Stratification of Prognosis in Patients With Ampullary Carcinoma After Surgery by Preoperative Platelet-to-lymphocyte Ratio and Conventional Tumor Markers.

BACKGROUND/AIM: The platelet-to-lymphocyte ratio (PLR) has recently been suggested as a new predictor of the prognosis in several carcinoma types. However, the clinical impact remains controversial in patients with ampullary carcinoma. Thus, the aim of this study was to investigate other useful biomarkers for identifying poor prognosis in patients with ampullary carcinoma. PATIENTS AND METHODS: Forty-one patients with ampullary carcinoma underwent pancreaticoduodenectomy (PD) with curative resection between April 2000 and April 2017. Various clinicopathological findings of the patients and their tumors were evaluated as potential prognostic factors which might enable better stratification of prognosis. RESULTS: Platelet-to-lymphocyte ratio, as well as other markers, was found to be a prognostic factor in patients with ampullary carcinoma. The 2-year disease-free survival percentage was significantly higher in the group with low PLR than in the high PLR group (70.2% vs. 28.6%; p=0.005). Combinational analysis of the PLR and conventional TMs enabled us to stratify prognosis of the patients more clearly than by each marker alone. CONCLUSION: PLR was a useful prognostic factor for patients with ampullary cancer. The combination of preoperative PLR and conventional TMs markers may be powerful predictive factors for postoperative prognosis in patients with ampullary carcinoma following PD.

Feasibility of Combination Therapy with Nab-paclitaxel Plus Gemcitabine in Patients with Recurrent Pancreatic Cancer.

BACKGROUND/AIM: Nab-paclitaxel plus gemcitabine (nab-P+Gem) is one of most reliable and effective regimens for borderline or unresectable pancreatic cancer (PC). However, the feasibility and clinical benefits of this regimen have never been evaluated for patients with recurrent PC after pancreatectomy. The aim of this study was to investigate the feasibility of combination therapy with nab-paclitaxel plus gemcitabine (nab-P+Gem) for patients with recurrent PC. PATIENTS AND METHODS: Twenty-two patients with recurrent PC received an intravenous infusion of nab-P (125 mg/m2) and Gem (1,000 mg/m2) on days 1, 8, and 15 of a 4-week cycle. The primary end-point of this study was completion of the 4 cycles. The secondary end-points were the safety, efficacy, and disease control rate. RESULTS: The treatment completion rate of the 4 cycles was 90.9%. The objective response rate was 13.6% and the disease control rate was 63.6%. The median progression-free survival was 7.2 months. The most common grade 3 or higher hematological toxicity was neutropenia (72.7%). There was no treatment-related death. Furthermore, the chemotherapeutic effects varied with the time of recurrence. CONCLUSION: Combination nab-P+Gem therapy was well-tolerated and effective in patients with recurrent PC.

Identification of GFAT1-L, a novel splice variant of human glutamine: fructose-6-phosphate amidotransferase (GFAT1) that is expressed abundantly in skeletal muscle.

Glutamine:fructose-6-phosphate amidotransferase (GFAT1) is the rate-limiting enzyme in the hexosamine biosynthetic pathway, which plays an important role in hyperglycemia-induced insulin resistance. To evaluate the role of GFAT1 expression, we analyzed the expression profiles of GFAT1 mRNA in various human tissues using reverse transcriptase-polymerase chain reaction. We report here the identification and cDNA cloning of a novel GFAT1 splice variant expressed abundantly in skeletal muscle and heart. This subtype, designated GFAT1-L, contains a 54-bp insertion within the GFAT1 coding sequence. Recombinant GFAT1-L protein possessed functional GFAT activities and biochemical characteristics similar to GFAT1. Previously, GFAT1 was considered a simplex enzyme. The identification of a novel GFAT1 subtype possessing functional enzymatic activity and tissue-specific expression should provide additional insight into the mechanism of skeletal muscle insulin resistance and diabetes complications.

Structure, expression, and chromosomal localization of the human gene encoding a germinal center-associated nuclear protein (GANP) that associates with MCM3 involved in the initiation of DNA replication.

A 210kDa protein named GANP is upregulated in germinal center (GC)-B cells in the spleen of antigen-immunized mouse. We studied a human ganp gene (hganp) encoding a putative polypeptide of 1980 amino acids. The carboxyl-terminal 721-amino-acid sequence of hGANP is identical to Map80, that is presumably generated by alternative splicing of hganp/Map80 gene. The genomic segment carrying hganp and Map80 genes was isolated, and the chromosomal location was determined on 21q22.3. Northern blot analysis with RNAs from various organs demonstrated a single band of 7kb hganp mRNA, which suggests a preferential transcription of hganp gene from the hganp/Map80 locus. The hGANP expression was upregulated in GCs of the tonsil, as demonstrated by in-situ RNA hybridization and immunohistochemical analyses. The hGANP, with the domain (Map-box) capable of binding to MCM3 in B cells, might be involved in regulation of cell-cycle progression and DNA replication of GC-B cells.

Identification and characterization of TMEFF2, a novel survival factor for hippocampal and mesencephalic neurons.

