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1.
Colorectal Dis ; 14(10): e740-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22709354

RESUMO

AIM: A case-controlled study was performed to investigate the association of colonic angiectasia with other conditions and to identify risk factors for bleeding. METHOD: Information was collected from all patients who underwent colonoscopy at our hospital between January 2008 and December 2010. Data on 90 individuals with angiectasia [58 men; median age 69 (26-92) years] were compared with those of 180 individuals without angiectasia, matched for gender and age. RESULTS: Multivariate analysis showed that occult gastrointestinal bleeding [odds ratio (OR) 2.523; 95% confidence interval (CI) 1.238-5.142], liver cirrhosis (OR 13.195; 95% CI 3.502-49.711), chronic renal failure (OR 6.796; 95% CI 1.598-28.904) and valvular heart disease (OR 6.425; 95% CI 1.028-40.165) were identified as significant predictors of the presence of colonic angiectasia. Eight patients were diagnosed with bleeding from angiectasia. Cardiovascular disease (OR 22.047; 95% CI 1.063-457.345) and multiple angiectasias (P-value 0.0019) were identified as significant risk factors for active bleeding. Medication and a large size were not associated with an increased risk of bleeding. CONCLUSION: The presence of colonic angiectasia was associated with valvular heart disease, liver cirrhosis and chronic renal failure. Valvular heart disease and multiple lesions increased the risk of bleeding.


Assuntos
Angiodisplasia/etiologia , Doenças do Colo/etiologia , Hemorragia Gastrointestinal/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiodisplasia/diagnóstico , Estudos de Casos e Controles , Doenças do Colo/diagnóstico , Colonoscopia , Feminino , Hemorragia Gastrointestinal/diagnóstico , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco
2.
Int J Obes (Lond) ; 34(1): 136-45, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19859077

RESUMO

OBJECTIVES: It is well known that body weight loss through a direct (supervised) lifestyle intervention (LSI) improves obesity-related metabolic disorders. The purpose of this study was to investigate the effects of an indirect LSI on weight loss and metabolic syndrome (MetS) in spouses of LSI participants. METHODS: A total of 104 men (abdominal circumference > or = 85 cm; age, 52.1 + or - 9.3 years) were assigned to one of three groups: no intervention (NI, n = 34), direct intervention (DI, n = 34) or indirect intervention (II, n = 36), the last of which consisted of subjects who did not participate in the direct LSI but whose wives did. Body weight and MetS components were measured before and after a 14-week intervention. Daily energy intake and activity-related energy expenditure were assessed before and during the intervention. The LSI program was mainly consisted of dietary modifications with a physical activity program. RESULTS: No differences were observed across the three groups in any of the measures at baseline. Significant differences were observed among the groups in weight loss (NI, -0.7 + or - 1.4; DI, -6.2 + or - 3.3 and II, -4.4 + or - 3.7 kg) during the intervention. Along with the body weight reductions, significant improvements were observed in most of MetS components within the DI and II groups. When analyzing the spouse pairs in group II, significant correlations were observed in weight loss (r = 0.57) and decreased total energy intake (r = 0.54) between wives and husbands. CONCLUSIONS: Indirect LSI in abdominally obese men whose wives were undergoing LSI led to loss of weight and a decreased incidence of MetS, suggesting that indirect LSI may be an effective program for eliciting beneficial change in health status.


Assuntos
Dieta Redutora/psicologia , Síndrome Metabólica/terapia , Atividade Motora/fisiologia , Obesidade/terapia , Comportamento de Redução do Risco , Cônjuges , Índice de Massa Corporal , Dieta Redutora/métodos , Feminino , Humanos , Japão/epidemiologia , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/psicologia , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/psicologia , Redução de Peso
3.
Science ; 242(4881): 1042-5, 1988 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-3194754

RESUMO

A rat kidney messenger RNA that induces a slowly activating, voltage-dependent potassium current on its expression in Xenopus oocytes was identified by combining molecular cloning with an electrophysiological assay. The cloned complementary DNA encodes a novel membrane protein that consists of 130 amino acids with a single putative transmembrane domain. This protein differs from the known ion channel proteins but is involved in the induction of selective permeation of potassium ions by membrane depolarization.


