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Biomedical subjects

M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 379 records · Page 21Linked to original sources

Renal primitive neuroectodermal tumor: a morphologic, cytogenetic, and molecular analysis with the establishment of two cultured cell lines.

We report two patients with renal primitive neuroectodermal tumor (PNET) in whom the diagnosis was established by both a cytogenetic and a molecular analysis. Histologically, both renal tumors were composed of uniform immature round cells with a positive immunoreactivity for O13 (p30/32 MIC2). The cytogenetic analysis with in situ hybridization (chromosome painting) demonstrated reciprocal translocation t(11;22)(q24;q12) specific to PNET in the cultured cells derived from each tumor. The reverse transcriptase-polymerase chain reaction (RT-PCR) in both tumors demonstrated EWS/ FLI-1 fusion transcripts, representing the molecular equivalent of t(11;22). A Southern blot analysis also confirmed EWS gene rearrangement in both renal tumors. In addition, the authors also established two new cell lines (designated as FU-RPNT-1 and FU-RPNT-2) from renal PNETs. When transplanted into athymic mice, FU-RPNT-1 and FU-RPNT-2 reproduced and maintained the morphologic and molecular characteristics of the original tumors. In conclusion, the detection of t(11;22) and EWS/FLI-1 fusion transcripts is considered to provide a novel adjunctive method for diagnosing renal PNET. These newly established cell lines thus may be used to investigate the biologic behavior related to renal PNETs.

Adult↗

Detection of MAGE-4 protein in sera of lung cancer patients.

We investigated the level of MAGE-4 protein in sera of patients with primary lung cancer to understand better the biological roles of the MAGE proteins. MAGE-4 protein was detected as a non-degraded form in both the supernatant of a MAGE-4+ tumor cell line and in a patient's serum. Serum level of the MAGE-4 protein in lung cancer patients (n=100, mean=1.17 ng/ml) was significantly higher than that in either patients with benign pulmonary diseases (n=80, 0.33 ng/ml) or healthy donors (n=68, 0.32 ng/ml). It was higher than the cutoff level (1.15 ng/ml) in 34 of 100 cancer patients, but not in anyone in the other groups.

Adult↗

Case report: eosinophilic colitis with high antibody titre against Ascaris suum.

Eosinophilic gastroenteritis (EGE) is an inflammatory disease characterized by eosinophilic infiltration of the gastrointestinal tract accompanied by varying abdominal symptoms and usually by peripheral blood eosinophilia. Although the precise aetiology of EGE remains to be determined, contribution of allergic process to certain allergens, such as foods, drugs and parasites, has been repeatedly proposed as the pathogenesis of the disease. Here we report on a rare case of a woman who had extensive eosinophilic infiltration in the descending and rectal colon with a high titre of IgG antibody against Ascaris suum. The patient was successfully treated with prednisolone.

Animals↗

Kidney transplantation and liaison psychiatry, part I: anxiety before, and the prevalence rate of psychiatric disorders before and after, transplantation.

We examined psychiatric problems before and after kidney transplantation in a sample of 36 patients with end-stage renal failure. The prevalence rate of psychiatric disorders was 11.1% (4 of 36 cases) before the transplantation and 36.1% (13 of 36 cases) within 2 months after the transplantation. Except for a patient with schizophrenic disorder, no patients were found to have a psychiatric disorder from 2 to 6 months after the transplantation. In this study, we also examined anxieties and/or conflicts related to the transplantation using the synthetic house-tree-person (HTP) drawing test, a measure of mood states by means of a non-verbal expression method. The upper part of the tree trunk was not drawn in 25% of this sample (5 of 20 cases). In the HTP drawing tests immediately after the transplantation, however, trees missing the upper part of trunk were not drawn. Based on these findings, we discussed psychiatric problems in kidney transplantation.

Adolescent↗

A human gall-bladder signet ring cell carcinoma cell line.

