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Biomedical subjects

K Fujisawa

Publications and source records attributed to K Fujisawa.

At least 19 recordsLinked to original sources

Chewing ability and quality of life in an 80-year-old population.

As quality of life (QOL) could be influenced by oral status in the elderly, we examined whether chewing ability or number of teeth affected QOL in 80-year olds. A cross-sectional survey included dental examination, chewing self-assessment, and a QOL questionnaire. A total of 823 people who were 80 years old participated in this study. QOL was assessed in terms of satisfaction with physical condition, meals, daily living and social interactions, and with face-scale scores. After adjustment for gender, spouse and activities of daily living, dissatisfaction with social interactions was 3.9 times more prevalent in individuals able to chew four foods or fewer than in those chewing 15. Dissatisfaction with physical condition, meals and daily living, and poor face-scale scores, were 2.7, 2.4, 3.4, and 2.4 times more prevalent, respectively, in subjects chewing four foods or fewer. The number of teeth showed little effect. In conclusion, self-assessed chewing ability but not number of teeth was associated with QOL in 80-year-old subjects.

Activities of Daily Living↗

Preliminary laboratory based diagnostic criteria for immune thrombocytopenic purpura: evaluation by multi-center prospective study.

BACKGROUND: We proposed diagnostic criteria for immune thrombocytopenic purpura (ITP) by modifying the existing guidelines for diagnosis of ITP and by incorporating laboratory tests found useful for predicting its diagnosis, for example erythrocyte count, leukocyte count, anti-GPIIb/IIIa antibody-producing B cells, platelet-associated anti-GPIIb/IIIa antibodies, percentage of reticulated platelets, and plasma thrombopoietin. OBJECTIVE AND METHODS: To validate our criteria, we conducted a multi-center prospective study involving 112 patients with thrombocytopenia and a morphologically normal peripheral blood film at the first visit. Each patient underwent a physical examination, routine laboratory tests, and specialized tests for the anti-GPIIb/IIIa antibody response and platelet turnover. RESULTS: Ninety-one patients (81%) satisfied the proposed criteria at first visit. Clinical diagnosis was made by skilled hematologists > 6 months after the first visit; ITP was diagnosed in 88 patients and non-ITP disorders in 24. The proposed criteria had 98% sensitivity, 79% specificity, a 95% positive predictive value, and a 90% negative predictive value. A relatively low specificity appears to be attributed to a few patients who had both ITP and aplastic anemia or myelodysplastic syndrome. CONCLUSIONS: Our preliminary diagnostic criteria based on ITP-associated laboratory findings were useful for the differential diagnosis of ITP, but additional evaluations and modifications will be necessary to develop criteria that can be used routinely.

Adolescent↗

Novel mutation in ABCC6 gene in a Japanese pedigree with pseudoxanthoma elasticum and retinitis pigmentosa.

PURPOSE: To report a novel mutation of the ABCC6 gene in a Japanese family that had a case of pseudoxanthoma elasticum (PXE) another with PXE and retinitis pigmentosa. METHODS: Ophthalmologic examinations were performed, and the ABCC6 gene was analysed by direct genomic sequencing. RESULTS: Fundus examinations of the 48-year-old proband disclosed angioid streaks and a peud'orange appearance of the retina of the both eyes, whereas both of his 25- and 20-year-old daughters had pigmentary degeneration and angioid streaks. In the sibilings, the mixed cone-rod ERG was almost nondetectable, whereas that of the proband was well-preserved. Molecular genetic analysis revealed that the proband has a homozygous nonsense mutation at the 595 bp in the ABCC6, and the siblings were heterozygous for the same mutation. This mutation was not detected in Japanese subjects in the JSNP database (http://snp.ims.u-tokyo.ac.jp/). CONCLUSIONS: Our results demonstrated an association between a novel mutation in the ABCC6 gene and PXE in a Japanese family.

Adult↗

Injuries in elite motorcycle racing in Japan.

OBJECTIVES: To investigate the incidence and pattern of injuries, relative risks, and factors affecting incidence among elite motorcycle competitors in Japan. METHODS: A total of 117 elite motorcycle competitors including 36 road racers, 60 motocross racers, and 21 trial bike riders completed a questionnaire about injuries. RESULTS: Sixty major injuries (25 in road racing, 32 in motocross, and three in trial bike riding) were reported. The most common injuries were fractures (45), followed by ligament injuries (8), dislocations (5), and soft tissue injuries (2). The overall injury rate was 22.4 per 1000 hours, and the death rate was zero. There was no significant correlation between risk of injury and age, experience, or accumulated competition points. CONCLUSIONS: Injury rates in competitions such as road racing and motocross are high, and therefore additional safety measures are needed to protect competitors from injury.

