Pregnancy and delivery complicated by mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.
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Adult↗
Biomedical subjects
R Nakano
Publications and source records attributed to R Nakano.
Immunohistochemical localization of activin A in human endometrial tissues during the menstrual cycle and in early pregnancy.
OBJECTIVE: To investigate the possible localization of activin A in human endometrial tissue. METHODS: Human endometrial tissue was collected from 33 patients who were undergoing abdominal hysterectomy. Human decidual tissue was collected from 11 patients, who were having a therapeutic abortion. Tissue was fixed in Bouin's solution and made into paraffin sections. Tissue sections were stained with monoclonal antibodies against the inhibin/activin alpha- and betaA-subunits and activin A using an avidin-biotin-peroxidase complex technique. RESULTS: No immunostaining with antibody against the alpha-subunit was observed in the human endometrium during the menstrual cycle or in the decidua during early pregnancy. By contrast, immunostaining for the betaA-subunit and activin A was observed in the cytoplasm of endometrial glands at all phases of the menstrual cycle and in the decidua during early pregnancy. The intensity of immunostaining for the betaA-subunit was strong during the menstrual phase, became weaker during the early proliferative phase, and was intense again at the late proliferative phase. The immunostaining for the betaA-subunit was weak during the early secretory phase and became very intense toward the midsecretory and late secretory phases. The intensity of immunostaining for activin A changed during the menstrual cycle and showed a tendency similar to that for betaA-subunit. The stromal cells were weakly immunoreactive with antibodies against the betaA-subunit and activin A from the menstrual to the midsecretory phase and became strong in the late secretory phase. Intense staining for the betaA-subunit and activin A was observed in the cytoplasm of decidual cells during early pregnancy. CONCLUSION: Activin A, but not inhibins, is localized in the endometrial tissue. The endometrium may be a major source of activin A during the normal menstrual cycle, and the decidua may be one of the sources of activin A during early pregnancy.
Activins↗
Apoptosis in human chorionic villi and decidua during normal embryonic development and spontaneous abortion in the first trimester.
To investigate possible apoptotic changes, the cleavage of DNA in human chorionic villi and decidua was examined during the first trimester of pregnancy by molecular biochemical techniques. Very limited but detectable cleavage of DNA was recognized in the chorionic villi and decidua in normal pregnancy. The characteristic apoptotic breakdown of DNA was recognized in the chorionic villi and decidua in cases of spontaneous abortion. Quantitative analysis of low molecular weight fragments of DNA revealed a significant increase in cases of spontaneous abortion compared to those in normal pregnancy. However, the extent of apoptosis was not correlated with either urinary levels of human chorionic gonadotropin (hCG) and/or gestational age. An analysis in situ revealed cells undergoing apoptosis in the cytotrophoblast in normal pregnancy, and apoptotic cells were predominant in the syncytiotrophoblast in cases of spontaneous abortion. It is shown that apoptosis occurs in the human conceptus during the first trimester of normal pregnancy and is greatly intensified in cases of spontaneous abortion. In addition, the results indicate that apoptosis might play a critical role in embryonic development and wastage in humans.
Abortion, Spontaneous↗
Noninvasive hemodynamic measurements of superior mesenteric artery in the prediction of portal pressure response to propranolol.
BACKGROUND/AIMS: The portal pressure response to propranolol administration is heterogeneous in patients with cirrhosis. The aim of this study was to examine the diagnostic accuracy of noninvasive hemodynamic parameters of superior mesenteric artery (SMA) and femoral artery (FA) in the prediction of portal pressure response to propranolol. METHODS: Twenty-six patients with cirrhosis were studied. Portal pressure was assessed by measurements of hepatic venous pressure gradient. Mean arterial pressure and heart rate were also recorded. Cardiac index, and flow velocity of SMA and FA, and pulsatility index of SMA and FA were then measured by means of Doppler ultrasonography. After intravenous propranolol administration (0.10 mg/kg), the above measurements were repeated. RESULTS: Propranolol significantly reduced cardiac index, heart rate, SMA flow velocity, and FA flow velocity and increased SMA pulsatility index and FA pulsatility index. Although propranolol significantly decreased hepatic venous pressure gradient, a reduction of > or =20% was seen in only 10 patients (good responders); the remaining 16 patients exhibited <20% reduction (poor responders). No significant differences in clinical and baseline hemodynamic data were found in the two groups. There were no also significant differences in changes in heart rate and cardiac index. However, reductions in SMA and FA flow velocity were significantly greater in good responders than in poor responders. Although there was no the increase in FA pulsatility index, the increase in SMA pulsatility index was significantly greater in good responders than in poor responders. When appropriate cut-off points were determined for these variables, overall predictive values of SMA flow velocity (-20%) and SMA pulsatility index (+15%) were 91% and 83%, whereas the overall predictive value of FA flow velocity (-25%) was only 69%. CONCLUSIONS: These results suggest that SMA flow velocity and SMA pulsatility index, but not FA flow velocity and FA pulsatility index, are useful noninvasive parameters in the prediction of portal pressure response to propranolol administration.
