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Background An increase in oral squamous cell carcinoma (OSCC) cases was observed despite the reduction in exposure to classic risk factors. Although the exact cause of this trend remains unknown, epigenetic factors could be contributing to an increased occurrence of these tumors. This study aims to assess the influence of PMS2 protein immunoexpression on the prognosis of patients with OSCC. Material and Methods This study comprised 76 cases of OSCC treated between 2011 and 2016. Immunohistochemical staining for PMS2 was performed. For evaluation, 10 fields per histological section were photographed at a 400x magnification and positively-stained cells were counted with Image J. Mann-Whitney and Kruskal-Wallis tests were used to compare the immunolabeling pattern with the clinical-pathological and prognostic characteristics. Survival analysis was performed with Chi-square, Long-Rank Mantel-Cox and Cox regression tests (p60%; p=0.041) were associated with low survival (p=0.029). In multivariate analysis, surgery combined with chemotherapy (p=0.030) and high PMS2 immunoexpression (p=0.042) significantly increased the risk of death for ≤60 years old patients. Conclusions The findings of this study indicate that PMS2 can be a potential prognostic protein marker in OSCC patients 60 years of age and younger. Key words:Squamous cell carcinoma, mouth neoplasms, mismatch repair endonuclease PMS2, survival.

Following-up on previous studies that investigated genetic relationships among several world-wide cattle breeds using genome-wide SNP data, we focus here on the central and western part of the Mediterranean. Notably, 50K genotypes from 30 Marismeña (Spain); 24 Guelmoise (Algeria); 46 Brune de l’Atlas Fauve, 15 Brune de l’Atlas Grise, and 15 Blonde du Cap (Tunisia); 29 Modicana and 30 Cinisara (Sicily); 24 Podolica Italiana (Southern continental Italy); 34 Chianina and 24 Romagnola (Central Italy); 23 Modenese, 24 Reggiana, 23 Alpine Grey and 50 Pezzata Rossa Italiana (Northern Italy); 50 Bruna Italiana and 50 Frisona Italiana were considered. When included in a world-wide dataset, the three Tunisian, the Algerian, the two Sicilian, the Podolica, the Chianina and the Romagnola were the taurine breeds showing the highest closeness to the Indian zebu group in the MDS plot of the IBS distance. These results were also confirmed by ADMIXTURE analysis (K = 2). This relatively lower influence of zebu material into cattle breeds from Northern Italy suggests a major maritime-mediated route of dispersal of zebu material into Southern Europe and Northern Africa. Interestingly, breeds from the Iberian peninsula showed lower evidence of zebu introgression, suggesting that zebu introgression was likely not mediated by Moors, and possibly occurred at earlier times. Clear evidence of more recent introgression of material from improved dairy cattle breeds (Bruna Italiana and Brown Swiss) into the two Brune de l’Atlas populations from Tunisia highlights the need for urgent conservation of this cross-border cattle.

Evaluation of the uncertainty for the measurement of a gauge block by optical interferometry is presented. The measurement method which serves as the basis for the uncertainty evaluation is consistent with popular measurement techniques which apply the method of exact fractions. This uncertainty evaluation is an example of rigorous application of the ISO Guide to the Expression of Uncertainty in Measurement including treatment of higher-order terms and correlation.

The toxicity of 3′-azido-3′-deoxythymidine (AZT) and the appearance of drug-resistant mutants in patients treated with AZT emphasizes the critical importance of the development of alternative strategies for the therapy of AIDS patients. Combination antiviral chemotherapy provides an attractive therapeutic strategy since the dose of the individual agents may be lowered to reduce toxicity and the use of two potent antiviral agents may limit the development of drug resistance. Two analogues of tetrahydro-imidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione (TIBO) potently and selectively inhibit the replication of HIV-1 in cell culture. In combination with AZT, either of the two TIBO compounds, R82913 and R86183, was highly synergistic in cell culture against HIV-1. However, in biochemical enzyme inhibition assays, utilizing recombinant HIV-1 reverse transcriptase, synergy was not detected at the enzymatic level. These results suggest that one of these two known inhibitors of HIV-1 reverse transcriptase may have a secondary mechanism of action distinct from inhibition of the reverse transcriptase.