Assuntos
Proteínas de Membrana/genética , Canais de Potássio/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Clonagem Molecular , DNA/genética , Condutividade Elétrica , Potenciais da Membrana , Dados de Sequência Molecular , Peso Molecular , Ratos , Xenopus laevis
4.
Neurogastroenterol Motil ; 29(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28631871

RESUMO

BACKGROUNDS: Chronic intestinal pseudo-obstruction (CIPO) is an intractable rare digestive disease manifesting persistent small bowel distension without any mechanical cause. Intestinal decompression is a key treatment, but conventional method including a trans-nasal small intestinal tube is invasive and painful. Therefore, a less invasive and tolerable new decompression method is urgently desired. We conducted a pilot study and assessed the efficacy and safety of percutaneous endoscopic gastro-jejunostomy (PEG-J) decompression therapy in CIPO patients. METHODS: Seven definitive CIPO patients (2 males and 5 females) were enrolled. All patients received PEG-J decompression therapy. The number of days with any abdominal symptoms in a month (NODASIM), body mass index (BMI), serum albumin level (Alb), and small intestinal volume before and after PEG-J were compared in all patients. RESULTS: Percutaneous endoscopic gastro-jejunostomy was well tolerated and oral intake improved in all patients. NODASIM has significantly decreased (24.3 vs 9.3 days/months) and BMI/Alb have significantly increased (14.9 vs 17.2 kg/m2 and 2.6 vs 3.8 g/dL, respectively), whereas total volume of the small intestine has not significantly reduced (4.05 vs 2.59 L, P=.18). Reflux esophagitis and chemical dermatitis were observed in one case but was successfully treated conservatively. CONCLUSIONS & INFERENCES: Percutaneous endoscopic gastro-jejunostomy decompression therapy can contribute greatly to improvement of abdominal symptoms and nutritional status in CIPO patients. Although sufficient attention should be paid to acid reflux symptoms, PEG-J has the potential to be a non-invasive novel decompression therapy for CIPO available at home. However, accumulation of more CIPO patients and long-term observation are needed (UMIN000017574).


Assuntos
Endoscopia Gastrointestinal/métodos , Gastrostomia/métodos , Pseudo-Obstrução Intestinal/cirurgia , Jejunostomia/métodos , Adulto , Idoso , Doença Crônica , Descompressão Cirúrgica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
5.
Biochim Biophys Acta ; 914(3): 246-58, 1987 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-3620474

RESUMO

Three fractions of cytochrome P-450scc (denoted as fractions a, b, and c) were purified by a new procedure from bovine adrenocortical mitochondria. The amino-acid content analyses of these three fractions showed no difference. NH2-terminal amino-acid sequences of cytochrome P-450scc fractions, a and b agreed completely with the sequence deduced by nucleotide sequence of cDNA of cytochrome P-450scc mRNA (Morohashi, K., Fujii-Kuriyama, Y., Okada, Y., Sogawa, K., Hirose, T., Inayama, S. and Omura, T. (1984) Proc. Natl. Acad. Sci. USA 81, 4647-4651), whereas the sequence of fraction c showed a missing of isoleucine at the NH2-terminal. COOH-terminal ámino-acid sequences of fractions a, b and c were -Gln-Ala-COOH, identical with the deduced sequence from the cDNA. Measurements of the enzymatic activities of cholesterol side-chain cleavage reaction revealed no distinct difference among these three fractions. Although each of these fractions appeared as a single protein staining band upon SDS-polyacrylamide gel electrophoresis, these fractions showed heterogeneities upon two-dimensional electrophoresis and chromatofocusing. Fraction a contained the major form of cytochrome P-450scc, and its isoelectric point was estimated to be pH 7.8 by isoelectric focusing under both native and denatured conditions, and this value was confirmed by chromatofocusing. Neither of the carbohydrate-specific stainings (such as periodic acid-Schiff staining and lectin-peroxidase stainings using concanavalin A, wheat-germ agglutinin, and soybean agglutinin) of purified cytochrome P-450scc fractions after the electrophoretic resolution on SDS-polyacrylamide gel could show cytochrome P-450scc fractions as glycoproteins, suggesting that the heterogeneities were not due to the glycosylation state.


