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Biomedical subjects

F Ishikawa

Publications and source records attributed to F Ishikawa.

At least 55 records · Page 3Linked to original sources

Mechanical properties of several nickel-titanium alloy wires in three-point bending tests.

The purpose of this study was to clarify the mechanical properties of 42 brands of nickel-titanium alloy orthodontic wires from 9 manufacturers by conducting three-point bending tests under uniform testing conditions. Manufacturers included A-Company, Hoya Medical, Lancer, Ormco, Rocky Mountain, Sankin, Tomy (GAC), TP, and 3M/Unitek. Cobalt-chrome, and titanium-molybdenum alloy wires were also tested as a reference for comparison of force levels. All reported data were recorded during the unloading process to simulate the force that a wire exerts on a tooth as it is moved into the dental arch from a position of malocclusion. The following results were obtained for the nickel-titanium wires tested. (1) Among the 0.016 inch round wires tested under a maximum deflection of 1.5 mm, the difference between the smallest (Copper nickel-titanium 35) and the largest (Aline) load values was 136 g. For the 0.016 x 0.022 inch rectangular wires tested, the difference between the smallest (Copper nickel-titanium 40) and the largest (Aline) load values was 337 g. (2) The change in load between 1.5 and 0.5 mm of deflection was examined to clarify the superelastic properties of the wires tested. For the 0.016 inch wires, 17 wire brands produced a load difference of less than 100 g, and two brands produced a difference of at least 100 g (Aline and Titanal = 100 g). For the 0.016 x 0.022 inch wires, 15 brands produced a load difference of less than 100 g, and eight brands produced a difference of over 100 g. The smallest and largest load differences were 3 g (Copper nickel-titanium 35) and 200 g (Aline). (3) The majority of the samples with a smaller load difference between deflections of 1.5 mm and 0.5 mm in the unloading process were found among super-elastic wires, while samples with a larger load difference were predominantly found among work-hardened wires. Compared with cobalt-chrome and TMA wires, nickel-titanium alloy wires exert significantly less force. However, the amount of force varies greatly from brand to brand. Consequently, when using nickel-titanium alloy wires, brands must be selected carefully by taking into consideration the severity of the malocclusion and the stage of orthodontic treatment in each case. It is the intent of this study to offer clinicians an unbiased guide for the selection of appropriate nickel-titanium alloy wires.

Dental Alloys↗

Presence of telomeric G-strand tails in the telomerase catalytic subunit TERT knockout mice.

BACKGROUND: Telomerase consists of two essential subunits, the template RNA (TR; telomerase RNA) and the catalytic subunit TERT (telomerase reverse transcriptase). Knockout mice with a mTR (mouse TR) deletion have been described and well characterized. However, mice with a mTERT (mouse TERT) deletion have not been reported. RESULTS: mTERT-knockout mice have been constructed. The first generation mTERT -/- mice were fertile, and did not show any noticeable macroscopic or microscopic phenotypic change. All tissue cells derived from mTERT -/- mice that were examined lacked telomerase activity, indicating that mTERT is the only gene encoding the telomerase catalytic subunit. Pulse field gel electrophoresis (PFGE) and nondenaturing in-gel hybridization analyses showed that mouse telomeric DNA has G-strand 5'-overhangs, as demonstrated for human and yeast cells. This telomeric single-stranded G-tail was also observed in MEF (mouse embryonic fibroblast) and liver cells derived from mTERT -/- mice. CONCLUSIONS: mTERT-knockout mice show phenotypes that are apparently normal at least during the early generations. This observation is similar to that obtained with the mTR-knockout mice. The presence of the telomeric G-strand tails in mTERT -/- mice suggests that these telomeric 5'-overhangs are produced by telomerase-independent mechanisms, as has been proposed for yeast and human.

Amino Acid Sequence↗

Enhancement of B7-1 (CD80) expression on B-lymphoma cells by irradiation.

