Biomedical subjects
Publications and source records attributed to M Kikuchi.
A case history of a 39-year-old woman with a follicular, medium-size cell type lymphoma (Nodular poorly differentiated lymphocytic lymphoma) is reported. In spite of receiving no treatment, her lymphoma had changed little for 13 years. This case is regarded as a good example for considering the treatment of low grade malignant lymphomas.
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A 51-year-old woman with leiomyosarcoma of the stomach treated effectively with FT 600 mg/day p.o., is reported. Leiomyosarcoma of the stomach was found in the greater curvature on the fornix by examinations involving X-ray and gastrofiberscopy with biopsy. She was subsequently treated with MMC 6 mg/2 alpha/w x 5 weeks and FT 600 mg/day continuously on account of liver metastasis determined by liver scintigram and CT. After one year, both gastrofiberscopy and X-ray pictures showed a decrease in the size of the SMT. An evaluation of the treatment showed partial response (PR), and the state of PR was maintained for more than 5 years. Six years and 9 months after chemotherapy, however, unresponsiveness to the therapy appeared and regrowth of the SMT followed. Furthermore, intrahepatic SOL was definitely diagnosed to be cavernous hemangioma of the liver. Consequently, proximal gastrectomy was performed using R1-absolute curative resection, after confirming that the histology of the SMT was leiomyosarcoma of the stomach by endoscopic partial tumorectomy.
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We report the clinical, histological, immunophenotypic, and cytogenetic findings in ten patients with T-cell lymphoproliferative disorders demonstrating reactive "angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-type" features. Fifteen available specimens were diagnosed as atypical hyperplasias (four) or malignant lymphomas (11). The latter were classified as AILD-type (five), T-zone (four), lymphoepithelioid (one), and low-grade, unclassified lymphoma (one). Despite the histologic differences, all these lesions shared minor nuclear atypicalities and reactive AILD-type features such as prominent vascularity, plasma cells, eosinophils, macrophages, and residual germinal centers. All lesions were immunophenotyped as predominantly T cell. The chromosome pattern was characterized by the frequent presence of karyotypically unrelated abnormal clones and/or cells with nonclonal chromosome abnormalities, a large population of normal mitotic cells, and a high incidence of trisomies 3 and 5. Sequential cytogenetic and histologic studies in five patients revealed that atypical hyperplasia and lymphoma with AILD-type features shared the same cytogenetic characteristics, ie, an unstable coexistence of normal mitotic cells and small-clonal and/or nonclonal abnormal cells, and that histologic transformation from low-grade lymphoma to immunoblastic lymphoma was accompanied by a selective proliferation of abnormal clonal cells. The AILD-type histology and the characteristic karyotypic pattern may be the expression of a specific pathogenesis and may warrant the separation of these neoplasias from other peripheral T-cell lymphomas.
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From April, 1982 to March, 1987, we have performed 36,566 gastrofiberscopic examinations and have detected 793 gastric cancers among 7,618 biopsies. Of these 55 cancerous lesion (6.9%) diagnosed as benign at the time of endoscopic examinations were analyzed and the following results were noted. 1. Most such lesions were small in size and superficial in nature. 2. The gross appearances of the cancers were mainly IIc, IIc + III or IIa. 3. The lesions were most frequently located on the gastric angulus or the side with a lesser curvature. 4. Histologically, well differentiated adenocarcinomas were relatively frequent. 5. False-negative cases determined by endoscopic examination were not infrequent in cases of lesions involving an ulcer, or showed redness, erosion or a polyp.
Eighty-two adult patients with advanced B-lymphoma, treated between 1981 and 1983 with VEPA (vincristine, cyclophosphamide, prednisolone and doxorubicin) or VEPA-M (VEPA plus methotrexate) in a prospective randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 74% and 45%, respectively. The relapse rate was 51%. Stage of disease only was negatively associated with the CR rate in a multivariate analysis. The primary extranodal tumor site other than upper gastrointestinal (GI) tract and high grade pathology were found to affect disease-free survival adversely in a Cox proportional hazards model. Poor performance status, advanced stage, primary extranodal tumor site other than upper GI tract, advanced age, high grade pathology and prior therapy by either surgery or radiation, were significantly associated with shortened survival in a Cox proportional hazards model. These results indicate advanced B-lymphoma in Japan to be generally similar to advanced non-Hodgkin's lymphoma in the West in terms of prognostic factor characteristics, but the importance of the primary site in predicting survival has not been reported in the West. Also, the lack of a survival plateau in patients with diffuse large cell lymphoma indicates more intensive chemotherapy regimens than VEPA or VEPA-M to be needed. It was also found that the significant prognostic factors in patients with advanced B-lymphoma were very different from those with T-lymphoma. The five factors: pathology, stage, primary site, age, prior therapy by surgery or radiation, for which the risk ratio was more than 2.3, were used to construct a model containing 23 categories of patients running an increasing risk of shortened survival; this divided patients into three groups. The CR and 4-year survival rates of low-, moderate- and high-risk groups were 90% and 74%, 74% and 58%, and 50% and 5%, respectively. The risk-grouping provides indications for determining optimal therapy for individual patients and the need for new therapeutic trials in patients at high risk.