Assuntos
Córtex Suprarrenal/metabolismo , Enzima de Clivagem da Cadeia Lateral do Colesterol/isolamento & purificação , Isoenzimas/isolamento & purificação , Mitocôndrias/metabolismo , Oxirredutases/isolamento & purificação , Sequência de Aminoácidos , Aminoácidos/análise , Animais , Carboidratos/análise , Bovinos , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Isoenzimas/metabolismo , Cinética , Mapeamento de Peptídeos
6.
Biochim Biophys Acta ; 868(1): 30-8, 1986 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-3756168

RESUMO

The present study was undertaken to find out whether or not sexual dimorphism in biological activities and amino acid compositions of mouse prolactin might be due to heterogeneity in mRNA for mouse prolactin Cloned cDNAs for mouse prolactin were first isolated from a mouse pituitary cDNA library by hybridization with a rat prolactin cDNA. Then, one clone of about 140 positive clones obtained from 2000 transformants was subjected to nucleotide sequence analysis and verified to contain a nearly full length of cDNA sequence coding for mouse prolactin precursor. The deduced complete amino acid sequence indicates that the precursor molecule consists of 31 amino acids as the signal peptide and 197 amino acids of prolactin, in which two amino acids were found to be different from the amino acid sequence previously published elsewhere. S1 nuclease mapping analysis using male and female pituitary RNAs indicates that mouse preprolactin is encoded by two mRNAs in both sexes. The two mRNAs differ from each other based upon the deletion of three nucleotides in the coding region for the signal peptide determined by the nucleotide sequence analysis in other cDNA clones. In the present study, no sexual difference was revealed in murine prolactin mRNA.


Assuntos
DNA/genética , Prolactina/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hibridização de Ácido Nucleico , RNA Mensageiro/genética , Fatores Sexuais
7.
Diabetes ; 48(2): 416-9, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10334323

RESUMO

NeuroD/BETA2, a transcription factor of the insulin gene, also plays an important role in the development of pancreatic beta-cells. Recently, the NeuroD/BETA2 gene has been mapped to the long arm of human chromosome 2 (2q32) where the IDDM7 gene has previously been mapped, implying its involvement in diabetes. To identify mutations in the NeuroD/BETA2 gene that may predispose patients to develop diabetes, we studied the gene in 50 Japanese subjects with diabetes (4 with type 1 and 46 with type 2) by the polymerase chain reaction (PCR) followed by single-strand conformation polymorphism and sequencing analyses. Further analysis was performed in 392 Japanese subjects (60 with type 1 and 158 with type 2 diabetes and 174 healthy control subjects) by mismatch PCR restriction fragment length polymorphism. We found a DNA polymorphism of the NeuroD/BETA2 gene. A nucleotide G-to-A transition results in the substitution of alanine to threonine at codon 45 (Ala45Thr). The frequencies of heterozygotes for the Ala45Thr variant were 9.8% in the control subjects, 9.5% in the patients with type 2 diabetes, and 25.0% in the patients with type 1 diabetes, a significant difference (P = 0.006). Because the variant of the NeuroD/BETA2 gene (Ala45Thr) is associated with type 1 but not type 2 diabetes, it may be implicated in the loss of pancreatic beta-cells in type 1 diabetes.


