Risk factors for postoperative nausea and vomiting after video-assisted thoracic surgery esophagectomy: a prospective cohort study.

Video-assisted thoracic surgery esophagectomy (VATS-E) may increase the risk of postoperative nausea and vomiting (PONV) because it uses a high dosage of anesthesia through a long operative duration. However, no study has examined the risk factors for PONV after VATS-E. Therefore, we investigated the risk factors for PONV to support the appropriate risk management of PONV after VATS-E. This prospective cohort study included 155 patients who underwent VATS-E at the Showa University Hospital between April 1st, 2020 and November 30th, 2022. The primary outcome was the incidence of PONV within 24 h after surgery. Significant independent risk factors associated with the incidence of PONV were selected using multivariate analysis. The association between the number of risk factors for PONV and incidence of PONV was analyzed. One-hundred fifty-three patients were included in the analysis. The patients' median age was 67 years (range, 44-88), and 79.1% were male. PONV occurred in 35 (22.9%) patients. In the multivariate analysis, remifentanil dosage > 89.0 ng/kg/ min, albumin ≤ 3.5 g/dL, and eGFR < 60 mL/min/1.73 m 2 were independent significant risk factors for PONV. A significant association was observed between the incidence of and the number of risk factors for PONV (0 factor, 5.8%; 1 factor, 27.3%; ≥ 2 factors, 40.0%; p = 0.001). These three risk factors are useful indicators for selecting patients at high risk of developing PONV after VATS-E. In these patients, avoiding the development of PONV will be possible by performing appropriate risk management.

Effects of prior osteoporosis treatment on the treatment response of romosozumab followed by denosumab in patients with postmenopausal osteoporosis.

In patients with postmenopausal osteoporosis, prior osteoporosis treatment affected the bone mineral density increase of following treatment with 12 months of romosozumab, although it did not affect that of following treatment with 12 months of denosumab after romosozumab. PURPOSE: To investigate the effects of prior osteoporosis treatment on the response to treatment with romosozumab (ROMO) followed by denosumab (DMAb) in patients with postmenopausal osteoporosis. METHODS: In this prospective, observational, multicenter study, treatment-naïve patients (Naïve; n = 55) or patients previously treated with bisphosphonates (BP; n = 37), DMAb (DMAb; n = 45) or teriparatide (TPTD; n = 17) (mean age, 74.6 years; T-scores of the lumbar spine [LS] - 3.2 and total hip [TH] - 2.6) were switched to ROMO for 12 months, followed by DMAb for 12 months. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 24 months. RESULTS: A BMD increase was observed at 12 and 24 months in the following patients: Naïve (18.2% and 22.0%), BP (10.2% and 12.1%), DMAb (6.6% and 9.7%), and TPTD (10.8% and 15.0%) (P < 0.001 between the groups at both 12 and 24 months) in LS and Naïve (5.5% and 8.3%), BP (2.9% and 4.1%), DMAb (0.6% and 2.2%), and TPTD (4.3% and 5.4%) (P < 0.01 between the groups at 12 months and P < 0.001 at 24 months) in TH, respectively. The BMD increase in LS from 12 to 24 months was negatively associated with the levels of bone resorption marker at 24 months. Incidences of major fragility fractures for the respective groups were as follows: Naïve (5.5%), BP (16.2%), DMAb (11.1%), and TPTD (5.9%). CONCLUSIONS: Previous treatment affected the BMD increase of following treatment with ROMO, although it did not affect that of following treatment with DMAb after ROMO.

Correlation between portal vein anatomy and bile duct variation in 407 living liver donors.

Our aim was to determine whether variant bile duct (BD) anatomy is associated with portal vein (PV) and/or hepatic artery (HA) anatomy. We examined the associations between BD anatomy and PV and/or HA anatomy in 407 living donor transplantation donors. We also examined whether the right posterior BD (RPBD) course was associated with the PV and/or HA anatomy. Variant PV, HA and BD anatomies were found in 11%, 25% and 25%, respectively, of 407 donors enrolled in this study. The presence of a variant BD was more frequently associated with a variant PV than with a normal PV (61% vs. 20%, p < 0.0001). By contrast, the presence of a variant HA was not associated with a variant BD. A supraportal RPBD was found in 357 donors (88%) and an infraportal RPBD was found in 50 donors (12%). An infraportal RPBD was significantly more common in donors with a variant PV than in donors with a normal PV (30% vs. 10%, p = 0.0004). Variant PV, but not variant HA, anatomies were frequently associated with variant BD anatomy. Additionally, an infraportal RPBD was more common in donors with a variant PV than in donors with a normal PV.

