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Biomedical subjects

R Mizuno

Publications and source records attributed to R Mizuno.

At least 19 recordsLinked to original sources

The male/female ratio of fetal deaths and births in Japan.

The decline in the male/female ratio of births has not yet been explained. In Japan, the male/female ratio of fetal deaths has been increasing since the 1970s, reaching over 2.0 in 1996. The increased male/female ratio of births could explain the decrease In the male/female ratio of births during the past two decades. This trend could suggest the increasing prenatal vulnerability of the male fetus especially at earlier stages of gestation.

Abortion, Spontaneous↗

Inhibitory effect of TNP-470 on hepatic metastasis of mouse neuroblastoma.

PURPOSE: TNP-470 is a strong inhibitor of angiogenesis. The present study was designed to determine whether the angiogenesis inhibitor TNP-470 inhibits metastasis of mouse neuroblastoma cells to the liver and thus increases survival. METHODS: A murine neuroblastoma cell line, C1300, and A/J mice were used in this study. First, to demonstrate the inhibitory effects of TNP-470 on angiogenesis, we quantified the area of angiogenesis on images made with SP-500 image analyzer (Olympus) 7 days after implanting a millipore chamber and compared the areas for the TNP-470-treated mice and control mice. Next, to determine the inhibitory effect of TNP-470 on metastasis of neuroblastoma cells to the liver, we made a murine hepatic metastasis model by implanting C1300 cells (1 x 10(6)) in the spleen of the mice and compared histologic findings, sizes, and weights of the livers of treated mice and control mice 14 days after the beginning of a 7-day infusion of TNP-470 (60 mg/kg). We also compared survival rates using the Kaplan-Meier method. RESULTS: When the angiogenesis inhibitor TNP-470 was infused into mice that received tumor cells, the area of angiogenesis in the TNP-470-treated mice was smaller than that in the control mice (52.5 +/- 6.3 SD vs 94.1 +/- 27.6 mm(2), P < 0.001). After the same treatment in other mice, no histologic evidence of metastasis was found, whereas control mice had countless tumor cell masses. Similarly, the weight of the liver was less in TNP-470-treated mice (0.8 +/- 0.1 g vs 4.5 +/- 0.3 g, P < 0.001). Survival was longer in the TNP-470-treated mice than in controls (80% of treated mice were alive more than 60 days after treatment, whereas all control mice died by Day 20). CONCLUSION: TNP-470 inhibits metastasis of mouse C1300 neuroblastoma cells to the liver, and thus increases survival. TNP-470 inhibits metastasis by inhibiting angiogenesis.

Angiogenesis Inhibitors↗

Reduced early diastolic inflow velocities in the antero-posterior transverse direction in the left ventricle of patients with dilated cardiomyopathy.

UNLABELLED: In patients with dilated cardiomyopathy (DCM), the left ventricular (LV) inflow jet is narrow and has a high pressure gradient. A pulsed Doppler restrictive transmitral flow pattern is a characteristic feature of severe left ventricular disease. However, Doppler flow analysis is limited by the angle between the blood flow jet and the ultrasonic beam. In this study we used gated magnetic resonance imaging (MRI) to investigate the inflow velocity in the LV transverse directions during early diastole in patients with DCM. METHODS: We studied 10 patients with DCM (mean age: 47 y). Ten age-matched healthy volunteers were also examined. Gradient echo images of the LV were obtained. Left ventricular short axis phase contrast images were obtained at the level of the mitral valve tip and 1 cm inside the LV. Long axis images were also obtained. Through-plane peak velocities at peak early diastolic filling were measured along the LV long axis, antero-posterior short axis, and right-left short axis. Blood velocity was measured in 50 ms blocks. RESULTS: Early diastolic inflow velocity along the long axis, especially at the center of the LV, was well preserved in DCM. However, the inflow velocity in the antero-posterior transverse direction of the LV (i.e., in the direction of mitral valve excursion) was significantly reduced in DCM. CONCLUSIONS: Early diastolic inflow velocity in the antero-posterior transverse direction of the LV is reduced in patients with DCM indicating that the vector component of the forces acting in the antero-posterior transverse direction of the LV may be decreased in patients with DCM during early diastolic filling.

