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Biomedical subjects

M Nakatsuka

Publications and source records attributed to M Nakatsuka.

At least 19 recordsLinked to original sources
PubMed2005

Accumulation of advanced glycation end products in women with preeclampsia: possible involvement of placental oxidative and nitrative stress.

Advanced glycation end products (AGEs) are known to cause oxidative damage in various cells by binding with its receptor, RAGE. We measured the serum level of AGEs and examined the AGEs, RAGE, and the other biomarkers of oxidative stress in the placentas from preeclamptic women. Competitive ELISA was carried out to measure the AGEs in serum. Western blotting was performed to analyze AGEs and RAGE in the placenta. Immunohistochemical analyses were performed to examine the localization of AGEs, RAGE, and other biomarkers of oxidative stress in the placenta. The mean level of serum AGEs in preeclamptic women was significantly higher than that in healthy non-pregnant women or healthy pregnant women. Western blotting revealed that the level of AGEs or RAGE in preeclamptic placenta was significantly higher than that in normal placenta. Immunohistochemical analyses showed that levels of nitrotyrosine and nitroguanosine, which are formed by reactive nitrogen species, in preeclamptic placenta were higher than those in normal placenta. Accumulation of 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine indicated enhanced oxidative modifications of lipids and DNA in preeclamptic placenta. The AGE-RAGE system, which is upregulated in preeclampsia, is likely to be involved in the oxidative stress of preeclampsia.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

Advanced glycation end products induce secretion of chemokines and apoptosis in human first trimester trophoblasts.

BACKGROUND: We studied the effects of advanced glycation end products (AGEs), which are known to accumulate in patients with diabetes, autoimmune diseases, or that smoke, on human trophoblasts. METHODS: First trimester human chorionic villi of 6-10 week gestation were obtained. Expression and localization of the receptor for AGEs (RAGE) was examined by western blotting and immunohistochemistry. Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, regulated upon activation, normal T-cell expressed and secreted (RANTES), and human chorionic gonadotropin (hCG) in culture medium were measured by ELISA. Trophoblastic apoptosis was evaluated by the Hoechst 33258 staining and the in situ nick end labeling technique. RESULTS: RAGE was localized in trophoblasts. AGEs significantly stimulated secretion of both MIP-1alpha and MIP-1beta from trophoblasts in a time- and dose-dependent manner. AGEs significantly induced apoptosis and reduced secretion of hCG. Increased secretions of MIP-1alpha and MIP-1beta by AGEs were significantly suppressed by inhibitors of nitric oxide synthase (NOS) or nafamostat mesilate, a synthetic serine protease inhibitor and a suppressor of transcription factor, NF-kappaB activation. These agents also suppressed the effects of AGEs on hCG secretion and trophoblastic apoptosis. CONCLUSIONS: These AGE-mediated changes in trophoblasts may lead to impairment of implantation and placentation. NOS inhibitors or nafamostat mesilate may modify these effects.

Apoptosis↗
PubMed2002

Extravasation on three-dimensional CT angiography in patients with acute subarachnoid hemorrhage and ruptured aneurysm.

Three-dimensional computed tomographic angiography (CTA) is a noninvasive technique for detecting lesions after acute subarachnoid hemorrhage. We encountered extravasation on CTA, a finding that has not been reported previously. Three patients with saccular aneurysms showed extravasation on CTA performed within 3 h of the onset of hemorrhage, and all three patients died within 2 weeks. At autopsy, the site of rupture of the aneurysm was confirmed in all three cases. There were two patterns of extravasation shown by CTA, which seemed to depend on the direction of rupture. Extravasation on CTA might represent the natural progression of ruptured aneurysm and may indicate a poor prognosis.

Acute Disease↗
PubMed2002

Elevated blood flow resistance in uterine arteries of women with unexplained recurrent pregnancy loss.

