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K Kaneshiro

Publications and source records attributed to K Kaneshiro.

10 recordsLinked to original sources
PubMed2001

All kinesin superfamily protein, KIF, genes in mouse and human.

Intracellular transport is essential for morphogenesis and functioning of the cell. The kinesin superfamily proteins (KIFs) have been shown to transport membranous organelles and protein complexes in a microtubule- and ATP-dependent manner. More than 30 KIFs have been reported in mice. However, the nomenclature of KIFs has not been clearly established, resulting in various designations and redundant names for a single KIF. Here, we report the identification and classification of all KIFs in mouse and human genome transcripts. Previously unidentified murine KIFs were found by a PCR-based search. The identification of all KIFs was confirmed by a database search of the total human genome. As a result, there are a total of 45 KIFs. The nomenclature of all KIFs is presented. To understand the function of KIFs in intracellular transport in a single tissue, we focused on the brain. The expression of 38 KIFs was detected in brain tissue by Northern blotting or PCR using cDNA. The brain, mainly composed of highly differentiated and polarized cells such as neurons and glia, requires a highly complex intracellular transport system as indicated by the increased number of KIFs for their sophisticated functions. It is becoming increasingly clear that the cell uses a number of KIFs and tightly controls the direction, destination, and velocity of transportation of various important functional molecules, including mRNA. This report will set the foundation of KIF and intracellular transport research.

Animals↗
PubMed2001

TNFalpha induces expression of transcription factors c-fos, Egr-1, and Ets-1 in vascular lesions through extracellular signal-regulated kinases 1/2.

Migration, proliferation and differentiation of vascular smooth muscle cells (VSMC) and macrophages are important pathological responses that contribute to the development and progression of vascular lesions. Cytokines such as TNFalpha are present at sites of vascular injury and regulate a variety of cellular functions of inflammatory cells and VSMC. Cell migration, proliferation and differentiation require de novo gene transcription resulting from extracellular signals being transduced to the nucleus, where multiple genes are regulated to participate in lesion formation. In VSMC and macrophages, TNFalpha induces activation of the extracellular signal-regulated kinases 1/2 (ERK 1/2), which transmit signals from the cytosol to the nucleus. Potential nuclear targets of TNFalpha-activated ERK 1/2 include the transcription factors Ets-1, Egr-1, and c-fos, which are known to regulate cellular growth, differentiation, and migration. The aim of this study was to investigate the expression of the transcription factors Ets-1, Egr-1 and c-fos in different types of vascular lesions, their regulation by TNFalpha and the role of ERK 1/2 in these signaling events. Atherosclerotic lesions from fructose-fed LDL-receptor deficient mice and neointimal lesions from rat aortae 2 weeks post balloon injury demonstrated the presence and colocalization of TNFalpha, phosphorylated and activated ERK 1/2, and transcription factors Ets-1, Egr-1 and c-fos. Neointimal lesions consisted primarily of VSMC, whereas atherosclerotic lesions predominantly contained macrophages. In cultured rat aortic VSMC, TNFalpha (100 U/ml) stimulated a rapid and transient expression of Ets-1, Egr-1 and c-fos with a maximal induction 1 h after stimulation. In cultured RAW 264.7 mouse macrophages, TNFalpha similarly induced the expression of Ets-1, Egr-1, and c-fos. Induction of these transcription factors was mediated via ERK 1/2 activation, since the ERK 1/2-pathway inhibitor PD98059 (10-30 microM) significantly inhibited their TNFalpha-induced expression. TNFalpha induced ERK 1/2 activation in both cell types. These findings underscore the importance of the ERK 1/2 pathway in the expression of TNFalpha-regulated transcription factors, which may participate in different forms of vascular lesion formation.

Animals↗
PubMed2001

Peroxisome proliferator-activated receptor-gamma ligands inhibit nuclear but not cytosolic extracellular signal-regulated kinase/mitogen-activated protein kinase-regulated steps in vascular smooth muscle cell migration.

