Antitumor effect of DT-5461, a lipid A derivative, against human tumor xenografts is mediated by intratumoral production of tumor necrosis factor and affected by host immunosuppressive factors in nude mice

PURPOSE OF THE STUDY: The purpose of this report was to study the repercussions of rotator cuff condition on unconstrained shoulder arthroplasty results. METHODS: Between 1986 and 1993, 40 unconstrained shoulder prostheses were performed (24 total and 16 hemiarthroplasties). At the time of the operation, rotator cuff condition was reported to be normal in 15 shoulders, atrophic in 10, scarred in 3, torn in 12. Clinical and radiographical results were analyzed and supplemented with a rotator cuff echography. Postoperative follow-up averaged 42.25 months (12 to 97 months). RESULTS: When the rotator cuff was intact at the time of operation, clinical results were the best at the time of review. Constant score, overall mobility, forward elevation, external rotation with the elbow along the side were better for intact than for atrophic, scarred or torn rotator cuffs (p < 0.01). Ruptures repaired by local tissue transfer or trapezo deltoidal flap substitution (3 cases) gave satisfactory results, whereas two dacron cuff prostheses failed. In the non repaired ruptures (7 cases), arthroplasty resulted in 3/4 fair or poor results. At the time of review, the total incidence of postoperative rotator cuff tears was high (12 cases), functional repercussions were variable. Among the 15 rotator cuff tears observed at the time of the review, the long head of the biceps was present and in place in 9 cases and ruptured in 6 cases. In these latter cases, Constant score (p < 0.01), the forward elevation (p < 0.01), external rotation with elbow along side (p < 0.05) and overall mobility (p < 0.05) were worse; moreover, humeral head superior migration was greater (p < 0.01). DISCUSSION: Our study confirms the superiority of clinical results when the cuff was intact at the time of the operation. The repair of rotator cuff tears seems to be justified. When the rupture has not been repaired, clinical results were fair or poor in 5 cases out of 7, the initial rupture spread to the other tendons in 3 cases out of 7. Secondary ruptures were frequent (12 cases). No predictive factor was identified, but an overlapping of the greater tuberosity appears to be detrimental. Among rotator cuff tears present at the time of review, long head of the biceps rupture jeopardized clinical results and was associated with a proximal migration of the humeral head which was significantly more severe than with an intact non displaced long head of the biceps. CONCLUSION: During unconstrained shoulder prosthesis implantation, it is therefore recommend to systematically repair any associated rotator cuff rupture, in order to avoid any greater tuberosity overlap relative to the prosthetic head and to preserve the long head of the biceps tendon which limits upward migration of the humeral head and improves prosthetic kinetics.     

Novel anion exchange membranes having fluorocarbon backbone: Preparation and stability

Anion exchange membranes with excellent durability were prepared by chemical modification of Nafion. The modification was achieved by transformation of the sulfonic acid group into quaternary ammonium group. Namely, Nafion membrane was first converted into an amide-type membrane. Reduction of the carbonxyl group to methylene followed by quaternarization with alkyl iodide resulted in the formation of an anion exchange membrane. The electric resistance of the resulting membranes depends on the equivalent weight of the starting membranes (4.4–6.0 Ω cm² in 0.5N NaCl). The characteristics of the membranes are the excellent stability toward chemical substances such as organic solvents, oxidizing agents, acids, etc. For example, the membranes are stable in aqueous saturated chlorine solution at 60°C for 1000 hr.     

The role of repeat transurethral resection in stage A1 carcinoma of the prostate

In order to evaluate the significance of repeat transurethral resection (TUR) in differentiating stage A1 prostatic adenocarcinoma from those with stage A2, we performed repeat TUR in 34 patients with an initial diagnosis of stage A1 prostatic adenocarcinoma. It was found that residual adenocarcinoma was present in five cases (14.7%), but the diagnosis was changed from stage A1 to stage A2 in only one case (2.9%). In one patient with final diagnosis of stage A1 carcinoma, bone metastases were detected seven months after the repeat TUR. It was concluded that repeat TUR for stage A1 prostatic adenocarcinoma did not yield clinically significant information.     

