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Biomedical subjects

Hitoo Nakano

Publications and source records attributed to Hitoo Nakano.

At least 19 recordsLinked to original sources
PubMed2006

Long-term outcome of infants with twin-to-twin transfusion syndrome.

OBJECTIVE: To clarify the long-term neurodevelopmental outcome of twin-to-twin transfusion syndrome (TTTS) survivors. METHODS: From January 1994 to December 2003, 33 newborns with TTTS who were derived from 18 monochorionic twin gestations were enrolled for the study. The development and growth at 3 or 6 years of age were compared between TTTS survivors and weight-matched singleton controls. RESULTS: The mortality in TTTS (8/33: 24%) was significantly higher than that of the controls (7/80: 9%). Of all 12 TTTS patients who were diagnosed before 25 weeks and born before 28 weeks of gestation, in 10 (83%) it led to neonatal or intrauterine death. The morbidity of cerebral palsy, epilepsy, and mental retardation did not differ between TTTS and control patients. The morbidity and severity of neurological deficits at school age were similar in both groups. No growth parameters at 3 or 6 years of age differed between TTTS and controls. CONCLUSIONS: Morbidity, growth and development of TTTS survivors attained comparable levels of weight-matched controls, despite the higher neonatal mortality. These results suggest that the early management of TTTS is critical for refining the total outcome of the affected twins.

Child Development↗
PubMed2006

Adenovirus-mediated calponin h1 gene therapy directed against peritoneal dissemination of ovarian cancer: bifunctional therapeutic effects on peritoneal cell layer and cancer cells.

PURPOSE: Calponin h1 (CNh1), one of the family of actin-binding proteins, stabilizes the filaments of actin and modulates various cellular biological phenotypes. Recent studies revealed the close correlation between the invasive tumor spread and the reduced expression of CNh1 and alpha-smooth muscle actin in the surrounding stromal cells. The purpose of this study is to evaluate the efficacy of i.p. CNh1 gene therapy against peritoneal dissemination of ovarian cancer. EXPERIMENTAL DESIGN: We used an adenoviral vector to induce the CNh1 gene into peritoneal cells and ovarian cancer cells as a means of enhancing or inducing the expression of alpha-smooth muscle actin as well as CNh1. The efficacy of gene transfer was examined by in vitro cell culture and in vivo animal experiments. RESULTS: The formation of longer and thicker actin fibers was observed in each transfected cell line, and the localization of these fibers coincided with that of externally transducted CNh1. With respect to changes in cell behavior, the CNh1-transfected peritoneal cells acquired an ability to resist ovarian cancer-induced shrinkage in cell shape; thus, cancer cell invasion through the monolayer of peritoneal cells was inhibited. In addition, CNh1-transfected ovarian cancer cells showed suppressed anchorage-independent growth and invasiveness, the latter of which accompanied impaired cell motility. The concomitant CNh1 transfection into both peritoneal cells and ovarian cancer cells produced an additive inhibitory effect with respect to cancer cell invasion through the peritoneal cell monolayer. By in vivo experiments designed to treat nude mice that had been i.p. inoculated with ovarian cancer cells, we found that the i.p. injected CNh1 adenovirus successfully blocked cancer-induced morphologic changes in peritoneal cell surface and significantly prolonged the survival time of tumor-bearing mice. Moreover, CNh1 adenovirus could successfully enhance the therapeutic effect of an anticancer drug without increase in side effects. CONCLUSIONS: Thus, CNh1 gene therapy against peritoneal dissemination of ovarian cancer is bifunctionally effective (i.e., through inhibitory effects on the infected peritoneal cell layers that suppress cancer invasion and through direct antitumor effects against invasion and growth properties of cancer cells).

Adenoviridae↗
PubMed2006

Noninvasive measurement of isovolumetric contraction time by Doppler cardiography can be substituted for fetal cardiac contractility: evaluation of a fetal lamb study.