Irradiation of A20.2J mouse B-lymphoma cells enhanced their antigen-presenting ability to induce interleukin-2 (IL-2) production by 42-6A T cells specific for ovalbumin (OVA)323-339/I-Ad. Irradiated and fixed A20.2J cells were more efficient antigen-presenting cells (APC) to present OVA323-339 peptide than the unirradiated and fixed cells. Irradiation selectively increased the expression of B7-1 molecules, but not of the major histocompatibility complex class II molecules, B7-2, lymphocyte function-associated antigen-1, or intracellular adhesion molecule-1. Irradiation of A20.2J cells with 100 Gy followed by overnight incubation was optimal for the enhancement of B7-1 expression. Anti-B7-1 monoclonal antibody inhibited the irradiation-induced enhancement of APC function. Irradiation of A20.2J cells induced the accumulation of B7-1 mRNA. Thus, it was concluded that the enhancement of APC function by irradiation was due to the up-regulation of B7-1 molecules through the accumulation of its mRNA. Although partial inhibition of protein synthesis has been shown to enhance the accumulation of B7-1 mRNA and its expression, irradiation did not decrease the protein synthesis in A20.2J cells. The incubation with irradiated A20.2J cells stimulated unirradiated A20.2J cells to increase B7-1 expression, suggesting that irradiation of A20.2J cells induced expression or secretion of some molecule(s) to enhance B7-1 expression.

Animals↗

Genetic control of telomere integrity in Schizosaccharomyces pombe: rad3(+) and tel1(+) are parts of two regulatory networks independent of the downstream protein kinases chk1(+) and cds1(+).

The Schizosaccharomyces pombe checkpoint gene named rad3(+) encodes an ATM-homologous protein kinase that shares a highly conserved motif with proteins involved in DNA metabolism. Previous studies have shown that Rad3 fulfills its function via the regulation of the Chk1 and Cds1 protein kinases. Here we describe a novel role for Rad3 in the control of telomere integrity. Mutations in the rad3(+) gene alleviated telomeric silencing and produced shortened lengths in the telomere repeat tracts. Genetic analysis revealed that the other checkpoint rad mutations rad1, rad17, and rad26 belong to the same phenotypic class with rad3 with regard to control of the telomere length. Of these mutations, rad3 and rad26 have a drastic effect on telomere shortening. tel1(+), another ATM homologue in S. pombe, carries out its telomere maintenance function in parallel with the checkpoint rad genes. Furthermore, either a single or double disruption of cds1(+) and chk1(+) caused no obvious changes in the telomeric DNA structure. Our results demonstrate a novel role of the S. pombe ATM homologues that is independent of chk1(+) and cds1(+).

Adenosine Triphosphatases↗

Inhibitory effects of of L-2'-deoxyguanosine 5'-triphosphate (L-dGTP) and L-2'-deoxythymidine 5'-triphosphate (L-dTTP) on human telomerase.

Telomerase, which synthesizes telomeric DNA in eukaryotic cells, is classified as a reverse transcriptase. To clarify the recognition of 2'-deoxyribonucleoside 5'-triphosphate (dNTP) chirality by telomerase, we studied the inhibitory effects of L-dGTP on HeLa cell telomerase activity using a quantitative 'stretch PCR' assay. L-dGTP had a weakly inhibitory effect (IC50 = 200 microM) in the presence of 10 microM dGTP. This effect was less obvious when the concentration of dGTP was higher. L-dTTP had a similar inhibitory effect. These findings suggest that telomerase may bind to L-dGTP and L-dTTP, and that the ability of telomerase to bind to dGTP or dTTP is changed.

Base Sequence↗

Immunohistochemical detection of human telomerase reverse transcriptase in normal mucosa and precancerous lesions of the stomach.

Telomerase activity confers cell immortality through stabilization of the chromosome, participating in the development of a majority of human cancers. Human telomerase reverse transcriptase (TERT) has been identified as a catalytic subunit of telomerase, and is overexpressed in most gastric carcinomas. We immunohistochemically examined the expression of TERT in normal gastric mucosa and candidate precancerous lesions such as intestinal metaplasia and adenoma. In non-neoplastic gastric mucosa including intestinal metaplasia and normal fundic mucosa, weak but significant expression of TERT was detected in nuclei of epithelial cells located in the lower two-thirds of the glands (wider than the proliferative zone). The telomerase activity was found in a half of gastric adenomas, whose levels of the activity were about 10% of those in gastric carcinomas. TERT protein was expressed in the nuclei of the adenoma cells at moderate levels, that were not necessarily comparable with the telomerase activities. These findings overall suggest that TERT expression may be one of the prerequisites for telomerase activation in an early stage of stomach carcinogenesis.

