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Biomedical subjects

T Araki

Publications and source records attributed to T Araki.

At least 55 records · Page 3Linked to original sources
PubMed2001

Influence of mild hypothermia on delayed mitochondrial dysfunction after transient intrauterine ischemia in the immature rat brain.

The aim of this study was to determine the effect of different maternal thermal conditions during transient intrauterine ischemia on the mitochondrial respiratory activities in the immature rat brain. On 17 days of gestation, transient intrauterine ischemia was induced by 30 min of right uterine artery occlusion under hypothermic (33.5-34.5 degrees C, n=6), normothermic (36.5-37.5 degrees C, n=6), and hyperthermic conditions (39.5-40.5 degrees C, n=6). All of the pups were delivered by cesarean section at 21 days of gestation and cerebral neocortical tissue was sampled 1 h after delivery. The mitochondrial respiration was measured polarographically in homogenates. In the ischemic uterine horn, ADP-stimulated respiration of the normothermia and the hyperthermia groups decreased significantly to 73 and 74% of the non-ischemic controls, respectively. Since non-stimulated respiration remained unchanged, the respiratory control ratio (RCR) of the normothermia and the hyperthermia groups decreased significantly to 59 and 54% of the non-ischemic levels, respectively. In contrast, the mitochondrial respiratory activities of the hypothermia group showed no differences between the non-ischemic and the ischemic uterine horns. The results demonstrate that mild maternal hypothermia ameliorates the cerebral mitochondrial dysfunction in neonatal rats after intrauterine ischemia due to transient uterine artery occlusion and suggest that maternal thermal conditions, particularly during uteroplacental insufficiency, have important implications for the neuropathological outcome of the newborn.

Animals↗
PubMed2001

An SH2-domain-containing kinase negatively regulates the phosphatidylinositol-3 kinase pathway.

SHK1 is a novel dual-specificity kinase that contains an SH2 domain in its C-terminal region. We demonstrate that SHK1 is required for proper chemotaxis and phagocytosis. Mutant shk1 null cells lack polarity, move very slowly, and exhibit an elevated and temporally extended chemoattractant-mediated activation of the kinase Akt/PKB. GFP fusions of the PH domain of Akt/PKB or the PH-domain-containing protein CRAC, which become transiently associated with the plasma membrane after a global stimulation with a chemoattractant, remain associated with the plasma membrane for an extended period of time in shk1 null cells. These results suggest that SHK1 is a negative regulator of the PI3K (phosphatidylinositol-3 kinase) pathway. Furthermore, when a chemoattractant gradient is applied to a wild-type cell, these PH-domain-containing proteins and the F-actin-binding protein coronin localize to its leading edge, but in an shk1 null cell they become randomly associated with the plasma membrane and cortex, irrespective of the direction of the chemoattractant gradient, suggesting that SHK1 is required for the proper spatiotemporal control of F-actin levels in chemotaxing cells. Consistent with such functions, SHK1 is localized at the plasma membrane/cortex, and we show that its SH2 domain is required for this localization and the proper function of SHK1.

Actins↗
PubMed2001

FASCIATA genes for chromatin assembly factor-1 in arabidopsis maintain the cellular organization of apical meristems.

Postembryonic development of plants depends on the activity of apical meristems established during embryogenesis. The shoot apical meristem (SAM) and the root apical meristem (RAM) have similar but distinct cellular organization. Arabidopsis FASCIATA1 (FAS1) and FAS2 genes maintain the cellular and functional organization of both SAM and RAM, and FAS gene products are subunits of the Arabidopsis counterpart of chromatin assembly factor-1 (CAF-1). fas mutants are defective in maintenance of the expression states of WUSCHEL (WUS) in SAM and SCARECROW (SCR) in RAM. We suggest that CAF-1 plays a critical role in the organization of SAM and RAM during postembryonic development by facilitating stable maintenance of gene expression states.

