Search PubMed⌕ Search

Biomedical subjects

K Miyazaki

Publications and source records attributed to K Miyazaki.

At least 235 records · Page 13Linked to original sources

Gianturco stents for the venous system: a detailed pathological study.

This study was designed to examine the short-term performance of Gianturco stents placed in the venous system, in comparison with that of stents placed in the arterial system. Single-bodied modified Gianturco stents were surgically placed in six dogs (group 1), while in another six dogs, only exposure of the vessels was performed (group 2). Segments with an outer diameter 0.9 times smaller than those of the stents were targeted in the infrarenal inferior vena cava (IVC), the portal vein (PV), and the infrarenal abdominal aorta (AA). The animals were killed 4 weeks postoperatively for pathological analysis. All the segments were patent in both groups. Although the stents placed in the infrarenal IVC and PV were completely covered with neointima, those placed in the infrarenal AA were only partially covered. Furthermore, the venous stents were deeply embedded in the media, while the aortic stents remained in the intima. Medial hyperplasia occurred in the venous stents, while intimal hyperplasia occurred in the aortic stents. In conclusion, Gianturco stents placed in the IVC and PV performed better in the short term than the stents placed in the AA.

Animals↗

Expression of trypsin by epithelial cells of various tissues, leukocytes, and neurons in human and mouse.

It has long been believed that trypsin is normally synthesized only in the pancreas. In the present study, expression of trypsin in human and mouse nonpancreatic tissues was examined. Northern blot analysis of normal human tissues indicated that the trypsin gene is expressed at high levels in the pancreas and spleen and considerably in the small intestine. However, in situ hybridization and immunohistochemistry demonstrated that trypsin is widely expressed in epithelial cells of the skin, esophagus, stomach, small intestine, lung, kidney, liver, and extrahepatic bile duct, as well as splenic and neuronal cells. In the spleen, trypsin message was detected in macrophages, monocytes, and lymphocytes in the white pulp. In the brain, it was detected in the nerve cells of the hippocampus and cerebral cortex. Analysis by gelatin zymography confirmed the presence of a latent or an active form of trypsin in various normal mouse tissues. Reverse transcription-polymerase chain reaction analysis also confirmed the expression of trypsin genes in the spleen, liver, kidney, and brain of normal mice. Such a broad distribution of trypsin suggests its general roles in the maintenance of normal epithelial cell functions, the immune defense system, and the central nervous system.

Animals↗

Thymidine phosphorylase activity and prodrug effects in a three-dimensional model of angiogenesis: implications for the treatment of ovarian cancer.

Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is associated with angiogenesis and the progression of human ovarian cancer. The enzyme converts thymidine to thymine and 2'-deoxyribose-1-phosphate and can also metabolize the prodrug 5'-deoxy-5-fluorouridine (Furtulon) to 5-fluorouracil and 5'-deoxy-D-ribose-1-phosphate. The aim of this study was to obtain information about the activities of Furtulon in an established three-dimensional model of angiogenesis. The plan was to study partial and complete effects of Furtulon (in the absence and presence of PD-ECGF/TP or ovarian cancer cyst fluids) on the formation and destruction of microvessels from cultured segments of rat aorta in serum-free media. The endpoint was the number and form of microvessels compared with controls after 4, 7, 11, and 14 (and sometimes 17) days in culture. Furtulon (10 micromol/L) gradually reduced the size and number of microvessels over 17 days of culture (100 micromol/L significantly reduced the number by day 4). PD-ECGF/TP (10 ng/ml) and ovarian cancer cyst fluids (2% in medium, v/v) stimulated the production of microvessels. The culture of explants with Furtulon and PD-ECGF/TP or ovarian cancer cyst fluids (from day 1 or day 11 of culture) enhanced the vasoclastic activity of the drug. The effect of Furtulon at the highest dose (1000 micromol/L) or at a lower dose (100 micromol/L) in the presence of ovarian cancer cyst fluid was not reversible after culture day 11.

