Search PubMed⌕ Search

Biomedical subjects

Y Tomoda

Publications and source records attributed to Y Tomoda.

At least 55 records · Page 3Linked to original sources

Levels of hepatocyte growth factor and its messenger ribonucleic acid in uncomplicated pregnancies and those complicated by preeclampsia.

The purpose of this study was to elucidate the possible relationship between hepatocyte growth factor (HGF) expression and the pathogenesis of preeclampsia. The concentration of immunoreactive HGF was measured and the expression of HGF messenger ribonucleic acid (mRNA) assessed in human placentas obtained from two groups: uncomplicated and preeclamptic pregnancies at various gestational weeks. In addition, the localization of HGF mRNA and c-met protein was analyzed using in situ hybridization and immunohistochemical staining, respectively. The expression of HGF mRNA and the concentration of immunoreactive HGF were highest in second trimester and were significantly decreased in preeclamptic placentas compared with the uncomplicated cases in third trimester. HGF mRNA was localized to placental mesenchymal cells, whereas c-met protein was demonstrated on cytotrophoblast. These results provide evidence of an abnormality of HGF expression in the preeclamptic placentas. Such placentas exhibit the abnormally shallow trophoblast invasion of the uterus, and reduced expression of HGF could well account for this morphometric change.

Blotting, Northern↗

Heart rate variability and ventricular arrhythmia in clinically stable patients with hypertrophic cardiomyopathy.

To investigate whether autonomic nervous dysfunction exists and to determine the relationship between autonomic nervous activity and ventricular arrhythmias in clinically stable patients with hypertrophic cardiomyopathy (HCM), we studied heart rate variability (HRV) in 21 patients with HCM and 10 age-matched healthy control subjects. Patients were divided into 2 groups: HCM I (14 patients without nonsustained ventricular tachycardia, defined as 3 or more consecutive ventricular premature beats) and HCM II (7 patients with nonsustained ventricular tachycardia). HRV was measured on 24-h ECG monitorings using both nonspectral and spectral methods (fast Fourier transform, FFT). We assessed autonomic nervous activity based on high-frequency (HF; 0.15-0.40 Hz, an index of parasympathetic nervous activity) and the low- to high-frequency power ratio (L/H ratio; an index of sympathetic nervous activity) during daytime and night-time separately. There were no significant differences in any index of HRV between the HCM I and control groups. HF in the HCM II group was significantly lower than that of both the HCM I and control groups during the day and at night, whereas the L/H ratio at night-time was significantly higher in the HCM II group than in the HCM I and control groups. These data demonstrate that, in clinically stable HCM patients without nonsustained ventricular tachycardia, autonomic nervous activity was not different to that of healthy control subjects, whereas in HCM patients with nonsustained ventricular tachycardia, parasympathetic nervous activity was reduced throughout the 24-h period, and sympathetic nervous activity at night was increased compared with healthy control subjects. Thus, HCM patients with nonsustained ventricular tachycardia have to be treated even if they do not exhibit significant clinical manifestation.

Adult↗

Expression of syndecan-1 and -3 during embryogenesis of the central nervous system in relation to binding with midkine.

Midkine (MK) is a 13-kDa heparin-binding growth/differentiation factor, and its interaction with heparan sulfate proteoglycan is important in promotion of neurite outgrowth. This study was performed to reveal the species of syndecans that interact with MK during embryogenesis of the central nervous system in the rat. Northern blot analysis and immunohistochemical staining using antibodies to syndecans showed that syndecan-1 was strongly expressed in the brain and spinal cord of the 10-day rat fetus, and the expression became weak as embryogenesis proceeded. On the other hand, syndecan-3 expression was stronger both in the brain and spinal cord in the later developmental period (day 14-16 of gestation). No significant expression of ryudocan (syndecan-4) was detected in fetal brains by Northern blot analysis. Syndecan-3 isolated from 16-day rat fetus bound to MK strongly, as did syndecan-1 isolated from 10-day rat fetus. Thus, both syndecan-1 and syndecan-3 were considered to be involved in interaction with MK during construction of the central nervous system; syndecan-1 is expected to play important roles in the earlier periods, and syndecan-3 in the later periods.

Animals↗

[Effects of physical training on autonomic nerve activity in patients with acute myocardial infarction].