Assuntos
Proteínas de Ligação a DNA/genética , Diabetes Mellitus Tipo 1/genética , Polimorfismo Genético/genética , Transativadores/genética , Adulto , Sequência de Aminoácidos/genética , Povo Asiático/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos , DNA/genética , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Japão , Masculino
8.
J Mol Biol ; 201(2): 443-50, 1988 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-3047403

RESUMO

We have isolated the renin gene from a Sprague-Dawley rat genomic library and determined its complete nucleotide sequence. The single rat renin gene is approximately 11,000 bases in length and consists of nine exons and eight introns. The amino acid sequence predicted from the genomic sequence indicates that the rat renin precursor consists of 402 amino acid residues, and shows 85%, 82% and 68% homology to the mouse Ren-1 and Ren-2, and human renins, respectively. The canonical promoter "TATA" boxes, TATAAA and TAATAA, are found 27 and 57 base-pairs upstream from the putative cap site, respectively. Several attractive regulatory sequences analogous to glucocorticoid, estrogen receptor-binding sites, cAMP-responsive element and SV40 enhancer core sequences were noted in the 5'-flanking region of the gene. In the first intron, segments with an average size of 38 base-pairs containing a NcoI site are present at 46 tandem repeats within 1710 base-pairs. A "CA" element consisting of (CA)27 was identified in intron 3. Furthermore, intron 8 contains a sequence that shows about 93% homology to that of the neuronal identifier sequence.


Assuntos
Genes , Renina/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA , Dados de Sequência Molecular , Ratos , Ratos Endogâmicos
9.
J Invest Dermatol ; 113(2): 251-7, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10469312

RESUMO

We report here a patient (Ops1) with clinical photosensitivity, including pigmented or depigmented macules and patches, and multiple skin neoplasias (malignant melanomas, basal cell carcinomas, and squamous cell carcinomas in situ) in sun-exposed areas. These clinical features are reminiscent of xeroderma pigmentosum. As cells from Ops1 showed normal levels in DNA repair synthesis in vivo (unscheduled DNA synthesis and recovery of RNA synthesis after ultraviolet irradiation), we performed a postreplication repair assay and recovery of replicative DNA synthesis after ultraviolet irradiation to investigate if Ops1 cells belonged to a xeroderma pigmentosum variant pattern. Ops1 cells were normal, but there was an incomplete pattern repair in (6-4) photoproducts in contrast to a normal pattern repair in cis-syn cyclobutane pyrimidine dimers by repair kinetics using the enzyme-linked immunosorbent assay. Moreover, Ops1 cells were defective in a damage-specific DNA binding protein and carried a non-sense mutation in the DDB2 gene. These results suggest that (i) the DDB2 gene is somewhat related to skin carcinogenesis, photoaging skin, and the removal of (6-4) photoproducts; (ii) although it is believed that cyclobutane pyrimidine dimers are the principal mutagenic lesion and (6-4) photoproducts are less likely to contribute to ultraviolet-induced mutations in mammals, Ops1 is one of the ultraviolet-induced mutagenic models induced by (6-4) photoproducts.


Assuntos
Proteínas de Ligação a DNA/genética , Xeroderma Pigmentoso/genética , Cafeína/farmacologia , Códon sem Sentido , Reparo do DNA/genética , Replicação do DNA , Feminino , Mutação da Fase de Leitura , Humanos , Cinética , Pessoa de Meia-Idade , Fenótipo , Transtornos de Fotossensibilidade/tratamento farmacológico , Dímeros de Pirimidina/genética , Dímeros de Pirimidina/metabolismo , Raios Ultravioleta
10.
Hypertension ; 6(2 Pt 2): I95-100, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6202637

RESUMO

The primary structure of human renin precursor was deduced from its complementary DNA (cDNA) sequence. The predicted sequence consists of 406 amino acids with a pre- and a prosegment carrying 20 and 46 amino acids, respectively. A high degree of sequence homology, especially in the catalytically important region, was found upon comparison of the mouse and human renins. An overall homology, including presequence between the two renins, is 68.7%. Close similarities were also observed in the primary structure of renins and other aspartyl proteinases with defined three-dimensional structures, suggesting a tertiary structure for renin that is similar to the other enzymes. A bilobal model of the tertiary structure of human renin with two approximately equal domains separated by a cleft was constructed using the homology of amino acid sequence of renins and other aspartyl proteinases. These results indicate that human kidney renin is homologous with mouse submandibular renin in primary and tertiary structures, proteolytic processing, and catalytic apparatus with small differences. The major structural difference distinguishing the two renins was the presence of the two possible glycosylation sites in human kidney renin, which was not observed in mouse submandibular gland renin.