OBJECTIVE: The objective of this study is to clarify whether the isovolumetric contraction time obtained from Doppler cardiography (Doppler ICT) can be an index substituted for fetal cardiac contractility. MATERIALS AND METHODS: In 10 pregnant ewes, fetal hypoxemia was induced by giving a variable mixture of gases. Through experiment, the Doppler ICT, pre-ejection period (PEP), and the maximum first derivative of the left ventricular pressure waveform (Max dp/dt) were simultaneously recorded every 10min. The relationship between both the Doppler ICT and PEP, and the Max dp/dt were analyzed. RESULTS: A significant negative linear regression was founded between the Doppler ICT and the Max dp/dt. A significant negative linear regression was also shown between PEP and the Max dp/dt. Moreover, the regression of Max dp/dt on ICT had significantly less residual variance than the regression of Max dp/dt on PEP (p=0.0004). CONCLUSION: In contrast to PEP, Doppler ICT is a reliable, and non-invasive index which can be substituted for fetal cardiac contractility.

Animals↗
PubMed2006

Clinical significance of RCAS1 as a biomarker of uterine cancer.

OBJECTIVES: Expression of RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is associated with prognosis of various malignancies including uterine cancer. Proteolytic cleavage of RCAS1 at extracellular domains (ectodomain shedding) yields soluble RCAS1. Although RCAS1 can induce apoptosis in normal peripheral lymphocytes, its biologic function in cancer patients is unclear. Here, we evaluated serum RCAS1 concentrations to clarify its biologic activity in uterine cancer. METHODS: Via ELISA, we measured serum RCAS1 concentrations in samples from 54 healthy blood donors and 113 patients-63 with cervical cancer and 50 with endometrial cancer. We also counted the peripheral lymphocyte number. We correlated via statistical means the RCAS1 values with patients' clinicopathologic variables. We assessed inhibition of growth of K562 cells, which express the putative RCAS1 receptor, via WST-1 assay of serum samples to clarify RCAS1's biologic activity. RESULTS: Uterine cancer patients had significantly higher serum RCAS1 concentrations than did healthy blood donors (P<0.05). Patients with adenocarcinoma had significantly higher RCAS1 concentrations than did those with squamous cell carcinoma (P=0.0340). RCAS1 values were also significantly associated with response to treatment (P<0.001). FasL and TNF-alpha serum concentrations were not significantly different for the different groups, however. The WST-1 assay showed that patients' serum induced K562 cell growth inhibition, but this effect partially recovered after immunodepletion of RCAS1. Peripheral lymphocyte number and serum RCAS1 concentration were inversely related (P=0.0310). CONCLUSION: RCAS1 may be a biomarker of uterine cancer because of its potential to predict results of uterine cancer treatment and inhibit growth of immune cells.

Adenocarcinoma↗
PubMed2006

Simplified ultrasound screening for fetal brain function based on behavioral pattern.

Despite the longstanding conclusion that behavior can reveal aspects of underlying anatomy and function, no generalized antenatal behavior screening has been developed to identify fetuses that may have central nervous system defects requiring further evaluation. We devised a brief ultrasound examination to distinguish fetuses with compromised central nervous system function from the general population and evaluated it with this study. The study design compared behavioral findings obtained by retrospectively reviewing the ultrasound examinations of 5 fetuses that had abnormal behavior with prospectively obtained findings of 29 normal fetuses. Median time for brief examination criteria was 50 min (range, 30-60 min). The only case undetectable by this brief ultrasound examination has an eye-movement period significantly longer than the normal upper limit. Using this method as a screening test may make it possible to include assessment of fetal brain function as part of routine antenatal care.

Central Nervous System↗
PubMed2006

Prophylactic effect of pemirolast, an antiallergic agent, against hypersensitivity reactions to paclitaxel in patients with ovarian cancer.

