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Using nucleotide sequences of the mitochondrial DNA (mtDNA) cytochrome b and SRY genes, we examined the genetic status of two major groups of domestic cattle, the humpless taurine (Bos taurus) and humped zebu (B. indicus), using 10 cattle populations in Asia. Several sequence polymorphisms specific for each major group were found, although the frequency of these polymorphisms varied in each population. Six major mtDNA-SRY composite types were observed. The Mishima, Mongolian, Korean, Chinese Yellow and Sri Lanka cattle populations had a full match between the mtDNA and SRY sequences, specifically the taurine/taurine type or zebu/zebu type. A non-match type (zebu/taurine type) was found at a high frequency in the Bangladesh (83.4%) and Nepal populations (83.3%). Our results suggest that these non-match type populations developed from genetic hybridization of different strains. Also, the domestication history of modern Asian domestic cattle could be explained by male-mediated introgression. Additionally, our results suggest the occurrence of introgression of mtDNA from other Bibos or Poephagus species into native cattle populations. The existence of other mtDNA-SRY composite types, such as the Bali-zebu and yak-zebu types in Indonesia (85.7%) and Nepal (16.7%), respectively, suggests that genetic introgression also occurred from other genera into domestic cattle during the process of domestication.

A method for finding the direction of arrival (DOA) of a single short pulse is proposed. The method is based on a waveform reconstruction technique using complex antenna factors (CAF). Since the frequency characteristics of CAF has angle dependency, the DOA of an electromagnetic pulse can be determined by the waveforms reconstructed with CAF. The result of an experiment shows the possibility to apply the two-dimensional DOA finding.

Distance learning methodology will receive more and better recognition in the near future. This is because it can be expected to contribute to democratization and equalization. On the basis of this belief, we designed some sample teaching materials for a distance learning program for use in higher education, and tested them with university students. Then we evaluated the effectiveness of the materials. We used a sample group which worked with the sample materials and a control group which studied in traditional classroom lectures. The evaluation was made by means of (1) a questionnaire designed to ascertain students' reactions to the distance learning materials, (2) an analysis of questions from students, which we took to be an indication of their motivation, and (3) examinations to clarify the students' understanding of the materials. For each measure, we took the data from each group and compared and analyzed them. The distance learning materials were original materials which we designed for use in a business management course on the Internet. These materials were made using presentation application software and were loaded on the teacher's home page so the students could use them either on campus or in any other environment where they could access the Internet. They could ask questions about the contents from any place by e-mail. The students worked with the materials by downloading data and other relevant information from the Internet, which they then analyzed and processed. We report on the results of the case study and make some suggestions for improvements to distance learning methods.

Effects of 7-hydroxy-2-(N,N-di-n-propylamino)tetralin (7-OH-DPAT), a dopamine D3-receptor agonist, on neuronal activities of the nucleus accumbens (Acc) were examined in chloral hydrate-anesthetized rats. Spikes elicited by stimulation of the parafascicular nucleus were dose-dependently inhibited by microiontophoretic application of dopamine and 7-OH-DPAT. Glutamate-induced firing was also inhibited by these drugs. These findings suggest that D3 receptors are also involved in the postsynaptic inhibition of Acc neuron by dopamine.

By combining the key capability of Super Solder precoat to supply high volumes of solder with the new pad geometry, major improvements are demonstrated in volume production mountability and mounting reliability for fine pitch components. In particular, a solder precoat supporting repair of a 0.3 mm pitch tape automated bonding (TAB) components is possible. A pad design permitting reflow mounting of quad flatpack (QFP) packages is discussed. >

An efficient Vpp generator with a charge recycle pump and a charge transfer pump have been proposed. The charge recycle operation can reduce the Vpp generating current by 38% without decreasing the Vpp supply current. The charge transfer operation enables the generation of the Vpp supply current at over the 2/spl middot/Vcc level. These techniques are highly effective in low voltage DRAMs.

An ultrasonic actuator with multi-degree of freedom with a single stator is proposed and has been constructed for trial. Three sets of piezoelectric elements are installed in the stator, and two bending vibrations perpendicular to each other and a longitudinal vibration can be excited independently with three separate electrical ports. A spherical rotor is revolved on all the three axes by the combination of these vibrations.

We design a volumetric neutron source based on a steady-state tokamak device with superconducting coils. It is found that the neutron flux of 1 MW/m/sup 2/ is available in the medium-sized device (R=4.5 m, a=1.0 m, /spl kappa/=1.8 and I/sub p/=5.6 MA) under the conditions of H=2 and /spl beta//sub N/=3 with a NBI power of 60 MW. We demonstrate the controllability of the current profiles required for high beta plasma up to /spl beta//sub N/=3 with the combination of the bootstrap current and NB-driven current. The Li-Pb blanket is adopted with water-cooled and austenitic stainless steel-structured system. The calculated local TBR reaches 1.4 or more in Li-Pb breeder at a sufficient thickness of breeding zone. The net TBR might be available only with the outboard Li-Pb blanket.