To date, very few reports of the establishment of gall-bladder cancer cell lines have appeared, although many cancer cell lines of various kinds have been established. On the other hand, no reports could be found on signet ring cell carcinoma cell lines derived from the gall-bladder and only five cell lines from the stomach. A human gall-bladder cancer cell line (FU-GBC-2) was established in tissue culture from the ascitic fluid of a 69-year-old Japanese female patient. The tumor cells growing in tissue culture exhibited the morphological characteristics of signet ring cells in phase contrast and electron microscopy. The population doubling time was 43 hours. Heterotransplantation was succeeded by inoculation into the dermis of BALB/c nude mice. An immunocytochemical study showed that most of the cultured cells were positive for carcinoembryonic antigen, CA19-9 and epithelial membrane antigen, but negative for vimentin. The modal chromosome number was 120 with a range of 100-124. Flow cytometry showed an aneuploidy pattern in the cultured cells at passage 30. Markedly amplified c-myc oncogene was observed by Southern blot analysis. This cell line may be useful in the study of the morphological and biological characteristics of signet ring cell carcinoma and gall-bladder adenocarcinoma.

Aged↗

Spindle cell carcinoma of the breast: a case report and an immunohistochemical study including p53 and Ki-67 expression.

A rare case of spindle cell carcinoma (SpCC) of the breast occurring in a 51-year-old Japanese woman is reported. A firm and well-circumscribed tumor, measuring 9 x 8.5 x 8.5 cm, was located on the upper lateral region of the right breast. Microscopically, the tumor consisted of sheets of both malignant spindle cells and poorly differentiated ductal carcinoma containing squamoid islands with gradual transition to the spindle cell component. The immunocytochemical expression of epithelial markers was recognized in the spindle cells, as well as in the carcinomatous cells. Moreover, the spindle cell component expressed vimentin, alpha-smooth muscle actin and S-100 protein. Ultrastructurally, in addition to the features of adenocarcinoma, squamous or myoepithelial differentiation was confirmed in the spindle cell component. These findings thus suggest an epithelial origin with squamous differentiation and myoepithelial participation in the genesis of SpCC. In a comparative study, the expression of p53 protein and Ki-67 as a proliferation marker in each component of this tumor was also investigated. The mean p53 labeling index (LI) in both the carcinomatous and spindle cell area was similar, however the mean MIB-1 LI in the spindle cell area was significantly higher than that in the carcinomatous area. The results indicate that p53 overexpression is involved in the tumorigenesis of both components in the SpCC, and the spindle cell component shows a higher degree of proliferative activity than the carcinomatous component.

Biomarkers↗

Gastric carcinosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentiation.

A rare case of carcinosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentiation occurring in the gastric remnant is reported. A 69-year-old Japanese man who had undergone a partial gastrectomy for a duodenal ulcer 30 years earlier, presented with anemia, epigastralgia, and an abdominal mass. The diagnosis of gastric carcinosarcoma was made based on the findings of endoscopic biopsies. The patient was thus scheduled to undergo a surgical operation, but he died of respiratory failure. At autopsy, a huge polypoid tumor measuring 20 x 18 x 8 cm was located on the greater curvature of the gastric remnant. Microscopically, the tumor consisted of intimately mixed tubular adenocarcinoma and heterologous mesenchymal elements containing rhabdomyosarcoma and osteosarcoma. Between these components, a morphological transition from the adenocarcinoma element to the sarcomatous element was observed. Ultrastructually, rhabdomyoblastic differentiation was confirmed in the sarcomatous areas. Immunocytochemical expressions of epithelial markers including epithelial membrane antigen and cytokeratins (35bH11 and 34bE12) were recognized not only in the carcinomatous cells but also in the sarcomatous cells. These findings suggest that carcinomatous cells appear to transform into cells with sarcomatous features.

Aged↗

Studies on the site of renal tubular defect in Bartter's syndrome.

