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Chronic low-grade inflammation is a hallmark of obesity and thought to contribute to the development of obesity-related insulin resistance. Toll-like receptor 4 (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are protected from diet-induced insulin resistance and inflammation; however, which Tlr4-expressing cells mediate this effect is unknown. Here we show that mice deficient in hepatocyte Tlr4 (Tlr4LKO) exhibit improved glucose tolerance, enhanced insulin sensitivity and ameliorated hepatic steatosis despite the development of obesity after a high-fat diet (HFD) challenge. Furthermore, Tlr4LKO mice have reduced macrophage content in white adipose tissue, as well as decreased tissue and circulating inflammatory markers. In contrast, the loss of Tlr4 activity in myeloid cells has little effect on insulin sensitivity. Collectively, these data indicate that the activation of Tlr4 on hepatocytes contributes to obesity-associated inflammation and insulin resistance, and suggest that targeting hepatocyte Tlr4 might be a useful therapeutic strategy for the treatment of type 2 diabetes. Mice lacking Toll-like receptor 4 (Tlr4) do not develop diet-induced insulin resistance. Here Jia et al.create two tissue-specific Tlr4 knockouts to demonstrate that hepatic Tlr4, but not Tlr4 expressed in myeloid cells, is driving obesity-induced inflammation and insulin resistance.

Resistin was originally identified as an adipocyte-derived factor upregulated during obesity and as a contributor to obesity-associated insulin resistance. Clinically, resistin has also been implicated in cardiovascular disease in a number of different patient populations. Our aim was to simultaneously address these phenomena.We generated mice with modest adipocyte-specific resistin overexpression. These mice were crossed with mice deficient in the LDL receptor (Ldlr (-/-)) to probe the physiological role of resistin. Both metabolic and atherosclerotic assessments were performed.Resistin overexpression led to increased atherosclerotic progression in Ldlr (-/-) mice. This was in part related to elevated serum triacylglycerol levels and a reduced ability to clear triacylglycerol upon a challenge. Additional phenotypic changes, such as increased body weight and reduced glucose clearance, independent of the Ldlr (-/-) background, confirmed increased adiposity associated with a more pronounced insulin resistance. A hallmark of elevated resistin was the disproportionate increase in circulating leptin levels. These mice thus recapitulated both the proposed negative cardiovascular correlation and the insulin resistance. A unifying mechanism for this complex phenotype was a resistin-mediated central leptin resistance, which we demonstrate directly both in vivo and in organotypic brain slices. In line with reduced sympathetic nervous system outflow, we found decreased brown adipose tissue (BAT) activity. The resulting elevated triacylglycerol levels provide a likely explanation for accelerated atherosclerosis.Resistin overexpression leads to a complex metabolic phenotype driven by resistin-mediated central leptin resistance and reduced BAT activity. Hypothalamic leptin resistance thus provides a unifying mechanism for both resistin-mediated insulin resistance and enhanced atherosclerosis.

Mice lacking 5-HT 2C receptors (5-HT(2C)Rs) displayed hepatic insulin resistance, a phenotype normalized by re-expression of 5-HT(2C)Rs only in pro-opiomelanocortin (POMC) neurons. 5-HT(2C)R deficiency also abolished the anti-diabetic effects of meta-chlorophenylpiperazine (a 5-HT(2C)R agonist); these effects were restored when 5-HT(2C)Rs were re-expressed in POMC neurons. Our findings indicate that 5-HT(2C)Rs expressed by POMC neurons are physiologically relevant regulators of insulin sensitivity and glucose homeostasis in the liver.

Smad family proteins play a pivotal role in transmitting the transforming growth factor-beta (TGF-beta) superfamily signals from the cell surface to the nucleus. In response to ligand stimulation, Smad4 forms a complex with respective receptor-specific Smads, and the complex translocates into the nucleus and regulates gene expression. Thus, the nuclear entry of the Smad complex is one of the key steps in signal transduction. However, little is known about regulatory mechanisms for nucleocytoplasmic transport of Smads. Here we report identification of a functional, leucine-rich nuclear export signal (NES) in Smad4, which regulates subcellular distribution of Smad4. We then show evidence suggesting that the NES-dependent cytoplasmic localization of Smad4 is important for ensuring optimal TGF-beta responsivenesses in transcriptional activation. Moreover, we show that the NES of Smad4 is specifically inactivated by the stimulus-dependent hetero-oligomerization with receptor-specific Smads during the TGF-beta-induced nuclear translocation of Smad4. Taken together, these results suggest an important regulatory role of the NES of Smad4 in TGF-beta signaling.

