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Both genetic and environmental factors have been considered causative agents for schizophrenia (SZ). However, no single gene has been shown responsible for the development of SZ. Furthermore, the pathophysiological roles of environmental factors including psychological stress, autoimmunity, and microbial infection have not been fully understood. Previous studies have suggested the involvement of one of the human endogenous retroviruses (HERVs), HERV-W, in SZ. In this study, prevalence of antibodies against the HERV-W Syncytin-1 protein was examined using a newly developed ELISA test. Fifty percent of patients with SZ (24 out of 48 cases) were antibody-positive, with a specificity of greater than 95% (less than 5% of control cases, 3 out of 79). No significant effect of medication was evident, nor did any SZ cases become seropositive after diagnosis. These findings indicate a possible involvement of HERV-W expression in the development of SZ and support its applicability to laboratory diagnoses.

Aims: The purposes of this study were to clarify the changes in smoothness of each phase by making use of the angular jerk cost for the smoothness of the knee joint motion at the stance phase in patients with osteoarthritis, to verify the relationship between the kinetics variables and the smoothness, and to clarify the dynamics in osteoarthritis by comparison with healthy subjects using the angular jerk cost of knee flexion or extension. Methods: The osteoarthritis group comprised 19 knees of 12 subjects with a Kellgren– Lawrence grade of 1 in at least one knee. The control group comprised 10 healthy adults. The subjects walked barefoot along a 10-m walkway at their self-selected habitual speeds. The stance phase of gait was defined as four periods To calculate the smoothness of the knee joint movement, the angular jerk cost of the knee joint angle during the stance phase was calculated by differentiation three times using the knee joint angle data. Results: The angular jerk cost was increased in the early stance phase in both groups. Only the osteoarthritis group showed a large angular jerk cost in the late stance phase. The ground reaction force in the osteoarthritis group showed a small value in the stance Original Research Article British Journal of Medicine & Medical Research, 4(6): 1345-1354, 2014 1346 phase compared with the control group. Conclusion: The movement of the knee joint at the initial stance phase had a strategy to ensure the smoothness of the movement by decreasing the change in the angular acceleration in accordance with the impairment disorder. In addition, the smoothness of the knee joint movement was decreased at the late stance phase compared from the loading response to mid-stance period in the osteoarthritis group, and the propulsion for forward movement of the body was exerted by a change involving a large angular acceleration with a large force.

Nuruk is a traditional fermentation starter used for making starch-based Korean alcoholic drinks. The yeast strain Pichia kudriavzevii N77-4 was newly isolated from nuruk. Resistance to ethanol stress is a crucial characteristic in alcoholic beverage production, but the ethanol stress-resistance of P. kudriavzevii remains to be clarified. In this study, we attempted to analyze the ethanol resistance of P. kudriavzevii N77-4, and to improve it by ethyl methanesulfonate (EMS) mutagenesis. After 4 h of cultivation in 5% ethanol, N77-4 showed a growth defect accompanied with accumulation of reactive oxygen species (ROS). In addition, exposure of N77-4 to ethanol stress induced a more than 3-fold increase in the expression of PkSOD2, which encodes a superoxide dismutase, indicating that the strain was able to generate PkSOD2 to decrease ROS. EMS mutagenesis was performed to improve the ethanol resistance of N77-4. An isolated mutant, HER8, exhibited higher ethanol resistance, a 50% decrease in ROS accumulation, and enhanced expressions of PkGPX2, which encodes a glutathione peroxidase, and PkSOD1. Moreover, HER8 showed 10% greater ethanol production, indicating that up-regulation of these antioxidant genes is important for improving ethanol resistance in P. kudriavzevii, and use of the HER8 strain will improve the brewing fermentation.