Renal tubular function was studied in an 8-month-old male infant with Bartter's syndrome, which is characterized by hypokalemic metabolic alkalosis, normotensive hyperreninemic hyperaldosteronism, and reduced pressor response to angiotensin II. Chloride transport along the diluting segment (CH2O/CH2O + CCl) was impaired. Furthermore, furosemide did not elicit normal natriuresis, which suggested impaired chloride reabsorptive capacity at the furosemide-sensitive ascending limb of Henle's loop. Loss of antidiuretic hormone-mediated urinary concentration was in support of this. These findings pointed to the thick ascending limb of Henle's loop as the site of the primary defect in this child.

Bartter Syndrome↗

Contribution of neutrophils to lipopolysaccharide-induced tumor necrosis factor production and mortality in a carrageenan-pretreated mouse model.

Carrageenan (CAR) pretreatment primes mice for lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production in sera and increases their mortality rate. To study the contribution of neutrophils in this model, blood neutrophil count was regulated with cyclophosphamide. After LPS challenge, both serum TNF-alpha activity and mortality risk ratio were significantly higher in neutrophilic mice, but significantly lower in neutropenic mice. In vitro, CAR treatment primed for TNF-alpha production of blood neutrophils, but conversely, that of monocytes was suppressed. We suggest that neutrophils are the major cells to produce TNF-alpha and to determine mouse mortality after LPS challenge in the mouse CAR model.

Animals↗

[Immunodeficiency and carcinogenesis in patients with chronic active Epstein-Barr virus infection].

Three adult patients with chronic active Epstein-Barr virus infection (CAEBV) had high anti-EBV-VCA antibody, positive anti-EA, low anti-EBNA and were associated with systemic lymphadenopathies and immunosuppression. The case 1 and 2 had elevated serum immunoglobulin levels, and recurrent infections, and case 3 showed pancytopenia. These 3 cases developed both EBV and latent membrane protein (LMP) positive malignant histiocytosis, EBV positive but LMP negative plasmacytoma, and EBV negative acute myelogeneous leukemia, respectively. It was suggested that CAEBV belonged to high risk groups for the development of malignant neoplasms. Since HLA of the case 1 and his father was identical, we conducted a in vitro cytotoxicity test using EBV transformed autologous B lymphocytes, K562 cells, and Raji cells to clarify the association of immunosuppression and HLA. The case 1 showed a low level of specific cytotoxicity to autologous EBV transformed B cells, while his parents were negative for the specific cytotoxicity. The patient and his parents developed inducible cytotoxicity to all targets after in vitro incubation of peripheral mononuclear cells with recombinant interleukin 2 (rIL-2) for 7 days. The patient and his mother showed lower enhancement of cytotoxicity, while HLA identical father could induce good cytotoxic activity to all targets as well as normal controls, indicating that a low IL-2 induced cytotoxic activity observed in CAEBV was independent of HLA associated immunoregulation at least in the case 1. Further studies are required to clarify the exact mechanisms responsible for the development of CAEBV.

Adult↗

Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45.

Accumulating evidence suggests an important role of interleukin-8 (IL-8) in Helicobacter pylori infection-associated chronic atrophic gastritis and peptic ulcer. We observed in this study that a gastric cancer-derived cell line, MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori but not with killed H. pylori, H. pylori culture supernatants, or live H. pylori separated by a permeable membrane, indicating that IL-8 production requires a direct contact between the cells and live bacteria. Moreover, the tyrosine kinase inhibitor herbimycin but neither a protein kinase C inhibitor (staurosporine) nor a protein kinase A inhibitor (H89) inhibited IL-8 production by MKN45 cells cocultured with live bacteria, suggesting the involvement of a tyrosine kinase(s) in H. pylori-induced IL-8 production. In addition, coculture of H. pylori induced IL-8 mRNA expression in MKN45 cells and an increase in luciferase activity in cells which were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44), indicating that the induction of IL-8 production occurred at the transcriptional level. This region contain three cis elements important for induction of IL-8 gene expression: AP-1 (-126 to -120 bp), NF-IL6 (-94 to -81 bp), and NF-kappaB (-80 to -70 bp) binding sites. Mutation of the NF-kappaB binding site abrogated completely the induction of luciferase activity, whereas that of the AP-1 site partially reduced the induction. However, mutation of the NF-IL6 binding site resulted in no decrease in the induction of luciferase activity. Moreover, specific NF-kappaB complexes were detected in the nuclear proteins extracted from MKN45 cells which were infected with H. pylori. Collectively, these results suggest that H. pylori induced the activation of NF-kappaB as well as AP-1, leading to IL-8 gene transcription.