Adult↗

Catastrophic antiphospholipid antibody syndrome in systemic lupus erythematosus: an autopsy case report of a young woman.

Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of antiphospholipid syndrome (APS) characterized by disseminated microangiopathy that results in multiorgan failure. CAPS mainly occurs in association with systemic lupus erythematosus (SLE). Clinically, CAPS mimics disseminated SLE vasculitis, intravascular coagulation (DIC), and particularly thrombotic thrombocytopenic purpura (TTP). We describe an autopsy case of young woman with CAPS in SLE, which is difficult to differentiate from TTP secondary to SLE.

Adult↗

Development of an experimental apparatus for investigating lymphatic pumping activity of murine mesentery in vivo.

The present study has been attempted to establish a modified intravital microscope system for investigating murine lymphatic pumping activity in vivo and evaluate whether or not there is rhythmic pumping activity of murine mesenteric lymphatic vessels in vivo. We designed and constructed a custom organ chamber with a semicircular channel (8 mm in radius, 5 mm in width, 3 mm in depth), being suitable for the superfusing of murine mesentery in vivo. A marked lymphatic pumping activity was observed in the mesenteries of DDY mice. The maximal and minimal diameter and frequency in the pumping activity were 60.9 +/- 1.0 microm, 53.7 +/- 1.8 microm and 12.8 min(-1) (n = 5), respectively. Both NE (norepinephrine, 10(-8)-10(-6) M) and TEA (tetraethylammonium, 1-10 mM) caused dose-dependent constriction of the mesenteric lymphatic vessels in the mice. These findings suggest that a modified intravital microscope system with a specially designed and constructed edge-monitoring device enables us to investigate in vivo lymphatic circulation in murine mesenteries.

Animals↗

Effects of VEGF on Ca(2+)-transient in cultured lymphatic endothelial cells and mechanical activity of isolated lymph vessels.

We investigated the effects of vascular endothelial growth factor (VEGF(165)) on [Ca(2+)](i)-transient in cultured lymphatic endothelial cells (LEC) and mechanical activity of isolated dog thoracic ducts. VEGF (0.1-10 ng/ml) caused a dose-dependent increase of the [Ca(2+)](i) in LEC. Pretreatment with 10(-5) M genistein or 5x10(-6) M herbimycin A produced a significant reduction of the VEGF-induced [Ca(2+)](i)-transient. In the presence of 10(-6) M thapsigargin, VEGF caused no significant effect on the [Ca(2+)](i)-transient. Pretreatment with Ca(2+)-free solution containing 0.1 mM EGTA produced no significant effect on the peak increase of [Ca(2+)](i) induced by 0.1 or 10 ng/ml VEGF, but significantly depressed the sustained part of [Ca(2+)](i) observed at the higher concentration of VEGF. The VEGF (0.1-10 ng/ml) caused a significant dilation of the isolated lymph vessels with intact endothelium, which were precontracted with U46,619. The 10 ng/ml VEGF-induced dilation was significantly reduced by 3 x 10(-5) M N(omega)-nitro-L-arginine methyl ester (L-NAME). The action of L-NAME was inhibited by the simultaneous application of 10(-3) M L-arginine. Mechanical rubbing of the endothelium also caused significant inhibition of the VEGF-induced dilation. The findings suggest that VEGF(165) may activate the receptor-related tyrosine kinase and cause the release of Ca(2+) from the inositol 1,4, 5-triphosphate-sensitive intracellular Ca(2+) stores in LEC. VEGF(165) also produces endothelium-dependent nitric oxide-mediated dilation of the precontracted isolated lymph vessels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Spontaneous rupture of splenic hamartoma: a case report.

Splenic hamartomas are rare. The authors report a case of spontaneously ruptured splenic hamartoma in a 5-month-old boy. This rupture led to the death of the child. If abdominal pain is present and a mass is palpated, the splenic hamartoma should be managed surgically in an expeditious manner. There have been only two known previous reports of spontaneous rupture of splenic hamartoma in adults, but none in children.

Hamartoma↗

Ultrasonic tissue characterization in patients with dilated cardiomyopathy: comparison with findings from right ventricular endomyocardial biopsy.

