Search PubMed⌕ Search

Biomedical subjects

I Miyoshi

Publications and source records attributed to I Miyoshi.

At least 181 records · Page 10Linked to original sources

Secretion of parathyroid hormone-like activity from human T-cell lymphotropic virus type I-infected lymphocytes.

Because many patients with adult T-cell leukemia/lymphoma (ATLL) develop hypercalcemia with similar characteristics to those of humoral hypercalcemia of malignancy (HHM) (Arch. Intern. Med., 148: 921-925, 1988), we investigated if ATLL cells produce parathyroid hormone (PTH)-like activity. Conditioned media from cultures of human T-cell lymphotropic virus type I-infected cell line (MT-2) as well as peripheral lymphocytes from a hypercalcemic ATLL patient stimulated cyclic AMP production in osteoblast-like rat osteogenic sarcoma cells (UMR 106) and bone resportion in organ cultures of fetal mouse calvaria. Furthermore, the stimulation of cyclic AMP production by conditioned medium of MT-2 cells was inhibited by human PTH(3-34), indicating that MT-2 cells secrete PTH-like activity. The PTH-like activity from MT-2 cells was chromatographically indistinguishable from the one extracted from a solid tumor causing HHM. The present results along with our previous observation that MT-2 cells constitutively express mRNA for PTH-related protein (Biochem. Biophys. Res. Commun., 154: 1182-1188, 1988) demonstrate that a PTH-like activity is synthesized and secreted by these cells, and are consistent with the hypothesis that elaboration of PTH-like activity by ATLL cells may be the mechanism by which hypercalcemia develops in ATLL patients as well as in solid cancer patients with HHM. However, these results do not rule out the possibility that other factors such as interleukin 1 are also involved and may act in concert with PTH-like activity in the development of hypercalcemia in ATLL.

Adult↗

Direct and serial transplantation of Ph1-positive acute lymphoblastic leukemia into nude mice.

A new Philadelphia chromosome (Ph1-positive) acute lymphoblastic leukemia (ALL) cell line was established in nude mice by direct and serial transplantation of peripheral blood leukemia cells from an adult patient. Although the patient's leukemia cells did not grow in vitro, they were successfully transplanted for 8 serial passages, giving rise to progressive growth of tumors with frequent involvement of lymph nodes, liver, spleen, bone marrow, and meninges. The tumor cells could also be passaged in an ascites form. This in vivo cell line, designated PALL-I, retained the Ph1 chromosome, t(9;22) (q34;q11), and pre-B-cell phenotype (SmIg-, CpIg-, CD10+, CD19+, OKIaI+, and CD38+), like the original leukemia cells. Molecular genetic analysis of PALL-I cells revealed neither bcr rearrangement nor 8.5-kb abI-related mRNA that is characteristically seen in Ph1-positive chronic myelogenous leukemia (CML). Thus, the PALL-I cell line is genetically distinct from CML. It may provide a useful model for an understanding of the cellular and molecular biology of Ph1-positive ALL without classical bcr rearrangement.

Acute Disease↗

Antibody reactivity to different regions of human T-cell leukemia virus type 1 gp61 in infected people.

The primary protein product of the human T-cell leukemia virus type 1 (HTLV-1) env gene, gp61, is cleaved to produce both the exterior (gp46) and the transmembrane (gp21) portions of the HTLV-1 envelope protein. To compare the reactivity with human antibodies of different regions of this gp61 protein, five plasmids (A, B, B1, C, and D) were constructed to express recombinant proteins (RPs) in Escherichia coli. RP-A, RP-B, RP-B1, and RP-C contain amino acid residues 26 to 165, 166 to 229, 166 to 201, and 229 to 308, respectively, of the exterior envelope protein gp46. Serum samples from HTLV-1-seropositive subjects were assayed for reactivity with these RPs by Western immunoblotting. The percentages of positive reactivity with each of the RPs were as follows: 18.9% (23 of 122) for RP-A, 89.6% (112 of 125) for RP-B, 70.2% (85 of 121) for RP-B1, and 92.9% (117 of 126) for RP-C. These results indicate that the C-terminal half of gp46 (RP-B plus RP-C) can detect 97.6% (123 of 126) of positive samples, while the N-terminal half of gp46 (RP-A) can only detect 18.9% of the HTLV-1-positive sera (P less than 0.005). Furthermore, RP-A, -B, and -C, which together span the entire length of gp46 except the first five amino acids at the N terminus and the last four amino acids at the C- terminus, detected 99.2% (125 of 126) of the HTLV-1-positive subjects. In contrast, RP-D, which contains the HTLV-1 transmembrane envelope protein gp21 minus the first amino acid at the N terminus, had a lower rate of antibody reactivity at 73.7% (84 of 114) (P less than 0.005). The difference in seropositive rates for RP-D between HTLV-1 carriers (55.6%) and adult T-cell leukemia patients (85.5%) is statistically significant (P less than 0.01). This study therefore indicates that the C-terminal half of gp46, especially the amino acid sequence from 200 to 308, contains the most reactive epitopes of the HTLV-1 gp61 envelope glycoprotein.

