Search PubMed⌕ Search

Biomedical subjects

Hiroki Kato

Publications and source records attributed to Hiroki Kato.

35 records · Page 2Linked to original sources

Expression of vascular endothelial growth factor in hepatocellular carcinoma and the surrounding liver and correlation with MRI findings.

OBJECTIVE: The purpose of our study was to assess the correlation between the quantitative and qualitative imaging findings on unenhanced and gadolinium-enhanced MR images and the intensity of vascular endothelial growth factor (VEGF) expression in hepatocellular carcinomas and in the surrounding nontumorous liver. MATERIALS AND METHODS: The intensities of VEGF expression in hepatocellular carcinoma and in the surrounding liver by Western blot analysis were converted to VEGF expression indexes (VEGF(IND)) in 22 surgical specimens ranging in size from 14 to 126 mm (mean, 47.6 +/- 29.5 mm) that were resected in 22 patients (17 men and five women; age range, 41-85 years [mean, 64 years]) between April 2000 and October 2002. MR images were retrospectively evaluated to determine contrast-to-noise ratios (CNRs), signal intensity SD ratios, and phase-shift indexes. Signal intensity characteristics of hepatocellular carcinomas were reviewed independently by two experienced radiologists who were unaware of the pathologic diagnosis or the results of immunoblotting. CNRs, SD ratios, and phase-shift indexes were correlated with VEGF(IND) using a simple regression test, and signal intensity characteristics were correlated with VEGF(IND) using the Spearman's rank correlation test. RESULTS: On opposed-phase T1-weighted spoiled gradient-recalled echo (GRE) images, CNRs correlated inversely with the VEGF(IND) of hepatocellular carcinomas (r = -0.46, p = 0.038). CNRs on T2-weighted fast spin-echo images correlated directly with the VEGF(IND) of hepatocellular carcinomas (r = 0.49, p = 0.025), and on gadolinium-enhanced hepatic arterial phase GRE images marginally and inversely correlated with VEGF(IND) (r = -0.39, p = 0.081). On T2-weighted fast spin-echo images, SD ratios correlated directly with the VEGF(IND) of hepatocellular carcinomas (r = 0.44, p = 0.044). No correlation was found between phase-shift indexes and VEGF expression. The qualitatively assessed signal intensity heterogeneities of hepatocellular carcinomas correlated directly with the VEGF(IND) of hepatocellular carcinomas on opposed-phase T1-weighted GRE, T2-weighted fast spin-echo, hepatic arterial phase GRE, and equilibrium phase GRE images. CONCLUSION: Our results indicate that the signal intensity and heterogeneity of hepatocellular carcinomas on MR images correlate with the degree of VEGF expression in hepatocellular carcinomas.

Adult↗

Ferumoxide-enhanced MR imaging of hepatocellular carcinoma: correlation with histologic tumor grade and tumor vascularity.

PURPOSE: To evaluate ferumoxide-enhanced MR imaging findings of hepatocellular carcinomas (HCCs) in correlation with the histologic tumor grades and the tumor vascularity evaluated by CT hepatic arteriography (CTHA) and CT during arterial portography (CTAP) combined. MATERIALS AND METHODS: By searching the radiologic, surgical, and pathologic reports of our institution between January 1999 and February 2001, we identified 43 patients with 51 pathologically confirmed HCCs who underwent ferumoxide-enhanced MR imaging and combination CTHA and CTAP within two weeks. The HCCs consisted of 17 well-differentiated, 28 moderately differentiated, and six poorly differentiated tumors. The MR and CT were retrospectively reviewed by two radiologists in consensus for signal intensity on MR images and vascularity on CT. The Spearman's rank correlation coefficient was calculated to correlate the frequency of tumors with ferumoxide uptake with the histologic tumor grades and the tumor vascularity on CTHA and CTAP. RESULTS: A total of 45 tumors (88%) did not take up ferumoxide, and thus showed distinct, homogeneous hyperintensity. Six tumors (12%) ranging 5-16 mm in size (mean, 11 mm) took up ferumoxide, and thus showed isointensity, mixed intensity, or hypointensity, including five of 17 (29%) well-differentiated tumors and one of 28 (4%) moderately differentiated tumors. Five of the six tumors (83%) showed hyper- or hypovascularity on CTHA or hypovascularity on CTAP. The frequency of tumors with ferumoxide uptake showed weak correlation with tumor grades (coefficient = 0.26, P < 0.01) and vascularity on CTHA (-0.35, P < 0.05) and CTAP (0.39, P < 0.01). CONCLUSION: Although a small number of well-differentiated HCC take up ferumoxide and show iso-, mixed, or hypointensity, most such tumors show increased hepatic arterial or decreased portal venous perfusion. The present results suggest the limitation of reticuloendothelial contrast imaging, particularly in the diagnosis of small, well-differentiated HCC.