Amino Acid Sequence↗
PubMed2001

Standalone cutting balloon angioplasty for the treatment of stent-related restenosis: acute results and 3- to 6-month angiographic recurrent restenosis rates.

Despite excellent acute reperfusion results, 20%-30% of patients who undergo coronary stent implantation will develop angiographic restenosis and may require same additional treatments. Cutting Balloon angioplasty (CBA) causes less histological damage outside of the incised area than a regular balloon. However, regular plain old balloon angioplasty is sometimes required before CBA, as is adjunctive stenting and adjunctive angioplasty. These adjunctive strategies may negate the advantages of CBA. There is little data available on CBA as a standalone therapy for stent-related restenosis (SRS). The aim of this study was to evaluate the acute and 3- to 6-month angiographic recurrent restenosis rates following standalone CBA in a patient population treated for SRS and in whom optimal acute results were obtained. In this study, 40 patients with SRS (54 lesions) underwent standalone CBA with optimal acute results. For all lesions, coronary angiography was conducted before and after a standalone CBA procedure for SRS and systematically during 3-6 months to assess recurrent angiographic restenosis rates in the study population. In the study lesions, SRS was either diffuse disease (> 15 mm; 52%) or focal type (48%). Cutting Balloon diameter was 3.20 +/- 0.44 mm and maximal inflation pressure 8.7 +/- 1.2 atm. Ratio of Cutting Balloon diameter to restenotic stent diameter was 0.996 +/- 0.487. Multiple inflations (6 +/- 3 times) were performed. Number of used Cutting Balloon was 1.02 +/- 0.14. Complications were as follows; one non-Q-wave MI (1.9%); 0 death (0%), and 17 repeat target lesion revascularizations (TLRs; 32%). Follow-up coronary angiography (CAG) was not attained for one patient. The angiographic recurrent restenosis rate was 34%, with a higher rate observed when the SRS was diffuse type, 50% vs. 16% for focal-type SRS (P < 0.01). The recurrent restenosis rate for smaller vessels (vessel diameter < or = 3.0 mm) was the same as for larger ones. At follow-up CAG, diffuse-type recurrent restenosis (56%) presented nearly as frequently as that presenting in the original SRS lesions (52%). But four diffuse-type SRS (29%) changed into focal-type recurrent stenosis. In this study, standalone CBA for SRS with optimal acute results was associated with an angiographic restenosis rate of 34%. Diffuse-type disease had a higher recurrent restenosis rate. When CBA achieves acute optimal results, adjunctive stenting or adjunctive PTCA are not always necessary, particularly when the SRS is focal. As a result of CBA, some diffuse-type SRS may change into focal-type recurrent stenosis by the time of the next intervention.

Adult↗
PubMed2001

Doppler velocimetry of maternal renal circulation in pregnancy-induced hypertension.

PURPOSE: The purpose of this study was to evaluate whether the Doppler waveforms of the maternal main renal, segmental, and interlobar arteries are altered in women with pregnancy-induced hypertension (PIH) compared with healthy pregnant women. METHODS: Flow waveforms of the maternal main renal, segmental, and interlobar arteries were obtained from 42 healthy pregnant women between 24 and 41 weeks of gestation and 21 women with PIH between 28 and 40 weeks of gestation using pulsed Doppler sonography. We used spectral analysis to measure the peak systolic and end-diastolic velocities and the acceleration time. The presence or absence of the normal early systolic compliance peak-reflective-wave complex (ESP) was assessed in only the main renal artery. RESULTS: The acceleration times of the segmental and interlobar arteries were significantly prolonged in the PIH group compared with those in the healthy pregnant women. Of the 21 women with PIH, 3 showed loss of the ESP in the renal artery, but these changes were not significant. CONCLUSIONS: Decreased systolic acceleration and the absence of ESP, the hemodynamic indicators for significant proximal stenosis, suggest that severe stenosis or continuous vasospasm in the proximal arteries, such as the main renal or segmental artery, may be implicated in the pathogenesis of PIH.