Adult↗

Three-dimensional ultrasonographic assessments of fetal development.

OBJECTIVE: To visualize fetal surface anatomic structures in advancing gestation by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. METHODS: One hundred six normal fetuses from 9 to 40 weeks' 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 also can generate within seconds high-quality three-dimensional images in the surface and transparent modes with no need for an external workstation. We determined percentage of surface anatomic structures visualized at each trimester using two-dimensional and three-dimensional ultrasonography. RESULTS: The number and the clarity of surface anatomic structures increased from the first to the third trimester of pregnancy. The image quality was less distinct in the first trimester because of the small fetal size. The ability to view the fetal face, hands, and feet was better with three-dimensional ultrasonography than with two-dimensional ultrasonography in the first trimester (P < .05), whereas fetal genitals were viewed better with two-dimensional ultrasonography than with three-dimensional ultrasonography in the second and third trimesters (P < .05). CONCLUSION: Three-dimensional ultrasonography provides a new means of visualizing surface anatomic structures of the fetus in utero. Our results suggest that three-dimensional ultrasonography has the potential to be a supplement to two-dimensional ultrasonography and should be useful in evaluating fetal abnormalities in high-risk pregnancies.

Embryonic and Fetal Development↗

Production of trypsins by human gastric cancer cells correlates with their malignant phenotype.

Proteolytic degradation of extracellular matrix is a critical step in tumour invasion and metastasis. To examine the role of trypsin in tumour dissemination, we cloned two variants (S4 and R3 cells) from STKM-1, a trypsinogen 1-producing diffuse gastric cancer cell line. Western blot analysis with antitrypsin antibody showed that 26 and 24 kDa proteins were highly detected in S4 conditioned medium (CM) in comparison to R3 CM. In addition to the 26 and 24 kDa proteins, 25 and 23 kDa bands, which correspond to enterokinase-activated trypsin, were found only in S4 CM. When the CMs of the two clones were treated with enterokinase, the 25 and 23 kDa trypsin activities in S4 CM were effectively increased as compared with R3 CM. When the two clones were inoculated intraperitoneally (i.p.) into nude mice, S4 cells strongly invaded the liver, pancreas and peritoneum and killed the hosts more rapidly than R3 cells: the 50% survival time was 50 days for S4 and 82 days for R3 cells. These results suggest that trypsin production is associated with the invasive growth of STKM-1 gastric cancer cells.

Animals↗

A general approach for the prediction of the intestinal absorption of drugs: regression analysis using the physicochemical properties and drug-membrane electrostatic interaction.

A general method for predicting the intestinal absorption of a wide range of drugs using multiple regression analysis of their physicochemical properties and the drug-membrane electrostatic interaction was developed. The absorption rates of tested drugs from rat jejunum were measured by the in situ single-pass perfusion technique. The drugs used in this study were divided into three groups for regression analysis, and a smaller "test" set of compounds was used to assess the predictive capacity of the regression equation. When the analysis was applied to each respective group of drugs (i.e., anionic, cationic, and nonionized compounds), obtained regression coefficients were 0.569, 0.821, 0.728 by using the organic solvent (n-octanol)/buffer partition coefficient, 0.730, 0.734, 0.914 using the permeation rate across a silicon membrane, and 0.790, 0.915, 0.941 using an EVA membrane, respectively. However, smaller regression coefficients of 0.377, 0. 468, and 0.718 were obtained when these three groups of drugs were put together for prediction. Meanwhile, correlation was improved remarkably when drug-membrane electrostatic interactions, namely, hydrogen-bonding donor (Halpha) and acceptor (Hbeta) activity or index of electricity (Ec), were added to the other parameters of lipophilicity and permeation rate across the EVA membrane (r = 0.880 and 0.883, respectively). Moreover, the equation obtained from these regression analyses was applicable even to the prediction of the absorption of the zwitterionic drugs. These results suggest that including the electrostatic interaction parameters in addition to lipophilicity and permeability across artificial membranes would afford a better prediction for the intestinal absorption of the vast majority of drugs.