BACKGROUND: Uterine perfusion appears to regulate uterine receptivity. However, vascular changes in recurrent pregnancy loss (RPL) remain poorly studied. METHODS: One hundred and twenty one women were enrolled into this study: normal women with sterility caused by male factor (control group: n = 72) and women with RPL (n = 49). Women with uterine anomaly, impaired glucose tolerance, abnormal thyroid function, or anti-phospholipid antibodies were excluded from the study. In the mid-luteal phase of a non-pregnant cycle, transvaginal pulsed Doppler ultrasonography of the uterine artery was performed. Uterine arterial pulsatility index (PI), endometrial thickness, serum estradiol, progesterone, and nitrite/nitrate concentrations were determined. RESULTS: In the RPL group, the PI in the uterine artery of women with antinuclear antibodies was significantly higher than that of women without antinuclear antibodies (P < 0.05). Among women without antinuclear antibodies, the mean (+/-SD) uterine artery PI in the RPL group (2.44 +/- 0.41) was also significantly higher than in the control group (2.19 +/- 0.40; P < 0.01). The PI was inversely correlated with serum progesterone levels (r = -0.47, P < 0.01). CONCLUSIONS: Elevated uterine arterial impedance is associated with RPL. Pulsed Doppler ultrasonography is useful in identifying women with unexplained RPL who have impaired uterine circulation.

Abortion, Habitual↗
PubMed2001

Blast-wave-sphere interaction using a laser-produced plasma: an experiment motivated by supernova 1987A.

We present x-ray shadowgraphs from a high Mach number ( approximately 20) laboratory environment that simulate outward flowing ejecta matter from supernovae that interact with ambient cloud matter. Using a laser-plastic foil interaction, we generate a "complex" blast wave (a supersonic flow containing forward and reverse shock waves and a contact discontinuity between them) that interacts with a high-density (100 times ambient) sphere. The experimental results, including vorticity localization, compare favorably with two-dimensional axisymmetric hydrodynamic simulations.

Journal Article↗
PubMed2001

Effect of low-intensity warfarin therapy on left atrial thrombus resolution in patients with nonvalvular atrial fibrillation: a transesophageal echocardiographic study.

The presence of left atrial thrombus (LAT) is associated with an increased risk of embolic stroke. However, it has yet to be established definitively whether low-intensity warfarin therapy (INR: 1.5-2.0) can prevent LAT formation in patients with nonvalvular atrial fibrillation (NVAF). The present study analyzed the clinical and transesophageal echocardiography (TEE) features of 123 such patients to identify risk factors for LAT formation and the efficacy of prophylactic low-intensity warfarin therapy. Left atrial thrombi were found in 35 patients (28%) in whom systemic hypertension (49% vs 23%; p<0.01) and ischemic heart disease (17% vs 3%; p<0.01) were more frequent. Left ventricular ejection fraction (54+/-14% vs 60+/-11%; p<0.05), left ventricular end-diastolic dimension (51+/-7 mm vs 48+/-5 mm; p<0.05), spontaneous echo contrast (2.2+/-0.7 vs 1.4+/-0.9; p<0.01), left atrial diameter (50+/-6 mm vs 43+/-7 mm; p<0.01), left atrial appendage blood velocity (22.3+/-8.7 cm/s vs 37.2+/-21.5 cm/s; p<0.01) and the incidence of left ventricular hypertrophy (37% vs 15%; p<0.01) were also significantly different between the groups. Fourteen patients received continuous warfarin therapy (target INR: 1.5-2.0) and on the follow-up TEE study the left atrial thrombus resolved in 10 (71%). There were no thromboembolic events or major hemorrhagic complications in these patients, so it was concluded that low-intensity warfarin therapy is efficacious in treating LAT formation in patients with NVAF.

Adult↗
PubMed2001

[Measurement of apparent accommodation with a 20/20 near vision optotype].

PURPOSE: The value of apparent accommodation varies with methods of measurement. To discuss the details of apparent accommodation, it is appropriate to measure it with the smallest possible near vision optotype. In the present study, we used a 20/20 near vision optotype for the measurement of apparent accommodation. SUBJECTS AND METHODS: Forty-six eyes of thirty-eight patients (45-84 years old) who had undergone cataract surgery and intraocular lens implantation, and had at least 20/20 best corrected visual acuity at near and far distances, were used in this study. After the eyes were corrected by glasses to gain the best corrected long distance visual acuity, they were forced to watch a 20/20 near vision optotype. Then we gradually added plus lenses until they could recognize the optotype. The value of apparent accommodation was recorded by subtracting the value of plus lens by which the eye could first recognize the 20/20 near vision optotype from three diopters. RESULTS: The value of apparent accommodation was 0.00-3.00 D (medium 0.50 D). Two eyes had three diopters of apparent accommodation. CONCLUSION: In the present study with correction of astigmatism and small near vision optotype, most eyes showed smaller apparent accommodation than those in previous studies. Despite that, patients with three diopters of apparent accommodation do exist. To analyze high quality visual functions, we should use the smallest possible near vision optotype for the measurement of apparent accommodation.