Carp homologues of p38 mitogen-activated protein kinase (MAPK) and its activator MAPK kinase 6 (MAPKK6, referred to as MKK6) were identified. There exist at least two distinct carp p38s, cp38a and cp38b, both of which consist of 361 amino acids. The transcript of c38a was exclusively expressed in the ovary, whereas that of cp38b was ubiquitously expressed. Western blot analysis with anti-(phosphorylated MAPK) Ig specific to the active p38 or JNK has shown that p38 was activated in response to hypertonic stress (1 m sorbitol) in epithelioma papilosum cyprini carp epithelial cells (EPC) and that the activation of p38 proceeded faster to the maximal level than that of JNK. Carp homologue (cMKK6) of p38 activator MKK6 consists of 404 amino acids. It was expressed ubiquitously but was most abundant in the ovary. An in vitro kinase assay demonstrated that cMKK6 is an upstream activator of cp38 and cp38b in carp because it specifically phosphorylated and activated cp38a and cp38b. Interestingly, we found that cMKK6 has a nuclear export signal (NES) sequence in its N-terminal region although upstream activators of stress-activated MAPKs, p38 and JNK, do not in other animals. The NES sequence facilitated nuclear export of cMKK6 and ovalbumin. Leucine residues in the sequence were crucial for the NES activity, as the activity was lost on replacement of the leucines to alanines. The existence of an NES in cMKK6 implies the requisite of strict regulation of the p38 MAPK pathway in carp. The abundance of these components for the stress-activated pathway in the ovary might be related to ectogenetic early development.

The CD40 molecule plays important roles in B cell activation, proliferation, and immunoglobulin (Ig) class switching. In Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL), CD40 mediates growth inhibition and EBV reactivation via the CD40 signaling pathways. CD40 cross-linking with a monoclonal antibody arrests cell growth in G1 and induces expression of p27kip1 cyclin-dependent kinase inhibitor. CD40 cross-linking also induces EBV reactivation, as detected by the induction of EBV-specific early antigen, immediate early BZLF1 RNA, and its protein product ZEBRA. These results support hypotheses that the proliferation of EBV-infected B cells in vivo can be inhibited by interactions with the CD40 ligand on activated helper T cells, and latent EBV is reactivated via the signaling pathways controlled by CD40 interactions.

The natural environmental investigations were carried out on the source of NAGARA River and its basin. At the beginning, the method of natural environmental investigation was simply represented. In this report, in particular, the authors clarify the true character of source of NAGARA River. Moreover, the data of chemical analysis about water qualities of source zone of NAGARA River and natural water in its basin are shown and the real condition of water environment in the water system of NAGARA River is discussed.

Treatment of advanced or recurrent breast cancer with medroxyprogesterone acetate (MPA) shows high response rates and the accessory effects of appetite stimulation, improvement in performance status (PS) and bone marrow protection. In recent years, interleukin-6 (IL-6) has been reported to cause cachexia. In this study, to clarify the significance of IL-6 in advanced or recurrent breast cancer, the relationship between the IL-6 level and clinical findings or effect of MPA was investigated. Sixty-five patients with recurrent or advanced breast cancer participated in a prospective study. The age of patients ranged from 28 to 79 years with an average age of 51.3 years. IL-6 level was investigated in these patients dosed with 800 mg/day of MPA and in 17 postoperative nonrecurrent patients. Serum MPA level was measured by high-performance liquid chromatography and IL-6 level was measured prior to MPA administration, 4 weeks (in 59 cases) and 12 weeks (in 32 patients) after MPA administration by ELISA. Serum IL-6 level was significantly higher in recurrent cases, especially in those with visceral metastasis. Further, in patients for whom MPA therapy was effective, the IL-6 level prior to the treatment was clearly low. The IL-6 level was significantly increased after 4 weeks. However, response to MPA was significantly higher and PS was improved in those cases demonstrating less increased IL-6 levels after 4 weeks. In addition, the effect of MPA was significantly related to a higher serum concentration of MPA-positive ER, and longer disease-free interval, although there was no significant predictive factor for the clinical effect of MPA therapy in multivariate analysis. In conclusion, MPA therapy was effective in cases demonstrating a low IL-6 level and less increased IL-6 levels after 4 weeks. PS was improved in those cases in which the degree of IL-6 increase was suppressed by MPA, and many such cases showed low IL-6 levels prior to MPA therapy. Furthermore, PS was improved even in nonresponders to MPA. Therefore, it is suggested that MPA therapy might be useful in treating recurrent breast cancer, and its benefits might be mediated by IL-6.

In response to extracellular stimuli, mitogen-activated protein kinase (MAPK, also known as ERK), which localizes to the cytoplasm in quiescent cells, translocates to the nucleus and then relocalizes to the cytoplasm again. The relocalization of nuclear MAPK to the cytoplasm was not inhibited by cycloheximide, confirming that the relocalization is achieved by nuclear export, but not synthesis, of MAPK. The nuclear export of MAPK was inhibited by leptomycin B (LMB), a specific inhibitor of the nuclear export signal (NES)-dependent transport. We have then shown that MAP kinase kinase (MAPKK, also known as MEK), which mostly localizes to the cytoplasm because of its having NES, is able to shuttle between the cytoplasm and the nucleus constantly. MAPK, when injected into the nucleus, was rapidly exported from the nucleus by coinjected wild-type MAPKK, but not by the NES-disrupted MAPKK. In addition, injection of the fragment corresponding to the MAPK-binding site of MAPKK into the nucleus, which would disrupt the binding of MAPK to MAPKK in the nucleus, significantly inhibited the nuclear export of endogenous MAPK. Taken together, these results suggest that the relocalization of nuclear MAPK to the cytoplasm involves a MAPKK-dependent, active transport mechanism.

