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Biomedical subjects

Y Takagi

Publications and source records attributed to Y Takagi.

At least 181 records · Page 10Linked to original sources

New transmission-type X-ray filters consisting of amorphous multilayer films.

New transmission-type X-ray filters have been developed. The filters consist of X-ray-amorphous metal (less than 30 A)/metalloid ( approximately 10 A) multilayer films sputter-deposited on X-ray-transparent polymer substrates. Such metal/metalloid multilayer films show only very broad diffraction peaks, since the metal and metalloid layers forming the multilayer films are usually X-ray amorphous if the layers are sufficiently thin. The filters use the wavelength-dependent absorption phenomena near absorption edges of elements to reduce the intensity of transmitted X-rays, without generating any crystalline sharp peaks which cause serious problems in experiments such as fluorescence XAFS measurements. The multilayer-film filters were prepared by a multi-target magnetron sputtering deposition technique, paying special attention to the homogeneity of the layer thickness by spinning substrates of the films. The filters are useful in reducing the intensity of undesirable fluorescence emissions and improving the signal-to-background ratios of data acquired in various measurements using a solid-state detector.

Journal Article↗

Laminin-dependent integrin clustering with tyrosine-phosphorylated molecules in a Drosophila neuronal cell line.

To gain more insight into the molecular and cellular aspects of basement membranes during Drosophila morphogenesis, especially in neural development, we carried out cell biological screening to establish a cell culture system in which Drosophila cell-matrix interaction could be reconstituted. The screening showed that a Drosophila neuronal cell line, BG2-c6, established from the third-instar larval central nervous system, had a strong adhesion activity when purified Drosophila laminin was used as a substrate. Outgrowth of axon-like structures was stimulated on laminin. Histochemical analysis revealed clusters of integrin together with phosphotyrosine and alpha-actinin. These data indicate that the Drosophila integrin cascade triggered by the interaction between BG2-c6 and laminin was initiated at the integrin cluster with tyrosine-phosphorylated proteins, similar to the observations in vertebrate cells.

Animals↗

Spread of colorectal cancer micrometastases in regional lymph nodes by reverse transcriptase-polymerase chain reactions for carcinoembryonic antigen and cytokeratin 20.

BACKGROUND AND OBJECTIVES: Lymph node metastasis is known as a significant predictor of prognosis in colorectal cancer patients. Recently, reverse transcriptase polymerase chain reaction (RT-PCR) has been applied to detecting micrometastasis. To assess the risk of recurrence and accurately determine the spread of tumor cells, we examined lymph node micrometastases in a series of colorectal cancer patients. METHODS: We examined 202 lymph nodes obtained from 13 colorectal cancer patients who underwent curative operation and were histologically diagnosed to be node-negative, using RT-PCR to amplify mRNAs for two epithelial markers, carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20). RESULTS: All the cases, including early stage patients, had micrometastases. A total of 102 among 202 lymph nodes (50.5%) were positive for either CEA or CK-20, or both (47.0, 40.1, and 36.6% respectively). Positive lymph nodes were spread along the courses of vascular trunks as well as being located in more distant regions. CONCLUSIONS: Even in histologically negative lymph nodes, there is a considerable possibility that micrometastases may exist. Their detection by RT-PCR may improve clinical staging and indications for cancer therapy. We should also take care in the choice of surgical approach.

Adult↗

Percutaneous autotransplantation of parathyroid tissue into the forearm muscles.

We developed a simple and easy nonsurgical percutaneous method for autografting parathyroid tissue into the forearm muscles. This method was applied to 30 patients suffering from secondary hyperparathyroidism who were then refractory to medical treatment. The operative results were then compared with 16 patients who underwent treatment using Wells' method. The graft "take," judged by a significant intact parathyroid hormone (PTH) ratio (> 1.5) between grafted and nongrafted arm vein blood, was 82% for the percutaneous method group and 75% for the Wells' method group, respectively. The percentage of recurrent hyperparathyroidism necessitating a subtotal removal of the autograft was equal in the two groups. No complications were noted for either method. Wells' method can thus be replaced by this simple and easy nonoperative method.

Adult↗

Synthesis and antitumor activity of 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) daunomycinone derivatives modified at C-3' or C-4'.

