Factors possibly affecting the degree of malignancy in adenocarcinoma of the lung. DNA content and bromodeoxyuridine (BrdU) labeling index.
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Biomedical subjects
Publications and source records attributed to K Mukai.
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A 57-year-old male was introduced to our hospital for his drug resistant non-ischemic ventricular tachycardia causing faintness attack. Preoperative electrophysiological studies led to a diagnosis of ventricular tachycardia originating from the right ventricular outflow tract. After ventriculotomy, an abnormal muscle band was noticed in the right ventricular outflow tract, which seemed to be a focus of tachycardia by endocardial mapping. Myocardial excision with the abnormal muscle band was performed. In addition to, cryoablation was performed surrounding this area. After the operation, the ventricular tachycardia disappeared completely. No antiarrhythmic drug have been required at 18 months postoperative months.
Twenty two cases with Hodgkin's disease under 20 years of age who were diagnosed and treated in National Cancer Center during 1962-1986 were studied retrospectively. The most common initial symptom was swelling of lymph nodes (86%) and only 5 cases (23%) showed "B" symptoms. Laboratory findings showed that there were some cases with increased WBC counts but only 2 cases with an elevated LDH value. In 2 out of 4 cases serum copper value correlated well with their clinical state. Histologically lymphocyte predominance type, mixed cellularity type and nodular sclerosis type almost equally occurred in children younger than age 15 years. On the other hand nodular sclerosis type with mediastinal mass was predominantly encountered in older patients (especially female). The ten years' survival rate in stage I and II patients was 59% compared with 21% in stage III and IV patients. As for the results of initial treatment, complete remission and 10 years' survival rate were 91% and 87% in recent 12 years (1975-1986) compared with 55% and 36% in the preceding 13 years (1962-1974) respectively. Autopsy findings revealed rare involvements of the central nervous system and kidneys. Various late effects which may be caused by escalating doses of radiotherapy occurred in 6 out of 9 cases under the age of 15 years who survived. On the basis of these results lower-doses of radiotherapy combined with systemic chemotherapy appeared to be advisable for the treatment of childhood Hodgkin's disease.
Three cases with ectopic atrial tachycardia and two cases with atrial flutter (AF), unresponsive to drugs, are described clinically and electrophysiologically. The three patients of ectopic atrial tachycardia were treated by surgical removal of ectopic focus and cryocoagulation of the adjacent area, not using cardiopulmonary bypass. All of them have been in sinus rhythm and had shown no tachycardia since the operation. In one patient of AF, cryosurgical ablation around the atrioventricular (AV) node and His bundle has prevented AF without AV block. Another patient of AF underwent cryoablation around the orifice of the coronary sinus, which was the earliest activation area during AF in endocardial mapping. In this patient, AF reappeared, so cryoablation around the AV node and His bundle was performed. His heart rate decreased to 120 beat/min from 270 beats/min during AF and a radiofrequency pacemaker (Atricon) was implanted to interrupt the remaining AF. This cryosurgical procedure is successful to modify and preserve AV conduction.
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Kinetic study of the reaction between vitamin E radical and alkyl hydroperoxides has been performed, as a model for the reactions of lipid hydroperoxides with vitamin E radical in biological systems. The rates of reaction of hydroperoxides (n-butyl hydroperoxide 1, sec-butyl hydroperoxide 2, and tert-butyl hydroperoxide 3) with vitamin E radical (5,7-diisopropyl-tocopheroxyl 4) in benzene solution have been determined spectrophotometrically. The second-order rate constants, k-1, obtained are 1.34 x 10(-1) M-1s-1 for 1, 2.42 x 10(-1) M-1s-1 for 2, and 3.65 x 10(-1) M-1s-1 for 3 at 25.0 degrees C. The result indicates that the rate constants increase as the total electron donating capacity of the alkyl substituents at alpha-carbon atom of hydroperoxides increases. The above rates, k-1, are about seven order of magnitude lower than those, k1, for the reaction of vitamin E with peroxyl radical.