Aged↗

Nodule-in-nodule appearance of hepatocellular carcinomas: comparison of gadolinium-enhanced and ferumoxides-enhanced magnetic resonance imaging.

PURPOSE: To perform comparison of gadolinium-enhanced and ferumoxides-enhanced magnetic resonance imaging (MRI) in the detection of nodule-in-nodule appearance of hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: During a recent 45-month period, we had eight patients (five men and three women; age range, 63-84 years; mean, 71 years) with HCCs with nodule-in-nodule appearance who underwent gadolinium-enhanced MRI, ferumoxides-enhanced MRI, and computed tomography during arterial portography (CTAP) and computed tomography during hepatic arteriography (CTHA), combined and separately, within an interval of two weeks. Two blinded radiologists in consensus retrospectively evaluated three sets of sequences: unenhanced T1- and T2-weighted MR, gadolinium-enhanced MR, and ferumoxides-enhanced MR images in random order of patients and imaging sequences. The depiction degree of nodule-in-nodule appearance of HCC was evaluated in a semiquantitative fashion. The sensitivities of unenhanced T1- and T2-weighted, gadolinium-enhanced, and ferumoxides-enhanced MR images were compared with McNemar's test. RESULTS: The eight HCCs with nodule-in-nodule appearance ranged in size from 16-26 mm (mean, 20.0 +/- 4.0 mm), and there existed nine internal HCC foci ranging in size from 5-14 mm (mean, 7.9 +/- 3.5 mm). On gadolinium-enhanced MR images, the nodule-in-nodule appearance of HCC was typically seen as hypervascular foci in an iso- or hypovascular area: the depiction degree of nodule-in-nodule appearance was distinct in two lesions, equivocal in three, and absent in three. On ferumoxides-enhanced MR images, it was typically seen as hyperintense foci in a hypointense area: the depiction degree was distinct in four, moderate in one, and absent in three. The sensitivities for detection of nodule-in-nodule appearance were 25%, 25%, and 63% on T1- and T2-weighted, gadolinium-enhanced, and ferumoxides-enhanced MR images, respectively, but there was no significant difference in sensitivity. CONCLUSION: Nodule-in-nodule appearance of HCCs can be seen on ferumoxides-enhanced MR images, in some cases more clearly than on gadolinium-enhanced MR images, particularly when the background nodule shows hyperintensity on precontrast T1-weighted images. Ferumoxides-enhanced MRI may be considered when development of malignant foci is suspected during routine examinations.

Aged↗

Inflammatory pseudotumor of the liver: ferumoxide-enhanced MR imaging as a tiebreaker.

We examined a 70-year-old male patient with an inflammatory pseudotumor of the liver mimicking a peripheral-type cholangiocellular carcinoma. Ferumoxide-enhanced magnetic resonance (MR) imaging revealed residual Kupffer cell function in liver parenchyma in and surrounding the inflammatory pseudotumor involvement, which suggested the diagnosis of inflammatory pseudotumor of the liver. We correlate the MR imaging and pathologic findings in this report.

Aged↗

Expression of vascular endothelial growth factor in hepatocellular carcinoma and the surrounding liver: correlation with angiographically assisted CT.