The effects of early physical training on heart rate variability and autonomic nerve activity in acute myocardial infarction were studied in 20 patients (men, mean age 57 +/- 11 years) successfully treated by direct coronary angioplasty. Patients were randomly divided into the physical training group (training group: 10 patients) and conventional rehabilitation group (non-training group: 10 patients). Exercise tolerance (VO2 peak and anaerobic threshold: AT), heart rate variability indices, serum levels of catecholamines, and 24-hour urinary excretion of catecholamines were measured on the 14th and 28th days. The conventional cardiac rehabilitation program was followed by each group, and the training group patients were also instructed to follow a training program using the bicycle ergometer (80% AT, 10 min, 2 times a day) for 2 weeks from the 15th day. Autonomic nerve activity was assessed by non-spectral (24-hour averaged normal RR intervals: mean NN, standard deviation of normal RR intervals over 24 hours: SDNN and standard deviation of the mean RR intervals for each 5 min periods over 24 hours: SDANN) and spectral [high frequency power (HF) 0.15-0.40 Hz; represents parasympathetic activity, and the low/high frequency power (L/H ratio); represents sympathetic activity] indices of heart rate variability. There were no cardiac events during physical training. Comparison of the 14th and 28th day in the training group showed that the VO2 peak and VO2 AT significantly increased, SDNN and SDANN significantly increased, HF (82.5 +/- 56.2 to 131.1 +/- 99.8 msec2) increased and the L/H ratio (3.9 +/- 2.2 to 2.6 +/- 1.3) decreased significantly during the night-time, and serum noradrenalin concentration (0.47 +/- 0.11 to 0.35 +/- 0.13 ng/ml) and urinary noradrenalin excretion (195.6 +/- 130.7 to 139.6 +/- 73.3 micrograms/day) significantly decreased. In contrast, the non-training group showed no significant changes. These results suggest early physical training may be safe and improves the autonomic nerve balance and exercise tolerance in patients with acute myocardial infarction.

Aged↗

A live birth from intracytoplasmic injection of a testicular spermatozoon.

Testicular sperm was retrieved from a man with complete epididymal obstruction, and intracytoplasmic sperm injection was performed on his wife's oocytes. In four mature treated, two fertilized eggs were obtained, and a clinical pregnancy was established with embryo transfers. One healthy girl (2715 g) was delivered by cesarean section at 38 weeks' gestation. Our case shows that the use of testicular sperm can result in a normal live birth.

Adult↗

An unusual clinical course after mole evacuation: a case report.

A 27-year-old woman evacuated a hydatidiform mole at 11 weeks of gestation. Her serum human chorionic gonadotropin (hCG) levels declined progressively but reached a plateau of 2-3 mIU/ml thereafter. The patient was treated with two courses of methotrexate, which did not affect her hCG levels. She refused further chemotherapy and, for more than one year, she was managed expectantly until a significant rise in her hCG titer. Fortunately, an unexpected pregnancy and subsequent missed abortion led to a spontaneous regression of her hCG levels.

Abortion, Missed↗

Autocrine mechanism of epidermal growth factor in choriocarcinoma cell proliferation.

We examined four choriocarcinoma cell lines, NaUCC-1, NaUCC-3, NaUCC-4 and BeWo, for the presence of epidermal growth factor (EGF) by enzyme immunoassay and reverse transcription and polymerase chain reaction, and for EGF receptor (EGFR) by 125I-EGF binding assay. Specific EGF binding and EGF proteins were detected in these four choriocarcinoma cell lines. On the cell lines examined, NaUCC-4 had the greatest EGF binding capacity (18 x 10(5) sites/cell) and the highest amount of immunoreactive EGF (142 pg/ml). These results prompted us to assess the significance of EGF/EGFR autocrine mechanism in NaUCC-4 cells. Low doses of exogenous EGF stimulated 3H-thymidine incorporation, and monoclonal antibodies against EGF or EGFR dose-dependently inhibited 3H-thymidine incorporation. On the other hand, these antibodies did not significantly affect hCG production. These results suggested that EGF might function in an autocrine manner to stimulate proliferation rather than differentiation of NaUCC-4 choriocarcinoma cells.

Adult↗

Human placental leucine aminopeptidase/oxytocinase. A new member of type II membrane-spanning zinc metallopeptidase family.