The association between neutropenia and prognosis in stage III colorectal cancer patients receiving adjuvant chemotherapy.

Neutropenia during chemotherapy has been reported to be a predictor of better survival in patients with several types of cancer, although there are no reports on stage III colorectal cancer (CRC). The purpose of this study was to examine the association between neutropenia and prognosis in stage III CRC patients receiving adjuvant chemotherapy consisting of oral uracil and tegafur (UFT) plus leucovorin (LV). We retrospectively analysed 123 patients with stage III CRC who received UFT/LV as adjuvant chemotherapy. The end-point was disease-free survival (DFS). Survival curves of the two categories (neutropenia absent vs. present) were estimated using the Kaplan-Meier method and compared by the log-rank test. We estimated the hazard ratio (HR) for DFS according to neutropenia after adjustment for covariates by multivariate analyses using Cox's regression analysis. A total of 33 (26.8%) patients experienced neutropenia. Patients without neutropenia showed a significantly lower DFS than those with neutropenia (3-year DFS 57.3% vs. 81.2%, P = 0.0213). By multivariate analysis, neutropenia and histological type were independent prognostic factors, with HR of 0.410 (neutropenia absent vs. present, P = 0.045) and 4.793 (well to moderately differentiated vs. poorly differentiated, P = 0.004) respectively. We demonstrated that neutropenia occurring during adjuvant chemotherapy consisting of UFT/LV may be a prognostic factor of recurrence in stage III CRC patients.

Discovery of ultrafast spontaneous spin switching in an antiferromagnet by femtosecond noise correlation spectroscopy.

Owing to their high magnon frequencies, antiferromagnets are key materials for future high-speed spintronics. Picosecond switching of antiferromagnetic spin systems has been viewed a milestone for decades and pursued only by using ultrafast external perturbations. Here, we show that picosecond spin switching occurs spontaneously due to thermal fluctuations in the antiferromagnetic orthoferrite Sm0.7Er0.3FeO3. By analysing the correlation between the pulse-to-pulse polarisation fluctuations of two femtosecond optical probes, we extract the autocorrelation of incoherent magnon fluctuations. We observe a strong enhancement of the magnon fluctuation amplitude and the coherence time around the critical temperature of the spin reorientation transition. The spectrum shows two distinct features, one corresponding to the quasi-ferromagnetic mode and another one which has not been previously reported in pump-probe experiments. Comparison to a stochastic spin dynamics simulation reveals this new mode as smoking gun of ultrafast spontaneous spin switching within the double-well anisotropy potential.

Associations of time to return to performance following acute posterior thigh injuries with running biomechanics, hamstring function, and structure in collegiate sprinters: A prospective cohort design.

BACKGROUND: The time to return to sport from acute hamstring strain injuries is associated with several functional and structural impairments. However, not all previous studies assessed the preinjury level before acute hamstring strain injuries directly. The purpose of this study was to examine the associations of the time to return to performance following acute hamstring strain injuries with deficits in running biomechanics, hamstring function and structure in collegiate sprinters by a prospective study. METHODS: Using a prospective cohort design, 72 participants were recruited from a collegiate track and field team. At the preinjury assessment, a 60-m running-specific test, passive straight leg raise test and isometric knee flexion strength test were assessed at the beginning of the competitive season for three consecutive years (2017-2019). Afterwards, postinjury examinations were performed only in sprinters with acute hamstring strain injuries. FINDINGS: Twelve sprinters strained their hamstring muscle (incidence rate of hamstring strain injuries: 16.7%); the majority (n = 10) were classified as grades 0-2. The running speed deficit of the running-specific test was associated with the time to return to performance as well as the passive straight leg raise test deficit. In the running-specific test, lower-limb kinetic deficits were more strongly associated with the time to return to performance compared to lower-limb kinematic deficits. INTERPRETATION: A running-specific test may be considered one of the most convenient and valid tests for assessing rehabilitation progress after acute hamstring strain injuries.

Quantification of hepatitis C virus in patients treated with peginterferon-alfa 2a plus ribavirin treatment by COBAS TaqMan HCV test.