Gene Expression Regulation↗

Roles of PI 3-kinase and Ras on insulin-stimulated glucose transport in 3T3-L1 adipocytes.

The dominant negative p85alpha regulatory subunit (delta p85alpha) of phosphatidylinositol (PI) 3-kinase or dominant negative Ras (N17Ras) was overexpressed in 3T3-L1 adipocytes using an adenovirus-mediated gene transduction system. Functional expression of delta p85alpha and N17Ras was confirmed by marked inhibition of insulin-stimulated PI 3-kinase activity and mitogen-activated protein kinase activity, respectively. N17Ras expression did not affect glucose transport activity, whereas delta p85alpha expression inhibited insulin-stimulated glucose transport with impairment of GLUT-4 translocation, although inhibition of glucose transport activity was less remarkable than that of PI 3-kinase activity in delta p85alpha-expressing cells. Thus the Ras signaling pathway does not play a major part in either translocation or intrinsic activity of glucose transporters, but PI 3-kinase activation, via phosphotyrosyl proteins and heterodimeric PI 3-kinase, plays a pivotal role in insulin-stimulated glucose transport. However, a discrepancy was observed between PI 3-kinase activity and glucose transport activity, suggesting a possibility that a different pathway(s) is involved in insulin-stimulated intrinsic activity of glucose transporters.

3T3 Cells↗

The association among occlusal contacts, clenching effort, and bite force distribution in man.

The contact area during habitual biting can vary according to the activity of the jaw musculature. Forceful masticatory muscle activity may also induce deformations of the dento-alveolar tissues and the supporting skeleton, yielding various tooth loads despite an apparently even distribution of tooth contacts. To investigate this variability, we measured bite forces simultaneously at multiple dental sites during maximum-effort clenching tasks. In each of four healthy adults with complete natural dentitions, four strain-gauge transducers in the right side of an acrylic maxillary appliance occluded with the lower canine, second premolar, and first and second molars. These, and matching contralateral contacts, were balanced by means of articulating paper and a force monitor (type F appliance). Bite forces were recorded when the subjects, without visual feedback, clenched maximally on the appliance. Similar recordings were made when contralateral molar and all contralateral contacts were removed (type R and type U appliances, respectively). Although the relation between individual forces often changed during the initial increase in force, it was generally constant around the maximum. The maximum forces at the four dental locations varied in distribution between subjects, but were characterized by posteriorly increasing forces. Forces in the anterior region (especially at the canine) significantly increased (up to 10 times) when clenching took place on unilateral contacts only (type U) as compared with fully balanced ones (type F). Bite force distribution thus changed with biting strength and the location of occlusal contacts. Increased force in the canine region during unilateral clenching seems related to the pattern of jaw muscle co-activation and the physical properties of the craniomandibular and dental supporting tissues which induce complex deformations of the lower jaw.

Adult↗

Targeting of GLUT1-GLUT5 chimeric proteins in the polarized cell line Caco-2.