Since the discovery of human T-cell leukemia virus type 1 (HTLV-1) in patients with adult T-cell leukemia/lymphoma (ATLL), malignant neoplasms of mature (peripheral) T lymphocytes have attracted a great deal of attention. This type of neoplasm is more common in Japan than in Western countries, and may show distinct clinical pictures such as hypergammaglobulinemia, hypercalcemia, etc. T-cell lymphomas are more prone than B-cell lymphomas to become leukemic. Because of a marked intermingling of reactive cells (histiocytes, eosinophils, etc.), the histologic diagnosis of T-cell lymphoma is often difficult. Proliferation pattern and cellular size do not correlate with prognosis as in B-cell lymphoma. Since T-cell lymphomas often manifest with several distinct clinicopathologic settings, their categorization should be based on several parameters, such as the presence or absence of ATLL-associated antigen in serum, histology, phenotype of the neoplastic cell, and clinical features. Since a classification for T-cell lymphomas has not been established, a further multi-disciplinary approach is necessary for a better understanding of this interesting neoplasm.
Generation of hydroxyl radicals by the Fenton reaction resulted in lipid peroxidation of linoleic acid (LA) (H2O2-Fe2+-induced lipid peroxidation) in positively charged tetradecyltrimethylammonium bromide (TTAB) micelles, but not in negatively charged sodium dodecyl sulfate (SDS) micelles. However, more OH radicals formed via the Fenton reaction were trapped by N-t-butyl-alpha-phenylnitrone (PBN) in SDS micelles than in TTAB micelles. When detergent-dispersed LA was contaminated with linoleic acid hydroperoxide (LOOH), lipid peroxidation was catalyzed by Fe2+ via reductive cleavage of LOOH (LOOH-Fe2+-induced lipid peroxidation), and Fe2+ was oxidized simultaneously in SDS micelles, even when H2O2 was not present. In contrast, LOOH-Fe2+-induced lipid peroxidation and simultaneous oxidation of Fe2+ were not observed in TTAB micelles. An ESR spectrum presumed to be due to an alkoxy radical trapped by PBN was also detected in SDS micelles, but not in TTAB micelles in the LOOH-Fe2+-induced lipid peroxidation system. The results are discussed in the light of the localization of iron, the unsaturated bonding moiety of LA, the OOH-group of LOOH, and the trapping site of PBN in different charged micelles.
Second-order rate constants, kappa s, for H-atom abstraction by phenoxyl radicals from five tocopherol (vitamin E) derivatives have been measured spectrophotometrically at 25.0 degrees C by the stopped-flow method, as a model reaction of tocopherols with unstable free radicals (LOO., LO., and HO.) in biological systems. Three new tocopherol derivatives with a five-membered heterocyclic ring were found to be 1.9-2.1 times more active than the alpha-tocopherol which has the highest antioxidant activity among natural tocopherols. The proton hyperfine splittings for the five tocopheroxyl radicals derived from these tocopherols by the reaction with phenoxyl were also determined by ESR measurements.
A 49-year-old man developed adult T-cell leukemia (ATL) and acute myeloblastic leukemia (AML) at the same time. Using Southern blotting analysis, the leukemic cells of the ATL were found to contain the human T-cell leukemia virus type I (HTLV-I) proviral genome, whereas those of the AML did not, indicating the HTLV-I not to be associated with the AML oncogenesis. At the initial presentation, the serum anti-HTLV-I antibody was judged on screening by a routine particle-agglutination (PA) test and an indirect immunofluorescence assay (IF) to be negative. By Western blotting analysis, however, the serum was proved to be positive for anti-HTLV-I antibody. These results indicate that a routine PA-test and an IF may show false negative reactions on very rare occasions of low antibody titer. This is the first report of a coincidence of ATL with another type of leukemia.
An immunohistochemical study of keratin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), vimentin, desmin, myoglobin and S-100 protein in 15 cases of uterine mixed Müllerian tumor was performed in order to analyze the expression of various antigens in different elements of this tumor. In general, the epithelial and mesenchymal components were separated easily by the presence of keratin/EMA or vimentin, respectively. However, in eight cases vimentin was expressed by epithelial cells and in four cases keratin by solid "sarcomatous" element. EMA was also identified in the "sarcomatous" areas of two cases. Specific differentiation was much easier to identify by immunohistochemical staining than by routine histologic examination. Areas with muscle differentiation were positive for desmin; myoglobin was identified in rhabdomyoblasts. S-100 protein was present in chondrosarcomatous and liposarcomatous areas. S-100 protein was also widely distributed in other elements. Quite diverse expression of various antigens revealed by immunohistochemistry reflects the histologic multiplicity of this tumor.