Extremely low levels of serum hepatitis C virus (HCV) RNA can be detected by COBAS TaqMan HCV test. To investigate whether the COBAS TaqMan HCV test is useful for measuring rapid virological response (RVR) and early virological response (EVR) to predict sustained virological response (SVR), we compared the virological response to PEG-IFN-alfa 2a plus RBV in 76 patients infected with HCV genotype 1 when undetectable HCV RNA by the COBAS TaqMan HCV test was used, with those when below 1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test was used, which corresponded to the use of traditional methods. Among the 76 patients, 28 (36.8%) had SVR, 13 (17.1%) relapsed, 19 (25.0%) did not respond, and 16 (21.0%) discontinued the treatment due to side effects. The positive predictive values for SVR based on undetectable HCV RNA by COBAS TaqMan HCV test at 24 weeks after the end of treatment [10/10 (100%) at week 4, 21/23 (91.3%) at week 8 and 26/33 (78.7%) at week 12] were superior to those based on <1.7 log IU/mL HCV RNA [17/19 (89.4%) at week 4, 27/38 (71.0%) at week 8, and 27/43 (62.7%) at week 12]. The negative predictive values for SVR based on <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test [46/57 (80.7%) at week 4, 37/38 (97.3%) at week 8, and 32/33 (96.9%) at week 12] were superior to those based on undetectable HCV RNA [48/66 (72.7%) at week 4, 46/53 (86.7%) at week 8, and 41/43 (95.3%) at week 12]. The utilization of both undetectable RNA and <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test is useful and could predict SVR and non-SVR patients with greater accuracy.

Endoscopic hemostasis using covered metallic stent placement for uncontrolled post-endoscopic sphincterotomy bleeding.

Severe bleeding following endoscopic biliary sphincterotomy (EBS) can sometimes be difficult to manage, resulting in the need for an invasive intervention. The aim of this study was to retrospectively evaluate the feasibility and efficacy of endoscopic hemostasis using covered self-expandable metallic stents (SEMSs) for severe post- EBS bleeding. Eleven patients with bile duct stones underwent standard EBS using a standard sphincterotome-based technique at 4 endoscopic units of a university-affiliated hospital and a general hospital. Monotherapy or combined therapy were used to achieve hemostasis with either balloon tamponade, hypertonic saline epinephrine injection, or endoclip placement. When active bleeding could not be controlled, covered SEMSs were placed across the major papilla. Emergency endoscopy was performed on the day of admission or the subsequent day (ranging from 6 to 35 h after admission). Bleeding was classified as mild in 6 cases (54.5 %) and moderate in 5 (45.5 %). A covered SEMS 10mm in diameter and 6 cm long was placed across the papilla. After placement, complete hemostasis was achieved. The mean duration of stent placement was 8.2 days (range 5­10 days), and the SEMS was successfully removed in all cases. Although the present study has the limitations of a small sample size and lack of control patients, covered SEMS placement for endoscopic hemostasis may be useful in selected patients with uncontrolled post-EBS bleeding.

Evaluation of human muscle hardness after dynamic exercise with ultrasound real-time tissue elastography: a feasibility study.

AIM: To assess the feasibility of ultrasound real-time tissue elastography (RTE) for measuring exercise-induced changes in muscle hardness and to compare the findings of RTE with those of a tissue hardness meter for semi-quantitative assessment of the hardness of exercised muscles. MATERIALS AND METHODS: Nine male participants performed an arm-curl exercise. RTE measurements were performed by manually applying repetitive compression with the transducer on the scan position before exercise, immediately after exercise, and at 30 min after exercise; strain ratios between muscle and a reference material (hydrogel) were calculated (muscle strain/material strain). A tissue hardness meter was also used to evaluate muscle hardness. The intraclass correlation coefficients (ICCs) for the three repeated measurements at each measurement time were calculated to evaluate the intra-observer reproducibility of each technique. RESULTS: Immediately after exercise, the strain ratio and the value obtained using the tissue hardness meter significantly decreased (from 1.65 to 1.35) and increased (from 51.8 to 54.3), respectively. Both parameters returned to their pre-exercise value 30 min after exercise. The ICCs of the RTE (and the ICCs of the muscle hardness meter) were 0.971 (0.816) before exercise, 0.939 (0.776) immediately after exercise, and 0.959 (0.882) at 30 min after exercise. CONCLUSION: Similar to the muscle hardness meter, RTE revealed the exercise-induced changes of muscle hardness semi-quantitatively. The intra-observer reproducibility of RTE was very high at each measurement time. These findings suggest that RTE is a clinically useful technique for assessing hardness of specific exercised muscles.

Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes.

AIMS/HYPOTHESIS: Diabetic retinopathy is a progressive neurodegenerative disease, but the underlying mechanism is still obscure. Here, we focused on oxidative stress in the retina, and analysed its influence on retinal neurodegeneration, using an antioxidant, lutein. METHODS: C57BL/6 mice with streptozotocin-induced diabetes were constantly fed either a lutein-supplemented diet or a control diet from the onset of diabetes, and their metabolic data were recorded. In 1-month-diabetic mice, reactive oxygen species (ROS) in the retina were measured using dihydroethidium and visual function was evaluated by electroretinograms. Levels of activated extracellular signal-regulated kinase (ERK), synaptophysin and brain-derived neurotrophic factor (BDNF) were also measured by immunoblotting in the retina of 1-month-diabetic mice. In the retinal sections of 4-month-diabetic mice, histological changes, cleaved caspase-3 and TUNEL staining were analysed. RESULTS: Lutein did not affect the metabolic status of the diabetic mice, but it prevented ROS generation in the retina and the visual impairment induced by diabetes. ERK activation, the subsequent synaptophysin reduction, and the BDNF depletion in the diabetic retina were all prevented by lutein. Later, in 4-month-diabetic mice, a decrease in the thickness of the inner plexiform and nuclear layers, and ganglion cell number, together with increase in cleaved caspase-3- and TUNEL-positive cells, were avoided in the retina of lutein-fed mice. CONCLUSIONS/INTERPRETATION: The results indicated that local oxidative stress that has a neurodegenerative influence in the diabetic retina is prevented by constant intake of a lutein-supplemented diet. The antioxidant, lutein may be a potential therapeutic approach to protect visual function in diabetes.

Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor.

Chemokines are a structurally related family of cytokines that are important for leukocyte trafficking. The C-C chemokine monocyte chemoattractant protein-1 (MCP-1) is a potent monocyte activator in vitro and has been associated with monocytic infiltration in several inflammatory diseases. One C-C chemokine receptor, CCR2, has been identified that mediates in vitro responses to MCP-1 and its close structural homologues. CCR2 has also recently been demonstrated to be a fusion cofactor for several HIV isolates. To investigate the normal physiological function of CCR2, we generated mice with a targeted disruption of the ccr2 gene. Mice deficient for CCR2 developed normally and had no hematopoietic abnormalities. However, ccr2(-/-) mice failed to recruit macrophages in an experimental peritoneal inflammation model. In addition, these mice were unable to clear infection by the intracellular bacteria, Listeria monocytogenes. These results suggest that CCR2 has a nonredundant role as a major mediator of macrophage recruitment and host defense against bacterial pathogens and that MCP-1 and other CCR2 ligands are effectors of those functions.

C-reactive protein : albumin ratio in patients with resectable intrahepatic cholangiocarcinoma.

BACKGROUND: The C-reactive protein : albumin ratio (CAR) has been reported as a novel prognostic marker in several cancers. The aim of this study was to investigate the prognostic value of CAR in patients with intrahepatic cholangiocarcinoma (ICC). METHODS: This was a single-centre retrospective study of patients who underwent surgery for ICC in a university hospital in Japan between 1998 and 2018. CAR, Glasgow Prognostic Score (GPS) and modified GPS (mGPS) were calculated. Their correlation with recurrence-free survival (RFS) and overall survival (OS) was analysed with Cox proportional hazards models. RESULTS: Seventy-two patients were included in the study. Patients were divided into two groups according to the optimal CAR cut-off value of 0·02. CAR above 0·02 was associated with higher carbohydrate antigen 19-9 levels (20·5 versus 66·1 units/ml for CAR of 0·02 or less; P = 0·002), larger tumour size (3·2 versus 4·4 cm respectively; P = 0·031) and a higher rate of microvascular invasion (9 of 28 versus 25 of 44; P = 0·041). RFS and OS were shorter in patients with CAR above 0·02: hazard ratio (HR) 4·31 (95 per cent c.i. 2·02 to 10·63) and HR 4·80 (1·85 to 16·40) respectively. In multivariable analysis CAR above 0·02 was an independent prognostic factor of RFS (HR 3·29 (1·33 to 8·12); P < 0·001), but not OS. CONCLUSIONS: CAR was associated with prognosis in patients who had hepatic resection for ICC.

