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Biomedical subjects

K Ichimura

Publications and source records attributed to K Ichimura.

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

Gamma-rays enhance rAAV-mediated transgene expression and cytocidal effect of AAV-HSVtk/ganciclovir on cancer cells.

Adeno-associated virus (AAV) vector has several unique properties suited for gene therapy applications. However, relatively low efficiency of transgene expression, which is mainly due to a limited second-strand synthesis from the single-stranded AAV genome, can be a problem in some applications that require potent gene expression such as antitumor applications. Recently, gamma-ray irradiation has been reported to enhance the second-strand synthesis of the AAV genome, and consequently transgene expression. We demonstrate here that an AAV vector harboring the herpes simplex virus type-1 thymidine kinase (HSVtk) is able to kill cancer cells more efficiently when used in combination with gamma-ray irradiation. A human maxillary sinus cancer cell line, NKO-1, was efficiently killed in combination with HSVtk transduction and ganciclovir (GCV), as expected. More importantly, gamma-ray irradiation of practical dosages augmented the cytocidal effect of the HSVtk/GCV system. Southern analysis indicated that gamma-rays enhanced the double-strand synthesis of the rAAV genome in NKO-1 cells. These findings suggest that the combination of rAAVtk/GCV suicide gene therapy with radiotherapy has synergistic effects in the treatment of cancers and may lead to a reduction of the potential toxicity of both rAAVtk/GCV and gamma-ray irradiation.

Antiviral Agents↗
PubMed2001

Morphological spectrum of cyclin D1-positive mantle cell lymphoma: study of 168 cases.

Immunostaining for cyclin D1 is essential for reliable diagnosis of mantle cell lymphoma (MCL). However, a small number of cyclin D1-positive lymphomas other than MCL have been encountered. Our goal was to investigate the morphological spectrum of MCL as a disease entity, based on cyclin D1 overexpression. We reviewed 181 biopsy specimens obtained from 168 cases of cyclin D1-positive MCL. Typical findings were the presence of nodular (53.9% of cases) or diffuse (46.1%) histological patterns, containing mantle zone patterns (16.8%), naked germinal centers (33.5%) and perivascular hyaline deposition (83.2%). Unusual findings of residual germinal centers with a mantle cuff (four cases) and follicular colonization (two cases) were seen. High magnification showed a monotonous proliferation of tumor cells with cytological diversity including small (3.0%), intermediate (43.1%), medium (34.1%), medium-large (13.2%) and large (6.6%) cells. Pleomorphic and blastic/blastoid variants were encountered in 9.6 and 7.2% of cases, respectively. Three cases had foci of cells of considerable size, with a moderately abundant pale cytoplasm resembling marginal zone B cells. Two cases showed an admixture of cells which appeared transformed and mimicked the histology of chronic lymphocytic leukemia/small lymphocytic leukemia. In one, neoplastic mantle zones were surrounded by sheets of mature plasma cells, resembling the plasma cell type of Castleman's disease. An admixture of areas characteristic of MCL and of other larger cells, indicating histological progression or a composite lymphoma, were observed in seven cases. In high-grade lesions of five cases, nuclear staining of cyclin D1 was rarely detected. In our experience, cyclin D1 expression was also found in nine lymphomas other than MCL (five plasma cell myelomas, three Hodgkin's disease and one anaplastic large cell lymphoma). The application of cyclin D1 staining prompted us to recognize the broad morphological spectrum of MCL. MCL can be diagnosed with the application of cyclin D1 immunostaining, if careful attention is given to architectural and cytological features.

Adult↗
PubMed2001

A novel branching pattern of the superior mesenteric artery found in the bullfrog (Rana catesbeiana) amphibian.

