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Biomedical subjects

K Miyazaki

Publications and source records attributed to K Miyazaki.

At least 253 records · Page 14Linked to original sources

Maternal and fetal nitric oxide synthesis is decreased in pregnancies with small for gestational age infants.

Our purpose was to evaluate whether maternal and fetal nitric oxide synthesis in pregnancies with small for gestational age (SGA) infants are different from those in pregnancies with appropriate for gestational age (AGA) infants. Maternal and fetal circulating nitrate and nitrite concentrations were compared between 30 pregnancies with AGA and 10 pregnancies with SGA at birth. End-products of nitric oxide synthesis were measured in maternal and cord venous blood samples using a fluorometric assay. Umbilical artery blood pH and PO2 were also measured. Maternal circulating nitrite and nitrate concentrations (6.91 +/- 1.27 microM) in pregnancies with SGA were significantly lower than those (11.69 +/- 1.33 microM) in pregnancies with AGA (P = 0.015). Fetal circulating nitrite and nitrate concentrations (7.54 +/- 1.09 microM) in pregnancies with SGA were also significantly lower than those (11.24 +/- 1.08 microM) in pregnancies with AGA (P = 0.024). There were no significant differences in umbilical artery blood pH and PO2 between the two groups. These results suggest that maternal and fetal nitric oxide synthesis are decreased in pregnancies with SGA infants.

Adult↗

Endometriosis and uterine leiomyomata with ovarian granulosa cell tumour.

We report the first known case of right endometrial cyst and multiple uterine leiomyomata complicated by an ovarian granulosa cell tumour of adult type. A 42 year old woman had an adult type left granulosa cell tumour. Laparoscopy 13 years earlier had revealed a small endometrial implant on the peritoneum, without uterine leiomyomata or bilateral ovarian tumours. Findings in this case suggest that the aetiology of endometriosis and uterine leiomyomata are related to the presence of an oestrogen-secreting neoplasm and that the presence of a state of hyperoestrogenaemia due to granulosa cell tumour over several years might have stimulated the development of endometriosis and leiomyomata.

Adult↗

Role of tissue inhibitor of metalloproteinases-2 (TIMP-2) in regulation of pro-gelatinase A activation catalyzed by membrane-type matrix metalloproteinase-1 (MT1-MMP) in human cancer cells.

To clarify the regulatory mechanism of pro-gelatinase A (proGelA) activation at a cellular level, expression of gelatinase A (GelA), three MT-MMPs, and TIMP-2 was examined with 11 human cancer cell lines cultured in the presence and absence of stimulants. MT1-MMP mRNA was expressed in 8 cell lines, while MT2-MMP and MT3-MMP mRNAs were expressed in fewer cell lines. The cells with high proGelA activation strongly expressed MT1-MMP mRNA but not MT2-MMP and MT3-MMP mRNAs, suggesting that MT1-MMP was responsible for the proGelA activation in the cancer cells. Treatments with concanavalin A (Con A) and a phorbor ester (TPA) enhanced the MT1-MMP expression, but only Con A stimulated the proGelA activation in many cell lines. In HT1080 fibrosarcoma cells, however, TPA also stimulated the activation. The level of TIMP-2 secreted into culture medium inversely correlated with proGelA activation. For example, 2 squamous cell carcinoma lines (HSC-3 and HSC-4) and 3 HT1080 clones, which efficiently activated proGelA, secreted little TIMP-2 into medium, whereas other cell lines and other HT1080 clones, which hardly activated proGelA, secreted TIMP-2 at high levels. When HSC-3 cells were incubated with TIMP-2 protein or transfected with TIMP-2 cDNA, the proGelA activation was strongly inhibited. These results indicated that extracellular TIMP-2 was an important negative regulator of proGelA activation. However, the level of extracellular TIMP-2 was not consistent with that of TIMP-2 mRNA in some cell lines. Other experimental results suggested that TIMP-2 might be rapidly metabolized after binding to MT1-MMP, and Con A treatment might stabilize the complex of TIMP-2 and MT1-MMP on cell membranes.

