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Biomedical subjects

A Nakai

Publications and source records attributed to A Nakai.

At least 37 records · Page 2Linked to original sources

Development of Ag-Pd-Au-Cu alloys for multiple dental applications. Part 2. Mechanical properties of experimental Ag-Pd-Au-Cu alloys containing Sn or Ga for ceramic-metal restorations.

Eighteen Ag-Pd-Au-Cu alloys, consisting of nine Ag-Pd-Au-Cu mother compositions (Pd: 20, 30 or 40%, Au: 20%, Cu: 10, 15 or 20%, Ag: balance) containing either 5% Sn or 5% Ga as an additive metal, were experimentally prepared. Tensile strength, proof stress, elongation, elastic modulus, and Vickers hardness of these alloys were evaluated to clarify the potential of these alloys for use as ceramic-metal restorations as well as the effects of the Pd and Cu contents on their mechanical properties. The tensile strength, proof stress, elongation, elastic modulus and Vickers hardness of the 18 experimental alloys were in the range of 410.0-984.0 MPa, 289.7-774.3 MPa, 2.2-23.7%, 81.3-123.0 GPa and 135.7-332.3 HV1, respectively. Ten of the 18 experimental alloys can be used for ultra-low fusing ceramics based on their proof stress, elastic modulus, elongation and hardness. Between the Ga- and Sn-added alloys, differences in tensile strength, proof stress, elongation and hardness were found at several Ag-Pd-Au-Cu compositions.

Analysis of Variance↗

A nuclear localization signal is essential for stress-induced dimer-to-trimer transition of heat shock transcription factor 3.

Expression of heat shock genes is regulated mainly at the level of transcription by heat shock transcription factors (HSFs). In avian, HSF1 and HSF3 are maintained in a cryptic monomer and dimer form, respectively, in the cytoplasm in the absence of stress. Upon heat stress, they undergo conformational change associated with the formation of a trimer and nuclear translocation. In this study, we identified regions that are necessary for the dimer-to-trimer transition of chicken HSF3 (cHSF3) upon stress conditions. One of these regions coincides with a functional nuclear localization signal (NLS) of cHSF3 that was recognized by a nuclear transport receptor importin alpha. Point mutations of basic amino acids in the NLS inhibit both nuclear translocation and trimer formation of cHSF3. These results demonstrate that the NLS acts positively on the trimer formation of cHSF3 upon stress conditions.

Amino Acid Sequence↗

A Ca(2+) channel blocker-like effect of dehydrocurdione on rodent intestinal and vascular smooth muscle.

Effects of dehydrocurdione, a zedoary-derived sesquiterpene, on smooth muscle were investigated by recording the mechanical activity of intestines and aorta from guinea pigs and rats. Dehydrocurdione (0.1-3 mM) induced a sustained relaxation of rat duodenum and inhibited spontaneous motility. Dehydrocurdione (0.1-1 mM) inhibited the contractile response of guinea pig ileum induced by acetylcholine (0.01-10 microM), histamine (0.03-10 microM) and substance P (0.1-30 nM) in a non-competitive manner. Acetylcholine (0.5 microM) elicited a transient contraction followed by a sustained contraction of guinea pig ileum, and dehydrocurdione pretreatment inhibited the sustained component, which depends on Ca(2+) entry from the extracellular space. The high K(+)-induced contraction of rat aortic ring is reported to be blocked by Ca(2+) channel blockers, while the norepinephrine-induced contraction includes a Ca(2+) channel blocker-resistant component. Dehydrocurdione (1 mM) blocked the high K(+) (60 mM)-induced contraction of rat aortic ring by 81%, while it inhibited the norepinephrine (1 microM)-induced contraction by only 28%. Dehydrocurdione (1 mM) significantly reduced the high K(+)-stimulated increase in cytosolic Ca(2+) level of Fura-2-loaded mesenteric artery from rats. These results suggest that the inhibitory effects of dehydrocurdione on intestinal and vascular smooth muscle are mediated by blockade of Ca(2+) entry from the extracellular space.

Animals↗

p53 suppresses the c-Myb-induced activation of heat shock transcription factor 3.