As a part of a study to exploit anthracycline glycosides effective against resistant tumor cells, the 3'-O-methyl (3), 4'-O-methyl (4), 3'-deoxy (6), 3'-deoxy-3'-fluoro (7), and 3'-deoxy-3'-iodo (8) derivatives of 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)daunomycinone have been prepared by coupling suitably protected glycosyl bromides with daunomycinone. The doxorubicin-type analog (5) of 4 was also prepared. Among the compounds prepared, 5 showed the highest antitumor activity. Relationships between chemical structures of the synthetic products and antitumor activities, together with the degree of resistance were discussed.

Animals↗

Immunochemical and biochemical characteristics of enamel proteins in hypocalcified amelogenesis imperfecta.

Amelogenesis imperfecta is a hereditary disease of the enamel that is unassociated with generalized defects. Cases of the condition are clinically classified into three groups: hypoplastic, hypomaturation, and hypocalcified. In this study, soluble protein fractions of the enamel from three patients with hypocalcified amelogenesis imperfecta were examined through the use of immunochemical and biochemical techniques. In immunochemical analyses done with a polyclonal anti-amelogenin antibody, all samples from enamel in which there was amelogenesis imperfecta were found to contain considerable amounts of amelogenin peptides. When an enamel sample from one patient was examined by Western-blot transfer and immunobinding analysis, the amelogenin fraction was found to consist of a 26-kDa molecule thought to be normally present in the outer layer of secretory-stage enamel. This enamel was also found to contain albumin as one of the major constituents of the protein fraction. These results suggest that hypocalcified amelogenesis imperfecta may in part be caused by a disturbance in matrix protein degradation during the maturation phase.

Adolescent↗

p53 mutations in non-small-cell lung cancers occurring in individuals without a past history of active smoking.

Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies. We previously reported an association between the presence of p53 mutations and lifetime cigarette consumption. Although over 675 p53 mutations have been reported in lung cancers in the literature thus far, very little is known about the nature of such changes in lung cancers in the absence of a smoking background. In the present study, we therefore analysed 69 non-small-cell lung cancer specimens from individuals without any history of active smoking and identified p53 mutations in 26% of the cases. Statistical analysis of the present cohort of non-smokers also showed absence of significant relationship between p53 mutations and age, sex, histological type or disease stage. Comparison of mutational spectra between the present results in non-smokers and previously reported mutations in smokers clearly demonstrated G:C to T:A transversions to be significantly less frequent in non-smokers than in smokers (OR 5.35, 95% CI 1.77-16.12). Interestingly, G:C to C:G and G:C to A:T mutations were also observed in tumours of non-smokers at similar frequencies to G:C to T:A mutations, suggesting that these mutations can occur relatively frequently in the absence of active smoking. This study is, to our knowledge, the largest so far analysing a well-defined cohort of non-smokers in a single laboratory.

Adult↗

Somatic alterations of the SMAD-2 gene in human colorectal cancers.

The SMAD-2 gene, which is located at 18q21, has been identified as a candidate tumour-suppressor gene from work on colorectal cancers. The aim of the present study was to determine the clinical alterations and the significance of its mutations in a series of colorectal cancers previously examined for SMAD-4/DPC-4 gene. Mutation analyses of the SMAD-2 gene were carried out on cDNA samples from 36 primary colorectal cancer specimens using a combination of the polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and DNA sequencing. Only one missense mutation (2.8%), producing an amino acid substitution in the highly conserved region, and two homozygous deletions (5.5%) of the total coding region of the SMAD-2 gene were detected in the 36 cancers. The SMAD-2 gene may play a role as a candidate tumour-suppressor gene in a small fraction of colorectal cancers. However, allelic loss at 18q21 is very often seen in this type of tumour. Even in combination with changes in SMAD-4, the observed frequency was not sufficient to account for all 18q21 deletions in colorectal cancers. Thus, another tumour-suppressor gene, such as DCC, discovered as the first tumour-suppressor candidate in the region may also exist in this chromosome region.

Aged↗

Studies to determine the usefulness of the zinc clearance test to diagnose marginal zinc deficiency and the effects of oral zinc supplementation for short children.