Catalysis↗

Prognostic value of platelet-derived growth factor-A (PDGF-A) in gastric carcinoma.

OBJECTIVE: Because our previous study indicated that PDGF-A mRNA expression in biopsy specimens might identify a subgroup of high-risk patients with gastric carcinoma, in this study we analyzed the prognostic value of platelet-derived growth factor-A (PDGF-A) gene expression in gastric carcinoma biopsy specimens. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyze the PDGF-A gene expression in 65 gastric carcinoma endoscopic biopsy specimens. The 65 patients were divided into a PDGF-A-positive group (29 patients) and a PDGF-A-negative group (36 patients). RESULTS: On the basis of 2-year follow-up data, the PDGF-A-positive group demonstrated a shorter overall survival rate compared with the PDGF-A-negative group (p < 0.0001). A similar correlation was found in 34 advanced-stage patients (p = 0.003) and in 24 advanced-stage patients who underwent a curative resection (p = 0.003). Multivariance analysis indicated that the transcription of PDGF-A gene is a potent prognostic factor that is independent of the traditional pathologic parameters. CONCLUSIONS: Expression of PDGF-A mRNA in gastric biopsy specimens may be a new preoperative prognostic parameter in gastric carcinoma.

Aged↗

Inhibition of nitric oxide synthesis aggravates myocardial ischemia in hemorrhagic shock in constant pressure model.

In hemorrhagic shock (HS), nitric oxide synthase (NOS) inhibitor is known to increase blood pressure and prolong survival time. On the other hand, NOS inhibitor decreases coronary flow and worsens myocardial ischemia. Therefore, we hypothesized that the beneficial effect of NOS inhibitor is attributable to the increased coronary perfusion pressure and that it outcompetes the coronary vasodilating effects of nitric oxide. To investigate the direct effect of NOS inhibitor on the regulation of coronary circulation and the induction of myocardial ischemia in HS, we used a canine model at a constant aortic pressure of 40 mmHg with an aortic reservoir. In seven dogs, intravenous administration of Nomega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) at 10 min after induction of HS increased both systemic and coronary vascular resistances and further increased the serum catecholamine concentration at 10 min after L-NAME. In another 14 dogs, the beating hearts were rapidly cross-sectioned (120 ms) and freeze clamped (-190 degrees C) by a specially developed sampling device after 10 min of HS. Transmurally distributed myocardial ischemia was visualized by the enhanced reduced nicotinamide adenine dinucleotide fluorescence, which was significantly increased with L-NAME (n=7). Chemical analysis revealed a decrease in the myocardial ATP concentration with L-NAME in the subendocardial ischemic region in HS. In conclusion, with the use of an aortic reservoir to keep the aortic pressure constant in HS, NOS blockade significantly worsened myocardial ischemia by decreasing coronary flow and augmenting the serum catecholamine concentration.

Adenosine Triphosphate↗

Power Doppler enhancement of the placenta by dehydroepiandrosterone sulphate in term pregnancy.

We studied the effect of dehydroepiandrosterone sulphate (DHAS) on placental blood flow in 11 women with an uncomplicated pregnancy between 37 and 39 weeks of gestation. Power Doppler enhancement of the placenta was performed before and 60 minutes after the administration of a 200 mg intravenous dose of DHAS dissolved in 20 mL of 5% dextrose. Increased power Doppler enhancements of the placenta after DHAS injection were evident in each case studied. The power Doppler enhancement returned to the baseline imaging within 60 minutes. This DHAS loading test, assessed by means of power Doppler imaging, may be a useful technique when attempting to assess fetoplacental function in normal and high risk pregnancies.

Acetone↗

Ionic-diffusion potential-dependent transport of a new quinolone, sparfloxacin, across rat intestinal brush-border membrane.

