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Biomedical subjects

H Kitamura

Publications and source records attributed to H Kitamura.

At least 91 records · Page 5Linked to original sources

Sonographic detection of visceral adhesion in percutaneous drainage of afferent-loop small-intestine obstruction.

To facilitate the percutaneous drainage of an afferent-loop small-intestine obstruction, we used sonography to detect visceral adhesions and select a safe puncture route. The portion of the small intestine that was fixed to the anterior abdominal wall was sonographically identified by using a high-frequency transducer to locate the area of restricted visceral sliding. The needle was then inserted into the intestine. In 3 cases, we have found that this technique improves the confidence of the physicians who perform the percutaneous drainage and may help to minimize the risks associated with the percutaneous drainage.

Afferent Loop Syndrome↗

Reduced expression of p27/Kip1 is associated with the development of pulmonary adenocarcinoma.

p27/Kip1 (p27), a negative regulator of cell proliferation, is a powerful prognostic marker in non-small cell lung carcinoma. To clarify the significance of p27 aberrations in the tumourigenesis of lung adenocarcinoma, p27 expression was investigated by immunohistochemistry in lung adenocarcinoma and its precursor lesion, atypical adenomatous hyperplasia (AAH), and correlated with the expression of Ki-67, cyclin D1, and cyclin E. The p27 labelling index decreased in parallel with tumour progression (24.0% to 4.5%) and was found to be lower in neoplastic lesions than in normal bronchiolar epithelial cells (48.8%). There was a negative correlation between p27 and Ki-67 expression (rho=-0.384, p<0.001). Cyclin E-positive lesions (with labelling index >/=5%) were found only in overt adenocarcinomas. The Ki-67 labelling index of cyclin E-positive, high (>/=10%) p27 expressers was lower than that of cyclin E-positive, low (<10%) p27 expressers (16.8% vs. 42.6%; p=0. 046) and was similar to that of cyclin E-negative adenocarcinomas (15.0%). These results indicate that reduced p27 expression is associated with and may play a role in progression during the development of pulmonary adenocarcinoma.

Adenocarcinoma↗

Panic disorder and perceived parental rearing behavior investigated by the Japanese version of the EMBU scale.

Although recent studies have found dysfunctional parental rearing behaviour is associated with certain aspects of psychopathology of panic disorder (PD), the results are not in complete agreement. By using a translated Japanese version of the EMBU (Egna Minnen Beträffande Uppfostran), we investigated the parental rearing behavior perceived by 103 normal subjects, 71 PD patients with agoraphobia, and 32 PD patients without agoraphobia. The PD patients scored both parents as more rejecting and overprotective than did the controls. However, subgroup analysis showed that the patients with agoraphobia reported significantly more rejection from both parents and less emotional warmth from mothers, while the patients without agoraphobia, by contrast, reported more overprotection from both parents and more favouring subject from fathers than did the controls. Interestingly, these results were consistent with those documented in the Western literature, which reported "affectionless control" as a parenting style in PD, and, furthermore, indicated a cross-cultural similarity of parental rearing factor. In addition, it was suggested that a lack of care might be associated with the development of agoraphobia in Japan.

Adult↗

The critical role of Th1-dominant immunity in tumor immunology.

To investigate the precise role of antigen-specific Th1 and Th2 cells in tumor immunity, we developed a novel adoptive tumor-immunotherapy model using OVA-specific Th1 and Th2 cells and an OVA gene-transfected tumor. This therapeutic model demonstrated that both antigen-specific Th1 and Th2 cells had strong antitumor activity in vivo with distinct mechanisms. However, immunological memory suitable for the generation of tumor-specific cytotoxic T lymphocytes was induced only when tumor-bearing mice received Th1 cell therapy, but not Th2 cell therapy. Thus it was strongly suggested that Th1-dominant immunity is critically important for the induction of antitumor cellular immunity in vivo. We also proposed that several immunomodulating protocols using interleukin (IL)-12, IL-12 gene, the natural killer T cell ligand alpha-galactosylceramide, or Th1 cytokine-conditioned dendritic cells might be useful strategies for the induction of Th1-dominant immunity essential for the development of tumor-specific immunotherapy.

Animals↗

Ewing's sarcoma/peripheral primitive neuroectodermal tumor (pPNET) arising in the omentum as a multilocular cyst with intracystic hemorrhage.