Vascular smooth muscle cell (VSMC) migration involves adhesion, locomotion, and invasion regulated by various signaling molecules, among which the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK) play a critical role. We have shown that the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands troglitazone and rosiglitazone inhibit VSMC migration downstream of ERK MAPK. The purpose of the current study was to more specifically determine which step(s) in VSMC migration are targeted by inhibition of the ERK MAPK pathway or activation of PPAR-gamma. VSMC adhesion was not affected by the ERK MAPK pathway inhibitor PD98059 or PPAR-gamma ligands. Phosphorylation and activation of myosin light chain kinase (MLCK) play important roles in cell locomotion. Platelet-derived growth factor (PDGF)-induced MLCK phosphorylation (1.7-fold) was completely blocked by PD98059 at 30 microM (p < 0.05), but not by troglitazone or rosiglitazone. PDGF-directed migration (5.8-fold) was inhibited by PD98059 (-88% at 30 microM) and the MLCK inhibitor ML9 (0.1-1 microM, -84% at 1 microM) (all p < 0.05). The transcription factor Ets-1 mediates matrix metalloproteinase induction required for tissue invasion by VSMC. PDGF (20 ng/ml) stimulated an Ets-1 protein expression (14-fold at 60 min) in VSMC, which was inhibited by PD98059 (-72% at 30 microM), troglitazone (-69% at 20 microM), and rosiglitazone (-54% at 10 microM) (all p < 0.05). Immunohistochemistry of rat aortae 2 h after balloon injury showed a dramatic upregulation of Ets-1, which was markedly inhibited in animals that had received troglitazone treatment. In contrast, phosphorylated ERK MAPK was not affected by troglitazone. These data are consistent with PPAR-gamma ligands exerting their anti-migratory effects downstream of ERK MAPK activation by blocking nuclear events, such as Ets-1 expression, required for cell invasion in response to arterial injury.

Animals↗
PubMed1999

Interleukin-6 and soluble interleukin-6 receptor in the colonic mucosa of inflammatory bowel disease.

BACKGROUND: Interleukin-6 (IL-6) has multiple immunological effects on a wide variety of cells and tissues. The expression of IL-6 and IL-6 receptor (IL-6R) may be important to the pathogenesis of inflammatory bowel disease (IBD). METHODS: In the present study, we examined whether mucosal IL-6 and soluble IL-6R were associated with the pathophysiology of IBD using the colonic mucosal specimens obtained from patients with IBD. Enzyme-linked immunosorbent assay was used to measure the levels of IL-6 and sIL-6R in organ cultures of mucosal tissues and in cell cultures of fractionated mucosal cells as well as in the serum. Expression of IL-6 and IL-6R was analysed by reverse transcription-polymerase chain reaction analysis using freshly isolated lamina propria mononuclear cells (LPMC). RESULTS: The levels of IL-6 and sIL-6R in organ cultures were substantially elevated in patients with IBD, especially in those with histologically active inflammation. In contrast, considerably higher levels of sIL-6R were detected in patients with other types of colonic inflammation who were included as inflammatory controls, but elevation of IL-6 was less prominent in such patients. The positivity for expression of IL-6 and IL-6R mRNA in LPMC was in parallel with the results obtained in organ cultures. In cell cultures, mucosal macrophages were the main cell type producing both IL-6 and sIL-6R on a per cell basis and other cell fractions including colonic epithelial cells and lymphocytes produced substantially lower amounts of these molecules. The levels of IL-6 and sIL-6R in organ cultures, but not those in the serum, showed a significantly positive correlation with the degree of clinical disease activity in patients with IBD. CONCLUSIONS: Enhanced IL-6/sIL-6R-mediated immune and inflammatory responses may be implicated, at least partly, in the continuation of intestinal inflammation in patients with IBD.

Adolescent↗
PubMed1995

[Chemosensitivity test with endoscopic biopsy specimens].

In SDI test using tetrazolium salt, we compared MTT with XTT, which has been recently developed and is more sensitive than MTT. Further, a chemosensitivity test with endoscopic biopsy specimens using XTT was conducted. The reproducibility of the MTT assay was assessed under various conditions. The I.I of MTT assay did not vary according to type or concentration of anticancer drugs and the biopsy site of specimens. Then MTT and XTT assay were compared, revealing the results of these 2 assays were significantly correlated. Thus, XTT assay was performed with tissues from surgical specimens using biotome. Of the 16 specimens subjected to XTT assay, 6 showed an OD value of 0.100 or more, which was well within assessment. XTT assay was also performed in biopsy specimens from patients using a biotome manipulated under endoscopic guidance before operation. Three among 6 specimens showed an OD value of 0.100 or more. Our findings have demonstrated that the SDI test using XTT can be used for the chemosensitivity test, even when these specimens contain a relatively small number of cells collected using a biotome.

Animals↗
PubMed1993

Change in the signal-response sequence responsible for asymmetric isolation between Drosophila planitibia and Drosophila silvestris.