We have previously shown that sensory nerve peptides contribute to the pathogenesis of pulmonary hypersensitivity reactions (HSRs) to paclitaxel in rats. Moreover, pemirolast, an antiallergic agent, reverses the HSRs to paclitaxel, although the mechanism is considered to result from the blockade of paclitaxel-induced release of sensory peptides, rather than the inhibition of histamine release. In the present study, we investigated the preventive effect of pemirolast against acute HSRs in a total of 84 patients who undertook postoperative paclitaxel plus carboplatin chemotherapy every 4 weeks for ovarian cancer. Patients were assigned to receive oral lactose (placebo) or pemirolast (10 mg), 2 hr before paclitaxel infusion. All patients received conventional premedication, including oral diphenhydramine, intravenous ranitidine and intravenous dexamethasone, 30 min before paclitaxel infusion. The HSRs that led to the discontinuance of paclitaxel infusion (grade>or=2) occurred in 5 of 42 patients in placebo group, whereas none of pemirolast-treated 42 patients showed any signs of HSRs. Plasma histamine concentrations were not changed after paclitaxel infusion in either group. Our present findings suggest that pemirolast is potentially useful for prophylaxis of paclitaxel-induced HSRs. In this respect, the use of pemirolast as premedication is expected to be beneficial to the safety management in patients who undergo chemotherapy containing paclitaxel.

Administration, Oral↗
PubMed2006

Sudden fetal death associated with both duodenal atresia and umbilical cord ulcer: a case report and review.

We encountered one case of duodenal atresia complicated by massive intrauterine hemorrhage due to the perforation of an umbilical cord ulceration (UCU). UCU is an extremely rare complication in the perinatal period. Although the prenatal diagnosis of upper intestinal atresia has been established, little is known about the association between UCU and upper intestinal atresia. In this article, we report our case, review past articles, and discuss the underlying pathophysiological mechanisms of the cause of an UCU. Given the characteristic sites of upper intestinal atresia, we speculate that regurgitation of gastric or intestinal juice into the amniotic fluid could be responsible for the development of UCU. We also believe that close observation is required for patients who have upper intestinal atresia.

Adult↗
PubMed2006

Fetal aortic distension waveforms for evaluating cardiac function and changes in blood pressure: fetal lamb validation.

AIM: To investigate which part of the fetal aortic distension waveform is mainly influenced by changes in fetal cardiac contractility and aortic blood pressure. METHODS: In acute preparation, aortic distension waveforms were recorded using an echo-tracking system, and aortic and left ventricular pressure waveforms were obtained from six late-gestation catheterized fetal lambs. Dobutamine and angiotensin II were separately infused and the correlations between the maximum value in the first derivative of left ventricle pressure waveforms (Max dP/dt) and fetal blood pressure, and the parameters obtained from aortic distension waveforms were analyzed using linear regression analysis. RESULTS: With a change in cardiac contractility, the maximum value of first derivative of the systolic rising slope in the aortic distension waveform had a positive correlation with Max dP/dt (r = 0.93, P < 0.0001). With changes in fetal blood pressure, both the amplitude and the ratio of increase from the end diastolic diameter obtained from the aortic distension waveform had a significant positive correlation with aortic blood pressure amplitude (r = 0.60, P < 0.01; r = 0.61, P < 0.01, respectively). CONCLUSION: The maximum first derivative of the systolic rising slope in the aortic distension waveform and the amplitude in the aortic distension waveform enable us to non-invasively substitute for fetal cardiac contractility and aortic blood pressure amplitude, respectively.

Animals↗
PubMed2006

Complete mole coexistent with a twin fetus.

We report two cases of a complete hydatidiform mole coexistent with a live fetus diagnosed by DNA polymorphism analysis. A 27-year-old woman revealed symptoms of pre-eclampsia and ultrasound showed multicystic tumor and placenta coexistent with a live fetus at 16 weeks' gestation. The placenta with partly hydropic change and the fetus without anomaly were consequently evacuated. Another 30-year-old woman had a multicystic mass attached to a normal placenta with a 20-week live fetus on ultrasound examination. A hysterotomy was carried out because of persistent bleeding due to placenta previa. In both cases, DNA was extracted from the placental tissue and the tumor, as well as from maternal and paternal blood. Genetic analysis demonstrated that the placental tumor consisted of only paternal origin, which is consistent with the diagnosis of complete hydatidiform mole.