A rare case of Ewing's sarcoma/peripheral primitive neuroectodermal tumor arising in the greater omentum in a 41-year-old man is reported. The patient presented with a hemorrhagic mesenteric cyst that was disclosed by the results of an abdominal echogram, a computed tomography scan, and magnetic resonance imaging. A laparotomy showed a multilocular cyst with intra-cystic hemorrhage. Histologically, the tumor wall consisted of sheets of small round cells separated by thick desmoplastic stroma. Rosette formations or ribbon-like cell arrangements were absent. Further pathological examination revealed that the membrane of the tumor cells was positive for MIC-2, and negative for epithelial membrane antigen, cytokeratin, and desmin, which are usually positive in intra-abdominal desmoplastic small round-cell tumors. An EWS/FLI1 fused transcript was detected by reverse transcription-polymerase chain reaction. These findings confirmed the diagnosis of Ewing's sarcoma/peripheral primitive neuroectodermal tumor. The patient died of tumor recurrence 4 months after his first admission. The autopsied tumor tissue exhibited neural differentiation in certain regions. To our knowledge, this is the first case to be reported of Ewing's sarcoma/peripheral primitive neuroectodermal tumor arising in the omentum with unique pathological features and the occurrence of partial neural differentiation during the clinical course. This case pointed out to us, as gastroenterologists, that only thorough examination confirms a definitive diagnosis of small round-cell tumor of the abdomen, it also shows that Ewing's sarcoma/peripheral primitive neuroectodermal tumor should be included in the differential diagnosis of cystic lesions in the omentum.

Adult↗

Urinary macrophages as activity markers of renal injury.

The presence of macrophages (M&phi;) in the urine of patients with glomerulonephritis (GN) reflects the pathological events in the kidney, and we have discovered the following correlations between the M&phi; phenotype and the pattern of renal injury. (1) Urinary macrophage (M&phi;) counts increase in patients with proliferative GN, especially in the presence of active glomerular lesions (glomerular tuft necrosis, crescent, and endocapillary proliferation). In patients with hematuria, a combination of urinary M&phi; and T-lymphocyte counts can be used to differentiate proliferative GN from non-proliferative renal disease (hereditary nephropathy and idiopathic renal hematuria). (2) The urinary M&phi; of patients with active proliferative GN express FcgammaRIII (CD16) regardless of the type of GN. (3) There are two types of urinary CD68(+) cells, CD68(+)25F9(-) cells (infiltrating M&phi;) and CD68(+)25F9(+) cells (mature M&phi;). The CD68(+)25F9(-) cell counts in the urine correlate well with the activity of proliferative GN, and the CD68(+)25F9(+) cell counts in the urine correlate with the magnitude of non-selective proteinuria and with the subsequent decline of renal function. The CD68(+)25F9(+) cell count increases in the urine of patients with focal segmental glomerular sclerosis, but their numbers are negligible in minimal change nephrotic syndrome. These findings indicate that the analysis of the urinary M&phi; phenotype is a useful strategy for evaluating renal injury as a 'risk-free renal biopsy'.

Antigens, CD↗

C-ERBB-2 gene amplification as a prognostic marker in human bladder cancer.

OBJECTIVES: To evaluate c-erbB-2 gene amplification and its prognostic significance in transitional cell carcinoma of the bladder. METHODS: Alterations in the gene copy number of c-erbB-2 were detected in 57 bladder tumor samples using a method based on the polymerase chain reaction. RESULTS: Eighteen tumors (32%) showed gene amplification of c-erbB-2, which correlated with tumor grade and stage. A strong association of c-erbB-2 amplification with patient survival was also found. The amplification resulted in a significantly poorer prognosis among the patients with high-grade and/or invasive tumors. Multivariate analysis revealed that c-erbB-2 amplification and tumor grade were independent prognostic factors. CONCLUSIONS: Our data indicate a possible role of the c-erbB-2 gene in the development of aggressive behavior in bladder tumors. Moreover, the use of c-erbB-2 gene amplification, together with tumor grade and stage, could provide an accurate basis for determining the prognosis of bladder cancer.

Adult↗

Chromophobe renal cell carcinoma with sarcomatoid change. A case report.

