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Biomedical subjects

K Mukai

Publications and source records attributed to K Mukai.

At least 217 records · Page 12Linked to original sources

Skull base malignant lymphoma: a case report and review of the literature.

A case of primary malignant lymphoma of the skull base is reported. A 62-year-old man was admitted with headache and diplopia. Computed tomography and magnetic resonance imaging showed an abnormal mass in the right parasellar region. The final diagnosis after surgery was primary malignant lymphoma of the skull base. Primary malignant lymphomas sometimes occur in the central nervous system but those in the skull base are exceptional. The present paper presents just such a rare case of malignant lymphoma of the skull base. Diagnosis and combined therapy consisting of surgery, radiotherapy and chemotherapy for the disease are discussed, and the literature on recent clinical problems of central nervous system lymphomas is reviewed.

Brain Neoplasms↗

[A successful resection of recurrent right ventricular myxoma].

A successful surgical treatment of right ventricular myxoma of twenty-year-old male was presented, who healed already previous resection of left atrial myxoma two year and eight months prior to this operation. He has been followed up closely after the first resection of left atrial myxoma for the recurrence in the left atrium. Follow-up echocardiography demonstrated the development of myxoma in the free wall in the right ventricle. The resection for this myxoma was found to be relatively easy at the second operation. The tumor was removed with the stark, without any postoperative problem. According to the literature, this case seems to be the second Japanese case of surgical treatment of right ventricular myxoma following the removal of left atrial myxoma.

Adult↗

Structural differences in 5'-flanking regions of rat cytochrome P-450aldo and P-450(11) beta genes.

Two rat genomic clones, one for cytochrome P-450aldo and the other for P-450(11) beta, were isolated and characterized. The two genes, encoding structurally homologous proteins, were closely similar in their intron-exon organizations. Their 5'-flanking regions, however, contained only a few homologous regions. A putative cyclic AMP responsive element, TGACGTGA, was found in the P-450aldo gene, but this sequence was altered at two positions in the P-450(11) beta gene. S1 nuclease protection assay revealed a single transcription initiation site for the P-450aldo gene, while multiple sites were found for the P-450(11) beta gene. These results suggest that transcriptional regulation of the rat P-450aldo and P-450(11) beta genes is due to differences in the sequences of their 5'-flanking regions.

Animals↗

Peroxide-dependent and -independent lipid peroxidations catalyzed by chelated iron.

Oxidation of linoleic acid (LA) in tetradecyltrimethylammonium bromide micelles was induced by ferrous- and ferric-chelates in the presence of linoleic acid hydroperoxide (LOOH). Ferrous-chelates also induced lipid peroxidation in the presence of H2O2, but ferric-chelates did not, thought they could generate OH-radicals in the presence of H2O2, resulting in deoxyribose degradation. Of the chelators tested, nitrilotriacetic acid (NTA) chelated with iron showed the highest activity for induction of H2O2- and LOOH-dependent lipid peroxidations and H2O2-dependent deoxyribose degradation. NTA with ferrous ion, but not with ferric ion, also initiated oxidation of LA after a short lag period in the absence of peroxides such as H2O2 and LOOH, but other chelators with ferrous ion did not. The peroxide-independent lipid peroxidation and associated oxidation of ferrous-NTA to ferric-NTA progressed in two steps: an induction step in a lag period and then a propagation step. Ferrous ion complexed with NTA was autoxidized pH-dependently and synchronously with oxygen uptake. The rates of both reactions increased with increase of pH, but were not related to the length of the lag period, which was also dependent on pH, and was shortest at pH 4.2. The EPR spectrum of the ferric-NTA complex prepared directly from ferric salt was different from that of the complex prepared from ferrous salt, confirming that some ferric-type active oxygen participated in induction of peroxide-independent lipid peroxidation. From these results, we propose a possible mechanism of lipid peroxidation induced by ferrous-NTA without peroxides. The finding that iron-NTA had the highest activity for induction of the oxidations of LA and deoxyribose is discussed in relation to the carcinogenic and nephrotoxic effects of this chelating agent.