Accommodation, Ocular↗
PubMed2000

Heme insertion, assembly, and activation of apo-neuronal nitric-oxide synthase in vitro.

It has been established that in the case of inducible NO synthase (NOS), a functionally active homodimer is assembled from the heme-deficient monomeric apo-NOS in vitro by the addition of heme, whereas the heme-deficient neuronal isoform (apo-nNOS) is at best only partially activated. In the current study we have discovered that reactive oxygen species, which can be removed by the addition of superoxide dismutase and catalase, destroy the heme and limit the activation of apo-nNOS in vitro. With the use of these improved conditions, we show for the first time that heme insertion is a rapid process that results in formation of a heme-bound monomeric nNOS that is able to form the ferrous-CO P450 complex but is unable to synthesize NO. A slow process requiring more than 90 min is required for dimerization and activation of this P450 intermediate to give an enzyme with a specific activity of approximately 1100 nmol of NO formed/min/mg of protein, similar to that of the native enzyme. Interestingly, the dimer is not SDS-resistant and is not the same dimer that forms in vivo. These studies indicate at least two intermediates in the assembly of nNOS and advance our understanding of the regulation of nNOS.

Animals↗
PubMed2000

p53-independent transient p21(WAF1/CIP1) mRNA induction in the rat brain following experimental traumatic injury.

The expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) mRNA after traumatic brain injury in rats was investigated using an in situ hybridization technique, along with regulating gene p53 and stress response gene hsp70 mRNA levels. At 3 h postinjury, p21(WAF1/CIP1) mRNA was markedly increased in the cortex, white matter, thalamus, CA2, a part of CA1,3 and dentate gyrus of the injured side. Hybridization signals remained elevated at 6 h in injured cortex and hippocampus and returned to the baseline by 24 h post-insult. On the other hand, p53 mRNA induction was not observed in any brain sections throughout the post-injury time course. Slight expression of hsp70 mRNA was detected in the injured cortex 3-6 h following injury and this was similar to the temporary pattern of p21(WAF1/CIP1) mRNA expression. This study showed p21(WAF1/CIP1) mRNA to be transiently induced after traumatic brain injury, independent of p53, this possibly being an early stress response to protect cells by arresting them in the cycle and allow DNA repair.

Animals↗
PubMed2000

A case of an unclassified tumor closely resembling dysembryoplastic neuroepithelial tumor with rapid growth.

We describe a rare case of a tumor resembling dysembryoplastic neuroepithelial tumor. A 3-year-old girl had a generalized convulsion as the initial symptom, without other neurological deficits. Computed tomography showed a hypodense lesion with calcific hyperdensity in the left frontal lobe associated with deformity of the overlying calvarium. Four months later, she had a second seizure, and computed tomographic scan showed that the lesion had increased in size. Subtotal removal of the tumor was performed, and the postoperative course was uneventful without radiation therapy. Histological examination revealed a cortical lesion in which an oligodendrocyte-like area and an astrocyte-like area with cytological atypia were observed. Although the clinical course and the radiological findings closely resembled those of dysembryoplastic neuroepithelial tumor, specific glioneuronal elements were not found histologically. Daumas-Duport reported a complex form of dysembryoplastic neuroepithelial tumor that contained glial nodules in addition to a specific glioneuronal element. The histological findings of the glial nodules in this case were quite similar to those she described. We conclude that this could be an unclassified tumor closely resembling dysembryoplastic neuroepithelial tumor without a specific glioneuronal element.

Antigens, Nuclear↗
PubMed2000

Three-dimensional computed tomographic angiography in four patients with dissecting aneurysms of the vertebrobasilar system.