The pathogenesis of thrombocytopenia during the neonatal period in Down's syndrome (DS) infants remains unclear.To elucidate kinetic changes of serum thrombopoietin (TPO) level and platelet count, and their correlation in DS neonates.Twelve DS infants (male/female: 7/5, term/late preterm: 10/2) born between 1997 and 2007 were included. Blood samples were serially collected during the neonatal period and serum TPO levels were determined in 44 sera using an enzyme-linked immunosorbent assay.Thrombocytopenia150 x 10(9) per liter was observed in seven (58%) patients. In 12 DS patients, the median TPO value showed 2.86 fmol ml(-1) on day 0, rose to 4.64 fmol ml(-1) on day 2, and thereafter decreased to 4.30 fmol ml(-1) on day 5, 2.40 fmol ml(-1) on days 11-15, and 1.75 fmol ml(-1) on days 28-30. This kinetics parallels that in historical non-DS controls. In 35 pair sample analysis from 11 patients without transient myeloproliferative disease, TPO level inversely correlated with platelet count (r=-0.38, P=0.023). However, there was no significant difference in TPO concentrations between thrombocytopenic and non-thrombocytopenic DS individuals.This is the first study to describe the relationship between TPO level and platelet count in neonates with DS. Median TPO levels and their kinetic changes in DS neonates are comparable to those in non-DS controls. In contrast to earlier findings in several studies showing higher TPO concentrations in thrombocytopenic non-DS newborns than those in non-thrombocytopenic counterparts, the response of the TPO system to thrombocytopenia in DS during the neonatal period seems suboptimal.

Nanometer-sized α-Fe particles formed by the gas evaporation method were transferred into the microwave plasma region with a carrier gas of Ar including a small amount of CH4. Particles collected after the plasma region were found to show a composite phase of Fe-C system that consisted of α-Fe and γ-Fe (Austenite) and Fe3C. Moessbauer spectroscopy was used to estimate the relative yield of these three phases. An increase of γ- Fe is followed by the decrease of α-Fe with increasing CH4 content. Formation of Fe3C was recognized at 0.5 vol% of CH4 in Ar gas and became more remarkable when the CH4 content was increased. HRTEM observation revealed the individual particles to be a concentric shell structure composed of the Fe-C system.

Effects of the metal—metal distance on the third-order nonlinear optical property of one-dimensional platinum complexes were investigated. Glyoximes with several alkyl substituents were synthesized as a ligand for one-dimensional platinum complexes. All prepared platinum complexes had linear platinum chains in the solid state and had different platinum—platinum distance depending on the steric hindrance of alkyl substituents. They showed the 5dZ2—6pZ transition band in the visible region, of which peak wavelengths were well related to the platinum—platinum distance. Frequency dispersion of the third-order nonlinear susceptibilities ¢(3) for evaporated thin films of platinum—alkyldione-dioxime complexes was estimated by the third-harmonic generation measurements. It was revealed that the shorter metal—metal distance gave the larger ¢(3).

The third-order non-linear optical properties of evaporated thin films of d8 transition metal complexes with dionedioxime have been estimated by third harmonic generation. They formed one-dimensional structures and showed large optical non-linearities. Resonance effects were observed for respective metal complexes. The maximum χ(3) value of 5.6 × 10−11 esu was obtained at the near three-photon resonance wavelength for the platinum complex. The delocalized electrons in linear metal chains may be essential for exhibiting large non-linear optical effects.

Formation of ultra-shallow p+/n junction has been performed with the combination of low-temperature solid phase epitaxy and non-melt laser annealing. The former is aimed for improving crystallinity of junction region and the latter for activating implanted B ions. After pre-amorphization implantation of Ge, B ion implantation was performed at energy of 0.2keV with a dose of 1.2×1015/cm2. With adequate conditions, the junction depth around 8nm with sheet resistance of 920 Ω/□ is successfully formed in non-melting state. B dopant profile is kept almost with the as-implanted profile. In addition, the junction leakage current at reverse bias decreases dramatically with low-temperature solid phase epitaxy due to the reduction of residual defects.

Thermal nano-phase change of an Antimony (Sb) thin film sandwiched by dielectric layers were investigated, and the application for super-density optical data storage by optical near-field was described.

Program refactoring is a technique to enhance the maintainability of a program. Although the concept itself is considered to be effective, there are few quantitative evaluation of its impact to the software maintainability. It is sometimes difficult to judge whether the refactoring in question should be applied or not without knowing the effect accurately. We propose a quantitative evaluation method to measure the maintainability enhancement effect of program refactoring. We focused on the coupling metrics to evaluate the refactoring effect. By comparing the coupling before and after the refactoring, we could evaluate the degree of maintainability enhancement. We applied our method to a certain program and showed that our method was really effective to quantify the refactoring effect and helped us to choose appropriate refactorings.

