A spontaneous complete remission was observed in a 47-year-old female with acute monocytic leukemia. Resolution of all abnormalities, including systemic papule, thrombocytopenia, increased numbers of immature monocytoid cells in the peripheral blood and bone marrow, elevation of serum lysozyme and LDH, and trisomy 8 on chromosome analysis, occurred without any treatment. Moreover, the remission was not associated with any infection or blood transfusion, and is persistent for 12-month duration.

A case of acute megakaryoblastic leukemia with complex chromosomal aberrations is reported. A 63-year-old man was admitted to our hospital because of pancytopenia. Bone marrow aspiration resulted in a dry tap and biopsy showed hypoplastic marrow with fibrosis. Blast cells in the peripheral blood were identified as megakaryoblasts because they were positive for electron microscopic platelet peroxidase (PPO). In addition, monoclonal antibody, TP80, to platelet glycoprotein II b-III a reacted with in about 26% of the blast cells. Chromosomal analysis of the peripheral blood revealed a mosaic pattern of a normal karyotype and abnormal ones, including 44, XY, -5, -7, -18, 10q-, +marker.

Cytophotometric DNA analyses were performed on 35 primary esophageal cancer. Histograms of DNA measurement were classified into three patterns (diploid pattern, aneuploid pattern and mosaic pattern) and were compared with histological findings, prognosis, and degree of lymphocytes infiltration around the tumor. Survival rate was worse in patients with mosaic pattern than the others, and 4-year survival rates of each patterns were 66.7% (diploid), 53.6% (aneuploid) and 25.4% (mosaic). Diploid cell line was observed frequently in the superficial cancers, and as the cancers infiltrated more deeply, mosaic cell line increased. Mosaic cell line appeared more frequently in well differentiated squamous cell carcinomas. In patients with mosaic pattern, there was high frequency of lymphnode metastasis and vascular invasion, as compared with diploid pattern. The rate of vascular invasion tended to increase in the following order; diploid, aneuploid and mosaic types. Furthermore in the diploid tumors, the degree of lymphocyte infiltration around tumor tended to increase. These findings suggest that the change of DNA content may occur frequently during tumor progression and may be affected by tumor infiltrating lymphocytes. So the DNA ploid pattern will be also to be one of the conjecturable factors of the prognosis of esophageal cancer.

A 41-year-old woman was hospitalized for evaluation of diabetes mellitus and hypertension. The hormonal and radiological examinations revealed that she had pheochromocytoma of bilateral adrenal gland and medullary carcinoma of thyroid gland. Therefore, she was diagnosed as having Sipple's syndrome. She had no definite familial history, but her two sisters, already dead, had been strongly suspected of having had pheochromocytoma. First, bilateral adrenalectomy was performed and secondly, total thyroidectomy, excision of parathyroid and cervical lymph node dissection were performed. Histopathological diagnosis was pheochromocytoma of bilateral adrenal gland, medullary carcinoma of thyroid gland and chief cell hyperplasia of parathyroid gland. We report a case of Sipple's syndrome, which probably is the 88th case in Japan, with the review of the previous Japanese literature.

A 33-year-old female was diagnosed as having chronic myelocytic leukemia (CML) with Philadelphia (Ph1) chromosome and breakpoint cluster region (bcr) rearrangement. Physical examination revealed a huge splenomegaly and laboratory data showed WBC 490 x 10(3)/microliter and NAP score 44. She was treated with hydroxyurea, alpha-interferon, or busulfan, but severe adverse reaction such as skin rash, fever, and arthralgia, which allowed the therapy discontinue was occurred. When the patient was treated with the oral form of etoposide, a semisynthetic podophillotoxin, the number of leukocyte has been successfully maintained less than 10 x 10(3)/microliters at the dose of 50-100 mg/day and splenomegaly completely disappeared. Although Ph1 chromosome was unchanged in the percentage after the therapy for 5 months, etoposide may be effective agent for a chronic or accelerated phase of CML. Alopecia which was reversible and well tolerable was the only side effect of the drug.

A 28-year-old male was admitted to our hospital because of hepatosplenomegaly and granular lymphocytosis. His peripheral leukocyte count was 3,000/microliters with 43% of granular lymphocytes (GL). These GLs were immunologically phenotyped as CD2+CD3-CD4-CD8-CD16+CD56+HLA-DR+ and were found that TcR genes coding beta and gamma chains were not rearranged. Chromosomal analysis of his GLs stimulated with IL-2 showed 47 XY, +8. This patient was diagnosed as a granular lymphocyte leukemia of natural killer cell type. Blood chemistry showed elevation of serum GOT, GPT and LDH values. The fever persisted until administration of prednisolone was initiated. But 40 days after, high fever appeared again and the liver and spleen were extremely enlarged. Combined chemotherapy was then started but resulted in no effects. He died of hepatic failure on the 77th day from admission. 47 XY, +8, that has been reported in acute non-lymphocytic leukemia and myelodysplastic syndrome, may be related to the pathogenesis in some cases of granular lymphocyte leukemia.