Antigen-Antibody Reactions↗

Immune suppression in HTLV-I carriers: a predictive sign of adult T-cell leukemia.

Suppression of the cellular immune system appears to be a prerequisite for the manifestation of adult T-cell leukemia (ATL). In other words, ATL will develop when impairment of the immune system is caused by the infection of human T-lymphotropic virus type I (HTLV-I). This defect of immune surveillance against virus-infected cells may be a result of the impairment of the function of cytotoxic T-cells (CTLs) specific for the HTLV-I-infected cells. The manifestation of ATL could be predicted by examining the function of CTLs in HTLV-I carriers. A new strategy of prevention and therapy for ATL would include an attempt to restore and fortify the CTL function of the host.

HTLV-I Infections↗

[Seizure and tremor occurring in acute leukemia patients treated with imipenem/cilastatin].

We report here four patients with acute leukemia, who developed seizure or tremor following treatment with imipenem, a new broad-spectrum antibiotic. All four patients had no renal dysfunction and recovered after discontinuation of the drug. Two patients who developed seizure had a past history of cerebral hemorrhage with symptoms of meningitis in one and the other had received frequent intrathecal injections of methotrexate. Seizure also occurred in another patient who was given multiple intrathecal injections of methotrexate. The remaining old patient developed tremor after the first administration of imipenem which did not progress to convulsion. Cerebral hemorrhage or meningitis is known to predispose patients for convulsion following imipenem treatment. In addition, the present study suggests that central nervous system damage related with intrathecal injections of methotrexate may be a predisposing factor. Thus, imipenem should be given with caution to acute leukemia patients who often have risk factors for developing imipenem-related complications.

Acute Disease↗

Generalized lymph node metastasis of early uterine cancer in an HTLV-I carrier.

Generalized lymphadenopathy due to metastases of keratinizing squamous cell carcinoma developed in a 68-year-old woman who was a carrier of human T-cell leukemia Type I (HTLV-I). On her 74th hospital day, she died of massive metastases of the superficial and deep-seated lymph nodes, thyroid, lungs, pleura, liver, spleen, pancreas, kidneys, and retroperitoneum. At autopsy, the primary tumor was found in the uterine cervix. The depth of stromal invasion was approximately 4.0 mm. Such an extensive dissemination usually does not occur in cervical cancer with this type of early stromal invasion. It is conceivable that the chronic HTLV-I infection compromised the immunosurveillance against cancer and accelerated progression of the disease in this patient.

Carrier State↗

DNA blotting analysis of human retroviruses in cerebrospinal fluid of spastic paraparesis patients: the viruses are identical to human T-cell leukemia virus type-1 (HTLV-1).

The structure of the integrated provirus in cell lines established from the cerebrospinal fluid (CSF) of patients with human T-cell leukemia virus type-1 (HTLV-1)-associated myelopathy (HAM) was analyzed. The digestion patterns with 3 restriction endonucleases, Sac I, Eco RI and PstI, of the proviruses integrated in T-lymphoid cell lines derived from the CSF of 4 HAM patients were similar to those of HTLV-1 from adult T-cell leukemia (ATL) patients. Integrated proviruses in one of these cell lines derived from the CSF were further analyzed in detail with 2 more restriction enzymes, BamHI and Sma I. The results indicate that the retrovirus found in lymphocytes of the CSF from patients with HAM are very similar, if not identical, to HTLV-1 found in the leukemic lymphocytes of ATL patients.

Cell Line↗

Serial transplantation of an HTLV-I-transformed hamster lymphoid cell line into hamsters.