Source code copying for reuse (code cloning) is often observed in software implementations. Such code cloning causes difficulty when software functionalities are modified: i.e, cloned codes increase the maintenance cost of software. We aim to estimate the maintenance cost caused by clones. We propose a novel approach, which evaluates influence of cloned codes over the maintenance cost. The basic idea is to measure functional redundancy (FR): a degree of propagation of clone-potential functions. FR is measured as follows: first, we cluster functions in the software according to similarities between them. Second, we make an n-ary weighted tree(FR tree) based on the cluster. Finally, we measure FR by weight of each node in FR-tree. In this paper, we describe the details of our proposal. We also apply the approach to 17K-ELOC C code to demonstrate its effectiveness.

We propose a verification method for software specification. In order to avoid software faults, our method derives safety assertions using FTA, computes the behavioral graph of specification and analyzes statically whether this graph satisfies safety assertions. Moreover, when there exists an assertion which can not hold, our method localizes software design faults. >

Focusing on logic programming, a practical method is proposed for verifying and debugging large programs invoking many subprograms. If a programmer gives a few simple constraints on arguments of the top-level program, then the approach automatically verifies that these constraints hold with a method for propagating constraints to its subprograms. Using both propagated constraints and recursive structure of programs, the method verifies the correctness of there constraints with an inductive method. Moreover, when these exists a constraint which can not hold, the approach shows debugging information on the program. The authors have implemented a verifying and debugging system for Prolog programs based on their method. Some experimental results are described. >

The paper describes a quality assurance approach for source code to assure source code quality with less effort than conventional method. The paper introduces the data relation tracking method (DRTM) as a practical instance of data oriented program analysis, a key factor of our new quality assurance approach. DRTM helps comprehension of the source code by extracting the internal logic of the source code in declarative notation. An example and evaluation of DRTM for the C language is also described. The example shows that DRTM can deal in data structures and inter-data relations of any control structure. The evaluation shows that DRTM can extract the internal logic of the source code uniquely and that the extracted internal logic is useful for quality assurance of the source code.

The purposes of this study are to examine two points; 1) What effects do regular visits to hospitals have on the existence of friend?. and 2) Do the elderly use hospitals as substitutes for other meeting places or independent of other places?.Data concerning 2,447 older adults were obtained from a national survey for the elderly aged 60 and over, conducted in 1996. 1) To examine effects of regular visits to hospitals on friends, friendships as a dependent variable, regular visits to hospitals as a confounding variable, and some two way-interaction terms as independent variables were entered in logistic regression analysis. 2) To analyze relationships between hospitals and other meeting places, correspondence analyses and logistic regression were used. 3) Existence of friends whom the elderly contact at hospitals as a dependent variable, existence of friends whom they meet at other places as a confounding variable, and some two way-interaction terms as independent variables were entered in logistic regression analysis. 3) Relationships between clinics and other meeting places were also analyzed using correspondence analyses and logistic regression.1. Although regular visits to hospitals did not have a significant direct impact on existence of friends, the respondents with low activities of daily living who regularly visits hospitals were more likely to have friends than ones did not visits hospitals. 2. The respondents who meet friends at hospitals were also more likely to have contacts with friends at community centers for the elderly or community organization. 3. The respondents who meet friends at clinics had similar characteristics to those who meet friends at hospitals.Regular visits to hospitals may contribute to maintain contacts with friends, especially in the elderly with low ADL. The elderly may use hospitals as meeting places with friends independent of other places. Hospitals may have similar functions to what clinics as meeting places with friends.

We investigated the effects of melatonin on ischemia/reperfusion-induced oxidative damage to mitochondria in fetal rat brain. The utero-ovarian arteries were occluded bilaterally for 20 min in female Wistar rats on day 19 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation for 30 min. A sham operation was performed in control rats. Melatonin (10 mg/kg) or vehicle was injected intraperitoneally 60 min prior to occlusion. We measured the respiratory control index (RCI) and the adenosine 5-diphosphate (ADP)/oxygen ratio as indicators of mitochondrial respiratory activity, as well as the concentration of thiobarbituric acid-reactive substances (TBARS) in the mitochondria of fetal brain. Ischemia/reperfusion significantly elevated the concentration of TBARS and significantly reduced the RCI as well as the ADP/oxygen ratio. Melatonin treatment reversed the ischemia/reperfusion-induced reductions in the RCI (2.29 +/- 0.06-2.64 +/- 0.09, P0.05) and in the ADP/oxygen ratio (1.48 +/- 0.03-1.57 +/- 0.02, P0.05), and also reduced the elevation in concentration of TBARS (11.00 +/- 0.34-7.57 +/- 0.74 nM/mg protein, P0.01), resulting in values similar to those in untreated, sham-ischemic animals. The results indicate that administration of melatonin to pregnant rats may prevent ischemia/reperfusion-induced oxidative mitochondrial damage in fetal rat brain.

