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K Hirata

Publications and source records attributed to K Hirata.

At least 91 records · Page 5Linked to original sources
PubMed2001

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression.

PURPOSE: A disruption in the balance between the matrix metalloproteinases (MMPs) and their natural inhibitors, tissue inhibitors of metalloproteinases (TIMPs), has been implicated in the progression of many types of cancer. The aim of this study was to determine whether a specific MMP or TIMP has clinicopathologic and prognostic significance in pancreatic carcinoma. PATIENTS AND METHODS: Using immunohistochemistry, we analyzed 70 pancreatic ductal adenocarcinoma tissues for expression of MMP-1, MMP-2, MMP-3, MMP-7 (matrilysin), MMP-9, MT1-MMP, TIMP-1, and TIMP-2. The results were matched with clinicopathologic characteristics and patients' survival. The effects of the suppression of a specific MMP on in vitro invasiveness of pancreatic carcinoma cells were also examined. RESULTS: Expression of MMP-1, MMP-2, MMP-3, matrilysin, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 was detected in either tumor cells or tumor stromal cells, or in both components, at varying frequencies. Among MMPs, matrilysin showed a unique distribution in the tumor nests; its expression was usually most pronounced at the invasive front of the tumors. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 40 cases (57%), were judged to be positive for matrilysin. Matrilysin positivity was significantly correlated with pT, pN, and pM categories and with more advanced pathologic tumor-node-metastasis stages. Patients with matrilysin-positive carcinoma had a significantly shorter overall survival time than did those with matrilysin-negative carcinoma. Matrilysin was a significant independent prognostic factor for overall survival in multivariate analysis. In contrast, there was no correlation between the presence of other MMPs or TIMPs and clinicopathologic characteristics, nor was the presence of individual MMPs or TIMPs related to survival. Antisense matrilysin-transfected CFPAC-1 cells expressed reduced levels of matrilysin and demonstrated a similar growth potential but were less invasive in vitro compared with neotransfected CFPAC-1 cells. CONCLUSION: Our results suggest that matrilysin may play a key role in progression of pancreatic carcinoma and thereby contribute to a poor prognosis. Because different synthetic MMP inhibitors affect different types of MMPs to a different degree, examination of the expression of MMPs, especially that of matrilysin, may serve as an indicator for selecting the most effective MMP inhibitor.

Adenocarcinoma↗
PubMed2001

Low energy quasiparticle excitation in the vortex state of borocarbide superconductor yni2b2c.

We measured the heat capacity C(p) and microwave surface impedance Z(s) in the vortex state of YNi2B2C. In contrast to conventional s-wave superconductors, C(p) shows a square root[H] dependence. This square root[H] dependence persists even after the introduction of the columnar defects which change the electronic structure of the vortex core regime and destroy the regular vortex lattice. On the other hand, flux flow resistivity is nearly proportional to H. These results indicate that the vortex state of YNi2B2C is fundamentally different from the conventional s-wave counterparts, in that the delocalized quasiparticle states around the vortex core are important, similar to d-wave superconductors.

Journal Article↗
PubMed2001

Telomerase activity of cultured human pancreatic carcinoma cell lines correlates with their potential for migration and invasion.

BACKGROUND: Despite the recent clinical finding that high telomerase activity is an unfavorable prognostic marker for various human malignant tumors, there has been no experimental evidence supporting the link between telomerase and tumor aggressiveness. In the current investigation, the authors examined the relation between telomerase activity and potential for biologic aggressiveness in human pancreatic carcinoma cells. METHODS: Telomerase activity was measured in a poorly metastatic cell line HPC-3 and its highly metastatic variant HPC-3H4, as well as in many pancreatic carcinoma cell lines. Aggressive behavior of cancer cells was assessed by in vitro migration and invasion assay. RESULTS: Compared with parental HPC-3, HPC-3H4 displayed higher telomerase activity, which was associated with a scattered phenotype and enhanced migration activity. Furthermore, the authors found that relative telomerase levels correlated well with both motility (P = 0.0041) and invasion (P = 0.0114) in 13 pancreatic carcinoma cell lines. There was, however, no significant association between telomerase activity and cell proliferation. When telomerase activity of KP-1N cells was inhibited by transfection with antisense oligonucleotides, their motility and invasion rates were significantly decreased. CONCLUSIONS: The authors concluded that the magnitude of telomerase activation may reflect the potential for aggressive behavior within cancer cells. These findings support the clinical utility of telomerase activity as a prognostic indicator. Their results also suggest a therapeutic potential for telomerase inhibitors to prevent tumor invasion and possibly metastasis.

Biomarkers, Tumor↗
PubMed2001

Degradation of bovine complement C3 by trichomonad extracellular proteinase.

