Biomedical subjects

Tetsuya Ishikawa

Publications and source records attributed to Tetsuya Ishikawa.

At least 55 records · Page 3Linked to original sources

PubMed2003

Prevalence of diabetes mellitus in Japanese patients infected chronically with hepatitis C virus.

BACKGROUND: To examine the relationship between hepatitis C virus (HCV) infection and diabetes mellitus (DM) in Japanese populations, a retrospective study was done in 866 patients with chronic viral disease. METHODS: The present study included 707 HCV-infected and 159 hepatitis B virus (HBV)-infected patients. The prevalences of HBV- and HCV-related cirrhosis were 32% and 33%, respectively. A case-control study was also conducted to determine the seroprevalence of HCV infection in a cohort of 459 diabetics. RESULTS: The prevalence of DM was higher in HCV-infected patients (20.9%; P < 0.02) than in HBV-infected subjects (11.9%). In the cirrhotic patients, DM was observed in 30.8% of the subjects with HCV compared with 11.8% of those with HBV ( P < 0.01). Multivariate analysis revealed that the major independent variables associated with type II DM were male sex (odds ratio, 1.54; p = 0.020) and cirrhosis (odds ratio, 1.97; P = 0.0007). The relative odds of the development of DM were calculated to be 3.2 times higher in HCV-infected cirrhotic patients than in HBV-infected ones. In the case-control study of the diabetic cohort, 10.5% of patients were infected with HCV compared with 1.1% with HBV ( P < 0.0001). The results indicate that HCV infection is closely associated with DM, compared with HBV infection. Cirrhosis was an independent risk factor for DM. CONCLUSIONS: Taken together, the findings indicate that cirrhosis appears to be a more important predictor of glucose intolerance than HCV infection, and the combination of both factors increases the risk of DM in our populations.

Adult↗

PubMed2003

Functional and histological changes in rat femoral arteries by HIFU exposure.

This study was an investigation of arterial contractility in response to high-intensity focused ultrasound (HIFU) and of histologic changes to the artery with various intensities of HIFU. We constructed a prototype HIFU transducer in combination with an imaging probe that provides color Doppler imaging and Doppler velocimetry. HIFU was applied through the skin to deep femoral arteries in left thighs of Sprague-Dawley rats; color images of the blood flow were used to aim the HIFU beam. Peak intensities used were 530, 1080, 2750 and 4300 W/cm2. The duration of each HIFU exposure was 5 s. HIFU was applied to five focal spots of each leg. These focal spots were aligned with a spacing of 1.0 mm so as to form a line across the artery. Blood flow occlusion was accomplished by HIFU at an intensity of 4300 W/cm2, but the flow continued with the lower intensities. Peak systolic velocities (PSVs) of blood flow as measured by Doppler velocimetry increased in the arteries to which HIFU had been applied at 1080 and 2750 W/cm2. The increase corresponded with HIFU intensity. Exposure to HIFU at 530 W/cm2 did not change the blood flow velocity. Histologic studies have demonstrated that exposure to HIFU at 2750 and 4300 W/cm2 leads to vacuolar degeneration and destruction of elastic fibers of the tunica media of the artery. Exposure at 1080 W/cm2 led to increased PSV, but did not induce histologic changes in the vessel wall. In conclusion, the response of the artery to HIFU varied with intensity. Vascular contraction without tissue degeneration occurred at low intensity; with increasing intensity, the tissue degeneration detectable in histology reduced the vascular diameter and, finally, at high intensity, the blood flow was occluded. Although these phenomena appeared to be mainly due to thermal effects, mechanical effects might have some role, particularly on vascular contraction.

Animals↗

PubMed2003

Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic hepatitis C virus infection.