The branching and distribution patterns of the superior mesenteric artery were studied in 10 adult bullfrogs (Rana catesbeiana) after injection of coloured latex solution into the vasculature. The abdominal digestive organs in the bullfrog were mainly supplied by the coeliac artery and the superior mesenteric artery, both of which arose as a common trunk, the coeliacomesenteric artery, from the abdominal aorta. The coeliac artery supplied the stomach, liver, gallbladder and the pancreas, whereas the first branch of the superior mesenteric artery was the splenic artery with other branches supplying the greater part of intestine. The apex of the intestinal loop was defined as the region supplied by the trunk of the superior mesenteric artery, and its intestinal branches constituted a 'nested formation' which had the following characteristics. (1) The branches of the trunk were distributed to both sides of the apex, and the distribution regions of younger branches were located more distant from the apex than those of older branches. (2) Two branches directed towards both sides of the trunk frequently made a common stem arising from the trunk. The second branch of the superior mesenteric artery constituted a secondary trunk and its distribution region could be defined as a secondary apex, since 1 of its branches also constituted a nested formation which was distributed to both sides of the primary and secondary apices. The intestinal branches of the superior mesenteric artery were divided into 4 types on the basis of their pattern of branching and course. It is suggested that the nested formation of the superior mesenteric artery in the bullfrog is a remnant of the vascular pattern of the tadpole, which possesses a double spiral mode of intestinal convolution, probably supplied by arteries with the nested formation in a latent form.

Animals↗
PubMed2001

Oligodendroglial tumors frequently demonstrate hypermethylation of the CDKN2A (MTS1, p16INK4a), p14ARF, and CDKN2B (MTS2, p15INK4b) tumor suppressor genes.

We investigated 34 oligodendroglial tumors (7 oligodendrogliomas, 11 anaplastic oligodendrogliomas, 8 oligoastrocytomas, and 8 anaplastic oligoastrocytomas) for deletion, mutation, hypermethylation, and expression of the CDKN2A (MTS1, p16INK4a), p14ARF, and CDKN2B (MTS2, p15INK4b) tumor suppressor genes at 9p21. One anaplastic oligoastrocytoma carried a homozygous deletion including all 3 genes. None of the tumors demonstrated point mutations in any of the genes. Methylation-specific polymerase chain reaction (MSP) analysis and sequencing of bisulfite-modified DNA, however, revealed frequent hypermethylation of the 5'-CpG islands in CDKN2A, p14ARF, and CDKN2B. Partial or complete methylation of the majority of CpG sites analyzed from each gene was detected in 32% of the tumors at the CDKN2A gene and at a similar percentage (41%) of the tumors at the p14ARF gene and the CDKN2B gene. Most tumors with CDKN2A, p14ARF, and/or CDKN2B hypermethylation either lacked detectable transcripts from these genes or had lower mRNA levels than those determined for non-neoplastic brain tissue. There was a significant correlation between hypermethylation of these genes and the presence of allelic losses on chromosomal arms 1p and 19q. In addition, p14ARF hypermethylation was predominantly found in tumors without a demonstrated TP53 mutation. Taken together, our results indicate that hypermethylation of CDKN2A, p14ARF, and CDKN2B is an important epigenetic mechanism by which oligodendroglial tumors may escape from p53- and pRb-dependent growth control.

Adolescent↗
PubMed2001

Oxidative stress activates ATMPK6, an Arabidopsis homologue of MAP kinase.

Mitogen-activated protein kinase (MAPK) cascades function in biotic and abiotic stress responses in plants. We analysed effect of oxidative stress on the activation of ATMPK6, an Arabidopsis thaliana MAPK, in Arabidopsis T87 cultured cells and rosette leaves using anti-ATMPK6 specific antibody. ATMPK6 in T87 cells was strongly activated by reactive oxygen species (ROS) such as H(2)O(2) and KO(2). In leaves, ATMPK6 was activated by paraquat and 3-amino-1,2,4-triazole (a catalase inhibitor). These results indicate that ATMPK6 is one of the candidates for signal mediators in response to abiotic or biotic sources for ROS in Arabidopsis.

Adaptation, Physiological↗
PubMed2001

Harpin induces activation of the Arabidopsis mitogen-activated protein kinases AtMPK4 and AtMPK6.