It is an issue for debate why molar tissues are not rejected by an immunologically potent host, since all genes in complete moles and 2/3 genes in partial moles are considered to be paternally derived. Molar trophoblasts are in direct contact with host cells, and therefore HLA expression by these cells may hold the key to the elucidation of the immunological reaction between molar tissues and the host. It has been reported that villous trophoblasts are negative and extravillous trophoblasts are positive for HLA-A, B,C, but the expressed HLA-A,B,C molecule has been noted to lack their polymorphic determinants. We analyzed the reactivity of two monoclonal antibodies to a monomorphic determinant of HLA-A,B,C (W6/32 and Cappel anti-HLA-A,B,C) with molar trophoblasts, using three uteri containing complete moles and two containing partial moles. The reactivity was examined by an indirect immunoperoxidase method. The staining patterns were almost identical in complete moles and partial moles. Villous trophoblasts showed a negative reaction with both antibodies. On the other hand, extravillous trophoblasts exhibited intense staining for W6/32 and negative staining for Cappel anti-HLA-A,B,C, which may suggest that the expression of a constant region as well as a variant region of HLA-A,B,C molecule is incomplete.

MDR1 gene encodes a gp-170 membrane protein which acts as a energy-dependent pump to transport anticancer agents out of the cells. In this article, we briefly summarize the MDR gene family, gene amplification, gene expression by differentiation and gene expression in clinical tumors. We also describe the characterization of the promotor and tissue specific enhancer of the MDR1 gene and our recent study of the regulatory mechanism of this gene expression.

A 32-year-old female was admitted to our hospital because of abdominal fullness, jaundice and pretibial edema in November, 1987. Leukocyte count of peripheral blood showed 13300/microliters with 84% leukemic cells and bone marrow was normocellular with 63.6% leukemic cells. Leukemic cells had azurophilic large granules with basophilic cytoplasm and positive for CD 2, OKIa 1, NKH-1 and negative for CD 3, CD 4, CD 8, CD 16. T cell receptor (TCR) genes for beta, gamma and delta chain and immunoglobulin heavy chain gene were in germ line configuration. These cells also had natural killer (NK) activity and antibody dependent cell mediated cytotoxicity (ADCC) activity. These observations suggested that they were derived from NK cell lineage. It is often difficult to demonstrate their clonalities in lymphoproliferative disorder of granular lymphocytes (LDGL). In the present case, the analysis of EBV genome using termini probe demonstrated polyclonal bands, while we found constant chromosome abnormalities; 47 XX, +3. From these observations, this case was considered to have several clones, and one of which could be detected by chromosome analysis. The analysis of EBV genome using termini probe may be useful to demonstrate their clonalities in LDGL in addition to conventional chromosome analysis.

To elucidate the possible participation of the Mtv-2 gene in the background factors relevant to mammary tumorigenesis, DDD/1-Miv-2/Mtv-2 (DDD-Mtv-2) congenic and DDD/1 background mice were compared for endocrine and immune organs, mammary gland development, expression of mouse mammary tumor virus (MMTV)-gp 52 antigen, hyperplastic alveolar nodules (HAN) and mammary tumor incidence. The congenic strain had been established by introducing Mtv-2 from GRS/AJms (GR) into DDD/1 mice by repeated 12 backcrosses. Body, thymus, spleen, uterus, ovary, adrenal and pituitary weights, histology of the ovary and mammary gland development showed no differences ascribable to Mtv-2 between both strains of mice at 4,6 and 12 months of age. In contrast, MMTV-gp 52 antigen expression, HAN and mammary tumor occurred in DDD-Mtv-2 but not in DDD/1 mice. These results showed that the Mtv-2 gene stimulates mammary tumorigenesis by constitutional production of endogenous MMTV which transforms mammary epithelial cells but not by influencing the background factors relevant to mammary tumorigenesis. Furthermore, the expression of Mtv-2 appeared to be lower on the DDD/1 than on the GR background.