Chromophobe renal cell carcinoma (RCC) is a newly established entity of renal neoplasm with histological and molecular biological features different from those of common RCCs. Chromophobe RCC shows characteristically cloudy and reticular cytoplasm and cellular features resembling distal nephron. Its prognosis has been reported to be more favorable than that of common RCCs. Recently, however, several cases have been reported which showed sarcomatoid change to present poor prognosis. Here we present a case of chromophobe RCC with sarcomatoid change which was once resected surgically. The surgically resected tumor was histologically composed of chromophobe epithelial cell sheets and sarcomatoid elements. The former showed positivity for colloid iron staining, and was immunohistochemically positive for E-cadherin and epithelial membrane antigen (EMA), whereas the latter was positive for vimentin instead of colloid iron and E-cadherin. EMA was focally positive in the sarcomatoid element. The patient died with systemic metastases 14 months after the operation. Histologically, the metastatic tumors were composed only of sarcomatoid element lacking epithelial element. Based on these findings and previous reports, this case supports the existence of a tumor progression pathway from chromophobe to sarcomatoid RCC. It is necessary to perform careful postoperative investigation of chromophobe RCC due to its possible histological progression to the sarcomatoid subtype.

Adenocarcinoma↗

Repulsive axon guidance molecule Sema3A inhibits branching morphogenesis of fetal mouse lung.

Semaphorin III/collapsin-1 (Sema3A) guides a specific subset of neuronal growth cones as a repulsive molecule. In this study, we have investigated a possible role of non-neuronal Sema3A in lung morphogenesis. Expression of mRNAs of Sema3A and neuropilin-1 (NP-1), a Sema3A receptor, was detected in fetal and adult lungs. Sema3A-immunoreactive cells were found in airway and alveolar epithelial cells of the fetal and adult lungs. Immunoreactivity for NP-1 was seen in fetal and adult alveolar epithelial cells as well as endothelial cells. Immunoreactivity of collapsin response mediator protein CRMP (CRMP-2), an intracellular protein mediating Sema3A signaling, was localized in alveolar epithelial cells, nerve tissue and airway neuroendocrine cells. The expression of CRMP-2 increased during the fetal, neonate and adult periods, and this pattern paralleled that of NP-1. In a two-day culture of lung explants from fetal mouse lung (E11.5), with exogenous Sema3A at a dose comparable to that which induces growth cone collapse of dorsal root ganglia neurons, the number of terminal buds was reduced in a dose-dependent manner when compared with control or untreated lung explants. This decrease was not accompanied with any alteration of the bromodeoxyuridine-positive DNA-synthesizing fraction. A soluble NP-1 lacking the transmembrane and intracellular region, neutralized the inhibitory effect of Sema3A. The fetal lung explants from neuropilin-1 homozygous null mice grew normally in vitro regardless of Sema3A treatment. These results provide evidence that Sema3A inhibits branching morphogenesis in lung bud organ cultures via NP-1 as a receptor or a component of a possible multimeric Sema3A receptor complex.

Animals↗

Potentiation of antitumor effect of NKT cell ligand, alpha-galactosylceramide by combination with IL-12 on lung metastasis of malignant melanoma cells.

The combined therapeutic effect of natural killer T (NKT) cell ligand alpha-galactosylceramide (alpha-GalCer) and IL-12 against highly metastatic B16-BL6-HM melanoma cells was investigated. In comparison with a single administration of alpha-GalCer or IL-12, the combined treatment of tumor-bearing mice with alpha-GalCer plus IL-12 caused a super-induction of serum IFN-gamma levels, though alpha-GalCer-induced IL-4 production was rather inhibited. In parallel with the augmented IFN-gamma production, the natural killing activity against YAC-1 cells and syngeneic B16-BL6-HM melanoma was greatly augmented by the combined therapy. The major effector cells responsible for natural killing activity induced by alpha-GalCer plus IL-12 were enriched in both NK1.1+ TCRalphabeta+ NKT cells and NK1.1+ TCRalphabeta- NK cells. The preventing effect of alpha-GalCer or IL-12 alone against lung metastasis of B16-BL6-HM was also enhanced by the combination therapy. The antitumor activity of alpha-GalCer was totally abolished in NKT-deficient mice. However, IL-12-induced antitumor activity was not eliminated in NKT-deficient mice though it was inhibited by anti-asialo GM1 Ab treatment. These findings suggested that alpha-GalCer synergistically act with IL-12 to activate both NKT cells and NK cells, which may play a critical role in the strong prevention of distant tumor metastasis at early stages of tumor-bearing. These data will provide a novel tool for the prevention of tumor metastasis using NKT-specific ligands alpha-GalCer and IL-12.

