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Biomedical subjects

T Tanaka

Publications and source records attributed to T Tanaka.

At least 37 records · Page 2Linked to original sources

Genetic analysis of noroviruses associated with fatalities in healthcare facilities.

Norovirus outbreaks occurred in 236 healthcare facilities for the elderly in Japan during the winter of 2004-2005. Three norovirus strains associated with three fatal clinical courses were isolated from geographically separate facilities and genetically analyzed along with three strains from non-fatal cases in the same season. All six isolates were classified as the GII-4 genotype. No new variant strains like those observed in Europe in 2002 and 2004 were found in fatal cases, and the three outbreaks were deemed to have been caused by genetically close conventional norovirus GII-4 strains.

Aged, 80 and over↗

Virus-like particles in venom of Meteorus pulchricornis induce host hemocyte apoptosis.

Ultrastructural studies on the reproductive tract and venom apparatus of a female braconid, Meteorus pulchricornis, revealed that the parasitoid lacks the calyx region in its oviduct, but possesses a venom gland with two venom gland filaments and a venom reservoir filled with white and cloudy fluid. Its venom gland cell is concaved and has a lumen filled with numerous granules. Transmisson electron microscopic (TEM) observation revealed that virus-like particles (VLPs) were produced in venom gland cells. The virus-like particle observed in M. pulchricornis (MpVLP) is composed of membranous envelopes with two different parts: a high-density core and a whitish low-density part. The VLPs of M. pulchricornis is also found assembling ultimately in the lumen of venom gland cell. Microvilli were found thrusting into the lumen of the venom gland cell and seem to aid in driving the matured MpVLPs to the common duct of the venom gland filament. Injection of MpVLPs into non-parasitized Pseudaletia separata hosts induced apoptosis in hemocytes, particularly granulocytes (GRs). Rate of apoptosis induced in GRs peaked 48h after VLP injection. While a large part of the GR population collapsed due to apoptosis caused by MpVLPs, the plasmatocyte population was minimally affected. The capacity of MpVLPs to cause apoptosis in host's hemocytes was further demonstrated by a decrease ( approximately 10-fold) in ability of host hemocytes to encapsulate fluorescent latex beads when MpVLPs were present. Apparently, the reduced encapsulation ability was due to a decrease in the GR population resulting from MpVLP-induced apoptosis.

Animals↗

In Situ HREM observation of crystalline-to-gas transition in nanometer-sized Ag particles.

Sublimation of silver atoms from a nanometer-sized silver particle, namely, the crystalline-to-gas transition, has been directly observed by high resolution electron microscopy. Remarkable sublimation of silver atoms took place at 950 K from an approximately 9-nm-sized crystalline silver particle on the graphite substrate. The sublimation continued until the whole silver particle disappeared. No melting of the particle occurred during this process. The height-to-width ratio of a nanometer-sized silver particle on graphite at 950 K was about 0.65, and the ratio did not change so much during the sublimation-induced shrinkage of the particle.

Journal Article↗

Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer.

Hepatocyte nuclear factor-4alpha (HNF4alpha) exists in multiple isoforms that are generated by alternative promoter (P1 and P2) usage and splicing. Here we establish monoclonal antibodies (mAbs) for detecting P1 and P2 promoter-driven HNF4alpha, and evaluate their expression in normal adult human tissues and surgically resected carcinomas of different origins. Using immunohistochemical analysis, we demonstrate that, while P1 promoter-driven HNF4alpha is expressed in hepatocytes, small intestine, colon, kidney and epididymis, P2 promoter-driven HNF4alpha is expressed in bile duct, pancreas, stomach, small intestine, colon and epididymis. Altered expression patterns of P1 and P2 promoter-driven HNF4alpha were observed in gastric, hepatocellular and colorectal carcinomas. HNF4alpha was expressed in lung metastases from renal cell, hepatocellular and colorectal carcinoma but was not observed in lung tumours. The P1 and P2 promoter-driven HNF4alpha expression pattern of tumour metastases correlated with the primary site of origin. P1 promoter-driven HNF4alpha was also found in intestinal metaplasia of the stomach. These data provide evidence for the tissue distribution of P1 and P2 promoter-driven HNF4alpha at the protein level and suggest that HNF4alpha may be a novel diagnostic marker for metastases of unknown primary. We propose that the dysregulation of alternative promoter usage of HNF4alpha is associated with the pathogenesis of certain cancers.

Animals↗

Benefical effect of neutrophil elastase inhibitor on renal warm ischemia-reperfusion injury in the rat.