Adenoma↗

Y'-Help1, a DNA helicase encoded by the yeast subtelomeric Y' element, is induced in survivors defective for telomerase.

The yeast Y' element is a highly polymorphic repetitive sequence present in the subtelomeric regions of many yeast telomeres. The Y' element is classed as either Y'-L or Y'-S, depending on its length. It has been reported that survivors arising from telomerase-deficient yeast mutants compensate for telomere loss by the amplification of Y' elements. The total Saccharomyces cerevisiae genome DNA data base was searched for Y' elements, and 11 Y'-Ls and eight Y'-Ss were identified. As reported previously, many of the sequences were found to contain long open reading frames which potentially encode helicase. We examined the expression of the Y' elements in telomerase-deficient Deltatlc1 survivors, in which the TLC1 gene encoding the yeast telomerase template RNA had been disrupted, and found that the Y' element is highly expressed in the survivors, but not in the wild-type cells. Moreover, we demonstrated that the survivors produce a Y'-encoded protein designated as Y'-Help1 (Y'-helicase protein 1), and that this protein possesses helicase activity. Therefore, we suggest that the Y' element has a novel and potentially important role in trans, in addition to the well characterized role in cis, in telomerase-independent telomere maintenance in yeast.

Amino Acid Sequence↗

Shortened telomeres involved in a case with a jumping translocation at 1q21.

The jumping translocation (JT) is a rare chromosomal abnormality in which a specific chromosomal segment translocates onto the ends of various chromosomes (jumps). In most cases, the region distal to 1q21 jumps onto numerous different telomeres. Here we report a molecular study of the JT involving 1q21 found in a patient with acute myelomonocytic leukemia that had transformed from myelodysplastic syndrome (MDS). This is the first report describing the analysis of the molecular structure of the JT. We demonstrated the presence of a stretch of telomeric repeats at the breakpoint by means of a fluorescence in situ hybridization experiment, molecular cloning, and nucleotide sequencing of the fused region. A significant amount of variant telomeric repeats (a telomeric sequence having one-base mismatch within the authentic telomeric repeat TTAGGG) was found in this region. The variant telomeric repeat has been shown to be present in the proximal region of telomeres and does not perform telomeric functions by itself. Therefore, these results indicated that the telomeres had already been critically shortened when the jumps occurred. We suggest that the extended proliferation of cancer cells during the premalignant stage, such as MDS, results in chromosomal instability due to the loss of telomeric functions.

Base Sequence↗

Circular chromosome formation in a fission yeast mutant defective in two ATM homologues.

Telomeres, found at chromosomal ends, are essential for stable maintenance of linear chromosomes in eukaryotes. The ATM family of genes, including budding yeast TEL1 (refs 1,2), fission yeast rad3+ (ref. 3) and human ATM (ref. 4), have been reported to be involved in telomere length regulation, although the significance of the telomere phenotypes observed with the mutated genes remains elusive. We have cloned tel1+, another fission yeast ATM homologue, and found that a tel1rad3 double mutant lost all telomeric DNA sequences. Thus, the ATM homologues are essential in telomere maintenance. The mutant grew poorly and formed irregular-shaped colonies, probably due to chromosome instability, however, during prolonged culture of the double mutant, cells forming normal round-shaped colonies arose at a relatively high frequency. All three chromosomes in these derivative cells were circular and lacked telomeric sequences. To our knowledge, this is the first report of eukaryotic cells whose chromosomes are all circular. Upon meiosis, these derivative cells produced few viable spores. Therefore, the exclusively circular genome lacking telomeric sequences is proficient for mitotic growth, but does not permit meiosis.

