Prevalence of hypertension, its awareness and control in adult population in Japan.
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Biomedical subjects
Publications and source records attributed to T Hayakawa.
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BACKGROUND AND STUDY AIMS: Despite advances in endoscopic procedures and extracorporeal shock wave lithotripsy (ESWL), the removal of impacted pancreatic duct stones demands a certain amount of time. The aim of this study was to determine which patient group might suitable for our single-session treatment. PATIENTS AND METHODS: The study included 17 patients who were symptomatic due to relapsing pancreatitis with pancreatic duct stones. A 5-Fr miniscope was inserted via the papilla to the impacted pancreatic duct stone and pancreatoscopic laser lithotripsy (PSLL) was performed, under direct vision, in only one session. If complete extraction of the pancreatic duct stones was not achieved with PSLL, ESWL was adopted in subsequent sessions. RESULTS: Complete extraction of the pancreatic duct stones using PSLL in a single session was achieved in eight of 17 patients. Single-session PSLL was only suitable for patients with pancreatic duct stones smaller than 17 mm in diameter and with no severe stricture or sharp bend in the pancreatic duct proximal to the stones. CONCLUSIONS: Our single-session endoscopic treatment of pancreatic duct stones was useful in a selected patient group.
OBJECTIVES: We have tried to approach the aqueduct less invasively with the endoscope in combination with a small suboccipital craniectomy, especially for lesions of the aqueduct close to the fourth ventricle. METHODS: The patient is placed in the prone position and a small suboccipital craniectomy is performed. After elevating the bilateral tonsils with retractors, the sheath of the endoscope is inserted from a small skin incision made on the posterior midline of the neck, far from the craniectomy site. The skin incision for endoscopic insertion is planned on the linear extension connecting the aqueduct and the foramen of Magendi on the craniocervical MRI. A rigid endoscope is inserted through the fourth ventricle to the aqueduct for exploration and surgical manipulation. RESULTS: Two cases with hydrocephalus due to aqueductal stenosis, with gait disturbance were operated. After exploration of the aqueduct via the fourth ventricle, endoscopic aqueductal plasty was performed. The postoperative courses were uneventful. The patients' symptoms disappeared. CONCLUSIONS: This approach can be applied for less invasive endoscopic exploration and surgery around the aqueduct close to the fourth ventricle with a rigid endoscope, without overflexion of the neck, or a large craniectomy, or overretraction of the tonsils, or incision of the inferior vermis.
In this study, flagellin is purified biochemically from eight urease-positive thermophilic camplylobacters (UPTC) isolated from river water, sea water and mussels, and purified also from two isolates of Campylobacter jejuni and C. coli and fractionated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Results showed that no flagellin components were detected in the two Japanese UPTC isolates (CF89-12 and CF89-14) and the two UPTC NCTC strains (NCTC12893 and NCTC12894). Flagellin components, each consisting of a single peptide, with a heterogeneous molecular mass of approximately 52-63 kDa were demonstrated in the other four UPTC isolates (NCTC12892, NCTC12895, NCTC12896 and NI15F [from Northern Ireland]) and the two Japanese isolates of C. jejuni (JCM2013 and C. coli 27). The approximate molecular mass of flagellin from the flagellin-positive UPTC isolates was smaller than those of C. jejuni and C. coli. Flagella were not detected by electron microscopy in the four flagellin-negative UPTC isolates but they were detected in the four flagellin-positive UPTC isolates and the two isolates of C. jejuni and C. coli. Thus, significant phenotypic diversity for flagellin, which must be due to genotypic variations, was demonstrated among the UPTC isolates.
A novel method for forming dye-containing nano-domains in thin films using a polymer alloy system has been developed. The polymer alloy system (PS-b-PMMA), which consists of polystyrene (PS) and polymethyl methacrylate (PMMA), forms microphase separation in thin films. The film was treated using a previously reported technique under vacuum conditions, and an organic dye was selectively dispersed into the PS. Selective association of the dye (diarylethene; cis-1, 2-dicyano-1, 2-bis (2,4,5-trimethyl-3-thienyl) ethene) with the PS nano-domains was then observed, with both transmission electron microscopy and scanning near-field optical microscopy with an absorption spectrum.