Animals↗

Stimulation of cellular growth and adhesion to fibronectin and vitronectin in culture and tumorigenicity in nude mice by overexpression of trypsinogen in human gastric cancer cells.

It has previously been reported that the trypsinogen gene is expressed in various human cancers. To investigate the possible role of trypsin in tumor malignancy, trypsinogen-1 cDNA was introduced into the human gastric carcinoma cell line MKN-1. The overexpression of trypsinogen-1 in MKN-1 cells stimulated cellular growth and adhesion to fibronectin and vitronectin when the trypsinogen activator enterokinase was added into the culture. Enterokinase treatment of the conditioned medium of the MKN-1 transfectants partially converted the proforms of gelatinases B and A to their apparent active forms. When the MKN-1 transfectants expressing trypsinogen-1 were intraperitoneally transplanted into nude mice, the mice frequently produced tumors in the colon, spleen and liver. However, the mice implanted with control MKN-1 cells produced no tumors. These results strongly suggest that tumor-derived trypsin contributes to the disseminated growth of some types of cancer cells including gastric cancer.

Adenocarcinoma↗

Elevated serum level of thioredoxin in patients with hepatocellular carcinoma.

Thioredoxin (TRX) is known to contain an active site with a redox-active disulfide and has various biological activities. The objective of the present study was to investigate whether circulating TRX levels are elevated in patients with chronic hepatitis (CH) or liver cirrhosis (LC) and hepatocellular carcinoma (HCC). An anti-TRX monoclonal antibody and polyclonal antibodies that specifically recognize TRX, were generated and used for the development of an ELISA system to measure TRX levels in human serum. The geometric mean and its 95% confidence interval of serum level of TRX in healthy volunteers was 81.75 ng/ml (74.60-89.59 ng/ml). The serum level of TRX in LC/CH patients without HCC was 80.87 ng/ml (69.66-93.88 ng/ml). The value was not statistically different from that in serum from normal volunteers (p=0.69). In contrast, the serum level of TRX in patients with HCC was 147.35 ng/ml (125.53-172.96 ng/ml), which was significantly higher when compared with the level in serum of normal volunteers (p<0.001) and in serum of LC/CH patients without HCC (p<0.001). In four patients with HCC, the initially high level of serum TRX (>150 ng/ml) decreased below 150 ng/ml after surgical removal of the tumor. The data reported herein revealed that patients with HCC had a significantly elevated serum level of TRX, suggesting that measurement of serum of TRX might be a useful clinical parameter when HCC is suspected.

Adult↗

Transforming growth factor beta1 (TGF-beta1) is a preoperative prognostic indicator in advanced gastric carcinoma.

It has been generally accepted that transforming growth factor beta1 (TGF-beta1) has both negative and positive effects on tumour growth and progression. This study analysed the prognostic value of TGF-beta1 mRNA in advanced gastric carcinoma. A reverse transcriptase-polymerase chain reaction analysis (RT-PCR) was used for TGF-beta1 in endoscopic biopsy specimens from 42 advanced gastric carcinomas. Thirty specimens expressed TGF-beta1 mRNA while 12 specimens did not. The follow-up duration ranged from 4 to 37 months (mean 22.8 months). TGF-beta1-positive group demonstrated a shorter overall survival compared with the TGF-beta1 -negative group (P=0.0014). A significant correlation was also found in the 32 patients who underwent curative resection (P=0.0048). Significant correlations were found between TGF-beta1 mRNA expression and both stage (P=0.0015) and nodal involvement (P=0.0060). Multivariate analysis demonstrated that only TGF-beta1 mRNA expression (P=0.0306) was an independent prognostic factor. All of ten patients who underwent non-curative resection expressed TGF-beta1 mRNA. Expression of TGF-beta1 mRNA in gastric biopsy specimens may be an important preoperative prognostic variable for advanced gastric carcinoma.

Aged↗

Inhibition of sea urchin fertilization by jaspisin, a specific inhibitor of matrix metalloendoproteinase.