Adult↗

Comparison of diagnostic methods for diabetes mellitus based on prevalence of retinopathy in a Japanese population: the Hisayama Study.

AIMS/HYPOTHESIS: The aims of this study were to compare the ability of tests measuring fasting plasma glucose, 2-h plasma glucose and HbA1c levels in predicting specific diabetic retinopathy, and to determine the cut-off level of each measurement for diagnosing diabetes in a Japanese population. METHODS: In a total of 1637 subjects, fasting plasma glucose, 2-h plasma glucose and HbA1c levels were measured in a 75-g oral glucose tolerance test, and diabetic retinopathy was assessed by ophthalmic examination. We calculated receiver operating characteristic (ROC) curves as well as the prevalence of diabetic retinopathy by deciles of the distribution of these glycaemic measurements. RESULTS: Of the subjects, 37 (2.3%) had diabetic retinopathy. The prevalence of retinopathy dramatically increased in the tenth decile of each variable. Analysis with ROC curves showed that the optimal cut-off levels for diagnosis of diabetes were 6.4 mmol/l for fasting plasma glucose, 11.1 mmol/l for 2-h plasma glucose, and 5.7% for HbA1c. The sensitivities for the cut-off point of the three measurements were identical (86.5%), and the specificities were similar (fasting plasma glucose 87.3%; 2-h plasma glucose 89.6%; HbA1c 90.1%). The area under the ROC curve for 2-h plasma glucose (96.1%) was slightly but not significantly larger than that for fasting plasma glucose (90.0%) and that for HbA1c (94.5%). CONCLUSIONS/INTERPRETATION: . Our findings suggest that measuring fasting plasma glucose or HbA1c is just as useful as measuring 2-h plasma glucose for the diagnosis of diabetes, and that the cut-off point for diagnostic fasting plasma glucose level is lower than that of the current diagnostic criteria.

Blood Glucose↗

Prevention of critical telomere shortening by oestradiol in human normal hepatic cultured cells and carbon tetrachloride induced rat liver fibrosis.

BACKGROUND AND AIM: Significant telomere shortening of hepatocytes is associated with replicative senescence and a non-dividing state in chronic liver disease, resulting in end stage liver failure and/or development of hepatocellular carcinoma. To prevent critical telomere shortening in hepatocytes, we have focused on oestrogen dependent transactivation of the human telomerase reverse transcriptase (hTERT) gene as a form of telomerase therapy in chronic liver disease. METHODS: We examined expression of hTERT mRNA and its protein, and telomerase activity (TA) in three human normal hepatic cell lines (Hc-cells, h-Nheps, and WRL-68) before and after treatment with 17beta-oestradiol. The effects of exogenous oestradiol administration were examined in a carbon tetrachloride (CCl(4)) induced model of liver fibrosis in rats. RESULTS: Expression of hTERT mRNA and its protein was upregulated by oestradiol treatment. Telomere length decreased in Hc-cells and h-Nheps with accumulated passages whereas with long term oestradiol exposure it was greater than without oestradiol. The incidence of beta-galactosidase positive cells, indicating a state of senescence, decreased significantly in oestradiol treated cells in comparison with non-treated cells (p<0.05). TA in both male and female rats with CCl(4) induced liver fibrosis was significantly higher with oestradiol administration than without (p<0.05). Long term oestradiol administration markedly rescued the hepatic telomere from extensive shortening in both male and female rats. CONCLUSION: These results suggest that oestradiol acts as a positive modulator of the hTERT gene in the liver. Oestrogen dependent transactivation of the hTERT gene is a new strategy for slowing the progression of chronic liver disease.

Animals↗

CCR4 is an up-regulated chemokine receptor of peripheral blood memory CD4+ T cells in Crohn's disease.