Renal ischemia-reperfusion (I/R) injury is a significant problem in renal transplantation. Neutrophils play an important role in renal I/R injury. Several reports have demonstrated that neutrophil elastase derived from the activated neutrophils might play an important role in this injury. We investigated the effect of a neutrophil elastase inhibitor in renal I/R injury. Male Lewis rats (270-320 g) were used in the model. The right kidney was harvested and the left renal artery and vein were clamped at laparotomy. The kidney was reperfused after 90 minutes of ischemia. Neutrophil elastase inhibitor (ONO-5046: 30 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent neutrophil activation. In the nontreatment I/R group, no hosts survived 4 days. However, after treatment with neutrophil elastase inhibitor, 3 of 10 rats in the I/R group, survived more than 7 days. These results demonstrated that treatment with neutrophil elastase inhibitor ameliorated renal I/R injury.

Animals↗

Intraperitoneal injection of oxygenated perfluorochemical improves the outcome of intraportal islet transplantation in a rat model.

A 50% to 75% early graft loss upon engraftment has been suggested to in intraportal islet transplantation (IPIT). Hypoxia in the portal vein contributes to graft loss in immediately posttransplantation. Herein we examined the effect on the outcome of IPIT of intraperitoneal oxygenated perfluorochemical (PFC) as an oxygen carrier. Isolated Lewis rat islets were transplanted into the portal vein of a chemically induced diabetic syngeneic rat. First, 1500 IEQ was determined to be the optimal dose in this study. When oxygenated PFC (group 1) was intraperitoneally injected following IPIT of 1500 IEQ, the success rate of transplantation was 5/6, in contrast to 1/6 when PFC with no oxygen was injected (group 2) and 1/6 in IPIT without PFC, respectively. The area under the glucose profile curve on intraperitoneal glucose tolerance tests on posttransplant day 28 in group 1 was significantly smaller than that for group 2. In conclusion, intraperitoneal oxygenated PFC improved the outcome of IPIT.

Animals↗

Antiangiogenic activity of BAI1 in vivo: implications for gene therapy of human glioblastomas.

Glioblastomas are the most common primary brain tumors in adults. These tumors exhibit a high degree of vascularization, and malignant progression from astrocytoma to glioblastoma is often accompanied by increased angiogenesis and the upregulation of vascular endothelial growth factor and its receptors. In this study, we investigated the in vivo antiangiogenic and antitumor effects of brain-specific angiogenesis inhibitor 1 (BAI1) using human glioblastoma cell lines. Glioblastoma cells were transduced with an adenoviral vector encoding BAI1 (AdBAI1), and Northern and Western blot analyses, respectively, demonstrated BAI1 mRNA and protein expression in the transduced tumor cells. Using an in vivo neovascularization assay, we found that angiogenesis surrounding AdBAI1-transduced glioblastoma cells transplanted into transparent skinfold chambers of SCID mice was significantly impaired compared to control treated cells. Additionally, in vivo inoculation with AdBAI1 of established subcutaneous or intracerebral transplanted tumors significantly impaired tumor growth and promoted increased mouse survival. Morphologically, the tumors exhibited signs of impaired angiogenesis, such as extensive necrosis and reduced intratumoral vascular density. Taken together, these data strongly indicate that BAI1 may be an excellent gene therapy candidate for the treatment of brain tumors, especially human glioblastomas.

Adenoviridae↗

Hypertrophy of the posterior longitudinal ligament in the thoracic spine.

STUDY DESIGN: This is a case report of a patient with hypertrophy of the posterior longitudinal ligament (HPLL) in the thoracic spine. This patient was followed for 10 years after surgery. OBJECTIVES: The purpose of this study was to report the long-term outcome of HPLL in the thoracic spine. SETTING: Department of orthopedic surgery, Hiroshima Red Cross and Atomic-bomb Survivors Hospital, Hiroshima, Japan. METHODS: A 58-year-old-woman with thoracic HPLL was reported. Magnetic resonance image (MRI) and computed tomography (CT) showed the expanded spinal cord compression from Th4 to Th12 due to HPLL. Anterior decompression and fusion (Th10-12) was performed. Histological findings of the surgical specimens showed thickening of the posterior longitudinal ligament with proliferation of chondroid tissue. The clinical outcome and the radiological findings (CT and MRI) were evaluated 10 years after surgery. RESULTS: The patient was asymptomatic postoperatively. However, the subsequent CT examination revealed ossification of the previously hypertrophied posterior longitudinal ligament. CONCLUSIONS: HPLL in the thoracic spine is a rare pathological condition causing myelopathy. The results of this study support the hypothesis that HPLL is one of the prodromal conditions of HPLL.