The mechanism of uptake of sparfloxacin, a new quinolone, by intestinal brush-border membrane vesicles was investigated to clarify whether there is a common transport process for new quinolones mediated by the diffusion potential across the intestinal membrane bilayer. Sparfloxacin was taken up pH-dependently by rat intestinal brush-border membrane vesicles, behaviour analogous to that of organic cations including enoxacin and ciprofloxacin. Transient overshooting uptake of this quinolone was observed in the presence of an outward H+ gradient. Momentary dissipation of the H+ gradient by addition of carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone did not affect the uptake of sparfloxacin, and a marked but incomplete reduction in the H+-sensitive overshooting uptake of sparfloxacin was apparent in the voltage-clamped brush-border membrane vesicles. Furthermore, a valinomycin-induced K+-diffusion potential (interior negative) and an inward C1--diffusion potential stimulated the initial uptake of sparfloxacin at pH 5.5. Sparfloxacin uptake was inhibited by tetracaine and imipramine. The inhibitory effect of these cations correlated well with changes in membrane surface charges induced by the presence of tetracaine or imipramine. These results indicate that sparfloxacin transport across the brush-border membrane depends upon the inside-negative ionic diffusion potential, that the H+- or K+-diffusion-potential-dependent uptake of sparfloxacin by intestinal brush-border membrane vesicles is affected by the membrane surface potential and that inhibition of sparfloxacin uptake originates from changes in the membrane surface potential caused by the organic cations.

Animals↗

Three-dimensional ultrasonographic assessment of the umbilical cord during the 2nd and 3rd trimesters of pregnancy.

OBJECTIVE: To evaluate the umbilical cord and its abnormalities by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. PATIENTS AND METHODS: Ninety-five pregnancies (92 normal, 2 with hydrops fetalis, and 1 with omphalocele) from 14 to 40 weeks of gestation were studied with a specially developed abdominal three-dimensional transducer (3.5 MHz). This system can provide conventional two-dimensional ultrasonography images and can also generate within seconds high-quality three-dimensional images in the surface and transparent mode with no need for an external workstation. A proportion of the umbilical cords (coiled or noncoiled free loop, abdominal insertion, and placental insertion) visualized at each gestational age interval is presented. RESULTS: The proportion of the umbilical cords visualized during pregnancy except for between 24 and 27 weeks of gestation was about 70% (range 64-83%). Optimal visualization of the umbilical cord was achieved between 24 and 27 weeks of gestation. During this period it was possible to adequately depict the umbilical cord in 93% of the cases. The proportions of the noncoiled umbilical cord depicted during pregnancy ranged from 8 to 45%. The detection rate of abdominal insertion of the umbilical cord visualized at 14-19 weeks was 44%; the detection rate decreased thereafter. Placental insertion of the umbilical cord could not be identified after 28 weeks of gestation. In 2 cases with hydrops fetalis, edematous umbilical cord was evident. In 1 fetus, omphalocele was clearly depicted. CONCLUSIONS: The new three-dimensional ultrasound technology generates within seconds high-quality three-dimensional images of the umbilical cord, although limitation of viewing direction exists. These results suggest that the new three-dimensional ultrasonography has the potential to be a supplement to two-dimensional ultrasonography and might be useful in identifying abnormal umbilical cords in utero.

Edema↗

Three-dimensional ultrasonographic visualization of multiple pregnancy.

Our purpose was to describe interrelationships and contacts between twins in utero by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. Thirteen twin pregnancies (3 monochorionic and 10 dichorionic pairs) and one triplet pregnancy (trichorionic triplet) from 9 to 36 weeks of gestation were studied with a specially developed abdominal three-dimensional transducer (3.5 MHz). This imaging system can provide conventional two-dimensional ultrasonography images and can also generate within seconds high-quality three-dimensional images in the surface and transparent mode with no need for an external workstation. Interrelationships and contacts between twins or triplets are described. Various types of contacts (head/body/arm/leg) and interrelationships were clearly visualized. Crowding of in utero twin fetuses increased with advancing gestation. Sometimes two placentas and dividing membrane were beautifully depicted. In one triplet pregnancy, the interrelationships among 3 fetuses and dividing membranes were easily recognized. Three-dimensional ultrasonography provides a novel means of visualizing multiple pregnancies in utero. These results suggest that three-dimensional ultrasonography has the potential to be a supplement to two-dimensional ultrasonography and would be useful in evaluating the interhuman contacts and crowdings of twin and triplet fetuses in utero.