AIM: The clinical usefulness of integrated backscatter (IB) imaging was compared with right ventricular endomyocardial biopsy for assessing myocardial damage in patients with dilated cardiomyopathy (DCM). METHODS: We examined 15 patients with DCM and 20 healthy controls. In addition to the conventional M-mode echocardiographic parameters, we determined the cyclic variation in IB values (CV-IB) obtained from parasternal short axis views of the left ventricle just under the transducer for both the interventricular septum (IVS) and the left ventricular posterior wall (PW). The per cent fibrosis area (%) and the transverse diameter of myocytes (microm) were measured in right ventricular endomyocardial biopsy specimens by computer image analysis. To analyze the relationship between pathological findings and CV-IB, we divided patients into four subgroups on the basis of the pathological characteristics of endomyocardial biopsy specimens as follows: degeneration dominant group (n = 5), fibrosis dominant group (n = 5), dilated phase hypertrophic cardiomyopathy (n = 2), and mixed type (n = 3). RESULTS: CV-IB in the IVS and the PW was lower in patients with DCM (8.8 +/- 2.9, 8.3 +/- 2.7 dB, respectively) than in normal subjects (14.4 +/- 2.9, 13.6 +/- 2.6 dB, respectively). Biopsy findings showed a mean per cent fibrosis area of 24.0 +/- 12.3%, and a mean myocyte diameter of 14.3 +/- 2.9 microm in patients with DCM. CV-IB was correlated with both of these findings: per cent fibrosis area (r = -0.56 in IVS, r = -0.56 in PW) and myocyte diameter (r = 0.67 in IVS, r = 0.71 in PW). CV-IB was decreased in all DCM subgroups compared with normal subjects, but there was no significant difference between subgroups. CONCLUSIONS: CV-IB was correlated with both the extent of fibrosis in myocardial tissue and the myocyte diameter. These findings suggest that ultrasonic tissue characterization is a good indicator of the severity of fibrosis and myocyte atrophy in patients with DCM.

Biopsy↗

Involvement of ATP-sensitive K(+) channels in spontaneous activity of isolated lymph microvessels in rats.

Physiological roles of ATP-sensitive K(+) channels for spontaneous activity in isolated rat mesenteric lymph microvessels (maximum diameter approximately 80-150 microm) were investigated. The lymph microvessels were cannulated with glass micropipettes and pressurized at a perfusion pressure of 6 cmH(2)O. Changes in the diameter and frequency of spontaneous contractions in the lymphatics were measured with videomicroscopy. Pinacidil (K(+)-channel opener) inhibited the spontaneous activity. In the presence of glibenclamide (selective ATP-sensitive K(+)-channel blocker; 10(-7) and 10(-6) M) and tetraethylammonium (TEA; nonselective K(+)-channel blocker; 10(-4) and 10(-3) M), the pinacidil-induced inhibition of the spontaneous contractions in lymph microvessels was significantly reversed. Glibenclamide and TEA themselves, however, did not affect the frequency of spontaneous activity in the lymph microvessels. These results suggest that ATP-sensitive K(+) channels are involved in the regulation of spontaneous activity in the smooth muscles of isolated lymph microvessels of rat mesenteries.

Adenosine Triphosphate↗

Flow reduces the amplitude and increases the frequency of lymphatic vasomotion: role of endothelial prostanoids.