Adult↗
Upright posture decreases esophageal varices flow velocity in patients with cirrhosis.
BACKGROUND/AIMS: Patients with cirrhosis tend to have esophageal variceal bleeding episodes at night, rather than during the day time. Since human beings carry on ordinary activities in the upright posture in the day time and are recumbent at night, we hypothesized that posture may be a factor related to a circadian variation of variceal bleeding. The aim of this study was to examine the effect of upright posture on esophageal varices hemodynamics in patients with cirrhosis. METHODS: Nine patients with cirrhosis and esophageal varices were included in a crossover study performed on 2 separate days. On the non-endoscopic day, cardiac output, portal vein flow velocity, and superior mesenteric artery flow velocity were measured with percutaneous Doppler ultrasonography. Plasma renin activity and plasma norepinephrine concentrations were also determined. On the endoscopic day, in addition to the above measurements, esophageal varices flow velocity was measured using transesophageal Doppler ultrasonography. These measurements were performed in the supine position and 20 min after the assumption of the upright position. RESULTS: On the non-endoscopic day, the upright posture significantly decreased cardiac output, portal vein flow velocity, and superior mesenteric artery flow velocity. Plasma renin activity and plasma norepinephrine concentration were significantly increased after assumption of the upright position. On the endoscopic day, similar hemodynamic and hormonal changes were observed. In addition, the upright posture significantly decreased esophageal varices flow velocity. Furthermore, the magnitude of the reduction in esophageal varices flow velocity (-42%) was significantly greater than that in portal vein flow velocity (-22%, p<0.01) and that in superior mesenteric artery flow velocity (-25%, p<0.01). Although the change in esophageal varices flow velocity was not significantly correlated with that in plasma renin activity (r=-0.28) and that in plasma norepinephrine concentration (r=-0.10), it was significantly correlated with the change in superior mesenteric artery flow velocity (r=0.73, p<0.05). CONCLUSIONS: The upright posture decreases esophageal varices flow velocity mainly because of the reduction in splanchnic blood flow. This effect may contribute to a low prevalence of esophageal variceal bleeding in the day time in patients with cirrhosis.
Aged↗
Deterministic annealing EM algorithm.
This paper presents a deterministic annealing EM (DAEM) algorithm for maximum likelihood estimation problems to overcome a local maxima problem associated with the conventional EM algorithm. In our approach, a new posterior parameterized by `temperature' is derived by using the principle of maximum entropy and is used for controlling the annealing process. In the DAEM algorithm, the EM process is reformulated as the problem of minimizing the thermodynamic free energy by using a statistical mechanics analogy. Since this minimization is deterministically performed at each temperature, the total search is executed far more efficiently than in the simulated annealing. Moreover, the derived DAEM algorithm, unlike the conventional EM algorithm, can obtain better estimates free of the initial parameter values. We also apply the DAEM algorithm to the training of probabilistic neural networks using mixture models to estimate the probability density and demonstrate the performance of the DAEM algorithm.
Journal Article↗
Learning dynamical systems by recurrent neural networks from orbits.
This paper investigates the problem of approximating a dynamical system (DS) by a recurrent neural network (RNN) as one extension of the problem of approximating orbits by an RNN. We systematically investigate how an RNN can produce a DS on the visible state space to approximate a given DS and as a first step to the generalization problem for RNNs, we also investigate whether or not a DS produced by some RNN can be identified from several observed orbits of the DS. First, it is proved that RNNs without hidden units uniquely produce a certain class of DS. Next, neural dynamical systems (NDSs) are proposed as DSs produced by RNNs with hidden units. Moreover, affine neural dynamial systems (A-NDSs) are provided as nontrivial examples of NDSs and it is proved that any DS can be finitely approximated by an A-NDS with any precision. We propose an A-NDS as a DS that an RNN can actually produce on the visible state space to approximate the target DS. For the generalization problem of RNNs, a geometric criterion is derived in the case of RNNs without hidden units. This theory is also extended to the case of RNNs with hidden units for learning A-NDSs.