Bandera's neonatal ataxia (BNAt) is an autosomal recessive cerebellar ataxia that affects members of the Coton de Tulear dog breed.To identify the mutation that causes BNAt.The study involved DNA from 112 Cotons de Tulear (including 15 puppies with signs of BNAt) and 87 DNA samples from dogs of 12 other breeds.The BNAt locus was mapped with a genome-wide association study (GWAS). The coding exons of positional candidate gene GRM1, which encodes metabotropic glutamate receptor 1, were polymerase chain reaction (PCR)-amplified and resequenced. A 3-primer PCR assay was used to genotype individual dogs for a truncated retrotransposon inserted into exon 8 of GRM1.The GWAS indicated that the BNAt locus was in a canine chromosome 1 region that contained candidate gene GRM1. Resequencing this gene from BNAt-affected puppies indicated that exon 8 was interrupted by the insertion of a 5'-truncated retrotransposon. All 15 BNAt-affected puppies were homozygous for the insert, whereas all other Cotons de Tulear were heterozygotes (n = 43) or homozygous (n = 54) for the ancestral allele. None of the 87 dogs from 12 other breeds had the insertion allele.BNAt is caused by a retrotransposon inserted into exon 8 of GRM1. A DNA test for the GRM1 retrotransposon insert can be used for genetic counseling and to confirm the diagnosis of BNAt.

The aim of this study was to investigate the benefits of the preprocessing scheme "Adaptive Dynamic Range Optimization" (ADRO) in children using Nucleus cochlear implants. Previous research with adults indicates improved speech perception in quiet and improved sound quality in everyday listening environments with the ADRO scheme.Children were given 4 wk of take-home experience with ADRO, with a minimum of 2 wk in which ADRO was "locked-in." After 1 wk of ADRO use and again after 4 wk of ADRO use, Bench-Kowal-Bamford (BKB) sentence perception in quiet at a low input level of 50 dB SPL (unweighted root mean square) and sentence perception in noise were compared with the child's everyday (Standard) program and the ADRO program. Children also rated the loudness of a variety of environmental sounds and indicated which program provided the best hearing in a variety of everyday listening situations.On average, BKB sentence perception in quiet at 50 dB SPL was significantly better with the ADRO program compared with the Standard program. The group mean improvement was 8.60%. Similarly, group mean scores for BKB sentences presented at 65 dB SPL in multitalker babble were significantly higher with the ADRO program (an improvement of 6.87%). The ADRO program was the preferred program in 46% of the listening situations, whereas the Standard program was preferred in 26% of situations. Everyday sounds were not unacceptably loud with ADRO.There was an ADRO benefit for this group of children in quiet and in noise. These findings suggest that young children would benefit from the ADRO programming option being locked in along with other processor settings in the SPrint processor once their MAP levels have stabilized. Some older children and teenagers may choose to use ADRO selectively for specific listening situations.

We established and achieved our goal to (1) fabricate and evaluate test structures based on the micromirror design optimized for maskless lithography applications, (2) perform system analysis and code development for the maskless lithography concept, and (3) identify specifications for micromirror arrays (MMAs) for LLNL�s adaptive optics (AO) applications and conceptualize new devices.

The technique of external rhinoplasty has enjoyed a renaissance over the last ten years, primarily for cosmetic and functional septorhinoplasty, and we have found this to be an effective method for nasal reconstruction. Moreover, we have recognized the versatility of this approach for a variety of rhinologic problems and have utilized it for transsphenoidal hypophysectomy, sphenoidotomy, unilateral choanal atresia, septal perforation, nasal valvuloplasty and rhinophyma. We describe our technique and the rationale for employing it. We conclude that the enhanced exposure provided by the cutaneous decortication of the nose facilitates surgery of both the soft tissues and the supportive architecture of the nose.

Optical interference lithography offers a robust patterning technology capable of achieving high spatial resolution over extremely large field sizes ( {approx}1 m ). Here, we compare two different approaches for fabricating arrays of holes using interferometric techniques. We show that by applying an image reversal process to standard two-beam interference lithography, arrays of high aspect ratio holes can be generated. This process scales to submicron periods and allows holes as small as 0.1 micron to be patterned. Next, we present an analysis of the multiple-beam approach for patterning holes. We demonstrate that while the formation of higher contrast intensity patterns is possible by interfering four or more beams, the shape and modulation depth of such patterns are inherently sensitive to relative phase variations.