Several chemokine receptors are expressed selectively on the surface of T cells depending on their polarization. The aim of this study was to characterize chemokine receptor expression in peripheral blood memory T cells in Crohn's disease (CD) and ulcerative colitis (UC), and to correlate the expression with disease activity. Peripheral blood mononuclear cells (PBMCs) were obtained from 24 patients with CD, 30 patients with UC, 24 normal controls and 10 disease controls. PBMCs were stained by anti-CCR3, CCR4, CCR5, CXCR3, CD4, CD8, CD45RO and beta 7 integrin, and the expression of the chemokine receptors were determined by flow cytometry. CCR4 expression on memory T cells was significantly lower in UC than in CD or normal controls, and that of memory CD4+ T and beta 7(high) memory CD4+ T cells was significantly higher in CD than in UC or normal controls. CCR4 expression on memory CD4+ T cells exhibited significant positive correlation with disease activity in CD, and this decreased significantly after treatment. Such a decrease was not found in the disease controls. CCR5 and CXCR3 expression on memory CD8+ T cells was significantly lower in CD than in normal controls. CXCR3 expression on beta 7(high) memory CD4+ T and CXCR3 expression on memory CD8+ T cells were lower in UC than in normal controls. These findings suggest that in peripheral blood memory T cells, chemokine receptor expression is different between CD and UC. Enhancement of CCR4 and suppression of CCR5 and CXCR3 seem to be the characteristic chemokine receptor profile in peripheral blood memory T cells of CD.

Acute Disease↗

Chromosomal translocation t(11;18)(q21;q21) in gastrointestinal mucosa associated lymphoid tissue lymphoma.

AIMS: To evaluate the chromosomal translocation t(11;18)(q21;q21) in gastrointestinal lymphomas. METHODS: A possible API2-MLT fusion transcript specific to t(11;18)(q21;q21) was examined by means of reverse transcription-polymerase chain reaction (RT-PCR) in tumours from 47 cases of primary gastrointestinal lymphoma (28 low grade mucosa associated lymphoid tissue (MALT) lymphomas, four low grade MALT lymphomas with a high grade component, nine secondary diffuse large B cell lymphomas, four primary diffuse large B cell lymphomas, and two T cell lymphomas). RESULTS: API2-MLT fusion was seen in four of 28 cases of low grade MALT lymphoma, but it was not seen in other types of lymphoma. Among the low grade MALT lymphomas, the fusion transcript was seen more frequently in colonic tumours than in gastric tumours (two of three compared with two of 24) and in tumours with submucosal invasion than in those confined to the mucosa (four of 13 compared with 0 of 15). Helicobacter pylori negative tumours tended to show a higher positive rate than H pylori positive tumours (three of six compared with one of 21). None of the gastric tumours that responded to H pylori eradication expressed the API2-MLT fusion transcript. CONCLUSIONS: t(11;18)(q21;q21) seems to be one of the genetic alterations related to the development of gastrointestinal low grade MALT lymphoma. Such translocations may be predominantly associated with the development of intestinal MALT lymphoma.

Adult↗

anti-bis(mu-2-ammonioethanethiolato-kappa2S:S)bis[dichloropalladium(II)] dihydrate.

Each of two square-planar Pd(II) ions in the title compound, [Pd2Cl4(mu-Haet-S)2]*2H2O (Haet = 2-ammonioethanethiolate, C2H7NS), which was obtained by rearrangement of [Pd2[Pd(aet-N,S)2]4]4+ in acidic solution, is coordinated by two bridging S atoms from two Haet ligands and by two terminal Cl atoms, forming the dinuclear structure. Since the complex is situated on a center of symmetry, the two monodentate Haet arms are located on opposite sides of the central Pd2S2 square plane, i.e. the present complex is the anti isomer. The S-C-C-N torsion angle is 177.3 (6) degrees and some intermolecular hydrogen bonds are observed.

Journal Article↗

Electroytic partial fluorination of organic compounds. 52. Regio- and diastereoselective anodic fluorination of thiazolidines.

Anodic fluorination of N-benzoyl, N-acethyl-, and N-formylthiazolidine derived from L-cysteine was carried out in dimethoxyethane (DME) and acetonitrile containing various supporting fluoride salts using an undivided cell. Highly regioselective fluorination proceeded to provide the corresponding 5-monofluorinated thiazolidine derivatives in good yields in DME, and the diastereoselectivitiy was moderate to high regardless of the supporting fluoride salts. The diastereoselectivitiy of the fluorination was greatly affected by the bulkyness of the subsitituent on the nitrogen atom, and N-benzoylthiazolidine gave much higher diastereoselectivity compared with N-formyl derivative. The fluorination of the thiazolidines was not achieved by commercially available fluorinating reagents such as N-fluoropyridinium salts.

Electrochemistry↗

C. elegans slit acts in midline, dorsal-ventral, and anterior-posterior guidance via the SAX-3/Robo receptor.

Robo receptors interact with ligands of the Slit family. The nematode C. elegans has one Robo receptor (SAX-3) and one Slit protein (SLT-1), which direct ventral axon guidance and guidance at the midline. In larvae, slt-1 expression in dorsal muscles repels axons to promote ventral guidance. SLT-1 acts through the SAX-3 receptor, in parallel with the ventral attractant UNC-6 (Netrin). Removing both UNC-6 and SLT-1 eliminates all ventral guidance information for some axons, revealing an underlying longitudinal guidance pathway. In the embryo, slt-1 is expressed at high levels in anterior epidermis. Embryonic expression of SLT-1 provides anterior-posterior guidance information to migrating CAN neurons. Surprisingly, slt-1 mutants do not exhibit the nerve ring and epithelial defects of sax-3 mutants, suggesting that SAX-3 has both Slit-dependent and Slit-independent functions in development.