Journal Article↗
Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch.
To elucidate the molecular mechanisms whereby expanded polyglutamine stretches elicit a gain of toxic function, we expressed full-length and truncated DRPLA (dentatorubral-pallidoluysian atrophy) cDNAs with or without expanded CAG repeats in COS-7 cells. We found that truncated DRPLA proteins containing an expanded polyglutamine stretch form filamentous peri- and intranuclear aggregates and undergo apoptosis. The apoptotic cell death was partially suppressed by the transglutaminase inhibitors cystamine and monodansyl cadaverine (but not putrescine), suggesting involvement of a transglutaminase reaction and providing a potential basis for the development of therapeutic measures for CAG-repeat expansion diseases.
Animals↗
YM268 increases the glucose uptake, cell differentiation, and mRNA expression of glucose transporter in 3T3-L1 adipocytes.
The purpose of this study was to examine the effects of bis[4-[2,4-dioxo-5-thiazolidinyl)methyl]phenyl]methane (YM-268), a thiazolidinedione derivative, on glucose uptake, adipocyte differentiation through peroxisome proliferator-activated receptor gamma(PPARgamma), and phosphatidylinositol 3-kinase (PI 3-kinase) activity in cultured cells. YM268 and pioglitazone dose-dependently increased the 2-deoxyglucose uptake in 3T3-L1 cells. YM268 facilitated the insulin-stimulated triglyceride accumulation in 3T3-L1 adipocytes and increased the mRNA expression of fatty acid-binding protein. YM268, with and without insulin, increased the mRNA expression of glucose transporter isoforms such as GLUT1 and GLUT4, indicating enhancement of adipocyte differentiation. Additionally, YM268 and pioglitazone showed activity of the PPARgamma ligand, a member of the nuclear receptor superfamily responsible for adipogenesis. To examine the possible involvement of the increased activity of PI 3-kinase in YM268-stimulated glucose uptake, the enzyme activity was estimated by measuring the phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) concentration in human monocytic cells. Insulin dose-dependently increased the PI-3,4,5-P3 production but YM268 had no significant effect on the insulin-dependent and -independent PI 3-kinase activation. These results indicate that the mechanism by which YM268 increased glucose uptake, may be accounted for in part by the enhancement of GLUT1 and GLUT4 expression through PPARgamma activation.
3T3 Cells↗
Apoptosis in human chorionic villi and decidua in normal and ectopic pregnancy.
To investigate possible effects of implantation on apoptosis, we examined the cleavage of DNA in human chorionic villi and decidua in intrauterine and ectopic pregnancy. Very limited but detectable cleavage of DNA was recognized in the chorionic villi and decidua in normal pregnancy. A ladder pattern, characteristic of the apoptotic breakdown of DNA, was present in the villi in tubal pregnancy. High molecular weight DNA was predominant in the decidua in tubal pregnancy. Quantitative analysis of low molecular weight fragments of DNA revealed a significant increase in the villous tissue, together with a significant decrease in the decidual tissue, in tubal pregnancy as compared to those in normal pregnancy. An analysis in situ revealed that apoptotic cells were predominant in the syncytiotrophoblast in tubal pregnancy. In decidual tissue, labelled cells were occasionally seen in normal pregnancy, and their numbers decreased in tubal pregnancy. The present study demonstrates that apoptosis occurs in the villi, but not in the decidua in tubal pregnancy, unlike the situation in normal pregnancy. Our results suggest that the implantation site might affect the occurrence of apoptotic changes in early pregnancy of humans.
Apoptosis↗
Differential expression and internal feedback regulation of 1-aminocyclopropane-1-carboxylate synthase, 1-aminocyclopropane-1-carboxylate oxidase, and ethylene receptor genes in tomato fruit during development and ripening.