BACKGROUND AND AIM: Evidence showing a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection has been accumulating. However, the reason why chronic HCV infection promotes DM remains unknown. In the present study, the authors focused on non-cirrhotic and non-diabetic patients with chronic HCV infection and evaluated the factors responsible for increases in insulin resistance. METHODS: Fifty-six patients diagnosed with HCV-related chronic liver disease were included. Biochemical information including body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase, cholinesterase, triglyceride, total cholesterol, hemoglobin, platelet count, glycosylated hemoglobin, immunoreactive insulin (IRI), and serum levels of tumor necrosis factor (TNF)-alpha and HCV-RNA were determined using venous blood samples obtained from each patient after overnight fasting. Homeostasis model assessment of insulin resistance (HOMA-IR), a simple and convenient measure of insulin resistance, was also calculated. The relationship between the stage of liver fibrosis and HOMA-IR, and the clinical factors responsible for the increase in HOMA-IR in non-diabetic patients was investigated. RESULTS: Homeostasis model assessment of insulin resistance and IRI levels increased parallel with the progression of fibrosis. Among the non-diabetic patients with mild to moderate liver fibrosis, BMI, serum levels of AST and TNF-alpha were related with HOMA-IR (BMI: r = 0.395, P = 0.041; AST: r = 0.465, P = 0.014; TNF-alpha: r = 0.396, P = 0.040). In contrast, HOMA-IR related to TNF-alpha (r = 0.526, P = 0.013) in non-diabetic patients with advanced liver fibrosis. CONCLUSION: Collectively, hepatic fibrosis and inflammation appear to play key roles in the increase in insulin resistance in patients with chronic HCV infection.

Aged↗

PubMed2003

Delivery of a growth factor fusion protein having collagen-binding activity to wound tissues.

Recently, we established a collagen-binding growth factor consisting of epidermal growth factor and the fibronectin collagen-binding domain (FNCBD-EGF). FNCBD-EGF is a biologically active fusion protein that could stably bind to collagen materials, and exert its growth factor activity even after collagen binding. In this study, we investigated the concept that FNCBD moiety with high collagen affinity may enhance the effective local concentration of EGF at the site of administration in the following tissues: skin wounds, catheter-injured arteries, and hind limb muscles. In an animal model of impaired wound healing, application of FNCBD-EGF in combination with collagen gel induced granulation tissue formation in the wounds due to its sustained retention. In the injured artery, infused FNCBD-EGF remained bound to collagen exposed on the injured tissues even after blood circulation was restored. Injection of the fusion protein into the hind limbs revealed that our delivery system was effective for direct administration to muscular tissue.

Administration, Topical↗

PubMed2003

Lack of tumor necrosis factor alpha induces impaired proliferation of hepatitis B virus-specific cytotoxic T lymphocytes.

Recent studies have shown that tumor necrosis factor alpha (TNF-alpha) plays critical roles in not only viral clearance but also lymphoid tissue development and stem cell differentiation. In this study, we attempted to induce hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) by immunization of TNF-alpha knockout (TNF-alpha(-/-)) mice with HBsAg-encoding plasmid DNA. An immunization with the HBV plasmid failed to induce CTL responses in TNF-alpha(-/-) mice, although CTLs were readily induced in wild-type mice by the same protocol. Weak CTL responses were produced in TNF-alpha(-/-) mice after two sessions of immunization with the HBV plasmid; however, TNF-alpha was required to maintain the responses of these CTL lines to in vitro stimulation and, even then, the responses were lost after 3 weeks. Interestingly, a limiting dilution of a CTL line showed that HBV-specific CTL clones with high specific cytotoxicity were present in TNF-alpha(-/-) mice, but these clones again failed to proliferate for more than 3 weeks. Furthermore, since exogenously added TNF-alpha enhanced the proliferation of a TNF-alpha(-/-) clone but suppressed that of a TNF-alpha(+/+) clone in vitro, TNF-alpha also has a direct effect on the proliferation of CTLs. In conclusion, TNF-alpha is essential rather than important for the proliferation of HBV-specific CTLs both in vivo and in vitro and this effect is not only due to the activation of dendritic cells but is also induced by the direct effect on CTLs.

Animals↗

PubMed2003

Usefulness of a second temporary vena cava filter for preventing acute pulmonary thromboembolism.

The usefulness of a temporary inferior vena cava filter (t-IVC-f) for the prevention of acute pulmonary thromboembolism (APTE) associated with venous thromboembolism (VTE) has been established, but not the requirement for an additional therapeutic method when the t-IVC-f has captured a thrombus. A woman underwent implantation of a t-IVC-f just caudal to the bifurcation of the renal vein immediately before cesarean section (C/S) for VTE that had occurred during the third trimester of pregnancy. After receiving a combination of anticoagulant and fibrinolytic therapies after the C/S, the t-IVC-f was found to contain a thrombus and in order to prevent its dissemination during the removal of the closed filter, another filter was inserted and expanded proximal to the first. Insertion of an additional t-IVC-f may prevent occurrence of APTE during removal of the primary filter containing a friable thrombus after fibrinolytic therapy, and the technique proved useful in the present case of VTE during pregnancy.