ANTECEDENTES: La relación proteína C reactiva/albumina (C-reactive protein/albumin ratio, CAR) ha sido descrita como un marcador pronóstico novedoso en varios tipos de cáncer. El objetivo de este estudio fue investigar el valor pronóstico de CAR en pacientes con colangiocarcinoma intrahepático (intrahepatic cholangiocarcinoma, ICC). MÉTODOS: Se trata de un estudio retrospectivo y unicéntrico de pacientes sometidos a cirugía por ICC en un hospital universitario de Japón entre 1998 y 2018. Se calcularon CAR, puntuación pronóstica de Glasgow (Glasgow prognostic score, GPS), y GPS modificada (mGPS). Se analizó su correlación con la supervivencia libre de recidiva (recurrence-free survival, RFS) y con la supervivencia global (overall survival, OS) mediante modelos de riesgos proporcionales de Cox. RESULTADOS: Se incluyeron un total de 72 pacientes. El valor de corte óptimo de CAR fue de 0,02. Los pacientes se dividieron en dos grupos de acuerdo a este valor de corte. La presencia de CAR > 0,02 se asoció con niveles más elevados de antígeno carbohidrato 19-9 (20,5 U/ml versus 66,1 U/ml; P = 0,002), mayor tamaño tumoral (3,2 cm versus 4,4 cm; P = 0,031) y una tasa más elevada de invasión microvascular (32,1% versus 56,8%; P = 0,041). La RFS y OS fueron más cortas en pacientes con CAR > 0,02 (cociente de riesgos instantáneos, hazard ratio, HR 4,305; i.c. del 95% 2,016-10,63 y HR 4,803; i.c. del 95% 1,846-16,40, respectivamente). En los análisis multivariables, CAR de > 0,02 fue un factor pronóstico independiente para RFS (HR 3,286; i.c. del 95% 1,330-8,118; P < 0,001), pero no para la OS. CONCLUSIÓN: CAR se asoció con el pronóstico en pacientes sometidos a resección hepática por ICC.

A yeast protein that binds nuclear localization signals: purification localization, and antibody inhibition of binding activity.

Short stretches of amino acids, termed nuclear localization sequences (NLS), can mediate assembly of proteins into the nucleus. Proteins from the yeast, Saccharomyces cerevisiae, have been identified that specifically recognize nuclear localization peptides (Silver, P., I. Sadler, and M. A. Osborne. 1989. J. Cell Biol. 109:983-989). We now further define the role of one of these NLS-binding proteins in nuclear protein localization. The NLS-binding protein of 70-kD molecular mass can be purified from salt extracts of nuclei. Antibodies raised against the NLS-binding protein localized the protein mainly to the nucleus with minor amounts in the cytoplasm. These antibodies also inhibited the association of NLS-protein conjugates with nuclei. Incubation of nuclei with proteases coupled to agarose removed NLS-binding protein activity. Extracts enriched for NLS-binding proteins can be added back to salt or protease-treated nuclei to restore NLS-binding activity. These results suggest that the first step of nuclear protein import can be reconstituted in vitro.

A yeast gene important for protein assembly into the endoplasmic reticulum and the nucleus has homology to DnaJ, an Escherichia coli heat shock protein.

When nuclear localization sequences (termed NLS) are placed at the N terminus of cytochrome c1, a mitochondrial inner membrane protein, the resulting hybrid proteins do not assemble into mitochondria when synthesized in the yeast Saccharomyces cerevisiae. Cells lacking mitochondrial cytochrome c1, but expressing the hybrid NLS-cytochrome c1 proteins, are unable to grow on glycerol since the hybrid proteins are associated primarily with the nucleus. A similar hybrid protein with a mutant NLS is transported to and assembled into the mitochondria. To identify proteins that might be involved in recognition of nuclear localization signals, we isolated conditional-lethal mutants (npl, for nuclear protein localization) that missorted NLS-cytochrome c1 to the mitochondria, allowing growth on glycerol. The gene corresponding to one complementation group (NPL1) encodes a protein with homology to DnaJ, an Escherichia coli heat shock protein. npl1-1 is allelic to sec63, a gene that affects transit of nascent secretory proteins across the endoplasmic reticulum. Rothblatt, J. A., R. J. Deshaies, S. L. Sanders, G. Daum, and R. Schekman. 1989. J. Cell Biol. 109:2641-2652. The npl1 mutants reported here also weakly affect translocation of preprocarboxypeptidaseY across the ER membrane. A normally nuclear hybrid protein containing a NLS fused to invertase and a nucleolar protein are not localized to the nucleus in npl1/sec63 cells at the nonpermissive temperature. Thus, NPL1/SEC63 may act at a very early common step in localization of proteins to the nucleus and the ER. Alternatively, by affecting ER and nuclear envelope assembly, npl1 may indirectly alter assembly of proteins into the nucleus.