In preeclampsia, placental production of lipid peroxides is abnormally increased, while placental glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are decreased. Administration of melatonin, a powerful scavenger of oxygen free radicals, also may protect the placenta from free radical-induced damage by increasing the activity of antioxidant enzymes. To test this hypothesis we administered melatonin to pregnant women before they underwent voluntary interruption of pregnancy between 7 and 9 wk of gestation. Melatonin (6 mg) was administered orally at 12:00 hr, and samples of chorion and maternal blood were obtained at the time of the procedure, 1, 2 or 3 hr later. We measured the melatonin concentration in maternal serum and activities of GSH-Px and SOD and levels of melatonin in chorionic homogenates. Melatonin administration was reflected by markedly increased melatonin concentrations in maternal serum and in chorion, with peak levels achieved 1 hr after melatonin administration (serum, 46.87 +/- 10.87 nM/L; chorionic homogenate, 4.36 +/- 1.56 pmol/mg protein). Between 1 and 3 hr after melatonin administration, GSH-Px activity in chorionic homogenates increased significantly (P0.001), with peak levels occurring at 3 hr (51.68 +/- 3.22 mU/mg protein per min, 137.3% of GSH-Px activity in untreated control subjects). No significant changes in chorionic SOD activity occurred during the 3-hr post-administration period. These results indicate that exogenous melatonin increases GSH-Px activity in the chorion and thereby may protect indirectly against free radical injury. Melatonin could be useful in treating preeclampsia and possibly other clinical states involving excessive free radical production, such as intrauterine fetal growth retardation and fetal hypoxia.

We evaluated mechanisms underlying the antioxidant property of melatonin as related to vasospastic effects in the human umbilical artery from lysophosphatidylcholine (LPC), a component of oxidized lipoprotein. Helical sections of umbilical artery without endothelium were obtained at elective cesarean delivery between 37 and 39 wk of gestation. Changes in 5-hydroxytryptamine (5-HT)-induced vasoconstriction were measured. Arterial sections were treated with LPC (15 or 30 microM) alone or pretreated with a hydroxyl radical (.OH) scavenger, mannitol (20 mM), an H2O2 scavenger, catalase (1,200 U/mL), or melatonin (0.1 or 1.0 microM). The effect of LPC on the response of arterial sections to external calcium in the presence of KCl (20 mM) was determined. LPC potentiated 5-HT-induced vasoconstriction in a concentration-dependent manner; pretreatment with mannitol or catalase significantly reduced this vasospastic effect. LPC (30 microM) significantly augmented the contractile response to external calcium. Melatonin (1.0 microM) pretreatment significantly suppressed the contractile response to external calcium. The results suggest that LPC potentiates 5-HT-induced umbilical artery vasoconstriction, in part by increasing the calcium influx into smooth muscle cells via activation of voltage-dependent calcium channels. Given a previous finding, the vasospastic effect of LPC on the umbilical artery also appears to involve the suppression of endothelial nitric oxide production. Melatonin significantly suppresses the vasospastic effect of LPC, probably by scavenging .OH arising from LPC.

Our objective was to investigate the effects of melatonin on the free radical-induced oxidative damage to mitochondria in fetal rat brain. Female Wistar rats on day 19 of pregnancy were used. Melatonin (10 mg/kg) or vehicle (control) was injected intraperitoneally 60 min prior to laparotomy for removal of the fetuses. The mitochondrial fraction was isolated from the fetal rat brain of each group. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured. As indicators of mitochondrial respiratory activity, we determined the respiratory control index (RCI) and the adenosine 5-diphosphate/oxygen (ADP/O) ratio in the presence and absence of 2.5 microM hypoxanthine and 0.02 units/mL xanthine oxidase. Mitochondrial lipid peroxidation was determined by measuring the concentration of thiobarbituric acid reactive substances in fetal brain mitochondria in the presence or absence of 2.5 microM hypoxanthine, 0.02 units/mL xanthine oxidase, and 50 microM FeSO4. The free radical-induced rates of inhibition of mitochondrial RCI and the ADP/O ratio were both significantly lower in the fetal rat brains treated with melatonin compared with those of the controls (RCI, 44.25 +/- 15.02% vs. 25.18 +/- 5.86%, P0.01; ADP/O ratio, 50.74 +/- 23.05% vs. 13.90 +/- 7.80%, P0.001). The mitochondrial lipid peroxidation induced by free radicals was significantly reduced in the melatonin-treated group compared with the controls (484.2 +/- 147.2%) vs. 337.6 +/- 61.0%, P0.01). Pretreatment with melatonin significantly increased the activity of GSH-Px (20.35 +/- 5.27 to 28.93 +/- 11.01 mU/min mg(-1) protein, P0.05) in fetal rat brain mitochondria, but the activity of SOD did not change significantly. Results indicate that the administration of melatonin to the pregnant rat may prevent the free radical-induced oxidative mitochondrial damage to fetal rat brain by a direct antioxidant effect and the activation of GSH-Px.