OBJECTIVE: To evaluate the usefulness of the body zinc clearance test in the diagnosis of marginal zinc deficiency and to estimate the efficacy of oral zinc supplementation on growth in short children. METHODS: Zinc status was evaluated in 30 (19 boys and 11 girls) Japanese children with short stature using the body zinc clearance test. Changes in growth after oral zinc supplementation (ZnSO4,7H2O; 5 mg/kg/day in two divided doses) were studied. RESULTS: Basal serum zinc concentrations were 75.0 +/- 12.7 micrograms/dl and zinc clearance values were 19.1 +/- 5.8 ml/kg/hour in the 30 subjects. The correlation coefficient between serum zinc concentrations and zinc clearance values was as small as -0.36. There were nine cases whose body zinc clearance values were high and serum zinc concentrations were low, indicating definite zinc deficiency. There were nine cases whose body zinc clearance values were high, despite normal serum zinc concentrations, indicating marginal zinc deficiency. The mean height velocity for males was 5.3 cm/year before zinc supplementation and 7.8 cm/year after the therapy; and the mean SD score for height for age improved from -1.85 to -1.53. The mean height velocity for females was 5.1 cm/year before zinc supplementation and 5.9 cm/year after the therapy, and the mean SD score for height for age changed from -2.02 to -2.03. CONCLUSION: The body zinc clearance test was much more useful than serum zinc concentrations in diagnosing marginal zinc deficiency. Oral zinc supplementation improved the height velocity in short males, but not in short females.

Administration, Oral↗

Zinc deficiency enhances interleukin-1alpha-induced metallothionein-1 expression in rats.

This study investigated whether interleukin-1alpha-induced metallothionein gene expression is affected by zinc deficiency. Weaning male rats were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) or a zinc-supplemented diet [50.8 mg zinc/kg; controls for the diet included pair-fed (PF) and ad libitum consumption groups (AL)] for 4 wk. All rats except those that served as controls for interleukin-1alpha administration, (injected with vehicle and killed at 0 h) were then injected subcutaneously with interleukin-1alpha (2 x 10(7) units/kg body wt) and killed at 3, 6, 12, 24 and 72 h after the injection. Compared with AL and/or PF rats, zinc depletion significantly reduced zinc concentrations in plasma and liver but not in kidney or intestine, and significantly reduced hepatic, renal, and intestinal metallothionein-1 mRNA levels analyzed by competitive reverse transcription-polymerase chain reaction (RT-PCR). Interleukin-1alpha injection reduced plasma zinc concentration and enhanced liver zinc concentration, but did not affect zinc levels in kidney or intestine. Metallothionein-1 mRNA was significantly elevated by interleukin-1alpha in liver, kidney and intestine of all groups; the levels in liver and kidney of ZD rats 6 h after the injection were significantly higher than those of AL or PF rats. Liver metallothionein protein levels were enhanced after interleukin-1alpha injection in both AL and ZD rats. Semiquantitative RT-PCR revealed significantly higher hepatic levels of interleukin-1 receptor type-I mRNA in ZD rats than in AL and PF rats but no differences in renal or intestinal tissues among groups before interleukin-1alpha challenge. In conclusion, zinc deficiency induces upregulation of metallothionein-1 gene expression in response to interleukin-1alpha challenge in rats.

Animals↗

Redox control of neuronal damage during brain ischemia after middle cerebral artery occlusion in the rat: immunohistochemical and hybridization studies of thioredoxin.

Thioredoxin (TRX) is a small, multifunctional protein with a redox-active site and multiple biological functions that include reducing activity for reactive oxygen intermediates. We assayed TRX and TRX mRNA by immunohistochemical methods and hybridization experiments in the rat brain after middle cerebral artery (MCA) occlusion. During ischemia, the immunoreactivity for TRX decreased; it disappeared after MCA occlusion in the ischemic regions. It rapidly decreased and nearly disappeared at 4 and 16 hours after MCA occlusion in the lateral striatum and frontoparietal cortex, respectively. On the other hand, in the perifocal ischemic region, the penumbra, TRX immunoreactivity began to increase 4 hours after MCA occlusion and continued to increase until 24 hours after occlusion. In hybridization experiments, TRX mRNA decreased and nearly disappeared 4 hours after MCA occlusion in the lateral striatum. In the frontoparietal cortex, it decreased until 24 hours after MCA occlusion. In the perifocal ischemic region, TRX mRNA began to increase 4 hours after MCA occlusion and continued to increase until 24 hours. Northern blot analysis showed that total TRX mRNA in the operated hemispheres was induced from 8 hours and increased until 24 hours after the surgical procedures. We previously reported that recombinant TRX promotes the in vitro survival of primary cultured neurons. We now suggest that TRX in the penumbra has neuroprotective functions and that decreased levels of TRX in the ischemic core modify neuronal damage during focal brain ischemia.