In order to realize positioning of nano-meter precision, it is important to eliminate friction and backlash from mechanical parts making relative sliding and/or rolling motion. This paper first describes the principle of an Air Bearing Lead Screw(ABLS)in which the lead screw surface is completely separated from the nut surface by the pressured air film. Then a positioning system comprised of ABLS, a table, an air guideway and air bearings used for supporting the screw shaft is introduced. The system is free from friction except that by DC motor brushes. The basic dynamic characteristics of the system are examined and some controllers are designed and implemented. Experimental results show that the system can position the table with the accuracy of a few nano-meters.

In response to extracellular stimuli, mitogen-activated protein kinase (MAPK, also known as ERK) translocates from the cytoplasm to the nucleus. MAP kinase kinase (MAPKK, also know as MEK), which possesses a nuclear export signal (NES), acts as a cytoplasmic anchor of MAPK. Here we show evidence that tyrosine (Tyr190 in Xenopus MPK1/ERK2) phosphorylation of MAPK by MAPKK is necessary and sufficient for the dissociation of the MAPKK-MAPK complex, and that the dissociation of the complex is required for the nuclear translocation of MAPK. We then show that nuclear entry of MAPK through a nuclear pore occurs via two distinct mechanisms. Nuclear import of wild-type MAPK (mol. wt 42 kDa) was induced by activation of the MAPK pathway even in the presence of wheat germ agglutinin or dominant-negative Ran, whereas nuclear import of beta-galactosidase (beta-gal)-fused MAPK (mol. wt 160 kDa), which occurred in response to stimuli, was completely blocked by these inhibitors. Moreover, while a dimerization-deficient mutant of MAPK was able to translocate to the nucleus upon stimulation, this mutant MAPK, when fused to beta-gal, became unable to enter the nucleus. These results suggest that monomeric and dimeric forms of MAPK enter the nucleus by passive diffusion and active transport mechanisms, respectively.

The new biocompatible cellulosic membrane (AM-BC-F[AM-BIO-HX], Asahi-Medical Co. Ltd., Tokyo, Japan) has been developed, which has a higher flux than conventional membranes and more excellent antithrombogenicity because of its smoother membrane surface. The roughness of the inner surface of the AM-BC-F membrane was smaller than that of conventional membranes, as observed by Atomic Force Microscopy, because it was produced by the newly developed spinning method of cuprammonium cellulose solution, which has a different composition from that of a conventional cuprammonium cellulose solution. The degree of platelet adhesion (number of platelets adhered) on the membrane surface was evaluated in vitro by the measurement of the amount of the LDH released from the adhered platelets on the membrane surface after contact with fresh blood of Japanese male white rabbits weighing 2.5–3.0 kg. The number of platelets adhered of AM-BC-F was far smaller than that of conventional membranes. It was deduced from the smoother surface of the membrane. It can be expected that AM-BC-F will have an excellent antithrombogenicity on a dynamic state during actual dialysis treatments, because it is considered that the shearing stress of blood on the inner surface and the interaction between platelets and the membrane surface are less than that of conventional membranes. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 72: 1249–1256, 1999

Background CRM1, an evolutionarily conserved protein, was shown to be a receptor for leucine-rich nuclear export signal (NES)-dependent protein transport. In lower eukaryotes CRM1 is reported to be required for the export of mRNA, however, involvement of the NES-dependent transport pathway in mRNA export in higher eukaryotes has not been established. Results We have found that treatment of mammalian cells with leptomycin B (LMB), a specific inhibitor of CRM1, induces the nuclear accumulation of endogenous mRNA, probably due to the inhibition of its export. In fission yeasts, the nuclear accumulation of mRNA also occurred in cells treated with LMB or in a temperature-sensitive crm1 mutant at a restrictive temperature. A synthetic mRNA that was injected into the nucleus of mammalian cultured cells was exported from the nucleus within 5 h. This export was inhibited by both wheat germ agglutinin and a temperature of 4 °C. Importantly, this mRNA export was inhibited by LMB or by an excess amount of the NES peptide-conjugates. LMB treatment, on the other hand, rapidly induced the nuclear entry of RanBP1, a factor involved in the active nucleocytoplasmic transport, although the treatment did not interfere with a nuclear localization signal-dependent transport system within 7 h. Conclusion These results suggest that CRM1 is involved in mRNA export in eukaryotic cells.