The serum level of placental leucine aminopeptidase (P-LAP) increases during pregnancy. P-LAP degrades several peptide hormones such as oxytocin and vasopresin, suggesting a role in maintaining homeostasis during pregnancy. In the study reported here, we have isolated a cDNA clone with 4084 base pairs encoding P-LAP from a human placental cDNA library. The amino acid sequence deduced from the cDNA contained all of the sequences of the peptide fragments obtained by digestion of the purified protein with trypsin. The predicted P-LAP contains the HEXXH consensus sequence of zinc metallopeptidases, indicating that the enzyme belongs to this family, which includes aminopeptidase N and aminopeptidase A. The deduced sequence also contains a hydrophobic region near the N terminus, suggesting that the enzyme is a type II integral membrane protein. Northern blot analysis revealed that P-LAP was expressed in several tissues, some of which expressed two forms of mRNAs. These results suggest that the enzyme is synthesized as an integral membrane protein and is released into blood under some physiological conditions.

Amino Acid Sequence↗

Clinical value of CA125, CA19-9, CEA, CA72-4, and TPA in borderline ovarian tumor.

Five tumor markers were analyzed clinically in 101 patients with borderline ovarian tumors who were treated by the Tokai Ovarian Tumor Study Group, an association comprising Nagoya University and its affiliated hospital, between January 1986 and December 1994. The positive rate of CA125 was 68.2% in serous tumor and 51.9% in mucinous tumor. The positive rate of CA19-9 was 51.5% in serous tumor and 44.7% in mucinous tumor. The positive rates and mean serum levels of CA125 in serous and mucinous tumor by stage had rising tendencies with an increase in each stage. The mean serum levels of CA19-9 in serous and mucinous tumor by stage had rising tendencies with an increase in each stage. CA125 and CA19-9 were useful for screening of borderline ovarian tumors. The positive rates of CEA and TPA in mucinous tumor were 32.5 and 27.3%, respectively, although none of the patients with serous tumor were positive in CEA and TPA. The positive rates and mean serum levels of CEA in mucinous tumor by stage had rising tendencies with an increase in each stage. The positive rate of CA72-4 was significantly lower than that of CA125 (P < 0.05).

Adenocarcinoma, Mucinous↗

Clinical factors for successful cryopreserved-thawed embryo transfer.

PURPOSE: To study how clinical factors such as embryo quality, cell stage of embryo at cryopreservation, and synchronization of developmental stages between embryo and endometrium at thawing affect the implantation rate after cryopreserved-thawed embryo transfer (ET), these factors were examined in 106 cryopreserved-thawed ETs including 204 embryos. RESULTS: In 86 embryos graded as high quality before transfer by morphological evaluation, 31 implantations were successful, while the other, low-quality embryos did not implant at all. High-quality embryos received less cryoinjury during cryopreservation compared to the injuries sustained by embryos in moderate and poor quality. When cyopreservation was performed at the 1-, 2-, and 3-day cell stages, pregnancies were similiarly achieved among most of the embryos at all cell stages. At thawed ETs in natural ovulation cycles, there were some differences among the developmental stages between thawed embryo and endometrium that received the thawed transferred embryos. Although the transfer timelag ranged a day or more, asynchronism of endometrium growth to the cell stage did not reduce pregnancy rates. CONCLUSIONS: These results indicated that embryo quality evaluated morphologically was the most important clinical factor for successful implantation of cryopreserved-thawed ET.

Blastocyst↗

Successful glucocorticoid treatment for patients with abnormal autoimmunity on in vitro fertilization and embryo transfer.

PURPOSE: To analyze the effects of glucocorticoid treatment for patients with abnormal autoimmunity on IVF-ET outcomes, low-dose predonisolone or dexamethasone was administered in 51 IVF-ET cycles of 41 patients with positive antinuclear antibody (ANA), anti-DNA antibody, and/or lupus anticoagulant (LAC). Rates of clinical pregnancy and implantation in these patients were compared with those in 48 cycles without corticosteroid therapy. Autoantibody-negative patients were also treated with IVF-ET combined with (29 cycles) or without (57 cycles) glucocorticoid administration, and the pregnancy and implantation rates were investigated. RESULTS: Without glucocorticoid treatment, the pregnancy rate per cycle and implantation rate per embryo in antibody-positive patients were 10.4 and 3.8%, respectively. Significant increases in pregnancy (35.3%) and implantation (13.2%) rates were observed with corticosteroid treatment. In antibody-negative patients, the rates of pregnancy and implantation showed no significant differences with versus without the glucocorticoid administration. CONCLUSIONS: Our results indicate that because autoimmune abnormalities may be at least one cause of implantation failure following IVF-ET, the combined use of low-dose corticosteroid can be effective for autoantibody-positive women.