Animals↗

Corticosteroid irrigation of parotid gland for treatment of xerostomia in patients with Sjögren's syndrome.

OBJECTIVE: To determine the efficacy of corticosteroid irrigation of the parotid gland in relieving salivary flow deficiency in patients with Sjögren's syndrome. METHODS: The parotid glands of 31 patients with primary (24) or secondary (seven) Sjögren's syndrome were irrigated either with saline solution followed by corticosteroid solution, or with saline solution alone. Salivary function was assessed by Saxon test. RESULTS: Corticosteroid irrigation significantly increased the salivary flow rate in patients with Sjögren's syndrome (p < 0.0001), with clinical improvement detectable 3.7 (2.4) weeks (mean (SD)) after initial corticosteroid irrigation. The extent of improvement in salivary function was reciprocal to the clinical severity of the disease, with patients at the early stages obtaining 1.20 (0.57) g net increase in salivary flow rate, and patients at the most advanced stages obtaining 0.20 (0.47) g net increase. Repeated corticosteroid irrigations did not evoke corticosteroid refractoriness of the salivary gland; similar levels of net increase in salivary flow rate were observed after the second to fourth challenge of the corticosteroid in these patients. The sustained period was 8.4 (3.5) months (mean (SD)). CONCLUSION: These findings suggest the clinical usefulness of corticosteroid irrigation therapy in relieving xerostomia in patients with Sjögren's syndrome.

Adult↗

Beat-to-beat variation of the ST segment in a patient with right bundle branch block, persistent ST segment elevation, and ventricular fibrillation: a case report.

The authors describe a patient with ventricular fibrillation associated with right bundle branch block-like QRS morphology and persisting ST segment elevation in the precordial leads, in whom the morphology of the ST segment changed from the coved type to the saddle-back type or vice versa on a beat-to-beat basis. Such an observation has never been reported in the previous literature.

Adult↗

Localized aberrant expression of cytochrome P450 aromatase in primary and metastatic malignant tumors of human liver.

The present study was designed to demonstrate localized aberrant expression of aromatase in primary and metastatic malignant liver tumors. Immunocytochemistry revealed the presence of locally increased aromatase protein in regions around tumors in all specimens from seven primary and seven metastatic liver tumors. This observation was further confirmed by Western blotting analysis and assay of aromatase activity in tumorous, proximal, and distal regions. Western blots showed most intensely immunoreactive bands at the position corresponding to aromatase in proximal tissues where aromatase activities also were higher (2.75 +/- 1.59 pmol/mg.h) than in tumors (0.137 +/- 0.115 pmol/mg.h) and distal tissues (1.90 +/- 1.47 pmol/mg.h), in spite of a gradient decline of NADPH-cytochrome P-450 reductase activity from the distal regions to the tumors. RT-PCR analysis indicated that the aberrant increase in aromatase protein and enzyme activity in the regions proximal to tumors is caused by locally elevated aromatase messenger RNA.

Adult↗

Actions of the novel oral antidiabetic agent HQL-975 in genetically obese diabetic db/db mice.

The hypoglycemic effect of the novel oral agent 3-[4-12-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl]-2S-propyla mino-propionic acid (HQL-975) was examined in db/db mice with genetically obese non-insulin dependent diabetes mellitus (NIDDM). The oral administration of HQL-975 at 3.5 and 35.3 mg/kg/d for 7 d decreased the plasma glucose level of these mice in a dose-dependent manner. HQL-975 also significantly decreased the plasma triglyceride, total cholesterol, non-esterified fatty acid and insulin levels. In the oral glucose tolerance test, HQL-975-treated mice showed improved glucose tolerance and decreased endogenous insulin secretion. HQL-975 increased glycemic response to exogenous insulin in the mice. In the HQL-975-treated db/db mice adipocytes, the glucose uptake, insulin binding, and GLUT4 expression were increased compared with those in untreated db/db mice adipocytes. These results indicate that HQL-975 improved insulin action in db/db mice through receptor and post-receptor effects. In conclusion, HQL-975 is a new oral antidiabetic agent with a hypoglycemic effect which is associated with an insulin-sensitizing effect. This agent may therefore be effective for the treatment of NIDDM.

3T3 Cells↗