BACKGROUND Bone metastases from breast carcinoma are frequently observed as postoperative pathologic conditions; however, in many cases, diagnosis and treatment are difficult. Although most diagnoses of bone metastases are made by plain radiography (X-P) or bone scintigraphy, the use of magnetic resonance imaging (MRI) has enabled detailed imaging of foci, and many more lesions have become detectable. In the current study, the authors evaluated the relation between the diagnosis of bone metastases of breast carcinoma and clinicopathologic factors, especially those of proliferative activity and effects of treatment. METHODS The subjects consisted of 51 breast carcinoma patients (mean age, 51.2 years) with vertebral metastases diagnosed by plain radiography, bone scintigraphy, or MRI. Twenty-eight of the 51 patients were premenopausal and 27 of the 51 had bone metastases only. The patients were classified into the following groups: Group A, 24 patients who showed similar findings in plain radiography, bone scintigraphy, and MRI; Group C, 14 who showed no abnormalities on radiography or bone scintigraphy but whose lesions were diagnosed by MRI only; and Group B, 13 patients with findings intermediate between Groups A and C. The proliferative activity of tumors was evaluated by determining the level of DNA polymerase α. RESULTS Regarding the relation to clinicopathologic factors, a significant number of patients with estrogen receptor (ER) negative tumors who had a high level of DNA polymerase α, short disease free intervals (DFI), and metastases to other organs were included in Group C. Prognoses of patients in Group C were poor. CONCLUSIONS For the diagnosis of breast carcinoma with bone metastasis, different correlations were noted among the various biologic characteristics, such as ER status and proliferative activity. That is, bone scintigraphy sufficiently reflected foci in patients with ER positive tumors or tumors with low proliferation, whereas bone scintigraphy was false-negative in patients with ER negative or highly proliferative tumors, showing that MRI was useful in diagnosing such patients. Therefore, consideration of malignant features, such as proliferative activity and ER status, is believed necessary during the postoperative follow-up of breast carcinoma patients. Cancer 1999;85:1782–8. © 1999 American Cancer Society.

The mitogen-activated protein kinase kinase (MAPKK)/MAP kinase (MAPK) cascade plays an important role in the growth control of mammalian cells. We have found that expression of constitutively active MAPKK induces rapid morphological changes of fibroblastic cells, which are accompanied by disruption of stress fibers and disappearance of focal adhesions. These changes took place under the conditions that inhibited cellular Ras function, suggesting a linkage between the MAPK cascade and the control of cell morphology. We further show that constitutively active MAPKK can induce expression of endogenous Fos protein, an immediately early gene product, and cause the S phase entry of G0-arrested cells. Finally, expression of the N-terminal fragment of MAPKK which encompasses the nuclear export signal sequence and the MAPK-binding site blocked both the serum-induced S phase entry of quiescent cells and the oncogenic Ras-induced morphological changes. All these results demonstrate that MAPKK is one of key molecules involved in the control of both cell morphology and cell proliferation and suggest an important role for the N-terminal region of MAPKK in the regulation of the MAPK signaling.

Second-harmonic components generated from plastic-deformed metal rods are detected in real time using a double-layered piezoelectric transducer (DLPT). The DLPT is composed of two transducers with the resonance frequency f0; its resonance frequencies are f0/2 when the transducers are connected in parallel and f0 when the transducers are connected in series. The performance of the DLPT used in this ultrasonic system is evaluated. Samples of plastic-deformed metal rods are prepared using tensile test equipment. The relative amplitude of the second-harmonic component of the metal rod increased by approximately 25 dB after the tensile tests compared with that before the tensile tests. The variation in tensile load of the second-harmonic components generated by plastic-deformed metal rods is accurately measured by our system.

The objectives of the present study are to clarify the phenomenon of solute transfer occurring inside dialyzers made from asymmetric membranes, to examine the structure of asymmetric membranes capable of suppressing the inflow of endotoxins from the dialysate, and thereby to contribute to the design of a more effective dialysis membrane. Using membranes that have tight layers on both sides (drum-shaped membrane) with the outer one tighter, solutes are more easily transferred from the inside out than from the outside in, leading to effective removal of pathogenic substances from the blood and a significant lowering of endotoxin inflow from the dialysate. The anisotropy of solute permeability of asymmetric dialysis membranes is caused by the difference in the amount of solute transfer due to filtration from the inside out and from the outside in.

M-phase-promoting factor (MPF), a complex of cdc2 and a B-type cyclin, is a key regulator of the G2/M cell cycle transition. Cyclin B1 accumulates in the cytoplasm through S and G2 phases and translocates to the nucleus during prophase. We show here that cytoplasmic localization of cyclin B1 during interphase is directed by its nuclear export signal (NES)-dependent transport mechanism. Treatment of HeLa cells with leptomycin B (LMB), a specific inhibitor of the NES-dependent transport, resulted in nuclear accumulation of cyclin B1 in G2 phase. Disruption of an NES which has been identified in cyclin B1 here abolished the nuclear export of this protein, and consequently the NES-disrupted cyclin B1 when expressed in cells accumulated in the nucleus. Moreover, we show that expression of the NES-disrupted cyclin B1 or LMB treatment of the cells is able to override the DNA damage-induced G2 checkpoint when combined with caffeine treatment. These results suggest a role of nuclear exclusion of cyclin B1 in the DNA damage-induced G2 checkpoint.

The natural environmental investigations were carried out on the source of Shinano river and its basin. At the beginning, the method of natural environmental investigation was simply represented.In this report, in particular, the authors clarifly the ture character of source of Shinano river.Moreover, the data of chemical analysis about water qualities of source zone of Shinano river and natural water in its basin and Kanto area are shown, and the real condition of water environment in the water system of Shinano river is discussed.