Flip chip mounting technology is currently being considered for use in consumer information equipment, and industry is waiting for the establishment of solder bump forming technology as an essential constituent of flip chip (FC) mounting technology. At the present, however, no bump forming technology offers a combination of simple process and low cost. Furukawa Electric has developed a lattice substitution solder generation technique (Super Solder, or SS) to supply solder to the pads on PC boards. Taking advantage of the unique characteristics of the SS technique, the authors have developed a solder bump formation technology for FC, under the key concepts of simple process, low cost and non-bridging solder supply. The technique has proven successful in forming solder bumps with ample volume for practical application.

Specific performance from imposes loads on other supporting subsystems and subsystems. This paper overviews system requirements dictated by the plasma's needs and impacts. Overall device parameters have been derived from the performance goals using plasma transport and stability models based on physics R and D results. Most transport issues relate to the extrapolation of the plasma behavior to ITER's large size (especially relative to the gyroradius). Plasma control systems must achieve shape and position flexibility sufficient for the performance of the power handling and auxiliary power systems. Induced currents in the conducting structures between the poloidal coils and the plasma both provide passive stabilization of plasma disturbances and delay plasma responses to external magnetic controls. Auxiliary power systems must heat the plasma to ignition and drive noninductive currents for steady state operation, and may have to drive plasma rotation if physics confirms the need for rotation indicated by recent theories of resistive wall stabilization. Diagnostics must support plasma control and performance assessment and contribute to physics understanding. The first wall must handle steady state power and energetic neutral bombardment, and will experience transient power and runaway electron loads. The divertor system must disperse the incoming power while confining the divertor's higher concentration neutral gas and pumping the helium. In-vessel structural design is driven by the forces related to plasma disruptions, which induce currents in the conducting structures and drive non-axisymmetric "halo currents" between the plasma and the conductors. Such plasma control needs and impacts from power and disruption handling are described.

The new material Gd/sub x/Y/sub (1-x)/Ca/sub 4/O(BO/sub 3/)/sub 3/ (GdYCOB) exhibits excellent optical (SHG) characteristics, and their single crystals can be grown with CZ technique at a low cost. Hence, their piezoelectric properties are also very interesting, however, few studies on the piezoelectricity and SAW properties have been reported. In this study, SAW properties of GdYCOB are first presented. In order to investigate the properties IDTs were fabricated on YCa/sub 4/O(BO/sub 3/)/sub 3/(x=0) and GdCa/sub 4/O(BO/sub 3/)/sub 3/ (x=1) crystals, and frequency response of radiation admittance and filter properties were measured. The X, Y and Z-cut crystals of YCOB were evaluated, revealing that the SAW velocity measured ranged from 2500 to 4300 m/s, and the high coupling factor (k/sup 2/=0.5% at Z-axis propagation) and relatively low temperature coefficient of delay (TCD=50 ppm/K) were found at the X-cut sample. The higher coupling factor (k/sup 2//spl sim/1.0%) was measured on GdCOB crystal. It is expected that the SAW properties comparable to those of LiTaO/sub 3/ can be obtained in GdYCOB.

Recently, micromanipulation for bio-engineering has been developed. The purpose of this research is to develop the minute size knife for the cutting of the minute object such as the cell. In this paper, we report on the microknife that cuts off the object by using ultrasonic vibration of the sharp needle. We applied the multilayer piezoelectric actuator for generating the ultrasonic vibration for cutting. We developed the touch probe sensor for microknife by the PZT thin film which is made by the hydrothermal method. We evaluated the performance of cutting and the touch probe sensor by experiments.

The purpose of this research is to develop a minute size knife for cutting of minute objects such as cells. We report on a microknife that cuts the object by using ultrasonic vibration of a sharp needle. We employed a multilayer piezoelectric actuator for generating the ultrasonic vibration for cutting. Also, we made a tactile sensor for the microknife by using PZT thin film made by the hydrothermal method. We evaluated the cutting performance and the tactile sensor by experiments.

This paper proposes the virtual socket architecture in order to reduce the design turn around time (TAT) of the embedded DRAM. By using the proposed architecture, the DRAM control circuitry is provided as the software macro to take advantage of the automated tools based on the synchronous circuit design. With array generator technology, this architecture can achieve high quality, quick turn around time (QTAT) flexible eDRAM design almost the same as the CMOS ASIC. We applied this virtual socket architecture to the 0.18 /spl mu/m embedded DRAM test device and confirmed over 166 MHz operation.