Polyanion induced preferential multinucleation in macrophages at a low level of TNF-alpha secretion

When rat bone marrow macrophages were incubated with acetyl lignin (EP3) in the presence of a 10% solution of fetal bovine serum, the macrophages secreted tumor necrosis factor (TNF-alpha) in a dose-dependent manner. This was followed by macrophage multinucleation. EP3 was found to have a significant effect on TNF-alpha secretion at a minimum dose of 5 micrograms/ml and produced no significant further increase at levels above 50 micrograms/ml, while multinucleation was most active at 10 micrograms/ml. However, multinucleation did not occur at higher concentrations of EP3 (50 micrograms/ml and 100 micrograms/ml). Secretion of TNF-alpha was significantly reduced in the absence of fetal bovine serum, whereas multinucleation was very active, starting after 6 h of incubation. At concentrations of 100 micrograms/ml, sulfonyl lignin (LS) and dextran sulfate (DS) only induced low levels of TNF-alpha secretion from macrophages, but induced active multinucleation. The multinucleation induced by addition of LS or DS was inhibited by further addition of EP3. Thus, macrophage multinucleation was most active when a low level of TNF-alpha was secreted from the macrophages.     

Pixel-selected ray tracing

An acceleration method based on an idea that T. Whitted (Commun. ACM, vol.23, no.6 pp.343-349, June 1980) presented on ray tracing is discussed. He proposed making antialiased images by hierarchical adaptive oversampling. The present authors use hierarchical adaptive undersampling to reduce the number of pixels whose intensity must be calculated by ray tracing. To implement pixel-selected ray tracing (PSRT), homogeneous regions in images must first be found. Generally, adaptive undersampling can result in some image-quality defects, because small objects and parts of thin or wedge-shaped objects may disappear when they are located between the initially sampled pixels. PSRT has an improved algorithm that uses pixels with the correct object information from among the sampled pixels to find pixels with erroneous color and correct them. Moreover, PRST uses ray-object intersection trees for precise classification of the homogeneity of regions and for fast intensity calculation in homogeneous regions. Experimental results are presented. They show that PSRT is two to nine times faster than standard ray tracing     

Changes in Aging Behavior and Defect Structure of Yttria-Fully-Stabilized ZrO2 with Sc2O3 Doping

Methods of suppressing decreased conductivity in 8 mol% Y₂O₃-stabilized–92 mol% ZrO₂ (8YSZ) with aging were investigated. Different amounts of Sc₂O₃ were doped into 8YSZ. The electrochemical properties of Sc₂O₃-doped 8YSZ were measured, and the microstructural and local structural changes were characterized. The present results indicate that an appropriate amount of Sc₂O₃ doping, 3 or 4 mol%, effectively suppresses decreased conductivity with aging in 8YSZ.     

Identification of Tumor Suppressive Genes Regulated by miR-31-5p and miR-31-3p in Head and Neck Squamous Cell Carcinoma

We identified the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC) tissues by RNA sequencing, in which 168 miRNAs were significantly upregulated, including both strands of the miR-31 duplex (miR-31-5p and miR-31-3p). The aims of this study were to identify networks of tumor suppressor genes regulated by miR-31-5p and miR-31-3p in HNSCC cells. Our functional assays showed that inhibition of miR-31-5p and miR-31-3p attenuated cancer cell malignant phenotypes (cell proliferation, migration, and invasion), suggesting that they had oncogenic potential in HNSCC cells. Our in silico analysis revealed 146 genes regulated by miR-31 in HNSCC cells. Among these targets, the low expression of seven genes (miR-31-5p targets: CACNB2 and IL34; miR-31-3p targets: CGNL1, CNTN3, GAS7, HOPX, and PBX1) was closely associated with poor prognosis in HNSCC. According to multivariate Cox regression analyses, the expression levels of five of those genes (CACNB2: p = 0.0189; IL34: p = 0.0425; CGNL1: p = 0.0014; CNTN3: p = 0.0304; and GAS7: p = 0.0412) were independent prognostic factors in patients with HNSCC. Our miRNA signature and miRNA-based approach will provide new insights into the molecular pathogenesis of HNSCC.     