Organic dyes are suitable for solid-state dye laser media, and we have been studying many types of solid-state dye lasers. Distributed feedback (DFB) lasers in particular have both superior wavelength tunability and superior narrow-spectrum characteristics. In DFB lasers, gratings are key devices for tuning the laser wavelength. We have developed a method of fabricating gratings quickly and at low cost. Using this "etchless" method, we fabricated a dual-beam DFB solid-state dye laser with two-dimensional photoresist grating, and successfully achieved laser oscillation at two different wavelengths simultaneously.

Galanin-like peptide (GALP) neurones participate in the metabolic control of reproduction and are targets of insulin and leptin regulation. Phosphoinositide 3-kinase (PI3K) is common to the signalling pathways utilised by both insulin and leptin. Therefore, we investigated whether PI3K signalling in neurones expressing GALP plays a role in the transcriptional regulation of the GALP gene and in the metabolic control of luteinising hormone (LH) release. Accordingly, we deleted PI3K catalytic subunits p110α and p110β via conditional gene targeting (cKO) in mice (GALP-p110α/β cKO). To monitor PI3K signalling in GALP neurones, these animals were also crossed with Cre-dependent FoxO1GFP reporter mice. Compared to insulin-infused control animals, the PI3K-Akt-dependent FoxO1GFP nuclear exclusion in GALP neurones was abolished in GALP-p110α/β cKO mice. We next used food deprivation to investigate whether the GALP-neurone specific ablation of PI3K activity affected the susceptibility of the gonadotrophic axis to negative energy balance. Treatment did not affect LH levels in either sex. However, a significant genotype effect on LH levels was observed in females. By contrast, no genotype effect on LH levels was observed in males. A sex-specific genotype effect on hypothalamic GALP mRNA was observed, with fed and fasted GALP-p110α/β cKO males having lower GALP mRNA expression compared to wild-type fed males. Finally, the effects of gonadectomy and steroid hormone replacement on GALP mRNA levels were investigated. Compared to vehicle-treated mice, steroid hormone replacement reduced mediobasal hypothalamus GALP expression in wild-type and GALP-p110α/β cKO animals. In addition, within the castrated and vehicle-treated group and compared to wild-type mice, LH levels were lower in GALP-p110α/β cKO males. Double immunofluorescence using GALP-Cre/R26-YFP mice showed androgen and oestrogen receptor co-localisation within GALP neurones. Our data demonstrate that GALP neurones are direct targets of steroid hormones and that PI3K signalling regulates hypothalamic GALP mRNA expression and LH levels in a sex-specific fashion.

The evaluation method of the bolt conclusion for ultrasonic waves using reflection coefficient S 11 of scattering parameter was proposed. Ultrasonic waves of 2 MHz were used because variation of reflection coefficient S 11 was the greatest. Reflection coefficient S 11 was decreased as the axial force was increased. Usefulness of the evaluation method of the bolt conclusion using reflection coefficient S 11 was demonstrated.

The chiral U(1) anomalies associated with a fermion of spin 1/2 interacting with nonabelian vector and axial-vector fields in four- and six-dimensional curved space are given in tensorial form., Comment: 7 pages

Mitogen-activated protein kinase (MAPK) kinase (MAPKK, also known as MEK), a direct activator for MAPK/extracellular signal-regulated kinase, localizes to the cytoplasm excluded from the nucleus during signal transmission. This nuclear exclusion of MAPKK is directed by its nuclear export signal (NES), but its physiological significance has been unknown. We have found that disruption of the NES dramatically potentiates the ability of constitutively active MAPKK to induce morphological changes and malignant transformation of fibroblastic cells. Readdition of the NES sequence reversed the effects induced by the NES disruption. Moreover, we observed that a dramatic increase of activated MAPK in the nucleus was induced by the NES-disrupted MAPKK and that coexpression of MAPK phosphatase-1 (CL-100) or a kinase negative form of MAPK counteracted the phenotypes induced by the NES-disrupted MAPKK, indicating the crucial role of MAPK in the responses. These findings reveal a novel regulatory role of the NES of MAPKK that may be essential for proper signal transductions.

Most of requirements for hemodialysis hollow fiber membranes depend on their micro pore structure and distribution. Therefore, not only the averaged pore radius but also the pore radius distribution should be noted in the optimal design of hollow fiber hemodialysis membranes. Herein some advantageous characteristics of newly developed cellulose hemodialysis membrane, pore radius distribution pattern of which may be so called “symmetricall gradient structure”, are presented with those of the conventional and well known homogeneous, gradient, and reverse gradient structure membranes.