Mitogen-activated protein kinases (MAPKs) are key enzymes that mediate adaptive responses to various abiotic and biotic stresses, including pathogen challenge. The proteinaceous bacterial elicitor harpin (secreted by Pseudomonas syringae pv syringae) activates two MAPKs in suspension cultures of Arabidopsis var. Landsberg erecta. In this study, we show that harpin and exogenous hydrogen peroxide (H(2)O(2)) activate myelin basic protein kinases in Arabidopsis leaves. Using anti-AtMPK4 and anti-AtMPK6 antibodies, we identify the harpin-activated MAPKs in both leaves and suspension cultures as AtMPK4 and AtMPK6, and show that H(2)O(2), generated by Arabidopsis cells in response to challenge with harpin, activates only AtMPK6. However, treatments with catalase, which removes H(2)O(2), or diphenylene iodonium, which inhibits superoxide and H(2)O(2) production, do not inhibit harpin-induced activation of AtMPK4 or AtMPK6. In addition, activation of AtMPK4 but not AtMPK6 is inhibited by the MAPK kinase inhibitor PD98059. Neither harpin nor H(2)O(2) has any effect on AtMPK4 or AtMPK6 gene expression. In addition, the expression of AtMEKK1, AtMEK1, or AtMKK2, previously shown to be potential functional partners of AtMPK4, were not affected by either harpin or H(2)O(2) treatments. These data suggest that harpin activates several signaling pathways, one leading to stimulation of the oxidative burst and others leading to the activation of AtMPK4 or AtMPK6.

Arabidopsis↗
PubMed2001

Globosal basal cells are identified as proliferating cells in mouse olfactory epithelium.

Although anti-bromodeoxyuridine (BrdU) antibodies are used for detecting proliferating cells, they may stain proliferating cells in phases following the S-phase, except for G1. Anti-Ki67 antibodies are widely used for detecting proliferating cells in all phases of the cell cycle (G1-, S-, G2-, and M-phase), but not in resting cells (G0-phase). Anti-cyclin D1 antibodies are used to detect proliferating cells in the G1-phase. The present study investigated the olfactory epithelium of mice by double immunostaining using antibodies to BrdU, Ki67. cyclin D1, and cytokeratin 14 (CK14). The cells positive to the anti-BrdU antibody, the anti-Ki67 antibody, and the anti-cyclin D1 antibody differed from the cells positive to the anti-CK14 antibody. Thus, we confirmed that the proliferating cells in all the phases of the cell cycle, including the G1-phase, were globosal basal cells, which were the precursors of the olfactory cells.

Animals↗
PubMed2001

Follicular lymphoma of the salivary gland: a clinicopathological and molecular study of six cases.

To clarify the clinicopathologic, immunohistologic, and genotypic features of follicular lymphoma arising from the salivary glands, we examined 20 cases of operatively resected primary salivary gland lymphoma and identified 6 such cases. There were 4 women and 2 men with ages ranging from 38 to 64 years (median 50 years). The tumor arose from the parotid gland in 4 cases and the submandibular gland in the remaining 2. Four patients were stage IE and 2 were stage IIE-1. The median follow-up period was 49 months and all patients were alive and well at the time of going to press. Histologically, 5 patients were follicular lymphoma grade 2, and 1 was grade 3. In all specimens in noninfiltrating salivary gland tissue, there was periductal lymphocytic infiltration near the lymphoma. Moreover, myoepithelial sialoadenitis was noted in 2 lesions. An immunohistochemical study revealed all 6 cases were CD10+, CD79a+, bcl-6+, CD3-, CD5-, CD21-, CD23-, and CyclinD1-. The tumor cells expressed bcl-2 in 3 cases and p53 oncoprotein in 4 cases. Two cases revealed clonal bands with polymerase chain reaction (PCR) assay for the immunoglobulin heavy (IgH) gene. The bcl-2/IgH translocation at the major breakpoint region was detected in 1 case (16%). We found a relatively high incidence of follicular lymphomas (30%) in salivary gland lymphomas. Among the mucosa-associated lymphoid tissue (MALT) system, follicular lymphomas appeared to occur frequently in the salivary glands as well as the duodenum and skin. Moreover, follicular lymphoma arising from the salivary glands appeared to have some of the characteristics of MALT-type lymphoma including indolent prognosis, presence of myoepithelial sialoadenitis, and rarity of the BCL-2 gene rearrangement.

Adult↗
PubMed2001

Haemangiopericytoma of infratemporal fossa.