Adult↗
PubMed2006

Neutrophil function during pregnancy: is nitric oxide production correlated with superoxide production?

PROBLEM: Oxygen radical formation by neutrophils during pregnancy is not well studied. METHOD OF STUDY: We studied neutrophil-derived superoxide anion (O) and nitric oxide (NO) values in 75 normal pregnant women, 12 postpartum women, and 10 non-pregnant women. O production was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome c. NO production was measured by accumulation of the stable end product nitrite using a modified Griess reaction method. RESULTS: O production of neutrophils stimulated by chemotactic peptide was significantly enhanced in the early second trimester of pregnancy. l-arginine analogue-inhibitable nitrite production was induced in neutrophils from pregnant women, but not from postpartum and non-pregnant subjects. In third-trimester subjects but not non-pregnant subjects, neutrophils pre-treated with l-arginine analogues enhanced O production compared with untreated neutrophils. CONCLUSION: These findings indicate that O and NO production by neutrophils during pregnancy were modulated separately, whereas neutrophil-derived NO might function as a regulator of O.

Case-Control Studies↗
PubMed2006

Pleural fluid/serum immunoglobulin ratio is a diagnostic marker for congenital chylothorax in utero.

OBJECTIVE: To distinguish congenital chylothorax from other causes of hydrothorax in utero. METHODS: Serum and pleural fluid samples from 8 fetuses with congenital chylothorax and 5 control fetuses with other causes of hydrothorax were tested for total protein, albumin, IgG, IgA, and IgM. RESULTS: Fetuses with congenital chylothorax had higher levels of IgG in pleural fluid, but not the other four proteins, than control fetuses (P<0.05). There were no significant differences in serum proteins among fetuses. When we examined pleural fluid to serum ratios, the IgG ratio in fetuses with congenital chylothorax was significantly higher than that of control fetuses (P<0.05). The IgG ratio in chylothorax was greater than 0.6 regardless of lymphocyte count. CONCLUSION: Pleural fluid/serum IgG ratio may be a diagnostic marker for congenital chylothorax in utero.

Albumins↗
PubMed2005

Chronic treatment with 17beta-estradiol increases susceptibility of smooth muscle cells to nitric oxide.

The purpose of this study was to evaluate the role of estrogen as a vasodilator or relaxing modulator during vascular tonus through chronic estrogen treatment. Experiments were conducted using isolated basilar arteries from ovariectomized female rabbits divided into two groups (the with and without estrogen replacement groups, respectively). Both acetylcholine and carbachol relaxed the basilar arteries of rabbits in the with estrogen replacement group (pre-contracted by 30 mM K(+)) more strongly than in the without estrogen replacement group. Vasodilatation effects of (+/-)-(E)-4-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3 -hexenamide (NOR1) and S-nitroso-N-acetyl-penicillamine (SNAP) were greater in rabbits in the with estrogen replacement group than the without estrogen replacement both with endothelium-intact and denuded preparations. On the other hand, vasodilatation effects of nicardipine, 17beta-estradiol and membrane-permeable cyclic-GMP or cyclic-AMP were the same in both groups. These results suggest that chronic administration of estradiol potentiates reactivity to nitric oxide (NO) in smooth muscle cells, which could be a therapeutic target for cardiovascular diseases in postmenopausal women.

Acetylcholine↗
PubMed2005

Generation of reactive oxygen species by neutrophils and endothelial cell injury in normal and preeclamptic pregnancies.