Assuntos
Clonagem Molecular , DNA/análise , Renina/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Humanos , Rim/enzimologia , Substâncias Macromoleculares , Camundongos , Modelos Moleculares , Pepsina A/genética , Poli A/genética , Conformação Proteica , RNA/genética , RNA Mensageiro , Especificidade da Espécie , Suínos
11.
Gene ; 90(2): 249-54, 1990 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-2119324

RESUMO

The primary structure of bovine thymus poly(ADP-ribose) synthetase, as deduced from the nucleotide sequence of a cloned cDNA, indicated that this enzyme is composed of 1016 amino acids (aa) with an Mr of 113,481. An abundance of Lys and Arg residues was in accord with the known basic nature of this protein. A comparison with reported sequences of human counterparts revealed: (1) three functional domains separated by partial proteolysis, i.e., DNA-binding (N-terminal), automodification (central), and NAD-binding (C-terminal) domains, have, in this order, increasing degrees of homology; (2) the DNA-binding domain is composed of two distinct regions: one, less conserved, containing zinc-binding fingers and the other, more conserved, containing helix-turn-helix motifs; (3) all Glu and Asp residues in the automodification domain are conserved; and (4) a 78-aa stretch encompassing the nucleotide-binding fold in the NAD-binding domain is completely conserved. These results are compatible with specific features of each domain, i.e., complex DNA-enzyme interactions, multiple automodification at acidic aa residues, and a stringent specificity for the substrate, NAD.


Assuntos
Evolução Biológica , DNA/biossíntese , Poli(ADP-Ribose) Polimerases/genética , Timo/enzimologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Bovinos , Clonagem Molecular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Biblioteca Genômica , Humanos , Recém-Nascido , Metaloproteínas/genética , Metaloproteínas/metabolismo , Dados de Sequência Molecular , NAD/metabolismo , Poli(ADP-Ribose) Polimerases/biossíntese , Mapeamento por Restrição , Homologia de Sequência do Ácido Nucleico , Relação Estrutura-Atividade , Zinco/metabolismo
12.
AIDS Res Hum Retroviruses ; 17(6): 569-75, 2001 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-11350671

RESUMO

We collected blood samples from 70 HIV-1-infected pregnant women and 76 babies born to HIV-1-infected women in Japan, from 1989 to 1999. To analyze the genetic diversity of HIV-1 among mothers and children, we sequenced the C2-V3 regions of HIV-1 gp120. Phylogenetic tree analysis of these regions revealed that multiple HIV-1 subtypes, A, B, D, E, and G, were circulating among mothers and children in Japan. Thus, the genetic heterogeneity of HIV-1 among mothers and children in Japan is steadily increasing, although the number of cases remains small. Perhaps the longest term survivor, an 11-year-old child with a vertical HIV-1 subtype G infection in Japan, is one of our subjects.


Assuntos
Heterogeneidade Genética , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/virologia , HIV-1/genética , Fragmentos de Peptídeos/genética , Complicações Infecciosas na Gravidez/virologia , Sequência de Aminoácidos , Sequência de Bases , Criança , DNA Viral , Feminino , Infecções por HIV/sangue , HIV-1/classificação , Humanos , Recém-Nascido , Japão , Masculino , Dados de Sequência Molecular , Mães , Filogenia , Gravidez , Complicações Infecciosas na Gravidez/sangue
13.
Brain Res Mol Brain Res ; 77(1): 37-46, 2000 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-10814830