Expression of heat shock proteins (HSPs) is controlled by heat shock transcription factors (HSFs). Vertebrates express multiple HSFs whose activities may be regulated by distinct signals. HSF3 is specifically activated in unstressed proliferating cells by direct binding to the c-myb proto-oncogene product (c-Myb), which plays an important role in cellular proliferation. This suggests that the c-Myb-induced HSF3 activation may contribute to the growth-regulated expression of HSPs. Here we report that the p53 tumor suppressor protein directly binds to HSF3 and blocks the interaction between c-Myb and HSF3. In addition, p53 stimulates the degradation of c-Myb through a proteasome-dependent mechanism, which is, at least partly, mediated by induction of Siah in certain types of cells. Induction of p53 by a genotoxic reagent in DT40 cells disrupts the HSF3-c-Myb interaction and down-regulates the expression of certain HSPs. Mutated forms of p53 found in certain tumors did not inhibit c-Myb-induced HSF3 activation. The regulation of HSF3 activity by c-Myb and p53 sheds light on the molecular events that govern HSP expression during cellular proliferation and apoptosis.

Animals↗

Developmental changes in mitochondrial activity and energy metabolism in fetal and neonatal rat brain.

Experiments were undertaken to investigate mitochondrial activity and energy metabolism in the developing rat brain from the late fetal stage to the neonatal stage. Samples of cerebral cortical tissue were obtained from fetuses at 14, 16, 18, and 20 days of gestation, and from pups at 1 h, 1 day and 7 days after birth. Mitochondrial respiration was measured polarographically using homogenates. Fetal and neonatal brains were frozen in situ and fluorometric enzymatic techniques were used for the analysis of ATP, ADP, AMP, and lactate. In the fetal brain, there was a gradual increase in stimulated (+ADP) and uncoupled respiratory rates using glutamate and malate as substrates, from 14 days to 20 days of gestation, together with a moderate increase in ATP concentration and in the sum total of adenine nucleotides, and a significant decrease in lactate. Since non-stimulated (-ADP) respiratory rates did not change with increasing gestational age, the respiratory control ratio appeared to increase over the same period. An increase in mitochondrial activity was more pronounced immediately after birth, together with a marked increase in ATP concentration and in the sum total of adenine nucleotides. The highest rate of mitochondrial respiration was observed in 1-hour-old pups. These results indicate that, in the rat brain, there is maturation of oxidative metabolism in mitochondria that is initiated in late gestation. Acceleration in mitochondrial respiration occurs immediately after birth in order to maintain high-energy phosphate levels, and this may be crucial for the successful outcome of the newborn.

Adenosine Diphosphate↗

Arrest of spermatogenesis in mice expressing an active heat shock transcription factor 1.

In mammals, testicular temperature is lower than core body temperature, and the vulnerable nature of spermatogenesis to thermal insult has been known for a century. However, the primary target affected by increases in temperature is not yet clear. We report here that male mice expressing an active form of heat shock transcription factor 1 (HSF1) in the testis are infertile due to a block in spermatogenesis. The germ cells entered meiotic prophase and were arrested at pachytene stage, and there was a significant increase in the number of apoptotic germ cells in these mice. In wild-type mice, a single heat exposure caused the activation of HSF1 and similar histological changes such as a stage-specific apoptosis of pachytene spermatocytes. These results suggest that male infertility caused by thermal insult is at least partly due to the activation of HSF1, which induces the primary spermatocytes to undergo apoptosis.

Animals↗

Long-term results of fractionated strontium-90 radiation therapy for pterygia.

PURPOSE: The long-term safety and effectiveness of fractionated strontium-90 radiation therapy (RT) for pterygium were reviewed retrospectively. METHODS AND MATERIALS: Between 1984 and 1996, 399 patients with 490 pterygia were treated with a strontium-90 eye applicator following surgical removal of the pterygium. The median follow-up period was 61 months (range 2-178). Of the 490 pterygia, 452 were fresh, 17 were recurrences after surgical removal alone, and 21 were recurrences after surgical removal plus postoperative RT. Fractionated RT of 31-42 Gy/4-5 fractions/22-29 days was given for 95.1% of the pterygia. RESULTS: In total, 58 (11.8%) local recurrences of pterygia were noted. The median time of local recurrences was 10 months, ranging from 2 to 93 months, and 16 recurrences (28%) were noted later than 24 months after treatment. The interval between surgery and the start of RT (1-3 days vs. >3 days) and recurrent pterygia were significant variables for local control in the multivariate analysis, while total RT dose (7-29 Gy vs. 31-50 Gy) was a marginally significant variable. Late toxicities that may be associated with strontium-90 RT were scleromalacia (scleral thinning) in 4 eyes, adhesion of eyelids in 3 eyes, and scleral ulcer in 2 eyes. CONCLUSION: Fractionated strontium-90 RT of approximately 40 Gy/4-5 fractions was safe and effective for preventing recurrence of pterygia, when RT was started within 3 days of surgery.