The aim of the present study was to study the mineral formation on a phosphorylated dental bonding agent using a mineralization inductive solution. Clearfil Photobond, which contained phosphate monomer, was cured by photo-irradiation and heat treated, and was then immersed in Hanks' balanced salt solution (HBSS) with pH = 7.4 for 1, 3, 5, 7, 14, and 28 days at 37 degrees C. The white substances were deposited on the phosphorylated polymer, i.e. cured Photobond disk, after the immersion in HBSS. The white substances become visible after 3 days immersion. After 7 days immersion, surface of the phosphorylated polymer disk was almost covered with white substance layers. The measurement of white substances by means of X-ray diffraction, Fourier-transform infrared and electron probe microanalysis revealed that their main component was carbonate-containing hydroxyapatite. Scanning electron microscopy pictures showed that a large number of globules of hydroxyapatite were fused together, and that each globule was composed of a group of numerous thin-film form flakes uniting and/or clustering together. The results obtained in this study concluded that the presence of phosphonic acid and phosphate group of phosphorylated dental bonding agent enhanced the nucleation and growth of hydroxyapatite crystals on its surface.
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In this study, fiber-mutant adenovirus vectors encoding chemokines, Ad-RGD-mCCL17, Ad-RGD-mCCL21 and Ad-RGD-mCCL22 were constructed. The insertion of integrin-targeting RGD sequence into fiber knob of adenovirus vectors notably enhanced the infection efficiency into tumor cells. Among three chemokine-encoding vectors evaluated, Ad-RGD-mCCL22 showed significant tumor-suppressive activity via transduction into OV-HM cells.
In the present study, a first-generation adenovirus (Ad) vector was modified with the RGD peptide inserted into the fiber. The insertion of an integrin-targeting sequence into the Ad vector notably enhanced the luciferase expression in the Coxsackie virus and Adenovirus Receptor-deficient A2058 and B16BL6 melanoma cells. The results of an in vivo study with tumor-bearing mice also showed that Ad-RGD-Luc had enhanced gene expression in many organs and in the B16BL6 tumor compared to that induced by a conventional Ad vector after intravenous injection.
The purpose of this study was to investigate the antibacterial activity of newly developed amphiphilic lipids and DNA/lipid complexes against two types of oral bacteria and two types of hospital infection bacteria. Nine amphiphilic lipids were quantitatively prepared from the reaction of n-alkyl alcohol, alpha-amino acids, and p-toluenesulfonic acid. Nine DNA-lipid complexes were prepared by the simple mixing of DNA and amphiphilic lipids. The DNA-lipid complexes were insoluble in water. The antibacterial activity of lipids and DNA-lipid complexes against Porphyromonas gingivalis, Streptococcus mutans, Staphylococcus aureus, and Pseudomonas aeruginosa were evaluated by the disk-diffusion method. Seven artificial lipids showed antibacterial behavior; in particular, the lipids prepared from n-decyl alcohol and glycine and from n-decyl alcohol and L-alanine showed antibacterial activity against the four bacterial strains used in this study. On the other hand, the lipids of glutamic acid derivatives did not show any antibacterial activity against the four bacteria strains except for the lipid with an n-octyl group. Five DNA-lipid complexes also had an antibacterial effect. The complex prepared from DNA and glycine decyl ester p-toluenesulfonic acid salt exhibited antibacterial activity against the four types of bacteria strains. In this study it was found that lipids and DNA-lipid complexes with a mono-decyl group or a mono-dodecyl group have more favorable antibacterial activity.
We are pursuing a positional cloning strategy to isolate the fertility restoration gene Rfk1 from radish. Random polymorphic DNA-sequence-tagged site (RAPD-STS) markers tightly linked to the gene in radish were isolated, and a RAPD map surrounding the Rfk1 locus was constructed. We surveyed 948 F2 plants with adjacent RAPD-STS markers to isolate recombinants for bulk segregant analysis. This analysis was effective in isolating tightly linked amplification fragment length polymorphism (AFLP) markers surrounding the gene of interest. Ten tightly linked AFLP markers were obtained and used to construct a high-resolution map of the region. The closest AFLP-STS markers flanking Rfk1 were 0.1 cM and 0.2 cM away. Using the four adjacent AFLP markers, we screened lambda and cosmid libraries. The lambda and cosmid clones were aligned by examination of end sequences and restriction fragment length polymorphism (RFLP) patterns for each clone, and by hybridization to the DNA isolated from recombinants. Finally, we constructed a 198-kb contig encompassing the Rfk1 gene and comprising 20 lambda and two cosmid clones. By analysis of the breakpoints in recombinants with the rfk1/rfk1 or Rfk1/- genotype, the Rfk1 locus could be assigned to a 43-kb region comprising four lambda clones and one cosmid clone. This pinpoint localization in the radish genome has made it possible for us to identify the gene by sequence analysis and genetic transformation of cytoplasmic male-sterile Brassica napus plants.
