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Mono- (or few) layer black phosphorus (BP) is highly expected to be a next-generation two-dimensional (2D) atom-thin semiconductor. Compared with other 2D atom-thin layers, BP has a significantly anisotropic atomic structure, which can provide unique electronic, optical, and magnetic properties. Herein, we report the observation of B2/3 magnetic-field (B) dependence of the Hall resistance with extremely small quantized levels in the low-B regime of the few-layer BP, which are associated with the anisotropic electronic structure confirmed by largely anisotropic hole mobilities. One of the qualitative interpretations for the B2/3 dependence is the possible presence of a uniaxial Dirac spectrum (arising from a closed band gap caused by uniaxial stretch along the buckling armchair direction, which is occasionally introduced by a process for cutting and wire-bonding samples, confirmed by Raman spectroscopy) and its hybridization with a Schrodinger spectrum existing along a zigzag direction. The observed phenomena imply significant potential due to strong anisotropy of atom-thin (few-layer) BP, which is highly expected to open doors to novel physics and its application for innovative 2D atom-thin devices.

This study investigated the anatomical consequences of a photoreceptor toxin, iodoacetic acid (IAA), in the rabbit retina. Retinae were examined 2 weeks, 1, 3, and 6 months after systemic IAA injection. The retinae were processed using standard histological methods to assess the gross morphology and topographical distribution of damage, and by immunohistochemistry to examine specific cell populations in the retina. Degeneration was restricted to the photoreceptors and was most common in the ventral retina and visual streak. In damaged regions, the outer nuclear layer was reduced in thickness or eliminated entirely, with a concomitant loss of immunoreactivity for rhodopsin. However, the magnitude of the effect varied between animals with the same IAA dose and survival time, suggesting individual differences in the bioavailability of the toxin. In all eyes, the inner retina remained intact, as judged by the thickness of the inner nuclear layer, and by the pattern of immunoreactivity for protein kinase C-α (rod bipolar cells) and calbindin D-28 (horizontal cells). Müller cell stalks became immunoreactive for glial fibrillary acidic protein (GFAP) even in IAA-treated retinae that had no signs of cell loss, indicating a response of the retina to the toxin. However, no marked hypertrophy or proliferation of Müller cells was observed with either GFAP or vimentin immunohistochemistry. Thus the selective, long lasting damage to the photoreceptors produced by this toxin did not lead to a reorganization of the surviving cells, at least with survival as long as 6 months, in contrast to the remodeling of the inner retina that is observed in inherited retinal degenerations such as retinitis pigmentosa and retinal injuries such as retinal detachment.

The time-course of dark adaptation provides valuable insights into the function and interactions between the rod and cone pathways in the retina. Here we describe a technique that uses the flash electroretinogram (ERG) response to probe the functional integrity of the cone and rod pathways during the dynamic process of dark adaptation in the mouse. Retinal sensitivity was estimated from the stimulus intensity required to maintain a 30 μV criterion b-wave response during a 40 min period of dark adaptation. When tracked in this manner, dark adaptation functions in WT mice depended upon the bleaching effects of initial background adaptation conditions. Altered dark adaptation functions, commensurate with the functional deficit were recorded in pigmented mice that lacked cone function (Gnat2 cplf3 ) and in WT mice injected with a toxin, sodium iodate (NaIO3), which targets the retinal pigment epithelium and also has downstream effects on photoreceptors. These data demonstrate that this adaptive tracking procedure measures retinal sensitivity and the contributions of the rod and/or cone pathways during dark adaptation in both WT control and mutant mice.

Androids that replicate humans in form also need to replicate them in behaviour to achieve a high level of believability or lifelikeness. We explore the minimal social cues that can induce in people the human tendency for social acceptance, or ethopoeia, toward artifacts, including androids. It has been observed that people exhibit a strong tendency to adjust to each other, through a number of speech and language features in human-human conversational interactions, to obtain communication efficiency and emotional engagement. We investigate in this paper the phenomena related to prosodic alignment in human-computer interactions, with particular focus on human-computer alignment of speech characteristics. We found that people exhibit unidirectional and spontaneous short-term alignment of loudness and response latency in their speech in response to computer-generated speech. We believe this phenomenon of prosodic alignment provides one of the key components for building social acceptance of androids.