OBJECTIVE: The purpose of our study was to assess the correlation between the intensity and characteristics of contrast enhancement on angiographically assisted CT and the intensity of vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) and in the surrounding nontumorous liver. MATERIALS AND METHODS: The intensity of VEGF expression in HCC and in the surrounding liver was expressed as a VEGF expression index by Western blot analysis in 20 surgical specimens resected in 20 patients between March 2000 and August 2002. Findings on CT during arterial portography (n = 20) and CT hepatic arteriography (n = 17) were retrospectively evaluated to determine contrast enhancement indexes and the enhancement characteristics of HCCs and of the surrounding liver. Contrast enhancement indexes and VEGF expression indexes were correlated using a simple regression test, and enhancement characteristics and VEGF expression indexes were correlated using the Spearman's rank correlation test. RESULTS: On CT hepatic arteriography, the contrast enhancement indexes of HCCs showed moderate inverse correlation with the VEGF expression indexes of HCCs (r = -0.57, p = 0.017) and high inverse correlation with the differences between the VEGF expression indexes of HCCs and those of livers (difference in the VEGF expression index, -0.80; p = 0.0001). The contrast enhancement index of the liver showed marginal moderate direct correlation with the VEGF expression index of the liver (0.44, p = 0.076) and high inverse correlation with the difference in the VEGF expression index (-0.71, p = 0.0013). On CT during arterial portography, the contrast enhancement indexes of HCCs showed moderate inverse correlation with the difference in the VEGF expression index (-0.51, p = 0.023). The qualitative degree of heterogeneity of hepatic artery enhancement in HCC on CT hepatic arteriography showed moderate direct correlation with the VEGF expression indexes of HCCs (0.55, p = 0.033) and high direct correlation with the difference in the VEGF expression indexes (0.73, p = 0.004). CONCLUSION: Our results indicated that the intensity and heterogeneity of hepatic artery enhancement of HCCs on CT hepatic arteriography correlated with the degree of VEGF expression in HCCs.

Adult↗

Reversible light-driven structural changes between the mono- and bilayer stacking alignments in 4-octadecyloxystilbazolium arylcarboxylate films.

The present investigation deals with the light-driven morphological changes in multilamella films of N-methyl-4-octadecyloxystilbazolium arylcarboxylates (C18OStz+X-) cast on glass slides. The results of XRD analysis show a photostimulated layer expansion and shrinkage of the stacked thin films along the c-axis under alternative illumination at >350 and 254 nm, respectively. It was revealed that such lamellar changes could be switched either way by a reversible transformation between the mono- and bilayer units in these stacked multilamella films. Moreover, such controlled structural adjustments in the alignment could be initiated by the photocyclodimerization of the stilbazolium moieties of the arylcarboxylate salts; i.e., a monolayer-to-bilayer transformation could be induced at a stage of only 10% cyclodimer formation. The photoinduced patterning on the surface of the films was also analyzed by SEM and fluorescence microscopic investigations.

Journal Article↗

Identification of TIFA as an adapter protein that links tumor necrosis factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) transduces signals from members of the Toll/interleukin-1 (IL-1) receptor family by interacting with IL-1 receptor-associated kinase-1 (IRAK-1) after IRAK-1 is released from the receptor-MyD88 complex upon IL-1 stimulation. However, the molecular mechanisms underlying regulation of the IRAK-1/TRAF6 interaction are largely unknown. We have identified TIFA, a TRAF-interacting protein with a forkhead-associated (FHA) domain. The FHA domain is a motif known to bind directly to phosphothreonine and phosphoserine. In transient transfection assays, TIFA activates NFkappaBeta and c-Jun amino-terminal kinase. However, TIFA carrying a mutation that abolishes TRAF6 binding or mutations in the FHA domain that are known to abolish FHA domain binding to phosphopeptide fails to activate NFkappaBeta and c-Jun amino-terminal kinase. TIFA, when overexpressed, binds both TRAF6 and IRAK-1 and significantly enhances the IRAK-1/TRAF6 interaction. Furthermore, analysis of endogenous proteins indicates that TIFA associates with TRAF6 constitutively, whereas it associates with IRAK-1 in an IL-1 stimulation-dependent manner in vivo. Thus, TIFA is likely to mediate IRAK-1/TRAF6 interaction upon IL-1 stimulation.

