[Diversion colitis and proctitis].
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Biomedical subjects
Publications and source records attributed to K Toriya.
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We describe 4 cases of adult T-cell leukemia (ATL) with unusual morphology and aberrant immunophenotype. All patients were Japanese and born in the Nagasaki district, an area endemic for HTLV-I. Peripheral blood and/or bone marrow films revealed bizarre giant cells with and without large nucleoli; the cells were 5 to 6 times the diameter of erythrocytes, resembling Hodgkin's cells. Some peripheral blood cells were morphologically similar to prototypic ATL cells, while many other cells in the bone marrow showed unusual morphology. Furthermore, leukemic cells had aberrant immunophenotypes such as the CD8-positive type in patients 1 and 2, the CD4-.CD8- double-negative type in patient 3, and the CD5 antigen defect in patient 4. All patients had marked elevations of the serum calcium and LDH and organomegaly, while all had a short survival. Anti-HTLV-I antibodies and provirus DNA monoclonality were demonstrated in all patients. The results suggested that the unusual morphology and aberrant ATL cell immunophenotype may be indicative of a high grade malignant behaviour of ATL.
We examined phenotypically 107 patients with adult T-cell leukemia (ATL), using a panel of monoclonal antibodies, in order to clarify the occurrence of aberrant phenotypes, and to determine the correlation between phenotypic diversity and prognosis. The incidence of the typical (CD4+.CD8-) phenotype, the double-negative (CD4-.CD8-), the double-positive (CD4+.CD8+), and the CD8-positive (CD4-.CD8+) phenotypes was 81%, 7%, 7%, and 4%, respectively. The median survival time (MST) for all patients was 10.0 months with 17% survival at 2 years. The patients with typical phenotypes had a 10.2 month MST with 20% survival at 2 years, significantly better than the patients with the unusual phenotypes whose MST were 4.9, 7.8, and 2.6 months, respectively, for the double-negative, double-positive, and CD8-positive phenotypes. Lack of antigens reactive with CD2, CD3, CD5, and WT31 monoclonal antibody panels was one factor in bad prognosis, but the presence of CD4 and CD8 antigen abnormalities was much more significant.
Particle agglutination (PA; Serodia-ATLA) and ELISA (Ei-test ATL) assays have been used as routine anti-HTLV-I antibody detection in Japan. However, inconsistent results were obtained by the above methods. We wished to develop criteria for serological confirmation of HTLV-I infection in Hospital samples. Sera obtained in our Hospital from October, 1988 to September, 1989 were tested by five methods of PA (Serodia-ATLA), new PA (improved on the PA; Serodia.HTLV-I), ELISA-I (coated by HTLV-I infected cell lysates as antigens; Ei-test ATL), ELISA-II (coated by recombinant gag-env hybrid proteins as antigens) and IF. The HTLV-I seropositive rates using five methods were not different, ranged from 29.7 to 32.3% in 155 sera. However, PA assays appeared more false positive and rare false negative in some high titer sera. 13 sera as demonstrated negative for ELISA-I and positive for PA (ELISA-I(-)/PA(+] were reevaluated. As results, the antibody were confirmed in only 3 by new PA, 1 by ELISA-II and 2 cases by IF, respectively. On the other hand, 2 by new PA, 4 by ELISA-II and 2 by IF in 18 sera with ELISA-I(+)/PA(-) were interpreted as positive. Therefore, new PA is a remarkable improvement on the PA current model.
We investigated antibodies against pX gene product, p40tax, by ELISA using recombinant p40tax protein in HTLV-I seropositive carriers as well as patients with adult T cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM). Seventy (49.0%) out of 143 HTLV-I healthy carriers were found to be positive for antibody against p40tax antigen and the follow-up samples at two-year intervals revealed constant reactivity by ELISA in each carrier. The onset of antibody production was delayed 4 to 12 weeks as compared with anti-HTLV-I in primary infection cases. The anti-p40tax-positive rate (90%) in HAM patients was significantly higher than that of healthy carriers, acute and chronic ATL patients and their family members. Furthermore, HAM patients and a few healthy carriers showed high reactivities by ELISA. Children from mothers with anti-p40tax showed a higher anti-HTLV-I-positive rate than that of children from mothers without anti-p40tax (54.5% versus 12.5%). Two men without anti-p40tax and one female with low anti-p40tax developed ATL during follow-up studies. These results suggest that HTLV-I carriers could be divided into 2 or 3 sub-populations according to antibody response to p40tax. A smaller population with anti-p40tax, especially a high antibody reactivity, could have a high risk of developing HAM and of transmission from mother to child. In addition, ATL may occur in a population with low or absent anti-p40tax.
Combination of aztreonam/amikacin/ticarcillin (AAT) and latamoxef/amikacin/ticarcillin (LAT) were compared in a prospective randomized trial of empiric therapy for febrile neutropenic patients with hematological malignancies. Low dose amphotericin B was also added to each regimen from the beginning. Of 45 evaluable episodes, 23 were treated with AAT and 22 with LAT. The response rates were 61 percent for AAT and 50 percent for LAT, statistically not significant. There was one infection-related death among patients assigned to AAT therapy and also one among those assigned to LAT therapy. Dose escalation of amphotericin B seemed to be effective for those patients who did not improve with initial therapy.