Bovine trichomoniasis is a local infection of the reproductive tract making interaction with mucosal host defenses crucial. Since the parasite is susceptible to killing by bovine complement, we investigated the role of the third component of complement (C3) in host parasite interactions. Bovine C3 was purified by anionic and cationic exchange chromatography. The purified protein was characterized by immunoreactivity, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and peptide sequencing of the amino terminus of the beta chain. When purified bovine C3 was incubated for varying time periods with trichomonad extracellular proteinases, SDS-PAGE gels revealed digestion of the alpha chain to small fragments. Such degradation in vivo would prevent formation of C3b and completion of the complement cascade, resulting in evasion of killing. To evaluate the relevance of this data, we determined whether C3 was present in bovine genital secretions. With a quantitative ELISA assay, C3 could be demonstrated in both uterine and vaginal washes. To our knowledge, this is the first demonstration of bovine C3 in genital secretions. The C3 concentration increased significantly in vaginal secretions by 8 and 10 weeks in heifers infected with Tritrichomonas foetus. An increase was also seen in uterine secretions of infected heifers, but sample numbers were insufficient for statistical analysis. Transcription of the major extracellular cysteine proteinase (TFCP8) was demonstrated in T. foetus cells from uterine secretions of infected heifers by RT-PCR and Southern blotting. The results indicate that C3 may be important in genital defense and that trichomonad extracellular proteinases may play a role in evasion of complement-mediated killing.

Animals↗
PubMed2001

Features of sensory ataxic neuropathy associated with anti-GD1b IgM antibody.

Some reports have called sensory ataxic neuropathy (SAN) associated with IgM antibody against b-series gangliosides a chronic form of Miller Fisher syndrome (MFS), but this has yet to be established. We examined five patients with SAN and eight patients with IgG anti-GQ1b-positive MFS. Only one patient with SAN complained of diplopia, whose ocular movement was not limited. The other four patients had neither diplopia nor limitation of ocular movement. All the SAN patients had severe deep sense impairment, whereas one patient with MFS showed only mild vibratory sense impairment. All sera from the SAN patients had remarkably high IgM antibody titers to the b-series gangliosides GD3, GD2, GD1b, GT1b, GQ1b, GQ1b alpha, fucosyl-GD1b, and alpha galactosyl [alpha fucosyl] GD1b. An absorption study confirmed that the anti-GQ1b antibodies cross-reacted with GD3, GD2, GD1b, and GT1b. In contrast, only two samples from the MFS patients had IgG antibody to GD3, and no sample reacted with GD2, GD1b, or GT1b. SAN has different clinical or serological features from MFS, and therefore is not a chronic form of it.

Adult↗
PubMed2001

Parameters for monitoring treatment effects in CIDP with anti-MAG/SGPG IgM antibody.

We used cycles of plasma exchange and intravenous cyclophosphamide to treat a patient who had chronic inflammatory demyelinating polyneuropathy with anti-myelin-associated glycoprotein/sulfoglucuronylparagloboside IgM antibody. After treatment, serum anti-sulfoglucuronylparagloboside IgM antibody titers were reduced significantly, and clear symptomatic improvement followed. The percentage of CD57-positive lymphocytes and natural killer cell activity had also returned to normal. Our findings indicate that serial measurements of these parameters are useful for monitoring treatment effect in this disease.

Antibodies, Blocking↗
PubMed2001

Signaling mechanism underlying COX-2 induction by lysophosphatidylcholine.

Lysophosphatidylcholine, a component of oxidized low density lipoprotein, is critical for pathological conditions including atherosclerosis. However, the signaling mechanism of lysophosphatidylcholine remains poorly understood. Here we reported that lysophosphatidylcholine induces phosphorylation of p38 and the transcription factors, CREB and ATF-1 with concomitant up-regulation of cyclooxygenase-2 expression in cultured vascular endothelial cells. Lysophosphatidylcholine induced p38 phosphorylation in a time- and concentration-dependent manner partly via pathway depending on protein tyrosine kinase. Both lysophosphatidylcholine-stimulated phosphorylation of CREB and ATF-1 and lysophosphatidylcholine-increased expression of cyclooxygenase-2 mRNA and protein were effectively inhibited by a combination of SB203580 and PD98059, specific inhibitors of p38 and MEK1, respectively, as well as Ro31-8220 and H89, potent inhibitors of MSK1. These results suggest that both p38 and ERK may function as upstream signaling pathways capable of activating CREB and ATF-1 with subsequent induction of cyclooxygenase-2 expression by lysophosphatidylcholine.

Activating Transcription Factor 1↗
PubMed2001

Role of endogenous nitric oxide generation in the regulation of vascular tone and reactivity in small vessels as investigated in transgenic mice using synchrotron radiation microangiography.