Decompression, Surgical↗

Semi-purification of the immunoglobulin E-sweat antigen acting on mast cells and basophils in atopic dermatitis.

BACKGROUND: Sweating aggravates the symptoms of atopic dermatitis (AD). We have recently reported positive skin reactions and histamine release from basophils in response to autologous sweat in patients with AD. OBJECTIVE: To characterize the biochemical and immunological properties of the substance in sweat that evokes histamine release and to study the usability of the basophil-histamine release test with the sweat antigen for AD. METHODS: Sweat collected from healthy volunteers was purified using chromatographies. Serum immunoglobulin (Ig)E of four patients with AD were purified using an affinity-chromatography column with anti-IgE antibodies. The amount of semi-purified sweat antigen (138 ng protein/ml) that induced a half-maximum reaction of basophils of a patient with AD was utilized for the basophil histamine release test. The involvement of specific IgE and high-affinity IgE receptor (FcepsilonRI) in the reactions was examined using basophils of healthy volunteers, a human mast cell line (LAD2), and a rat basophilic leukemia cell line transfected with human alpha-subunit of FcepsilonRI (RBL-48). RESULTS: The semi-purified sweat antigen induced histamine release from the basophils of 47 of 61 (74.6%) patients with AD and four of 46 (8.7%) healthy controls. Both basophils and mast cells sensitized with the patient-derived IgE showed degranulation upon stimulation with the sweat antigen. However, no reaction was observed when cells were sensitized with myeloma IgE or the antigen was treated with proteases. CONCLUSION: The semi-purified standardized sweat antigen consists of a protein that induces degranulation of basophils and mast cells via antigen-specific IgE and FcepsilonRI in patients with AD.

Adolescent↗

Changes in the number of Merkel cells with the hair cycle in hair discs on rat back skin.

BACKGROUND: Hair discs are known to contain a large number of Merkel cells and are ideal for investigating Merkel cell biology. Hair follicles, which are important elements of hair discs, undergo unique cyclical morphological and biological changes. OBJECTIVES: To define the relationships between the number and the morphology of Merkel cells within the hair disc in association with the hair cycle on rat back skin. METHODS: Merkel cells in hair discs were observed three-dimensionally using immunohistochemistry. Epidermal sheets were incubated with monoclonal murine antibody to CK20. As a result, Merkel cells in hair discs were clearly demonstrated as whole shapes and were counted under a light microscope. RESULTS: Merkel cells in hair discs increased during the early to middle phase of anagen and decreased during the middle phase of anagen to catagen and telogen in perinatal and postnatal rat back skin. We observed the morphological variation of Merkel cells in hair discs of rat back skin, and consequently divided them into two subtypes at the light microscopic level: the oval type and the dendritic type. The number of oval-type Merkel cells was not markedly affected by the hair cycle. In contrast, the number of dendritic-type Merkel cells markedly changed with the hair cycle. CONCLUSIONS: This difference of the hair cycle dependency between oval and dendritic-type Merkel cells suggests some functional differences, such as a secretory function, related to the hair cycle.

Aging↗

ATM activation and histone H2AX phosphorylation as indicators of DNA damage by DNA topoisomerase I inhibitor topotecan and during apoptosis.

Damage that engenders DNA double-strand breaks (DSBs) activates ataxia telangiectasia mutated (ATM) kinase through its auto- or trans-phosphorylation on Ser1981 and activated ATM is one of the mediators of histone H2AX phosphorylation on Ser139. The present study was designed to explore: (i) whether measurement of ATM activation combined with H2AX phosphorylation provides a more sensitive indicator of DSBs than each of these events alone, and (ii) to reveal possible involvement of ATM activation in H2AX phosphorylation during apoptosis. Activation of ATM and/or H2AX phosphorylation in HL-60 or Jurkat cells treated with topotecan (Tpt) was detected immunocytochemically in relation to cell cycle phase, by multiparameter cytometry. Exposure to Tpt led to concurrent phosphorylation of ATM and H2AX in S-phase cells, whereas G1 cells were unaffected. Immunofluorescence (IF) of the S-phase cells immunostained for ATM-S1981P and gammaH2AX combined was distinctly stronger compared to that of the cells stained for each of these proteins alone. However, because of the relatively high ATM-S1981P IF of G1 cells, the ratio of IF of S to G1 cells, that is, the factor that determines competence of the assay in distinction of cells with DSBs, was 2- to 3-fold lower for ATM-S1981P alone, or for ATM-S1981P and gammaH2AX IF combined, than for gammaH2AX alone. ATM activation concurrent with H2AX phosphorylation, likely triggered by induction of DSBs during DNA fragmentation, occurred during apoptosis. The data suggest that frequency of activated ATM and phosphorylated H2AX molecules, per apoptotic cell, is comparable.