Adult↗
PubMed2001

Mitotic index and ki-67 nuclear antigen labeling index as predictors of chemotherapy response in uterine cervical carcinoma.

OBJECTIVE: The aim of this study was to determine if the mitotic index (MI) and the Ki-67 nuclear antigen labeling index (Ki67LI) obtained from biopsy specimens could be used as predictors of chemotherapy response in uterine cervical carcinomas. METHODS: Six patients with squamous cell carcinoma who received neoadjuvant chemotherapy before radical surgery were entered into the study. The MI and the Ki67LI were evaluated using hematoxylin and eosin (H&E)-stained and immunostained slides before and after chemotherapy. Tumor size was measured three-dimensionally by magnetic resonance imaging. We compared the values of MI and Ki67LI with changes in tumor size. RESULTS: The cases were classified according to the percentage reduction in tumor mass: one case showed a marked response (98%), four showed a moderate response (53-78%), and one showed a slight response (approximately 0%). In the case with a marked response, the MI values before chemotherapy and 3 and 7 days after chemotherapy were 15, 2, and 0, respectively. The corresponding Ki67LI values were 51, 16, and 0, respectively. In the moderate response cases, the corresponding MI values before and 3 and 7 days after chemotherapy were 3.9-13.6, 0.8-1.6, and 1.6-4.0, respectively. The Ki67LI was 21.8-44.2 before chemotherapy, with two cases increasing and two decreasing at 7 days after chemotherapy. In the case showing a slight response, the MI values before chemotherapy and 3 and 7 days after chemotherapy were 0.5, 0.8, and 1.0, respectively. The Ki67LI was 4.0 before chemotherapy and increased slightly to 6.0 at 7 days after chemotherapy. CONCLUSIONS: In six cases examined, high MI and Ki67LI values before chemotherapy and a marked decrease in MI shortly after chemotherapy appeared to be predictors of good neoadjuvant chemotherapy response in uterine cervical carcinomas.

Adult↗
PubMed2001

Brain perfusion measured by flow-sensitive alternating inversion recovery (FAIR) and dynamic susceptibility contrast-enhanced magnetic resonance imaging: comparison with nuclear medicine technique.

The aim of this study was to compare cerebral perfusion images and regional cerebral blood flow (rCBF) of SPECT study with the images and regional intensity of relative cerebral blood flow (CBF) images acquired by contrast-enhanced perfusion MR imaging (pMRI) and flow-sensitive alternating inversion recovery (FAIR). Twelve patients with various cerebral diseases were underwent I-123-IMP SPECT, pMRI, and FAIR studies to measure rCBF. A total of 12 regions of interest (ROI) were created over cerebrum and cerebellum to acquire the corresponding rCBF from I-123-IMP study and regional average signal intensity from CBF images of pMRI and FAIR studies. Left-to-right (L/R) and cerebral-to-cerebellar (CCR) ratios were created from the rCBF of I-123-IMP and signal intensity of CBF images of pMRI and FAIR. Image quality of FAIR was the poorest among all; however, CBF images of pMRI and FAIR images show comparatively decreased intensity at the corresponding site of decreased perfusion on I-123-IMP images. Both FAIR and pMRI images showed high intensity along the sinuses, choroid plexus, and large vessels in sulci. No significant correlation was found among all imaging modalities. But L/R ratio of I-123-IMP showed significant correlation with those of pMRI and FAIR, but for CCR, significant correlation was observed only between I-123-IMP and FAIR. Perfusion images of both pMRI and FAIR may produce images comparable to SPECT study. But to calculate absolute CBF more easy-to-apply and accurate algorithms are needed to overcome the artifacts from large vessels.

Adult↗
PubMed2001

MR imaging of clear cell carcinoma of the ovary.