Adaptor Proteins, Signal Transducing↗

Primary localized amyloidosis of the urinary bladder.

We report a rare case of localized form of primary amyloidosis (amyloidoma) of the urinary bladder with CT and MR findings. Clinically, it is difficult to distinguish from invasive transitional cell carcinoma and inflammatory lesion. We think that the MR intensity on T2-weighted images is helpful in making the diagnosis.

Amyloidosis↗

Evaluation of carcinoembryonic antigen mRNA in living, necrotic, and apoptotic gastric cancer cells by reverse transcriptase-polymerase chain reaction.

PURPOSE: Positive mRNA expression of carcinoembryonic antigen (CEA) is often found in histologically negative lymph nodes, even in early gastric cancer. Therefore, we examined the differences in mRNA expression in MKN45 gastric cancer cells obtained under various cell conditions, namely, living cells, necrosis, and apoptosis, and assessed the possibility of detecting micrometastasis from these results. METHODS: MKN45 cells were cultured with low-dose anticancer drugs (5-fluorouracil (5FU) + cisplatin (CDDP)) or cytokines (tumor necrosis factor alpha (TNFAlpha) + interferon gamma (INFGamma)) to induce apoptosis, or subjected to freezing-thawing to induce necrosis. All the treated cells were stained with propidium iodide and Hoechst and the numbers of living, apoptotic, and necrotic cells were counted. CEA mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and DNA fragmentation was confirmed. RESULTS: mRNA expression of CEA and CEA/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) tended to decrease as the apoptotic index (AI) increased in the 5FU + CDDP group. On the other hand, almost no change was seen, even when the AI increased, in the TNFAlpha + IFNGamma group. mRNA expression in the necrotic cells was the almost same as that in the living cells. CONCLUSION: Positive CEA mRNA expression by RT-PCR could suggest the existence of living cancer cells.

Apoptosis↗

Significance of apoptosis induced by tumor necrosis factor-alpha and/or interferon-gamma against human gastric cancer cell lines and the role of the p53 gene.

PURPOSE: The expression of the p53 gene in target cells plays an important role in the induction of apoptosis by tumor necrosis factor (TNF)-Alpha and interferon (IFN)-Gamma. We herein present a study suggesting the existence of a caspase-independent pathway from p53 via insulin-like growth factor binding protein 3 (IGF-BP3) which acts as an apoptosis induction mechanism. METHODS: MKN-45 (wild-type p53) or MKN-28 (mutant-type p53) was cultured with TNF-Alpha or IFN-Gamma either alone or together. After 24 and 48 h, the apoptotic index (AI) was determined by Hoechst staining and then compared. To clarify whether the mechanism of apoptosis is induced by TNF-Alpha and/or IFN-Gamma, apoptosis-related genes were examined by a cDNA on microarray analysis and a Western blot analysis. RESULTS: (1) The AI for MKN-45 increased at 48 h in the presence of TNF-Alpha or IFN-Gamma alone. (2) In the case of combination treatment using TNF-Alpha and IFN-Gamma, the AI for MKN-45 was higher than those in the groups with a single treatment. (3) A cDNA microarray analysis showed that IGF-BP3, the TNF superfamily, and caspase 1 were all upregulated after treatment with the combination of TNF-Alpha and IFN-Gamma. (4) A Western blot analysis of MKN-45 showed a reaction with an anti-IGF-BP3 antibody. CONCLUSIONS: These results suggest that the induction mechanism underlying apoptosis induced by TNF-Alpha and IFN-Gamma might therefore involve the caspase-independent pathway via IGF-BP3.

Apoptosis↗

Effects of polyamines on histone polymerization.