Inositol 1,4,5-trisphosphate (IP3) is considered to be important for activation of mammalian oocytes at the time of fertilization, and activation induces a rise in intracellular Ca2+ concentration ([Ca2+]i) by release from the Ca2+ stores in the oocytes. Therefore, IP3 could act as an artificial activator of porcine oocytes. Activation and development, and rise in [Ca2+]i in matured oocytes injected with various concentrations of IP3 were investigated in this study. Porcine oocytes were recovered from the ovaries of prepubertal gilts, matured for 46-48 h and cultured in vitro for 7 days in following treatments as non-injected oocytes (NI), injected with carrier buffer, 2.5, 5 and 500 microM of IP3. The result showed that IP3 activated porcine oocytes matured in vitro (NI 3.8%, buffer 7.1%, 2.5 microM IP3 73.5%, 5 microM IP3 76.2%, 500 microM IP3 85.2%). There was a slight but not significant increase in the proportion of oocytes activated as the level of IP3 increased. The rate of development to the cleavage stage increased remarkably when the concentration of IP3 increased (NI 4.9%, buffer 5.7%, 2.5 microM IP3 30.3%, 5 microM IP3 47.1%, 500 microM IP3 78.1%). Blastocyst development was only observed in oocytes that had been injected with a higher concentration of IP3 (5 microM IP3 6.1% and 500 microM IP3 5.3%). Both the peak value and duration of [Ca2+]i rise also increased as the concentration of IP3 increased. Baseline values (ratio value, R) for [Ca2+]i ranged from 1.51 to 1.57 and was not affected by the buffer treatment. The peak value of [Ca2+]i rose significantly with increasing level of IP3 treatment (2.5 microM IP3, 3.54 +/- 0.32; 5 microM IP3, 7.50 +/- 0.37; 500 microM IP3, 8.54 +/- 0.33). Similarly, the duration of the [Ca2+]i rise increased as the level of IP3 increased (2.5 microM IP3, 43.7+/- 7.00 s; 5 microM IP3, 93.5 +/- 9.17 s; 500 microM IP3, 160.6 +/- 18.9 s). It was concluded that injected IP3 promotes the development of porcine matured oocytes and that their developmental ability is positively correlated with the rise in [Ca2+]i induced by IP3.

This review article focused on the primary neurotransmitters involved in transmission from the otolith to the vestibular nucleus (VN), especially in relation to the neurotransmission to the VN neurons (gravity-sensitive neurons) activated by tilt stimulation. The medial vestibular nucleus (MVN) neurons were classified in 8 types (alpha-theta) according to the patterns in response to the clockwise and counterclockwise tilt-stimulations. The tilt-induced firing was inhibited by GDEE (a non-selective glutamate receptor antagonist) and/or atropine (a muscarinic receptor antagonist). Thus, glutamate and/or acetylcholine may serve as the primary neurotransmitters. This conclusion is supported by the previous findings that glutamate exists in the vestibular nerve and is released from the nerve besides the presence of glutamate receptor subtypes in the VN. In addition, acetylcholine induced atropine-reversible firing of MVN neurons, and the enzymes involved in acetylcholine synthesis/metabolism are also found in the VN. Furthermore, serotonin was found to inhibit the MVN neuronal activities via the 5-HT1A receptors. As such, the 5-HT1A agonist, tandospirone, may be effective in preventing and/or treating motion sickness and/or space sickness.

We examined whether microgravity influences the induced-mutation frequencies through in vivo experiments during space flight aboard the space shuttle Discovery (STS-91). We prepared dried samples of repair-deficient strains and parental strains of Escherichia (E.) coli and Saccharomyces (S.) cerevisiae given DNA damage treatment. After culture in space, we measured the induced-mutation frequencies and SOS-responses under microgravity. The experimental findings indicate that almost the same induced-mutation frequencies and SOS-responses of space samples were observed in both strains compared with the ground control samples. It is suggested that microgravity might not influence induced-mutation frequencies and SOS-responses at the stages of DNA replication and/or DNA repair. In addition, we developed a new experimental apparatus for space experiments to culture and freeze stocks of E. coli and S. cerevisiae cells.

Approximately 10% of cases of hypertensive intracerebral hemorrhage are cerebellar hemorrhage. We report a case of intracerebellar hemorrhage in which the initial symptoms were hearing loss and tinnitus. A 45-year-old man suddenly complained of hearing loss and tinnitus on the right side. Computed tomography demonstrated a high-density area 1.2 cm in diameter in the right cerebellar peduncle. Because of enlargement of the high-density area, the patient underwent surgery based on the diagnosis of hypertensive intracerebellar hemorrhage, and the hematoma was evacuated. The right-sided acoustic nerve was remarkably swollen by a subpial hematoma. In this case, hemorrhage of the right cerebellar peduncle extended to the eighth nerve through the subpial space, causing hearing loss and tinnitus.

A high-gain and high-saturation output power optical amplifier operating in the 1.3- mu m wavelength region that was fabricated using a compressive-strained multiple-quantum-well active region is described. It is shown that optical gain as high as 27 dB and 3-dB saturation output power as high as 14 dBm were obtained simultaneously. >

The present study examined the causes of the low developmental potential of enucleated oocytes that have received ES cells and consequent postnatal death of the young. The inner cell masses (ICM) of nuclear-transferred blastocysts or diploid blastocysts were injected into tetraploid blastocysts (group B) or nuclear-transferred tetraploid blastocysts (group C), respectively. The developmental potential of these groups was compared with tetraploid blastocysts injected with ICM of diploid blastocysts (group A). The potential of reconstituted blastocysts to develop into live young in group B increased slightly (5%) but was significantly lower than that in group A (45%). The rate of postnatal death of young in group B did not decrease. The implantation rate of reconstituted blastocysts in group C was very low and no live fetuses were obtained. The results of the present study indicate that the inferior potential of both ICM and trophectoderm cells of nuclear-transferred blastocysts underlies the low developmental rate of nuclear-transferred oocytes receiving ES cells and the higher rate of postnatal death of ES cell-derived young.