The aim of this study was to investigate the role of neutrophil-derived reactive oxygen species on endothelial cell dysfunction in preeclampsia. We first assessed the correlation between nitrite and superoxide anion production in normal nonpregnant (n=10), normal pregnant (n=15), and preeclamptic women (n=12). We then examined neutrophil-mediated oxygen radical damage to human umbilical vein endothelial cells in vitro. Neutrophil superoxide release was measured by cytochrome C reduction; nitrite release was measured by the modified Griess reaction, and endothelial cell injury was measured by 51Cr release. N-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide release by neutrophils was significantly increased in women with preeclampsia compared with the other 2 groups. Nitrite release by neutrophils was significantly decreased in preeclampsia compared with normal pregnancy. When neutrophils were pretreated with superoxide dismutase, nitrite release by neutrophils did not differ between normal pregnancy and preeclampsia, suggesting that excess superoxide anion in preeclampsia could reduce bioavailability of nitric oxide through neutrophil autocrine function. Neutrophil-mediated endothelial cell injury was significantly greater in women with preeclampsia than in the other 2 groups. Hydrogen peroxide was important in neutrophil-mediated endothelial cell injury in preeclampsia as catalase inhibited endothelial cell injury. When neutrophils were pretreated with NG-nitro-L-arginine methyl ester, neutrophil-mediated endothelial cell injury in preeclampsia was decreased, indicating a role for peroxynitrite formation as a mechanism of endothelial cell injury. In conclusion, the modulation of neutrophils causing superoxide production to dominate over nitrite release provides a reasonable explanation for endothelial cell dysfunction in preeclampsia.

Adult↗
PubMed2005

Functional analysis of organic cation transporter 3 expressed in human placenta.

The aim of this study is to investigate the placental transport mechanism of cationic compounds by comparison of the uptake of an organic cation into human placental basal membrane vesicles (BLMVs) with that into organic cation transporter 3 (OCT3)-expressing cells. Reverse transcription-polymerase chain reaction analysis demonstrated that OCT3 is the only OCT isoform expressed in the human placenta. The function of OCT3 was investigated by measuring the uptake of 1-methyl-4-phenylpyridinium (MPP(+)) into human embryonic kidney (HEK)293 cells stably expressing OCT3 (HEK/OCT3 cells). The OCT3-mediated uptake of MPP(+) was sodium- and chloride-independent and saturable, with a Michaelis constant (K(m)) of 82.5 microM. The OCT3-mediated uptake was inhibited by various cationic drugs in a concentration-dependent manner but not by anionic compounds, such as p-aminohippuric acid and captopril, or a zwitterion, carnitine. Western blotting analysis of membrane vesicles prepared from human term placenta revealed that OCT3 is expressed only in BLMVs but not in microvillous membrane vesicles. The uptake of MPP(+) into BLMVs was membrane potential-dependent and saturable, with a K(m) value of 51.8 muM, which is similar to that in HEK293/OCT3 cells. The inhibitory spectrum of various compounds on MPP(+) uptake by BLMVs was also similar to that in HEK293/OCT3 cells. These results suggest that OCT3 is expressed on the basal membrane of human trophoblast cells and plays an important role in the placental transport of cationic compounds.

Adult↗
PubMed2005

Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer.