Ataxia Telangiectasia Mutated Proteins↗

Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas.

Telomerase is a specialized type of reverse transcriptase which catalyzes the synthesis and extension of telomeric DNA (for review, see ref.1). This enzyme is highly active in most cancer cells, but is inactive in most somatic cells. This striking observation led to the suggestion that telomerase might be important for the continued growth or progression of cancer cells. However, little is known about the molecular mechanism of telomerase activation in cancer cells. Human telomerase reverse transcriptase (hTRT) has recently been identified as a putative human telomerase catalytic subunit. We transfected the gene encoding hTRT into telomerase-negative human normal fibroblast cells and demonstrated that expression of wild-type hTRT induces telomerase activity, whereas hTRT mutants containing mutations in regions conserved among other reverse transcriptases did not. Hepatocellular carcinoma (20 samples) and non-cancerous liver tissues (19 samples) were examined for telomerase activity and expression of hTRT, the human telomerase RNA component (hTR; encoded by TERC) and the human telomerase-associated protein (hTLP1; encoded by TEP1). A significant correlation between hTRT expression and telomerase activity was observed. These results indicate that the hTRT protein is the catalytic subunit of human telomerase, and that it plays a key role in the activation of telomerase in cancer cells.

Amino Acid Sequence↗

Autoreactive antibodies following autologous peripheral blood stem cell transplantation.

A 35-year-old woman diagnosed with multiple myeloma (IgG, lambda type, stage IIIA) received an autologous peripheral blood stem cell transplant (PBSCT). She was euthyroid without autoreactive antibodies prior to the transplant. The patient complained of malaise, weight loss and low grade fever 1 month after transplant, despite rapid haematopoietic recovery. Thyroid function tests on day 34 revealed hyperthyroidism associated with anti-thyroid peroxidase antibody. Antinuclear antibody was also detected, and platelet-associated immunoglobulin was increased. These findings disappeared spontaneously by day 62 without treatment. Autoimmune diseases may occur transiently after autologous PBSCT.

Adult↗

Effects of soya milk and Bifidobacterium-fermented soya milk on plasma and liver lipids, and faecal steroids in hamsters fed on a cholesterol-free or cholesterol-enriched diet.

The effects of freeze-dried soya milk (SM) and Bifidobacterium-fermented soya milk (FSM) on plasma and liver lipids, and faecal steroid excretion were estimated in hamsters fed on a cholesterol-free or cholesterol-enriched diet. Hamsters fed on the cholesterol-free diet containing 300 g FSM/kg had lower levels of plasma VLDL + LDL cholesterol than the animals fed on the control diet. SM in the diet produced a similar pattern without significant differences. In the cholesterol-enriched diet group, SM and FSM decreased the levels of plasma total cholesterol and VLDL + LDL-cholesterol. SM and FSM decreased the plasma triacylglycerol level in both the cholesterol-free and -enriched diet groups. The liver total cholesterol contents in the SM and FSM groups were lower than that in the control group, for hamsters fed on the cholesterol-free diet. The liver triacylglycerol content was not modified by SM or FSM in hamsters fed on either the cholesterol-free or -enriched diet. SM and FSM increased the total bile acid excretion and the proportion of cholesterol entering the cholic acid biosynthesis pathway in both the cholesterol-free and -enriched diet groups. SM and FSM did not affect neutral steroid excretion in the cholesterol-free or -enriched diet group. There was an inverse relationship between VLDL + LDL-cholesterol and faecal bile acid excretion in hamsters fed on the cholesterol-free (r -0.670, P < 0.01) and cholesterol-enriched (r -0.761, P < 0.001) diets respectively. These results indicated that SM had an anti-atherogenic effect, and that this effect was not diminished by prior fermentation.

Analysis of Variance↗

Maxillofacial morphology and masseter muscle thickness in adults.