High-temperature and controlled humidity treatment before drying has proven to be highly effective in preventing surface checks by forming drying sets in the surface layer of boxed-heart square timber in Japan. In this study, we examined the differences of the surface drying sets on sugi timber under different treatment temperatures. As a result, the width of a surface check after drying was much smaller at a treatment temperature of 120°C than at 80°C, and this indicates that the drying set with 120°C treatment would be larger than that with 80°C treatment. Also we observed that treatment temperature had a greater effect on the drying set as the drying advanced.

We propose and demonstrate a method for improving optical-frequency sweepers that uses a disk-shaped optical bandpass filter operated under the synchro-scan mode. We optimize the filter layer structure to achieve high linearity in optical-frequency tuning with the rotation angle of the disk, while maintaining a constant band-inhibition performance. We introduce an optical system that narrows the bandwidth by using an optimized beam coupler and improves the filtering performance by using a multiple-path method. The optimized filter enables a stable linear optical-frequency sweep when it is used with a motor stabilized by phase locking. The improved optical frequency sweepers can extend the sweep range to above 2 THz, while suppressing the accumulation of spontaneous emission noise.

Germinal vesicle transplantation (GVT) has been proposed as a possible treatment to correct age-related oocyte aneuploidy caused by dysfunctional ooplasm. How healthy ooplasm regulates normal meiosis and subsequent development has yet to be elucidated, but impaired mitochondrial metabolism may be attributable to incomplete segregation of the oocyte chromosomes. In the present study, after ooplasmic mitochondrial damage by photoirradiating chloromethyl-X-rosamine, examination of the oocyte nuclei’s ability to survive after transfer into healthy ooplasts was performed. To assess their fertilizability and potential for development, GVT oocytes were fertilized by intracytoplasmic sperm injection (ICSI) and transferred to foster mice. Condition of the offspring at birth was assessed, and epigenetic analysis was performed. Photosensitization consistently inhibited oocyte maturation. However, after GVT of photosensitized nuclei into healthy ooplasts, 67.2% were reconstituted, and 76.2% of these matured normally, with an overall rate of 51.2%, much higher than that (6.0%) in the mitochondrially injured oocytes. After ICSI, 65.8% (52/79) of GVT oocytes were fertilized normally, and 21.1% (11/52) eventually reached the blastocyst stage. The transfer of 132 two-cell GVT embryos into the oviducts of pseudopregnant females resulted in 17 apparently healthy live offspring. For some key developmental genes, a high level of expression was identified in the GVT and ‘‘rescue’’-derived fetal adnexa. Thus, one can induce in oocyte mitochondria a photosensitization-based type of damage, which consistently inhibits GV breakdown, meiotic spindle formation, chromosomal segregation, and polar body extrusion. Germinal vesicle transplanted and rescued oocytes were able to undergo maturation, fertilization, and embryonic cleavage and, ultimately, to develop to term. This approach may provide a model with which to study the age-related ooplasmic dysfunction seen in human oocytes. fertilization, gamete biology, gene regulation, genomic imprinting, germinal vesicle transplantation, meiosis, mitochondrial photosensitization, oocyte development, ooplasmic dysfunction

Among various atomically thin two-dimensional materials, molybdenum disulphide (MoS2) is attracting considerable attention because of its direct energy bandgap in the 2H-semiconducting phase. On the other hand, a 1T-metallic phase, which is very important for unique applications, has been created by various methods. Recently, we demonstrated the creation of in-plane 1T-metal/2H-semiconductor MoS2 lateral Schottky junctions by using electron beam irradiation techniques and revealed their unique electrical properties. Here, we report the optoelectronic measurements proving the formation of this few-layer MoS2 lateral Schottky junction. A large photocurrent is confirmed in the reverse bias voltage regime, while it decreases with increasing distance between an electrode placed on the 2H region and the 2H/1T junction. These results suggest a concentration of high electric field and rapid dissociation of photogenerated excitons at the few-layer lateral Schottky junction, which are beneficial for highly efficien...