Female↗

Wide distribution of laminin-5 gamma 2 chain in basement membranes of various human tissues.

Laminin 5 (LN5), a heterotrimer of laminin alpha 3. beta 3. and gamma 2 chains. is a laminin isoform which strongly promotes adhesion. migration. and scattering of cells through binding to integrins alpha 3 beta 1, alpha 6 beta 1 and alpha 6 beta 4. To get an insight into the physiological functions of LN5, we prepared a mouse monoclonal antibody to human laminin gamma 2 chain and used it for immunohistochemical analysis of laminin gamma 2 chain in normal human tissues. The basement membranes of various epithelial tissues, such as the skin, lung, small intestine, stomach, kidney and prostate, were immunostained with the anti-laminin gamma 2 chain monoclonal antibody. In addition, the basement membrane of the surface germinal epithelium in the ovary was also positive for laminin gamma 2 chain. These results suggest general roles of LN5 in the anchorage of various types of epithelial cells to the underlying basement membrane and in the expression of their cellular functions. Moreover, deposition of laminin gamma 2 chain around small arteries and veins was observed in the thymus and spleen. This lymphatic organ-specific expression of vascular LN5 might provide a novel function of LN5 in immune responses.

Adult↗

Three-dimensional sonographic visualization of the fetal face.

OBJECTIVE: This study was done to show the potential of using three dimensional (3D) sonography to reveal fetal facial anomalies. SUBJECTS AND METHODS: Ninety-four healthy fetuses from 15 to 40 weeks' gestation were studied with a specially developed 3.5-MHz abdominal 3D transducer. This imaging system provided conventional two-dimensional (2D) sonographic images and also generated within seconds high-quality 3D images in the surface and transparent modes with no need for an external workstation. RESULTS: Using this imaging system, we obtained 2D and 3D images of fetal faces (forehead, eyes, nose, lips, and chin) at six gestational ages. At less than 24 weeks' gestation, 65% of facial structures were visualized. The image quality was slightly degraded because of the small fetal size. At or after 24 weeks' gestation, 84% of facial structures were revealed. We found no significant difference in image quality of the fetal face between 2D and 3D sonography. CONCLUSION: The new 3D sonographic technology can generate within seconds high-quality 3D images of the fetal face. The 3D technology seems to perform at least as well as conventional 2D sonography. Our results suggest that 3D sonography has the potential to supplement 2D sonography and might be useful in identifying malformations of the fetal face and chromosomal abnormalities in utero.

Face↗

Impact loading on the foot and ankle and its attenuation during level walking.

We studied impact loading on the foot and ankle at heel strike during level walking. Cadaveric testing was carried out on a skin-mounted accelerometer to estimate the bone or joint impact, and gait analysis was performed to evaluate the impact on the foot and ankle and its attenuation during level walking. Simulation using a rigid-body model estimated the impulse at landing during level walking. The skin-mounted accelerometer showed the same tendency as the bone-mounted accelerometer in cadaveric testing. In the gait analysis, impact at the calcaneus was attenuated at the medial malleolus and was less attenuated with the ankle fixation. In the simulation, impact became greater if the foot and ankle functions were eliminated. These results suggest that the foot and ankle are directly involved in attenuating the impact at heel strike during level walking.

Acceleration↗

Effect of regular aerobic exercise on cerebrovascular tone in young women.

