Safety and feasibility of minimally invasive esophagectomy for elderly esophageal cancer patients.

The number of elderly patients with esophageal cancer has increased in recent years. The use of thoracoscopic esophagectomy has also increased, and its minimal invasiveness is believed to contribute to postoperative outcomes. However, the short- and long-term outcomes in elderly patients remain unclear. This study aimed to elucidate the safety and feasibility of minimally invasive esophagectomy in elderly patients. This retrospective study included 207 patients who underwent radical thoracoscopic esophagectomy for thoracic esophageal squamous cell carcinoma at Kobe University Hospital between 2005 and 2014. Patients were divided into non-elderly (<75 years) and elderly (≥75 years) groups. A propensity score matching analysis was performed for sex and clinical T and N stage, with a total of 29 matched pairs. General preoperative data, surgical procedures, intraoperative data, postoperative complications, in-hospital death, cancer-specific survival, and overall survival were compared between groups. The elderly group was characterized by lower preoperative serum albumin levels and higher American Society of Anesthesiologists grade. Intraoperative data and postoperative complications did not differ between the groups. The in-hospital death rate was 4% in the elderly group, which did not significantly differ from the non-elderly group. Cancer-specific survival was similar between the two groups. Although overall survival tended to be poor in the elderly group, it was not significantly worse than that of the non-elderly group. In conclusion, the short- and long-term outcomes of minimally invasive esophagectomy in elderly versus non-elderly patients were acceptable. Minimally invasive esophagectomy is a safe and feasible modality for elderly patients with appropriate indications.

Time-Reversal Measurement of the p-Wave Cross Sections of the

The cross sections of the ^{7}Be(n,α)^{4}He reaction for p-wave neutrons were experimentally determined at E_{c.m.}=0.20-0.81 MeV slightly above the big bang nucleosynthesis (BBN) energy window for the first time on the basis of the detailed balance principle by measuring the time-reverse reaction. The obtained cross sections are much larger than the cross sections for s-wave neutrons inferred from the recent measurement at the n_TOF facility in CERN, but significantly smaller than the theoretical estimation widely used in the BBN calculations. The present results suggest the ^{7}Be(n,α)^{4}He reaction rate is not large enough to solve the cosmological lithium problem, and this conclusion agrees with the recent result from the direct measurement of the s-wave cross sections using a low-energy neutron beam and the evaluated nuclear data library ENDF/B-VII.1.

Analysis of cellular functions by multipoint fluorescence correlation spectroscopy.

The biophysical investigation of living cells is currently possible by single molecular detection methods such as fluorescence correlation spectroscopy (FCS). FCS is applied for measuring the dynamic mobility of target molecules in living cells; however, the conventional FCS systems still lack quantitative analysis for many regions of interests (ROI) in real time. To improve this situation, we have developed a novel multipoint FCS system (M-FCS) that can measure multipoint correlation functions in the cell simultaneously. To evaluate its performance, we measured correlation functions for rhodamine 6G (Rh6G) in homogeneous conditions and for green fluorescence protein (GFP) in HeLa cells. We conclude that M-FCS possesses reliable performance. As a pharmacological application, glucocorticoid receptor protein fused GFP (GR-GFP) was transfected in HeLa cells and FCS measurements were carried out in the cytoplasm and the nucleus simultaneously. The translocation of GR-GFP from the cytoplasm to the nucleus by ligand stimulation was observed with laser scanning microscopy (LSM) and M-FCS. Particularly in the nucleus, the slower diffusion of GR-GFP suggested molecular interactions after the translocation. These data imply that M-FCS can be applied for quantitative analysis of kinetic processes in living cells.

The dithiane Ro 44-5912 enhances vinblastine sensitivity of drug resistant and parental KB lines in vivo.