We report 2 cases of cutaneous apocrine ductal carcinoma (CADC) of the axilla in a 64- and a 54-year-old male. Histological examination revealed 2 solid, ductal and glandular tumors with decapitation secretion. Tumor cells showed cellular and nuclear atypism, and infiltrative growth of tumor cell nests was also observed. Although there were no characteristic features of extramammary Paget’s disease on the overlying skin, case 1 exhibited a typical Paget’s phenomenon. We concluded that the Paget’s phenomenon of case 1 was a result of upward extension of the tumor in the dermis. The neoplastic cells of both cases were immunohistochemically positive for gross cystic disease fluid protein, lysozyme, CD15 and carcinoembryonic antigen but negative for S-100 protein. Based on these findings, we concluded that these tumors were cutaneous apocrine ductal carcinomas. There was no evidence of tumor remnants in the axilla, and the patients have shown no signs of local recurrence or metastasis. We also reviewed the literature and summarize here the clinical features of CADC.

Activated platelets expressing P-selectin in their surfaces are known to adhere to monocytes and neutrophils. We examined the possibility that the leukocytes are functionally modified by their adhesion to activated platelets. We used human peripheral blood monocytes and neutrophils and measured superoxide anion generation by these cells cultured with platelets. The levels of superoxide anion production were found to be markedly elevated when thrombin-activated platelets were used. The extent of this enhancement was much smaller when leukocytes were cultured with resting platelets than activated platelets. The increase depended on incubation time and platelet concentration. The membranes prepared from activated platelets also induced superoxide anion production, but the culture supernatant of activated platelets did not. The enhanced superoxide anion production was inhibited by anti-P-selectin antibody, anti-sialyl-Lewis X antibody, or a soluble recombinant P-selectin fusion protein. These results indicate that the adhesion of activated platelets to the leukocytes through P-selectin was a crucial step for the activation of leukocyte function, and support the idea that activated platelets are actively involved in inflammation processes.

A monolithic three-channel LD-PD array with vertically staggered facets is proposed for an autofocusing reflectivity sensor which uses light feedback. The focus-sensing characteristics are investigated using an array with a radiation facet displacement of 12 mu m and an interchannel distance of 130 mu m, fabricated on an 830-nm AlGaAs/GaAs multiple-quantum-well laser substrate with buried-heterostructure stripe geometry waveguides. High focus-sensing accuracy is achieved. A potential application of the array to optical heads for phase change media is discussed. >

We observed a propagation of surface plasmon polaritons (SPPs) along bent Au-wires on a thin SiO 2 -coat-InP substrate with the bending radius R from 20 to 1000 μm and evaluated the bending-part attenuation coefficients, i.e., the bending losses of propagating SPPs along them with R from 20 to 400 μm by measuring the transmittance of SPPs. We discussed about the SPP propagation and the applicability to an optical electronic device and circuit of SPPs.

This paper demonstrates Airy Notes system, which monitors environmental condition using tiny sensor modules and shows the characteristics of places intuitively on a map and on a cell phone. The system is designed to help the user's easy understanding of the effect of green by densely placed sensor nodes. We conducted the experiment of the system in Shinjuku Gyoen Garden with 160 sensors. The garden is known for its effect of keeping temperature of nearby area calm with its green. We monitored the distribution of temperature, and observed that the temperature of the inner place was lower than the edge of the garden.