Acute Disease↗

PubMed2002

Imaging whole Escherichia coli bacteria by using single-particle x-ray diffraction.

We report the first experimental recording, to our knowledge, of the diffraction pattern from intact Escherichia coli bacteria using coherent x-rays with a wavelength of 2 A. By using the oversampling phasing method, a real space image at a resolution of 30 nm was directly reconstructed from the diffraction pattern. An R factor used for characterizing the quality of the reconstruction was in the range of 5%, which demonstrated the reliability of the reconstruction process. The distribution of proteins inside the bacteria labeled with manganese oxide has been identified and this distribution confirmed by fluorescence microscopy images. Compared with lens-based microscopy, this diffraction-based imaging approach can examine thicker samples, such as whole cultured cells, in three dimensions with resolution limited only by radiation damage. Looking forward, the successful recording and reconstruction of diffraction patterns from biological samples reported here represent an important step toward the potential of imaging single biomolecules at near-atomic resolution by combining single-particle diffraction with x-ray free electron lasers.

Escherichia coli↗

PubMed2002

Nearly diffraction-limited line focusing of a hard-X-ray beam with an elliptically figured mirror.

An elliptical mirror for X-ray microfocusing was manufactured using the new fabrication methods of elastic emission machining and plasma chemical vaporization machining. Surface profiles measured using stitching interferometry showed a maximum deviation around the ideal figure of 7 nm peak-to-valley. The mirror showed nearly diffraction-limited focusing performance, with a 200 nm line width at the focus. Wave-optical calculations, taking the measured surface profile into consideration, reproduced well the measured focusing properties both at and around the beam waist.

Journal Article↗

PubMed2002

High resolution 3D x-ray diffraction microscopy.

We have imaged a 2D buried Ni nanostructure at 8 nm resolution using coherent x-ray diffraction and the oversampling phasing method. By employing a 3D imaging reconstruction algorithm, for the first time we have experimentally determined the 3D structure of a noncrystalline nanostructured material at 50 nm resolution. The 2D and 3D imaging resolution is currently limited by the exposure time and the computing power, while the ultimate resolution is limited by the x-ray wavelengths. We believe these results pave the way for the development of atomic resolution 3D x-ray diffraction microscopy.

Microscopy↗

PubMed2002

The Goos-Hänchen effect at Bragg diffraction.

The strong incident-angle dependence of the phase of complex reflectivity causes a shift of the reflected beam from the geometrically expected path. This effect, known as the Goos-Hänchen effect in the visible region, was observed for Bragg-case diffraction in the hard X-ray region. The shift was found to be in good agreement with the theory.

Journal Article↗

PubMed2002

Functional analysis of the 5'-flanking region of the human alanine:glyoxylate aminotransferase gene AGXT.

Primer extension of human liver poly(A)(+) RNA revealed that the main transcription start site of the human alanine:glyoxylate aminotransferase gene (AGXT) is situated near 45 bp upstream from the translation start site. Deletion analysis using the 1203 bp 5'-flanking region of the AGXT gene and a luciferase reporter suggested that the promoter sequence is most likely located 2-325 bp upstream from the translation start site, possibly with enhancer elements 440-700 bp upstream. It was also suggested that the region -2 to -64 is important for the expression of the AGXT gene. The region -2 to -325 has two TATA boxes and some initiator elements.

Base Sequence↗

PubMed2002

Fast multigrid fluorescent ion chamber with 0.1 ms time response.

A fast multigrid ion chamber for the detection of fluorescent X-rays has been developed. The structure of 17 grids with close separation was employed to maximize the time response as well as to give sufficient detection efficiency. The measured rise/fall response time to cyclic X-rays was shorter than that of an existing three-grid ion chamber by more than one order of magnitude. A 0.13 ms time response was obtained at the 500 V applied voltage, where the detector can stably operate without any discharge. The available frequency range is as high as 1 kHz with a practical amplitude response.

Journal Article↗

PubMed2002

Optical switching of X-rays using laser-induced lattice expansion.