Lst1p and Sec24p cooperate in sorting of the plasma membrane ATPase into COPII vesicles in Saccharomyces cerevisiae.

Formation of ER-derived protein transport vesicles requires three cytosolic components, a small GTPase, Sar1p, and two heterodimeric complexes, Sec23/24p and Sec13/31p, which comprise the COPII coat. We investigated the role of Lst1p, a Sec24p homologue, in cargo recruitment into COPII vesicles in Saccharomyces cerevisiae. A tagged version of Lst1p was purified and eluted as a heterodimer complexed with Sec23p comparable to the Sec23/24p heterodimer. We found that cytosol from an lst1-null strain supported the packaging of alpha-factor precursor into COPII vesicles but was deficient in the packaging of Pma1p, the essential plasma membrane ATPase. Supplementation of mutant cytosol with purified Sec23/Lst1p restored Pma1p packaging into the vesicles. When purified COPII components were used in the vesicle budding reaction, Pma1p packaging was optimal with a mixture of Sec23/24p and Sec23/Lst1p; Sec23/Lst1p did not replace Sec23/24p. Furthermore, Pma1p coimmunoprecipitated with Lst1p and Sec24p from vesicles. Vesicles formed with a mixture of Sec23/Lst1p and Sec23/24p were similar morphologically and in their buoyant density, but larger than normal COPII vesicles (87-nm vs. 75-nm diameter). Immunoelectronmicroscopic and biochemical studies revealed both Sec23/Lst1p and Sec23/24p on the membranes of the same vesicles. These results suggest that Lst1p and Sec24p cooperate in the packaging of Pma1p and support the view that biosynthetic precursors of plasma membrane proteins must be sorted into ER-derived transport vesicles. Sec24p homologues may comprise a more complex coat whose combinatorial subunit composition serves to expand the range of cargo to be packaged into COPII vesicles. By changing the geometry of COPII coat polymerization, Lst1p may allow the transport of bulky cargo molecules, polymers, or particles.

Antibodies against 70-kD heat shock cognate protein inhibit mediated nuclear import of karyophilic proteins.

Previously, we found that anti-DDDED antibodies strongly inhibited in vivo nuclear transport of nuclear proteins and that these antibodies recognized a protein of 69 kD (p69) from rat liver nuclear envelopes that showed specific binding activities to the nuclear location sequences (NLSs) of nucleoplasmin and SV-40 large T-antigen. Here we identified this protein as the 70-kD heat shock cognate protein (hsc70) based on its mass, isoelectric point, cellular localization, and partial amino acid sequences. Competition studies indicated that the recombinant hsc70 expressed in Escherichia coli binds to transport competent SV-40 T-antigen NLS more strongly than to the point mutated transport incompetent mutant NLS. To investigate the possible involvement of hsc70 in nuclear transport, we examined the effect of anti-hsc70 rabbit antibodies on the nuclear accumulation of karyophilic proteins. When injected into the cytoplasm of tissue culture cells, anti-hsc70 strongly inhibited the nuclear import of nucleoplasmin, SV-40 T-antigen NLS bearing BSA and histone H1. In contrast, anti-hsc70 IgG did not prevent the diffusion of lysozyme or 17.4-kD FITC-dextran into the nuclei. After injection of these antibodies, cells continued RNA synthesis and were viable. These results indicate that hsc70 interacts with NLS-containing proteins in the cytoplasm before their nuclear import.

Rendezvous Technique Using Double Balloon Endoscope for Removal of Multiple Intrahepatic Bile Duct Stones in Hepaticojejunostomy After Living Donor Liver Transplant: A Case Report.