Sesamin is a potent and specific inhibitor of Δ5 desaturase in polyunsaturated fatty acid biosynthesis

Incubation with sesame oil increases the mycelial dihomo-γ-linolenic acid content of an arachidonic acid-producing fungus,Mortierella alpina, but decreases its arachidonic acid content [Shimizu, S., K. Akimoto, H. Kawashima, Y. Shinmen and H. Yamada (1989)J. Am. Oil Chem. Soc. 66, 237–241]. The factor causing these effects was isolated and identified to be (+)-sesamin. The results obtained in experiments with both a cell-free extract of the fungus and with rat liver microsomes demonstrated that (+)-sesamin specifically inhibits Δ5 desaturase at low concentrations, but does not inhibit Δ6, Δ9 and Δ12 desaturases. Kinetic analysis showed that (+)-sesamin is a noncompetitive inhibitor (K_i for rat liver Δ5 desaturase, 155 μM). (+)-Sesamolin, (+)-sesaminol and (+)-episesamin, also inhibited only Δ5 desaturases of the fungus and liver. These results demonstrate that (+)-sesamin and related lignan compounds present in sesame seeds or its oil are specific inhibitors of Δ5 desaturase in polyunsaturated fatty acid biosynthesis in both microorganisms and animals. On leave from Suntory Ltd.     

Plasma etching durability of poly(methyl methacrylate)

The decomposition of poly(methyl methacrylate) (PMMA), as a positive resist, in CF₄/O₂ plasma etching has been studied in the thin film state in order to clarify the factors influencing the dry etching durability of resists. It becomes clear that the major PMMA decomposition in CF₄/O₂ plasma etching proceeds by the mechanism of random chain scission because very small kinetic chain lengths are estimated from the gel permeation chromatography data. The Arrhenius plots for the plasma etching rate of PMMA bend above about the glass transition temperature (T_g), where rapid increase of the etching rate and remarkable pattern deformation are observed. Activation energy of the PMMA etching rate which is changed by oxygen concentration and rf power indicates various values from 3.1 to 6.5 kcal/mol below about T_g. The result of molecular weight variation in the cross section of the film suggests that the active species permeate into the film with fairly large speed and the PMMA decomposition occurs not only at the film surface but also at deep layer of the film.     

Production of dihomo-γ-linolenic acid byMortierella alpina 1S-4

The mycelial dihomo-γ-linolenic acid content of an arachidonic acid-producing fungus,Mortierella alpina 1S-4, was found to increase, with an accompanying marked decrease in its arachidonic acid content, on cultivation with sesame oil. The resultant mycelia were found to be a rich source of dihomo-γ-linolenic acid. This unique phenomenon was suggested to be due to specific repression of the conversion of dihomo-γ-linolenic acid to arachidonic acid by the oil. After fractionation of the oil with acetone into oil and non-oil fractions, it was found that the effective factor(s) was present in the non-oil fraction. In a study on optimization of the culture conditions for the production of dihomo-γ-linolenic acid byM. alpina 1S-4, a medium containing glucose, yeast extract and the non-oil fraction was found to be suitable for the production. Under the optimal conditions in a 50-1 fermentor, the fungus produced 107 mg of dihomo-γ-linolenic acid/g dry mycelia (2.17 g/l of culture broth). This value accounted for 23.1% of the total fatty acids in the lipids extracted from the mycelia. The mycelia were also rich in arachidonic acid (53.5 mg/g dry mycelia, 11.2%). Other major fatty acids in the lipids were palmitic acid (24.1%), stearic acid (7.0), oleic acid (20.1), linoleic acid (6.6) and γ-linolenic acid (4.1). On leave from Suntory Ltd.