[Congenital stomatocytosis associated with decreased sodium content in red cells].
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Biomedical subjects
Publications and source records attributed to H Mizoguchi.
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Studies were undertaken to determine whether leukemia and lymphoma cells would be lysed by autologous and allogeneic lymphokine-activated killer (LAK) cells. Peripheral blood mononuclear cells (PBMC) from patients and normal donors were cultured for five days, 2 weeks, and 4 weeks with medium containing 2,500 units of recombinant interleukin 2 (IL-2) per mL, and their cytotoxicity was assayed by a five-hour 51Cr-release test. Of primary tumors isolated from patients with acute nonlymphoblastic leukemia, acute lymphoblastic leukemia, and non-Hodgkin's lymphoma, tumors of 37 out of 40 patients tested were shown to be susceptible to normal donors' LAK, and tumors of 18 of 20 patients tested were shown to be susceptible to autologous LAK. LAK cultured for longer periods showed a tendency to have lower cytotoxicity. LAK had also low, but significant, levels of cytotoxicity for nonmalignant target cells. Because PBMC expanded in IL-2-containing medium consisted mainly of OKT3-positive pan T cells, OKT8-positive suppressor/cytotoxic cells, and Leu-11-positive natural killer (NK) cells, and treatment with OKT3 and Leu-11 monoclonal antibodies (mAb) reduced LAK activity for autologous and allogeneic tumor cells, both T and NK cells appeared to be effector cells for LAK activity. Mechanisms of target-cell recognition in the LAK system seem to be different from those in alloreactive cytotoxic T lymphocytes (CTL) based on the results that, while cytotoxicity of alloreactive CTL was inhibited by the treatment of effector cells with mAb, OKT3, and OKT8, and by the treatment of target cells with a mAb that reacts with HLA class I antigen, LAK activity was not inhibited by the above treatment. When chromosomes of IL-2-expanded PBMC in nine patients and two normal individuals were analyzed, PBMC from one patient showed chromosomes of clonal abnormalities, and PBMC from five donors showed those of nonclonal abnormalities.
We conducted a randomized crossover study comparing the hemopoietic effect of partially purified human urinary colony-stimulating factor (CSF-HU, an active drug) and human serum albumin (HSA, a control drug) in 24 patients with malignant lymphoma, solid tumors, or multiple myeloma who were receiving two consecutive courses of the same chemotherapeutic regimen. Patients received daily 2-4 X 10(6) units of CSF-HU or an equal amount of protein HSA for five days after the end of the courses of chemotherapy. Assignment to CSF-HU or HSA was determined by the envelope method. The average number of blood granulocytes of 24 cases on day 7 after chemotherapy was 2116 +/- 1649 in CSF-HU-infused courses, which was significantly higher than in HSA-infused courses (1520 +/- 1022) (p less than 0.05). The average time that patients had fewer than 2000 granulocytes/mm3 was 7.6 +/- 4.4 days in CSF-HU-infused courses and 10.3 +/- 5.0 days in HSA-infused courses (p less than 0.02). Fever greater than 38 degrees C was the most frequent side effect, occurring in 32% of the patients receiving CSF-HU infusions. A reduction in the neutropenic interval in CSF-HU-infused courses was observed in patients with fever, as well as in those without fever. Infusions of CSF-HU did not change the number of other hematological parameters, such as erythrocytes, platelets, monocytes, and lymphocytes. These results suggest that CSF-HU infusions may partially protect the patients from granulocytopenia after anticancer chemotherapy.
Seventeen untreated human acute non-lymphocytic leukemias (ANLL) were classified into four groups according to the presence or the absence of complement receptor and Fc receptor for IgG and IgM: Group I having neither C3 nor Fc receptors, Group II having either C3 or Fc receptor and Group III having both C3 and Fc receptors. ANLL of Group II was further subdivided into two groups: Group IIa having only Fc receptor and Group IIb having only C3 receptor. The morphologic and cytochemical analysis of ANLL in these groups revealed that the most immature type with regard to their myeloid-monocyte lineage was Group IIb followed by Groups I, IIa and III. Two cases of Group IIb were regarded as M1 type by French-American-British (FAB) group classification and one of them had a Ph1-chromosome. The survival rate of patients in each group was investigated and Group IIb patients showed the tendency for the longest period of survival.
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All 269 patients underwent surgery as pancreatic cancer in our institute from 1965 to 1985. Resectability rate was 20.3% (32/158) in the head, 20.7% (19/92) in the body and tail and 0% in the combined lesion. Pancreaticoduodenectomy (PD) was performed for the head in 30 patients. Distal pancreatectomy was performed for the body and tail in 16 patients. There were three postoperative deaths in the case which underwent the resection. Operative survival rate in the head was 43.9% at the first year and 27.4% at the 5 th year. Two patients survived more than five years after PD. On the other hand, survival rate in the body and tail was 40% at the first year and 26.4% at the 5 th year. Only one patient is alive 5 years 10 months after distal pancreatectomy.