We evaluated the antioxidant property of melatonin as related to the vasospastic effect of lysophosphatidylcholine (LPC), a component of oxidized lipoprotein, on the human umbilical artery. Helical sections of umbilical arteries with intact endothelium were obtained at elective cesarean delivery between 37 and 39 weeks of gestation. Changes in 5-hydroxytryptamine (5-HT)-induced vasoconstriction were measured. Arterial sections were treated with LPC alone (15 or 30 microM) or pretreated with an hydroxyl radical (.OH) scavenger (mannitol), a cyclooxygenase inhibitor (indomethacin, 20 microM), nitric oxide (NO) synthesis inhibitor (L-N(G)-monomethylarginine, LNMA, 2 x 10(-4) M), or melatonin (1 or 10 microM). LPC potentiated 5-HT-induced contraction in a concentration-dependent manner. Pretreatment with mannitol significantly suppressed the vasospastic effect of LPC. LNMA augmented the vasospastic effect of LPC, but indomethacin did not. Melatonin significantly suppressed the vasospastic effect of LPC in a concentration-dependent manner. Considering a previous finding that .OH and oxidized low-density lipoprotein decrease NO production in the human umbilical artery, the vasospastic effect of LPC appear to involve suppression of endothelial NO synthesis. Melatonin significantly suppresses the vasospastic effect of LPC, probably by scavenging .OH arising from LPC.

We evaluated the antioxidant property of melatonin as related to the vasospastic effect of lysophosphatidylcholine (LPC), a component of oxidized lipoprotein, on the human umbilical artery. Helical sections of umbilical arteries were obtained from healthy pregnant women who were delivered between 37 and 39 wk of gestation. Changes in maximal tension induced by KCl were measured in arterial sections having intact endothelium. Sections were treated with LPC alone (15 or 30 microM), or were pretreated either with a hydrogen peroxide (H2O2) scavenger (catalase, 1,200 U/mL), a hydroxyl radical scavenger (mannitol, 30 mM), a nitric oxide (NO) synthesis inhibitor (L-N(G)-monomethyl arginine, LNMA, 2 x 10(-4) M) or melatonin (1 or 10 microM). The effect of LPC (30 microM) on the vasorelaxation induced by 5-hydroxytryptamine (5-HT) was also determined, with or without melatonin pretreatment (10 microM). LPC potentiated vascular tension in a concentration-dependent manner. Pretreatment with LNMA significantly suppressed this vasospastic effect of LPC. Pretreatment with catalase or mannitol significantly reduced the vasospastic effect of LPC. Melatonin significantly lessened the vasospastic effect of LPC in a concentration-dependent manner. Pretreatment with LPC significantly inhibited the relaxation induced by 5-HT. Treatment with melatonin prior to LPC exposure significantly restored the relaxation induced by 5-HT. Results suggest that LPC potentiates vascular tension in human umbilical artery, perhaps by suppressing the endothelial synthesis of NO. Melatonin significantly suppressed the vasospastic effect of LPC. This agent probably scavenges the hydroxyl radicals arising from LPC.