We previously reported that RGD fiber-mutant adenovirus vector carrying human TNFalpha cDNA (AdRGD-TNFalpha) could more effectively induce mouse B16 BL6 melanoma regression than conventional Ad-TNFalpha on intratumoral injection at less than 10(9) vector particles (VP). Although mice treated with either Ad type at 10(10) VP showed remarkable tumor regression due to hemolytic necrosis, severe adverse effects including extreme reduction in body weight were also induced by Ad treatment. Here, we attempted to elucidate the cause of the adverse effects to optimize the application of AdRGD-TNFalpha. More than 99% of systemically administered Ad accumulated in the liver, and the rate of Ad leakage into systemic circulation from the B16 BL6 tumors injected with AdRGD or conventional Ad at 10(10) VP was about 1% of the administered VP. Although the leaked Ad did not directly induce hepatotoxicity or body weight reduction, excessive TNFalpha produced in the tumors leaked into the blood at high concentrations and caused systemic inflammation, tissue denaturation, and body weight reduction in mice injected intratumorally with AdRGD-TNFalpha or Ad-TNFalpha at 10(10) VP. Our results demonstrated that an exact AdRGD-TNFalpha dosage must be determined to prevent TNFalpha leakage from tumors into systemic circulation, thereby enabling safe application of AdRGD-TNFalpha to clinical melanoma gene therapy in the future.
Efficient gene transfer into human hematopoietic stem cells (HSCs) is the most important requirement for gene therapy of hematopoietic disorders and for study of the hematopoietic system. An adenovirus (Ad) vector based on the Ad serotype 5 (Ad5) is known to transduce HSCs, including CD34(+) cells, with very low efficiency because of low-level expression of its primary receptor, coxsackievirus and adenovirus receptor (CAR). In the present study, we developed a recombinant Ad vector composed of the whole Ad serotype 35 (Ad35), which recognizes an unidentified receptor different from CAR for its infection. A transduction study showed that the Ad35-based vectors exhibit a higher transduction efficiency in human CD34(+) cells than the conventional Ad5 vectors and the Ad5F35 vectors, which are fiber-substituted Ad5 vectors containing Ad35 fiber proteins. The mean of fluorescence intensity in the CD34(+) cells transduced with the Ad35 vectors was 12-76 and 1.4-3 times higher than that in the cells transduced with the Ad5 and Ad5F35 vectors, respectively. The percentages of green fluorescent protein (GFP)-positive CD34(+) cells by transduction with Ad35, Ad5, and Ad5F35 vectors expressing GFP at 300 PFU/cell were 53%, 5%, and 52%, respectively, suggesting that Ad35 vectors mediate a more efficient gene transfer into human CD34(+) cells than Ad5 and Ad5F35 vectors, although the percentage of transduced cells was similar between Ad35 and Ad5F35 vectors. The Ad vector based on Ad35 could be very useful in gene therapy for blood disorders and gene transfer experiments using HSCs.
For cancer gene therapy, replicative adenovirus is a promising vector to overcome low infectivity and poor gene delivery of nonreplicative adenovirus in vivo, but its therapeutic efficacy is still unsatisfactory because of the limited spread of replicative virus in a solid tumor. Therefore, the combined therapy with other antitumor agents may be necessary. Nonreplicative adenovirus expressing a therapeutic gene may be a promising candidate because E1 proteins expressed by replicative adenovirus would render nonreplicative adenovirus replicative, augmenting a transgene expression. In this study, we first found that mouse hepatoma Hepa 1-6 cells were permissive for the replication and cytopathic effect of human adenovirus, which enabled us to examine the potential of combined replicative adenovirus and nonreplicative adenovirus expressing an immunostimulator in an immunocompetent mouse-syngeneic Hepa 1-6 tumor model. Nonreplicative adenovirus expressing interleukin-12 (AdIL-12) was used as a model. In vitro coinfection of two adenoviruses produced higher concentrations of IL-12 than infection of AdIL-12 alone in this cell line. In vivo experiments with Hepa 1-6 tumors in syngeneic immunocompetent C57BL/6 mice showed higher concentrations of serum IL-12 and greater therapeutic efficacy in the combination therapy than infection of either adenovirus. These data indicate that the combination of replicative adenovirus and nonreplicative adenovirus expressing an immunostimulator appears to be very efficacious for cancer gene therapy.