Caco-2, a human differentiated intestinal epithelial cell line, is a promising model for investigating the mechanism of polarized targeting of apical and basolateral membrane proteins. We stably transfected rat GLUT5 cDNA and rabbit GLUT1 cDNA into Caco-2 cells with an expression vector. Immunohistochemical study revealed that the GLUT5 protein expressed was localized at apical membranes and that the GLUT1 expressed was present primarily in the basolateral membranes of cells grown on permeable support. Next, to investigate the domain responsible for determining apical vs. basolateral sorting in glucose transporters, we prepared several GLUT1-GLUT5 chimeric cDNAs and transfected them into Caco-2 cells. A GLUT1 [N terminus approximately sixth transmembrane domain (TM6)]-GLUT5 [intracellular loop (IL) approximately C terminus] chimera was observed exclusively at the apical membrane, while GLUT1 (N terminus approximately IL)-GLUT5 (TM7 approximately C terminus) and GLUT1 (N terminus approximately TM12)-GLUT5 (C-terminal domain) chimeras were observed mainly at the basolateral membrane, a localization similar to that of GLUT1. Moreover, using a recombinant adenovirus expression system, we expressed a GLUT5 (N terminus approximately TM6)-GLUT1(IL)-GLUT5(TM7 approximately C-terminus) chimera, which was observed at the basolateral membrane. Based on these results, the C-terminal domain does not determine isoform-specific targeting of GLUT1 and GLUT5. Rather, it is the intracellular loop in glucose transporters that appears to play a pivotal role in apical-basolateral sorting signals in Caco-2 cells.

Animals↗

Right bundle block in a patient with acute posterior myocardial infarction.

We present here a patient with the unusual combination of a newly developed right bundle branch block (RBBB) and an acute posterior myocardial infarction (MI). A dissecting MI with interventricular septal (IVS) rupture was initially thought to have caused RBBB. However, histologic examination revealed that the right bundle branch (RBB) had no ischemic involvement, but did show fibrosis, which suggests that this chronic damage of the RBB was a major contributor to the development of RBBB. This case confirms that the RBB is rarely involved by a posterior MI even in the presence of a dissecting IVS rupture.

Acute Disease↗

[Anti-allergic activity of betotastine besilate (TAU-284), a new anti-allergic drug].

The anti-allergic activity of betotastine besilate (betotastine), a new anti-allergic drug, was investigated in several allergy models of rats in comparison with other anti-allergic drugs.1) Orally administered betotastine (0.1-30 mg/kg) inhibited homologous passive cutaneous anaphylaxis (PCA) in rats in a dose-dependent manner (ID30-value: 0.38 mg/kg). The inhibitory activity of betotastine was significant at 1 mg/kg and was more potent than that of ketotifen, terfenadine, cetirizine and epinastine. The PCA-inhibitory activity of betotastine lasted more than 8 hr after administration, and the repeated administration of betotastine lasted more than not induce drug-tolerance. 2) Orally administered betotastine inhibited the histamine-induced skin reaction in rats in a dose-dependent manner (ID30:0.10 mg/kg), and the inhibitory activity lasted more than 4 hr after the administration. Its inhibitory activity was significant at 0.1 and 1 mg/kg and was more potent than those of ketotifen, terfenadine, cetirizine and epinastine. 3) Betotastine suppressed histamine release from rat peritoneal mast cells at a high concentration (10(3)(10(-3)M). These results suggest that betotastine has a potent and long acting anti-allergic activity, and these effects are mainly due to histamine antagonistic activity.

Administration, Oral↗

Alexithymic characteristics in responses to the Synthetic House-Tree-Person (HTP) Drawing Test.

This study examined the association of certain complex personality traits assessed by the Synthetic House-Tree-Person Drawing Test and alexithymic characteristics assessed by the 20-item Toronto Alexithymia Scale for a sample of 589 Japanese college students. Alexithymic students who scored over 61 points on the Toronto Alexithymia Scale-20 exhibited two characteristics relative to the test: poor relationships between figures and additional written explanations. These two characteristics projected on the Synthetic House-Tree-Person Drawing Test may be related to alexithymic characteristics and related factors.

Adult↗