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Biomedical subjects

H Hamada

Publications and source records attributed to H Hamada.

At least 37 records · Page 2Linked to original sources
PubMed2001

Nuclear factor-kappaB-dependent expression of metastasis suppressor KAI1/CD82 gene in lung cancer cell lines expressing mutant p53.

KAI1/CD82 has been shown to be a metastasis suppressor for several human cancers, and a recent study revealed that wild-type tumor suppressor p53 can directly activate KAI1/CD82 gene expression. However, the response of KAI1/CD82 expression in cancer cells to exogenous stimulants has not been investigated. The present study examined whether tumor necrosis factor (TNF), which mediates many of the cellular responses associated with inflammatory reactions or cancer progression, can affect the KAI1/CD82 expression in lung cancer cells and, if so, whether nuclear factor (NF)-kappaB, a key molecule in TNF-mediated gene expression, is involved in the mechanism of KAI1/CD82 induction. Our results demonstrated that expression of KAI1/CD82 in PC-14 cells expressing mutant p53 could be augmented by TNF-alpha, and that transfer of the gene for a specific inhibitor of NF-kappaB, IkappaB alphaSR (mutant IkappaB alpha; NF-kappaB super-repressor), into PC-14 cells could inhibit this augmentation. The amount of NF-kappaB in the nucleus of PC-14/IkappaB alphaSR cells correlated well with KAI1/CD82 mRNA and protein expression. In addition, IkappaB alphaSR gene transfer inhibited the spontaneous expression of KAI1/CD82 protein in KAI1/CD82-high-expressing RERF-LC-OK cells, which contain a mutant-type p53. These observations indicate that NF-kappaB activation may play a role in the regulation of KAI1/CD82 expression in lung cancer cells independently of wild-type p53, and suggest that KAI1/CD82 expression may be regulated by interaction with the host microenvironment.

Antigens, CD↗
PubMed2001

Abundance of unconventional CD8(+) natural killer T cells in the large intestine.

Natural killer T (NKT) cells are mainly present in the liver and thymus, and the majority of these T cells express either a CD4(+) or a double-negative (DN) CD4(-)8(-) phenotype. In the present study, we examined whether such NKT cells were present in the intestine. NKT cells were rare in all sites of the small intestine, including an intraepithelial site. However, a considerable number of NKT cells were found at an intraepithelial site in the large intestine. This result was confirmed by both immunofluorescence and immunohistochemistry. In contrast to conventional NKT cells, NKT cells in the large intestine were CD8(+) or DN CD4(-)8(-). In the case of conventional NKT cells, their existence is known to depend on non-classical MHC class I-like antigens (i. e. CD1d) but not on classical MHC class I antigens. However, the NKT cells in the large intestine were independent of the presence of both CD1d and classical MHC class I antigens. These results were obtained using knockout mice lacking the corresponding genes and molecules. NKT cells in the large intestine were mainly alpha betaTCR(+) (> 75 %) but did not use an invariant chain of Valpha14Jalpha281, which is preferentially used by conventional NKT cells. These NKT cells did not bias the TCR-Vbeta usage toward Vbeta8. These findings suggest that the large intestine is a site in which unconventional NKT cells carrying the CD8(+) phenotype (or DN CD4(-)8(-)) are abundant and that these cells are independent of MHC and MHC-like antigens.

Animals↗
PubMed2001

Intramedullary spinal teratoma with spina bifida.

Spinal intramedullary teratoma is a rare tumor. We report a case of intramedullary teratoma of the conus medullaris with spina bifida. A 5-year-old boy was admitted to our hospital for removal of a lumbosacral tumor sited in an intramedullary location at the conus medullaris, which was totally resected with neuroendoscopic assistance. The pathological diagnosis was mature teratoma consisting of three germ cell layers. The pathogenesis of spinal intramedullary teratoma is discussed with special reference to spina bifida.

Adolescent↗
PubMed2001

Intracranial hemorrhage associated with congenital organic disease in neonates. Report of two cases and review of literature.