PURPOSE: Lysophosphatidic acid, which is enriched in the peritoneal fluid of ovarian cancer patients, plays a key role in the progression of ovarian cancer. Lysophosphatidic acid can generate epidermal growth factor receptor (EGFR) signal transactivation involving processing of EGFR ligands by ADAM (a disintegrin and metalloprotease) family metalloproteases. We aimed to investigate the clinical significance of EGFR ligands and ADAM family in the lysophosphatidic acid-induced pathogenesis of ovarian cancer. EXPERIMENTAL DESIGN: We examined the expression of EGFR ligands and ADAM family members in 108 patients with normal ovaries or ovarian cancer, using real-time PCR, immunohistochemistry, and in situ hybridization, and analyzed the clinical roles of these molecules. Statistical analyses of these data were done using the Mann-Whitney test, Kaplan-Meier method, or Spearman's correlation analysis. RESULTS: Large differences in expression were found for heparin-binding EGF-like growth factor (HB-EGF) and other EGFR ligands and for ADAM 17 and other ADAM family members. HB-EGF expression was significantly increased in advanced ovarian cancer compared with that in normal ovaries (P < 0.01). HB-EGF expression was significantly associated with the clinical outcome (P < 0.01). ADAM 17 expression was significantly enhanced in both early and advanced ovarian cancer compared with that in normal ovaries (both P < 0.01), although it had no clinical significance in the progression-free survival. HB-EGF expression was significantly correlated with ADAM 17 expression (gamma = 0.437, P < 0.01). CONCLUSIONS: Our findings suggest that HB-EGF and ADAM 17 contribute to the progression of ovarian cancer and that HB-EGF plays a pivotal role in the aggressive behavior of a tumor in ovarian cancer.

ADAM Proteins↗
PubMed2005

Association between RCAS1 expression and microenvironmental immune cell death in uterine cervical cancer.

OBJECTIVE: : The presence of regional lymph node metastasis is one of the prognostic factors for uterine cervical cancer. The development of metastasis requires that cancer cells avoid lymphocyte attack. Impaired lymphocyte function is mediated by apoptotic factors including receptor-binding cancer antigen expressed on SiSo cells (RCAS1), Fas ligand (FasL), and tumor necrosis factor-alpha (TNF-alpha). Our aim was to evaluate the association between expression of these factors and microenvironmental lymphocyte apoptosis in this disease. METHODS: : Immunohistochemical methods were used to determine the relationship between the expression of RCAS1, FasL, and TNF-alpha, and the number of apoptotic lymphocytes in primary lesions and metastatic lymph nodes in patients with cervical cancer. RESULTS: : Expression of these apoptosis-inducing molecules was quite different in primary tumors and metastatic lymph nodes: RCAS1 expression in lymph nodes was significantly higher than that in primary lesions (P < 0.0001), whereas FasL and TNF-alpha expressions at these two locations were not significantly different. The number of cells with positive expression of RCAS1, but not of FasL or TNF-alpha, was significantly correlated with the number of apoptotic lymphocytes in uterine cervix and metastatic lymph nodes (P < 0.0001 for both). CONCLUSION: : RCAS1 expression may be related to tumor cell evasion of immune surveillance via induction of lymphocyte apoptosis in primary lesions and metastatic lymph nodes in uterine cervical cancer.

Adult↗
PubMed2005

Incidence and risk factors for paclitaxel hypersensitivity during ovarian cancer chemotherapy.

Hypersensitivity reaction (HSR) is still a major concern during cancer chemotherapy with paclitaxel. In the present study, we investigated retrospectively the incidence of HSRs to paclitaxel and the risk factors in 105 patients (553 courses) who received adjuvant chemotherapy (paclitaxel and carboplatin) for ovarian cancer. Moderate to severe HSRs that led to cessation or discontinuation of the chemotherapy, including respiratory distress and hypotension, were observed in 14 patients (13.3%) and 16 courses (2.9%), regardless of the use of conventional premedication with glucocorticoid, and histamine H(1) and H(2) antagonists. The incidence of HSRs to paclitaxel in patients with ovarian cancer seemed to be considerably higher than those reported by other investigators in patients with other carcinomas such as non-small-cell lung cancer and breast cancer. Four risk factors were identified: (1) history of mild dermal reactions such as facial flushing and urticaria in previous courses, (2) presence of respiratory dysfunction, (3) obesity (body mass index >25), and (4) postmenopausal at the time of ovariectomy. The incidence of hypersensitivity increased linearly as the number of risk factors increased (r=0.992, P=0.008). It is likely that disappearance of the estrous cycle facilitates the occurrence of HSRs to paclitaxel.

Adult↗