Adult↗

Scavenging effect of nicorandil on free radicals and lipid peroxide in streptozotocin-induced diabetic rats.

Free radicals and lipid peroxide (LPO), easily formed in the diabetic state, play an important role in the development of diabetic complications. Potentially, nicorandil may reduce the production of free radicals and LPO in various organs. In fact, increased LPO levels in the serum, kidney, and cardiac muscle of diabetic (DM) rats were reduced by nicorandil treatment (N treatment). Xanthine oxidase (XOD), which produces free radicals, was decreased in the liver and increased in the kidney of DM rats compared with control rats, and these changes were prevented by N treatment. The concentration of Cu, Zn-superoxide dismutase (SOD) decreased in the cardiac muscle and increased in the kidney of DM rats, and these changes returned to normal after N treatment. The decreased concentration of Mn-SOD in the liver, kidney, and cardiac muscle from DM rats was also reversed by N treatment. The changes in catalase and glutathione peroxidase (GSH-PX) activities in DM rats were not improved effectively by N treatment. Another K-adenosine triphosphate (K-ATP) channel opener, tilisolol hydrochloride, had an effect similar to that of nicorandil. The effects of nicorandil and tilisolol were studied only in DM rats. These data imply that N treatment, as an antioxidative therapy, may be beneficial in preventing diabetic complications due to lipoperoxidation and free radicals in DM rats.

Animals↗

Reverse transcriptase is elevated in the thyroid tissue from Graves' disease patients.

OBJECTIVE: Hypertrophy of the thyroid gland in Graves' disease is related to an autoimmune response directed against TSH receptors found in thyroid cells. Recently, investigators have suggested that autoimmune diseases, including thyroid diseases may, at least in part, correlate with the expression of proteins encoded by the retroviral genome. In the present study, to confirm the correlation between thyroid autoimmune disorders and retroviral infections, we examined reverse transcriptase (RT) activity in thyroid tissues as a marker of retroviral infection. PATIENTS AND MEASUREMENTS: Thyroid tissues obtained at surgery from patients with various thyroid disorders (normal thyroid adjacent to adenoma, six cases; Graves' disease thyroid tissue, 25 cases; adenoma, eight cases; papillary carcinoma, 12 cases; Graves' disease peripheral blood lymphocytes, 11 cases) were used for RT assay, using a specific, improved assay system. RESULTS: Thyroid tissue extracts from patients with Graves' disease contained high RT activity which resembled that demonstrated in retroviruses. The RT existed in the thyroid tissue as a complex, with endogenous template RNA, and the activity was confirmed not to be due to other DNA polymerases. CONCLUSION: Retroviral RT distinguished from known cellular DNA polymerases is expressed in the thyroids of patients with Graves' disease. In a permissive genetice and immunological environment, retroviral DNA integrated into genomic DNA could precipitate the onset of Graves' disease.

Adenoma↗

Secondary mitochondrial dysfunction after transient intrauterine ischemia in the fetal rat brain.

OBJECTIVE: Recirculation following transient intrauterine ischemia has previously been found to cause partial recovery and secondary deterioration of cellular bioenergetic states in the fetal rat brain. Our objective was to assess whether secondary bioenergetic failure is due to mitochondrial dysfunction. STUDY DESIGN: Cerebral cortical tissues were obtained from 20-day-old fetal rats at the end of 30 minutes of intrauterine ischemia (n = 6) and after 1 hour (n = 6), 2 hours (n = 6), and 4 hours (n = 6) of recirculation. Mitochondrial respiratory activities were measured polarographically using homogenates. RESULTS: Mitochondrial activities decreased to 45% of sham-operated controls at the end of ischemia. Recirculation (1 hour) brought about partial recovery, but continued reflow (2 hours and 4 hours) was associated with a secondary deterioration of mitochondrial activities. CONCLUSION: The results indicate that although during the early time period after ischemia mitochondrial respiratory capacity is restored, secondary mitochondrial dysfunction develops in the immature rat brain.