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Diagnosis of thyroid cancer has been based mainly on palpation and also soft X-rays because of its calcification. As the gland itself is very small and Aspiration Biopsy Cytology (ABC) has had a high level of diagnostic accuracy the clinical significance of ultrasonography did not become apparent for a long time. However, recently it has become possible to carry out detailed study and to detect suspect histological structures, following the remarkable progress which has been made in ultrasonography, using a high-frequency piezoelectric transducer. A single mechanical arch scanner, with a piezoelectric 7.5-MHz transducer (SAL-25A Toshiba Corp.) was employed for examination using the water bath method. The rates of correct diagnosis for each of the above methods among 847 nodular goiters including 184 malignant tumors which were microscopically examined were shown to be: ultrasonography 89.7%, soft X-rays 66.9% and ABC 86.4%. Ultrasonography was capable to revealing a few cases which could not be shown by ABC or soft X-rays. Using these three methods jointly, there was 1 false positive and no false negative cases. This study revealed that combined diagnosis with ultrasonography using a high-frequency piezoelectric transducer improved the accuracy of examination of malignant thyroid tumors.
We report phenotypic and functional characterization of lymph node cells from 27 patients with T lymphoma from the Nagasaki district of Japan. Nagasaki is one of several areas where adult T-cell leukemia is endemic, and sera from 18 of 23 patients examined (78.3%) were positive for antibody to adult T-cell leukemia-associated antigen. The majority of cases (24 of 27) showed the Leu-2a-, 3a+, MASO36c- phenotype similar to adult T-cell leukemia, but seemed to be subdivided into four groups according to the presence or absence of Leu-1 antigen and the receptor for sheep erythrocytes (SRBC). Eleven cases had both Leu-1 antigen and the receptor for SRBC (E-RFC+, Leu-1+, 2a-, 3a+), but 6 cases lacked Leu-1 antigen (E-RFC+, Leu-1-, 2a-, 3a+), 4 cases lacked receptors for SRBC (E-RFC-, Leu-1+, 2a-, 3a+), and 3 cases lacked both of these markers (E-RFC-, Leu-1-, 2a-, 3a+). The effects of lymph node T cells on pokeweed mitogen (PWM)-induced normal B-cell differentiation was studied in 10 cases. Lymph node T cells of 5 cases showed helper activity without any suppressor activity, and 2 cases showed suppressor activity with almost no detectable helper activity, similar to adult T-cell leukemia cells. Two other cases lacked particular functional effects. These results suggest the possibility that Leu-3a+ T-cell lymphoma may be functionally subdivided into at least two types, a helper type and a suppressor (adult T-cell leukemia) type.
We report the clinical, hematologic, and immunologic features of 18 preleukemic adult T cell leukemia (pre-ATL) cases with abnormal T lymphocytosis induced by human adult T cell leukemia-lymphoma virus (HTLV/ATLV). The patients were from the Nagasaki district, which is one of the most endemic areas of ATL in Japan. Pre-ATL is a subclinical T cell abnormality differing from ATL. It is characterized by an insidious onset and appearance of abnormal T lymphocytes (10% to 40%) in the peripheral blood without clinical symptoms except for a few cases transiently presenting fever, skin eruptions, and slight lymphadenopathies. Most abnormal T lymphocytes were small and mature with incised or lobulated nuclei and formed E rosettes with sheep RBCs. Virologic and biomolecular analysis revealed that all cases were infected with HTLV, and proviral DNA was integrated in host lymphocytes from 12 of the 14 cases examined. Furthermore, the lymphocyte populations, including abnormal T lymphocytes, were monoclonal with respect to the site of the provirus integration. Abnormal T lymphocytosis persisted from one to more than seven years in six cases, three of which developed ATL after a one- to five-year pre-ATL stage, whereas abnormal T lymphocytes spontaneously decreased in the other seven patients. However, HTLV-infected monoclonal lymphocytes were detected in four cases examined, even after most of the abnormal T lymphocytes had disappeared. Moreover, the same clonally provirus-integrated lymphocytes persisted in two of four cases not only during the course of abnormal lymphocytosis, but also in the subsequent almost-normal blood. These results indicate that the majority of the cases were in a pre-ATL state with a potential to develop ATL.
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The expression of adult T-cell leukemia virus (ATLV/HTLV) antigen was demonstrated by the indirect immunofluorescence method in phytohemagglutinin-cultured mononuclear cells of milk samples from 3 out of 22 sero-positive mothers after delivery. This result raises the possibility that milk might be the source of ATLV/HTLV infection of infants.
Surface phenotypes of leukemic cells from six patients with adult T cell leukemia (ATL) were analyzed by the use of monoclonal antibodies, both at the time of initial diagnosis and at either relapse or exacerbation phase after chemotherapy. Changes of cell surface antigens were observed in four of the six cases. The majority of the leukemic cells of these patients were reactive with anti-Leu-1 and anti-Leu-3a, but unreactive with anti-Leu-2a and MAS 036c monoclonal antibodies at the time of initial diagnosis, indicating that ATL cells are of peripheral inducer/helper T cell origin. In three cases, the Leu-1 antigen disappeared at relapse or at exacerbation phase, and in one of these cases, a small percentage of ATL cells became reactive with MAS 036c, which identifies cortical thymocyte antigen. ATL cells of one other case did not have Leu-1 antigen from the start, but gained Leu-2a antigen at exacerbation phase and became double-labeled cells (Leu-2a+, 3a+), which is known to be a feature of thymocytes. Thus, it appeared that ATL cells sometimes change their surface phenotype to that of an earlier stage of T cell differentiation at relapse or at exacerbation phase. Chronic myelocytic leukemia (CML) cells also usually change to immature cells at blastic crisis involving morphological change. However, this morphological change was not so prominent in the ATL cases studied, except one, in which typical ATL cells with nuclear indentation changed to large immature cells with basophilic cytoplasm at relapse.