Animals↗

Structure and expression of human mitochondrial adenylate kinase targeted to the mitochondrial matrix.

The previously isolated cDNA encoding human adenylate kinase (AK) isozyme 3 was recently renamed AK4. Consequently, human AK3 cDNA remains to be identified and we have little information about the functional relationship between human AK3 and AK4. In pursuit of the physiological roles of both the AK3 and AK4 proteins, we first isolated an authentic human AK3 cDNA and compared their expression. Nucleotide sequencing revealed that the cDNA encoded a 227-amino-acid protein, with a deduced molecular mass of 25.6 kDa, that shares greater homology with the AK3 cDNAs isolated from bovine and rat than that from human. We named the isolated cDNA AK3. Northern-blot analysis revealed that AK3 mRNA was present in all tissues examined, and was highly expressed in heart, skeletal muscle and liver, moderately expressed in pancreas and kidney, and weakly expressed in placenta, brain and lung. On the other hand, we found that human AK4 mRNA was highly expressed in kidney, moderately expressed in heart and liver and weakly expressed in brain. Western-blot analysis demonstrated expression profiles of AK3 and AK4 that were similar to their mRNA expression patterns in each tissue. Over expression of AK3, but not AK4, in both Escherichia coli CV2, a temperature-sensitive AK mutant, and a human embryonic kidney-derived cell line, HEK-293, not only produced significant GTP:AMP phosphotransferase (AK3) activity, but also complemented the CV2 cells at 42 degrees C. Subcellular and submitochondrial fractionation analysis demonstrated that both AK3 and AK4 are localized in the mitochondrial matrix.

Adenylate Kinase↗

Polo-like kinase (PLK) expression in endometrial carcinoma.

Polo-like kinase (PLK) is a cell cycle-regulated, cyclin-independent serine/threonine protein kinase. Recent reports have shown a critical role for PLK during tumorigenesis. To explore whether PLK plays a general role as a tumor marker of endometrial carcinomas, we examined the expression of PLK mRNA and protein in endometrial carcinomas and normal endometrium, and analyzed the relationship between PLK protein expression and malignant potential. We found that PLK mRNA was expressed in all specimens from endometrial carcinoma patients using RT-PCR methods, although some specimens from normal endometria were negative. Immunohistochemically, most of the PLK was found in the cytoplasm (around the nucleus), and partly in the nucleus of endometrial carcinoma glands and also secreted tissues from endometrial carcinoma glands. PLK was expressed at the basement membrane of carcinoma glands and partly expressed in the head portion of papillary carcinoma tissues. There was a significant correlation between percentages of PLK-positive cells and histological grade of endometrial carcinoma (P<0.0001). However, the expression of proliferating cell nuclear antigen and Ki-67 was independent of PLK expression. Moreover, we noted that PLK is strongly expressed in invading carcinoma cells. PLK expression could reflect the degree of malignancy and proliferation in endometrial carcinoma. Thus, in addition to being of diagnostic value, modulation of PLK activity in the tumors by chemotherapeutic agents or gene therapy may prove to be of therapeutic value.

Adult↗

The fused protein kinase regulates Hedgehog-stimulated transcriptional activation in Drosophila Schneider 2 cells.

The Drosophila segment polarity gene fused encodes a putative protein-serine/threonine kinase, and plays a critical role in the signal transduction for Hedgehog (Hh)-dependent gene expression. We show that the Drosophila Schneider 2 (S2) cell line has the potential to transduce the Hh-triggered intracellular signals, leading to the activation of target gene expression, when a transcription factor, Cubitus interruptus (Ci), is provided exogenously. Using S2 cells transfected with the Ci-expressing plasmid and a patched promoter reporter construct, we demonstrate that the forced expression of Fused (Fu) stimulates Hh-triggered and Ci-dependent transcriptional activation. The N-terminal kinase domain of Fu is required for this activity, but the C-terminal domain is not. Two kinase-inactive Fu mutants fail to enhance the reporter activation, indicating that the kinase catalytic activity is essential for this function. Negative components of the Hh-signaling pathway, Costal-2 and Suppressor of Fused, strongly antagonize the Fu activity, irrespective of the presence or absence of the Fu C-terminal domain, suggesting an indirect mechanism for the inhibition of Fu by these proteins. Furthermore, mutational analyses of threonine 158 and serine 159, in the activation segment of the Fu protein kinase, indicate that threonine 158 is essential for Fu activity and that phosphorylation of this threonine residue may be involved in the activation of the kinase catalytic activity upon Hh stimulation.