Animals↗

Changes in uterine and ovarian arterial impedance during the periovulatory period in conception and nonconception cycles.

OBJECTIVE: To evaluate whether the Doppler velocimetry of uterine and ovarian arteries during the periovulatory period in conception cycles differs from that in nonconception cycles. DESIGN: Transvaginal color Doppler sonography was used to assess uterine and ovarian perfusion in 63 infertile women during the periovulatory period. RESULTS: In the conception cycles (n = 16), the PI values of uterine arteries at the day of ovulation were significantly less than those in nonconception cycles (n = 47). There were no significant differences in the PI values of ovarian arteries between the conception and nonconception cycles. CONCLUSIONS: In the present study, the conception cycles showed lower vascular impedance in the uterine during the periovulatory period than did the nonconception cycles. This endometrial perfusion presents an accurate noninvasive assay of uterine receptivity that can be used to predict the successful outcome of implantation and to reveal unexplained infertility problems.

Adult↗

Effect of alpha-phenyl-N-tert-butyl nitrone (PBN) on fetal cerebral energy metabolism during intrauterine ischemia and reperfusion in rats.

The objective of the present study was to explore whether a free radical spin trap agent, alpha-phenyl-N-tert-butyl nitrone (PBN), influences bioenergetic failure induced in the 20-day-old fetal brain by 30 min of intrauterine ischemia in Wistar rats. Fetal brains were frozen in situ at the end of ischemia and after 1, 2, and 4 h of recirculation for analysis of ATP, ADP, AMP, and lactate. PBN or vehicle was given 1 h after recirculation. Tissue oxygen tension was evaluated in placental and fetal cerebral tissues throughout the whole periods of 30 min of ischemia and 4 h of recirculation. Ischemia was associated with a decrease in ATP concentration and an increase in lactate concentration (p < 0.001). Recirculation (1 and 2 h) led to a recovery of ATP concentration, but continued reflow (4 h) was associated with a secondary deterioration of high-energy phosphates (p < 0.01). Lactate concentration increased during this recovery period. This deterioration was prevented by PBN (p < 0.05). After 30 min of ischemia, tissue oxygen tension in placenta and fetal brain decreased to about 30% and 50% of control, respectively. However, recirculation brought about a recovery of oxygen delivery. The results indicate that although during the early time period after ischemia fetal cerebral energy metabolism is maintained by an acceleration of the anaerobic glycolytic rate, secondary deterioration of cellular bioenergetic state develops in the immature fetal brain. This deterioration may be due to mitochondrial dysfunction, which may be induced by oxygen-derived free radicals, and not by compromised microcirculation.

Animals↗

Prediction of uterine dehiscence by measuring lower uterine segment thickness prior to the onset of labor: evaluation by transvaginal ultrasonography.

OBJECTIVE: Lower uterine segment thickness was measured by transvaginal ultrasound examination and its correlations with the occurrence of uterine dehiscence and rupture was examined. METHODS: The thickness of the muscular layer of the lower uterine segment was measured in 186 term gravidas with previous uterine scars and its correlation with uterine dehiscence/rupture was investigated. RESULTS: Uterine dehiscence was found in 9 cases or 4.7%. There were no cases of the uterine rupture. The thickness of the lower uterine segment among the gravidas with dehiscence was significantly less in than those without dehiscence (p< 0.01). The cut-off value for the thickness of the lower uterine segment was 1.6 mm as calculated by the receiver operating characteristic curve. The sensitivity was 77.8%; specificity 88.6%; positive predictive value 25.9%; negative predictive value 98.7%. CONCLUSION: Measurement of the lower uterine segment is useful in predicting the absence of dehiscence among gravidas with previous cesarean section. If the thickness of the lower uterine segment is more than 1.6 mm, the possibility of dehiscence during the subsequent trials of labor is very small.

Adult↗

Changes in maternal lipid peroxidation levels and antioxidant enzymatic activities before and after delivery.