Antineoplastic Agents↗

Synchronization in the cell cycle by inhibitors of DNA replication induces histone H2AX phosphorylation: an indication of DNA damage.

Several methods to synchronize cultured cells in the cell cycle are based on temporary inhibition of DNA replication. Previously it has been reported that cells synchronized this way exhibited significant growth imbalance and unscheduled expression of cyclins A and B1. We have now observed that HL-60 cells exposed to inhibitors of DNA replication (thymidine, aphidicolin and hydroxyurea), at concentrations commonly used to synchronize cell populations, had histone H2AX phosphorylated on Ser-139. This modification of H2AX, a marker of DNA damage (induction of DNA double-strand breaks; DSBs), was most pronounced in S-phase cells, and led to their apoptosis. Thus, to a large extent, synchronization was caused by selective kill of DNA replicating cells through induction of replication stress. In fact, similar synchronization has been achieved by exposure of cells to the DNA topoisomerase I inhibitor camptothecin, a cytotoxic drug known to target S-phase cells. A large proportion of the surviving cells 'synchronized' by DNA replication inhibitors at the G1/S boundary had phosphorylated histone H2AX. Inhibitors of DNA replication, thus, not only selectively kill DNA replicating cells, induce growth imbalance and alter the machinery regulating progression through the cycle, but they also cause DNA damage involving formation of DSBs in the surviving ('synchronized') cells. The above effects should be taken into account when interpreting data obtained with the use of cells synchronized by inhibitors of DNA replication.

Aphidicolin↗

Extent of constitutive histone H2AX phosphorylation on Ser-139 varies in cells with different TP53 status.

In response to DNA damage by genotoxic agents, histone H2AX is phosphorylated on Ser-139. However, during the cell cycle, predominantly in S and G(2)M phase, histone H2AX is also phosphorylated in untreated normal and tumour cells. This constitutive H2AX phosphorylation is markedly reduced by exposure of cells to the reactive oxygen species scavenger N-acetyl-L-cysteine. Therefore, it appears likely that constitutive H2AX phosphorylation reflects the ongoing oxidative DNA damage induced by the reactive oxygen species during progression through the cell cycle. Because the tumour suppressor p53 (tumour protein p53) is known to induce transcription of genes associated with cell response to oxidative stress, we have compared the intensity of constitutive H2AX phosphorylation, and the effect of N-acetyl-L-cysteine on it, in cells with different tumour protein p53 status. These were human lymphoblastoid cell lines derived from WIL2 cells: TK6, a p53 wt line, NH32, a tumour protein p53 knock-out derived from TK6, and WTK1, a WIL2-derived line that expresses a homozygous mutant of tumour protein p53. Also tested were the tumour protein p53-null promyelocytic HL-60 cells. The degree of constitutive H2AX phosphorylation was distinctly lower in NH32, WTK1 and HL-60 compared to TK6 cells in all phases of the cell cycle. Also, the degree of attenuation of constitutive H2AX phosphorylation by N-acetyl-L-cysteine was less pronounced in NH32, WTK1, and HL-60, compared to TK6 cells. However, the level of reactive oxygen species detected by the cells' ability to oxidize carboxyl-dichlorodihydrofluorescein diacetate was not significantly different in the cell lines studied, which would suggest that regardless of tumour protein p53 status, the level of oxidative DNA damage was similar. The observed higher level of constitutive H2AX phosphorylation in cells harbouring wt tumour protein p53 may thus indicate that tumour protein p53 plays a role in facilitating histone H2AX phosphorylation, an important step in the mobilization of the DNA repair machinery at the site of DNA double-strand breaks.

Acetylcysteine↗

Development of a rapid strain differentiation method for methicillin-resistant Staphylococcus aureus isolated in Japan by detecting phage-derived open-reading frames.