We evaluated the antioxidant property of melatonin in countering the vasospastic effect of oxidized low-density lipoprotein (ox-LDL), which has been reported to be the most important risk factor for atherosclerosis and also may be linked to preeclampsia. Helical sections of umbilical arteries were obtained from human placentas at elective cesarean deliveries between 37 and 39 weeks of gestation. Changes in maximal tension induced by potassium chloride were measured in arterial sections with intact endothelium. ox-LDL (200 or 300 microg protein/mL) increased vascular tension by 15.6 +/- 2.3 or 31.9 +/- 4.0%, respectively. In contrast, native LDL only slightly increased vascular tension (2.7 +/- 1.0% for 200 microg protein/mL and 6.0 +/- 1.7% for 300 microg protein/mL). Pretreatment with L-N(G)-monomethyl-arginine (2 x 10(-4) M) significantly reduced the vasospastic effect of ox-LDL, as did pretreatment with mannitol (30 mM). Melatonin (10 microM) significantly reduced the vasospastic effect of ox-LDL. These findings suggest that ox-LDL potentiates vascular tension in the human umbilical artery, possibly by suppressing endothelial synthesis of nitric oxide. Melatonin significantly suppressed the vasospastic effect of ox-LDL, probably because it scavenges hydroxyl radical arising from ox-LDL.

Publisher Summary This chapter proposes a heating model of nanoparticles in a plasma and explains the quenching of the high-temperature phase of iron (γ-Fe). The heating mechanism of nanoparticles in a plasma helps understand the mechanism of phase transition and allows a precise application such as the surface decoration of nanoparticles. The temperature rise of Fe-nanoparticles with the size ranging from 10 to 100nm is calculated by using the measured electron temperature and ion density, the maximum values of them being 6.6eV and 1.7*1018m-3, respectively. It is found that in one heat cycle of pulsed plasma with repetition of 120Hz the temperature of Fe-nanoparticles varies drastically from gas temperature to 2460K with the increase of the heat input from the plasma. The chapter illustrates the results of the heating model of nanoparticles in the form of an electron micrograph and an X-ray diffraction profile of plasma processed Fe-nanoparticles.

With recent advances in laparoscopic surgery, many reports have described laparoscopic cornual resection for interstitial pregnancy as a safe alternative to laparotomy. We report a laparoscopic cornuostomy for unruptured interstitial pregnancy with myometrium reconstruction.A 32-year-old woman presented with complaints of abdominal cramps and vaginal spotting after 6 weeks of amenorrhea. Ultrasonographic examination revealed a gestational sac 7 mm in diameter in the left uterine corner. There was clear separation between the endometrium and gestational sac. A 3-mm periumbilical trocar for the laparoscope and a 3-mm trocar in the lower abdomen were used, and the left interstitial pregnancy was confirmed. An additional, 5-mm trocar was used in the lower abdomen for the laparoscopic surgery. The patient underwent a laparoscopic cornuostomy. Myometrium reconstruction was performed by suturing and tying with a laparoscopic technique.In this case, minilaparoscopy was useful in the diagnosis and treatment of interstitial pregnancy.

The purpose of this study was to examine the impact of social support on life satisfaction among Japanese elderly aged 60 and over (N = 1,285), using the longitudinal data of a national representative sample. An initial survey was carried out in 1987, and a follow-up was conducted in 1990. We measured life satisfaction by the Life Satisfaction Index A. Social support was measured from two aspects, providing support and receiving support. The impact of social support and changes in support during a period of three years on life satisfaction were assessed by sex after controlling for influences of socioeconomic status, physical functioning, and initial life satisfaction. Providing support predicted a high life satisfaction three years later only in females. Receiving support was not significantly associated with life satisfaction for either males or females. However changes in providing and receiving support had a significant impact on life satisfaction of the elderly. The findings of this study suggest that the effects of social support on life satisfaction differ by sex and the impacts of changes in support are strong determinant predicting life satisfaction of the elderly.

We examined the expression of a recently characterized novel estrogen receptor (ER) beta in 25 cases of invasive ductal carcinoma of the breast, using messenger RNA (mRNA) in situ hybridization, and compared the findings with those of ERalpha, to study its localization and its possible biological significance in human breast cancer. ERalpha and ERbeta hybridization signals were both detected, predominantly in carcinoma cells and in some stromal cells, in 18 of 25 (72%) and 11 of 25 (44%) cases, respectively. The cases in which more than 25% of carcinoma cells demonstrated mRNA hybridization signals were 13 of 25 (52%) and 2 of 25 (8%) cases for ERalpha and ERbeta, respectively. Among the cases expressing ERbeta, 10 of 11 (91%) also expressed ERalpha mRNA; and in these 10 cases, coexpressing both ERalpha and beta, the number of carcinoma cells expressing ERalpha was greater than that expressing ERbeta in 9 cases. Eight cases demonstrated only ERalpha mRNA hybridization signals in carcinoma cells. These results indicate that ERbeta is coexpressed with ERalpha in most ERbeta-positive breast carcinoma cells, which suggests that the expression of ERbeta depends on the presence of ERalpha in the great majority of human breast cancer. In addition, the number of carcinoma cases and/or the ratio of carcinoma cells expressing ERalpha was much greater than those expressing ERbeta. The relative ratio of ERalpha and ERbeta expression in carcinoma cells may be related to various estrogen-dependent biological features of human breast cancer.