Jaspisin, originally isolated from a marine sponge as an inhibitor of the hatching of the sea urchin (Hemicentrotus pulcherrimus) embryo, causes inhibition of sea urchin fertilization. Electron microscopic examination revealed that the acrosome reaction was induced in jaspisin-treated sperm when they were incubated with an intact egg. The acrosome-reacted sperm bound to the vitelline layer by the acrosomal material surrounding the acrosomal process. However, fusion of the acrosomal process and the egg plasma membrane failed to take place. Membrane potential changes were monitored using eggs preloaded with a membrane potential-sensitive fluorochrome, di-8-ANEPPS. Depolarization of the membrane potential, normally observed in the fertilized egg was not observed in the egg inseminated in the presence of jaspisin, indicating the absence of electrical continuity between the jaspisin-treated egg and sperm. Jaspisin inhibited the activities of matrix metallo-endoproteinase members but not of other types of proteinases. These results provide strong, albeit indirect, evidence that a matrix metallo-endoproteinase(s) is involved in the process of gamete fusion during sea urchin fertilization.

Acrosome↗

Maternal ophthalmic artery Doppler velocimetry in normotensive pregnancies with small-for-gestational-age infants.

Our purpose was to evaluate whether the maternal ophthalmic artery pulsatility index in normotensive pregnancies with small-for-gestational-age (SGA) fetuses is different from that in normotensive pregnancies with appropriate-for-gestational-age (AGA) fetuses. The cross-sectional study involved a group of normotensive pregnant women at > 34 weeks' gestation; 16 had fetuses that were AGA and 13 had fetuses that were SGA. Color and pulsed Doppler ultrasonography was performed in the ophthalmic arteries in each case and the pulsatility index and mean velocity were calculated. The heart rate and mean arterial blood pressure were also recorded. The pulsatility index of the ophthalmic artery (2.04 +/- 0.39) in normotensive pregnant women with SGA fetuses was significantly lower than that (2.87 +/- 0.64) in normotensive pregnant women with AGA fetuses (p < 0.05). The mean velocity (15.0 +/- 2.7 cm/s) in the women with SGA fetuses was significantly higher than that (10.2 +/- 2.7 cm/s) in the women with AGA fetuses (p < 0.05). There was no significant difference in maternal heart rate or mean arterial blood pressure between the groups. These results suggest that vascular resistance in the maternal orbital circulation is reduced in pregnancies that are normotensive but which are associated with SGA fetuses.

Adult↗

Expression of thymidine phosphorylase in malignant ovarian tumors: correlation with microvessel density and an ultrasound-derived index of angiogenesis.

OBJECTIVE: The aim of this study was to determine whether the expression of thymidine phosphorylase by ovarian cancer cells correlates with the density of microvessels within the tumor, and with ultrasound-derived indices of blood flow. METHODS: Transvaginal ultrasonography with color Doppler imaging and pulsed Doppler spectral analysis was used to scan patients with an overt ovarian mass immediately before laparotomy. Sections of malignant tumors were analyzed for the cellular expression of thymidine phosphorylase and the intratumoral density of microvessels by immunohistochemistry using monoclonal antibodies to thymidine phosphorylase and factor VIII-related antigen, respectively. The main outcome measures were the histological classification of the tumor, the stage of the disease, whether or not the tumor cells were positive or negative for thymidine phosphorylase, the microvessel count and the peak systolic velocity (PSV). RESULTS: Forty-two tumors were studied (three of low malignant potential, 29 epithelial, four granulosa cell, two germ cell and four metastatic); 18 were stage I, six stage II, 11 stage III and three stage IV. Twenty-seven tumors (64%) were classified as thymidine phosphorylase-positive. The proportion of stage I tumors that was thymidine phosphorylase-positive (44%) was significantly lower (p = 0.022) than the corresponding value for stages II-IV (85%), but the values for microvessel count and PSV were similar. The microvessel count in thymidine phosphorylase-positive tumors was significantly higher than in thymidine phosphorylase-negative tumors (p = 0.005). Similarly, the PSV was significantly higher in thymidine phosphorylase-positive tumors (p = 0.009). There was a significant correlation between the microvessel count and the PSV (r = 0.354, p = 0.022). CONCLUSIONS: The expression of thymidine phosphorylase by malignant tumor cells is associated with an increase in microvessel density and PSV in patients with ovarian cancer.