The multidrug resistance modifying activity of a dithiane analogue of tiapamil, Ro 44-5912, was examined in vivo. Results of acute toxicity studies in mice indicated that lethal toxicity occurred with doses greater than 1 mmol/kg of body weight. In a preliminary pharmacokinetic investigation, Ro 44-5912 appeared to have a longer half-life in mice than did its (R) enantiomer Ro 44-5911 (3.15 +/- 0.02 h versus 2.15 +/- 0.14 h) as measured by total radiolabel in plasma. In non-tumour bearing mice, Ro 44-5912 enhanced the toxicity of vinblastine in a manner that was dependent on the dose of both drugs. Vinblastine did not have a significant effect on tumour growth when given to nude mice bearing the parental cell line KB-3-1 at a dose of 1.5 mg/kg once per week for 3 weeks. Combination treatment with Ro 44-5912 markedly enhanced the antitumour activity of vinblastine. Similar results were seen when KB-3-1 tumours were treated with the combination of vinblastine plus cyclosporin A. Another tiapamil analogue, Ro 11-2933, had no enhancing activity with this tumour when used at an equitoxic combination dose. Ro 44-5912 also significantly enhanced vinblastine activity with P-glycoprotein-expressing KB-8-5 tumours. In three independent experiments, Ro 44-5912 enhanced the growth inhibiting activity of vinblastine by a mean of approximately 40%. Neither Ro-11-2933 nor cyclosporin A, at the maximal tolerated doses in combination with vinblastine, led to significant inhibition of KB-8-5 tumour growth compared to treatment with the two vehicles alone. These results show that Ro 44-5912 is an active modulator of drug resistance in vivo.

Isolation and expression of the full-length cDNA encoding CD59 antigen of human lymphocytes.

To identify the primary structure of CD59 antigen and to elucidate its function, a full-length cDNA clone of CD59 was isolated. The cDNA sequence contained an open reading frame that encodes an 128-amino-acid peptide. The amino-terminal 25 amino acids represented a typical signal peptide sequence and the carboxy-terminal hydrophobic amino acids were characteristic for phosphatidylinositol-anchored proteins. The predicted mature protein sequence showed 35% homology with murine Ly-6C.1 and 31% with Ly-6A.2. The number and the distribution of cysteine residues were conserved, implying that the CD59 represented a human homologue of murine Ly-6. RNA blot hybridization analysis revealed the expression of CD59 mRNA in placental, lung, and pancreatic tissues. The mRNA was not only expressed in T-cell lines but in some of monocytic, myeloid, and B-cell lines. In all of these tissues and cell lines, at least four mRNA species were detected. DNA blot hybridization analysis revealed a rather simple genomic structure, which suggested a single gene as compared with the complex multigene family of murine Ly-6.

The metabolism and distribution of sesame lignans (sesamin and episesamin) in rats.

In this study, we examined the distribution and metabolism of refined sesame oil lignans (sesamin and episesamin) in rat. For 8 wk rats were fed the diet including 0.5% (w/w) sesame lignans (sesamin and episesamin) with 5% (w/w) corn oil or eicosapentaenoic acid (EPA)-rich oil. The concentrations of sesamin and episesamin in rat liver after their administration for 8 wk were very low; both of them were less than 0.5 microgram/g liver. These were observed in both oil groups although the fatty acid compositions of dietary oils were completely different. No significant difference existed in lymphatic absorption between sesamin and episesamin. To investigate the distribution of sesamin and episesamin in rats, the concentrations of sesamin and episesamin were determined in tissues and serum within 24 h after administration to rats. Sesamin and episesamin may be, at first, incorporated into the liver and then transported to the other tissues (lung, heart, kidney, and brain). They are lost from the body within 24 h after administration. There was no significant difference in lymphatic absorption between sesamin and episesamin, but the amount of sesamin was significantly lower than that of episesamin in all tissues and serum. These results suggest that sesamin is absorbed in lymph the same as episesamin, but that sesamin is subsequently metabolized faster by the liver.