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays a central role in regulation of vascular tone and reactivity. The purpose of this study is to clarify the basal tone and microvascular reactivity in eNOS-overexpressing transgenic (Tg) mice in vivo with a microangiography system using monochromatic synchrotron radiation (SR). The mouse femoral artery was cannulated, nonionic contrast media was injected, and microangiography was performed in hindlimbs of mice. Serial images of the small blood vessels (diameter <200 microm) were recorded by the SR microangiography system. At basal conditions, the diameter of tibial arteries in eNOS-Tg mice was larger than that of wild-type mice (179 +/- 8 versus 132 +/- 8 microm; P < 0.01). l-NAME treatment decreased the vessel diameter and canceled the difference in vessel diameters between two genotypes. Acetylcholine- and sodium nitroprusside-induced relaxations of small vessels were significantly reduced in Tg mice compared with wild-type mice (35.0 +/- 9.4 versus 61.6 +/- 6.7%, 85.0 +/- 10.2 versus 97.3 +/- 6.7% of the maximum relaxation, respectively). Our data provide the evidence that overproduced NO from endothelium reduces vascular tone and plays a pivotal role in regulation of vascular tone in small vessels. Furthermore, the reduced NO-mediated relaxation in small vessels of eNOS-Tg mice is demonstrated for the first time in vivo. SR microangiography allows us to evaluate the reactivity in small-sized vessels and appears to be a powerful tool for assessing the microvascular circulation in vivo.

Angiography↗
PubMed2001

Isolation and characterization of a bacterium that produces hydrocarbons extracellularly which are equivalent to light oil.

A halotorelant bacterial strain that produces a significant amount of lipids from short-chain fatty acids was isolated from the sludge of a sewage disposal plant. This strain displayed a significant extracellular accumulation of lipids. The yield of lipids including hydrocarbons was highest (120% of cell dry weight) at the end of the linear growth phase. Fractionation of the lipids using thin-layer chromatography and subsequent gas chromatography showed that hydrocarbons were also obtained following an increase in total lipids. Their yield was the highest (50% of cell dry weight) in the linear growth phase. Additional analysis using infrared absorption spectrum and gas chromatography-mass spectrometry showed that the hydrocarbon fraction was composed of alkanes, such as C15H32, C18H38, C21H44, C22H46 and C24H50. Homology analysis of the 16s rDNA sequence as well as studies of the morphological and physiological characteristics indicated that the bacterium is a strain of Vibrio furnissii.

DNA, Ribosomal↗
PubMed2001

Expression of telomerase-associated genes: reflection of telomerase activity in gastric cancer?

Telomerase activation is a characteristic of immortalized tumor cells but not of normal cells. Telomerase activity has been detected in approximately 85% of malignant tumors, and assaying for telomerase activity is thought to be useful for diagnosing cancer. Three telomerase-associated molecules [human telomerase RNA component (hTR), telomerase-associated protein (TEP1), and human telomerase reverse transcriptase (hTERT)] have been cloned. We semiquantitatively measured telomerase activity and the expression of these genes in cancerous and noncancerous regions of gastric cancer patients. We also investigated whether the expression of these genes correlated with telomerase activity. Telomerase activity in cancerous regions was significantly higher than in noncancerous regions, but there was no correlation between telomerase activity and the expression of these genes. Furthermore, no clear difference was observed between cancerous and noncancerous regions. These data indicate that the level of three telomerase-associated genes (i.e., hTR, TEP1 mRNA, hTERT mRNA), do not reflect telomerase activity, and the RNA levels of these genes are not useful markers for diagnosing gastric cancer.

Carrier Proteins↗
PubMed2001

Liver metastatic model for human gastric cancer established by orthotopic tumor cell implantation.

We have established an orthotopic implantation model that is highly metastatic to the liver. A human gastric carcinoma cell line, AZ521, with low capacity for liver metastasis was implanted as a single-cell suspension in the stomach of nude mice. The tumor cells derived from a few liver metastatic foci were subsequently implanted orthotopically, and we established a cell line, AZH5G, by repeating the in vivo stepwise selection method. This metastasizing line (AZH5G) developed liver metastasis in seven of eight (87.5%) cases, whereas parental AZ521 developed in 3 of 20 (15.0%). The in vitro growth activities of AZH5G were lower than that of AZ521, although the in vivo tumorigenicity of AZH5G was clearly higher than that of AZ521. Motility assays demonstrated higher motility of AZH5G than of AZ521. Flow cytometric analysis demonstrated that the expression of alpha 6-integrin significantly decreased in AZH5G (4.9% +/- 4.1%) compared to in AZ521 (17.7% +/- 8.1%) (p < 0.05). The adhesive activity of AZH5G cells to laminin was lower than that of AZ521 cells. In contrast, the adhesive activity of AZH5G cells to fibronectin was clearly higher than that of AZ521 cells. These findings suggested that changes in the expression of integrins on the cell surface might play an important role in metastatic ability. This well characterized line and its in vivo experimental model should be useful to investigate the mechanisms of liver metastasis and to develop a new therapeutic approach for human gastric cancer.