Catalysis↗

Stopped-flow investigation of the reaction of vitamin C with tocopheroxyl radical in aqueous triton X-100 micellar solutions. The structure-activity relationship of the regeneration reaction of tocopherol by vitamin C.

A kinetic study of the reaction between vitamin C (L-ascorbic acid, AsH2) and a tocopheroxyl radical (7-tert-butyl-5-isopropyltocopheroxyl) in Triton X-100 micellar solution has been performed using stopped-flow spectrophotometry. The second-order rate constants (k2) obtained showed notable pH dependence with a broad maximum around pH 8. For instance, the k2 values obtained were 26 M-1 S-1 at pH 3, 322 M-1 S-1 at pH 7, and 273 M-1 S-1 at pH 10. A good correlation between the rate constants and the mole fraction of ascorbate monoanion (AsH-) was observed, showing that ascorbate (AsH-) can regenerate the tocopherol from tocopheroxyl in biological systems. Furthermore, the results indicate that reduced ascorbic acid (AsH2) does not have the ability to regenerate the tocopherol in aqueous solution. On the other hand, it was found that AsH2 can reduce the tocopheroxyl to tocopherol in benzene/ethanol (2:1) mixtures, although the rate of reaction is only approximately 15% of that observed in micellar solution at pH 7.

Ascorbic Acid↗

The AMeX method: a multipurpose tissue-processing and paraffin-embedding method. III. Extraction and purification of RNA and application to slot-blot hybridization analysis.

RNA was extracted from tissues processed by a new fixation and paraffin-embedding method (the AMeX method) and examined by Northern blot analysis and slot-blot analysis. The RNA extraction method for AMeX-processed tissue sections after the deparaffinization step was the same as that for fresh materials. The total amount of cellular RNA extracted from AMeX-processed mouse liver tissue was slightly less than that extracted from fresh tissue. In tissues of malignant lymphoma, the total amount of cellular RNA extracted from 25 sections each 20 microns thick was about 1.6-1.8 micrograms/mm2, regardless of the histological subtype and period of storage. The extracted RNA was moderately degraded, and usually could not be used for Northern blot hybridization analysis. The intensity of ethidium bromide staining and the hybridization signals of RNA extracted from AMeX-processed tissues were usually reduced in comparison with RNA from fresh material, but specific signals could be detected by slot-blot hybridization analysis. We have demonstrated previously that the AMeX method preserves high-molecular-weight DNA and various antigens. Since the present study showed that information on mRNA can be obtained from AMeX-processed tissue, the versatility and usefulness of this method were further proven.

Animals↗

Close similarity between cultured human omental mesothelial cells and endothelial cells in cytochemical markers and plasminogen activator production.

The mesothelial cells obtained from human omental adipose tissue showed a typical cobblestone monolayer and reacted strongly with keratin, but did not have Von Willebrand factor. Ultrastructurally these cells revealed the existence of desmosome-like cell junctions as well as intracellular canaliculi, tubular structures surrounded by microvilli, and tonofilament-like filaments. The mesothelial cells grew much faster in the medium containing epidermal growth factor, actively took up acetylated-low density lipoprotein into their cytoplasm, and released angiotensin-converting enzyme. They also released urokinase-type plasminogen activator, but only half as much as do human umbilical vein endothelial cells; release of tissue-type plasminogen activator was not observed. Inasmuch as the mesothelial cells also released plasminogen activator inhibitor-1, as do human umbilical vein endothelial cells, we could not detect u-PA activity in culture medium. u-Pa may play a role in the protection against adhesion among visceral organs. These observations indicate that cultured human mesothelial cells have characteristics closely related to those found in human endothelial cells.

Adipose Tissue↗

Epstein-Barr virus (EBV) genome carrying monoclonal B-cell lymphoma in a patient with adult T-cell leukemia-lymphoma.