Animals↗

Decreased graft-versus-host disease after haplotype mismatched bone marrow allografts in miniature swine following interleukin-2 treatment.

Graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation after transplants between HLA-mismatched donor/recipient pairs. In mice, giving IL-2 post transplant decreases GVHD in this setting. We studied high-dose IL-2 therapy in pigs. Transplants were carried out after conditioning with fractionated total body radiation and cyclophosphamide. Fourteen pigs received a fully mismatched bone marrow transplant (six with IL-2; eight without IL-2), and six received a single haplotype class II mismatched transplant (three with IL-2; three without IL-2). GVHD was evaluated by skin histology. All fully mismatched recipients had severe GVHD (grade 2-3) and died within 13 to 51 days whether or not they received IL-2. Pigs receiving a one haplotype class II mismatched transplant without IL-2 developed severe skin GVHD lasting for 8-45 days; all died within 57 days. Similar pigs receiving IL-2 post transplant had no or only mild skin GVHD for less than 15 days; two are long-term survivors. Bone Marrow Transplantation (2000) 25, 47-52.

Animals↗

Myoepithelioma of the lacrimal gland: report of a case with potentially malignant transformation.

Myoepithelioma of the lacrimal gland is extremely rare and only four cases, one of which was malignant, have been reported in detail. The present report describes a case of lacrimal gland myoepithelioma in a Japanese male with histological features suggestive of potentially malignant transformation. The excised tumor consisted of two components, a central nodular component and a peripheral component surrounding the former. These components were separated by a fibrous tissue. Microscopically, both components were comprised almost entirely of spindle-shaped cells, but with some epithelioid cells containing glycogen granules. Extracellular spaces in the peripheral component were filled with eosinophilic materials with the occasional crystalloid structures, which were immunoreactive for collagen type I. Neoplastic cells were immunoreactive focally for vimentin and S-100, but negative for cytokeratins, epithelial membrane antigen, muscle actin, smooth muscle actin, desmin, myosin, and glial fibrillary acidic protein. The neoplastic cells in the central component showed nuclear pleomorphism and atypia with a higher frequency of mitotic figures, and higher labelings of proliferation markers than those in the peripheral component. Neither invasion, necrosis, nor hemorrhage was observed in the tumor. From these findings we proposed a diagnosis of potentially malignant myoepithelioma.

Adult↗

Aggressive surgical approach to recurrent tumors after hepatectomy for metastatic spread of colorectal cancer to the liver.

BACKGROUND: Liver resection is currently accepted as the only potential cure for patients with metastases of colorectal tumors in the liver. However, cancer will recur in more than 70% of patients. METHODS: In the 7 years to December 1997, 60 patients underwent liver resections for colorectal metastases at our institute. Of these, 20 patients had repeated surgical resections for recurrent disease of the liver and other organs. Another 2 patients had undergone previous hepatectomy elsewhere. The clinical data for these patients were reviewed. RESULTS: The median interval between the 2 resections was 16 months. Eighteen hepatectomies, 6 lung resections, and 1 pancreatoduodenectomy were performed in 22 patients. Operative mortality and complication rates were 0% and 18%, respectively. At a median follow-up of 25 months after repeated resection, the survival rate in these patients was 73% at 2 years (12 of 16 evaluable patients are surviving) and 22% at 5 years (2 of 10 evaluable patients are surviving); the median survival time was 44 months. CONCLUSIONS: Repeated resections for recurrent colorectal metastases yield comparable results to first liver resections in operative mortality and morbidity rates, survival time, and pattern of recurrence. Although the number of patients surviving more than 5 years is still limited, the absence of other proven treatments supports the concept of an aggressive resectional approach for these patients.

Adult↗

The interface between innate and acquired immunity: glycolipid antigen presentation by CD1d-expressing dendritic cells to NKT cells induces the differentiation of antigen-specific cytotoxic T lymphocytes.