The metabolism and n-6/n-3 ratio of essential fatty acids in rats: effect of dietary arachidonic acid and a mixture of sesame lignans (sesamin and episesamin).

In this study, we examined the effect of dietary arachidonic acid (AA) and sesame lignans on the content and n-6/n-3 ratio of polyunsaturated fatty acid (PUFA) in rat liver and the concentrations of triglyceride (TG) and ketone bodies in serum. For 4 wk, rats were fed two types of dietary oils: (i) the control oil diet groups (CO and COS): soybean oil/perilla oil = 5:1, and (ii) the AA-rich oil group (AO and AOS): AA ethyl esters/palm oil/perilla oil = 2:2:1, with (COS and AOS) or without (CO and AO) 0.5% (w/w) of sesame lignans. Dietary AA and sesame lignans significantly affected hepatic PUFA metabolism. AA content and n-6/n-3 ratio in the liver were significantly increased in the AO group, despite the dietary total of n-6 PUFA being the same in all groups, while AOS diet reduced AA content and n-6/n-3 ratio to a level similar to the CO and COS groups. These results suggest that (i) dietary AA considerably affects the hepatic profile and n-6/n-3 ratio of PUFA, and (ii) dietary sesame lignans reduce AA content and n-6/n-3 ratio in the liver. In the AO group, the concentration of acetoacetate was significantly increased, but the ratio of beta-hydroxybutyrate/acetoacetate was decreased. On the other hand, the AO diet increased the concentration of TG in serum by almost twofold as compared to other groups. However, the AOS diet significantly reduced serum TG level as compared to the AO group. In addition, the AOS diet significantly increased the acetoacetate level, but reduced the beta-hydroxybutyrate/acetoacetate ratio. These results suggest that dietary sesame lignans promote ketogenesis and reduce PUFA esterification into TG. This study resulted in two findings: (i) sesame lignans inhibited extreme changes of the n-6/n-3 ratio by reducing hepatic PUFA content, and (ii) the reduction of hepatic PUFA content may have occurred because of the effects of sesame lignans on PUFA degradation (oxidation) and esterification.

Effect of sesamin on mitochondrial and peroxisomal beta-oxidation of arachidonic and eicosapentaenoic acids in rat liver.

The effects of dietary sesamin on the hepatic metabolism of arachidonic (AA) and eicosapentaenoic (EPA) acids, were investigated with respect to their beta-oxidation and secretion as triacylglycerol (TG). For 2 wk, rats were fed three types of dietary oils: (i) corn oil (control) group; (ii) EPA group: EPA ethyl esters/rapeseed oil = 2:3; (iii) AA group: AA ethyl esters/palm oil/perilla oil = 2:2:1, with or without 0.5% (w/w) of sesamin. Dietary sesamin significantly increased the activities of hepatic mitochondrial and peroxisomal fatty acid oxidation enzymes (mitochondrial carnitine acyltransferase I, acyl-CoA dehydrogenase, and peroxisomal acyl-CoA oxidase). Dietary EPA increased mitochondrial carnitine acyltransferase I and peroxisomal acyl-CoA oxidase. Dietary AA, however, had an effect on peroxisomal acyl-CoA oxidase only. In whole liver and the TG fraction, EPA and AA concentrations were significantly increased by dietary EPA and AA, respectively, and were decreased by dietary sesamin. In hepatic mitochondria and peroxisomes, EPA concentration was increased by dietary EPA, but AA was not changed by dietary AA. The addition of dietary sesamin to the EPA-supplemented diet significantly decreased the EPA concentration compared to concentrations found with consumption of dietary EPA alone. These results suggest that sesamin increased beta-oxidation enzyme activities and reduced hepatic EPA and AA concentrations by degradation. The stimulating effect of sesamin on beta-oxidation, however, was more significant in the EPA group than in the AA group. Hepatic AA concentration was altered by the joint effect of sesamin through esterification into TG and the stimulation of beta-oxidation.