A 54-year-old woman with chronic renal failure presented with tumoral calcinosis manifesting as progressive radiculomyelopathy. Magnetic resonance imaging revealed a spinal epidural mass in the C-2 to C-4 levels. The clinical and radiological findings suggested malignant tumor. Resection of the lesion was performed with total C-2 laminectomy and C-3 and C-4 laminoplasty. The symptoms totally disappeared after surgery. The histological diagnosis was tumoral calcinosis. Tumoral calcinosis is a rare tumoral calcium pyrophosphate dihydrate crystal deposition disease which presents as periarticular soft tissue calcification. Tumoral calcinosis should be considered in patients with a mass lesion involving the upper cervical spine and associated with metabolic abnormalities. Surgical excision is the treatment of choice, because this is completely curative without known recurrence.

A 70-year-old man with bladder cancer received a total cystectomy and an ileal conduit 64 months before he visited our hospital with complaints of lower abdominal pain, shaking and chilliness. Bilateral hydronephrosis due to an ileal conduit obstruction were observed on the ultrasonography. Bacterial culture from blood and urine samplings revealed E. coli. Under the diagnosis of urosepsis, the administration of anti-biotics and bilateral percutaneous nephrostomy were performed. However, he suffered from septic shock and disseminated intravascular coagulation (DIC). Therefore, the treatments for DIC were done, and they were effective. The obstruction of the ileal conduit was cured spontaneously. No recurrence or metastases were found on ultrasonography and computed tomographic scan for 12 months after these treatments.

We experienced a 3 months infant with thalamic hemorrhage penetrating to lateral ventricle with abnormal Protein S. Although the coagulation factor and fibrinogenolysis factors were evaluated, there were no remarkable abnormal laboratory data except for slightly decline of Protein S. The DNA analysis was performed for Protein S, and a missense mutation(A to G transmission) was found, which was resulting in Lys-155 to Glu. The total Protein S antigen was normal level, but co-factor activity for activated Protein C was declined. That mutation is named Protein S-Tokushima, and the patient who has abnormal Protein S tends to suffer recurrent coagulopathy. In our patient, it was interesting that any thrombotic disease had not occurred, but cerebral hemorrhage had occurred.

We report a patient with motor neuron syndrome similar to amyotrophic lateral sclerosis (ALS) and with spontaneous recovery. At the age 40, the woman developed progressive muscular weakness, atrophy and fasciculation in extremities. She also noted a dyspnea, tongue atrophy and dysphagia. A neurological examination 6 months after onset revealed i) a tongue atrophy and fasciculation, ii) diffuse muscule weakness and atrophy in face, neck and extremities, and iii) marked hyperreflexia in the four limbs and bilateral Babinski reflex, but iv) neither sensory disturbance nor ophthalmoplegia. Electromyogram (EMG) detected such denervation potentials as fibrillation potentials, fasciculation potentials, positive sharp waves and polyphasic or giant MUPs diffusely in the limb muscles. Peripheral nerve conduction study detected neither conduction block nor delay. Thus, she was diagnosed as suffering from ALS. However, since approximate 1 year after onset, her muscle weakness has gradually been getting better. Simultaneously, the dyspnea and dysphagia gradually improved. Two years after onset, an EMG examination detected chronic denervation potentials in the left musculus sternocleidomastoideus and a few on-going denervation potentials in the left musculus extensor carpi radialis, but no denervation potentials in other limb muscles. Fasciculation potentials were found in tongue muscles. Thus, the present case was thought to have a reversible motor neuron syndrome clinically quite similar to ALS. A mild increase in IgE (346 U/ml) and a low-titer IgM-class anti-GM1 antibody were found in her serum though its pathological significance was uncertain. Any immunological aberrance may account for the pathogenesis. It should be noted that clinically diagnosed cases of ALS may rarely recover spontaneously.