The aim of this study was to investigate how the thickness of the masseter muscle relates to the maxillofacial morphology, including the thickness of alveolar process in the mandibular incisor region, and the thickness of the mandibular symphysis. The subjects consisted of 80 adult male volunteers (mean age: 23 years 8 months). The relationship between masseter muscle thickness and the maxillofacial skeleton was investigated by measuring the former by ultrasonography and the latter by roentgenographic cephalometry. The data were initially analysed using a multiple regression analysis. Thereafter, correlation coefficients were obtained by a simple regression analysis. The following results were found: 1. The thickness of the masseter muscle (mean +/- SD) was 15.8 +/- 3.0 mm in the relaxed state and 16.7 +/- 2.7 mm at maximal clenching. 2. Masseter muscle thickness was negatively correlated with the mandibular plane angle. 3. Masseter muscle thickness was positively correlated with the mandibular ramus height (Cd-Go), and the thickness of the alveolar process and that of the mandibular symphysis. It is therefore suggested that masticatory function influences the morphology of the mandible.

Adult↗

Expression of telomerase catalytic component, telomerase reverse transcriptase, in human gastric carcinomas.

Telomerase activity is believed to be crucial for cellular immortality, which is considered to participate in the development of a majority of human cancers. Human telomerase reverse transcriptase (TERT) has recently been identified as a catalytic subunit of telomerase. We examined the expression of TERT and other telomerase components such as human telomerase RNA component (hTR, encoded by TERC) and human telomerase-associated protein (TEP1) by reverse transcription-polymerase chain reaction in human gastric carcinomas and non-neoplastic mucosa, in addition to measuring the telomerase activity. Of 20 gastric carcinomas examined, 18 (90%) and 18 (90%) showed increased expression of TERT and higher telomerase activity in comparison with corresponding non-neoplastic mucosa, respectively. Increased expression of hTR/TERC was also observed in 15 (75%) of the gastric carcinomas. Immunohistochemically, strong expression of TERT protein was detected in the nuclei of the tumor cells of all carcinoma tissues, while the expression of TERT in non-neoplastic mucosal cells as well as stromal elements (except lymphocytes) was weak or negative. These findings suggest that increased TERT expression associated with telomerase activity may serve as a novel marker for the diagnosis of stomach cancer.

Aged↗

Effects of soy milk and bifidobacterium fermented soy milk on lipid metabolism in aged ovariectomized rats.

The effects of soy milk and fermented soy milk on lipid metabolism were studied in aged ovariectomized rats. Twenty 8-mo-old Wistar rats were randomly assigned to four treatment groups: sham-operated + control diet (sham-C); ovariectomized (OVX) + control diet (OVX-C); OVX + soy milk diet (OVX-SM); and OVX + fermented soy milk diet (OVX-FSM). The rats were fed on these diets for 6 weeks. Ovariectomy induced an increase in the plasma cholesterol level by 40%. The plasma total cholesterol level of the OVX-FSM rats was decreased by 20% compared to that of the OVX-C rats. The plasma total cholesterol level of the OVX-SM group was not significantly different from that of the OVX-C and sham-C rats. The plasma triglyceride level of the OVX-FSM rats was lower than that of the sham-C rats. The liver cholesterol content in OVX-SM and OVX-FSM rats was lower than that of the OVX-C rats. The liver triglyceride contents of the sham-C, OVX-SM, and OVX-FSM groups were lower than that of the OVX-C group. Fecal steroid excretion did not differ among the groups. Ovariectomy decreased the uterus weight. The OVX-SM and OVX-FSM groups had the same uterus weights as those of the OVX-C group. Thus, the diet including fermented soy milk prevented the cholesterol elevation induced in rats by ovarian hormone deficiency.

Aging↗

Development of vibration protection seats for agricultural machinery.

Seats have been newly developed with an anti-vibration suspension system for agricultural machinery. These seats were examined in a series of laboratory tests to determine their static and dynamic physical characteristics. These seats are specifically designed for the Japanese physique. An artificial track was constructed to simulate a farm field based on BSI (British Standard) and to examine vibration the transmissibility of the seats when installed in machinery. The results indicated that the transmissibility from under the seat to on the seat in the vertical direction was approximately 0.25, although little reduction of vibration was observed in the fore-aft direction. This suggests that these seats are applicable to the agricultural field.

Agricultural Workers' Diseases↗