Drosophila planitibia and Drosophila silvestris form a species pair that is an example of species diverged through a founder event. These species exhibit asymmetric sexual isolation, courtships between D. planitibia males and D. silvestris females being more successful than courtships between D. silvestris males and D. planitibia females. When analyzing the signal-response courtship sequence in these species, we found that D. silvestris females responded to male circling by standing or preening while D. planitibia females required further signals from the male to stop walking. The main reason for the reduced mating success rate of D. silvestris males with D. planitibia females was that the females responded to male circling by walking and the males did not proceed to the head-under-wings (HUW) position of a walking female. Another critical phase in these courtships was the HUW position in D. silvestris, where males proceeded almost immediately to wing and leg vibration. The courtships between D. planitibia male and D. silvestris female proceeded in a signal-response coordination until the male went to the HUW position, where he fanned his wings for too long a period before proceeding to wing and leg vibration. Thus, it seems that the asymmetric isolation between D. planitibia (ancestral species) and D. silvestris (derived species) is mainly due to a loss of transitions in the signal-response chain of D. silvestris. A change in the behavior of the males in the HUW position has caused further isolation between the species in both directions.

Animals↗
PubMed1988

Hawaiian courtship songs: evolutionary innovation in communication signals of Drosophila.

In Hawaii, flies of the genus Drosophila have undergone spectacular adaptive radiation, resulting in the evolution of more than 500 species of Drosophila that are found nowhere else on earth. This taxonomic uniqueness is reflected in behavior and morphology. Hawaiian Drosophila sing songs, as do continental Drosophila; however, the Hawaiian songs have diverged strongly in form and mechanism of production. The click-song of D. fasciculisetae's (Maui) has a carrier frequency an order of magnitude higher than those reported in familiar continental species, such as D. melanogaster (170 hertz). Drosophila fasciculisetae's song resembles a cicada's more than a fly's song. The song of D. cyrtoloma (Maui) has a complex pulse rhythm more typical of crickets than flies. The pulse song of D. silvestris (Hawaii) closely resembles that of D. melanogaster in both pulse rhythm and carrier frequency, but D. melanogaster sings by vibrating its wings, whereas D. silvestris sings through abdominal vibrations. These mechanisms are radical departures from the continental wing song mechanism and are further examples of the remarkable behavioral innovation that has occurred in the Drosophila of Hawaii during their evolutionary transit through these islands.

Animal Communication↗
PubMed1988

[FEP and FAP combination chemotherapy in advanced gastric cancer. Research Group for Gastric Cancer].

Twenty-six patients with unresectable gastric cancer, divided into two groups, were treated with combination chemotherapy of FEP (14 patients) or FAP (12 patients). The FEP regimen performed every 4 weeks was as follows: UFT 400 mg/m2 (p.o.) everyday, etoposide 50 mg/m2 (i.v.) and CDDP 30 mg/m2 (i.v.) on days 1, 8 and 15. FAP regimen was performed every 4 weeks was: UFT 400 mg/m2 (p.o.) everyday, adriamycin 10 mg/m2 (i.v.) and CDDP 30 mg/m2 (i.v.) on days 1, 8 and 15. In FEP group, (7 males and 7 females) the average age was 64 (range 53 to 75). Two patients were in PS 1, 4 in PS 2 and 8 in PS 3. In FAP group (7 males and 5 females) the average age was 55 (range 30 to 74). One patient was in PS 1, 5 in PS 2 and 6 in PS 3. No one in either group had prior chemotherapy. Response rates in FEP and FAP groups were 28.5% (4/14) and 33.3% (4/12), respectively. The median survival periods were 4.5 months in FEP group and 6.5 months in FAP group. As for side effects, myelosuppression appeared most frequently, being followed by alopecia and nausea, although the degree of alopecia was milder in FEP than in FAP. We conclude that new combination chemotherapies of either FEP or FAP are useful for advanced gastric cancer.

Adenocarcinoma↗
PubMed1986

[An autopsy case of malignant lymphoma of the pancreas].

Case reports of malignant lymphoma of the pancreas are extremely rare. We experienced a 36-year-old man with malignant lymphoma involving the pancreas associated with obstructive jaundice, confirmed by autopsy. It is very difficult to differentiate between pancreatic carcinoma and pancreatic malignant lymphoma. Age, icterus, diffuse pancreatic enlargement, pathological findings and tumor markers may be useful in suggesting lymphoma. Trials of positive biopsy, appropriate radiotherapy and chemotherapy are necessary in patients who may have malignant lymphoma of the pancreas.

Adult↗