We have identified a novel mammalian gene, TMEFF2, that encodes a putative transmembrane protein containing two follistatin-like domains and one epidermal growth factor (EGF)-like domain. The TMEFF2 gene is predominantly expressed in the brain. In situ hybridization analysis revealed that TMEFF2 is widely expressed in the brain, including hippocampal cornu ammonis, dentate gyrus, and substantia nigra pars compacta. We evaluated the survival effect of TMEFF2 using primary cultured neurons from several regions of fetal rat brain following treatment with a recombinant TMEFF2 protein fragment consisting of the putative extracellular domain. TMEFF2 increased survival of neurons from the hippocampus and midbrain, but not from the cerebral cortex, indicating that the survival effects of TMEFF2 are specific to certain cell types. Recombinant TMEFF2 also promoted survival of mesencephalic dopaminergic neurons. Together, these findings suggest that TMEFF2 may be a novel survival factor for hippocampal and mesencephalic, but not for cortical, neurons.

Human aiolos, an ikaros-related zinc finger DNA binding protein: cDNA cloning, tissue expression pattern, and chromosomal mapping.

The Ikaros gene (symbol ZNFN1A1) encodes the hematopoietic zinc finger DNA binding protein, which is now recognized as a central regulator of lymphoid differentiation and has been implicated in leukemogenesis. Recently, an Ikaros-related zinc finger protein, called Aiolos (ZNFN1A3), has been identified and characterized, thus establishing the presence of a gene family whose members may be hematopoietic transcription factors. Among Aiolos-mutant mice, development of B-cell lymphoma was frequently seen. As an initial approach to examining the possible involvement of Aiolos in the pathogenesis of human lymphoid proliferative disease, we isolated cDNA clones for human Aiolos from a B-cell cDNA library. The human Aiolos protein predicted from the cDNA sequence consists of 509 amino acid residues and shares 86% sequence identity with its mouse counterpart. As in the case with mouse Aiolos, no isoform for human Aiolos has been found. Northern blot analysis of various human tissues revealed that the Aiolos transcripts are expressed most strongly in peripheral blood leukocytes, the spleen, and the thymus, supporting the notion that Aiolos plays an important role in lymphoid lineages. Fluorescence in situ hybridization using a BAC clone established that the Aiolos gene is mapped to human chromosome band 17q11.2.

Cloning and characterization of two novel human cDNAs (NELL1 and NELL2) encoding proteins with six EGF-like repeats.

From a human fetal-brain cDNA library we isolated two novel genes encoding peptides containing six EGF-like repeats. Both showed significant homologies with nel, a gene strongly expressed in neural tissues of chicken. The cDNAs, designated NELL1 (nel-like, type 1) and NELL2 (nel-like, type 2), contained open reading frames encoding 810 and 816 amino acids, respectively. NELL2 is strongly expressed in brain of adult and fetus but only weakly in fetal kidney. NELL1 and NELL2 were mapped by FISH to chromosomal bands 11p15.1-p15.2 and 12q13.11-q13.12, respectively.

Cloning and mapping of a human RBP56 gene encoding a putative RNA binding protein similar to FUS/TLS and EWS proteins.

The EWS gene was found at the chromosome breakpoints in Ewing sarcoma, and the FUS/TLS gene was found at the breakpoints of myxoid liposarcoma and acute myeloid leukemia. These genes encode proteins that carry a highly homologous RNA binding domain. Fusion proteins made of the N-terminal half of EWS or FUS/TLS and transcriptional regulatory proteins, also derived from genes located at breakpoints, have been suggested to be involved in the pathogenesis of tumors. By PCR amplification of human Namalwa cell cDNA using degenerate primers made from the conserved amino acid sequences in the RNA binding domain of EWS and FUS/TLS, we obtained a cDNA fragment (RBP56 cDNA), the predicted amino acid sequences of which were similar but not identical to those of EWS and FUS/TLS. Using this fragment as a probe, we obtained two isoforms of cDNAs consisting of 2144 and 2153 bp, respectively, which encode proteins consisting of 589 and 592 amino acid residues, respectively. The predicted amino acid sequences of RBP56 protein have a serine-, tyrosine-, glutamine-, and glycine-rich region in the N-terminal region, an RNA binding domain and a C2C2 finger motif in the central region, and degenerate repeats of DR(S)GG(G)-YGG sequences in the C-terminal region. The expression of RBP56 mRNA was observed in all of the human fetal and adult tissues examined, as was the expression of EWS and FUS/TLS mRNAs. The RBP56 gene was mapped to chromosome 17q11.2 to q12.

Human gene encoding prostacyclin synthase (PTGIS): genomic organization, chromosomal localization, and promoter activity.