The clonality of epithelial cells in ovarian endometriotic cysts was evaluated on the basis of a polymorphism of the X-linked phosphoglycerate kinase gene (PGK). The problems associated with clonality analysis of DNA samples extracted from archival formalin-fixed, paraffin-embedded tissue were addressed with the use of newly designed primers and a modified stepdown program for PCR amplification. The method relies on digestion of DNA with the methylation-sensitive restriction enzyme SnaBI, PCR amplification of PGK, and detection of a BstXI polymorphism. With this approach, only the inactive (methylated) PGK allele is selectively amplified by PCR. A total of 25 epithelial cells in endometriotic cysts and 25 matched normal ovarian stromal tissue specimens were analyzed. All of the control tissue samples yielded PCR products, with 11 of the 25 samples found to be heterozygous for the BstXI polymorphism. Ten of the 25 epithelial cells in endometriosis specimens were informative at this locus, and all of these 10 were shown to be monoclonal on the basis of PGK methylation. The results indicate that this new method of clonal analysis with archival formalin-fixed tissue is reliable and confirm that endometriotic cysts are monoclonal in origin.

MOSFETs scaling-down is an effective way to attain high-performance CMOS operating with lower power and leakage current. However, short channel effects have become a serious problem due to the shortening of channel length. One of the promising methods to suppress this problem is by forming a shallow, highly doped and activated source/drain extension region. Fabricating ultra shallow p+/n junction is difficult due to the channeling of boron ions and anomalous boron diffusion during fabrication processes. A combination of Ge pre-amorphization implantation, low-energy boron implantation and two-step annealing, involving low-temperature solid phase epitaxy preannealing followed by non-melt laser annealing was used for forming ultra shallow p+/n junction in silicon. The physical relationship among the regrowth of implanted layer, boron activation and diffusion, and leakage current is investigated. We have succeeded in forming ultra shallow p+/n junction with junction depth of 8 nm and sheet resistance of 920 Ω/□.

Growth hormone (GH) is believed to be involved in reproductive function. Recent reports demonstrate the presence of the growth hormone receptors (GHR) in reproductive organs and fetal tissues suggesting that the contribution of GH to reproductive phenomena may be mediated through GHR. In this study we assessed the expression of GHR in mouse preimplantation embryos using immunofluorescent staining with a monoclonal antibody directed against GHR. The messenger RNA (mRNA) for GHR was investigated in mouse preimplantation embryo by reverse transcription-polymerase chain reaction (RT-PCR). The anti-GHR monoclonal antibody Mab 263 was detected by immunofluorescent staining after the compaction of the morula stage. GHR mRNA transcript was identified in 8-cell stage embryos. Our findings indicate that GHR is localized in mouse preimplantation embryos, and suggests that GH has a direct effect on preimplantation embryos mediated by GHR.

In October 1988, a six year old Japanese girl with restrictive cardiomyopathy underwent heart transplantation (HTx) at Harefield Hospital in the U.K. Six years 9 months after her HTx, she is doing well and is the longest survivor among the Japanese HTx recipients. Cardiac catheterization 5 years after her HTx showed good cardiac function with LVEF of 54.7%. Coronary angiogram at that time showed no abnormal findings. Cardiac biopsy revealed no sign of rejection or myocyte degeneration. LVDd (Left Ventricular Diastolic Dimension) grew from 35.5 mm at the time of transplant to 42.6 mm 5 years later by echocardiogram, suggesting the growth of the transplanted heart. Her good progress, including catch-up growth and good QOL, reflects the excellent benefit of HTx today. The authors deeply appreciate the courtesy of Harefield Hospital in accepting to perform her HTx.