We report on two patients with intracranial hemorrhage associated with primary organic lesions who underwent surgery within 24 h after birth. The primary lesions in the two cases were an arteriovenous malformation (AVM) and a brain tumor. The patient with AVM has exhibited normal growth without neurological deficits during follow-up over 18 years, but the patient with brain tumor has exhibited various degrees of neurological deficits and developmental retardation. Timely diagnosis and aggressive surgery may be required for the management of neonatal AVMs with intracerebral hemorrhage.

Adolescent↗
PubMed2001

A case of surgically treated acute cerebellitis with hydrocephalus.

We report a pediatric case of acute cerebellitis with hydrocephalus requiring emergency placement of external ventricular drainage. A 7-year-old boy presented with acute development of headache, nausea and vomiting. Magnetic resonance (MR) examination revealed obstructive hydrocephalus and marked bilateral cerebellar swelling on T2-weighted imaging. After the placement of external ventricular drainage, symptoms of intracranial hypertension promptly improved, and other clinical and radiological abnormalities gradually resolved following intravenous injection of corticosteroids. Surgical treatment and timing in the treatment of acute cerebellitis are discussed.

Acute Disease↗
PubMed2001

The potent antitumor effects of combined p16 gene and GM-CSF gene therapy through efficient induction of antitumor immunity.

PURPOSE: Tumor suppressor gene therapy and cytokine gene therapy have limited antitumor effects when used alone. Thus, in the present study, we investigated the antitumor potentials of the combined transfer of the p16 tumor suppressor gene and the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) gene. METHODS: The adenovirus-harboring p16 gene (Adp16) and adenovirus-harboring GM-CSF (AdGMCSF) gene were utilized for the treatment of established tumors in vivo. The mice were inoculated s.c. with Renca renal carcinoma cells and 3 days later received an intratumoral injection of Adp16 in combination with AdGMCSF. RESULTS: The results demonstrated that tumor-bearing mice treated with Adp16 and Ad-GMCSF showed more potent inhibition of tumor growth and a prolonged survival period than mice treated with Adp16. AdGMCSF, adenovirus-expressing beta-galactosidase or PBS (P<0.01). Treatments of the mice with Adp16 alone or AdGMCSF alone also showed obvious antitumor effects as compared with those mice treated with PBS (P<0.05). After combined p16 and AdGMCSF gene therapy, the expression of H2Kd and Fas molecules on freshly isolated tumor cells increased markedly, and more CD(4)+ T cells and CD(8)+ T cells infiltrated in the tumor sites. The cytotoxicity of natural killer cells and specific cytotoxic T lymphocytes increased more significantly after the combined therapy. CONCLUSIONS: Our results demonstrated that combination p16 gene and GM-CSF gene therapy could inhibit the growth of established tumors in mice more significantly through efficient induction of antitumor immunity.

Adenoviridae↗
PubMed2001

Adenovirus-mediated transduction of Escherichia coli uracil phosphoribosyltransferase gene increases the sensitivity of esophageal cancer cells to 5-fluorouracil.

Esophageal cancer is associated with the poorest prognosis among the digestive tract cancers, and chemotherapy is the treatment of choice for many patients. In this study, we experimentally introduced an Escherichia coli-derived uracil phosphoribosyltransferase (UPRT) gene to cultured esophageal cancer cell lines to potentiate the antitumor effects of a representative anticancer drug, 5-fluorouacil (5-FU). UPRT is a pyrimidine salvage enzyme that catalyzes the synthesis of uridine monophosphate from uracil and PRPP. The UPRT gene was transduced into five cultured esophageal cancer cell lines, TE1, TE2, TE3, NUEC1, and T.T, using an adenovirus vector. It was confirmed that the sensitivities of all cultured cell lines to 5-FU were increased in vitro. Subsequently, the T.T line was subcutaneously inoculated into nude mice to induce tumors, after which 5-FU was administered intraperitoneally. When a UPRT gene-recombinant adenovirus vector was directly injected into the tumors, tumor proliferation was markedly inhibited compared with that in the group treated with 5-FU alone, suggesting potentiation of 5-FU sensitivity by UPRT gene transduction in vivo. Therefore, we potentiated the effects of commercially available anticancer drugs by gene transduction. Our method may prove useful as a new form of cancer gene therapy in the future.

Adenoviridae↗
PubMed2001

Biotransformation of (+)- and (-)-camphorquinones by plant cultured cells.