We determined the association of androgen receptor (AR) (CAG)n lengths among fertile and infertile males and offspring conceived by intracytoplasmic sperm injection (ICSI). Assessment of (CAG)n repeats in the AR was performed in a Caucasian population by gene sequencing in fertile men (n=13), infertile men (n=64), boys conceived after ICSI (n=21), and boys conceived naturally (n=11). In the AZF region of the Y chromosome, a total of 22 STSs were analyzed by multiplex PCR; selected spermatozoa were also analyzed by fluorescent in situ hybridization (FISH) for chromosomes 18, 21, X, and Y. The average age was 43.7+/-7 yr for infertile, 44.8+/-7 yr for fertile men, and 5.0+/-0.5 yr for the children. The mean (CAG)n was 22.2+/-3 for the infertile men and 19.3+/-5 for fertile controls. There was a significant difference in CAG repeat length in the severely oligo-/azoo-spermic men vs. controls (p=0.02). An inverse correlation was evident between CAG length and semen parameters. For ICSI male children, the AR (CAG)n lengths were 21.4+/-3.2 vs. 20.8+/-3.4 for boys conceived naturally. While all peripheral karyotypes of fertile and infertile men were normal, de novo gonosomal abnormalities were observed in the ICSI offspring. The incidence of Y microdeletions was 1.6% in infertile men; all the ICSI sons had an intact Y chromosome. In conclusion, severely oligo- and azoospermic men had longer CAG repeat length than fertile controls, suggesting that certain AR gene mutations may have a negative effect on spermatogenesis. An increased incidence of de novo gonosomal abnormalities was found in the ICSI offspring when compared to children conceived naturally. Our assessment of the polymorphic region of the AR gene, in the absence of other specific genomic abnormalities, suggests that the fertility of children conceived by ICSI may be conserved.

Intracytoplasmic sperm injection (ICSI) is now the preferred technique for treatment of male factor infertility and many children have been born worldwide. However, concerns about the risk of transmitting genetic defects and development of ICSI children have been raised. We report clinical outcome of ICSI in Cornell University and results of screening for genetic defects in ICSI parents and their children.Pregnancy and obstetrical outcomes as well as congenital malformations were analyzed. Chromosomal karyotyping and Yq deletion assessments were performed on blood samples. In addition, medical and developmental outcome were assessed in 3 and 5 year old ICSI children.We have performed 8 575 ICSI cycles with ejaculated spermatozoa that resulted in a 75.4% fertilization and a 42.8% clinical pregnancy rates while for surgically retrieved specimen resulted in 66%, 48.8% respectively. The incidence of Y deletion was within the expected range for an infertile population, with identical deletions transmitted to the male offspring. There were no differences in cognitive, motor and behavioral development observed between ICSI children and these conceived naturally.The large majority of infertile men were treatable by ICSI, which resulted in the transmission of a specific abnormality but did not enhance the incidence of de novo deletions. There is no indication that ICSI children develop more congenital defects or express a lower psychomotor development that children conceived naturally. Nonetheless, genetic screening and counseling of couples undergoing ICSI would seem to be appropriate.

The aetiology of compromised spermatogenesis is often genetic in nature. There are only a few reports of father/son cohorts that have been evaluated to assess heritability of mutations associated with male factor infertility and the psychological well-being of the children. In the present study, multiple tissues were sampled from consenting male patients and their sons derived from intracytoplasmic sperm injection (ICSI) and underwent chromosomal and genetic analyses. Paediatric and psychological examinations were also conducted. In 87 men and 47 boys, 22 sequence tagged sites (STS) were analysed by multiplex PCR and deletion breakpoints were defined with additional loci. In one patient, the breakpoints map to the highly unstable palindrome-rich region within AZFb and proximal AZFc was investigated. A total of 86 blood, 26 semen, and 73 cheek cells samples were collected from adults, and 36 blood samples and 44 cheek cell specimens were obtained from the boys. Though all of the fathers had normal karyotypes, the incidence of chromosomal abnormalities in the somatic cells of male progeny was 8.3% (3/36). The incidence of germ line aneuploidy in these men was 0.5-2.8%. A CF mutation (Delta508) was detected in one of 87 men (1.2%) and microdeletions in Yq AZF were detected in 3.4% of 87 adults and in 2.1% of their sons (n = 47). In conclusion, screening for Y chromosome microdeletions provides crucial information in the counselling of couples seeking infertility treatment. Moreover, DNA extraction and Y deletion assessments of cheek cells provide a non-invasive approach. Inheritance of Yq deletions appears not to affect the psychological and physical development of children derived from ICSI.

