 3 and 9 weeks of age with loss of weight, enlargement of the os urethral externum, anuria and general marasmus. All of the affected rats died from anuria 3 to 4 days after the onset. The affected rats had one to ten infected stones or many fine crystals of sand, which consisted of magnesium ammonium phosphate, in the urinary bladder and/or urethra. Analysis of microorganisms revealed that Corynebacterium renale, known as a causative agent of bovine pyelonephritis, was the most probable candidate for producing infection stones. This is the first report that the rat is spontaneously infected with C. renale. This could be a useful animal model for human urinary calculus and also for C. renale infection in the field of veterinary science.
Animals↗
Immunoglobulin prophylaxis against human T cell lymphotropic virus type II in rabbits.
Hyperimmune globulins, I-IgG and II-IgG, prepared from healthy persons seropositive for human T cell lymphotropic virus (HTLV) types I and II, respectively, were tested for their prophylactic effect against HTLV-II infection in rabbits. Three groups (A, B, and C) of 3 female rabbits each were used. Group A rabbits were inoculated intravenously with HTLV-II-carrying rabbit lymphoid cell line RII. Group B and C rabbits were immunized, respectively, with II-IgG and I-IgG and challenged with RII cells 24 h later. All group A and C rabbits seroconverted for HTLV-II after 2 weeks, but all group B rabbits were protected from HTLV-II infection. Gene amplification by polymerase chain reaction revealed the presence of HTLV-II provirus sequences in all group A and C rabbits but in none of the group B rabbits. These findings indicate that passive immunization with II-IgG is effective in preventing HTLV-II infection and that there is no cross-neutralization between HTLV-I and -II.
Animals↗
[Structure and regulation of human thyroid-stimulating hormone (TSH) gene].
This article describes the structure of human thyroid-stimulating hormone (TSH) gene and the regulation of its expression. TSH is a heterodimer composed of common alpha subunit and unique beta subunit encoded by genes located on different chromosomes. It is known that the expression of these subunit genes is regulated in different mechanism by several extracellular factors. The DNA sequencing data of the gene demonstrated that these genes were regulated by interaction of several potential regulatory elements with transcription factors. This transcriptional regulation was analyzed by transient expression of chimeric gene fragments and DNA-protein binding assay, in vitro. To identify the essential DNA regulatory elements of the human TSH beta gene in vivo, we introduced 1.1 kbp of the 5' flanking region of the human TSH beta gene-simian virus 40 T-antigen (SVT) fusion gene into the mouse. This region could direct pituitary-specific expression of SVT and tumorigenesis in transgenic mice.
Animals↗
Prophylaxis against a Melanesian variant of human T-lymphotropic virus type I (HTLV-I) in rabbits using HTLV-I immune globulin from asymptomatically infected Japanese carriers.
Molecular variants of human T-lymphotropic virus type I (HTLV-I), which diverge significantly from the so-called cosmopolitan prototypes, have been discovered in Melanesia. In this study, HTLV-I IgG (I-IgG) prepared from seropositive healthy Japanese carriers was evaluated for its protective effect against a Melanesian isolate, HTLV-IMEL5, in rabbits. Normal IgG (N-IgG) prepared from seronegative healthy Japanese was used as control. Both preparations contained 50 mg/mL of IgG and I-IgG had a high neutralizing antibody titer, as determined by vesicular stomatitis virus--HTLV-I pseudotype assay. Of four experimental groups (A, B, C, and D), each with three rabbits, groups A and B were infused with 10 mL of N-IgG and I-IgG, respectively, and animals were challenged immediately by transfusion of 5 mL of blood from a rabbit infected with HTLV-IMEL5. Animals in groups C and D were immunized with 10 mL of I-IgG 24 and 48 hours, respectively, after being transfused with 5 mL of blood from the virus-infected rabbit. HTLV-I infection, as determined by seroconversion and verified by polymerase chain reaction, occurred in all rabbits in groups A and D after 2 to 6 weeks, but in none of the animals in groups B and C. These data indicate that I-IgG is protective against HTLV-IMEL5 infection when administered before or within 24 hours of transfusion with virus-contaminated blood. Moreover, our study shows that the neutralizing domains of the so-called cosmopolitan and Melanesian strains of HTLV-I are functionally indistinguishable.
Animals↗
Enzyme-linked immunoglobulin which binds both lactate dehydrogenase and hydroxybutyric dehydrogenase.
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Adolescent↗
High level expression of human alpha-fetoprotein in transgenic mice.