The BF state is known as a simple wave function that satisfies three constraints in canonical quantum gravity without a cosmological constant. It is constructed from a product of the group delta functions. Applying the chiral asymmetric extension, the BF state is generalized to the state for real values of the Barbero-Immirzi parameter., 8 pages; v2 minor corrections

Background: Double free muscle transfer for the treatment of traumatic total brachial plexus injury provides useful prehensile function. We studied the outcome of this muscle transfer procedure, including the changes in disability and quality-of-life scores. Methods: Thirty-six patients with traumatic total brachial plexus injury who underwent double free muscle transfer for reconstruction from 2002 to 2008 and had a minimum follow-up of twenty-four months after the second free muscle transfer were studied. All were evaluated preoperatively and postoperatively with use of the Disabilities of the Arm, Shoulder and Hand (DASH) and Short Form-36 (SF-36) questionnaires. A separate questionnaire was used to determine job status, pain, use of the reconstructed hand, and satisfaction with the procedure. Results: The mean patient age was twenty-nine years (range, sixteen to forty-nine years), and the mean duration of follow-up was thirty-six months (range, twenty-four to seventy-nine months). The mean active range of motion was 23° (range, 0° to 80°) for shoulder flexion, 31° (range, 0° to 90°) for shoulder abduction, −18° (range, −80° to 40°) for shoulder external rotation, 62° (range, 0° to 130°) for the shoulder rotation arc, 119° (range, 90° to 150°) for elbow flexion, and −33° (range, −60° to −20°) for elbow extension. The power of elbow flexion was M4 in twenty-five patients and M3 in eleven. Twenty-three patients had triceps nerve reconstruction; extension was M0 in two of these patients, M1 in seven, M2 in ten, and M3 in four. Total active motion of the fingers was 46° (range, 0° to 98°), with a mean hook grip strength of 4 kg (range, 0 to 12 kg). Wilcoxon tests revealed significant improvements in the DASH score and the SF-36 physical functioning, role physical, and physical component summary scores. The majority of patients worked but had changed their type of work, used the reconstructed hand in activities of daily living that required both hands, and were satisfied with the procedure. Conclusions: Double free muscle transfer yielded satisfactory function and allowed use of the reconstructed hand in activities that required both hands. The improvement in the DASH score was greater than that in the SF-36 score. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

A real-time detection system for second harmonic ultrasonic pulse waves using a double-layered piezoelectric transducer (DLPT) has been constructed. We also analyzed the effective detection of the second-harmonic ultrasonic pulse waves generated by closed-cracks and/or contact surfaces of solids (CAN: contact acoustic nonlinearity) using DLPT and the pulse inversion averaging (PIA) method. Lamb waves were also detected in a double-layered piezoelectric transducer (DLPT). The second harmonic components generated from a closed crack in the glass plate were detected in the pulse-echo method. The second harmonic components in the received waveform in the closed crack area were approximately 6 dB higher than that in the crack-free area. To confirm the origin of the second harmonic components, vibration velocities were detected by using laser Doppler vibrometry. As a result, the threshold amplitude for the generation of the second harmonic components of the Lamb wave was confirmed. This result indicates the exi...

The distribution volume of water contained in 31 hemodialysis membranes made from seven polymers was measured by three different methods. Water contained in the membranes was classified into three groups according to thermal mobility of the molecules. Structural analysis of the membranes was feasible through determining proportion of nonfreezing water to total water contained in the membranes.

Swelling layers formed by poly(ethylene glycol) (PEG) chains grafted onto surfaces of a cellulosic membrane are known to improve hemocompatibility of the membrane. Three types of hemodialysis membranes were derived from the same regenerated-cellulose hollow-fiber membrane by grafting PEG with different formulas onto the surfaces to clarify the influence of the grafted PEG chains on solute permeability of the membranes. Determination of volume fractions of nonfreezing water contained in the membranes by differential scanning calorimetry revealed that most of the PEG chains were grafted onto the external surfaces and less into the pores in the membranes. Permeability of vitamin B12 for the PEG-grafted membranes except for the one with the shortest PEG chains was reduced as compared with the original membrane, while that of tritium-labeled water for all the PEG-grafted membranes was the same as that of the original membrane. Structural parameters only of the PEG-grafted membrane with the largest alkyl groups at the terminal of the PEG chains were different from those of the other PEG-grafted and original membranes. The shorter PEG chains with the larger terminal alkyl groups are suitable for grafting onto a cellulosic membrane to increase hemocompatibility of the membrane without significant reduction in the solute permeability of the membrane. © 1995 John Wiley & Sons, Inc.

We have been studying solid-state dye lasers with dye-doped xerogel as a laser active medium. It is known that irradiation with a pumping light photobleaches dye molecules. For practical purposes, therefore, an active medium must be easily replaceable once it has become photobleached. Therefore, we have developed a low-cost distributed feedback (DFB) solid-state dye laser. The grating for this laser is fabricated in what we tentatively call an "etchless" process. Using this new laser with an etchless grating, we achieved laser oscillation in the 600 nm wavelength region.

This study examines the use of ultrasonic second harmonic components in the quality control of bolt-fastened structures. An improved method for detecting the second harmonic components, from a bolt fastened with a nut, using the transmission method is constructed. A hexagon head iron bolt was used in the experiments. The bolt was fastened using a digital torque wrench. The second harmonic component increased by approximately 10 dB before and after the bolt was fastened. The sources of second harmonic components were contact acoustic nonlinearity in the screw thread interfaces of the bolt-nut and were the plastic deformation in the bolt with fastening bolt. This result was almost same compared with previous our method. Consequently, usefulness of the novel method for detecting second harmonic ultrasonic components generated from fastened bolt was confirmed.