Intracytoplasmic sperm injection (ICSI) entails the mechanical insertion of a chosen spermatozoon directly into the cytoplasm of an oocyte. Due to the consistent fertilization and pregnancy outcome, ICSI is routinely used to treat azoospermic patients where spermatozoa are retrieved by epididymal aspiration or testicular biopsy. Since male subfertility has been associated with a higher incidence of genomic defects, ranging from numerical chromosomal abnormalities to Yq microdeletions, concerns have been raised as to the risk of transmitting genetic defects to the offspring. Screening for such defects can provide invaluable information for appropriate counselling prior to ICSI treatment. In order to address these concerns, a follow-up of the children born after ICSI treatment was conducted.

Summary form only given. Future ultrahigh-speed optical transparent networks require optical time-division multiplexed (TDM) signal processing nodes that can control optical short pulses of several picoseconds. We have proposed an add/drop multiplexer based on optical wavelength conversion by four-wave mixing (FWM), and confirmed its operation with synchronized signals. In this report, we propose an optical TDM add/drop multiplexer using a phase-lock loop timing extraction circuit and demultiplexer based on photonic downconversion for a stable add/drop operation with a simple configuration.

The data transmission performance of a previously proposed high-speed optical backboard bus, whose transmission-signal waveforms are theoretically unchanged even when the number and placement of its package boards are changed, has been estimated. The proposed bus is composed of an 8/spl times/8 optical star coupler, optical fibers, optical-transmitter modules, and optical-receiver modules. These modules are grouped on an optical backboard attached to the back side of a plug-in unit for an existing backboard bus assembly. Data can be transmitted at up to 1 Gb/s, which is about ten times faster than electrical bus rates, with no errors, even when changing the package boards. The proposed bus is adaptable to multi-channel lower-rate data transmission by using multiplexers and demultiplexers on the package boards to change the transmission rate.

A 10-GHz-spacing dense wavelength division multiplexing (DWDM) channel selector with a cascade configuration consisting of disk-shaped tunable filters controlled according to their individual calibration table and distributed optical amplifiers is demonstrated by 2.5 Gbit/s NRZ selection experiments.

This study aims to seek method on travel path and transport mode identification in case positions of travellers are detected in low frequency. The survey in which ten test travellers with GPS logger move around Tokyo city centre was conducted. Travel path datasets of each traveller in which position data are selected every five minutes are processed from our survey data. Coverage index analysis based on the buffer analysis using GIS software is conducted. The condition and possibility to identify a path and a transport mode used are discussed.

We report 2 cases of cutaneous apocrine ductal carcinoma (CADC) of the axilla in a 64- and a 54-year-old male. Histological examination revealed 2 solid, ductal and glandular tumors with decapitation secretion. Tumor cells showed cellular and nuclear atypism, and infiltrative growth of tumor cell nests was also observed. Although there were no characteristic features of extramammary Paget's disease on the overlying skin, case 1 exhibited a typical Paget's phenomenon. We concluded that the Paget's phenomenon of case 1 was a result of upward extension of the tumor in the dermis. The neoplastic cells of both cases were immunohistochemically positive for gross cystic disease fluid protein, lysozyme, CD15 and carcinoembryonic antigen but negative for S-100 protein. Based on these findings, we concluded that these tumors were cutaneous apocrine ductal carcinomas. There was no evidence of tumor remnants in the axilla, and the patients have shown no signs of local recurrence or metastasis. We also reviewed the literature and summarize here the clinical features of CADC.

Osteopontin (OPN) is an Arg-Gly-Asp-containing phosphoprotein that is secreted by activated T cells. The concentration of serum OPN protein is elevated in autoimmune-prone MRL-lpr mice as well as in patients with systemic lupus erythematosus. Previously, it was shown that OPN induces the polyclonal activation of B cells, resulting in the augmented production of immunoglobulin, indicating that OPN plays some role in the development of autoimmune disease. However, the link between OPN and development of autoimmune disease remains unclear. To analyze the role of OPN in immune system and autoimmune diseases, we have generated two kinds of transgenic mice: one carries the immunoglobulin (Ig) enhancer/SV40 promoter and the other carries the cytomegalovirus enhancer/chicken beta-actin (CAG) promoter. In both groups of transgenic mice, the B1 cell population in peritoneal cavity was markedly increased and titer of IgM and IgG3 antibodies in the serum was considerably higher than that in wild-type mice. Most important, the titer of the IgM class of anti-double-stranded DNA antibody was significantly elevated in transgenic mice. These results strongly suggest that OPN may have an important role in the propagation and differentiation of B1 cells and production of autoantibodies.