The polypeptide of uromodulin, an immunosuppressive glycoprotein isolated from human urine, has been shown to be identical to that of Tamm-Horsfall glycoprotein and is synthesized exclusively in the kidney (Hession, C., Decker, J. M., Sherblom, A. P., Kumar, S. (1987) Science 237, 1479-1484). Uromodulin binds recombinant murine interleukin 1 alpha with high affinity, and this binding can be inhibited by addition of specific saccharides (Muchmore, A. V., and Decker, J. M. (1987) J. Immunol. 138, 2541-2546). We now report that uromodulin binds recombinant human tumor necrosis factor (rTNF) with high affinity. Both diacetylchitobiose and Man(alpha 1-6)(Man(alpha 1-3]-Man-O-ethyl are effective inhibitors of the binding, whereas a wide variety of other saccharides are not inhibitory. Although Tamm-Horsfall glycoprotein contains predominantly tetraantennary N-linked chains, the binding to rTNF is unaffected by removal of terminal sialic acid, galactose, and N-acetylhexosamine residues. Fractionation of a Pronase digest of uromodulin by gel filtration yields material that inhibits the binding of uromodulin to rTNF but is of lower molecular weight than the major oligosaccharide. Uromodulin does not inhibit the cytotoxic activity of rTNF as monitored by lysis of tumor cell targets but effectively protects mice from lethal challenge with lipopolysaccharide, an event that may involve lymphokine toxicity. We have previously shown that rTNF binds to sections of human kidney and is localized in the same region as uromodulin. Thus, rTNF interacts with uromodulin via carbohydrate chains that are less processed than the major tetraantennary chain, and this interaction may be critical in promoting clearance and/or reducing toxicity of TNF and other lymphokines.

Uromodulin is an 85-kDa immunosuppressive glycoprotein originally isolated from human pregnancy urine. It exhibits immunosuppressive activity in vitro at concentrations between 10(-9) and 10(-11) M. Recent data demonstrate that uromodulin is able to specifically inhibit in vitro assays dependent upon interleukin 1 (IL-1). We now present evidence that uromodulin is a high affinity ligand for recombinant murine IL-1 alpha. Since uromodulin has been purified to homogeneity, this should allow extensive further characterization of the mechanism of action of both uromodulin and IL-1.

A method is described for assessing the in vivo oxygen consumption and lactate production rates of human knee joints. It is based on the rate of fall of P(o2) and the rate of rise in lactate concentration in an intra-articular saline pool after interruption of the circulation to the joint with an arterial tourniquet. Studies in 5 control patients with degenerative joint disease and 29 patients with rheumatoid arthritis showed a 2- to 3-fold higher mean oxygen uptake rate and a 10- to 12-fold higher mean lactate appearance rate in the saline in the rheumatoid joints with severe disease compared to the control joints. These metabolic variables correlated with tissue metabolic demand as estimated in synovial biopsies. (133)Xe washout from the intra-articular space, which reflects joint circulatory flow, showed a 3-fold greater mean washout rate from the rheumatoid joints (48 studies) than control joints (7 studies) with extensive overlap between the two groups. (133)Xe washout rate correlated with knee joint inflammation estimated both clinically and histologically. After synovectomy in four patients, the operated knee showed a greater fall in lactate production than the opposite knee in three of these patients. Neither knee joint oxygen uptake nor (133)Xe washout rate changed significantly. Intra-articular corticosteroid injection (eight patients) resulted in decreased lactate production and a decreased (133)Xe washout rate in the injected knee and variable results in the untreated knee. Oxygen uptake again was unchanged after therapy.

This study has shown that certain ring substitutions on aminobenzoic acids are possible without greatly affecting the favorable chelating properties of the parent ligand. It was also shown that para substitution of methyl groups yields more stable complexes than does ortho substitution relative to the amino group. Meta substitution of chlorine enhances chelate formation and yields very insoluble complexes in yields approaching one hundred per cent. Based on carbon-hydrogen analyses and other analytical data, the structures have been determined as square planar ones in which the ligand functions as a bidentate. Some water is usually incorporated in the crystal lattice, and occasionally a complex will contain one or more molecules of coordinated water. The variable amount of water in some compound crystals makes the carbonhydrogen data less exact and tends to obscure interpretation of at least some of the infrared data. Lack of solubility in water and in other polar and nonpolar solvents increases the difficulty of both infrared and ultraviolet-visible analyses; in every case potassium bromide tablets were made and were used in both infrared and ultraviolet-visible spectrophotometers; evidence obtained through study of the ultraviolet-visible data are not presented here, but there substantiate the data obtained by the other methods. With the ligands and metal cations used, fifty-five compounds were possible; forty-four of these were actually prepared and isolated, and of these, thirty-five were shown to be coordination complexes. Twenty-seven of these complexes were previously unreported including all the compounds reported for 3,5-dimethylanthranilic acid, 2-amino-4-chlorobenzoic acid, and 6-amino-3-methylbenzoic acid.