A Japanese patient with adult T-cell leukemia-lymphoma (ATL) showed a disease progression from the smoldering type to the chronic type and finally to the acute type. The patient was variously treated, including 2'-deoxycoformycin, with some beneficial effects. During the chronic type he developed a composite lymphoma consisting of T-cell lymphoma (ATL) of medium-sized cells and B-cell lymphoma of diffuse large cell type. At that time, he also suffered from miliary tuberculosis and adenovirus type 11-induced hemorrhagic cystitis, indicating that he was in a marked immunodeficient state. Southern-blot analysis revealed that the two malignancies have distinct clonal origin on the basis of the following results: (1) clonally rearranged T-cell receptor beta-chain gene (TcR-beta gene) and germline configuration of immunoglobulin heavy chain gene (IgH gene) in ATL leukemic cells, (2) clonal rearrangement of IgH gene in lymphoma cells, indicating a monoclonal B-cell lymphoma, (3) monoclonal integration of HTLV-I provirus in ATL leukemic cells, (4) definite presence and monoclonal origin of EBV genome in lymphoma cells. This is the first report of secondary EBV genome carrying monoclonal B-cell lymphoma in an ATL patient. It is suggested that the immunodeficient state in the patient with ATL allows the emergence of EBV-related B-cell lymphoma.

Adult↗

Genetic alteration of p53 in some patients with adult T-cell leukemia.

Abnormalities of p53 mRNA in adult T-cell leukemia (ATL) were analyzed using reverse transcription-polymerase chain reaction-single strand conformation polymorphism analysis. Mutations were present in two of 12 ATL patients studied, but not in 3 cell lines immortalized by human T cell leukemia virus type 1 (HTLV-1) infection in vitro. Direct sequencing analysis of the p53 gene from these two patients revealed missense point mutations at codon 153 (arginine to histidine) or codon 220 (cysteine to tyrosine), respectively. Immunohistochemical analysis revealed the elevated expression of p53 proteins in ATL cells from a patient carrying the mutated p53 gene at codon 158. Neither gross rearrangement of p53 gene nor abnormal size of mRNA for the gene was demonstrated by Southern or Northern blot analyses. Thus, there is a mutated p53 in some patients with ATL. The involvement of abnormalities in some suppressor oncogenes may play a role in the development of ATL.

Base Sequence↗

Relation between nucleolar size and growth characteristics in small cell lung cancer cell lines.

Relationships among cytological features, doubling time, S-phase percentage, expression of myc-family oncogenes, DNA ploidy and biochemical properties were studied in thirteen small cell lung cancer cell lines. Six cell lines that grew slowly (average doubling time 99 h) and had lower S-phase percentages (average 32%) showed inconspicuous nucleoli (average area of 1.5 microns 2), and the remaining seven cell lines that grew quickly (average doubling time 45 h) and had higher S-phase percentages (average 44%) showed large and prominent nucleoli (average area of 6.1 microns 2). DNA index value obtained from flow cytometric DNA histograms showed that all cell lines except for H-69 cell line displayed aneuploidy. Ribbon-like cell arrangements were observed in the 7 cell lines that grew quickly, and in 1 cell line that grew slowly. Biochemically, six slow-growing cell lines and four fast-growing cell lines showed high levels of aromatic L-amino acid decarboxylase activity, while in the remaining three fast-growing cell lines its level was low. A high level of c-myc or N-myc oncogene expression was observed in all 7 cell lines that grew quickly, but not in any of the 6 cell lines that grew slowly. It appears that small cell lung cancer cell lines that grow quickly can be expected to have large nucleoli and ribbon-like cell arrangements and to express high levels of myc-family oncogenes, and that nucleolar size is a good indicator for growth characteristics.