Dendritic cells (DCs) are the most potent professional antigen-presenting cells for the initiation of antigen-specific immune responses, and antigen-loaded DCs have been regarded as promising vaccines in cancer immunotherapy. We previously demonstrated that RGD fiber-mutant adenovirus vector (AdRGD) could attain highly efficient gene transduction into human and murine DCs. The aim of the present study is to demonstrate the predominance of ex vivo genetic DC manipulation using AdRGD in improving the efficacy of DC-based immunotherapy targeting gp100, a melanoma-associated antigen (MAA). Vaccination with murine bone marrow-derived DCs transduced with AdRGD encoding gp100 (AdRGD-gp100/mBM-DCs) dramatically improved resistance to B16BL6 melanoma challenge and pulmonary metastasis as compared with immunization with conventional Ad-gp100-transduced mBM-DCs. The improvement in antimelanoma effects upon immunization with AdRGD-gp100/mBM-DCs correlated with enhanced cytotoxic activities of natural killer (NK) cells and B16BL6-specific cytotoxic T lymphocytes (CTLs). Furthermore, in vivo depletion analysis demonstrated that CD8(+) CTLs and NK cells were the predominant effector cells responsible for the anti-B16BL6 immunity induced by vaccination with AdRGD-gp100/mBM-DCs, and that helper function of CD4(+) T cells was necessary for sufficiently eliciting effector activity. These findings clearly revealed that highly efficient MAA gene transduction to DCs by AdRGD could greatly improve the efficacy of DC-based immunotherapy against melanoma.
OBJECTIVE: In a population with a markedly lower coronary mortality such as in Japan, the benefit of cholesterol screening may be different from Western populations. We attempted to assess the importance of cholesterol screening in Japan. DESIGN: A 13.2-year cohort study for cause-specific mortality. SETTING: Three hundred randomly selected districts throughout Japan in which the National Survey on Circulatory Disorders 1980 was performed. SUBJECTS: A total of 9216 community dwelling persons aged 30 years and over, with standardized serum cholesterol measurement and without a past history of cardiovascular disease. RESULTS: There were 1206 deaths, which included 462 deaths due to cardiovascular disease with 79 coronary heart diseases. Hypercholesterolemia (>6.21 mmol L-1) showed a significant positive relation to coronary mortality (relative risk; 2.93, 95% confidence interval; 1.52-5.63) but not to stroke. Although hypocholesterolemia (<4.14 mmol L-1) was significantly associated with an increased risk of liver cancer, noncardiovascular, noncancer disease and all-cause mortality, these associations, except for liver cancer, disappeared after excluding deaths in the first 5 years of the follow-up. The multivariate adjusted attributable risk of hypercholesterolaemia for coronary disease was 0.98 per 1000 person-years, which was threefold higher than that of hypocholesterolemia for liver cancer: 0.32 per 1000 person-years. The attributable risk percentage of hypercholesterolaemia was 66% for coronary heart disease. CONCLUSION: Similar to Western populations, it is recommended to provide screening for hypercholesterolaemia in Japan, especially for males, although its attributable risk for coronary disease might be small.
For patients who have esophageal carcinoma with tracheal invasion surgery is usually not indicated because operative complications are considerable and the prognosis is poor. We experienced complete regression of a large esophageal carcinoma with tracheal stenosis due to tumor invasion without tracheo-esophageal fistula. Irradiation of 68 Gy was delivered to a long T field from the neck to the lower thoracic esophagus, and was combined with chemotherapy using cisplatin and 5-fluorouracil. The tumor decreased markedly in size and the tracheal stenosis resolved. The patient has survived for 4 years, although second primary early esophageal carcinoma and hypopharyngeal carcinoma were detected 2 years after his initial chemoradiotherapy. Although the prognosis of advanced esophageal carcinoma with invasion of other organs is usually poor, the effect of chemoradiotherapy can sometimes be dramatic and a good result can be achieved in such patients.
PURPOSE: In this study, we evaluated the diagnostic usefulness of contrast-enhanced transabdominal ultrasonography (CE-US) in pancreatic mass lesions that could be detected by US. MATERIAL AND METHODS: CE-US was performed in 37 patients with various pancreatic mass lesions to evaluate the characteristic vascular findings. RESULTS: Pancreatic tubular adenocarcinoma showed negative enhancement pattern in 16 cases and a slight spotty enhancement pattern in 5 cases. Poorly differentiated adenocarcinoma showed slight homogeneous enhancement pattern in 1 case and acinar cell carcinoma was expressed as a heterogeneous enhancement pattern in 3 cases on CE-US. Endocrine cell tumor had a strong homogeneous enhancement pattern in 3 cases, a strong central enhancement in 1 case and a strong peripheral enhancement in 2 cases. Pseudotumorous pancreatitis showed an iso-enhancement pattern in 6 cases. CONCLUSION: CE-US is useful in evaluating the vascularity of the lesions in various pancreatic mass lesions in real-time images, and may be useful for the differential diagnosis of pancreatic mass lesions.