We investigated the feedback regulation of ethylene biosynthesis in tomato (Lycopersicon esculentum) fruit with respect to the transition from system 1 to system 2 ethylene production. The abundance of LE-ACS2, LE-ACS4, and NR mRNAs increased in the ripening fruit concomitant with a burst in ethylene production. These increases in mRNAs with ripening were prevented to a large extent by treatment with 1-methylcyclopropene (MCP), an ethylene action inhibitor. Transcripts for the LE-ACS6 gene, which accumulated in preclimacteric fruit but not in untreated ripening fruit, did accumulate in ripening fruit treated with MCP. Treatment of young fruit with propylene prevented the accumulation of transcripts for this gene. LE-ACS1A, LE-ACS3, and TAE1 genes were expressed constitutively in the fruit throughout development and ripening irrespective of whether the fruit was treated with MCP or propylene. The transcripts for LE-ACO1 and LE-ACO4 genes already existed in preclimacteric fruit and increased greatly when ripening commenced. These increases in LE-ACO mRNA with ripening were also prevented by treatment with MCP. The results suggest that in tomato fruit the preclimacteric system 1 ethylene is possibly mediated via constitutively expressed LE-ACS1A and LE-ACS3 and negatively feedback-regulated LE-ACS6 genes with preexisting LE-ACO1 and LE-ACO4 mRNAs. At the onset of the climacteric stage, it shifts to system 2 ethylene, with a large accumulation of LE-ACS2, LE-ACS4, LE-ACO1, and LE-ACO4 mRNAs as a result of a positive feedback regulation. This transition from system 1 to system 2 ethylene production might be related to the accumulated level of NR mRNA.
Alkenes↗
Effect of meal induced splanchnic arterial vasodilatation on renal arterial haemodynamics in normal subjects and patients with cirrhosis.
AIMS: To investigate the relation between changes in splanchnic arterial haemodynamics and renal arterial haemodynamics in controls and patients with cirrhosis. METHODS: Superior mesenteric artery pulsatility index (SMA-PI) and renal artery pulsatility index (R-PI) were measured using Doppler ultrasonography in 24 controls and 36 patients with cirrhosis. These measurements were repeated 30 minutes after ingestion of a liquid meal or placebo. Sixteen controls and 24 patients received the meal, and eight controls and 12 patients received placebo. RESULTS: In the fasting condition, patients with cirrhosis had a lower SMA-PI (p<0.01) and a greater R-PI (p<0.01) compared with controls. Placebo ingestion had no effect on splanchnic and renal haemodynamics. In contrast, ingestion of the meal caused a notable reduction in SMA-PI (p<0.01, p<0.01) and an increase in R-PI (p<0.01, p<0.01) in controls and patients with cirrhosis. The meal induced haemodynamic change in SMA-PI was inversely correlated with that in R-PI in controls (t=-0.42, p<0.05) and in patients with cirrhosis (t=-0.29, p<0.05). CONCLUSIONS: Results support the hypothesis that renal arterial vasoconstriction seen in patients with cirrhosis is one of the kidney's homoeostatic responses to underfilling of the splanchnic arterial circulation.
Blood Pressure↗
Decreased type V collagen expression in human decidual tissues of spontaneous abortion during early pregnancy.
AIM: To provide some insight into the aetiology of spontaneous abortion, the contents of type V collagen was investigated in human decidual tissues in spontaneous abortion and normal pregnancy. METHODS: Collagens were extracted from decidual tissues in spontaneous abortion (n = 19) and normal pregnancy (n = 25). The different types of collagen alpha chains were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), stained with Coomassie brilliant blue, and measured by densitometry. The relative amounts of the alpha 1 (III) and alpha 1 (V) chains were calculated by dividing the band intensities of the alpha 1 (III) and alpha 1 (V) chains by that of the alpha 1 (I) chain. RESULTS: The ratio of the alpha 1 (V) chain to that of the alpha 1 (I) chain in decidual tissues in spontaneous abortion was significantly lower than that found in normal pregnancy (p < 0.05). CONCLUSIONS: These results suggest that type V collagen might play an important role in the maintenance of pregnancy and that decreased expression of this collagen could be associated with spontaneous abortion.
Abortion, Spontaneous↗
Familial amyotrophic lateral sclerosis with widespread vacuolation and hyaline inclusions.
This report presents a familial amyotrophic lateral sclerosis (FALS) patient with widespread vacuoles and hyaline inclusions strongly immunostained with the anti-superoxide dismutase (SOD1) antibody. The overall pathologic similarity between our non-SOD1-linked FALS patient and transgenic mice expressing a mutated human SOD1 gene suggests that common pathogenetic mechanisms other than an SOD1 mutation exist in the development of these diseases.
Aged↗
The role of tyrosine kinase in gonadotropin-induced ovulation in the rat ovary.
