Search PubMed⌕ Search

Biomedical subjects

M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 361 records · Page 20Linked to original sources

Terminal deoxynucleotidyl transferase staining of malignant lymphomas in paraffin sections: a useful method for the diagnosis of lymphoblastic lymphoma.

Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase located in the cell nucleus which catalyses the polymerization of deoxynucleotides at the 3'hydroxyl ends of oligo- or polydeoxynucleotide initiators without a template. TdT is known as a useful marker for the diagnosis of acute lymphoblastic leukaemia/lymphoma, but its detection usually requires fresh tissue specimens or cell suspensions, using either an enzyme analysis or immuno-fluorescence or -peroxidase staining. Until the recent development of the use of microwave-treated paraffin sections for immunoperoxidase staining, detection of TdT in paraffin sections required rather complicated processes. This new simple technique was applied to paraffin sections from the tumour tissue specimens of 16 patients with lymphoblastic lymphoma and of seven patients with non-endemic Burkitt's lymphoma, which is sometimes difficult to differentiate from lymphoblastic lymphoma because of their similar clinicopathological characteristics. In addition, as a control, ten cases each were examined of adult T-cell leukaemia/lymphoma (ATLL) and angioimmunoblastic lymphoma (AILD), which are both peripheral T-cell lymphomas. The tumour cells from 15 of the 16 (94 per cent) patients with lymphoblastic lymphoma were found to be TdT-positive. The specificity of the anti-TdT antibody used was confirmed by immunoblot and the specific 60 kD band was detected only in a specimen of lymphoblastic lymphoma. These results show that the immunostaining of TdT on paraffin-embedded sections is a useful method for differentiating lymphoblastic lymphoma from other lymphomas. This method is applicable to a routine diagnostic service.

Adolescent↗

Seasonal changes in follicle-stimulating hormone in free-living great tits.

We describe the annual cycle in plasma levels of FSH in free-living male and female great tits from southwest Sweden. Both juvenile (here defined as first-time breeders or birds <1 year old) and adult great tits, of both sexes, showed clear annual cycles with three periods of elevated FSH levels: period from territorial establishment till end of breeding (mid-March to June), October (a time when the birds break photorefractoriness), and winter (January-February). Significant differences between ages and between sexes occurred only during March and April (period of territorial establishment and gonadal recrudescens). Male FSH levels increased significantly as early as between early February and early March. Levels continued to increase until mid-April when maximal values had been reached in paired males. Territorial, but unpaired, males had significantly lower plasma levels of FSH in mid-April than did territorial and paired males. After this, FSH levels did not change until levels had decreased to basal in early July. On average, females did not show a vernal increase in FSH levels until early/mid April. However, just as in males, female FSH levels were dependent upon whether she was paired or unpaired. Females having a mate in mid-April had significantly higher FSH levels than did single females. Contrary to the males, females showed a transitory FSH peak during egg-laying. Females showed no differences between other breeding stages, until basal levels were reached during incubation of the second clutch in July. Adult birds (of both sexes) had significantly higher plasma levels of FSH than juvenile birds of the same sex during the period March-April. Furthermore, during this period adult males continually had higher FSH levels than did adult females, and juvenile males continually had higher levels than did juvenile females. In all groups a second period of elevated FSH levels occurred during early October, a time when the great tits break photorefractoriness. All groups showed basal levels during November and December. By January all four groups had increased their circulating levels of FSH to moderately high. This elevated level was maintained during February and was at the same level as that observed in October.

Aging↗

Transforming growth factor-alpha (TGF alpha)-producing gastric carcinoma with acanthosis nigricans: an endocrine effect of TGF alpha in the pathogenesis of cutaneous paraneoplastic syndrome and epithelial hyperplasia of the esophagus.