It is well known that gonadotropin controls a major part of follicular development. However, the mechanism of local regulation under the control of gonadotropins in still unclear. In this study, we focused on the local regulation of steroidogenesis, growth factors and cell proliferation to evaluate the human follicular development. To assess steroidogenesis, it is important to detect the expression of steroidogenic enzymes in the granulosa and theca cells during folliculogenesis. We initially tried to find out the transcription factor Ad4BP that binds the Ad4 site and regulates the function of steroidogenic enzyme. By immunohistochemistry, the expression of Ad4BP was confirmed sporaf1p4lly in preantral granulosa cells. In the antral follicles, the expression of Ad4BP was observed both in the granulosa and theca cell. According steroidogenic enzyme, we evaluated temporal and spatial localization of cholesterol side chain cleavage (scc), 3 beta hydroxysteroid dehydrogenase (3 beta HSD), 17 alpha hydroxylase (17 alpha) and aromatase, and steroid receptors. In briefly, the localizations of scc, 3 beta HSD and 17 alpha were observed in preantral follicles and the mRNA expressions of these enzymes were confirmed in the theca cell by in situ hybridization method. Expression of aromatase was generally observed in only one follicle (antral or mature follicle) per case in mid proliferative to premenstrual phase. The localization of androgen and estrogen receptor was observed in the antral follicle granulosa cells, and estrogen receptor was detected only in aromatase positive follicles. These results suggested that Ad4BP initially controls the function of steroidogenic enzymes and steroidogenic enzymes gradually express from primary follicles to mature follicles. At antral follicle stage, steroid metabolism completes to produce testosterone. When aromatase and estrogen receptor express in antral follicle, this antral follicle develops as the dominant follicle and produces estradiol to promote follicle maturation. We therefore speculate that the expression of aromatase and estrogen receptor have an important role for the selection of dominant follicle in human. According growth factors for follicular development, it has been demonstrated to be important in the biological activity in the ovary. In this study, we examined the localization of EGF, TGF alpha and their receptor (EGFR). The localization of EGF was not confirmed both mRNA and protein level through follicular development. On the other hand, the localization and expression of TGF alpha was confirmed in theca cells and EGFR in granulosa cells at antral stage.(ABSTRACT TRUNCATED AT 400 WORDS)

It has been demonstrated that co-administration of growth hormone (GH) augments ovarian response to human menopausal gonadotrophin, and GH itself increases steroidogenesis in cultured ovarian cells. It is not clear, however, whether the effects of GH on the ovary are direct or not. We performed immunohistochemistry using specific monoclonal antibodies against human GH receptor on 51 specimens of pre-menopausal human ovaries from various phases of the menstrual cycle to detect and localize GH receptors. Immunohistochemical localization of P450 aromatase and 3 beta-hydroxysteroid dehydrogenase was performed using these enzymes as immunohistochemical markers for steroidogenesis in these ovaries. GH receptor immunoreactivity was observed in luteinized granulosa cells in corpora lutea in the luteal phase, which are considered to be active in steroid production. In the follicular phase, GH receptor immunoreactivity was detected in the granulosa layer of only three out of 35 antral follicles. These results demonstrate that immunoreactivity of GH receptor is present in human ovaries, suggesting a direct action of GH on human ovarian functions, especially during luteal phase.

Diagnosis of sinus venosus atrial septal defect based on transthoracic color Doppler and two-dimensional echocardiography is often difficult. We recently experienced two cases of sinus venosus atrial septal defect which were correctly diagnosed using transesophageal color Doppler and two-dimensional echocardiography. Transthoracic color Doppler flow imaging did not demonstrate the atrial septal defect or the shunt flow across the defect in either case. Transesophageal two-dimensional echocardiography visualized a defect in the upper most portion of the interatrial septum in one case, and transesophageal color Doppler flow mapping detected a left-to-right shunt across the defect in both cases. Transesophageal color Doppler flow mapping also demonstrated the flow signal of the right upper pulmonary vein into the right atrium near its junction with the superior vena cava in each case. The diagnoses of sinus venosus atrial septal defect and combined partial anomalous pulmonary venous return were confirmed by surgery in both cases. Transesophageal color Doppler and two-dimensional echocardiography are very useful in diagnosing sinus venosus atrial septal defect and combined partial anomalous pulmonary venous return.

During recording of spinal cord evoked potentials, a monophasic positive potential is observed when a nerve impulse approaches but does not pass beyond the recording site. This type of potential has been termed a killedend evoked potential (KP). While this potential is useful for localizing the injured site clinically, no other clinical value has yet been reported for it. The KP is usually higher in amplitude than the positive wave of normal evoked potentials. The higher amplitude has been attributed to background injury currents resulting from a low transmembrane resistance at the damage site of axons. The amplitude of the KP may therefore represent a clinically available indicator of injury currents, which have been implicated in secondary processes of axonal degeneration.