Adolescent↗

Three-dimensional ultrasonographic assessment of fetal hands and feet.

OBJECTIVE: The aim of this study was to describe fetal hands and feet using three-dimensional ultrasonography. DESIGN: This was a randomized prospective study. METHODS: Ninety-seven fetuses from 12 to 40 weeks' gestation were studied with a specially developed trans-abdominal three-dimensional transducer (3.5 MHz). The imaging system used in this study can provide conventional two-dimensional ultrasound images and can also generate, within seconds, high-quality three-dimensional images in the surface and transparent modes with no need for an external workstation. The rate of visualization of the hands/fingers and feet/toes at each gestational-age interval was calculated using two-dimensional and three-dimensional ultrasonography. RESULTS: The ability to visualize fetal hands/fingers and feet/toes was better with three-dimensional than with two-dimensional ultrasonography in the late first trimester (detection rates were 65% and 41% by three-dimensional ultrasonography for hands and feet, respectively, and 41% and 12%, respectively, by two-dimensional ultrasonography). For the early second trimester, detection rates were 82% for hands and 72% for feet by three-dimensional ultrasonography, and 54% for hands and 45% for feet by two-dimensional ultrasonography. Optimal visualization of the fetal fingers using three-dimensional ultrasonography was achieved between 28 and 35 weeks of gestation, although at this stage there were no significant differences in detection rates for hands and feet between two- and three-dimensional imaging. During this period it was possible with three-dimensional ultrasonography adequately to depict at least one hand in 93% of the fetuses at 28-31 weeks and in 88% at 32-35 weeks. The percentage of visualization of at least one fetal foot between 16 and 35 weeks using three-dimensional ultrasonography ranged from 50 to 85%. Before 15 weeks or after 36 weeks, the respective percentages decreased. CONCLUSIONS: Three-dimensional ultrasonography provides a novel means of visualizing fetal fingers and toes. Our observations suggest that three-dimensional ultrasonography may enhance the diagnostic potential of two-dimensional ultrasonography and might be useful in identifying fetal malformations and anatomical markers of chromosomal abnormalities prenatally in high-risk pregnancies.

Embryonic and Fetal Development↗

Expression of endothelial and inducible nitric oxide synthase in human glomerulonephritis.

The presence of nitric oxide (NO) in the kidney has been implicated in the pathogenesis of human glomerulonephritis. However, the exact type of glomerular cells that express NO synthase (NOS) and the NOS isoform involved in the local production of NO has not been identified in the human diseased kidney. We examined the expression of three isoforms of NOS, inducible NOS (iNOS), endothelial NOS (eNOS) and brain NOS (bNOS) in the renal tissue of patients with IgA nephropathy (IgAN, N = 10), lupus nephritis (LN, N = 5), membranous nephropathy (MN, N = 5) and minimal change nephrotic syndrome (MCNS, N = 5). Sections were immunostained and the correlation between the expression of each NOS and the degree of glomerular injury in that section was also examined. Normal portions of surgically resected kidneys served as controls. eNOS was present in glomerular endothelial cells and endothelium of cortical vessels in the control and diseased kidneys. iNOS was localized in mesangial cells, glomerular epithelial cells and infiltrating cells in the diseased glomeruli, whereas immunostaining for iNOS was hardly detected in control kidneys. In addition, the expression pattern of eNOS in each glomerulus was the reverse of that of iNOS. In IgAN and LN, the extent of staining for eNOS correlated negatively with the degree of glomerular injury, while the extent of staining for iNOS correlated positively with the degree of glomerular injury in the same tissues. bNOS was not detected in normal or nephritic glomeruli. Our results indicate the presence of a NO pathway in human diseased kidney, and suggest that NO derived from eNOS and iNOS may be involved in the progression of renal diseases and that NO derived from each NOS may play an important role in different way in human inflamed glomeruli.