A case of well-differentiated adenocarcinoma (Borrmann type 3) of the stomach in a 76-year-old man associated with the typical skin manifestations of acanthosis nigricans and with multiple protruding lesions showing epithelial hyperplasia of the esophagus is reported. The advanced tumor was located in the cardiac region of the stomach, and measured approximately 8 cm in diameter, with partial invasion to the esophagus. The associated cutaneous lesions were characterized by hyperpigmentation and by protruding verrucous papules on the torso, head, face, neck, upper extremities, perineum, and inguinal region. Histologically, the protruding skin lesions showed keratinocytes proliferation throughout the epidermis, resulting in diffuse hyperkeratosis, papillomatosis, and acanthosis of the skin. Immunohistological analysis showed coexpression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) receptors in the tumor from the stomach. It is reasonable to conclude from this evidence that gastric carcinoma cells secrete TGF alpha in an autocrine for auto-stimulation. EGF receptor expression was also noted on the papillomatous hyperplasia of the cutaneous lesion. Serum level of TGF alpha, determined by an enzyme-linked immunosorbent assay, was high (144 pg/ml; normal, 22.0 +/- 16 pg/ml (Mean +/- SD)). Serum TGF alpha abruptly decreased to 49 pg/ml on day 7 after the total gastrectomy, and then gradually increased to 77 pg/ml within 28 days. Amelioration of the cutaneous lesions and the protruding lesions in the esophagus was observed after surgical resection of the gastric carcinoma. This suggests that the TGF alpha stimulates the proliferation of keratinocytes involved with EGF receptor. Large amounts of circulating TGF alpha in the blood over a long period released by the primary tumor seem to act as an endocrine-like mechanism causing epidermal and esophageal epithelial cells to proliferate. There is a possible link in the pathogenesis of the acanthosis nigricans as a cutaneous paraneoplastic syndrome, and epithelial hyperplasia of the esophagus.

Acanthosis Nigricans↗

Strain-related differences in Sephadex bead-induced airway hyperresponsiveness and inflammation in rats.

OBJECTIVE: The aim of this study was to compare Sephadex G-200 (Sephadex)-induced airway hyperresponsiveness (AHR) and pulmonary eosinophilia among some rat strains. MATERIALS: Sprague-Dawley (SD), Brown-Norway (BN), Fischer 344 (Fischer), Lewis and Wistar-Kyoto (WKY) rats were used. METHODS: Sephadex (0.5 mg/animal) was intravenously administered on days 0, 2 and 5. Measurement of AHR using serotonin and bronchoalveolar lavage (BAL) was performed on day 7. RESULTS: The Lewis strain exhibited significant AHR to Sephadex but the BN, Fischer and WKY strains did not. Additionally, the degree of AHR in Lewis rats was smaller than in SD rats throughout the study. Eosinophils in BAL fluid, however, increased in each strain, and the magnitude of the response was BN > Lewis > WKY > Fischer. Both the AHR and pulmonary eosinophilia in Lewis rats were inhibited by dexamethasone (0.1 mg/kg, p.o. x3). CONCLUSION: These results indicate that the Lewis rat is a useful strain for analysis of the mechanism of Sephadex-induced AHR and airway inflammation.

Animals↗

Characteristics of rhabdomyosarcoma cell lines derived from uterine carcinosarcomas.

Rhabdomyosarcoma (RMS) is occasionally found in the female genital tract, and mostly appears as one of the heterologous mesenchymal components in uterine carcinosarcoma designated as malignant mixed mullerian tumour (MMMT). We examined the biological properties of a pure rhabdomyosarcoma (RMS) cell line designated FU-MMT-3, which was newly established from a surgical specimen taken from a patient with uterine MMMT. We also evaluated c-myc and MYCN gene amplification in three RMS cell lines (including FU-MMT-3) derived from three MMMTs by Southern blot analysis. FU-MMT-3 cells were propagated continuously for 57 serial passages over a 2-year period in vitro. FU-MMT-3 was able to produce tumours demonstrating pure RMS in athymic nude mice. Cytogenetically, FU-MMT-3 showed a triploidy pattern, with complex karyotypic abnormalities including trisomy of chromosome 8. All three RMS cell lines, including FU-MMT-3, showed amplification of the c-myc gene (approximately fourfold to eightfold), while no cell lines demonstrated MYCN gene amplification. FU-MMT-3 is considered to provide a useful system for the study of the biological behaviour of RMS in MMMTs. Extra copies of chromosome 8 and c-myc gene amplification may be associated with the rhabdomyoblastic differentiation in MMMT.

Animals↗

T-stem cell leukemia/lymphoma with both myeloid lineage conversion and T-specific delta recombination.