Adenocarcinoma↗
PubMed2001

The STR locus D11S554: allele frequencies and sequence data in a Japanese population.

A population study on the short tandem repeat (STR) locus D11S554 was carried out in a sample of 362 unrelated Japanese individuals living in the Gifu Prefecture. A total of 46 different alleles ranging from 180 bp to 340 bp and 135 genotypes were revealed. Sequence analysis of alleles was carried out for 185 samples. The sequence structures of the repeat regions of the alleles were found to be complex and the alleles were classified into nine sequence types, including four new sequence types. According to the system of Adams et al. (1993), we designated the new sequence types IA3, IA4, IA5 and IB3, respectively. Out of the 46 different alleles, 11 showed sequence heterogeneity. The results of this study demonstrated that the D11S554 locus is a powerful and useful genetic marker for forensic practice in the Japanese population.

Alleles↗
PubMed2001

Blood supply to the duodenal papilla and the communicating artery between the anterior and posterior pancreaticoduodenal arterial arcades.

The communicating artery (ComA) between the anterior and posterior pancreaticoduodenal arterial arcades is little understood, although it has been described several times during the past 100 years. In 44 of 51 cadaveric specimens in the present study, the typical ComA was observed to pass between the major and accessory pancreatic ducts. In addition, a second ComA was sometimes found crossing inferior to the major pancreatic duct. The typical ComAs often (36 of the 44) issued papillary branch(es). Although direct papillary branches of the posterior arcade were often observed to either coexist with (9 specimens) or exist independently (4 specimens), the ComA-derived branch seemed to be critical for papillary blood supply, because of its shorter length, greater thickness, and higher frequency. Moreover, the typical ComA could be a good landmark during limited pancreatic resection, such as duodenum-preserving subtotal resection of the pancreatic head or pancreatic segment resection, because the artery is likely to be an indicator of the borders between the celiac and superior mesenteric arterial territories, as well as those between the ventral and dorsal segments of the pancreas.

Aged↗
PubMed2001

Ventral margin of the paracaval portion of human caudate lobe.

The topographic anatomy of the ventral margin of the caudate lobe of the human liver is still obscure. We hypothesized the existence of a "precaudate plane", as a flat or slightly curved plane defined by the ventral margins of both the ligamentum venosum and hilar plate. Using 61 cadaveric liver specimens, without great differences in external shape or significant variations in the hilar bifurcation, we examined whether the paracaval caudate branches (PCs) ran through the plane to the ventral side. In 22 of the 61 specimens (36.1%), the PC extended over the plane for less than 10 mm (10 specimens), for 10-20 mm (7 specimens), or for more than 20 mm (5 specimens). The ventral extension consistently included the dome-like area under the terminals of the middle and right hepatic veins. Therefore, the ventrally extended PCs often interdigitated with these veins and their tributaries. The ventral extension often reached the upper, diaphragmatic surface. However, several branches were too difficult to discriminate from the PC, especially those with morphologies intermediate between the PC and segmental portal branches to S4 or S2. We discuss how to identify and manage the ventrally extended PCs before and during surgery.

Aged↗
PubMed2001

Sepsis and cholestasis: basic findings in the sinusoid and bile canaliculus.

It is well known that the liver plays a major role in the clearance of systemic toxemia and is postulated as a regulational organ in the host-defense system. The well-controlled interaction between hepatic parenchymal cells and sinusoidal lining cells including macrophages and Kupffer cells can systematically regulate even critical infections. However, when patients are under the overload condition caused by severe infection, rejection of a transplanted liver and other hapatic dysfunction often are experienced following surgery. Among various signs and symptoms of hepatic dysfunction, progressive cholestasis is recognized as a polarized representation of the irreversible changes in hepatic constitutional cellular functions, especially in hepatic parenchymal cells. Bile canaliculi, the smallest components of the biliary tree, lie between the apical surfaces of adjacent hepatocytes. Septic cholestasis might be a result of disturbance of the total bile canalicular system, i.e., bile secretion, canalicular contraction, and so on. Recently, the molecular biology of the hepatocellular transport system has become better understood, and the pathophysiological condition of cholestasis can be explained as a representation of the intracellular molecular transcriptional system. Cellular changes in surgical cholestasis and molecular findings concerning the bile canaliculus are introduced in this article.

Animals↗