BACKGROUND: Recently, three-dimensional computed tomographic angiography (CTA) has been used for the diagnosis and treatment planning of cerebral aneurysm presenting with or without subarachnoid haemorrhage, but the diagnostic value of CTA has not been established. This study evaluated the usefulness of CTA in patients with dissecting aneurysms of the vertebrobasilar system. METHOD: Four patients with acute dissecting aneurysms were examined by CTA, including 3 women and 1 man with a mean age of 60.5 +/- 8.5 years (range: 52-67 years). There were three patients with subarachnoid haemorrhage and one patient presenting with ischaemia. One patient underwent CTA twice and digital subtraction angiography (DSA) once, while one patient had both examinations three times. CTA was performed with a nonionic contrast medium (100 ml of iomeprol 350 mg I/ml) administered via an auto-injector into an antecubital vein at 1.5-1.7 ml/s. To reconstruct three-dimensional images, the volume rendering method was utilized. FINDINGS: All initial CTA studies were performed safely within 5 hours after onset. In patients with subarachnoid haemorrhage, all lesions were demonstrated by finding either the "pearl and string sign" or a "double shadow" on CTA. In the patient presenting with ischaemia, "pearl and string sign" and "double shadow" was shown after the second CTA, and follow-up CTA was able to demonstrate the change of the lesion morphology. All lesions had more irregular luminal surfaces than the non-lesional segments of the involved vessels. INTERPRETATION: CTA was safe in patients with acute vertebrobasilar dissection and demonstrated either the "pearl and string sign" or a "double shadow" which were commonly showed on DSA. An "irregular luminal surface sign" on CTA seems to be one of the characteristics of vertebrobasilar dissection. The view shown by CTA is not less useful than that by DSA to diagnosis and treatment planning in the acute phase of vertebrobasilar dissection, and can also be employed to follow the changes of lesion morphology over time.

Aged↗
PubMed2000

Nafamostat mesilate, a serine protease inhibitor, suppresses lipopolysaccharide-induced nitric oxide synthesis and apoptosis in cultured human trophoblasts.

We investigated the effects of nafamostat mesilate, a synthetic protease inhibitor clinically used for patients with pancreatitis or disseminated intravascular coagulopathy, on NO synthesis and apoptosis in lipopolysaccharide (LPS)-treated human trophoblasts. Nafamostat mesilate or aminoguanidine, an inhibitor of NO synthase, suppressed NO synthesis and apoptosis in trophoblasts induced by LPS. Both agents also suppressed matrix metalloproteinase-2 activity induced by LPS. LPS also stimulated secretion of IL-6 and IL-8 in cultured trophoblasts, which was suppressed by nafamostat mesilate. Protease inhibitors including nafamostat mesilate may be therapeutic agents for chorioamnionitis and various diseases including septic shock, ischemia-reperfusion injury in brain and heart, graft rejection, and acute phase inflammatory diseases, in which overproduction of NO or peroxynitrite is involved in tissue injury.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Elevation of total nitrite and nitrate concentration in vaginal secretions as a predictor of premature delivery.

We measured the total concentration of nitrite and nitrate, metabolites of nitric oxide, in vaginal secretions from pregnant women at 22 to 32 weeks' gestation. Total nitrite and nitrate concentrations in patients with preterm premature rupture of membranes and in those with preterm labor and subsequent premature delivery were significantly higher than concentrations in patients who were delivered at term. Elevated total nitrite and nitrate concentration may predict premature delivery.

Biomarkers↗
PubMed2000

Investigation of blood flow in meningothelial and fibrous meningiomas by xenon-enhanced CT scanning.

We investigated whether xenon-enhanced computed tomography was able to separate meningothelial meningioma from fibrous meningioma. Cerebral blood flow was studied by xenon-enhanced computed tomography in six patients with incidentally detected intracranial meningiomas. All of the tumors were small (< 32 mm) and there was little or no peritumoral edema. Three patients had meningothelial meningioma and three patients had fibrous meningioma. The tumor blood flow and the contralateral tissue blood flow were determined. The ratio of these parameters was 1.753 +/- 0.467 for meningothelial meningiomas and 0.809 +/- 0.105 for fibrous meningiomas, with a significant difference between the two tumor subtypes (p = 0.0185). There was no correlation between the signal intensity on magnetic resonance imaging and tumor subtype, and the findings on cerebral angiography also did not indicate the subtype. In conclusion, xenon-enhanced computed tomography showed a difference between smaller meningothelial and fibrous meningiomas in patients with normal surrounding brain tissue. We could not confirm that xenon-enhanced computed tomography was able to distinguish the subtype of meningioma because of the small number of subjects in this study, but our findings might expand interest in the clinical use of this method.

Aged↗
PubMed2000

GnRH agonist-suppressed expression of nitric oxide synthases and generation of peroxynitrite in adenomyosis.