The NADP+-dependent dehydrogenase activity of a predominant isoenzyme of human liver 3alpha-hydroxysteroid dehydrogenase was activated by antihyperlipidemic drugs, such as bezafibrate and clinofibrate, and by clofibric acid and fenofibric acid (active metabolites of clofibrate and fenofibrate, respectively). The optimal pH of the activation by the drugs was about 7.5, and the concentrations giving maximum stimulation (1.8- to 2.4-fold) were 100, 50, 400 and 50 microM for bezafibrate, clinofibrate, clofibric acid and fenofibric acid, respectively. Clofibrate and fenofibrate acted as weak inhibitors, and the clofibric acid derivatives that lack the chloro group, methyl group on the alpha-carbon or carboxyl group greatly decreased the stimulatory effects. The activation by the drugs increased both Km and kcat (turnover number) values for the coenzyme and substrates. Kinetic analysis with respect to NADP+ showed that bezafibrate, clinofibrate, clofibric acid and fenofibric acid were nonessential activators showing dissociation constants of 32, 6, 103 and 11 microM, respectively. The combined activators experiments with one of the above drugs and sulfobromophthalein, a known activator specific for this enzyme, and comparison of their effects on the activities of mutant enzymes (with Met replacing Lys-270 or Arg-276) indicated that sulfobromophthalein and the drugs bind to an identical site on the enzyme. These results suggest that the long-term therapy with the antihyperlipidemic drugs influences the metabolism of steroid hormones, bile acids and several ketone-containing drugs mediated by the enzyme.

We studied the influence of intermittent ischemic injury on thioacetamide-induced liver cirrhosis in rats. Wistar rats were divided into group A, intermittent ischemic injury to liver cirrhosis, and group B, continuous ischemic injury to liver cirrhosis. Total ischemic time was 60 min in both groups. In group A, ischemic injury consisted of a repetition 4 times of 15 min ischemia and 5 min reperfusion. The ATP level of the liver was measured before ischemia, before reperfusion, and 60 min after reperfusion. Bile was collected to determine bile flow rate. The ATP level in the liver tissue 60 min after reperfusion was significantly (p < 0.05) higher in group A than in group B. The ATP level immediately before reperfusion was also significantly (p < 0.05) higher in group A than in group B. The survival rate 1 week after ischemic injury and bile flow rate 60 min after reperfusion were significantly (p < 0.01) higher in group A compared with those in group B. The energy level was much higher in intermittent ischemic injury than in continuous ischemic injury immediately before reperfusion and after reperfusion. Survival rate and bile flow rate were higher in intermittent ischemic injury than in continuous ischemic injury. Therefore it suggests that the viability of the liver was maintained better in intermittent ischemic injury than in continuous ischemic injury.

Broadband photonic networks based on WDM supported by wideband amplifiers are important to provide flexible multimedia services. One of the key devices for them is an optical filter with various functions including wavelength discrimination for monitoring the multiplexed channels. Although many filters, e.g., acousto-optic filters and electrically tuned Fabry-Perot etalons, have been presented, they cannot simultaneously satisfy all the practical requirements such as polarization insensitivity, wide tunability, and quick, high stability operation due to their individual drawbacks. The rotary motion of a disk promises high-speed performance as demonstrated in hard-disk system. Here, we present and demonstrate a novel fast-filtering scheme using a synchro-scan rotating tunable disk filter with a circularly wedged interference layer, which has the merits of interference filters. The wavelength discrimination performance of this scheme was tested.