A patient with gastric carcinoma exhibited an excessive granulocytosis (58,000/microliter) preoperatively, in the absence of overt infection. After resection of the primary tumor, the peripheral leukocyte count decreased promptly to the normal value. In a search for a colony-stimulating factor (CSF), the tumor was transplanted into nude mice. A marked neutrophilia was observed in the tumor-bearing mice, suggesting the production of CSF by the tumor. Media conditioned by the primary culture of the tumor cells revealed the presence of CSF activity as well. CSF-producing carcinomas have been detected in various organs; nevertheless, no cases of gastric carcinoma have hitherto been described. It is of particular interest that in this patient hypercalcemia was not observed, although it often accompanied CSF-producing tumors reported previously. Therefore, it is suggested that this tumor secreted pure CSF and that the CSF produced by the tumor did not necessarily induce hypercalcemia.
After depletion of monocytes, natural killer (NK) cells were partially purified from peripheral blood by Percoll density gradient sedimentation. The NK cells were then cultured for 1 d and assayed for their cytotoxicity against various types of normal and malignant target cells. All types of target cells tested were found to be susceptible to NK cells. The susceptible targets were autologous T and B lymphocytes, mitogen-induced T and B blasts, monocytes, large granular lymphocytes, autologous or allogeneic lymphoma and leukemia cells isolated from patients, and cultured cell lines, including those resistant to interferon-activated lymphocytes. Such a broad spectrum of cytotoxicity was demonstrated in 1 d of culture, and freshly prepared NK cells were not cytotoxic, or, if anything, were less cytotoxic. Monocytes and their supernatants, added throughout the course of culture, markedly inhibited the development of their cytotoxicity. These results may suggest that, although NK cells having ability to lyse autologous normal and malignant target cells are present in vivo, their lytic activity is regulated by coexisting monocytes.
A case of T-cell chronic lymphocytic leukemia is reported. The leukemic cells had the morphologic features of medium-sized, mature-looking lymphocytes, and had an affinity for the central nervous system. Cytochemically, they were positive for alpha-naphthyl acetate esterase and acid phosphatase. They formed E-rosettes (E+) and reacted with OKT11 but not with OKT3/Leu-4, OKT4/Leu-3, OKT8/Leu-2, or OKM1, and did not possess IgG-Fc receptors (Fc gamma R). Functionally, they did not respond to phytohemagglutinin or concanavalin A, were not natural killer cells or antibody-dependent as well as alloantigen-reactive killer cells. Furthermore, they did not possess a helper or suppressor T-cell function for immunoglobulin synthesis. Results of immunologic studies suggest that the leukemic cells were derived from a normal counterpart of a lymphocyte subset present as a minor component of the peripheral blood, namely an E+, OKT3-, OKM1-, Fc gamma R- subset, the function of which is not yet identified.
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Neoplastic angioendotheliosis (NAE) is a rare, mostly fatal disease characterized by proliferation of large blastoid cells in small vessels of various organs. The origin of neoplastic cells remain undetermined. In this study, cell markers were studied immunohistologically on paraffin sections of six cases of NAE, by applying avidin-biotin-peroxidase (ABC) method and five antibodies which can demonstrate marker antigens on formalin fixed and paraffin embedded specimens. It was shown that the neoplastic cells were heavily stained with an anti-B lymphocyte monoclonal antibody LN-1 (6/6), moderately stained with another anti-B lymphocyte antibody LN-2 (5/6) and heavily stained with a monoclonal antibody which reacts with all levels of leukocytes (Dako-LC) (6/6). The cells did not show positive reaction with an anti-myelomonocytic antibody anti-Leu M1. The reaction against anti-Factor VIII, which can depict endothelial cells, was mostly negative, and if positive, was faint and indefinite, leading to an assumption that the reaction was against antigens in serum and not against neoplastic cells. These results suggest that the neoplastic cells of NAE are in the B lymphocyte lineage.
Fourteen cases of heart disease with hypereosinophilia were analyzed employing conventional cardiologic methods, including echocardiography, cardiac catheterization, and endomyocardial biopsy. The cases were divided into four types: Acute carditic (endocarditis, myocarditis, pericarditis; five cases); ventricular dilation (three cases); restrictive (three cases); electric disturbance (three cases). Biopsy revealed significant changes in all cases. In one case of the ventricular dilation type, endomyocardial fibrosis with myocardial degeneration was seen, and in another case mural thrombus formation was shown to be present. In three cases of the restrictive type, endomyocardial fibrosis (EMF) was observed. In two cases of the electric disturbance type, minor right ventricular myocardial degeneration was observed. In two of the three cases of the carditic type and in three of eight cases in other categories, postmyocarditic changes were observed. The course of the disease compared with the type of disorder revealed a short course in the carditic type and a longer course, ranging from 2 to 24 years, with one exception, in the other types. It is also confirmed that the various histopathologic changes can be related to particular clinical presentations. We have shown that the basic changes in eosinophilic heart disease are not restricted to the endomyocardium and that they occur in various parts of the heart causing more widespread manifestations. The more comprehensive term "eosinophilic heart disease" is a preferable description.