Left auricular appendages from 183 patients, removed at operation for mitral stenosis, have been studied with regard to presence of Aschoff bodies and endocardial thrombi. An over-all incidence of Aschoff lesions of 40 per cent was found. There was a significant decrease in Aschoff lesions in the presence of thrombosis. The occurrence of Aschoff bodies in the appendages is correlated with the findings in the remainder of the heart in autopsied cases.

The activity of phospholipase inhibitory protein, lipomodulin, partially purified from rabbit neutrophils, was markedly decreased after treatment with sera from patients with rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis. The decrease of the protein's inhibitory activity on phospholipase A2 paralleled the amount of [35S]methionine-labeled lipomodulin precipitated by the sera. Absorption of patients' sera with anti-human IgM (mu chain) or protein A-agarose, but not with anti-human IgG (gamma chain), decreased their ability to decrease the activity of lipomodulin on phospholipase A2 or to precipitate the radioactive lipomodulin. The IgM fraction of patients' sera could precipitate [35S]methionine-labeled lipomodulin (40,000 daltons) which comigrated with highly purified lipomodulin on gel electrophoresis with sodium dodecyl sulfate. All of these observations suggest that the sera of many patients with rheumatic diseases contain autoantibody against lipomodulin. A monoclonal antibody against lipomodulin was also obtained. Stimulating human fibroblasts with bradykinin in the presence of monoclonal antilipomodulin antibody markedly enhanced arachidonic acid release due to the activation of phospholipase(s) in the intact cells, and this stimulatory effect was blocked by adding purified lipomodulin. These findings suggest that lipomodulin regulates the activity of phospholipase(s) on the cell surface and that autoantibodies against lipomodulin may play a role in certain symptoms of rheumatic diseases, especially by the formation of prostaglandins and other metabolites of arachidonic acid.

Nine patients with active systemic lupus erythematosus entered a double-blind randomized trial to study the therapeutic effect of vigorous versus sham reinfusion plasmapheresis. Four of them received real plasmapheresis while five received sham reinfusion plasmapheresis. In the present communication we report the effects of these procedures on T lymphocytes in peripheral mononuclear cells, proliferative response to mitogens, allogeneic mixed lymphocyte reaction and cell-mediated lympholysis, as well as the effect of plasmapheresis on the spontaneous and pokeweed mitogen induced immunoglobulin secreting cells in peripheral blood. Several mononuclear cell functions were abnormal at the beginning of the study but no significant changes related to plasmaphersis occurred in any of the parameters studied.

Osteonectin/SPARC was most abundantly present in adherent osseous tissue of the cartilage explants. In cartilage explants with ossification fronts, it appears to be present in hypertrophic chondroblasts and in the mineralised extracellular cartilage matrix. In a number of cartilage explants it could be demonstrated in the fibroblastic cells of the perichondrium and, intra- and extracellularly, in cartilage located adjacent to the perichondrium. In young mandibular condylar cartilage (20 days post-conception up to 7 days of age) osteonectin/SPARC was characteristically present in the transitional zone, a small area of differentiating skeletoblasts. In cartilage, osteonectin/SPARC might play a role in the process of mineralisation and subsequent replacement by bone. It seems to be an important marker of skeletal differentiation processes.

Progress is reported on a broad and comprehensive series of biological experiments made under strictly controlled laboratory conditions to screen for possible effects of exposure to 60-Hz electric fields on small laboratory animals. Electric field strengths comparable to and exceeding those under existing and anticipated transmission line designs will be used. Dosimetry studies will complement the animal studies to establish the relationship between tissue dose and any observed biological effects. Information derived from this project will provide a better basis for evaluating potential hazards of exposure to 60-Hz electric fields and help define parameters to be studied in clinical evaluations on humans.

Purified subpopulations of human T lymphocytes bearing Fc-IgG and Fc-IgM receptors were studied for their ability to mediate mitogen (PHA) induced cellular cytotoxicity (MICC) to chicken erythrocyte (CRBC) and DBA/Mastocytoma P815Y tumour cell targets. There were marked differences in the ability of the Fc-IgG receptor-bearing T cell (T gamma) and the Fc-IgM (T mu) to mediating MICC to CRBC and P815Y target cells. T gamma cells were very efficient killers of CRBC and T mu cells had no cytotoxic activity to CRBC. On the other hand, both the T gamma and T mu subpopulations were able to mediate MICC to P815Y tumour cell targets.