A total of 33 human leukemia/lymphoma cell lines were classified into 4 groups with respect to the pattern of cell membrane (sm) expression of the CD3 and T cell receptor (TCR) molecules; (i) smCD3+TCR alpha beta (16 cell lines), (ii) smCD3+TCR beta delta (1 cell line), (iii) smCD3+TCR gamma delta (3 cell lines) amd (iv) smCD3-TCR- (13 cell lines), respectively. Using monoclonal antibodies (MoAbs) specific to CD3 (NU-T3), TCR alpha chain (alpha F1), TCR beta chain (beta F1), and TCR gamma chain (C gamma M1), respectively, cytoplasmic (cy) expression of these molecules was determined by immunofluorescence test. Expression of cyCD3 was present in all cell lines regardless of groups. In group (i), all 16 cell lines expressed both TCR alpha and beta chains. While only TCR beta chain was expressed in group (ii), TCR gamma chain was expressed in all 3 cell lines of group (iii). One (PEER) of the three in group (iii) expressed TCR beta chain as well. In group (iv), we found 8 cell lines with cyTCR alpha expression, 11 cell lines with cyTCR beta expression, and 10 cell lines with cyTCR gamma expression, respectively. For TCR genes, except 1 cell line all cell lines were found to present rearranged C beta gene and its mRNA, including all 3 TCR gamma/delta cell lines of group (iii). One of the TCR alpha beta cell lines exhibited rearranged C delta and J delta genes as well as its mRNA. Two cell lines of the 13 CD3-TCR- of group (iv) exhibited rearranged C delta and J delta and its mRNA. An NK-like activity and IL-2 production were induced in the TCR beta delta and gamma delta cell lines [group (ii) and (iii)] by treatment with PHA and PMA.

In 1985, Carney et al reported a complex of myxomas, spotty pigmentation, and endocrine overactivity and subsequently demonstrated dominant inheritance of the condition. The criteria for diagnosis of the complex is the presence of two or more of the following conditions: (1) cardiac myxoma, (2) cutaneous myxoma, (3) mammary myxoma, (4) spotty mucocutaneous pigmentation, (5) primary pigmented nodular adrenocortical disease (Cushing's syndrome), (6) testicular tumors (sexual precocity), (7) pituitary adenoma secreting growth hormone (acromegaly or gigantism). We encountered a family with an affected mother and daughter. Case 1 was a 43-year-old woman with multiple cutaneous myxomas, mammary myxomas and spotty mucocutaneous pigmentation. Case 2, the 19-year-old daughter of case 1 had multiple cutaneous myxomas and spotty cutaneous pigmentation. These two cases both met the criteria for the diagnosis of the complex. Our report is believed to be the first report on the complex in Japan.

A 33-year-old woman was hospitalized because of bleeding tendency. Hemoglobin was 10.7 g/dl, white blood cell 2,100/microliters and platelet 2.1 X 10(4)/microliters. Bone marrow showed marked dysplasia of trilineage blood cells. Atypical blasts and monocytoid cells accounted for 14.5% in the myelogram. Cytogenetic study of bone marrow cells revealed translocation with t(11;21) in all of 20 metaphasic cells analyzed by G-banding method. A diagnosis of RAEB was made. Familial survey revealed that her elder brother died of acute monocytic leukemia (AMoL). The patient received small dose therapy of Ara-C and BHAC-DMP therapy, but a remission was not obtained. The patient's general condition deteriorated with infection, bleeding tendency and chronic hepatitis due to transfusions, therefore we have followed up the patient with prednisolone and red blood cell transfusion. It has become evident that some types of acute leukemia with monocytic features have a cytogenetic change at 11 q 23. But it is rare that RAEB with increased monocytoid cells has a cytogenetic change at 11q23. In addition, the patient's elder brother died of AMoL. This case is important in relation to cytogenetic change at 11q23 and hematopoietic abnormalities.

A 46-year-old woman was admitted to our hospital because of leukocytosis. A diagnosis of acute lymphoblastic leukemia (FAB: L2 type) was made by reviewing peripheral blood smear and bone marrow aspirate. Chromosome analysis showed the presence of Philadelphia chromosome. A combination chemotherapy with L-asparaginase, doxorubicin, vincristine, and prednisolone was started, but complete remission was not achieved. During a neutropenic period after combination chemotherapy with doxorubicin, vincristine, vinblastine, and VP-16, high fever and tender swelling of the right cheek were noticed. A diagnosis of maxillary sinusitis was made with tomography and CT scan of the maxillary sinus. Since culture of the aspirate from the maxillary sinus grew aspergillus, a diagnosis of aspergillosis of the maxillary sinus was made. Immediately after the intravenous administration of amphotericin B and the lavage of the sinus with amphotericin B was started, high fever subsided and clinical improvement was observed. Several regimens of chemotherapy failed to obtain hematological remission, she died of sepsis of Enterobactor cloacae without evidence or relapse of dissemination of aspergillosis after initial successful treatment. While a few cases with aspergillus maxillary sinusitis were reported in leukemic patients, the possible occurrence of this complication must be kept in mind in a severe neutropenic period after intensive chemotherapy. The combination of intravenous administration and local lavage of amphotericin B appeared to be an effective treatment in the Aspergillus maxillary sinusitis.