Adult↗

Promotion of proliferation of murine hematopoietic stem cells by growth factors in murine amniotic fluid.

It has been shown that murine amniotic fluid (MAF) displays immunosuppressive activities. We examined the effect of MAF obtained from normal mice on a murine fetal liver cell (FLC) primary culture in vitro for the detection of the possible existence of cytokines that affect hematopoiesis. MAF promoted proliferation of murine FLC and adult bone marrow cells. Proliferation-promoting activity of MAF was observed throughout the period between days 12 and 15 of pregnancy, peaking at day 12. Pooled MAF was subjected to purification procedures to isolate the active molecule(s). After ion exchange and size exclusion chromatography, one of the active molecules was shown to react with anti-mouse stem cell growth factor (SCF) antibody and the molecular weight was determined as 40-45 kDa by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot. The proliferation-promoting activity of MAF was partially neutralised by the anti-SCF antibody. These results provide evidence that MAF may contain multiple growth factors for FLC, one of which may be a unique molecule related to SCF.

Amniotic Fluid↗

Oxytocin is hydrolyzed by an enzyme in human placenta that is identical to the oxytocinase of pregnancy serum.

The hydrolysis of oxytocin (OT) by human placental subcellular fractions and pregnant sera was studied in the presence of bestatin, a potent inhibitor of aminopeptidases, and the antibody against pregnant serum oxyotocinase (P-LAP)(EC 3.4 11.3) by measuring liberated amino acids by high performance liquid chromatography (HPLC). Our immunotitration study and the effect of bastatin on the oxytocin-degrading protease showed that the initiating and responsible protease in oxyotocin degradation in human placenta and pregnant serum is P-LAP.

Amino Acid Sequence↗

Effects of placental proteases on maternal and fetal blood pressure in normal pregnancy and preeclampsia.

Although many protease exist in human placenta, their physiologic roles are still unknown. Our study showed that placenta proteases metabolize vasoactive peptides possibly derived from the fetus. Because vasopressin and angiotensin are known to play an important role in normal and aberrant (preeclampsia) fetal-placental circulation, the clearance of these peptides in the placenta is important in controlling fetal blood pressure. Vasopressin and angiotensin act as a fetal-placental vasoconstrictor; therefore, placental proteases in human placenta are likely to work as a clearance factor for these peptides. Although human and animal pregnancy is normally associated with a refractory response to the pressor effect of exogenously infused angiotensin II, patients with preeclampsia, as well as nonpregnant women, are sensitive to the pressor effect of angiotensin II. Our study suggested that the decreased pressor responsiveness to angiotensin II in pregnancy is caused by increased inactivation of angiotensin II by angiotensinase in pregnant serum and the placenta. Although vasopressinase and angiotensinase activities increase with advancing gestation in normal pregnant sera, the activities of both enzymes in severe preeclampsia sera were clearly lower than those in normal pregnancy. Therefore, it is reasonable to speculate that the increased sensitivity to angiotensin II of preeclampsia is attributable to the decreased degradation of angiotensin II by placental angiotensinase. The negative correlations between the systolic to diastolic ratio obtained from pulsed Doppler measurement techniques and the activities of both enzymes in preeclampsia sera suggested that the systolic to diastolic ration, which reflected constriction of placental vessels, is influenced by the concentration of vasoactive peptides in the fetal-placental circulation due to changes in the activities of placental proteases. Placental proteases play important roles in controlling fetal and maternal blood pressure through regulation of the concentration of vasoactive peptides in the interface (placenta) between fetus and mother.

Blood Pressure↗

Timing of periventricular leukomalacia using neonatal electroencephalography.