Transgenic mice were produced by the microinjection of the cDNA of human alpha-fetoprotein (AFP) under control of the enhancer/promoter of the human beta-actin gene. Among the 4 mouse lines where the transgene were stable transmitted to the progeny, 3 produced human AFP. The expression was not developmental stage-specific nor tissue-specific as predicted from the properties of enhancer/promoter. The serum human AFP levels of adult mice were 30-600-fold higher than those of mouse AFP. These mice could be useful for the studies of possible biological functions of AFP during development as well as in malignancies.
Actins↗
Phenotypic and molecular analysis of Ph1-chromosome-positive acute lymphoblastic leukemia cell lines.
We have established 2 Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) cell lines, designated PALL-1 and PALL-2, from distinct adult Ph1-positive ALL patients. PALL-1 was established in nude mice, and PALL-2 was established in culture. Both retained the Ph1 chromosome and expressed the ALL type bcr/abl chimeric mRNA containing the junction of the first exon of BCR gene (e1) and second exon of c-abl gene (a2). PALL-1 and PALL-2 expressed CD34 surface antigen which is characteristic of early hematopoietic progenitor cells. PALL-2 expressed antigens for both pre-B and early myeloid cells and had rearrangements of both the heavy chain of immunoglobulin gene and the beta chain of T-cell-receptor gene. Both PALL-1 and PALL-2 expressed detectable levels of p53 gene RNA. Polymerase-chain-reaction-single-strand conformation polymorphism (PCR-SSCP) analysis of the p53 gene showed a normal pattern of mobility in both cell lines. Taken together, the 2 cell lines had features of Ph1-positive ALL: (i) hematopoietic progenitor cells with pre-B-cell phenotype and, (ii) activation of e1-a2 type bcr/abl oncogene without alterations of p53 gene. These unique lines should provide a valuable tool for studying the pathogenesis of Ph1-positive ALL.
Adult↗
Central nervous system involvement of adult T-cell leukemia-lymphoma with multinucleated giant cells in the brain, skin, and kidney.
BACKGROUND: A case of central nervous system (CNS) involvement in a patient with adult T-cell leukemia-lymphoma (ATLL) with multinucleated giant cells (MNGC) is presented. METHODS: A 48-year-old woman with human T-lymphotropic virus type I (HTLV-I) antibody titer had multiple focal brain symptoms and skin eruptions without lymphadenopathy, hepatosplenomegaly, or increased abnormal lymphocytes in the peripheral blood. No spastic paraparesis of the lower limbs was found. The encephalopathy was progressive, and she died 5 months later despite repeated intrathecal administration of methotrexate, cytosine arabinoside, and prednisolone and monthly systemic chemotherapy with doxorubicin, cyclophosphamide, vincristine, and prednisolone. RESULTS: Postmortem examinations identified unusual ATLL lesions composed of marked infiltrations of atypical mononuclear cells and bizarre MNGC with histiocytic granulomatous reactions in the leptomeninges, brain tissues along the Virchow-Robin spaces, skin, and kidney. Immunohistochemical stains confirmed the T-cell nature of such mononuclear cells and partially T-cell and partially macrophage nature of the MNGC, although no evidence of HTLV-I expression was found. CONCLUSIONS: ATLL presenting with CNS symptoms is rare. It was assumed that the direct cytopathic effects of HTLV-I were responsible for the formation of the MNGC after considering the similarity with MNGC in encephalopathy caused by the human immunodeficiency virus.
Brain↗
Functional conservation of the neutralizing domains on the external envelope glycoprotein of cosmopolitan and melanesian strains of human T cell leukemia/lymphoma virus type I.
To determine if the immunodominant neutralizing epitopes on the external envelope glycoprotein of the recently identified sequence variants of human T cell leukemia/lymphoma virus type I (HTLV-I) from Melanesia are functionally conserved, sera from Japanese patients with adult T cell leukemia and from HTLV-I-infected Melanesians of Papua New Guinea and the Solomon Islands were tested for neutralizing antibodies by use of vesicular stomatitis virus pseudotypes bearing envelope antigens of Japanese and Melanesian HTLV-I strains. Neutralizing antibody titers of the Japanese and Melanesian sera and of monoclonal and polyclonal antibodies directed against a known neutralizing epitope on the external envelope glycoprotein of HTLV-I were equivalent against the Japanese and Melanesian HTLV-I pseudotypes. The demonstrated two-way cross-neutralization between Japanese and Melanesian strains of HTLV-I indicates that their antigenic determinants for neutralization are functionally indistinguishable and that HTLV-I exists as a single serotype worldwide.
Amino Acid Sequence↗
Ganglioside distribution in the liver of inbred strains of rats and the cancerous liver of LEC rats.