Animals↗

Nuclear p53 immunoreaction associated with poor prognosis of breast cancer.

p53 protein has been frequently detected at high levels in the nuclei of human breast cancer cells. We analyzed immunohistochemically the association between nuclear localization of p53 protein and clinical and histological parameters of breast cancer patients. Surgically resected tissues of 73 primary breast cancers were processed by acetone fixation and paraffin embedding and examined using an anti-p53 monoclonal antibody, PAb1801. p53 immunoreactivity was detected in the nuclei of cancer cells in 17 cases (23%). The nuclear p53 immunoreaction was closely associated with overexpression of c-erbB-2 protein (P less than 0.05), high histologic grade (P less than 0.01), advanced clinical stage (P less than 0.05), and negative estrogen receptor status (P less than 0.01). When 31 cases which had been followed up for more than 50 months were examined, a positive nuclear p53 immunoreaction was found to be significantly associated with shorter overall survival of patients (P less than 0.01). These results suggest that immunohistochemical examination of nuclear p53 protein is clinically useful as an indicator of breast cancer aggressiveness.

Antibodies, Monoclonal↗

Giant cell fibroblastoma. A case report and immunohistochemical comparison with ten cases of dermatofibrosarcoma protuberans.

A 7-year-old boy with giant cell fibroblastoma (GCF) of the skin and subcutaneous tissue of the right chest wall is described. To date, the histogenesis of GCF has not been clarified. The reason for the diversity of immunohistochemical data among various authors may be because the specimens studied were from only part of the lesion, or reduction of antigenicity through the preparation process. However, our findings based on studies of many specimens from various parts of the tumor for accurate immunohistochemical evaluation suggest that GCF may be a myofibrohistiocytic tumor. Recently, the suggestion that GCF is a juvenile form of dermatofibrosarcoma protuberans (DFSP) has been reported. In addition to the present case, we performed immunohistochemical examination of 10 cases of definitely diagnosed DFSP for comparison. The immunohistochemical characteristics of these two neoplasms were concordant. However, from clinical and morphological viewpoints, it seems premature to recognize GCF as a juvenile form of DFSP.

Child↗

Altered phosphorylation of Bacillus subtilis DegU caused by single amino acid changes in DegS.

The Bacillus subtilis sacU locus consists of the degS and degU genes, which play a major role in controlling the production of degradative enzymes including extracellular proteases. DegS has been shown to be autophosphorylated and to transfer the phosphoryl group to DegU. In this study, we partially purified the DegS proteins which carry amino acid changes resulting from various mutations and examined the phosphorylation reaction. The mutations used were degS42, causing a reduction in exoprotease production, and degS100(Hy) and degS200(Hy), causing overproduction of the enzymes. The following results were obtained. The DegS protein derived from degS42 was deficient in both autophosphorylation and subsequent phosphate transfer to DegU. Compared with wild-type DegS, the DegS proteins derived from the overproduction mutations, degS100(Hy) and degS200(Hy), were less active in the autophosphorylation and phosphorylation of DegU. However, the DegU phosphates produced by the mutant DegS proteins were more stable than that produced by the wild-type DegS. These results suggest that phosphorylation is tightly linked to exoprotease production and that the prolonged retention of the phosphoryl moiety on DegU activates the genes for the extracellular proteases. It was also shown that the rate of dephosphorylation of DegU-phosphate was increased as the amount of DegS was increased. All of these results suggest that DegS is involved in the dephosphorylation of DegU-phosphate.

Amino Acid Sequence↗

Comparative study of five preoperative methods for the localization of accessory pathways in the Wolff-Parkinson-White syndrome.

One hundred and thirty-four cases of Wolff-Parkinson-White syndrome were studied to evaluate the relative usefulness of electrocardiography (ECG), electrophysiological studies (EPS), body surface mapping (BSM), gated blood-pool phase analysis (nuclear studies), and vectorcardiography (VCG) in the localization of the accessory pathway (ACP). In comparison with the final localization verified by intraoperative studies, 93.4% in 8-region ACP localization (97.7% in 4-region ACP localization) could be correctly localized by ECG using our criteria, 83.9% (86.8%) by EPS, 82.6% (95.8%) by BSM, 78.8% (87.7%) by nuclear studies, and 67.3% (78.0%) by VCG. It was concluded that: (a) ACP can be localized preoperatively with considerable accuracy by using our simple ECG criteria. (b) The EPS method has some limitation, especially with respect to 8-region ACP localization. (c) Our observation showed no evidence that BSM, VCG, or nuclear studies were superior to ECG in ACP localization. (d) Among the 5 methods studied, ECG and EPS appear to be the appropriate procedures for preoperative ACP identification.