Biotransformation of (+)- and (-)-camphorquinones with suspension plant cultured cells of Nicotiana tabacum and Catharanthus roseus was investigated. It was found that the plant cultured cells of N. tabacum and C. roseus reduce stereoselectively the carbonyl group of (+)- and (-)-camphorquinones to the corresponding alpha-keto alcohols.

Biotransformation↗
PubMed2001

Two-step regulation of left-right asymmetric expression of Pitx2: initiation by nodal signaling and maintenance by Nkx2.

Pitx2 is left--right (L--R) asymmetrically expressed initially in the lateral plate and later in primordial visceral organs. The transcriptional regulatory mechanisms that underlie L--R asymmetric expression of Pitx2 were investigated. Mouse Pitx2 has a left side-specific enhancer (ASE) that mediates both the initiation and maintenance of L--R asymmetric expression. This element contains three binding sites for the transcription factor FAST. The FAST binding sites function as Nodal-responsive elements and are sufficient for the initiation but not for the maintenance of asymmetric expression. The maintenance requires an Nkx2-5 binding site also present within the ASE. These results suggest that the left-sided expression of Pitx2 is directly initiated by Nodal signaling and is subsequently maintained by Nkx2. Such two-step control may represent a general mechanism for gene regulation during development.

Animals↗
PubMed2001

Diffusion of nodal signaling activity in the absence of the feedback inhibitor Lefty2.

The role of Lefty2 in left-right patterning was investigated by analysis of mutant mice that lack asymmetric expression of lefty2. These animals exhibited various situs defects including left isomerism. The asymmetric expression of nodal was prolonged and the expression of Pitx2 was upregulated in the mutant embryos. The absence of Lefty2 conferred on Nodal the ability to diffuse over a long distance. Thus, Nodal-responsive genes, including Pitx2, that are normally expressed on the left side were expressed bilaterally in the mutant embryos, even though nodal expression was confined to the left side. These results suggest that Nodal is a long-range signaling molecule but that its range of action is normally limited by the feedback inhibitor Lefty2.

Animals↗
PubMed2001

Protective effect of ammonia against reflux esophagitis in rats.

Although several recent studies have reported that curing Helicobacter pylori (H. pylori) may result in the development of reflux esophagitis (RE), the mechanisms leading to this complication are unknown. One by product of H. pylori infection is ammonia, which serves as an acid neutralizer. The aim of this study was to clarify whether ammonia, which is produced during H. pylori infection, has a protective effect on the esophagus. Eight-week-old male Sprague-Dawley rats were fasted for 24 hrs. Under anesthesia, both the pylorus and limiting ridge were simultaneously ligated. One hour postligation, 0.3 ml of saline or ammonia at various concentrations was administered intragastrically by gastric intubation. Three hours after ligation, the animals were killed, the esophagus and stomach were removed, and the length of esophageal hemorrhagic erosions was measured. The incidence of RE was 100% (7/7) in the control group, 71% (5/7) in the low-ammonia group, 29% (2/7) in the middle-ammonia group, and 14% (1/7) in the high-ammonia group. The severity of lesions decreased in correspondence to increases in ammonia concentration. The development of RE was significantly inhibited by ammonia in a dose-dependent manner. This study indicates that ammonia protects against development of RE. A decreased amount of ammonia in the stomach might be related to the development of RE after H. pylori eradication therapy.

Ammonia↗
PubMed2001

Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre/loxP system.