Magnetic resonance imaging findings are reported for 12 pathologically proven lesions of clear cell carcinoma (CCC) of the ovary in 11 women (mean age 50 years). T1- and T2-weighted MR images were obtained in all patients, and gadolinium-enhanced MR images were obtained in 9. The mean diameter of the tumors was 13 cm. Seven patients presented with stage-I tumors. All 12 lesions consisted of cystic masses with solid protrusions occurring in 10 and solid masses in 2. The cysts were unilocular in 9 lesions and multilocular in 1. In four lesions, the cysts displayed with high intensity on T1-weighted images. Round solid protrusions were identified in 8 lesions. In 5 lesions, the number of protrusions was only a few. The solid portions of 5 masses had slightly high-intensity regions on T1-weighted images. The number of patients with ascites was three. Magnetic resonance imaging of CCC usually shows a unilocular large cyst with solid protrusions, which are often round and few in number. Such MR imaging findings suggest malignant tumor but are not specific.

Adenocarcinoma, Clear Cell↗
PubMed2001

Incidence of intrauterine complications in monoamniotic twin gestation.

We compared the incidence of intrauterine complications, such as twin-twin transfusion syndrome, between monochorionic-monoamniotic (MM) and monochorionic-diamniotic (MD) twin gestations. We retrospectively evaluated a series of 11 MM and 211 MD twin gestations managed after 22 weeks' gestation at our hospitals. One MM twin gestation was diagnosed with twin-twin transfusion syndrome based on clinical presentation of polyhydramnios and hydrops. The incidence of twin-twin transfusion syndrome in MM twin gestations (9.1%) was not measurable different from that in the MD twin gestations (7.6%, p=0.09). There were no measurable differences in the incidence of other complications, such as growth discordance >25% or intrauterine fetal demise between the two groups. MM twin gestations should be kept under close management while carefully monitoring for any circulatory imbalance between the twins.

Adult↗
PubMed2001

Penile agenesis complicated by Potter sequence.

We present a case of penile agenesis complicated by multicystic dysplastic kidneys and urethral agenesis, which resulted in oligohydramnios, pulmonary hypoplasia and neonatal death. In this case, no external urethral opening was found, and the gastrointestinal tract showed no anomaly. Cases of penile agenesis complicated by Potter sequence with urethral agenesis should be differentiated from those with ectopic urethral openning.

Fatal Outcome↗
PubMed2001

Gene fusion involving HMGIC is a frequent aberration in uterine leiomyomas.

HMGIC, a high-mobility-group protein gene encoding an architectural transcription factor, was recently identified as the target of gene fusion in a variety of human benign mesenchymal tumors; some of these events were chromosomal translocations involving 12q13-15. HMGIC consists of three DNA-binding domains (encoded by exons 1-3), a spacer, and an acidic carboxyl-terminal regulatory domain (exons 4-5). To determine the spectrum and nature of the aberrations in uterine myomas in Japanese patients, we systematically examined the tumors of 45 patients for all possible types of gene fusions involving HMGIC, by means of 3'-rapid amplification of cDNA ends (RACE) and reverse transcriptase-polymerase chain reaction (RT-PCR) experiments. HMGIC gene fusions were found in 16 (36%) of the tumors; aberrant splicings to five cryptic sequences located in introns of the HMGIC gene were found in 11 of these cases, and translocations causing juxtaposition to other genes, such as COX6C and RA D51B, were found in 5. In all fusion transcripts, the first two or three exons of HMGIC were fused to ectopic sequences. Our results suggest that a fusion event, resulting in the separation of the DNA-binding domains of HMGIC from the spacer and the acidic carboxyl-terminal regulatory domain, is a common tumorigenic mechanism in the development of uterine myomas.

Alternative Splicing↗
PubMed2001

Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas.