Our objective was to evaluate the effect of regular aerobic exercise on cerebrovascular tone in young women. Color and pulsed Doppler ultrasonography were used to determine the pulsatility index in the ophthalmic artery in 20 normotensive, nonpregnant young women (aged 19 to 26 years) with a regular menstrual cycle on cycle day 5. Blood pressure and heart rate were recorded at each examination. Blood samples were collected from all the subjects to measure serum estradiol levels and serum lipid profiles. Ten of the 20 women (exercise group) have maintained aerobic exercise for 50 min, 3 to 5 days a week, for at least a year. The other 10 women (nonexercise group) never did regular exercise. There were no significant differences between the two groups regarding age, body mass index, mean blood pressure, and heart rate and serum estradiol, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels. The pulsatility index value (mean, 1.89; standard deviation, 0.33) of the ophthalmic artery in the exercise group was significantly lower than that (mean, 2.53; standard deviation, 0.26) in the nonexercise group. Regular aerobic exercise in young women significantly decreases the peripheral cerebrovascular tone, and this might be a favorable adaptation for early prevention of cerebrovascular disease, which is common in older women.

Adaptation, Physiological↗

Inhibitory effect of matrilysin antisense oligonucleotides on human colon cancer cell invasion in vitro.

In colorectal cancer, matrilysin (matrix metalloproteinase-7) is mainly produced by the tumor cells themselves and is thought to play an important role in tumor invasion and metastasis. In the study reported here, we examined the effects of matrilysin antisense phosphorothioate oligonucleotides on both the expression of matrilysin and the invasive potential of the human colon cancer cell line CaR-1 in vitro. To select the most specific and potent oligonucleotide sequence, we performed extensive analyses of the binding specificities of all antisense candidates in the GenBank database by using a computer program we developed. As a result, a 15-mer matrilysin-specific antisense oligonucleotide that hybridizes to the coding region of matrilysin mRNA (AS-1) and a random control oligonucleotide (CL-1) were designed. Reverse transcription-polymerase chain reaction and western blot analysis demonstrated that 10 microM AS-1 suppressed matrilysin expression at both the mRNA level (92%) and protein level (64%). In vitro invasion assays demonstrated that this same concentration of AS-1 inhibited the ability of cells to invade a reconstituted basement membrane by 50% as compared with the ability of untreated cells to do so. On the other hand, CL-1, which had the same length and GC content as AS-1, did not show any inhibitory effect. These results demonstrate that the antisense oligonucleotide AS-1 inhibits matrilysin activities in a sequence-specific manner and suggest that AS-1 has the potential to be used as an anti-metastatic agent in an in vivo experimental model of colon cancer.

Antineoplastic Agents↗

Evaluation of thrombopoiesis in thrombocytopenic disorders by simultaneous measurement of reticulated platelets of whole blood and serum thrombopoietin concentrations.

To evaluate thrombopoiesis in thrombocytopenic disorders, we simultaneously determined reticulated platelet counts in whole blood by FACScan flow cytometry and serum thrombopoietin (TPO) concentrations by a sensitive sandwich ELISA. The subjects were 40 healthy volunteers and 45 thrombocytopenic patients. In idiopathic thrombocytopenic purpura (ITP), the percentage of reticulated platelets was significantly elevated (5.61 +/- 2.02%: mean +/- SD) relative to normal controls (2.17 +/- 0.90%), but serum TPO concentrations (1.91 +/- 1.27 fmol/l) did not differ significantly from the normal range (1.43 +/- 0.62 fmol/l). The patients with aplastic anemia (AA) had decreased reticulated platelet counts and markedly increased serum TPO concentrations (13.65 +/- 10.64 fmol/l). In thrombocytopenic patients with liver cirrhosis (LC), the absolute number of reticulated platelets (1.65 +/- 1.11 x 10(9)/l) decreased similarly that in AA. However, serum TPO concentrations (1.38 +/- 0.50 fmol/l) did not increase in contrast to AA. Our findings suggested a possible dual mechanism of thrombocytopenia in LC; that is, thrombocytopenia in LC results from the decreased TPO production primarily in the liver adding to an increase in platelet sequestration in the spleen.

Anemia, Aplastic↗