Haemangiopericytomas (HPCs) are rare vascular tumours that commonly involve the soft tissues of the trunk and lower extremities. In the head and neck, the most common sites are the nasal cavity and the paranasal sinuses, and unusually, the orbital region, the parotid gland, and the neck. We report a patient with HPC that originated in the infratemporal fossa and involved the pterygopalatine and the middle cranial fossae, apparently the first such case to be reported. Although the patient has undergone resection on three separate occasions, the tumour recurred. We then performed an extended resection using the infratemporal fossa approach type D. The patient has shown no recurrence in the past five years. Although histopathologic confirmation of this malignancy may be difficult, extensive resection remains the most effective treatment in such cases.

Adult↗
PubMed2001

Effect of weak electric current on reducing oral bacteria in vitro.

The ions generated by weak electric current may be used for removal of dental plaque. Also, it has been judged from changes in the viable bacterial cell count and the amount of adenosine triphosphate (ATP) in the saliva that the passage of such a current also has a bactericidal effect on the oral microflora. We confirmed in vitro that 0.5 and 1.0 mA currents that passed for 10 min through phosphate buffered saline containing salivary bacteria were effective in killing the bacteria.

Adenosine Triphosphate↗
PubMed2000

Combined therapy with conservative surgery, radiotherapy, and regional chemotherapy for maxillary sinus carcinoma.

BACKGROUND: Current goals for the treatment of carcinoma of the maxillary sinus include the preservation of vision, ability to eat, ability to communicate, and appearance as well as cure. METHODS: Seventy-five Japanese patients who presented with maxillary sinus carcinoma between 1979 and 1997 were analyzed retrospectively. There were 48 males and 27 females with a median age of 62 years. The mean follow-up period was 73 months. All patients underwent multimodality therapy including surgery through a sublabial incision, radiotherapy, and regional chemotherapy. The regional lymph nodes were treated only in those patients with cervical lymph node involvement. RESULTS: The 5-year and 10-year overall survival rates were 76% and 66%, respectively. In 65 patients with squamous cell carcinoma, the 5-year and 10-year overall survival rates were 77% and 66%, respectively. All 23 patients with orbital involvement retained the orbital contents and 17 patients demonstrated adequate ocular function. There was no disease recurrence reported among patients with involvement of the foramen rotundum or the foramen ovale, whereas two of the three patients with invasion of the foramen lacerum developed disease recurrence. There were 12 complications in 12 patients, including double vision (4 patients), cataracts (3 patients), trismus (4 patients), and fistula formation (1 patient). CONCLUSIONS: Control of the primary tumor site is important in the curative treatment of patients with maxillary sinus carcinoma. Combined therapy with conservative surgery, radiotherapy, and regional chemotherapy appears to be an effective method for local control and the preservation of ocular function.

Antimetabolites, Antineoplastic↗
PubMed2000

Structure of the human retinoblastoma-related p107 gene and its intragenic deletion in a B-cell lymphoma cell line.

The human p107 protein shares many structural and functional features with the retinoblastoma gene product and retinoblastoma-related p130 protein. In this study, we have cloned and elucidated the complete intron-exon organization of the gene encoding the p107 protein. The gene contains 22 exons spanning over 100kilobase pairs of genomic DNA. The length of individual exons ranges from 50 to 840base pairs. The arrays of exons in the p107 gene are rather similar among members of the gene family, especially to those of the p130 gene, while the length of introns is extensively diverse. This study will provide a molecular basis for implementing comprehensive screening for p107 mutations using genomic DNAs from human malignancies. We also show a detailed structure of an intragenic deletion of the p107 gene found in a human B-cell lymphoma cell line, KAL-1, which was shown to occur by homologous recombination between the two directly repeated Alu family sequences.

Base Sequence↗
PubMed2000

Light-driven motion of liquids on a photoresponsive surface

The macroscopic motion of liquids on a flat solid surface was manipulated reversibly by photoirradiation of a photoisomerizable monolayer covering the surface. When a liquid droplet several millimeters in diameter was placed on a substrate surface modified with a calix[4]resorcinarene derivative having photochromic azobenzene units, asymmetrical photoirradiation caused a gradient in surface free energy due to the photoisomerization of surface azobenzenes, leading to the directional motion of the droplet. The direction and velocity of the motion were tunable by varying the direction and steepness of the gradient in light intensity. The light-driven motion of a fluid substance in a surface-modified glass tube suggests potential applicability to microscale chemical process systems.