Because overproduction of nitric oxide (NO) and peroxynitrite is known to cause tissue injury, the expression of NO synthases (NOS) and generation of peroxynitrite were investigated in adenomyosis. Immunoreactivities to endothelial and inducible NOS demonstrated phase-dependent changes in normal endometrium, and in eutopic endometrium of adenomyosis. However, NOS were expressed throughout the menstrual cycle in ectopic endometrium from the majority of patients with adenomyosis. Nitrotyrosine, a footprint of peroxynitrite, was detected concomitantly with NOS protein. This suggested that high doses of NO and superoxide are produced in the ectopic endometrium, presumably by stimulation with bioactive molecules such as cytokines and growth factors. The expression of NOS and generation of peroxynitrite were markedly reduced by administration of gonadotrophin-releasing hormone agonists (GnRHa). The suppression of serum concentrations of nitrite/nitrate, stable metabolites of NO, by long-term administration of GnRHa was also demonstrated. The suppression of synthesis of NO and/or peroxynitrite may be part of both the therapeutic and adverse effects of GnRHa therapy.

Adult↗
PubMed2000

Tissue distribution and pharmacological potential of SM-16896, a novel oestrogen-bisphosphonate hybrid compound.

Postmenopausal osteoporosis is caused mainly by a deficiency of oestrogen with rapid bone loss. To target oestrogen to the bone effectively, we have synthesized and evaluated the effects of a novel hybrid compound of oestrogen and bisphosphonate, SM-16896. The tissue distribution pattern and pharmacological potential are reported. Although the affinity for calf uterine oestrogen receptor was very low (IC50: 73.3 microM; 1/25000 of that of 17beta-oestradiol (2.84 nM)), SM-16896 showed oestrogenic activity. SM-16896 (1 microM) induced a 4.5-fold transcriptional activity in rat osteosarcoma UMR-106 cells compared with vehicle-treated control, when we used the expression vector for human oestrogen receptor and a CAT reporter plasmid containing an oestrogen-responsive element. The distribution of SM-16896 after a subcutaneous administration to 7-week-old female rats was examined by radioluminography using 3H-labelled SM-16896. At 30 min after the administration, significant radioactivity was detected in the bone. At 24 h after administration, a high level of radioactivity was detected in the bone, but in the uterus it was only at a background level. Daily subcutaneous administration of 0.5 mgkg(-1) SM-16896 for 12 weeks (five times per week) to 13-week-old ovariectomized rats suppressed the ovariectomized-induced reduction in bone mineral density. A bone mineral density ratio of 120% was maintained compared with sham-operated rats, whereas a relatively low suppression of uterine weight was observed (about 50% loss compared with sham-operated rats). In the same experiment, the implantation of a 17beta-oestradiol time-release pellet (0.25 mg/pellet/90 days) almost completely suppressed the reduction of both the bone mineral density and uterine tissue weight. It is likely that the effect of SM-16896 on bone was due to its oestrogenic activity, since 1.0 mgkg(-1) SM-18108, the bisphosphonate moiety of this compound, had no effect on bone in 7-week-old ovariectomized rats. The results suggest that SM-16896, a bisphosphonate-conjugated oestrogen, showed a preference profile in the uterus and bone due to its characteristic distribution pattern compared with the natural oestrogen analogue 17beta-oestradiol. Thus, bisphosphonate-conjugated oestrogens have the potential to improve patient compliance in oestrogen therapy by minimizing adverse effects and reducing the frequency of medication.

Animals↗
PubMed2000

Blood flow study of meningothelial and fibrous meningiomas by xenon-CT.

Cerebral blood flow was studied by xenon-enhanced computed tomography in six patients with incidentally detected intracranial meningiomas. All of the tumors were small (< 32 mm) and there was little or no peritumoral edema. Three patients had meningothelial meningioma and three patients had fibrous meningioma. The tumor blood flow(TBF) and the contralateral tissue blood flow(CLBF) were determined. The ratio of these parameters(TBF/CLBF) was 1.753 +/- 0.467 for meningothelial meningiomas and 0.809 +/- 0.105 for fibrous meningiomas, with a significant difference between the two tumor subtypes (p = 0.0185). There was no correlation between the signal intensity on magnetic resonance imaging and tumor subtype, and the findings on cerebral angiography also did not indicate the subtype. The small meningothelial and fibrous meningiomas with little effect on the surrounding brain tissue could be distinguished from each other by xenon-enhanced computed tomography.

Aged↗