AIMS: To develop a rapid genotyping method for investigating outbreaks of methicillin-resistant strains of Staphylococcus aureus (MRSA) isolated in Japan. METHODS AND RESULTS: Isolates were genotyped by detecting the keeping pattern of 16 open-reading frames (ORFs), a process we call phage ORF typing (POT). Thirteen of the ORFs were selected from phage genomes and one from a genomic island SaGIm in the genome of strain Mu50. The other two ORFs, one from Tn554 and one from staphylococcal cassette chromosome mec (SCCmec) type II, were used as strain markers. Three hundred and sixty-eight isolates from five hospitals were classified into 133 types by POT, whereas they were classified into 139 types by pulsed-field gel electrophoresis (PFGE) subtyping. The discriminatory power of POT (D=0.989) was equal to that of PFGE subtyping (D=0.986). CONCLUSIONS: MRSA isolates collected in Japan can be genotyped by detecting the keeping pattern of phage-derived ORFs with a discriminatory power equal to that of PFGE subtyping. SIGNIFICANCE AND IMPACT OF THE STUDY: MRSA isolates can be genotyped rapidly by detecting phage-derived ORFs. As particular pandemic clones can be found in a specific region, a typing method localized to a pandemic clone may be effective for the rapid genotyping of MRSA during outbreaks.

Bacterial Typing Techniques↗

Dynamic magnetic resonance sialography as a new diagnostic technique for patients with Sjögren's syndrome.

OBJECTIVE: To evaluate the clinical utility of dynamic magnetic resonance (MR) sialographic images as a diagnostic tool for patients with Sjögren's syndrome. METHODS: The morphological findings and various kinds of functional parameters in volunteers on dynamic MR sialographic images were compared with those in five patients with definite Sjögren's syndrome. RESULTS: On the MR sialographs of all five patients with Sjögren's syndrome, the so-called 'apple-tree appearance' was seen. The difference in two functional parameters using the dynamic MR sialographic data was elucidated between the two groups. The maximum area of the detectable ducts in the group of patients was significantly smaller (P < 0.001) than that in the group of volunteers. The ratio of change in the detectable ducts in the group of patients was significantly lower (P = 0.011) than that in the group of volunteers. CONCLUSIONS: Our study suggests that dynamic MR sialographic data in addition to MR sialographic images might be useful for the diagnosis of Sjögren's syndrome.

Adult↗

Clinical significance and variation of the advanced calcified stylohyoid complex detected by panoramic radiographs among 80-year-old subjects.

OBJECTIVES: To evaluate the clinical significance and variation of a calcified stylohyoid complex associated with advanced calcification as detected on panoramic radiographs among 80-year-old subjects. METHODS: Panoramic radiographs of 659 patients (262 men and 397 women) and data of their general and dental health conditions were used for the evaluation of the relationship between a calcified stylohyoid complex and general health among 80-year-olds. This study was part of the 8020 Data Bank Survey, which was designed to collect the baseline data of general and dental health conditions in 80-year-old subjects. The morphology of the calcified stylohyoid complexes was allocated to one of 12 patterns. The lengths of the calcified stylohyoid complex were measured directly on the radiographs from the caudal margin of the tympanic plate to the tip of the styloid process. RESULTS: All of the stylohyoid complexes from the 659 panoramic radiographs could be allocated to one of 12 morphological patterns, and some of their radiographic findings suggested calcification of the carotid artery and lymph nodes. In 80-year-old subjects, the average length of the calcified stylohyoid complexes was 36.7 mm, and ranged from 0.0 mm to 153.0 mm. There appeared to be correlations between the length of the calcified stylohyoid complex and serum calcium concentration and heel bone density, but not with the Community Periodontal Index (CPI). CONCLUSIONS: Dentists should recognize the existence of morphological variation in calcified stylohyoid complexes, especially in length, apparent on panoramic radiographs of 80-year-old patients. In addition, the longer length of the calcified stylohyoid complexes in 80-year-old patients may be a predictor of bone density and high serum calcium concentration level. The findings from the present study may provide potentially life-saving information about elderly people.

Aged, 80 and over↗

Correlation between the incidence of central nodal necrosis in cervical lymph node metastasis and the extent of differentiation in oral squamous cell carcinoma.

OBJECTIVES: To investigate the incidence of central nodal necrosis (CNN) in the cervical lymph nodes of patients with oral squamous cell carcinoma (SCC) and the factors that influence the formation of CNN. METHODS: Lymph nodes shown as CNN on computed tomography (CT) films in 107 lymph nodes from 27 patients with oral SCC were selected. Lymph nodes with CNN on CT films were compared with the pathological findings of lymph nodes on specimens. We compared many kinds of factors influencing the formation of CNN, including the differentiated type, with the incidence of CNN. RESULTS: Significant relationships were found between the incidence of CNN in metastatic lymph nodes and the presence of well-differentiated SCC and the presence of keratinization in tumour cells. CONCLUSIONS: The results indicated that if a patient had SCC with low-grade differentiation, CNN in small lymph nodes would be difficult to detect on CT scan. Therefore, noting changes in lymph node density in the absence of CNN on CT scans is necessary in case the primary tumour is low-grade SCC.

Adult↗