The metabolism and distribution of docosapentaenoic acid (n-6) in rats and rat hepatocytes.

In this study, a new marine oil that contains 45% docosahexaenoic acid (DHA, 22:6n-3) and 13% docosapentaenoic acid (DPA, 22:5n-6) was administered to rats. The metabolism and distribution of DPA in rats was investigated. In experiment 1, the effects of DHA and n-6 fatty acids (linoleic acid, LA; arachidonic acid, AA; and DPA) on AA contents were investigated in vivo. LA group: LA 25%, DHA 30%; LA-DPA group: LA 15%, DPA 10%, DHA 35%; LA-AA-DPA group: LA 10%, AA 5%, DPA 10%, DHA 35% were administered to rats for 4 wk. In the liver, the AA content in the LA-DPA and LA-AA-DPA groups was significantly higher than in the LA group. The decreased AA contents in the LA group might be caused by DHA administration. Although DHA also was administered in the LA-DPA and LA-AA-DPA groups, the AA contents in these two groups did not decrease. These results suggested that DPA retroconverted to AA, blunting the decrease in AA content caused by DHA administration. To conduct a detailed investigation on DPA metabolism and its relation with AA and DHA, rat hepatocytes were cultured with purified DPA and DHA for 24 h. We discovered the retroconversion of DPA to AA occurred only when AA content was decreased by a high DHA administration; it did not occur when AA content was maintained at a normal level.

Purification and some properties of sulfur reductase from the iron-oxidizing bacterium Thiobacillus ferrooxidans NASF-1.

Thiobacillus ferrooxidans strain NASF-1 grown aerobically in an Fe2+ (3%)-medium produces hydrogen sulfide (H2S) from elemental sulfur under anaerobic conditions with argon gas at pH 7.5. Sulfur reductase, which catalyzes the reduction of elemental sulfur (S0) with NAD(P)H as an electron donor to produce hydrogen sulfide (H2S) under anaerobic conditions, was purified 69-fold after 35-65% ammonium sulfate precipitation and Q-Sepharose FF, Phenyl-Toyopearl 650 ML, and Blue Sepharose FF column chromatography, with a specific activity of 57.6 U (mg protein)(-1). The purified enzyme was quite labile under aerobic conditions, but comparatively stable in the presence of sodium hydrosulfite and under anaerobic conditions, especially under hydrogen gas conditions. The purified enzyme showed both sulfur reductase and hydrogenase activities. Both activities had an optimum pH of 9.0. Sulfur reductase has an apparent molecular weight of 120,000 Da, and is composed of three different subunits (M(r) 54,000 Da (alpha), 36,000 Da (beta), and 35,000 Da (gamma)), as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This is the first report on the purification of sulfur reductase from a mesophilic and obligate chemolithotrophic iron-oxidizing bacterium.

Effects of sesamin on the fatty acid composition of the liver of rats fed N-6 and N-3 fatty acid-rich diet.

Sesamin is known as a specific inhibitor of delta 5-desaturation, the conversion from dihomo-gamma-linolenic acid (20:3(n=6)) to arachidonic acid (20:4(n-6)). In the previous paper, we reported that sesamin inhibited delta 5-desaturation of n-6 fatty acids in rat hepatocytes but not that of n-3 fatty acids, from 20:4(n-3) to 20:5(n-3). Then, we studied the effects of sesamin on delta 5-desaturation of n-6 and n-3 fatty acids in vivo. Rats were fed two types of diets containing sesamin (0.5% w/w) for 4 weeks as follows: in experiment 1 (Exp. 1) gamma-linolenic acid-rich diet and in experiment 2 (Exp. 2) alpha-linolenic acid-rich diet. The fatty acid composition of liver lipids was compared to those of control groups without sesamin. In both Exps. 1 and 2, sesamin increased the liver weight and phospholipid contents in liver. In Exp. 2, sesamin increased n-6 fatty acids and decreased n-3 fatty acids even though the diet was rich in n-3 fatty acids. Sesamin enhanced the composition ratio of 20:3(n-6) in both Exps. 1 and 2. Decrease of delta 5-desaturation index of n-6 fatty acid, the ratio of 20:4(n-6)/20:3(n-6), by the administration of sesamin suggested that sesamin inhibited the delta 5-desaturation of n-6 fatty acids in the liver. On the contrary, the delta 5-desaturation index of n-3 fatty acids, the ratio of 20:5(n-3) to 18:3(n-3), was increased by sesamin administration in the liver of rats fed alpha-linolenic acid-rich diet (Exp. 2).(ABSTRACT TRUNCATED AT 250 WORDS)