OBJECTIVES: Our purpose was to elucidate the involvement of the tyrosine kinase pathway in gonadotropin-induced ovulation in the rat ovary. STUDY DESIGN: We investigated the effect of a tyrosine kinase inhibitor, tyrphostin, on the rat ovulatory process in vivo and in vitro. METHODS: In cultured rat granulosa cells, the effect of tyrphostin on LH-, dibutyryl cyclic AMP ((Bu)2cAMP)- or forskolin-stimulated tissue type plasminogen activator (tPA) activities was examined by using a fibrin autography technique. In an in vivo system, tyrphostin was injected into the bursal cavity of the ovary in pregnant mare serum gonadotropin-treated rats, just before human chorionic gonadotropin administration. After 24 h, the number of oocytes in the oviduct was counted and the tyrphostin-treated ovaries were examined histologically. RESULTS: Tyrphostin inhibited LH-stimulated tPA activity but did not affect (Bu)2cAMP- or forskolin-stimulated ones. In an in vivo study, tyrphostin suppressed oocyte release dose-dependently. Histological observations revealed that tyrphostin-treated ovaries contained many large unruptured follicles and a few corpora lutea. CONCLUSION: This study suggests that the suppressive effect of tyrphostin on ovulation may be partly due to tPA activity inhibition in the granulosa cells via the suppression of tyrosine kinase activity. Additionally, tyrosine kinase phosphorylation may be involved in gonadotropin-activated signaling systems in the rat ovulatory process.
Animals↗
[A patient with an ACTH-releasing thymic carcinoid tumor presenting with proximal muscle weakness].
We report a 36-year-old man with proximal dominant muscle weakness, thymic tumor, diabetes mellitus, hypokalemia, and increased levels of plasma ACTH and cortisol. The diagnosis of carcinoid tumor was made on the basis of pathological findings in the biopsied specimen of the thymic tumor. The proximal muscle weakness was considered to be due to steroid myopathy resulting from the overproduction of cortisol from the adrenal glands induced by the ectopic ACTH secreted by the thymic carcinoid tumor. Although thymoma in frequently associated with myasthenia gravis, we should also consider carcinoid tumors in patients with a thymic tumor presenting with a proximal muscle weakness.
Adrenocorticotropic Hormone↗
Human canalicular multispecific organic anion transporter (cMOAT) is expressed in human lung, gastric, and colorectal cancer cells.
Human canalicular multispecific organic anion transporter (cMOAT), a glutathione conjugate membrane transporter, has been isolated from cisplatin-resistant cancer cells and is distributed mainly in normal liver. We analyzed the expression of human cMOAT in 14 lung, 11 gastric, and 9 colorectal non-drug-selected human cancer cells, two multidrug-resistant cells, and one cisplatin-resistant cells, using quantitative RT-PCR and newly developed anti-human cMOAT antibody. All cell lines analyzed here expressed human cMOAT at the level of mRNA and protein, and some of them expressed higher levels of human cMOAT than the cisplatin-resistant cells. The two multidrug-resistant cell lines co-expressed human cMOAT gene and both or either of MRP and MDR1 genes. Immunostaining showed that human cMOAT was predominantly localized to the cytoplasm of these single cells. Our results indicate that human cMOAT is expressed in various human cancer cells including drug-resistant cells.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Partial BFGS update and efficient step-length calculation for three-layer neural networks.
Second-order learning algorithms based on quasi-Newton methods have two problems. First, standard quasi-Newton methods are impractical for large-scale problems because they require N2 storage space to maintain an approximation to an inverse Hessian matrix (N is the number of weights). Second, a line search to calculate a reasonably accurate step length is indispensable for these algorithms. In order to provide desirable performance, an efficient and reasonably accurate line search is needed. To overcome these problems, we propose a new second-order learning algorithm. Descent direction is calculated on the basis of a partial Broydon-Fletcher-Goldfarb-Shanno (BFGS) update with 2Ns memory space (s < < N), and a reasonably accurate step length is efficiently calculated as the minimal point of a second-order approximation to the objective function with respect to the step length. Our experiments, which use a parity problem and a speech synthesis problem, have shown that the proposed algorithm outperformed major learning algorithms. Moreover, it turned out that an efficient and accurate step-length calculation plays an important role for the convergence of quasi-Newton algorithms, and a partial BFGS update greatly saves storage space without losing the convergence performance.
Algorithms↗