OBJECTIVE: To estimate the timing of brain damage involved in the onset of periventricular leukomalacia in the perinatal period we recorded and analyzed neonatal electroencephalograms (EEGs). METHODS: Twenty-four preterm birth infants proved by real time ultrasonic examination or MRI to be suffering from periventricular leukomalacia underwent serial electroencephalography from soon after birth. RESULTS: Thirteen (54%) demonstrated intrauterine injury patterns, 2 infants (8%) showed postnatal injury, and in the remaining 9 cases (38%) the time of injury could not be determined by electroencephalography. Antepartum maternal hemorrhage (6), premature rupture of membranes (3), twining (3), chorioamnionitis (2), and perinatal asphyxia (2) were complications encountered in the group with intrauterine injury patterns. CONCLUSIONS: Our observations suggest that more than half of periventricular leukomalacia cases are associated with premature birth infants showing intrauterine injury patterns on electroencephalography, indicating the existence of intrauterine insult.

Brain Injuries↗

Relationship between the changes in maternal serum placental leucine aminopeptidase (P-LAP) activity and umbilical artery waveforms in normal pregnancy.

The relation between placental leucine aminopeptidase (P-LAP) activity in maternal sera and umbilical artery waveforms (systolic/diastolic ratio, S/D) obtained by pulsed Doppler has been examined by cross-sectional study in 26 normal pregnancies during weeks 26-38. A negative correlation was seen to exist suggesting that P-LAP may have a role in the regulation of uteroplacental blood flow.

Adult↗

Detection of apoptosis in human endometriotic tissues.

To clarify whether apoptosis is involved in endometriosis, we obtained eutopic endometrial tissues along with endometriotic tissues from the uterus (adenomyosis) (n = 12) and from the ovary (n = 12) from patients undergoing gynaecological surgery. Apoptosis-induced DNA fragmentation was detected by the TdT-mediated dUTP-biotin nick-end labelling method, and immunostaining with a monoclonal antibody against the Fas, Le(y) or B-cell leukaemia/lymphoma-2 (bcl-2) was also performed using the same tissue section. Analysis showed that apoptosis was occurring in all the samples of ovarian endometriotic tissue but in only two of the 12 adenomyotic and in five of the 24 eutopic endometrial tissue samples. In none of these cases was apoptosis correlated with phases of the menstrual cycle. The expression of bcl-2 in the eutopic endometrial and adenomyotic tissues was limited to the proliferative phase, and was observed in only one of the 12 cases of ovarian endometriosis. Fas and Ley were expressed randomly across a wide range in both the eutopic and ectopic endometrial tissues. These results suggest that the features of ovarian endometriosis are different from those of adenomyosis and eutopic endometrium in terms of the involvement of apoptosis. In addition, the regulatory mechanism involved in ovarian endometriosis may differ from that in other endometrial cells.

Adult↗

Characterization of the growth factor activity of amniotic fluid on cells from hematopoietic and lymphoid organs of different life stages.

We investigated the proliferation-promoting effects of murine amniotic fluid (MAF) on in vitro cultured cells originally obtained from murine hematopoietic and lymphoid organs at different life stages. MAF promoted proliferation of the fetal liver cells (FLC), newborn spleen cells and adult bone marrow cells. The proliferation-promoting activity of MAF was extended to liver cells and spleen cells from mice younger than 2 weeks old. MAF did not, however, promote the proliferation of newborn or adult thymocytes, or of spleen cells, liver cells or peritoneal cells, liver cells or peritoneal cells from 2-week-old or older mice. Rather, it partially inhibited the proliferation of spleen cells, thymocytes and peritoneal cells from 1-year-old mice. These results suggest that MAF contains growth factors for hematopoietic stem cells but not for either mature or immature T lymphocytes. Supporting this view, the MAF activity was partially neutralized by a polyclonal anti-mouse stem cell factor (SCF) antibody. Moreover, the immunoblotting of MAF against anti-mouse SCF antibody revealed a band at 30-32 kDa corresponding to the previously reported SCF. Interestingly, MAF was able to maintain FLC and adult bone marrow cells alive in culture for a relatively long time (2 weeks). The MAF activity was further shown to be partially and cell type-dependently antagonized by TNF-alpha and TGF-beta. These results provided evidence that MAF contains potentially multiple growth factors preferentially affecting the early stage of hematopoiesis, one of which is SCF.

Age Factors↗