RESUMO

We have isolated and characterized the mouse gene for NDRF (neuroD-related factor), a basic helix-loop-helix transcription factor implicated in neural development and function. The gene consists of two exons and the entire protein-coding sequence is encoded by a single downstream exon. RNA blot hybridization analysis revealed that NDRF mRNA was detectable at day 4 and increased to a maximal level at day 6 during neuronal differentiation of P19 cells. To elucidate the regulatory mechanisms of the NDRF gene expression during this process, a construct containing the genomic DNA fragment of about 3 kbp upstream of the NDRF coding region fused to a luciferase reporter gene was transfected into P19 cells, and stable transformants were pooled for assay of luciferase activities. When the stable transformants were treated with RA and aggregated to induce neuronal differentiation, the luciferase activities were induced in a temporal expression pattern similar to that of the endogenous NDRF mRNA. Further experiments using a series of deletion and mutation constructs indicated that the 376-bp sequence in the 5'-flanking region of the NDRF gene is important, and that one of the E boxes in the sequence plays a critical role in the regulated expression. Transient transfection experiments also showed that the same E box is required for the transactivation of the NDRF promoter activity by neurogenin 1. These results suggest that the NDRF gene expression is regulated by an E box-binding factor during neuronal differentiation of P19 cells.


Assuntos
Diferenciação Celular/genética , Regulação da Expressão Gênica , Neurônios/metabolismo , Neuropeptídeos/genética , Animais , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Carcinoma Embrionário , Éxons , Biblioteca Gênica , Genes Reporter , Sequências Hélice-Alça-Hélice , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , RNA Mensageiro/genética , Proteínas Recombinantes/biossíntese , Transcrição Gênica , Transfecção , Células Tumorais Cultivadas
14.
Brain Res Mol Brain Res ; 74(1-2): 126-34, 1999 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-10640683

RESUMO

By the yeast two-hybrid screening of a human brain cDNA library with the amino-terminal regulatory region of PKN as a bait, a clone encoding a neuron-specific basic Helix-Loop-Helix (bHLH) transcription factor, NDRF/NeuroD2 was isolated. NDRF/NeuroD2 was co-precipitated with PKN from the lysate of COS-7 cells transfected with both expression constructs for NDRF/NeuroD2 and PKN. In vitro binding studies using the deletion mutants of NDRF/NeuroD2 synthesized in a rabbit reticulocyte lysate indicated that the internal region containing the bHLH domain of NDRF/NeuroD2 was necessary and sufficient for the interaction with PKN. In addition, recombinant NDRF/NeuroD2 purified from Escherichia coli could bind PKN, suggesting the direct interaction between NDRF/NeuroD2 and PKN. Transient transfection assays using P19 cells revealed that expression of NDRF/NeuroD2 increased the transactivation of the rat insulin promoter element 3 (RIPE3) enhancer up to approximately 12-fold and that co-expression of catalytically active form of PKN, but not kinase-deficient derivative, resulted in a further threefold increase of NDRF/NeuroD2-mediated transcription. These findings suggest that PKN may contribute to transcriptional responses through the post-translational modification of the NDRF/NeuroD2-dependent transcriptional machinery.


Assuntos
Sequências Hélice-Alça-Hélice , Neuropeptídeos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Fatores de Transcrição/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Células COS , Catálise , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Mutação , Neuropeptídeos/genética , Neuropeptídeos/isolamento & purificação , Ligação Proteica , Proteína Quinase C , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Coelhos , Ratos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/isolamento & purificação , Transcrição Gênica , Células Tumorais Cultivadas , Técnicas do Sistema de Duplo-Híbrido
15.
J Biochem ; 108(2): 200-6, 1990 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2229022

RESUMO

The ISK protein is a novel, probably epithelial potassium channel which differs from conventional potassium channels in its structure, electrophysiology, and tissue distribution. In this investigation, we isolated and analyzed genomic and cDNA clones coding for the rat ISK protein to characterize the structural organization and expression pattern of the ISK protein gene. This analysis, together with primer extension and RNase protection experiments, indicated that the ISK protein mRNA is initiated from two different upstream exons and then encoded by an uninterrupted downstream exon covering the protein-coding and the 3'-untranslated regions of the mRNA. RNA blot hybridization analysis showed additional generation of several large species of mRNAs which result from inclusion of a part of the intron sequence and the 3'-flanking region of the ISK protein gene. Thus, the single ISK protein gene is involved in the production of multiple species of mRNAs through a variety of cellular mechanisms including transcription initiation at different sites, alternative RNA splicing, and polyadenylation at different sites. The heterogeneity of the ISK protein mRNAs may be associated with the emergence of the functional and regulatory diversity observed for potassium ion permeation in epithelial cells.