The prostacyclin synthase gene isolated from human genomic libraries (PTGIS) consists of 10 exons spanning approximately 60 kb. All the splice donor and acceptor sites conform to the GT/AG rule. Genomic Southern blot and fluorescence in situ hybridization analyses revealed that the human prostacyclin synthase gene is present as a single copy per haploid genome and is localized on chromosome 20q13. 11-q13.13. The 1.5-kb sequence of the 5'-upstream of the translational initiation site contained both GC-rich and pyrimidine-rich regions and consensus sequences of the transcription factor recognition sites such as Sp1, AP-2, the interferon-gamma response element, GATA, NF-kappaB, the CACCC box, and the glucocorticoid response element. The core binding sequence (GAGACC) of the shear stress responsive element was also found in the 5'-flanking region of the gene. The major product of the primer extension analysis suggested that the transcription of the gene started from the positions around 49 bp upstream of the translational initiation codon. Transient transfection experiments using human aortic and bovine arterial endothelial cells demonstrated that the GC-rich region (positions -145 to -10) possessed a significant promoter activity. The 6-kb downstream sequence of the translational termination codon contained multiple polyadenylation signals, Alu repeat sequences, and the consensus sequence of the primate-repetitive DNA element, MER1. Two sizes of the prostacyclin synthase mRNAs (approximately 6 and 3.3 kb) were detected with the human aorta and lung. RNA blot hybridization analysis using the 3'-untranslated region as probe indicated that the sizes of the 3'-flanking regions were different in the major 6-kb and minor 3.3-kb mRNAs.

Physical mapping of the retinoblastoma interacting zinc finger gene RIZ to D1S228 on chromosome 1p36.

The retinoblastoma interacting zinc finger gene RIZ is a member of the recently discovered PR domain family that includes the MDS1-EVI1 breakpoint gene involved in human leukemia. To help understand the role of RIZ in human diseases, we have determined the cytogenetic and physical localizations of the RIZ gene. Using fluorescence in situ hybridization, we determined that RIZ maps to 1p36. On the physical map, RIZ is adjacent to the polymorphic marker D1S228. We suggest that the RIZ gene may be a candidate target of 1p36 alterations that commonly occur in neuroendocrine, breast, liver, colon, and lymphoid tumors.

Isolation and mapping of a novel human gene encoding a protein containing zinc-finger structures.

We have isolated and characterized a cDNA clone, termed OTK18, representing a novel human gene. The 3754 nucleotides of this clone contain an open reading frame of 2133 nucleotides. As the predicted 711-amino-acid protein contains 13 contiguous zinc-finger stuctures of the C2H2 type, it would be expected to function as a DNA-binding multi-finger protein. The 4.3-kb transcript was expressed in all adult human tissues examined by Northern analysis. The gene was assigned to chromosomal band 19q13.4 by fluorescence in situ hybridization.

[The physical assessment and the intensive care unit nurse]. / O exame físico e o enfermeiro de UTI.

The goal of this study was to analyse some practicing, teaching and learning aspects of physical examination done by ICU's nurses. It was accomplished with 26 ICU nurses that concluded the Intensive Care Nursing Specialization Course at the School of Nursing at São Paulo University. The results showed that 31 (68.9%) of the 45 presented items were done frequently by more than 50% of the nurses. The professional practice was considered the most important moment to physical examination learning. The responsibility by teaching was attributed to undergraduation course by 69.2% of the nurses.

[The basic needs of the spouses of infarct patients in the acute phase of the treatment]. / Necessidades básicas das esposas de pacientes infartados, na fase aguda do tratamento.

The purpose of this study was to identify the basic needs of the spouses of patients with myocardial infarction. The concepts of basic needs from Maslow were used as conceptual framework. The data's analysis showed the following needs affections of this population: safety, belongingness and love, esteem.

Chromosomal hypersensitivity in mutant M10 and Q31 mouse cells exposed to ultraviolet radiation (UV) and 4-nitroquinoline-1-oxide (4NQO).

2 mutant mouse cells M10 and Q31 were examined for chromosomal aberrations induced by ultraviolet radiation (UV) and 4-nitroquinoline-1-oxide (4NQO), as compared with mouse lymphoma L5178Y cells. Q31 cells are UV- and 4NQO-sensitive cells isolated from L5178Y cells. M10 cells are similar but are sensitive to ionizing radiation and 4NQO. After treatment with UV or 4NQO, chromatid-type aberrations in these cell strains were induced more frequently in the first mitotic cells, at late fixation times. After UV exposure (2.4 J/m2), the maximal frequencies of chromatid-type breaks in Q31 cells were about 5 times higher than in L5178Y cells. In M10 cells such breaks were only as frequent as in L5178Y cells. After 4NQO treatment (50 ng/ml) the frequencies of chromatid-type breaks in M10 and Q31 cells were significantly higher than in L5178Y cells. From these results and those of previous studies (Takahashi et al., 1982), M10 cells may be considered hypersensitive to gamma-rays and 4NQO, but not to UV, and thus react similarly to L5178Y cells. The hypersensitivity of M10 cells to 4NQO may result from a defect in the ionizing-radiation repair mechanism as has been suggested to occur in ataxia telangiectasia (AT) cells. Q31 cells are hypersensitive to UV and 4NQO, but not to gamma-rays. Q31 cells may be considered to be deficient in a UV-like repair pathway. In conclusion, characteristics of murine M10 and Q31 cells are compared with those of human AT and xeroderma pigmentosum (XP) cells.