Cell-mediated cytotoxicity may be involved in delayed and/or chronic xenograft rejection in which apoptosis is induced in the grafted cells via the Fas/Fas-ligand (FasL) and perforin/granzyme pathways. One barrier to the potential use of xeonogenic grafts for humans may be Fas/FasL-mediated apoptosis, which would be blocked by the gene expression of cytokine response modifier A (CrmA), a cowpox virus gene product. The purpose of this study is to explore whether crmA is an effective candidate gene for inhibiting apoptosis in an in vitro model of xenograft rejection, using Fas-expressing non-primate cells cultured with a soluble recombinant human FasL (sFasL). A recombinant adenovirus vector expressing CrmA (AxCALNLCrmA) was successfully generated with a Cre-mediated switching system. PK15 cells, derived from a porcine kidney and infected with AxCALNLCrmA and/or AxCANCre at a multiplicity of infection (MOI) ranging from 0.1 to 100, were cultured with human sFasL derived from KFL74.18, a human FasL-overexpressed cell line. The gene-expression level of the PK15 cells was confirmed by CrmA-immune staining. Approximately 70% of the control PK15 cells showed induced apoptosis when cultured with sFasL. In contrast, the apoptosis was dramatically reduced in crmA-gene-transduced PK15 cells. The inhibitory effect of apoptosis increased with an increase in the infection dose of AxCANCre. In addition, the activity of caspases 3 and 8 was significantly inhibited in the crmA-transduced cells. These results indicate that CrmA is an effective gene product for inhibiting Fas/FasL-mediated apoptosis, which suggests the potential therapeutic use of its gene transduction to protect against graft damage due to delayed and/or chronic xenograft rejection.

We investigated whether a compensatory vasoconstrictor action would be induced by a hypotensive intervention in the hindquarter vascular region of conscious spontaneously hypertensive rats (SHRs). Mean arterial pressure and hindquarter blood flow were recorded. After hemorrhage (withdrawing blood, 0.3 ml/100 g body weight), hindquarter resistance (HQR) was increased significantly. The decrease in HQR induced by the administration of a ganglionic blocker (C6; 25 mg/kg, i.v.) was significantly greater in SHRs with hemorrhage than in those without hemorrhage. The present results suggest that a detectable hindquarter compensator tone occurs due to hemorrhage in SHRs, although an abnormal substantial vasoconstrictor tone already exists in the hindquarters.

A 69-year-old man visited our hospital with a complaint of dysuria. Intravenous excretory urography, ultrasonography and CT scan showed a tumor at the base of the bladder and the prostate. Transrectal needle biopsy revealed signet ring cell carcinoma. Radical cystectomy and ileal conduit were performed, and a histological diagnosis was a primary signet ring cell carcinoma of the bladder. No recurrence or metastasis was found either on ultrasonography or CT scan at 26 months after the operation. He suddenly suffered from severe abdominal pain, and died of hypovolemic shock by ileus as a late complication of an ileal conduit at 27 months after the operation. An ileus with extensive necrosis of small intestine and cancer recurrence at the junction of the ureter and ileal conduit were observed at autopsy.

A 74-year-old man noticed weakness in bilateral lower limbs 2 months prior to admission. The weakness had rapidly progressed and he could not stand by himself on admission. All thoracic vertebral bodies showed mosaic pattern on T 2 weighted-image. At Th 10 and Th 11, two enhanced masses compressed spinal cord posteriorly. Basal-serum tumor markers, such as LDH, ALP, total-acid phosphatase and prostatic acid phosphatase were elevated, metastatic spine tumor from prostatic carcinoma was suspected. Biopsy specimen from its prostate revealed low differentiated adenocarcinoma. Because sphincter dysfunction progressed rapidly after admission, we started 3 Gy/day irradiation within 24 hr from its appearance targeting both Th 10 to L 1 vertebral bodies and the prostate in total 30 Gy. The clinical symptoms started to resolve immediately, and the disappearance completely within 7 months. This case illustrated that urgent irradiation was effective for broad metastatic spinal tumor with rapidly progressive neurological deficits.

The incidence of hemorrhage associated with venous angioma has been considered to be rare. We here report two cases of brain stem venous angioma which also showed brain stem hemorrhage. Case 1; a 15-year-old female had experienced weakness in the left upper extremity 8 months prior to admission. She developed dysfunction of the left cranial nerves, and magnetic resonance imaging (MRI) showed a huge enlarging hematoma in the pons. Cerebral angiography showed venous angioma penetrating through the pons. Evacuation of the hematoma was performed through the fourth ventricle and many small vessels were found in the hematoma. Although all symptoms were partially resolved after the operation, a re-hemorrhage occurred 1 month after the operation. Case 2; a 50-year-old man had suddenly developed headache and vertigo several days prior to admission. Computed tomography (CT) and MRI showed a small hematoma in the lesion with venous angioma adjacent to the hematoma. All symptoms gradually resolved with conservative therapy.

To investigate whether homogenous analysis of serum low-density lipoprotein cholesterol(LDL-C) was applicable in type III hyperlipoproteinemic subjects, 3 reagents were used to estimate LDL-C in 2 cases with apoE 2/2 phenotype. Each measurements were compared to LDL-C levels by ultracentrifugation(density: 1.019-1.063). LDL-C levels by homogenous analysis with any of the reagents were higher than those by ultracentrifugation, and the difference was varied between the reagents: +14-24% by LDL-EX, +29-55% by Cholestest LDL, and +89-115% by Determiner LDL-C. The cross-reaction by the reagents to intermediate density lipoprotein(IDL) and very low density lipoprotein(VLDL) cholesterol was studied in a case; 22% of cholesterol in these fractions was measured by LDL-EX, 32% by Cholestest LDL, and 110% by Determiner LDL-C. A part of the sample serum was stored at -60 degrees C for several days and melted for re-analysis of homogenous LDL-C levels. After the freezing process, IDL fraction pattern on electrophoresis had been changed and homogenous LDL-C levels by all reagents were different from the measurements of native serum. These results indicated that using reagents with low cross-reaction to IDL and VLDL fractions and careful sample handling are important in homogenous LDL-C analysis in type III hyperlipoproteinemia.