Adolescent↗

Detection of Epstein-Barr virus DNA in formalin-fixed paraffin-embedded tissue of nasopharyngeal carcinoma using polymerase chain reaction and in situ hybridization.

The polymerase chain reaction method for amplification of DNA in formalin-fixed, paraffin-embedded tissue sections was used to detect Epstein-Barr virus DNA in nasopharyngeal carcinomas from Japanese patients. Thirty-one cases of nasopharyngeal carcinoma and 8 cases of lymph node metastasis of nasopharyngeal carcinoma were studied. Detection rates of Epstein-Barr virus in various types of nasopharyngeal carcinoma according to the World Health Organization classification were as follows: 10 of 10 undifferentiated carcinomas, 8 of 13 nonkeratinizing carcinomas, and 5 of 7 keratinizing carcinomas. Eight lymph node metastases, for which the primary was positive for Epstein-Barr virus, also contained Epstein-Barr virus DNA. By in situ hybridization using a biotinylated Epstein-Barr virus probe, it was clearly demonstrated that Epstein-Barr virus DNA was localized in the nuclei of the neoplastic cells. The clinical features of nasopharyngeal carcinoma with or without Epstein-Barr virus were not different. These results demonstrate that nasopharyngeal carcinoma in Japanese patients is closely associated with Epstein-Barr virus infection, similar to nasopharyngeal carcinoma of other endemic and nonendemic areas.

Carcinoma↗

Non-Hodgkin's lymphoma in patients under twenty years of age. A clinicopathological study.

A retrospective clinicopathological study was performed on 149 patients who developed malignant lymphoma at under 20 years of age and were diagnosed and treated at the National Cancer Center Hospital between 1962-1986. Using the Japanese Lymphoma Study Group classification (and Working Formulation), we reclassified the 84 evaluable tissue specimens as follows: follicular large and mixed lymphoma (two cases), diffuse lymphoblastic lymphoma (40 cases), Burkitt's lymphoma (small noncleaved, SNC) (12 cases), diffuse large and mixed cell lymphoma (25 cases), and unclassified (five cases). The age of the patients ranged from 6 months to 20 years, with a median of 11 years. The clinical characteristics were found to depend upon the histological diagnosis, as reported previously. To evaluate the influence of various clinical and morphological parameters on survival, univariate analysis was performed for each histological subtype. In lymphoblastic lymphoma, patients with a mediastinal mass had significantly earlier development of leukemic conversion and a shorter survival than patients without a mass. Because of the small number of patients and their short survival, no significant prognostic factors were found in Burkitt's lymphoma (SNC). In large and mixed cell lymphoma, response to therapy was the most significant prognostic factor. As therapy became more intense and systematic throughout the study period, the complete remission rate and survival improved steadily. Autopsy findings confirmed that lymphoblastic lymphoma and Burkitt's lymphoma (SNC) spread systemically earlier than large and mixed cell lymphoma.

Adolescent↗

Adenocarcinoma and concomitant intraductal papillary adenoma in the pancreas.

A 72-year-old man was found to have a 12 mm solid lesion in the pancreatic tail and an 8 mm cystic lesion in the body of the pancreas by computed tomography carried out during a routine follow-up study of his adult-onset diabetes mellitus. A distal pancreatectomy was performed revealing the pancreas to have an adenocarcinoma in the tail and a conglomeration of intraductal papillary adenoma in the body. A review of the literature disclosed similar coexistences of cystadenoma and carcinoma in four patients, none of which was documented with preoperative imaging features such as we had.

Adenocarcinoma↗