The gangliosides in the livers of various inbred strains of rats and hepatoma of LEC rats were purified and analyzed by thin-layer chromatography. The patterns of ganglioside distribution in these rat livers were classified into three phenotypes depending on the strain, that is, a-type (ACI, LEA, LEW, BUF), b-type (WKAH, SHR/SP), and LEC type, which are characterized by dominance of a- or b-series of gangliosides, or a variation of a-type, respectively. A sex difference was also recognized in the molar ratio of GM3 which was much higher in males (60-75%) than in females (33-56%) except in LEC rats. In addition, the content of a-series gangliosides was lower and the content of b-series gangliosides was higher in a-type male rats than in a-type female rats. The opposite was true in b-type rats. LEC rats were an exception, characterized by no sex difference and a quite low content of b-series gangliosides. The LEC rat is a mutant strain that spontaneously develops fulminant hepatitis around 14 to 20 weeks of age and hepatoma at 1 to 1.5 years old. The gangliosides of the hepatoma were characterized by the appearance of the newly synthesized gangliosides, fucosyl-GM1 and alpha-galactosyl alpha-fucosyl GM1 (BGM1). In particular, BGM1 ganglioside accumulated in the hepatoma of female rats.
Animals↗
Aberrant expression of the p53 tumor suppressor gene in adult T-cell leukemia and HTLV-I-infected cells.
By immunoprecipitation analysis, enhanced p53 expression was detected in 3 of 4 adult T-cell leukemia (ATL) cell lines, 1 of 3 HTLV-I-infected cell lines and 1 of 5 fresh ATL samples, compared with phytohemagglutinin-stimulated peripheral blood lymphocytes. Among these 5 high expressers, p53 missense mutations were indicated in 2 ATL cell lines and 1 fresh ATL sample by extensive p53 cDNA and genomic DNA polymerase chain reaction single-strand conformation polymorphism analysis. No mutation was found throughout the entire coding region of the remaining 2 high expressers (1 ATL and 1 HTLV-I-infected cell lines) and low expressers of p53 (2 HTLV-I-infected cell lines). Tax oncoprotein expression was found in these 2 high p53 expressers in which p53 mutation was not present, but not in low p53 expressers or cells carrying this mutation. The levels of p53 mRNA were similar among the samples regardless of p53 levels. Posttranscriptional mechanisms other than missense mutation would thus appear to increase p53 in the Tax-expressing cells but not in cells containing undetectable levels of Tax. No complex formation between p53 and Tax was observed.
Adult↗
Neutralizing antibody to vesicular stomatitis virus (HTLV-I) pseudotype in infants born to seropositive mothers.
Breast feeding is the major route of mother-to-child transmission of human T-cell leukemia virus type I (HTLV-I). Our experiments with rabbits have shown that passive immunization is capable of blocking cell-to-cell infection of HTLV-I by blood transfusion or breast feeding. In this study, sera were collected serially from 3 infants born to seropositive mothers and were tested for the presence of neutralizing antibody to vesicular stomatitis virus (HTLV-I) pseudotype as well as antibodies to viral structural proteins. There was a good correlation between neutralizing and viral antibody titers, both of which were detectable until 3-6 months after birth. Whether maternally transmitted neutralizing antibody is protective against perinatal infection of HTLV-I remains to be studied.
Adult↗
Transgenic mice with antisense RNA against the nucleocapsid protein mRNA of mouse hepatitis virus.
In this study transgenic mice which expressed antisense RNA against the nucleocapsid protein gene of mouse hepatitis virus (MHV) under the control of RSV LTR were produced. These transgenic mice were able to transmit the foreign gene to their progeny in a Mendelian fashion. Antisense RNA was detected in various tissues from the transgenic mice including liver and brain, the target organs of MHV infection. One strain of transgenic mice derived from founder mouse No. 19 was more resistant to the lethal challenge of MHV than non-transgenic mice. The results of the present study show the ability of antisense RNA against the viral gene to protect against viral infection in vivo.
Animals↗
Bloom's syndrome complicated by myelodysplastic syndrome and multiple neoplasia.
The patient, a Japanese male born to a highly consanguineous family, was diagnosed as Bloom's syndrome at the age of 33 when he presented with diabetes mellitus and refractory anemia with excess blasts. Chromosome abnormalities of bone marrow cells included 5q-, -7/7q-, and unusual translocations. During the ensuing years, he developed squamous cell carcinoma of the external auditory meatus, adenocarcinoma of the colon, and squamous cell carcinoma of the tonsil. The patient died of pneumonia at the age of 38. Autopsy revealed intestinal polyposis and hemochromatosis secondary to massive blood transfusions.
Adult↗