Adult↗

Decreased maternal circulating hepatocyte growth factor (HGF) concentrations in pregnancies with small for gestational age infants.

Our purpose was to evaluate whether maternal and fetal hepatocyte growth factor (HGF) concentrations 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 HGF concentrations were compared between 55 pregnancies with AGA infants and 16 pregnancies with SGA infants at birth. HGF concentrations were measured from maternal and cord venous blood samples using an enzyme-linked immunosorbent assay. Umbilical artery blood pH and oxidative pressure (PO2) were also measured. Maternal circulating HGF concentrations (0.60+/-0.35 ng/ml) in pregnancies with SGA infants were significantly lower than those (0.91+/-0.44 ng/ml) in pregnancies with AGA infants (P = 0.012). There were no significant differences in fetal circulating HGF concentrations between both groups. No significant differences in umbilical artery blood pH and PO2 were found between both groups. These results suggest that the maternal serum circulating HGF concentration has a significant role in fetal growth during pregnancy.

Adult↗

Increased prevalence of luteinizing hormone beta-subunit variant in Japanese infertility patients.

To determine the frequency of a common luteinizing hormone variant in a Japanese population and to evaluate its significance in infertility, serum samples were collected from 169 healthy non-pregnant Japanese women, 105 healthy adult Japanese men and 97 female Japanese infertility patients. The luteinizing hormone variant includes two point mutations in the beta-subunit gene (Trp8 to Arg8 and Ile15 to Thr15). DNA from blood cells was studied in 10 healthy women, 10 men and five patients using polymerase chain reaction and direct sequencing. In immunoassays, results with a monoclonal antibody recognizing only the wild-type hormone and a polyclonal antibody recognizing the variant as well were compared as a ratio; ratios in heterozygotes and in individuals with only wild-type alleles ranged from 0.19 to 0.50 and from 0.56 to 1.21, respectively, and 0.50 was considered a 'cut-off' value for identifying individuals with the variant. For the larger subject groups, the frequency of the variant was 9.5% in normals. The mean ratio (0.80 +/- 0.35) in infertility patients was significantly lower (P < 0.01) than in healthy women (1.09 +/- 0.56), and the variant occurred more frequently in infertility patients (16.5%) than in healthy women (8.3%; P < 0.05). The variant was more frequent in patients with ovulatory disorders (43.8%) than other patients (16.0%; P < 0.05).

Adult↗

Three-dimensional intrauterine sonography in the early first-trimester of human pregnancy: preliminary study.

Our purpose was to visualize normal embryonal surface anatomic structures using three-dimensional (3D) intrauterine sonography with a 20 MHz flexible catheter-based high-resolution real-time miniature transducer in the early first trimester of pregnancy. A total of 15 women about to undergo therapeutic abortion at 7-9.9 weeks gestational age were studied by means of 3D intrauterine sonography with a specially developed catheter-based high-resolution real-time miniature (2.4 mm in outer diameter) ultrasound transducer (20 MHz). This imaging system can provide conventional 2D intrauterine sonographic images and can also generate within seconds high-quality 3D images in the surface and transparent mode. At week 8, prominent forehead was evident, and upper and lower limbs and midgut herniation were clearly depicted. At week 9, fingers and toes were depicted as small digital rays, and the sacral tail protruded caudally. The midline cranial ectodermal cleft was also identified. At week 10, embryonic face and fingers were clearly shown. 3D intrauterine sonography provides a novel means for visualizing of surface anatomic structures of the human embryo in utero. These results suggest that 3D intrauterine sonography can become an important modality in future embryological research and in detection of embryonic developmental disorders in the early first-trimester pregnancy.

Embryo, Mammalian↗