A hamster lymphoid cell line, HCT-2, transformed by human T-cell leukemia virus type I (HTLV-I) was serially transplanted for 9 passages in newborn hamsters. A total of 34 newborn hamsters inoculated intraperitoneally (i.p.) with 0.2-2 X 10(7) HCT-2 cells developed fatal lymphomas with dissemination to various organs within 5-10 days. The growth of i.p. inoculated HCT-2 cells was found to be dependent on the age of recipients: all 21 suckling hamsters inoculated when aged 5-10 days succumbed to disseminated lymphomas within 6-7 days, while 4 of 12 older hamsters inoculated at the age of 15-25 days developed less extensive disease with signs of tumor regression. To investigate the effect of immunosuppression on host resistance, 3 adult hamsters treated with anti-thymocyte serum were inoculated i.v. with 2-4 X 10(7) HCT-2 cells; all 3 developed fatal leukemias in 5-7 days. Irrespective of whether HCT-2 cells were inoculated into newborn, suckling, or adult hamsters, histopathological findings were similar, with frequent involvement of liver, spleen, lungs, kidneys, lymph nodes, blood, and bone marrow. Cells harvested from tumors and peripheral blood of some tumor-bearing hamsters could be readily recultured as cell lines. Chromosome analysis and Southern blot hybridization showed that tumors were caused by growth of HCT-2 cells.

Age Factors↗

Application of a monoclonal antibody for the detection of Trichosporon beigelii in paraffin-embedded tissue sections.

Trichosporon beigelii is a normal inhabitant of soil and is occasionally found as normal flora of the skin and mouth. Opportunistic infection by this fungus has been increasingly reported in immunocompromised patients. The diagnosis of this infection depends on positive cultures or histological evidence. However, it is sometimes difficult to distinguish this fungus from Candida species in tissue section. We have generated two monoclonal antibodies that can distinguish T. beigelii from other fungi including several species of Candida. One of these antibodies (K-16) reacts with T. beigelii in formalin-fixed, paraffin-embedded tissue sections and will be useful as an aid to the accurate diagnosis of trichosporonosis.

Antibodies, Fungal↗

Immunocytochemical and ultrastructural characterization of human T-lymphotropic virus type I (HTLV-I)-producing rabbit lymphoid cell lines.

Fine structural and immunocytochemical characterization of rabbit lymphoid cell lines transformed by human T-lymphotropic virus type I (HTLV-I) was carried out. All nine cell lines tested were reactive with anti-HTLV-I-positive human, monkey, and rabbit sera and monoclonal antibody to HTLV-Ip 19, but not with anti-HTLV-I-negative sera and monoclonal antibodies to human Ia and pan-T antigens. All cell lines were strongly positive for monoclonal antibodies to rabbit Ia and pan-T antigens. Ultrastructurally, each cell line contained C-type virus particles in varying numbers in the extracellular space. These particles showed replication patterns similar to those in HTLV-I or simian T-lymphotropic virus type I (STLV-I)-producing human or monkey cells. In addition, anti-HTLV-I-positive rabbit serum gave positive immunoreactivity to HTLV-I or STLV-I by indirect immunoferritin method. These results indicate that the ultramorphology and replication patterns of HTLV-I in rabbit cell lines are indistinguishable from those of HTLV-I in human and monkey cell lines, HTLV-I in rabbit cells shares the common surface antigenic determinants with HTLV-I or STLV-I in human or monkey cells, and that these cells are definitely rabbit T cells bearing their own Ia antigens.

Animals↗

Milk-borne transmission of human T-cell leukemia virus type I in rabbits.

The mode of vertical transmission of human T-cell leukemia virus type I (HTLV-I) was investigated by foster-nursing in rabbits. Two of five rabbits born to noninfected mothers and fostered by virus-infected females seroconverted for HTLV-I after 7 weeks, whereas all seven rabbits born to virus-infected mothers and fostered by noninfected females remained seronegative for the observation period of 6 months. Culture of peripheral blood lymphocytes gave rise to an HTLV-I-carrying T-cell line from each of the two seroconverted rabbits. These findings suggest that HTLV-I is transmitted through milk from mother to offspring.

Animals↗

Trisomy 4 in a case of acute nonlymphocytic leukemia (M2).

Trisomy 4 in a Japanese patient with type M2 acute nonlymphocytic leukemia is reported. Karyotypic analysis was unsuccessful at diagnosis and complete remission lasted 4 years. The cytogenetic change was detected in the first and second relapses as the only chromosome abnormality. Unusual nuclear irregularities were found in many leukemic cells.

Acute Disease↗