LIM-kinase 1 and 2 (LIMK1 and LIMK2) phosphorylate cofilin and induce actin cytoskeletal reorganization. LIMK1 is activated by Rho-associated, coiled-coil-forming protein kinase (ROCK) and p21-activated kinase 1 (PAK1), but activation mechanisms and cellular functions of LIMK2 have remained to be determined. We report here that LIMK1 and LIMK2 phosphorylate both cofilin and actin-depolymerizing factor (ADF) specifically at Ser-3 and exhibit partially distinct substrate specificity when tested using site-directed cofilin mutants as substrates. We also show that LIMK2 is activated by ROCK by phosphorylation at Thr-505 within the activation loop. Wild-type LIMK2, but not its mutant (T505V) with replacement of Thr-505 by Val, was activated by ROCK in vitro and in vivo. LIMK2 mutants with replacement of Thr-505 by one or two Glu residues (T505E or T505EE) increased the kinase activity about 3.6-fold but were not further activated by ROCK. When expressed in HeLa cells, wild-type LIMK2, but not the T505V mutant, induced the formation of stress fibres, focal adhesions and membrane blebs. Furthermore, inhibitors of Rho and ROCK significantly suppressed LIMK2-induced stress fibres and membrane blebs. These results suggest that LIMK2 functions downstream of the Rho-ROCK signalling pathway and plays a role in reorganization of actin filaments and membrane structures, by phosphorylating cofilin/ADF proteins.

Chloroplast ATP synthase is a thiol-modulated enzyme whose DeltamuH(+)-linked activation is strongly influenced by reduction and the formation of a disulphide bridge between Cys(199) and Cys(205) on the gamma subunit. In solubilized chloroplast coupling factor 1 (CF(1)), reduction of the disulphide bond elicits the latent ATP-hydrolysing activity. To assess the regulatory importance of the amino acid residues around these cysteine residues, we focused on the three negatively charged residues Glu(210)-Asp-Glu(212) close to the two cysteine residues and also on the following region from Leu(213) to Ile(230), and investigated the modulation of ATPase activity by chloroplast thioredoxins. The mutant gamma subunits were reconstituted with the alpha and beta subunits from F(1) of the thermophilic bacterium Bacillus PS3; the active ATPase complexes obtained were purified by gel-filtration chromatography. The complex formed with a mutant gamma subunit in which Glu(210) to Glu(212) had been deleted was inactivated rather than activated by reduction of the disulphide bridge by reduced thioredoxin, indicating inverse regulation. This complex was insensitive to the inhibitory CF(1)-epsilon subunit when the mutant gamma subunit was oxidized. In contrast, the deletion of Glu(212) to Ile(230) converted the complex from a modulated state into a highly active state.

The aim of this study was to elucidate the efficacy of 1 alpha hydroxy vitamin D3 for treatment of metabolic bone disorder after gastrectomy.MD-MS method was performed in 16 patients who underwent gastrectomy to evaluate the metabolic bone disorder and compared before and after 1 alpha hydroxy vitamin D3 treatment. The symp-toms related to the metabolic bone disorder were also analyzed through patient interview.The severity of the metabolic bone disorder analyzed by the MD-MS method improved after 1 alpha hydroxy vitamin D3 treatment in 56.3% of patients. The deviation degree of the cortical bone density was also significantly improved. The symptoms related to metabolic bone disorder disappeared in 80% of patients after treatment.The administration of 1 alpha hydroxy vitamin D3 may be useful for the metabolic bone disorder in the treatment of patients after gastrectomy.

A 79 year-old woman was admitted to Aioi City Hospital for a closer examination of hepatic dysfunction. A filling defect was observed at the distal end of the intrapancreatic common bile duct by computed tomography combined with drip infusion cholangiography. The diagnosis of adenoma with dysplasia at the papilla of Vater was obtained by a biopsy performed during duodenoscopy. As a result, we performed an ampullectomy. Histologic examination revealed a papillary adenocarcinoma which partly extended just beyond the muscle of Oddi. The patient made an uneventful recovery and was discharged on the 35th postoperative day. Here, based upon our experience, we discuss such problems as the accuracy of preoperative diagnosis and the indications for ampullectomy.