[Superoxide anion (O2-) production by polymorphonuclear leukocytes in insulin dependent diabetes mellitus (IDDM)].

The superoxide anion (O2-) production in polymorphonuclear leukocytes stimulated by phorbol myristate acetate in IDDM and non-insulin dependent diabetes mellitus (NIDDM) was determined by the method of Johnston et al, compared with that of each age matched controls. And the correlation between O2- production and hemoglobin (Hb) A1 and A1c value was investigated. The O2- production in IDDM was 24.4 +/- 7.4 (mean +/- SD, n mol per 4 X 10(5) cells) at 10 min. and 51.4 +/- 8.7 at 30 min., in NIDDM each 31.6 +/- 9.3, 60.2 +/- 14.4, and in controls each 40.5 +/- 4.2, 72.4 +/- 3.1. O2- production in IDDM was significantly lower than that in NIDDM (p less than 0.001 at 10 min. and p less than 0.01 30 min.) and controls (p less than 0.001 at 10 and 30 min.). O2- production at 10 and 30 min. possessed a negative correlation with Hba1 and A1c value (HbA1: p less than 0.01 at 10 min. p less than 0.05 at 30 min., HbA1c: p less than 0.01 at 10 and 30 min.). These findings suggest that impaired O2- production might be one of the factors accounting for depressed bactericidal activity of polymorphonuclear leukocytes in IDDM, and that a protracted hyperglycemia might shed some effect on O2- production.

Assessment of abnormal blood flow and efficacy of treatment in patients with systemic sclerosis using a newly developed microwireless laser Doppler flowmeter and arm-raising test.

Background Patients with systemic sclerosis (SSc) frequently suffer from recalcitrant digital ulceration because of impaired cutaneous blood flow (CBF). A simple and accurate CBF measurement would be helpful to evaluate the disease status and efficacy of treatment in such patients. Objectives To examine the feasibility of a newly developed, micromachined integrated laser blood flowmeter (MILBF) for evaluation of abnormal CBF responses in patients with SSc. Methods CBF of finger pulp was measured in eight patients with SSc and in six healthy controls using MILBF. CBF in the steady state and the responses to the arm-raising test and cold provocation were assessed. The therapeutic efficacy of a single and an intensive prostaglandin E(1) (PGE(1)) infusion treatment was also evaluated in some of the SSc patients. Results The patients with SSc showed significantly lower steady-state CBF than controls. The rate of blood flow with cold provocation and the velocity of blood flow recovery after cold provocation (VR-CP) tended to be lower in patients with SSc. Augmentation of amplitude of the digital pulse wave by arm raising (AA-AR) was observed in controls, but not in patients with SSc. We also found that VR-CP and AA-AR may be good markers for evaluating the efficacy of vasodilatory treatment. It should be noted that the examined patients did not complain of any pain and/or distress during the arm-raising test, as opposed to during cold provocation. Conclusions CBF assessment using MILBF and an arm-raising test is accurate, noninvasive and well tolerated and thus the combination may be a better alternative method to evaluate abnormal CBF and efficacy of treatment in patients with SSc.

Carbohydrate structures of recombinant soluble lamp-1 and leukosialin containing sialyl Le(x) terminus.