A case of 48-year-old man, with diffuse arterioportal fistula (APF) considered congenital in origin, is described. The patient presented with recurring intractable variceal hemorrhage which was treated by endoscopic ligation or sclerotherapy. In this case, gastroduodenal artery and branches of mesenterial artery were diffusely involved, so these lesions could not be resected. Portocaval shunt between the superior mesenteric vein and the right iliac vein was successfully performed. Follow-up endoscopic examination one year later revealed no evidence of esophageal and gastric varices. To our knowledge, this is the second case in which a patient underwent portocaval shunt successfully for congenital APF.

A 20 year-old female was admitted to our department because of an abnormal shadow in chest roentgenogram on a physical check-up. The barium swallowing study revealed an oppression of the middle of the esophagus. Endoscopy, chest CT and MRI failed to distinguish submucosal tumor from mediastinal tumor. Endoscopic ultrasonography showed the mass originated from the esophagus and a diagnosis of esophageal smooth muscle tumor was obtained. The tumor was tried to resect by thoracoscopic surgery but was failed because of its shape like a tortoise shell. The tumor was resected through the right thoracotomy and the diagnosis was confirmed histopathologically.

Phospholipase D (PLD) plays an important role in neutrophil activation. However, despite various proposed mechanisms, its detailed regulatory mechanism is not fully understood. The functional coupling between phosphatidylinositol 3-kinase (PI 3-kinase) and PLD was investigated in N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated human promyelocytic leukemia HL60 cells, using wortmannin, a fungal metabolite that is known as a selective inhibitor for phosphatidylinositol 3-kinase. Treatment of cells with this drug inhibited the formation of both phosphatidylinositol 3,4,5-trisphosphate (PIP3), a product of PI 3-kinase, and phosphatidylbutanol (PBut), the specific product of transphosphatidylation due to PLD in the presence of butanol, with similar concentration dependence (IC50 = 30-70 nM). Another PI 3-kinase inhibitor, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) also inhibited PBut formation in a concentration-dependent manner. However, wortmannin failed to inhibit phorbol 12-myristate 13-acetate-induced PLD activation in whole cells and membrane PLD activity in an in vitro assay system, indicating that inhibition of fMLP-induced PLD activation by wortmannin was not due to its direct effect on PLD activity. These results suggest that a major part of inhibition of PLD activation by wortmannin might be mediated through its effect on PI 3-kinase.

Bovine leukaemia virus (BLV) causes enzootic bovine leukosis (EBL) in cattle and represents a serious problem in Japanese meat and dairy industries (Ministry of Agriculture, Forestry and Fisheries). BLV can be vertically or horizontally transmitted through the transfer of infected cells via several potential routes. One of the major routes of horizontal transmission is by direct contact of mucosal surfaces, or broken skin, with a mixture of blood, exudates and tissues (Hopkins and DiGiacomo 1997). Furthermore, BLV can be horizontally transmitted through the transfer of infected cells by bites of insects, such as stable flies ( Stomoxys calcitrans ) (Buxton and others 1985). Thus, in addition to the prevention of iatrogenic and contact transmissions, vector control is important for preventing the spread of BLV infection. In this study, BLV from newly infected cattle was characterised to determine the virus source in a herd and a vector control measure was used to prevent the spread of the infection. The samples were collected from Japanese Black cattle (beef cattle) on a model farm (Farm A) in Yaeyama Island, Okinawa. BLV infection was tested by the passive haemagglutination assay (Nippon Institute for Biological Science, Tokyo, Japan), according to the manufacturer's instructions. In BLV-positive cattle, leukocytes were counted using Celltac α MEK-6258 (Nihon …

A 40-year old woman had experienced repeated spontaneous pneumothorax on the right side at the beginning of each menstrual period for one year. The level of serum CA125 was high at 60 ng/ml. Right thoracotomy revealed the presence of multiple darkly-pigmented spots and several pinhole like perforations near the central tendon of the diaphragm. The partial resection of the diaphragm was done, endometrial tissues were detected histologically. Tha patient has been asymptomatic after operation and the level of serum CA125 is normal.