Forty-nine cases of cutaneous malignant lymphoma were reviewed in order to analyze the clinicopathological features of these neoplasms. Excluding 13 cases of mycosis fungoides and 4 cases of cutaneous involvement of proven adult T-cell lymphoma/leukemia, the remaining 32 cases were further classified according to their pathological and clinical features. There were 12 primary cutaneous lymphomas, 15 cases of secondary cutaneous involvement of systemic lymphoma, and 5 cases of concurrent skin and lymph node involvement. Histologically, large cell lymphoma predominated in both primary and secondary cutaneous lymphomas. Immunohistochemical study using monoclonal antibodies reactive with B- and T-cells in paraffin sections revealed the cellular lineage in 30 cases. Nineteen cases were of T-cell origin and 11 cases were of B-cell derivation. The prognosis of these patients was rather poor; 25 patients died within 5 years. The predominance of T-cell lymphoma contrasts with a higher frequency of cutaneous B-cell lymphoma in Western countries. As the clinicopathological features of cutaneous lymphomas are diverse, it is suggested that cutaneous lymphomas should be classified and studied in a similar way to their nodal counterparts.
Eradication of immunologically-syngeneic tumors was achieved by adoptive chemotherapy using effector cells induced by Corynebacterium parvum-Pyridine Extract Residue (CP-PER). A mixture of 2 X 10(6) Meth A cells and 0.1 mg CP-PER was subcutaneously inoculated into the back of donor BALB/c mice, with the result that their spleen cells showed an antitumor effect 10 to 13 days after the inoculation. These cells were used as immune cells. Recipient mice were inoculated with 1 X 10(6) Meth A cells, and 2 days later were administered cyclophosphamide. On the following day, 1 X 10(8) immune cells were adoptively transferred into the recipient mice. As a result, the tumor began to regress 7 to 12 days after the adoptive transfer. An immuno-histochemical study of the donors' spleens and the recipients' regressing tumors revealed that the ratio of L3T4+ T cells to Lyt-2+ T cells in the donors' spleens was increased and that the infiltrating cells in the recipients' tumors were mainly composed of L3T4+ T cells. This confirmed that the transfer of L3T4+ T cells led to the infiltration of L3T4+ T cells into the recipients' tumors, causing their eradication.
Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is a distinct peripheral T-cell lymphoma, which closely resembles angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) and/or IBL, but is characterized by focal or sheet-like proliferation of immunoblasts and pale cells of T-cell nature. In this report, 36 patients with IBL-like T-cell lymphoma were analyzed. The disease is clinically characterized by generalized lymph node swelling, hepatosplenomegaly, fever, skin rash, polyclonal hypergammaglobulinemia, marked male predominance, predilection for the elderly, and poor prognosis. There was no association with human T-cell leukemia virus type I or human immunodeficiency virus. IBL-like T-cell lymphoma may be divided into two categories (CD4+ type and CD8+ type) by surface marker analysis. It can also be divided into three categories on the basis of the histologic findings of distribution of morphologically recognizable tumor cells: nine cases of "inconspicuous type," six cases of "patchy type," and 21 cases of "diffuse type." Two cases of "inconspicuous type" converted later to "diffuse type." DNA hybridization analyses in the ten recent cases revealed that three of four "inconspicuous types" and five of six "diffuse types" showed clonal rearrangement of T-cell receptor-beta chain gene without rearrangement of immunoglobulin heavy chain gene, providing strong evidence for clonal proliferation of T cells.
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For determination of the degree of malignancy among thymic epithelial tumors, the DNA content and area of nuclei in 13 cases each of noninvasive thymoma, invasive thymoma, and thymic carcinoma were investigated by cytofluorometry and morphometry. The nuclear DNA content was determined in terms of the mean nuclear DNA content, DNA histogram pattern, and the occurrence of the aneuploid stem cell line. The mean nuclear DNA content of the thymic carcinoma was significantly higher than that of both subgroups of thymoma (P less than 0.01), but there was no significant difference between noninvasive and invasive thymomas. The aneuploid stem cell line appeared in 92.3% of thymic carcinomas, one case (7.7%) of invasive thymomas, and none of noninvasive thymomas. Abnormal DNA histogram patterns were seen in 53.8% of thymic carcinomas and none of the thymomas. The mean nuclear area increased significantly in the increasing order of noninvasive thymoma, invasive thymoma, and thymic carcinoma (P less than 0.01). The cytofluorometric and morphometric results demonstrated a significant difference in degree of malignancy between thymic carcinoma and thymoma; however, there was a trend toward an increasing degree of malignancy from noninvasive to invasive thymomas, yet there was a sizeable overlap in results between the two groups. Therefore, these two methods are not satisfactory for predicting the behavior of an individual case of noninvasive or invasive thymoma.
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