The optical switching of X-rays using laser-induced crystal lattice expansion is described. Irradiation of a gallium arsenide (GaAs) crystal using picosecond laser pulses shifts the Bragg angle through the lattice expansion with a response time of a few hundred picoseconds. A single pulse was extracted from the synchrotron radiation pulse train using a double-crystal arrangement of GaAs, in which the two crystals were irradiated by way of two successive laser pulses with an appropriate time delay.

Journal Article↗

PubMed2002

A new type of antimetastatic peptide derived from fibronectin.

PURPOSE: We found previously that fibronectin (FN) has a cryptic functional site (YTIYVIAL sequence within the 14th type III repeat) opposing cell adhesion to extracellular matrix. A 22-mer FN peptide containing this site, termed FNIII14, inhibits beta1 integrin-mediated adhesion without binding to integrins. The present study shows that FNIII14 has the potential to prevent lymphoma cell metastasis. EXPERIMENTAL DESIGN: Antimetastatic effect of FNIII14 has been evaluated through in vitro or in vivo experiments. RESULTS: FNIII14 inhibited the integrin alpha4beta1-mediated B lymphoma Ramos cell adhesion to VCAM-1 on venule endothelial cells, as well as to FN. Murine T lymphoma L5178Y-ML25 cells, which are known to metastasize to liver and spleen, preferentially adhered to vitronectin (VN) and migrated toward VN concentration gradients. FNIII14 abrogated both the integrin alphavbeta3-mediated adhesion and migration of L5178Y-ML25 cells. Inhibition of the alphavbeta3mediated L5178Y-ML25 cell adhesion by FNIII14 was reversed by phenylarsine oxide, a protein tyrosine phosphatase inhibitor. In addition, FNIII14 abrogated the VN-stimulated tyrosine phosphorylation of intracellular signaling proteins, including focal adhesion kinase (p125(FAK)) and paxillin, suggesting that such a diversity of FNIII14 effects might be because of the negative regulation of p125(FAK) and paxillin tyrosine phosphorylation, which has been involved in adhesion signals transduced by different integrins. The in vivo experiment using a murine metastasis model showed that FNIII14 would inhibit liver and spleen metastases of L5178Y-ML25 cells at a dose much lower than that of RGDS. CONCLUSIONS: FNIII14 might be applicable as a new type of antimetastatic agent distinct from integrin-binding peptides.

Animals↗

PubMed2002

Adjustment function among antioxidant substances in acatalasemic mouse brain and its enhancement by low-dose X-ray irradiation.

The catalase activities in blood and organs of the acatalasemic (C3H/AnLCsbCsb) mouse of the C3H strain are lower than those of the normal (C3H/AnLCsaCsa) mouse. We conducted a study to examine changes in the activities of antioxidant enzymes, such as catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPX), the total gluathione content, and the lipid peroxide level in the brain, which is more sensitive to oxidative stress than other organs, at 3, 6, or 24 hr following X-ray irradiation at doses of 0.25, 0.5, or 5.0 Gy to the acatalasemic and the normal mice. No significant change in the lipid peroxide level in the acatalasemic mouse brain was seen under non-irradiation conditions. However, the acatalasemic mouse brain was more damaged than the normal mouse brain by excessive oxygen stress, such as a high-dose (5.0 Gy) X-ray. On the other hand, we found that, unlike 5.0 Gy X-ray, a relatively low-dose (0.5 Gy) irradiation specifically increased the activities of both catalase and GPX in the acatalasemic mouse brain making the activities closer to those in the normal mouse brain. These findings may indicate that the free radical reaction induced by the lack of catalase is more properly neutralized by low dose irradiation.

Acatalasia↗

PubMedDate not supplied

Advanced dynamic flow imaging with contrast-enhanced ultrasonography for the evaluation of tumor vascularity in liver tumors.