It is generally accepted that the nucleosome structure is not static, and that alternative conformations are adopted in response to several stimuli associated with the different functions. Histones are substrates for transglutaminase (TGase), and polymerized histone and polyamine binding histone have been suggested to play important roles in nucleus. We examined whether histone polymerization catalyzed by TGase was influenced by polyamines such as putrescine (PUT), spermidine (SPD), and spermine (SPM). PUT inhibited histone polymerization, and SPD slightly prevented it. However, SPM slightly enhanced histone polymerization. These results indicate that the nuclear accumulation of the polyamines may play an important role in nuclear remodeling by histone modification. We speculate that histone cross-linking by TGase may be involved in the chromatin structure. Also, we propose that histone cross-linking by TGase may be responsible for the changes in DNA function such as transcription and replication and that TGase may be involved in cell growth and differentiation.

Animals↗

Polo-like kinase 1 (PLK1) is overexpressed in primary colorectal cancers.

PLK (polo-like kinase), the human counterpart of polo in Drosophila melanogaster and of CDC5 in Saccharomyces cerevisiae, belongs to a family of serine/threonine kinases. It is intimately involved in spindle formation and chromosome segregation during mitosis. The purpose of this study was to determine whether PLK1 is overexpressed in primary colorectal cancer specimens as compared with normal colon mucosa and to assess its relation to other kinases as a potential new tumor marker. In the present study, immunohistochemical analyses were performed of PLK1 expression in 78 primary colorectal cancers as well as 15 normal colorectal specimens. Furthermore, we examined the relationship between other kinases, Aurora-A and Aurora-C, and PLK1 expression. In normal colon mucosa, some crypt cells showed weakly positive staining for PLK1 in 13 out of 15 cases, the remaining cases being negative. Elevated expression of PLK1 was observed in 57 (73.1%) of the colorectal cancers, statistically significant associations being evident with pT (primary tumor invasion) (P=0.0006, Mann-Whitney U test), pN (regional lymph nodes) (P=0.008, chi2 test) and the Dukes' classification (P=0.0005, Mann-Whitney U test). Mean proliferating cell nuclear antigen-labeling index was 52.3%, with a range of 24.1% to 77.3%. Values for lesions with high and low PLK1 expression were 54.7+/-10.3% (mean+/-SD) and 45.9+/-11.9% (P=0.002, Student's t test). PLK1 was significantly associated with Aurora-A, but PLK1 staining was more diffuse and extensive than for Aurora-A or Aurora-C. Interestingly, PLK1 overexpression was significantly associated with p53 accumulation in colorectal cancers. Our results suggest overexpression of PLK1 might be of pathogenic, prognostic and proliferative importance, so that this kinase might have potential as a new tumor marker for colorectal cancers.

Adenocarcinoma↗

Primary localized amyloidosis of the urinary bladder.

We report a rare case of localized form of primary amyloidosis (amyloidoma) of the urinary bladder with CT and MR findings. Clinically, it is difficult to distinguish from invasive transitional cell carcinoma and inflammatory lesion. We think that the MR intensity on T2-weighted images is helpful in making the diagnosis.

Amyloidosis↗

Pharmacokinetic and pharmacodynamic properties of a new thromboxane receptor antagonist (Z-335) after single and multiple oral administrations to healthy volunteers.