In this article, we evaluated the feasibility of the restricted replication-competent adenoviruses for treatment of anaplastic thyroid carcinomas (ATCs), which are very aggressive and difficult to treat. Because ATCs very often harbor p53 mutations, we used wt-p53 as a regulatory factor to restrict virus replication and cytopathic effect to p53-mutated cells. The recently reported "gene inactivation strategy" using p53-regulated Cre/loxP system was employed; this system consists of two recombinant adenoviruses. One has an expression unit of the synthetic p53 - responsive promoter and the Cre recombinase gene (Axyp53RECre), and another contains two expression units; the first consists of E1A gene flanked by a pair of loxP sites downstream of the constitutive CAG promoter and the second E1B19K gene under the control of the CMV promoter (AdCALE1AL). We expected that coinfection of these two adenoviruses into the cells with wt-p53 would lead to expression of the Cre, which excises E1A gene and switches off E1A expression resulting in no virus replication, whereas in the cells with mutant p53 E1A could be expressed that leads to virus replication and cell lysis. Our in vitro data demonstrate that although infection of AdCALE1AL alone led to E1A expression, viral replication and cytolysis in all the thyroid cells examined irrespective of their p53 status, the double infection did so in FRO cells (p53-null ATC) but not in FRO cells stably expressing wt-p53 and normal thyroid cells with wt-p53. These data indicate that our double infection method may have a potential for treatment of ATC and probably also other p53-defective cancer cells.

Adenovirus E1A Proteins↗
PubMed2001

Enhanced growth suppression in esophageal carcinoma cells using adenovirus-mediated fusion gene transfer (uracil phosphoribosyl transferase and herpes simplex virus thymidine kinase).

Advanced esophageal cancers are highly malignant and frequently resistant to 5-fluorouracil (5-FU). Escherichia coli uracil phosphoribosyltransferase (UP) is a pyrimidine salvage enzyme that alters 5-FU metabolism and sensitivity. A recombinant adenovirus encoding the UP gene (AxCA.UP) has been applied in gastric cancer gene therapy to sensitize cancer cells to lower concentrations of 5-FU. We have generated a recombinant adenovirus (AxCA.UT) encoding UP and herpes simplex virus thymidine kinase fusion protein (UT) to examine whether it would enhance the antitumor activity of AxCA.UP treatment. AxCA.UT treatment significantly enhanced the sensitivity of human esophageal cancer cells to and significantly enhanced the growth inhibition effects of UP gene therapy in vitro. Moreover, both 5-FU and ganciclovir showed bystander effects on growth inhibition. In an in vivo study, the therapeutic outcome of AxCA.UT treatment significantly enhanced the antitumor activity of AxCA.UP treatment. These observations suggest that AxCA.UT may be useful in esophageal cancer gene therapy.

Adenoviridae↗
PubMed2001

Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promotes collateral development in a rabbit model of hind limb ischemia.

Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor (bFGF), a new strategy for the treatment of chronic vascular occlusive disease, was examined in a rabbit model of hind limb ischemia. The left femoral artery was completely excised to induce an ischemic state in the hind limb of male rabbits. Simultaneously, a skin section was resected from the wound, and host fibroblasts were cultured. The cultured fibroblasts were infected with adenovirus vector containing modified human bFGF cDNA with the secretory signal sequence (AxCAMAssbFGF) or LacZ cDNA (AxCALacZ). At 21 days after femoral artery excision, the gene-transduced fibroblasts were administered through the left internal iliac artery. The fibroblasts significantly accumulated in the ischemic hind limb, and the AxCAMAssbFGF-treated cells secreted bFGF for less than 14 days without elevation of systemic bFGF level. At 28 days after cell administration, calf blood pressure ratio, angiographic score, capillary density of muscle tissue and blood flow of the left internal iliac artery were determined, and animals with AxCAMAssbFGF-treated cells showed significantly greater development of collateral vessels, as compared with those with AxCALacZ-treated cells. These findings suggest that adenovirus-mediated ex vivo gene transfer of bFGF was effective for improvement of chronic limb ischemia.

Adenoviridae↗
PubMed2001

Thyroid gland tumour, pemphigus foliaceus and myasthenia gravis in the daughter of a woman with myasthenia gravis.

We describe a rare case of pemphigus foliaceus associated with familial myasthenia gravis (MG). A 35-year-old woman developed MG during oral corticosteroid treatment for pemphigus foliaceus. She had been operated on for a thyroid gland tumour that was confirmed histopathologically to be papillary carcinoma without metastasis. At the time of treatment, her mother had had MG for 30 years and undergone thymectomy 22 years ago. A specific ELISA technique showed that antidesmoglein 1 antibody was present in the daughter. There are many reports of multiple diseases such as pemphigus, thymoma, malignancy, and other autoimmune diseases associated with MG. However, familial MG following pemphigus foliaceus has not been reported previously.

Adult↗