Four patients with active, severe rheumatoid arthritis were subjected to the removal of circulating lymphocytes (lymphapheresis) for a 6-week period by use of a continuous flow cell centrifuge. Repetitive venous access was gained through forearm arteriovenous fistulae. In all patients the Ritchie-Camp articular index declined rapidly in the first week and more slowly therafter for a total mean drop of 61% below the initial value. The index continued to decline after lymphapheresis but exacerbation of disease activity developed at an average of 19 weeks. No significant untoward effects of the procedure were observed; occasional transfusions were required to compensate for the small, unavoidable erythrocyte loss.

The polypeptide of uromodulin, an immunosuppressive glycoprotein isolated from human urine, has been shown to be identical to that of Tamm-Horsfall glycoprotein and is synthesized exclusively in the kidney (Hession, C., Decker, J. M., Sherblom, A. P., Kumar, S. (1987) Science 237, 1479-1484). Uromodulin binds recombinant murine interleukin 1 alpha with high affinity, and this binding can be inhibited by addition of specific saccharides (Muchmore, A. V., and Decker, J. M. (1987) J. Immunol. 138, 2541-2546). We now report that uromodulin binds recombinant human tumor necrosis factor (rTNF) with high affinity. Both diacetylchitobiose and Man(alpha 1-6)(Man(alpha 1-3]-Man-O-ethyl are effective inhibitors of the binding, whereas a wide variety of other saccharides are not inhibitory. Although Tamm-Horsfall glycoprotein contains predominantly tetraantennary N-linked chains, the binding to rTNF is unaffected by removal of terminal sialic acid, galactose, and N-acetylhexosamine residues. Fractionation of a Pronase digest of uromodulin by gel filtration yields material that inhibits the binding of uromodulin to rTNF but is of lower molecular weight than the major oligosaccharide. Uromodulin does not inhibit the cytotoxic activity of rTNF as monitored by lysis of tumor cell targets but effectively protects mice from lethal challenge with lipopolysaccharide, an event that may involve lymphokine toxicity. We have previously shown that rTNF binds to sections of human kidney and is localized in the same region as uromodulin. Thus, rTNF interacts with uromodulin via carbohydrate chains that are less processed than the major tetraantennary chain, and this interaction may be critical in promoting clearance and/or reducing toxicity of TNF and other lymphokines.

The purpose of this project is to determine if exposure to electric fields will have any detectable effect on a large experimental animal (the Hanford miniature swine). This interim report describes physical facilities developed for exposing the animals to electric fields.

THE structure of two forms of phosphorus pentoxide was determined several years ago1,2. Indications of the existence of a third form has been found in a study of the phase diagram by Hoeflake and Scheffer3. Actually, in our former investigations we found occasionally a third kind of crystals, and we determined their cell dimensions and space group4. However, we were not sure that these crystals were pure phosphorus pentoxide and not a reaction product with the glass wall, to which they adhere extremely firmly. Hill, Faust and Hendricks5 put the existence of a third form beyond doubt. They considered the modification as probably tetragonal (instead of orthorhombic, as found by us), as a result of optical investigation. According to their powder diagram data, however, it is certain that their crystals are identical with those described by us4.

A recent work investigating genetic origin, admixture and population history of primitive European cattle highlighted, by using genome-wide single nucleotide polymorphisms, zebu gene flow in the Balkan and Italian Podolic cattle populations. Haemoglobin protein polymorphism analysis in Italian breeds highlighted the presence of zebuine markers in both Italian Podolic and Alpine Grey cattle. Based on the above evidences, we here specifically look for genomic regions of zebuine ancestry in a different dataset of 50K genotypes from Mediterranean breeds including 29 Marismena (Spain); 30 Bazadaise and 30 Gasconne (France); 24 Alpine Grey, 97 Piemontese, 51 Chianina, 5 Marchigiana, 121 Romagnola, 24 Podolica, 24 Modenese, 30 Reggiana, 30 Cinisara and 30 Modicana (Italy); 24 Guelmoise (Algeria); 24 Cika (Slovenia), 43 Illyrian Mountain Buša (Albania). Additional taurine and zebuine breeds from previously published studies are also included in the analyses. Special emphasis in genetic analyses is also given to the identification of genomic regions potentially associated with a phenotypic trait observed in several taurine breeds as well as in some zebuine breeds, characterized by calves having a fawn coat at birth, while turning to various shades of grey in adult animals. The obtained results contribute to a better characterization of history and genetic structure of Mediterranean cattle breeds.