PTEN (MMAC1/TEP1), a tumor suppressor gene on chromosome subband 10q23.3, is variably mutated and/or deleted in a variety of human cancers. Germline mutations in PTEN, which encode a dual-specificity phosphatase, have been implicated in at least two hamartoma tumor syndromes that exhibit some clinical overlap, Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. Among several series of ovarian cancers, the frequency of loss of heterozygosity (LOH) of markers flanking and within PTEN, is approximately 30 to 50%, and the somatic intragenic PTEN mutation frequency is <10%. In this study, we screened primary adenocarcinomas of the ovary for LOH of polymorphic markers within and flanking the PTEN gene and for intragenic mutations of the PTEN gene and compared them to PTEN expression using immunohistochemistry. Furthermore, we sought to detect the expression of the presumed downstream targets of PTEN, such as P-Akt, p27, and cyclin D1 by immunohistochemistry. LOH at 10q23 was observed in 29 of 64 (45%) cases. Of the 117 samples, 6 somatic intragenic PTEN mutations, 1 germline mutation, and 1 novel polymorphism were found in 7 (6%) patients. Immunostaining of 49 ovarian cancer samples revealed that 13 (27%) were PTEN immunostain-negative, 25 (51%) had reduced staining, and the rest (22%) were PTEN expression-positive. Among the 44 informative tumors assessed for 10q23 LOH and PTEN immunostaining, there was an association between 10q23 LOH and decreased or absent staining (P = 0.0317). Of note, there were five (11%) tumors with neither mutation nor deletion that exhibited no PTEN expression and 10 (25%) others without mutation or deletion but had decreased PTEN expression. Among the 49 tumors available for immunohistochemistry, 28 (57%) showed P-Akt-positive staining, 24 (49%) had decreased p27 staining, and cyclin D1 was overexpressed in 35 (79%) cases. In general, P-Akt expression was inversely correlated with PTEN expression (P = 0.0083). These data suggest that disruption of PTEN by several mechanisms, allelic loss, intragenic mutation, or epigenetic silencing, all contribute to epithelial ovarian carcinogenesis, and that epigenetic silencing is a significant mechanism. The Akt pathway is prominently involved, but clearly not in all cases. Surprisingly, despite in vitro demonstration that p27 and cyclin D1 lies downstream of PTEN and Akt, there was no correlation between p27 and cyclin D1 expression and PTEN or P-Akt status. Thus, in vivo, although PTEN and Akt play a prominent role in ovarian carcinogenesis, p27 and cyclin D1 might not be the primary downstream targets. Alternatively, these observations could also suggest that pathways involving other than Akt, p27 and cyclin D1 that lie downstream of PTEN play roles in ovarian carcinogenesis.

Carcinoma↗
PubMed2001

Plasma adenosine levels and P-selectin expression on platelets in preeclampsia.

OBJECTIVE: To measure the correlation of plasma adenosine levels with platelet activation in women with preeclampsia. METHODS: Plasma adenosine concentration and expression of P-selectin, a marker for platelet activation, were measured in 18 normal pregnant women and 18 preeclamptic women. The effect of 8-sulfophenyltheophylline, an adenosine receptor blocker, on expression of P-selectin on platelets also was measured. RESULTS: Plasma adenosine level averaged 0.77 +/- 0.11 microM (standard error of the mean [SEM]) in women with preeclampsia, significantly higher than the mean level of 0.47 +/- 0.08 microM in women with normal pregnancies (P <.05). Expression of P-selectin on platelets averaged 7.8 +/- 1.2% in women with preeclampsia, also significantly higher than the mean level of 4.7 +/- 0.7% in normal pregnancy (P <.05). Adenosine receptor blockade significantly increased expression of P-selectin on platelets in women with preeclampsia by 26% (P <.05), which was significantly higher than the 13% increase of activation in those with normal pregnancies (P <.05). CONCLUSION: Adenosine is an established platelet activation suppressor. Increased plasma levels of adenosine in preeclampsia might partially compensate and tend to prevent further excessive platelet activation in women with preeclampsia.

Adenosine↗
PubMed2001

Spontaneous intracranial hypotension during pregnancy.