We evaluated retrospectively the clinical and biological characteristics of six patients with CD7+ early T-acute lymphoblastic leukemia and lymphoma (T-ALL/LBL) originating from prothymocyte stage I (pro-T I) or II cells. Patients exhibited mediastinal mass (five of six) and lymphoadenopathy (five of six) but without leukocytosis and circulating blast cells (six of six). All patients achieved a complete remission. All but one had a relapse with a transformation to the mixed type (triphenotype--three cases, biphenotype-two cases) including myeloid features in three patients. The altered phenotypes were myeloperoxidase (MPO)+ (three of five), CD13+ (four of five), CD33+ (three of five) and CD19+ (three of five). The difference for MPO-positivity were observed between the bone marrow (BM)- and lymph node (LN)-blast cells (three of three). On cytogenetic analysis, there is no common abnormality in these patients. Immunomolecular analysis revealed T-cell lineage specific delta gene rearrangements [D delta 2-J delta 1 (five of six) and V delta 1-J delta 1 (one of six)] in all cases. Furthermore, D delta 2-J delta 1 occurred even in the cases with the pro-T I phenotype. Rearrangements of TCR beta, gamma or immunoglobulin heavy chain genes occurred in three patients. The same rearranged band(s) appeared at both diagnosis and relapse, indicating the same originality of the pro-T leukemic cell clone (three of three). We suggest that this type of CD7+ early T-ALL/LBL was transformed from a pro-T I or II cell, such as T-stem cell leukemia/lymphoma, which is a subtype of CD7+ stem cell leukemia as defined by Kurtzberg et al. This study reveals that pro-T I and II cells might be capable of myeloid, T- and B-lymphoid differentiation, and T-cell lineage specific TCR delta recombination occurs.

Adult↗

Safety evaluation of tannase enzyme preparation derived from Aspergillus oryzae.

Tannase is an acylhydrolase enzyme preparation from Aspergillus oryzae that can be used as a processing aid for the manufacture of cold water-soluble tea beverages. A 91-day oral toxicity study in the rat and a gene mutation study in Salmonella typhimurium were performed to establish the safety of the enzyme preparation for the consumer. General toxicity was low, with no adverse effects observed at the highest dose tested, 1% in the diet. There was no evidence of mutagenic potential with or without metabolic activation. These results, together with knowledge of the production organism and the chemical and microbiological characterization of the enzyme preparation, indicate that tannase can be regarded as safe for its intended use in processing tea.

Administration, Oral↗

Heterogeneity of systemic extra-nodal Epstein-Barr virus-associated lympho-histiocytic tumor--ten autopsy cases of human immunodeficiency virus-negative Japanese.

Epstein-Barr virus associated T-Cell lymphoma mimicking malignant histiocytosis (MH) has been previously reported. We selected 10 autopsy cases of extranodal lymphoma or histiocytic tumor, which showed an EBV presence in the tumor cells as well as a fulminant clinical course. The detailed clinicopathologic features were thus clarified. A retrospective study was performed on ten adult patients, eight males and two females, and almost all cases presented with a fulminant clinical course, revealing pancytopenia, liver dysfunction and disseminated intravascular coagulopathy. Immunophenotypic and genotypic studies along with in situ hybridization (ISH) were performed. The autopsy findings mainly showed extra nodal involvement in the liver (10 patients), spleen (9 patients), intestinal tract (5 patients), bone marrow (5 patients), nasal cavity, lungs, adrenal glands, kidneys (2 patients) and brain. Histologically atypical pleomorphic lymphoid cells were observed to infiltrate with reactive histiocytes, some of which showed hemophagocytosis. Based on the histological and clinical findings, diagnosis of malignant histiocytosis was made. ISH showed an EBV-presence in almost all the tumor cells. The immunophenotype and/or genotype studies demonstrated T-cell lymphoma (2 patients), Histiocytic tumors (2 patients), B-cell lymphoma (1 patients), natural killer (NK) cell lymphoma (3 patients), and T/NK lymphoma (2 patients), in which T or NK could not be confirmed, due to a lack of fresh materials. Based on the above findings, the histological appearance of EBV-associated MH previously defined was shown to be common to extra-nodal malignant lymphomas having origin in various organs, although the cytological and genetic features were heterogenous.

Adolescent↗

Preparation and mechanical properties of calcium phosphate/copoly-L-lactide composites.