In vivo administration of NKT cell ligand, alpha-galactosylceramide (alpha-GalCer), caused the activation of NKT cells to induce a strong NK activity and cytokine production by CD1d-restricted mechanisms. Surprisingly, we also found that alpha-GalCer induced the activation of immunoregulatory cells involved in acquired immunity. Specifically, in vivo administration of alpha-GalCer resulted in the induction of the early activation marker CD69 on CD4(+) T cells, CD8(+) T cells and B cells in addition to macrophages and NKT cells. However, no significant induction of CD69 was observed on cells from CD1d- or V(alpha)14 NKT-deficient mice, indicating an essential role for the interaction between NKT cells and CD1d-expressing dendritic cells (DC) in the activation of acquired immunity in response to alpha-GalCer. Indeed, in vivo injection of alpha-GalCer resulted not only in the activation of NKT cells but also in the generation of CD69(+)CD8(+) T cells possessing both cytotoxic T lymphocyte (CTL) activity and IFN-gamma-producing ability. Tumor-specific CTL generation was also accelerated by alpha-GalCer. The critical role of CD40-CD40 ligand (CD40L)-mediated NKT-DC interaction during the development of CD69(+)CD8(+) CTL by alpha-GalCer was demonstrated by blocking experiments using anti-CD40L mAb. These findings provide direct evidence for a critical role of CD1d-restricted NKT cells and DC in bridging innate and acquired immunity.

Adjuvants, Immunologic↗

Norepinephrine stimulates interleukin-6 mRNA expression in primary cultured rat hepatocytes.

Non-invasive immobilization stress causes an increase in the plasma interleukin (IL)-6 level accompanied by increased IL-6 mRNA expression and IL-6 immunoactivity in the liver [Biochem. Biophys. Res. Commun. (1997) 238, 707-711]. In the present study, using rat primary cultured hepatocytes and non-parenchymal liver cells, the effect of norepinephrine (NE) on IL-6 mRNA expression was determined. IL-6 mRNA expression in hepatocytes, but not in non-parenchymal liver cells, increased when the cells were treated with NE. The stimulatory effect of NE was inhibited by the combined use of alpha- and beta-adrenergic antagonists. IL-6 mRNA expression in hepatocytes also increased on incubation with the culture medium of non-parenchymal liver cells treated with NE. The effect of the medium was blocked by an IL-1 receptor antagonist. Moreover, exogenous IL-1beta stimulated IL-6 mRNA expression in hepatocytes. IL-1beta was present in the medium of non-parenchymal liver cells and increased with NE-treatment. These results suggest that NE released from sympathetic nerve terminals during stress can directly increase IL-6 mRNA expression in hepatocytes and indirectly through IL-1beta production from non-parenchymal liver cells.

Adrenergic alpha-Agonists↗

Preventive effect of Ninjin-to (Ren-Shen-Tang), a Kampo (Japanese traditional) formulation, on spontaneous autoimmune diabetes in non-obese diabetic (NOD) mice.

We previously found that ingestion of an extract of Ninjin-to (NJT; Ren-Shen-Tang) suppressed the development of autoimmune diabetes in C57BL/KsJ mice induced by multiple low doses of streptozotocin. To verify this effects on spontaneous autoimmune diabetes, the effects of NJT on NOD mice were investigated in the present study. NJT, provided in drinking water (0.25%, 450 mg/kg/day) from 6 weeks of age, significantly prevented the incidence of spontaneous diabetes in female NOD mice at 30 weeks of age (2/10) compared with that of the controls (7/10), with no effects on body growth or food intake. Even in non-diabetic mice, the blood glucose levels of the NOD controls gradually increased with age, while such increase in NJT-treated mice was significantly suppressed by preventing any deficiency of glucose tolerance. NJT also significantly suppressed the progression of insulitis, which causes insulin deficiency and diabetes. It is well known that NOD mice develop insulitis and diabetes because of their Th1-dominant autoimmune response. IFN-gamma production from splenic T lymphocytes stimulated with anti-CD3 monoclonal antibodies was increased, whereas IL-4 production was decreased in NOD controls compared to age- and sex-matched normal ICR mice. NJT-treatment reduced these deviations of cytokine production in NOD mice. These data all suggest that NJT can prevent spontaneous insulitis and diabetes by the modification of deviated cytokine production in NOD mice.

Animals↗