Glucagon-like peptides (GLP-1/2) are co-produced and highlighted as key modulators to improve glucose homeostasis and insulin sensitivity after bariatric surgery. However, it is unknown if CNS GLP-2 plays any physiological role in the control of glucose homeostasis and insulin sensitivity. We show that mice lacking GLP-2 receptor (GLP-2R) in POMC neurons display glucose intolerance and hepatic insulin resistance. GLP-2R activation in POMC neurons is required for GLP-2 to enhance insulin-mediated suppression of hepatic glucose production (HGP) and gluconeogenesis. GLP-2 directly modulates excitability of POMC neurons in GLP-2R- and PI3K-dependent manners. GLP-2 initiates GLP-2R-p85α interaction and facilitates PI3K-Akt-dependent FoxO1 nuclear exclusion in POMC neurons. Central GLP-2 suppresses basal HGP and enhances insulin sensitivity, which are abolished in POMC-p110α KO mice. Thus, CNS GLP-2 plays a key physiological role in the control of hepatic glucose production through activating PI3K-dependent modulation of membrane excitability and nuclear transcription of POMC neurons in the brain.

Studies have suggested that manipulations of the central melanocortin circuitry by pharmacological agents produce robust effects on the regulation of body weight and glucose homeostasis. In this review, we discuss recent findings from genetic mouse models that have further established the physiological relevance of this circuitry in the context of glucose and energy balance. In addition, we will discuss distinct neuronal populations that respond to central melanocortins to regulate food intake, energy expenditure, insulin sensitivity, and insulin secretion, respectively. Finally, multiple hormonal and neural cues (e.g., leptin, estrogen, and serotonin) that use the melanocortin systems to regulate energy and glucose homeostasis will be reviewed. These findings suggest that targeting the specific branches of melanocortin circuits may be potential avenues to combat the current obesity and diabetes epidemics.

This study examines the use of ultrasonic second harmonic components in the quality control of bolt-fastened structures. An improved method for detecting the second harmonic components, from a bolt fastened with a nut, using the transmission method is constructed. A hexagon head iron bolt (12-mm diameter and 25-mm long) was used in the experiments. The bolt was fastened using a digital torque wrench. The second harmonic component increased by approximately 20 dB before and after the bolt was fastened. The sources of second harmonic components were contact acoustic nonlinearity in the screw thread interfaces of the bolt-nut and were the plastic deformation in the bolt with fastening bolt. This result was improved by approximately 10 dB compared with previous our method. Consequently, usefulness of the novel method for detecting second harmonic ultrasonic components generated from fastened bolt was confirmed.

Absorbancy of a solution in the narrow lumen of a tubular membrane under dialysis is continuously measurable with a newly-developed apparatus using quartz optical fibers. The solute permeability of the membrane was determined by calculating time-dependent changes in the absorbancy measured with the apparatus by the mathematical solution derived for unsteady-state concentration profiles in an infinitely long composite cylinder. This method was independent of convective mass transport and osmotic flow through membranes, leading to superiority to ordinary techniques with respect to accuracy.

SummaryLeptin regulates energy balance and glucose homeostasis. Shortly after leptin was identified, it was established that obesity is commonly associated with leptin resistance, though the molecular mechanisms remain to be identified. To explore potential mechanisms of leptin resistance, we employed organotypic brain slices to identify candidate signaling pathways that negatively regulate leptin sensitivity. We found that elevation of adenosine 3′, 5′-monophosphate (cAMP) levels impairs multiple signaling cascades activated by leptin within the hypothalamus. Notably, this effect is independent of protein kinase A activation. In contrast, activation of Epac, a cAMP-regulated guanine nucleotide exchange factor for the small G protein Rap1, was sufficient to impair leptin signaling with concomitant induction of SOCS-3 expression. Epac activation also blunted leptin-induced depolarization of hypothalamic POMC neurons. Finally, central infusion of an Epac activator blunted the anorexigenic actions of leptin. Thus, activation of hypothalamic cAMP-Epac pathway is sufficient to induce multiple indices of leptin resistance.

The second harmonic components before/after the bolt was fastened were detected by using double-layered piezoelectric transducer (DLPT). The resonance frequency of DLPT changes to 1 MHz (f 0/2) when connected in parallel, but remains at 2 MHz (f 0) when connected in series. An effective fundamental transmission (1 MHz) is obtained when the DLPT is electrically connected in parallel while efficient second harmonic reception (2 MHz) is obtained when the DLPT is connected in series. In our system, the pulse inversion averaging (PIA) method was applied to enhance the second harmonic component. A hexagon head bolt (the diameter of a screw: 12 mm, the length: 100 mm) was used in experimental. The bolt was fastened by 40 N-m. The detected second harmonic component after the bolt was fastened was increased by approximately 10 dB compared with before the bolt was fastened.