Indomethacin is well known to be metabolized via O-demethylation and N-deacylation. In this paper we found an enzyme involved in the hydrolysis of amide-linkage of indomethacin and partially characterized it as well as its substrate specificity.An indomethacin hydrolyzing enzyme was purified to homogeneity from pig liver microsomes using columns of Q-Sepharose, Red-Sepharose and Blue-Sepharose. The enzyme activity was assayed by measuring of rho-chlorobenzoic acid liberated from indomethacin by HPLC.The purified enzyme effectively hydrolyzed the amide linkage in indomethacin but not those in alpha-naphthylacetate and rho-nitrophenylacetate, which are typical substates for carboxylesterase. The subunit molecular mass of the enzyme was 65 kDa according SDS-polyacrylamide gel electrophoresis. The Michaelis constant (K(m)) and maximum velocity (Vmax) values for indomethacin were 67.8 microM and 9.02 nmol/min/mg protein, respectively. The amino acid sequence analysis of the enzyme after cyanogen bromide cleavage showed high homology with a mouse carboxylesterase isozyme designated as ES-male. The activity of indomethacin hydrolysis was relatively high in the pig, rabbit and human liver homogenate, but not in those from rat and mouse. On the other hand, purified human liver carboxylesterases pl 5.3 and 4.5, and pig liver carboxylesterases have no catalytic activity for indomethacin.These results indicate that the hydrolysis of amide-linkage of indomethacin in humans would be associated with an enzyme similar to the indomethacin hydrolyzing enzyme from pig liver microsomes described here.

Peripheral vascular disease is often complicated with ischemic heart disease and is associated with increased cardiac mortality. Latent progression of sclerotic changes in the arteries supplying the lower extremities is often present but undiagnosed. We examined the influence of sclerotic changes of the iliac arteries on the late outcome in 79 patients with ischemic heart disease. Lower abdominal aortography was performed at the time of cardiac catheterization between December 1989 and January 1991. The degree of sclerotic change in the iliac arteries was assessed according to aortography findings such as stenosis, dilatation or bend, with higher scores representing more advanced sclerosis (aortography score). The mean aortography score of all patients was 5.8 +/- 4.6. The patients were followed up for 4.4 +/- 1.2 years to monitor the occurrence of cardiac events (cardiac death, acute myocardial infarction, coronary bypass surgery, or coronary angioplasty for new lesion). The cardiac event-free rate at 5 years was 76.6% in the high score group (32 patients with scores of 6 or more) and 92.9% in the low score group (47 patients with scores of 5 or less). The difference was significant (p = 0.007) by log-rank test. The hazard rate of the aortography score for predicting risk of cardiac event was 1.11 by the Cox proportional hazards model (95% confidence intervals: 1.01-1.23, p = 0.039). When the analysis was adjusted for coronary bypass surgery as primary therapy, the number of diseased coronary arteries, or the presence of peripheral vascular disease, similar results were obtained. In conclusion, more severe sclerotic change in iliac arteries is associated with a higher incidence of cardiac events in patients with ischemic heart disease.

Using a new quantitative method, we compared the involvement of platelet alpha IIb beta 3 integrin in clot retraction with that in aggregation, and identified a receptor for fibrin gels on the cell surface in the nuclear cell-induced clot retraction. The platelets pretreated with thrombin in the presence of 4 mM EDTA at 37 degrees C completely lost aggregability in response to any agonist, while they were still able to retract clot, though to a less extent than controls. The clot retractions by these pretreated platelets as well as control platelets were inhibited by a monoclonal anti-beta 3 (T74) that also inhibits aggregation. These results suggest that a domain in alpha IIb beta 3 integrin involved in clot retraction is not exactly the same site involved in aggregation (the fibrinogen-binding site). C32TG cells expressing integrin alpha v beta 3 but not alpha IIb beta 3 complex showed an efficient clot retraction, which was inhibited by an anti-alpha v beta 3 antibody but not by Ro-43-5054, a potent inhibitor specific to platelet alpha IIb beta 3. When cDNA of beta 3 was transfected into 293 cells which otherwise lacked beta 3 and a retractile activity, the transfectants retracted significantly fibrin gels, which was specifically inhibited by the anti-beta 3 T74. These findings indicate that alpha v beta 3 is involved in mediating the clot retraction by tumor cells.