Journal Article↗
PubMed2000

The origin of alveolar macrophages in the transplanted lung: a longitudinal microsatellite-based study of donor and recipient DNA.

Transplanted lungs are initially populated by donor pulmonary alveolar macrophages (PAMs). These will form major antigen presenters for the recipient's suppressed immune system. They may be expected to be replaced by recipient major histocompatibility complex-compatible cells, with time. We have isolated CD14+ PAMs from bronchoalveolar lavage specimens for 6 months after transplantation and identified their origin by using microsatellite analysis. This DNA-based technology permits the reliable identification of the origin of cells from different individuals. We show that replacement of donor PAMs occurs with individual dynamics in each case. Recipient PAMs usually appeared within 2 weeks, whereas donor cells could be retained for as long as 6 months. In this limited series, there was no obvious correlation between the dynamics of this process and the occurrence of rejection episodes or infections.

Adult↗
PubMed2000

Deregulation of the p14ARF/MDM2/p53 pathway is a prerequisite for human astrocytic gliomas with G1-S transition control gene abnormalities.

Deregulation of G1-S transition control in cell cycle is one of the important mechanisms in the development of human tumors including astrocytic gliomas. We have previously reported that approximately two-thirds of glioblastomas (GBs) had abnormalities of G1-S transition control either by mutation/homozygous deletion of RB1 or CDKN2A p16INK4A), or amplification of CDK4 (K. Ichimura et al., Oncogene, 13: 1065-1072, 1996). However, abnormalities of G1-S transition control genes may induce p53-dependent apoptosis in cells. Recent investigations suggest that p14ARF is induced in response to abnormal cell cycle entry and results in p53 accumulation by inhibiting MDM2-mediated transactivational silencing and degradation of p53. To investigate the roles of the G1-S transition control system and the p14ARF/MDM2/p53 pathway in the development of astrocytic gliomas, we examined abnormalities of genes involved in these regulatory pathways in a total of 190 primary human astrocytic gliomas of different malignancy grades [136 GBs, 39 anaplastic astrocytomas (AAs) and 15 astrocytomas (As)]. Sixty-seven percent of GBs (91/136) and 21% of AAs (8/39) had abnormalities of the G1-S control system either by mutation/homozygous deletion of RB1, CDKN2A or CDKN2B, or amplification of CDK4. Seventy-six percent of GBs (103 of 136), 72% of AAs (28 of 39), and 67% of As (10 of 15) had deregulated p53 pathway either by mutation of TP53, amplification of MDM2, or homozygous deletion/mutation of p14ARF. When all of the data were combined and compared, 96% of GBs (87 of 91) and 88% of AAs (7 of 8) with abnormal G1-S transition control also had deregulated p53 pathway. Thus, we demonstrate that deregulation of the G1-S transition control system was almost always accompanied by inactivation of the p53 pathway, clearly illustrating the cooperative roles of these two systems in the development/progression of primary human astrocytic gliomas.

Astrocytoma↗
PubMed2000

MAP kinase cascades in Arabidopsis: their roles in stress and hormone responses.

Mitogen-activated protein kinase (MAPK) cascades have essential roles in diverse intracellular signaling processes in plants, animals and yeasts. In plants, MAPK and MAPK-like kinase activities are transiently activated in response to environmental stresses and plant hormones. In addition, transcription of genes encoding protein kinases involved in MAPK cascades in upregulated by environmental stresses. A possible MAPK cascade of Arabidopsis was identified based on both the yeast two-hybrid analysis and functional complementation analysis of yeast mutants. This MAPK cascade may have important roles in stress signal transduction pathways in Arabidopsis.

Adaptation, Physiological↗
PubMed2000

Pleomorphic adenoma of the pterygopalatine fossa: a case report.

Pleomorphic adenoma (PA) is the most common benign tumor of the major salivary glands. It can also Occur in the minor salivary glands, mainly in the oral cavity, and in other sites in the head and neck region. We present a very rare case of PA in the pterygopalatine fossa. Surgical resection of the tumor was performed via the transmaxillary approach. The patient has experienced neither surgical complications nor recurrence in the past 3 years. This case suggests that a localized benign tumor in the pterygopalatine fossa can be removed safely and efficaciously via a transmaxillary approach.

Adenoma, Pleomorphic↗