The pharmacokinetics and pharmacodynamics of a new oral thromboxane (TX) A2 receptor antagonist, Z-335, were studied in healthy male volunteers following single doses (0.5-40 mg, PO) in a dose-escalating manner and multiple doses (40 mg, PO, once daily for 7 consecutive days) with a single-blind, placebo-controlled design. Serial blood and urine samples were analyzed for Z-335 and its metabolites to obtain key pharmacokinetic parameters. In the single-dose (10, 20, and 40 mg) study, the maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) increased in proportion to the dose when administered afterfasting, while the mean elimination half-life (t1/2beta) was essentially unchanged (7.79-7.93 h). Recovery of the unchanged and taurine-conjugated drugs in the urine within 24 hours was 6.5% to 8.4% and 11.9% to 14.2%, respectively. These parameters essentially remained unchanged when the effect of meal intake was evaluated at the dose of 20 mg with a crossover design. Ex vivo platelet aggregation in the plasma by a TXA2 analogue, U46619, was completely inhibited within 2 hours after all doses, and complete inhibition was maintained for 12 to 14 hours, depending on the dose. The aggregation induced by collagen was also inhibited to a lesser extent, whereas that by adenosine diphosphate was hardly influenced. In the multiple-dose study, Cmax and AUC0-24 were increased by 34% after the last dose compared with the first dose. Z-335 afforded extensive inhibition of platelet aggregation by U46619 throughout the administration period, which returned, however, almost to the control level 48 hours after the last dose. The agent was well tolerated without any abnormalities in subjective and objective symptoms, blood biochemistry, hematology, and urinalysis definitely attributable to the agent, except for the changes expected from its TXA2 receptor-antagonizing actions. Z-335 was concluded to be safe and to provide long-lasting blockade of TXA2 receptors on the basis of a once-daily regimen, promoting further clinical evaluation.

Administration, Oral↗

Optimizing scan delays of fixed duration contrast injection in contrast-enhanced biphasic multidetector-row CT for the liver and the detection of hypervascular hepatocellular carcinoma.

OBJECTIVE: To determine the optimal scan delay required for fixed duration contrast injection in contrast-enhanced biphasic multidetector-row CT for the liver and the detection of hypervascular hepatocellular carcinoma (HCC). METHODS: CT images (2.5-mm collimation, 5-mm thickness with no intersectional gap) were obtained after an intravenous bolus injection of 2 mL/kg of nonionic iodine contrast material (300 mg I/mL) for a fixed 30-second injection in 206 patients, who were prospectively randomized into four groups, for which scans were initiated at -5, 15, and 35 seconds; at 0, 20, and 40 seconds; at 5, 25, and 45 seconds; or at 10, 30, and 50 seconds for the first (acquisition time: 4.3 seconds), second (4.3 seconds), and third (9.1 seconds) phases, respectively, after the completion of contrast injection. Mean CT values (HU) of the abdominal aorta, spleen, main portal veins, liver parenchyma, and hepatic veins were measured. Increases in CT values between pre- and post-contrast CTs (DeltaHU) for the organs, and spleen-to-liver and HCC-to-liver contrast differences (deltaHU) were assessed. RESULTS: Abdominal aorta reached 273-301 DeltaHU at -5 to 10 seconds with a peak (301 DeltaHU) at 5 seconds. Spleen peaked (115 DeltaHU) at 10 seconds. Liver parenchyma were enhanced weakly (11-34 DeltaHU) at -5 to 10 seconds, exceeded 50 DeltaHU at 20 seconds, peaked (61 DeltaHU) at 30 seconds, and then plateaued (54-58 DeltaHU) at 35-50 seconds. Hepatic veins were enhanced weakly (14-37 DeltaHU) at -5 to 10 seconds, and reached 67 DeltaHU at 15 seconds. Spleen-to-liver (65-69 deltaHU) and HCC-to-liver (31-34 deltaHU) contrast differences were highest at 5-10 seconds. Qualitative results corresponded well with quantitative results. CONCLUSIONS: For the detection of hypervascular HCCs, the optimal scan delay after a 30-second contrast injection of the hepatic arterial phase, was found to range from 5 to 10 seconds, and that of the portal venous phase was 35 seconds or somewhat longer.

Adult↗

An experimental study of a new pull-through technique for aortic arch aneurysm in a porcine model.

A new pull-through technique for placement of the aortic arch stent-graft was developed. Self-expandable curved stents (Matsui-Kitamura stents) were used on 4 pigs. With use of the endoscopic system, the sheath insertion was performed at the ascending aorta. By this pull-through method from the ascending aorta to the femoral artery, the stent was deployed into the aortic arch. All stents were successfully deployed into the correct position, and they fitted into the curvature of the aortic arch wall. By this method, stent-grafting for aortic arch aneurysm is expected to be performed with more accuracy and safety.

Animals↗