Nickel ferrite-dispersed carbon could be synthesized by pressure pyrolysis of divinylbenzene (DVB)-vinylferrocene (VF)-nickelocene (Cp2Ni) polymer in the presence of water under 125 MPa and at temperatures below 700°C. By heat treatment at 550°C with water, nickel ferrite particles could be dispersed finely in the carbon matrix, although a small amount of nickel-iron carbide also began to form above 600°C. The morphologies of the carbon particles formed were observed to be polyhedral, coalescing spherulitic and spherulitic. When 30 wt% H2O, spherulitic carbons a few micrometres in diameter were prepared, in which nickel ferrite particles from 10–30 nm were dispersed in the carbon matrix. The saturation magnetization of carbon composites formed from DVB-3.0 mol% Cp2Ni-6.0 mol% VF and 20 wt% H2O at 550°C was about 30 e.m.u.g−1 and increased with pyrolysis temperature. The coercive force of the carbon composite was 120 Oe and was affected by the amount of added water using pressure pyrolysis. Thermomagnetic measurement shows that the Curie temperature of nickel ferrite-dispersed carbon was about 580 °C.

Several neurodegenerative diseases involve the selective damage of neuron cells resulting from the accumulation of amyloid fibril formation. Considering that the formation of amyloid fibrils as well as their precursor oligomers is cytotoxic, the agents that prevent the formation of oligomers and/or fibrils might allow the development of a novel therapeutic approach to neurodegenerative diseases. Here, we show pyrroloquinoline quinone (PQQ) inhibits the amyloid fibril formation of the amyloid proteins, amyloid beta (1-42) and mouse prion protein. The fibril formation of mouse prion protein in the presence of PQQ was dramatically prevented. Similarly, the fibril formation of amyloid beta (1-42) also decreased. With further advanced pharmacological approaches, PQQ may become a leading anti-neurodegenerative compound in the treatment of neurodegenerative diseases.

We measured plasma epinephrine and norepinephrine concentrations in a rabbit model simulating subarachnoid hemorrhage (SAH), following the injection of prostaglandin F2α (PGF2α ) into the basal cistern. In this model, plasma epinephrine values increased significantly (to 4.2-fold those before injection), substantially more than norepinephrine (which increased 1.3-fold) at 5 minutes (min) after PGF2α injection. Dissection of autonomic outflow from the cervical spinal cord or ligation of the suprarenal veins reduced the changes in plasma catecholamine concentrations associated with PGF2α injection. These results suggest that the sympathetic discharge seen after PGF2α injection into the basal cistern in rabbits occurred through the sympatho-adrenal pathways.

Dialyzer performance strongly depends on the flow of blood and dialysis fluid as well as membrane performance. It is necessary, particularly to optimize dialysis fluid flow, to develop a highly efficient dialyzer. The objective of the present study is to evaluate by computational analysis the effects of dialyzer jacket baffle structure, taper angle, and taper length on dialysis fluid flow. We modeled 10 dialyzers of varying baffle angles (0, 30, 120, 240, and 360 degrees ) with and without tapers. We also modeled 30 dialyzers of varying taper lengths (0, 12.5, 25.0, and 50.0 mm) and angles (0, 2, 4, and 6 degrees ) based on technical data of APS-SA dialyzers having varying surface areas of 0.8, 1.5, and 2.5 m(2) (Rexeed). Dialysis fluid flow velocity was calculated by the finite element method. The taper part was divided into 10 sections of varying fluid resistances. A pressure of 0 Pa was set at the dialysis fluid outlet, and a dialysis fluid flow rate of 500 mL/min at the dialysis fluid inlet. Water was used as the dialysis fluid in the computational analysis. Results for dialysis fluid flow velocity of the modeled dialyzers indicate that taper design and a fully surrounded baffle are important in making the dialysis fluid flow into a hollow-fiber bundle easily and uniformly. However, dialysis fluid flow channeling occurred particularly at the outflowing part with dialyzers having larger taper lengths and angles. Optimum design of dialysis jacket structure is essential to optimizing dialysis fluid flow and to increasing dialyzer performance.

ビニルフェロセン-コバルトセン誘導体の有機金属化合物のジビニルベンゼン共重合体を,熱水の存在下において,加圧熱分解することにより,コバルトフェライト粒子が炭素マトリックス中に均一に高分散した,磁性体-炭素複合材料を合成することができた。このような材料は,導電性と磁性を兼ね備えており,電磁波シールド材,磁性トナーなどに塔用が期待できる。材料の合成の際,熱分解条件を調節することにより,試料の磁気的性質,炭素粒子の形態などを制御することが可能である。125MPa,600℃ の熱分解でコバルトフェライトが単相で炭素中に得られたが,熱分解温度の上昇とともに酸化コバルト,ウスタイトといった反強磁性相が生成し,試料の飽和磁化,残留磁化,保磁力はいちじるしく減少した。また,炭素粉体の形態も熱分解温度が600℃ から700℃ へと増加すると,合体多面体状炭素から球状炭素へと変化する傾向を示した。さらに,共重合体中の金属濃度が高いほど,炭素粒子の粒径は小さくなった。

Laser-dye-doped-DNA-CTMA-PMMA hybrid films have been studied as a potential material for waveguide type thin-film laser devices. For the purpose of evaluate improving processability, not only optical characteristics of the fluorescence intensity and ASE spectrum but also moisture resistance of the hybrid film have been investigated. It is found that optical characteristics of those films are equally matched to the conventional laser-dye-doped- DNA-CTMA films with better moisture resistivity.