This study was designed to clarify the clinicopathologic characteristics and survival in early gastric remnant cancer and compare with early primary cancer in the upper third of the stomach.Twenty-five patients with early gastric remnant cancer, who underwent resection at Kanagawa Cancer Center and First Department of Surgery, Yokohama City University between 1974 and 1996 were evaluated in this study. Various clinicopathologic characteristics, such as age, sex, symptoms, size of tumor, depth of invasion, lymph node metastasis, cell differentiation, and survival were investigated and early gastric remnant cancer was compared with early primary cancer in the upper third of the stomach.According to the macroscopic type, protruded type such as I or II type accounted for a great majority in early gastric remnant cancer, while II c depressed type was common in early primary cancer in the upper third of the stomach, comprising 64.2% of all cases. Pathological examination disclosed that well-differentiated carcinoma and mucosal carcinoma were more frequently observed in early gastric remnant cancer than in early primary cancer in the upper-third of the stomach. The 5-year survival rate was 83.5% for early primary cancer in the upper-third of the stomach. In contrast, no patients experienced recurrence after operation for early gastric remnant cancer.From the view point of clinicopathological evaluation, gastric remnant cancer is a special from of gastric cancer. A follow-up program is important in order to detect early gastric remnant cancer. A low incidence of lymph node metastasis suggests that endoscopic mucosal resection of the tumor or limited operation could be performed under strict indication.

In the present study of rat heart using (31)P-nuclear magnetic resonance, we examined the interaction between beta-adrenergic and insulin receptors in terms of the intracellular free Mg(2+) concentration ([Mg(2+)](i)) regulation. [Mg(2+)](i) was estimated from the separation of the chemical shifts of the alpha- and beta-adenosine triphosphate (ATP) peaks, using the dissociation constant of MgATP 87 microM (established recently). In normal (phosphate-free Krebs-Henseleit) solution, [Mg(2+)](i) was approximately 1.02 mM. Insulin at physiological and pathological concentrations increased [Mg(2+)](i) and contractility in a dose-dependent manner. Insulin (more than 100 micro(u) ml(-1)) suppressed the decrease in [Mg(2+)](i) caused by isoprenaline (100 nM), and these effects of insulin on [Mg(2+)](i) and contractility were blocked by LY333531 (macrocyclic bis (indolyl) maleimide, 100 nM), a protein kinase C (PKC) inhibitor. The isoprenaline-induced decrease in the concentrations of ATP ([ATP]) with insulin application was significantly smaller than that without insulin. Insulin modulates [Mg(2+)](i) and haemodynamics, presumably via activation of PKC, thereby antagonizing the reduction of [Mg(2+)](i) induced by beta-adrenoceptor stimulation.

The optimal dose of antibiotics for Helicobacter pylori eradication is not known. The aim of this study was to evaluate optimal dose of antibiotics (amoxicillin) for eradication of H. pylori in the remnant stomach.Biopsy specimens were obtained from 77 patients who underwent gastrectomy for gastric cancer. H. pylori was subsequently diagnosed by rapid urease test and culture. Gastritis was assessed by scoring. Patients with positive H. pylori were eligible for the eradication study. Amoxicillin 750 mg per day for 2 weeks and omeprazole 20 mg per day for 8 weeks were administered to them. Endoscopic reexamination and 13C-urea breath test were performed 12 weeks after the initiation of treatment.The positive rate of H. pylori was 38.9% in the remnant stomach. Eradication rate was 50.0%. Mean dose of amoxicillin in effective cases was 14.1 +/- 1.5 mg/kg/day. This was significantly higher than that in non-effective cases (12.5 +/- 1.5 mg/kg/day). Remnant gastritis was significantly improved after complete eradication.H. pylori was present in 38.9% of patients who underwent gastrectomy for gastric cancer. The optimal dose of amoxicillin was 15.6 mg/kg/day for 14 days with omeprazole-amoxicillin therapy.

The lowest rotational transitions of CH in the ground electronic state (X2Pi), J=3solm0;2, N=1--J=1solm0;2, N=1, have been observed in the laboratory in the 532.8 and 536.8 GHz regions. All six possible hyperfine components are identified, and the precise transition frequencies are determined.

A Phase 2 multicenter trial of 123I-IBF, (S)-5-iodo-7-N-[(1-ethyl-2- pyrrolidinyl)methyl]carboxamido-2,3-dihydrobenzofuran, was conducted to evaluate its clinical efficacy and safety in 158 patients with Parkinson's disease (PD) or Parkinson syndromes (PS). SPECT data were acquired at two hours (2H-SPECT), after intravenous injection of 123I-IBF (167 MBq). Additional SPECT scan at three hours (3H-SPECT) and dynamic SPECT scan at most until one hour were performed when possible. No severe side effects due to 123I-IBF injection were observed. The sensitivity, specificity and accuracy for discriminating PS from PD using the striatal specific binding count-to-frontal cortex count ratio (St/Fc-1) in 3H-SPECT were 72.7%, 81.0% and 78.1% in 64 clinically definite cases (i.e., typical cases), respectively. The putamen-to-caudate ratios were significantly lower in striatonigral degeneration compared with those in PD. The contralateral-to-ipsilateral ratios against the symptomatic side of tremor and/or rigidity in the patients with PD (HoehnYahr I) were significantly higher than the left-to-right ratios in the normal controls. St/Fc-1 in 3H-SPECT was significantly lower in the patients showing a poor response to levodopa than in those showing a good response. The dopamine D2 receptor binding potential (k3/k4), obtained by dynamic SPECT based on compartment model analysis, correlated well with the striatal specific binding count-to-occipital cortex count ratio. These results suggest that 123I-IBF is a promising agent for differential diagnosis and pathophysiological evaluation of PD and PS.