Fluid dynamic forces have substantial effects on the movement of lymph and activity of lymph vessels. The effect of increases in intraluminal flow on spontaneous pumping activity of isolated collecting lymphatics has not yet been characterized in a condition in which the intraluminal pressure is constant. Thus, in afferent lymph microvessels isolated from rat iliac lymph nodes, changes in maximum (Dmax) and minimum (Dmin) diameter to increases in perfusate flow were investigated in the presence of a constant perfusion pressure of 6 cmH2O. Intraluminal flow was elicited by increases in the difference between outflow and inflow pressures (Pdiff, from 0 to 6 cmH2O). Diameters were measured by videomicroscopy. In response to increases in perfusate flow, Dmax and Dmin of lymphatics decreased from 157.5 +/- 6.1 to 90.9 +/- 5.6 micron and from 91.9 +/- 5.3 to 66.3 +/- 3.6 micron, respectively, whereas vasomotion frequency increased from 18.0 +/- 0.7 min(-1) to 23.4 +/- 1.1 min(-1) (at Pdiff of 4 cmH2O). Removal of extracellular Ca2+ abolished spontaneous diameter oscillations; under these conditions the passive diameter of lymphatics was 216.0 +/- 7.1 micron and did not change in response to increases in perfusion. In the absence of endothelium, flow-induced changes in Dmax, Dmin, and oscillation frequency were eliminated. Nomega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, did not affect flow-induced changes in diameter of lymphatics. In contrast, indomethacin, an inhibitor of prostaglandin synthesis, or SQ-29,548, a PGH2/thromboxane A2 (PGH2/TxA2) receptor blocker, inhibited the perfusion-induced reduction of Dmax and Dmin of lymphatics and also the increase in the frequency of vasomotion. These findings suggest that the sensitivity of lymphatic endothelium to increases in intraluminal flow could provide an important local intrinsic mechanism for the control of lymphatic resistance by release of constrictor prostanoids PGH2/TxA2.

Animals↗

Atrial involvement in patients with progressive systemic sclerosis: relationship between ultrasonic tissue characterization of the atrium and interatrial conduction.

OBJECTIVE: The aim of this study was to assess atrial lesions using ultrasonic tissue characterization and to determine the contribution of atrial lesions to the interatrial electromechanical coupling conduction time in patients with progressive systemic sclerosis (PSS). METHODS: Twenty patients with PSS and 20 age-matched healthy controls were evaluated. The cyclic variation in integrated backscatter value (CV-IB) was measured at the interatrial septum (IAS) from apical four chamber view. M-modes of ventricular long axis motion along with phono- and electrocardiograms were recorded simultaneously at the right lateral (RT) and left lateral (LT) sites of the atrioventricular (AV) rings and central fibrous body (CFB) in the apical four-chamber view. Intervals from the P wave on ECG to the echocardiographic onset of atrial contraction as a point of inflection in long axis M-mode echocardiogram were measured at the RT and LT sites of AV rings and CFB (P-RT, P-LT, P-SEP, respectively). Interatrial electromechanical coupling conduction time was determined as [(P-LT) - (P-RT)]. RESULTS: In patients with PSS compared to normal controls, P-RT, P-SEP, P-LT, and interatrial conduction time were greater, while CV-IB in IAS decreased. Furthermore, CV-IB in IAS correlated well with interatrial conduction time (r = 0.7, p < 0.01) in patients with PSS. CONCLUSIONS: Interatrial electromechanical coupling times may be prolonged due to atrial tissue damage in patients with PSS.

Adult↗

Infant temperament and child-rearing stress: birth order influences.

The relationship between an infant's temperamental difficulty and the mother's child-rearing stress was investigated in a sample of 128 children. Children's temperament was assessed by the Revised Infant Temperament Questionnaire (RITQ) at 6-7 months, and by the Toddler Temperament Scale (TTS) at 18 months. The mothers' child-rearing stress was assessed by a self-report questionnaire. At the children's age of 18 months, mothers of difficult children reported higher child-rearing stress than mothers of easy children. Although difference in the level of child-rearing stress reflecting birth order was not evident at either 6-7 months or 18 months, the proportion of child-rearing stress which could be explained by the children's temperament was highest for mothers of first-borns when their children were 18 months old.

Birth Order↗

[A resected case of malignant peripheral nerve sheath tumor (MPNST) necessary to distinguish from Askin tumor].