To examine the usefulness of advanced dynamic flow imaging in diagnosing hepatic tumor and in assessing therapeutic effects in patients with hepatocellular carcinoma (HCC) and metastatic hepatic tumor, we performed contrast-enhanced ultrasonography (US) with Levovist, a microbubble contrast agent. Twenty-two patients of 35 HCC nodules infected with hepatitis C virus (HCV) and six patients with metastatic liver nodules were studied. They were diagnosed as having HCC or metastasis with helical dynamic computed tomography (CT) and/or celiac angiography. Tumor vascularities in the early arterial and postvascular phases were assessed by real-time scanning of advanced dynamic flow imaging and intermittent interval-delay scanning of contrast pulse subtraction imaging with a wide-band power Doppler technology. All patients showed hypervascular enhancement of HCC on contrast-enhanced US and/or dynamic CT. The advanced dynamic flow could be obtained as vascular and perfusion images of hepatic tumors. Tumor vascularities, including tumor vessels and parenchymal flow, were able to demonstrate in 27 of 29 nodules including 17 patients with 27 HCC nodules and 2 patients with 2 metastatic nodules before radiofrequency ablation (RFA) treatment by the advanced dynamic flow on contrast-enhanced harmonic US. Two nodules gave insufficient dynamic flow which were located approximately 12 cm in depth from the body surface. The advanced dynamic flow, which was done 7-10 days after RFA, indicated disappearance of the tumor vessels in 27 of visible 27 nodules. The study on early phase of helical dynamic CT revealed the same results as noted in early vascular phase of dynamic flow US. No major complication of RFA procedure was noted. The results indicated that contrast-enhanced advanced dynamic flow imaging on US clearly depicted intratumoral vascularity in real time and thus it is useful to diagnose and assess therapeutic efficacy in patients with HCC and metastatic liver tumor.

Aged↗

PubMedDate not supplied

Usefulness of contrast-enhanced ultrasonography with dynamic flow imaging to evaluate therapeutic effects for hepatocellular carcinoma.

BACKGROUND/AIMS: To examine the usefulness of dynamic flow imaging in identifying the therapeutic effects for hepatocellular carcinoma, we performed contrast-enhanced ultrasonography with Levovist. METHODOLOGY: Tumor vascularity of 48 hepatocellular carcinoma nodules in 27 patients infected with hepatitis C virus was assessed before and after radiofrequency ablation therapy by dynamic flow imaging with a wide-band power Doppler technology. RESULTS: All patients showed hypervascular enhancement of hepatocellular carcinoma on contrast-enhanced ultrasonography and/or dynamic computed tomography. The dynamic flow was obtained as vascular and perfusion images of hepatic tumors. The diameters of tumors were 1.1-2.0 cm in 12 nodules, 2.1-3.0 cm in 28, and 3.1-5.0 cm in 8, respectively. We were able to assess the tumor vascularities in 45 of 48 nodules before radiofrequency ablation by the dynamic flow. Three nodules showed insufficient dynamic flow which was located approximately 9 cm in depth from the body surface. The dynamic flow study for the therapeutic efficacy indicated that the tumor vessels disappeared in 43 of the 45 visible nodules. The tumor vascularities were noted in the remaining 2 nodules, and they were successfully retreated by radiofrequency ablation. The frequencies detecting positive enhancement in pretreatment and post-treatment were almost equivalent between vascular phase of dynamic flow on ultrasonography and early phase on helical dynamic computed tomography, although 5 nodules gave different findings; 2 were positive only on ultrasonography, and 3 were positive only on computed tomography. A major complication of radiofrequency ablation procedure was noted in only one case associated with intestinal edema, but it was cured by medical treatment. CONCLUSIONS: The results indicated that contrast-enhanced dynamic flow imaging on ultrasonography is a reliable tool to evaluate intratumoral vascularity both before and after radiofrequency ablation treatment in patients with hepatocellular carcinoma.

Aged↗

PubMedDate not supplied

A case of hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) using 4D real-time ultrasound system.

The patient was a 62-year-old man. The anamnesis revealed an alcoholic liver disease. The patient was admitted to the department of otolaryngology in our hospital with sudden deafness in March 2003. The liver damage was pointed out due to the laboratory data on admission. A liver tumor was identified on the subsequently performed CT scan and the patient was referred to another department at another ward for detailed examinations. Based on the results of contrast echography, CT findings and angiography a HCC was diagnosed and RFA was performed. The conventional B-mode ultrasound examination sometimes presented unclear cross-sectional images of the tumor at the target area, and so additional treatment had to be given from time to time. Simultaneously with the puncturing multi-slice imaging could be obtained, allowing exact and definite performance of the RFA using a 4D real-time ultrasound system. Additionally, ultrasound examination with contrast media was conducted to help determine the efficacy of treatment.

Carcinoma, Hepatocellular↗