Cholangitis is a major complication following transplantation. We report a living donor liver transplant (LDLT) patient with cholangitis due to multiple stones in the intrahepatic bile duct during hepaticojejunostomy anastomosis, who was successfully treated with the rendezvous technique using double balloon endoscope. A 64-year-old woman underwent LDLT with right lobe graft and hepaticojejunostomy for Wilson disease. There was bile leakage with biliary peritonitis, which was treated conservatively after transplant. Two years after surgery, she developed reiterated cholangitis due to stenosis of hepaticojejunostomy anastomosis and multiple stones in the intrahepatic bile ducts. Percutaneous transhepatic biliary drainage was performed. The size of the drainage tube was increased, and the anastomotic area was dilated in a stepwise manner using a balloon catheter. The stones were crushed and lithotomy was performed using electronic hydraulic lithotripsy through cholangioscopy. Finally, lithotomy was performed for the remaining stones through endoscopic retrograde cholangiography with the rendezvous technique using the double balloon endoscope. Rendezvous approach with percutaneous transhepatic biliary drainage and double balloon endoscopic retrograde cholangiography was an effective treatment for the multiple intrahepatic stones in hepaticojejunostomy following LDLT with right lobe graft.

The docking protein FRS2alpha is an essential component of multiple fibroblast growth factor responses during early mouse development.

The docking protein FRS2alpha is a major mediator of fibroblast growth factor (FGF) signaling. However, the physiological role of FRS2alpha in vivo remains unknown. In this report, we show that Frs2alpha-null mouse embryos have a defect in anterior-posterior (A-P) axis formation and are developmentally retarded, resulting in embryonic lethality by embryonic day 8. We demonstrate that FRS2alpha is essential for the maintenance of self-renewing trophoblast stem (TS) cells in response to FGF4 in the extraembryonic ectoderm (ExE) that gives rise to tissues of the placenta. By analyzing chimeric embryos, we found that FRS2alpha also plays a role in cell movement through the primitive streak during gastrulation. In addition, experiments are presented demonstrating that Bmp4 expression in TS cells is controlled by mitogen-activated protein kinase-dependent FGF4 stimulation. Moreover, both the expression of Bmp4 in ExE and activation of Smad1/5 in epiblasts are reduced in Frs2alpha-null embryos. These experiments underscore the critical role of FRS2alpha in mediating multiple processes during embryonic development and reveal a potential new link between FGF and Bmp4 signaling pathways in early embryogenesis.

Investigation of the neutron spectrum measurement method for dose evaluation in boron neutron capture therapy.

In boron neutron capture therapy, it is important to evaluate the dose administered to a patient's body outside the tumour area. The exposure dose is evaluated by calculation; however, the calculated value must be validated using a measured value. The dose evaluations based on the measured neutron spectrum are investigated. Multi-foil activation, combined with a LiCaAlF6 scintillation detector and an imaging plate, is proposed as a measurement method. The proposed method can measure the neutron spectrum at various points quickly.

Selectivity of a replication-competent adenovirus for human breast carcinoma cells expressing the MUC1 antigen.

The DF3/MUC1 gene is aberrantly overexpressed in human breast and other carcinomas. Previous studies have demonstrated that the DF3/MUC1 promoter/enhancer confers selective expression of diverse transgenes in MUC1-positive breast cancer cells. In this study, we show that an adenoviral vector (Ad.DF3-E1) in which the DF3/MUC1 promoter drives expression of E1A selectively replicates in MUC1-positive breast cancer cells. We also show that Ad.DF3-E1 infection of human breast tumor xenografts in nude mice is associated with inhibition of tumor growth. In contrast to a replication-incompetent adenoviral vector that infects along the injection track, Ad.DF3-E1 infection was detectable throughout the tumor xenografts. To generate an Ad.DF3-E1 vector with the capacity for incorporating therapeutic products, we inserted the cytomegalovirus (CMV) promoter upstream of the TNF cDNA. Infection with Ad.DF3-E1/CMV-TNF was associated with selective replication and production of TNF in cells that express MUC1. Moreover, treatment of MUC1-positive, but not MUC1-negative, xenografts with a single injection of Ad.DF3-E1/CMV-TNF was effective in inducing stable tumor regression. These findings demonstrate that the DF3/MUC1 promoter confers competence for selective replication of Ad.DF3-E1 in MUC1-positive breast tumor cells, and that the antitumor activity of this vector is potentiated by integration of the TNF cDNA.