Recombinant soluble lamp-1 and soluble leukosialin can be produced from CHO cells which express sialyl Le(x) structures after stable transfection of fucosyltransferase-III. It was shown previously that those soluble lamp-1 and leukosialin are potent inhibitors for E-selectin-mediated adhesion of human colonic tumor cells (Sawada, R.; Tsuboi, S.; Fukuda, M. J. Biol. Chem., 1994, 269, 1425). In the present study, we have determined the amount of the sialyl Le(x) structure present in recombinant, soluble lamp-1 and soluble leukosialin. CHO cells were metabolically labeled with [3H]-galactose and recombinant soluble lamp-1 and leukosialin were purified from the spent medium. Glycopeptides containing N-glycans derived from lamp-1 were fractionated by sequential lectin affinity chromatography. Similarly, O-glycans released from leukosialin were fractionated by Bio-Gel P-4 gel filtration. The terminal structures of carbohydrate chains were determined by sequential digestion with specific glycosidases. The results clearly indicate that soluble lamp-1 contains much more sialyl Le(x) structure than soluble leukosialin. Considering that soluble leukosialin and lamp-1 are almost equally effective as inhibitors for E-selectin-mediated adhesion, the results strongly suggest that densely clustered O-glycans are better presenters for E-selectin ligands than N-glycans.

Gradient-index microlens formed by ion-beam sputtering.

This paper describes the fabrication and characteristics of a gradient-index microlens by using a low-stress, high-transmittance film that is deposited by ion-beam sputtering. The key techniques in forming this film are sputtering with N(2) gas, performing ion-beam irradiation during deposition, and stabilizing the deposition acceleration current. An integrated device consisting of the microlens and a laser diode is demonstrated. The focusing spot size is 2 microm x 3 microm at a distance of 11 microm from the lens facet.

Differential E-selectin-dependent adhesion efficiency in sublines of a human colon cancer exhibiting distinct metastatic potentials.

Previously we have shown that high metastatic colonic carcinoma cells express relatively more lamp molecules and sialyl Le(x) structures on the cell surface than their corresponding low metastatic counterparts (Saitoh, O., Wang, W.-L., Lotan, R., and Fukuda, M. (1992) J. Biol. Chem. 267, 5700-5711). In the present study, we extended these findings by testing whether these high and low metastatic colonic carcinoma cells differ in their adhesion efficiency to E-selectin-expressing cells. First, it was found that the high metastatic cells, as compared to their low metastatic counterparts, bind more efficiently to activated human endothelial cells that express E-selectin. This was also true when the adhesion was tested for Chinese hamster ovary cells stably expressing E-selectin. In addition, it was found that the high metastatic cells also adhere more efficiently to mouse endothelioma cells after activation with interleukin-1 beta. It was also shown that the adhesion can be inhibited by soluble lamp-1 or soluble leukosialin that contain sialy Le(x) termini. The inhibition was not, however, observed when these soluble glycoproteins lack sialyl Le(x) structures. The results indicate that the efficiency of the E-selectin-mediated binding of colonic carcinoma cells to human and mouse endothelial cells correlates with the metastatic potential of the cells and suggest that this adhesive event may be one of the critical factors for the metastatic spread of tumor cells. Soluble forms of leukosialin or lamp-1 may be useful as therapeutic agents for the inhibition of E-selectin-mediated binding to tumor cells.

Monolithically integrated optical displacement sensor based on triangulation and optical beam deflection.

A monolithically integrated optical displacement sensor based on triangulation and optical beam deflection is reported. This sensor is simple and consists of only a laser diode, a polyimide waveguide, and a split detector (a pair of photodiodes) upon a GaAs substrate. The resultant prototype device is extremely small (750 microm x 800 microm). Experiments have shown that this sensor can measure the displacement of a mirror with resolution of better than 4 nm. Additionally, we have experimentally demonstrated both axial and lateral displacement measurements when we used a cylindrical micromirror (diameter, 125 microm) as a movable external object.