A case of 45-year-old female, who presented with temporal lobe epilepsy was reported. The patient was found to have old intracerebral hemorrhage due to capillary telangiectasis in the temporal lobe. On the intraoperative electrocorticography, frequent paroxysmal activities were recorded independently both on the medial and lateral aspects of the temporal lobe. Even after resection of the lateral temporal lobe, frequent paroxysmal discharges were noted on the hippocampus. Histologically, there are astrogliosis and hemosiderin deposits in the white matter around the telangiectasis and the old hematoma. It is postulated that the hippocampus gained secondary epileptogenicity.

This study was conducted to elucidate the relationship between the seropositive rates of Carcinoembryonic antigen (CEA), Sialyl Le(a) (CA 19-9), Sialyl Le(x) (SLX) and Sialyl Tn (STN) and the clinicopathological variables. The correlation of serum levels of these antigens between the peripheral venous blood and the venous blood draining from the tumor was also evaluated.The subjects were 113 patients with gastric cancer, who underwent gastrectomy at the First Department of Surgery, Yokohama City University, between 1991 and 1996. Serum levels of CA 19-9, SLX, STN and CEA in the peripheral blood and the draining venous blood were measured.The positive rates for CA 19-9, SLX, STN and CEA were closely correlated with tumor stage, lymph node metastasis, and depth of invasion. Although the seropositive rates for CA 19-9, SLX, STN, and CEA in the draining venous blood were lower than those in the peripheral blood, a close correlation for serum levels of 4 antigens between the peripheral venous blood and the draining venous blood was observed in advanced cancer.These results suggest that these antigens may be drained by the lymphatic route as well as the hematogenous route. Further studies must be performed to elucidate the mechanism of these antigens entering into the peripheral blood by devising a technique for collecting the lymph.

Primary small cell carcinoma of the esophagus, which is similar in appearance and behavior to its counterpart of the lung, is a rare tumor. We describe a 77 year-old woman whose esophagram revealed a well-defined mass in the lower third of the thoracic esophagus. A biopsy specimen showed an infiltration of small malignant cells. The individual cells were oval- or spindle-shaped with hyperchromatic nuclei and scant cytoplasm. Synaptophysin staining was positive. The mass was diagnosed as a small cell carcinoma of the esophagus. She underwent an esophagectomy with esophagogastric anastomosis. We discuss the treatment of small cell carcinoma of the esophagus.

This paper reports a case in which endoscopic hemostasis of a bleeding colonic diverticula was successful with endoscopic hemoclip. The patient, a 53 year-old man with painless hematochezia, was urgently admitted to our institute. After colonic cleaning preparation, colonoscopic examination was performed. At the bottom of the diverticulum of the ascending colon, a vessel with oozing blood was endoscopically noted. Hemoclips were placed on and around the visible vessel and immediate hemostasis was completed. Endoscopic clipping method for management of bleeding diverticular vessel is an effective, simple, and safe procedure.

Many authors have reported that Helicobacter pylori (H. pylori) is one of the major causes of gastritis and peptic ulcer. This study was conducted to evaluate the incidence of H. pylori infection and the curative effects of amoxicillin and omeprazole on H. pylori in the remnant stomach.Biopsy specimens were obtained from 70 patients who underwent gastrectomy for gastric cancer. H. pylori was subsequently diagnosed by CLO test and culture of H. pylori. Gastritis was assessed by the scoring of four characteristic pathological parameters. Patients with positive H. pylori were eligible for the eradication study. Amoxicillin, 750 mg per day for 2 weeks, and omeprazole, 20 mg per day for 8 weeks, were administered to them. Endoscopic reexamination was performed 12 weeks after the initiation of treatment.The overall positive rate of H. pylori was 37.1%; 39.6% in Billroth I reconstruction, 0% in Billroth II reconstruction, and 55.6% in pylorus preserving gastrectomy, respectively. The positive H. pylori rate of Billroth II reconstruction was significantly low. However, there was no association of positive rate of H. pylori with time. There was no significant difference of gastritis scores between H. pylori infected patients and non-infected patients. The eradication rate was 70.0%.H. pylori was present in 37.1% of patients who underwent gastrectomy. Gastritis was not significantly severe in H. pylori infected patients. The treatment with amoxicillin and omeprazole was effective for these patients.

A 71-year-old man visited our hospital with a complaint of a right intrascrotal mass. An elastic hard mass was palpable in the right intrascrotal extratesticular space. Ultrasonography, computed tomographic scan and magnetic resonance imaging showed a left intrascrotal extratesticular tumor. However, preoperative diagnosis was not decided. Tumor resection was performed, and the histological diagnosis was schwannoma. Intrascrotal extratesticular schwannoma is very rare, and this case was considered as the second report in Japan.