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A case of a 78-year old woman, complaining of epigastralgia, is reported. A series of gastrointestinal examinations revealed a small, elevated lesion with a central depression in the antrum. Since a fiberoptic biopsy had shown a Group V classification, a partial gastrectomy was performed. Tumor nodules, judged to be metastatic, were noticed in the liver and regional lymph nodes. Histologic scrutiny disclosed a keratinizing tumor that measured 1.0 X 0.9 cm in diameter and was largely a squamous cell carcinoma with a small focus indicating an adenocarcinoma. This tumor was confined to the muco-submucosal layers with prominent vascular permeation. No adenocarcinomatous components were found in the metastatic foci. The patient died eight months after operation. In light of our experience, together with what has been found in a review of the literature, we feel that a squamous carcinoma and an adenosquamous carcinoma of the stomach to be more aggressive than an ordinary adenocarcinoma and keeping this point in mind, they should be considered differentiated from an adenoacanthoma.
To elucidate the structure-function relationship of the signal sequence for the secretion of human lysozyme by Saccharomyces cerevisiae, we have systematically engineered the hydrophobic segment using the signal sequence of chicken lysozyme. Replacement of Cys 10 with leucine caused a 1.6 times increase in the secretion of human lysozyme. An idealized signal sequence L10 in which 10 consecutive leucines were distributed from the 3rd to the 12th position was 1.8 times as effective as the native sequence. L10 can be generalized as Ln = Met-Arg-(Leu)n-Pro-Leu-Ala-Ala-Leu-Gly, where n = 10. We have also studied the secretory capability of Ln, where n = 6,8,12, and 14, and found that the length, as well as hydrophobicity, of the hydrophobic segment is an important factor in the secretion of human lysozyme by yeast.
Saccharomyces cerevisiae secreted human lysozyme in the medium as an active form when the signal peptides of chicken lysozyme and a chicken lysozyme-Aspergillus awamori glucoamylase hybrid were used, whereas it did not synthesize any human lysozyme protein by using the signal peptide of A. awamori glucoamylase. The secreted lysozyme was easily purified and crystallized. On the other hand, Bacillus subtilis secreted an inactive human lysozyme, which seemed to have incorrect disulfide bonds, with the signal peptide of amylase and its mutants. The free energy changes for the membrane translocation of the signal peptides are related to the secretion of human lysozyme in S. cerevisiae, but not in B. subtilis. These results indicate that differences exist between S. cerevisiae and B. subtilis in the secretion of human lysozyme.
A new visible-ultraviolet labelling method for the high-performance liquid chromatographic analysis in serum of individual free fatty acids, including polyunsaturated fatty acids, is described. Without commonly used isolation steps, fatty acids in serum were directly derivatized by treatment with acidic 2-nitrophenylhydrazine hydrochloride. The derivatized fatty acids were extracted into n-hexane and separated isocratically on a reversed-phase C8 column within 15 min. The detection limits ranged from 400 fmol to 1 pmol and from 100 to 200 fmol per injection with visible and ultraviolet detection, respectively. Visible detection had better selectivity, and free fatty acid levels were determined in sera obtained from healthy controls and patients with diabetes mellitus. In all the subjects studied, the precise quantitation could be performed with 25 microliters of serum. Analytical recoveries ranged from 98.3 to 103.4%. The intra- and inter-assay coefficients of variation were less than 2.7 and 3.5%, respectively. The present method is superior to the previously published methods for routine analyses: it is cheaper, the procedure is simpler, the analysis time is shorter and both resolution and sensitivity are better.
Histopathologic slides of 368 cases collected from 16 institutions around the world for the Fifth International Chromosome Workshop were independently reviewed by a group of five hematopathologists consisting of two Americans and three Japanese. Agreement rates of their diagnoses using the Working Formulation (WF) for non-Hodgkin's lymphomas were studied. A modified classification scheme of the WF was used in order to define cytologic subtypes more specifically, enabling 65 possible diagnostic choices. Data analyses by computer revealed that at least four out of five diagnostic agreements were observed in 290 cases (78.9%). Similar agreements were observed in more than 80% of the cases for most of the categories of the WF, excepting diffuse small cleaved (73.3%), diffuse mixed (64.2%), diffuse large cell (76.5%), and immunoblastic lymphoma (70.2%). Agreement rates between American and Japanese pathologists did not demonstrate statistically significant differences against expected values. It was concluded that the WF was a reliable and useful classification system for multi-institutional as well as international projects, although refinements may be necessary in some categories for better diagnostic agreement.
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