Animals↗

fac-Trichloro(quinolin-8-ylimido-N,N')(triphenylphosphine-P)rhenium(V).

The Re atom in [Re(C(9)H(6)N(2))Cl(3)(C(18)H(15)P)] is octahedrally coordinated by three Cl atoms in facial positions, two N atoms from 8-imidoquinoline (imq) and one P atom from triphenylphosphine. The Re-N(imido) distance [1.760 (9) and 1.772 (8) A] for imq is very short and implies double-bond character. The trans influence of the P atom is indicated. Intra- and intermolecular pi-pi interactions between the pi-rings in the complex are also observed.

Journal Article↗

Id1 expression is associated with histological grade and invasive behavior in endometrial carcinoma.

Basic helix-loop-helix (bHLH) DNA-binding proteins have been reported to regulate tissue-specific transcription of cellular differentiation within multiple cell lineages. The Id family of helix-loop-helix proteins does not possess a basic DNA-binding domain and functions as a negative regulator of bHLH proteins by forming high-affinity heterodimers with bHLH proteins. Id proteins were originally characterized as inhibitors of DNA binding and cell differentiation. Thus, overexpression of Id proteins correlates with cell proliferation and arrested differentiation in many cell lineages. To elucidate the involvement of Id1 in endometrial carcinogenesis, we analyzed serial frozen sections for Id1 protein expression in 20 cases of endometrial carcinoma and 20 cases of normal endometria by fluorescent immunohistochemistry. We analyzed the relationship between the percentages of Id1-stained cells and the patient's characteristics, including histological grade, clinical stage, presence of invasion to >1/2 myometrium, and clinical outcome. In normal endometria, Id1 was not detected in either the proliferative or the secretory phase. There was, however, abundant Id1 immunoreactivity in the endometrial carcinoma cells. Moreover, Id1 was strongly expressed in the inflammatory cells. Scoring on the basis of the percentage of positive cells indicated that Id1 expression is significantly associated with histological grade (P<0.05) and the presence of invasion to >1/2 myometrium (P<0.05). Our results demonstrate that increased Id1 expression in endometrial carcinoma correlates with the malignant potential of this tumor.

Adult↗

Expression of polo-like kinase in ovarian cancer is associated with histological grade and clinical stage.

Polo-like kinase (PLK), a cell cycle-regulated, cyclin-independent serine/threonine protein kinase, has been shown in recent reports to play a critical role during tumorigenesis. To investigate whether PLK plays a general role as a tumor marker of ovarian cancers, we examined the expression of PLK protein in ovarian cancers, and analyzed the relationship between PLK protein expression and histological grade. Immunohistochemically, the majority of PLK was found in the cytoplasm (around the nucleus), and a portion was found in the nucleus of ovarian cancer glands and also in the fluid secreted from these glands. PLK was expressed at the basement membrane of cancer glands and partly expressed in the head portion of papillary cancer tissues. A significant correlation was found between percentages of PLK-positive cells and histological grade of ovarian cancer (P<0.001). However, the expression of proliferating cell nuclear antigen, Ki-67, and cyclin B1 was independent of PLK expression. Taken together, these findings suggest that PLK expression may reflect the degree of malignancy rather than the degree of proliferation in ovarian cancer. Thus, in addition to being of diagnostic value, PLK activity in ovarian tumors may be modulated by chemotherapeutic agents or gene therapy to therapeutic effect.

Adenocarcinoma↗

Expression of cathepsin L in normal endometrium and endometrial cancer.

OBJECTIVE: To evaluate the expression of cathepsin L in normal endometrium and endometrial adenocarcinoma. STUDY DESIGN: Tissue from eight cases of G1 and eight of G2 endometrioid adenocarcinoma, and 15 normal endometrial specimens were examined by immunohistochemistry. RESULTS: In the normal endometrium, cathepsin L was expressed in a few cell layers of the apical part of the glandular epithelium throughout the menstrual cycle. In the carcinomas, there was an inverse correlation between the grade of tumor and the cathepsin L expression. CONCLUSION: Cathepsin L expression may cease during endometrial carcinogenesis and its expression may be less important in tumor progression than it is in tumors of other tissues.

Adenocarcinoma↗