BACKGROUND: Spontaneous intracranial hypotension is characterized by postural headache associated with low cerebrospinal fluid pressure. CASE: A 37-year-old Japanese woman, gravida 3, para 2, had sudden onset of severe postural headache at 8 weeks' gestation, accompanied by nausea and vomiting. Results of medical and neurologic examinations were normal, and there was no measurable cerebrospinal fluid pressure on lumbar puncture. Brain magnetic resonance imaging showed diffuse subdural fluid collection and a narrowing of the ambient cistern, confirming the diagnosis of spontaneous intracranial hypotension. After a month of bed rest and intravenous fluid infusion, all symptoms subsided gradually and did not recur. CONCLUSION: Obstetricians should be aware that spontaneous intracranial hypotension can occur in pregnancy.

Adult↗
PubMed2001

Mesenchymal stem villous hyperplasia of the placenta and fetal growth restriction.

BACKGROUND: Mesenchymal stem villous hyperplasia of the placenta is a rare placental anomaly characterized by placental vascular malformation and the appearance of a partial mole. CASE: A multiparous woman presented with fetal growth restriction (FGR) at 35 weeks' gestation. Ultrasonographic examination showed multiple anechoic lesions on the placental surface. Cesarean delivery was performed at 37 weeks' gestation, and a healthy 1536-g female was delivered. The placenta had aneurysmal dilatations of the chorionic vessels. Unlike other cases, it also showed subamniotic hemorrhage and had no features of a partial mole. Histologic examination established the diagnosis of mesenchymal stem villous hyperplasia of the placenta with severe thrombosis. CONCLUSION: Fetal growth restriction can be caused by severe thrombosis in this placental anomaly.

Chorionic Villi↗
PubMed2001

EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression.

The identification of EGR2 mutations in patients with neuropathies and the phenotype Egr2/Krox20(-/-) have demonstrated that the Egr2 transcription factor is critical for peripheral nerve myelination. However, the mechanism by which these mutations cause disease remains unclear, as most patients present with disease in the heterozygous state, whereas Egr2(+/-) mice are phenotypically normal. To understand the effect of aberrant Egr2 activity on Schwann cell gene expression, we performed microarray expression profiling to identify genes regulated by Egr2 in Schwann cells. These include genes encoding myelin proteins and enzymes required for synthesis of normal myelin lipids. Using these newly identified targets, we have shown that neuropathy-associated EGR2 mutants dominant-negatively inhibit wild-type Egr2-mediated expression of essential myelin genes to levels sufficiently low to result in the abnormal myelination observed in these patients.

Animals↗
PubMed2001

Nitric oxide synthase inhibitors cause motor deficits in mice.

We investigated possible motor effects of 7-nitroindazole (7-NI), an neuronal nitric oxide synthase (nNOS) inhibitor, and N(G)-nitro-L-arginine methyl ester (L-NAME), an non-selective NOS inhibitor in mice using catalepsy and pole tests in comparison with dopamine D(2) receptor antagonist, haloperidol. We also studied the change in dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) contents of these compounds. The administration of 7-NI and L-NAME (40-160 mg/kg, s.c.) dose-dependently induced motor deficit in both catalepsy and pole tests. The motor deficit induced by 7-NI was more pronounced than the one produced by L-NAME. In contrast, haloperidol showed a marked motor deficit in mice. Haloperidol showed a marked motor deficit as compared with 7-NI and L-NAME. For dopamine, DOPAC and HVA contents, haloperidol exhibited a significant decrease in dopamine content and a significant increase in DOPAC and HVA content in the striatum. In contrast, 7-NI showed a significant increase in the striatal dopamine content. However, 7-NI had no significant change in the striatal DOPAC and HVA contents. On the other hand, no significant change in the striatal dopamine, DOPAC and HVA contents was observed in L-NAME-treated mice. The present study also showed that the motor deficit induced by 7-NI or L-NAME was significantly attenuated by the treatment with L-arginine. These results demonstrate that NOS inhibitors as well as dopamine D(2) receptor antagonist haloperidol can induce motor deficit in mice. The present study also suggests that the mechanism in the motor deficit caused by NOS inhibitors may be different from that in the motor deficit induced by haloperidol. Furthermore, our findings suggest that nNOS may play some role in control of motor behavior.

Animals↗