New artificial bone materials were prepared using calcium phosphates, hydroxyapatite and beta-tricalicum phosphate, and copoly-L-lactide, CPLA. Calcium phosphate powder and CPLA were mixed at 453 K for 10 min with various mixing ratios. Scanning electron microscope observations indicated that the composites of beta-tricalicum phosphate and CPLA were homogeneously dispersed and highly adhesive. Young's modulus of the composites was the same as bone, and bending strength was over half that of bone. The improvement of Young's modulus compared to the original two materials was due to a composite effect. The composites are expected to be usable as artificial bone materials.

Journal Article↗

Non-restricted T cell receptor (TCR)-V alpha and -V beta gene usage in patients with pulmonary sarcoidosis.

Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by the pronounced accumulation of CD4+ T cells and macrophages in the affected organs. TCR variable (V) alpha and V beta gene usage in patients with sarcoidosis is still a matter of discussion. In this investigation, we analysed TCR-V alpha and -V beta gene usage in bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) of 30 patients with active pulmonary sarcoidosis using an adapter ligation method, reverse transcriptase-polymerase chain reaction (RT-PCR), and sequence-specific oligonucleotide probe (SSOP) analyses. There was no significant difference in TCR-V alpha or -V beta gene usage between BALF (n = 12) or PBMC (n = 27) of patients and PBMC of healthy subjects (n = 10). Neither selective TCR-V alpha nor -V beta expansion was observed in the paired BALF and PBMC from seven of nine patients. However, selective expansions were observed in a few TCR-V alpha or -V beta subsets in the BALF or PBMC of some individuals. Although a modest increase in a few TCR-V alpha or -V beta subsets was observed in the BALF or PBMC of some individuals, the increased TCR-V alpha or -V beta subsets were not closely associated with the HLA-DRB1, DQA1, DQB1, and DPB1 alleles of these patients. These results suggest that TCR-V alpha or -V beta gene usage is not restricted in both lung and peripheral blood in the majority of patients with active pulmonary sarcoidosis.

Adult↗

Nasal T/NK cell lymphomas commonly express perforin and Fas ligand: important mediators of tissue damage.

AIMS: Two molecular mechanisms of T/natural killer (NK) cell-mediated cytotoxicity, one perforin based and the other Fas based, have been demonstrated, and both systems induce cytotoxicity in the target cells. The Fas-based mechanism involves the transducing molecule Fas and its ligand (FasL). In addition, perforin and/or FasL are also expressed in the cytotoxic T/NK cells. This study was thus designed to investigate the Fas and perforin pathways of the cytotoxic T/NK lymphoma cells in the nasal cavity. METHODS AND RESULTS: Eight patients with nasal lymphoma were analysed using immunohistochemical staining methods. Two cases were CD3+ CD56+ (T/NK cell) type, and six were CD3- CD56+ (NK cell) type. All cases showed Epstein-Barr virus genomes by in-situ hybridization. In addition, all cases showed the expression of TIA-1 (GMP-17), which is a marker of cytotoxic T and NK cells. FasL was expressed in the majority of the lymphoma cells and some histiocytes, while Fas was found in lymphoma cells and many non-neoplastic cells. In addition, the expression of perforin was detected in almost all lymphoma cells. In the double stainings, lymphoma cells expressed both FasL and perforin. Based on these findings, both the perforin- and Fas-based pathway of the cytotoxic T/NK lymphoma cells are thus considered to play an important role in the clinical features. CONCLUSIONS: Tissue damage is a common morphological feature in nasal T/NK cell lymphoma. The above findings therefore support the theory that tissue damage is due to both the cytotoxicity of T/NK lymphoma cells as well as to angiocentricity.

Adult↗

Proton-donative antioxidant activity of fucoxanthin with 1,1-diphenyl-2-picrylhydrazyl (DPPH).

Reactions between a carotenoid, fucoxanthin and 1,1-diphenyl-2-picrylhydrazyl were investigated both under anoxic and aerobic conditions. Fucoxanthin equimolarly reacted with 1,1-diphenyl-2-picrylhydrazyl under anoxic conditions. Under aerobic conditions, only a part of fucoxanthin consumed 1,1-diphenyl-2-picrylhydrazyl and the degree of reaction fluctuated with repeated trials. beta-Carotene or other carotenoids, beta-cryptoxanthin, zeaxanthin, licopen and lutein, were also examined in the reaction with 1,1-diphenyl-2-picrylhydrazyl under anoxic conditions. All these compounds scarcely reacted with 1,1-diphenyl-2-picrylhydrazyl.