We have treated a patient with malignant peripheral nerve sheath tumor (MPNST) for 7 years by interdisciplinary therapy. The diagnosis and treatment are reported with the clinical course so far. A 20-year-old man underwent surgical resection of a tumor on the left side of the chest in 1990, and a diagnosis of Askin tumor was made. In 1993, the disease recurred in the left axilla and was surgically resected. The surgical specimen was investigated histologically, and a diagnosis of MPNST was made instead of Askin tumor. Recently, a tumor began to grow in the left pleural cavity and was surgical resected. The tumor tissue contained both cells with oval and long spindle nuclei, which were intermingled with each other. Immunohistochemically, the tumor cells were positive for vimentin and some of them were positive for S100 protein. Because electron microscopy showed cytoplasmic processes on the tumor cell and basal lamina-like structures, a diagnosis of recurrent MPNST was made. Because this lesion resembled Askin tumor in its clinical manifestations and histological characteristics, differential diagnosis from Askin tumor was necessary. When a malignant soft tissue tumor arising from the mediastinum or chest walls is detected, immunohistochemical and electron microscopic studies should be performed. The diagnosis should be based on the overall findings including the location and clinical data.

Adult↗

Magnetic resonance velocity mapping of transtricuspid velocity profiles in dilated cardiomyopathy.

To investigate the velocity profiles and jet sizes of transtricuspid inflow by magnetic resonance imaging (MRI), we examined seven dilated cardiomyopathy (DCM) patients (mean age 37 +/- 15 years) and 20 normal subjects (mean age 32 +/- 7 years). We used a Siemens Magnetom Impact Expert (1.0 T) together with a surface receiver coil. Electrocardiographic gating, triggered by the R wave, was performed. Cine gradient echo images were obtained in the short axis of the right ventricle. Velocity mapping of right ventricular inflow was obtained at peak early diastolic filling. Velocity profile curves across the tricuspid inflow were obtained at 1-cm intervals from the tricuspid ring up to 3 cm into the cavity. Maximum/mean velocities in both groups were 1.1 +/- 0.1 at the ring level, unchanged at 1 cm from the tricuspid ring, and thereafter increased to 1.4 +/- 0.3 at 2 cm and 1.5 +/- 0.3 at 3 cm as peak velocity fell. Jet cross-sectional area was 10.4 +/- 2.1 cm2 at the ring level, and was unchanged at the 3-cm level in the normal subjects. However, in patients with DCM it was smaller than that in normals, and decreased in proportion to the distance from the tricuspid ring. Thus, tricuspid inflow velocity showed a relatively flat profile at the tricuspid ring and tip levels, becoming more dispersed at 2 and 3 cm from the ring. The cross-sectional area of the right ventricular inflow jet in the DCM patients was small and decreased in proportion to the distance from the tricuspid ring, although it appeared to be relatively constant in normal subjects.

Adult↗

Contribution of long axis motion of left ventricular outflow to calculation of left ventricular stroke volume.

Stroke volume can be calculated by using noninvasive Doppler techniques. The products of pulsed Doppler stroke distance of left ventricular outflow and left ventricular outflow area can often be used to calculate stroke volume. However, left ventricular outflow also moves longitudinally toward the apex of the ventricle during systole, so that zero velocity flow cannot be detected by the usual pulsed Doppler studies. We evaluated the contribution of these zero velocity flow to the noninvasive estimation of left ventricular stroke volume in 20 patients with left ventricular disease and in 20 age matched healthy controls. Left ventricular stroke distance was calculated by summing the Doppler stroke distance and the outflow long axis motion. The percentage of zero velocity flow for total stroke volume was calculated in each group. Cardiac output was also measured by thermo-dilution technique. The percentage of zero velocity flow for total noninvasive stroke volume in patients with left ventricular disease was 2.5 +/- 1.1 ml (4.0 +/- 1.5%), significantly lower than in normal subjects, 3.6 +/- 1.0 ml (5.5 +/- 1.5%) (p < 0.05). These long axis motions are significantly reduced, especially in left ventricular disease. Amplitudes of the left ventricular outflow long axis motion were correlated with Doppler stroke distance in all (r = 0.54, p < 0.01). In patients with myocardial infarction, stroke volume by thermo-dilution methods and calculated stroke volume showed good correlation both only by Doppler stroke distance (y = 1.044x + 0.547, r = 0.968) and by Doppler and long axis motion (y = 0.989x + 0.521, r = 0.974). Compared with stroke volume measured by thermodilution method, stroke volume calculated only by Doppler stroke distance was underestimated. We thus demonstrated the influence of zero velocity flow on left ventricular outflow both in patients with left ventricular disease and in normal subjects.

Adult↗