OBJECTIVE: Our goal was to characterize the changes in maternal lipid peroxidation levels and antioxidant enzymatic activities before and after delivery. METHODS: Predelivery and 1, 24, and 48 hours post-partum plasma concentrations of malondialdehyde, erythrocyte enzyme superoxide dismutase, glutathione peroxidase and catalase were measured in uncomplicated pregnancies. RESULTS: Malondialdehyde levels increased slightly from predelivery to 24 hours post-partum and then decreased significantly at 48 hours post-partum. At one hour post-partum superoxide dismutase and catalase levels increased significantly to about 125% and 170% of predelivery levels, respectively. Thereafter, these values decreased significantly from one hour to 48 hours post-partum. The relative changes in superoxide dismutase and catalase levels at one hour post-partum compared to predelivery values correlated significantly with the duration of labor. CONCLUSION: The results suggest that the uncontrolled lipid peroxidation caused by reactive oxygen species, which are produced in consequence of tissue reoxygenation, may occur during labor and that prolonged labor, may cause maternal oxidative stress.

Adult↗

Study of resin-bonded calcia investment: Part 1. Setting time and compressive strength.

This study was carried out to develop a new titanium casting investment consisting of calcia as the refractory material and a cold-curing resin system as the binder. The setting time of the investment was investigated under different N,N-dimethyl-p-toluidine (DMPT) contents in methyl methacrylate monomer (MMA) and benzoyl peroxide (BPO) contents in calcia without any sintering agent. The effects of the sintering agents, which were calcium fluoride (CaF2) and calcium chloride (CaCl2), on the compressive strength of the investments were investigated at room temperature before and after heating to two different temperatures. The shortest setting time (68 minutes) of the investment was obtained at 0.37 DMPT/BPO (1.5 vol% /1.0 mass%) ratio by mass. The highest strength (16.5 MPa) was obtained from the investment which contained 2 mass% CaF2 and was heated to 1,100 degrees C. It was found that the developed calcia investment containing 2 mass% CaF2 has a possibility for use in titanium castings.

Alloys↗

The mammalian HSF4 gene generates both an activator and a repressor of heat shock genes by alternative splicing.

The expression of heat shock genes is controlled at the level of transcription by members of the heat shock transcription factor family in vertebrates. HSF4 is a mammalian factor characterized by its lack of a suppression domain that modulates formation of DNA-binding homotrimer. Here, we have determined the exon structure of the human HSF4 gene and identified a major new isoform, HSF4b, derived by alternative RNA splicing events, in addition to a previously reported HSF4a isoform. In mouse tissues HSF4b mRNA was more abundant than HSF4a as examined by reverse transcription-polymerase chain reaction, and its protein was detected in the brain and lung. Although both mouse HSF4a and HSF4b form trimers in the absence of stress, these two isoforms exhibit different transcriptional activity; HSF4a acts as an inhibitor of the constitutive expression of heat shock genes, and hHSF4b acts as a transcriptional activator. Furthermore HSF4b but not HSF4a complements the viability defect of yeast cells lacking HSF. Moreover, heat shock and other stresses stimulate transcription of target genes by HSF4b in both yeast and mammalian cells. These results suggest that differential splicing of HSF4 mRNA gives rise to both an inhibitor and activator of tissue-specific heat shock gene expression.

Alternative Splicing↗

Ubiquitous and cell-specific members of the avian small heat shock protein family.

Small heat shock proteins (sHsps) have been suggested to act as molecular chaperones for many kinds of substrates and have protective roles in cells exposed to external stresses. Unlike other major Hsps such as Hsp70 and Hsp90, expression of many vertebrate sHsps is restricted to the muscle tissues and/or eye lens. Among the sHsps, the heat-inducible human Hsp27 (hHsp27) homologue is believed to be expressed ubiquitously in various cell types. Here, we distinguished the chicken homologue of hHsp27 (cHsp24) from the chicken major heat-inducible protein of molecular size 25 kDa (cHsp25). cHsp25 is not expressed in the absence of stress, but is highly expressed after hyperthermia in all tissues of developing embryos. In contrast, expression of cHsp24 is restricted to some specific tissues even in the presence of stress. Thus, cHsp25 is the first member of the sHsps in vertebrates the expression of which is ubiquitous in tissues exposed to external stresses similar to Hsp70.

Animals↗