Antioxidants↗

Direct evidence for the contribution of B cells to the progression of insulitis and the development of diabetes in non-obese diabetic mice.

The non-obese diabetic (NOD) mouse is an excellent animal model of autoimmune diabetes associated with insulitis. The progression of insulitis causes the destruction of pancreatic beta cells, resulting in the development of hyperglycemia. Although it has been well documented that T cells are required for the development of insulitis and diabetes in NOD mice, the importance of B cells remains unclear. To clarify the role of B cells in the pathogenesis of NOD mice, we therefore generated B cell-deficient NOD (B-NOD) mice. Surprisingly, none (of 13) of the B-NOD mice developed diabetes by 40 weeks of age, while the control littermates with B cells (B+NOD) suffered from a high proportion (43 of 49) of diabetes. The insulin reactivity of B+NOD mice was significantly impaired, while the B-NOD mice showed a good insulin response, thus suggesting the pancreatic beta cell function to be well preserved in B-NOD mice. Although B-NOD mice did develop insulitis, the extent of insulitis was significantly suppressed. These data thus provide the direct evidence that B cells are essential for the progression of insulitis and the development of diabetes in NOD mice.

Animals↗

ATP-induced dynamic fluorescence changes of a N-[p-(2-benzimidazolyl)phenyl]maleimide probe at Cys241 in the alpha-chain of pig stomach H+,K+-ATPase.

H+,K+-ATPase preparations from pig stomach were modified with a sulfhydryl fluorescence reagent, N-[p-(2-benzimidazolyl)phenyl] maleimide (BIPM). The addition of ATP to the modified enzyme preparations in the presence of Mg2+ decreased the BIPM fluorescence but increased the Trp fluorescence. After exhaustion of ATP, the fluorescence intensities increased and decreased to the original levels, respectively. The results of stopped flow and rapid quenching experiments suggested that the decrease in BIPM fluorescence (36/s) was accompanied by binding of Mg2+ and ATP or phosphorylation (35 36/s) which was followed by slower increases in Trp fluorescence (24/s) and light scattering (20/s). Tosylphenylalanyl chloromethyl ketone-trypsin treatment of the modified preparations, which showed an about 1% decrease in BIPM fluorescence accompanying phosphorylation, gave one major fluorescent peptide peak on reverse-phase chromatography. Amino acid sequence analysis of the peptide revealed the following sequence, Ser-Pro-Glu-X-Thr-His-Glu-Ser-Pro-Leu-Glu-Thr-Arg. On comparison with the amino acid sequence deduced from cDNA from pig stomach [Maeda, M., Ishizaki, J., and Futai, M. (1988) Biochem. Biophys. Res. Commun. 157, 203-209], X was shown to correspond to Cys241 of the alpha-chain in H+,K+-ATPase. These data and others suggest that the decrease in BIPM fluorescence at Cys241 reflects some molecular event triggered by the binding of ATP with Mg2+ and/or phosphorylation, whereas the increases in the intrinsic Trp fluorescence and light scattering reflect one after phosphorylation.

Adenosine Triphosphate↗

Lymphoblastic lymphoma expressing natural killer cell phenotype with involvement of the mediastinum and nasal cavity.

Most CD56+ lymphomas display polymorphic and angiocentric/angiodestructive histologic features and are closely related to Epstein-Barr virus (EBV) infection. We report a 47-year-old Japanese man with CD56+ lymphoma that showed histologic features of lymphoblastic lymphoma with mediastinal and nasal involvement and an aggressive course. A sample specimen showed the histology of lymphoblastic lymphoma with a positive reaction for terminal deoxynucleotidyl transferase (TdT) but no angiocentric/angiodestructive features. Transmission electron microscopy revealed a few membrane-bound electron-dense granules in their cytoplasm. Immunohistochemically, lymphoma cells exhibited CD56+ cytoplasmic CD3 (cCD3)+ TdT+. A Southern blot analysis showed no integration of EBV and human T-lymphotrophic virus 1 (HTLV-1) and no rearrangement of the T-cell receptors or immunoglobulin heavy chain genes. This unusual lymphoblastic lymphoma exhibiting cCD3 + CD56 + TdT + TCR- is assumed as an immature or progenitor natural killer cell lineage.

Anatomy, Cross-Sectional↗