Assuntos
Proteínas de Membrana/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/genética , RNA Mensageiro/genética , Animais , Sequência de Bases , DNA/química , DNA/genética , Eletroforese em Gel de Poliacrilamida , Immunoblotting , Proteínas de Membrana/química , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Canais de Potássio/química , RNA Mensageiro/biossíntese , Ratos , Ribonucleases , Glândula Submandibular/química
16.
Surgery ; 115(4): 516-20, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8165544

RESUMO

BACKGROUND: The clinicopathologic features of advanced gastric cancer have been analyzed in young or older patients; however, with regard to early gastric cancer, it remains unknown whether the features differ between young and older patients. Reported here is an analysis of clinicopathologic characteristics in young and in older patients. METHODS: This study is based on a retrospective review of 25 patients less than 40 years of age with early gastric cancer and of 64 patients more than 70 years of age with early gastric cancer. These patients were treated from 1977 through 1991. RESULTS: Because in the older group there were early double cancers in three patients and quadruple cancers in one, 70 early cancers were present in these 64 patients. Although the young group included a larger percentage of women, the ratio of mucosal cancer to submucosal and the incidence of nodal metastasis did not differ between the groups. Poorly differentiated adenocarcinoma was detected in 13 (52%) of the 25 younger patients, whereas in the older group it was present in 6 cancers (8.6%) alone. The number of metastatic nodes and extent of nodal metastasis were more severe in the young group, but survival rates did not differ between the groups. The depressed type of lesion was present in all patients in the young group, whereas it was only 41 of 70 cancers in the older group. CONCLUSIONS: These findings suggest that early gastric cancer in young adults has aggressive features as based on the histologic pattern, in particular with cancer invasion into the submucosal layer. For these patients nodal extirpation and postoperative adjuvant chemotherapy should be performed in an attempt to prevent lymphatic or hematogenic metastases.


Assuntos
Neoplasias Gástricas/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Análise Multivariada , Invasividade Neoplásica , Neoplasias Gástricas/mortalidade , Análise de Sobrevida
17.
Cancer Treat Res ; 81: 169-76, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8834583

RESUMO

In an attempt to prevent postoperative intraperitoneal recurrence in patients with advanced gastric cancer and consequently to improve survival time, we treated patients with intraperitoneal hyperthermic perfusion (IPHP) using mitomycin C (MMC) combined with surgery. There were 60 patients with advanced gastric cancer who were treated with IPHP (long-term study) group, and the survival of this group was compared with the outcome in 52 patients with advanced gastric cancer treated with surgery alone (control group). To avoid or diminish side effects derived from scald injury of the peritoneal surface due to IPHP, 50 mg/kg of cimetidine was given intravenously just before administration of IPHP. For prophylaxis of anastomotic leakage, duodenostomy using a Foley catheter was performed. The 60 patients who were treated with IPHP lived longer than the 52 patients in the control group (p = 0.000610). The 3 year survival rate was 45 percent for the former compared with 16 percent for the latter. The intravenous administration of cimetidine just prior to IPHP protected the peritoneoserosal surface from scald injury, even though the heated perfusate exposure was at 44.3-46.3 degrees C for 2 hours. Because the intraabdominal pressure within the duodenum and jejunum was decompressed postoperatively through catheter duodenostomy and the peritoneoserosal surface was protected from scald injury caused by IPHP, anastomotic leakage in the study group was nil. Therefore, IPHP treatment plus aggressive surgery combined with pre-IPHP cimetidine administration are indicated for patients with advanced gastric cancer. The side effects of IPHP and postoperative morbidity can thus be reduced and a favorable outcome obtained.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional , Hipertermia Induzida , Mitomicina/administração & dosagem , Neoplasias Gástricas/terapia , Adulto , Idoso , Terapia Combinada , Duodenostomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/efeitos adversos , Proteínas/análise , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida
18.
Naunyn Schmiedebergs Arch Pharmacol ; 338(3): 327-31, 1988 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3194040

RESUMO

Angiotensin II has numerous biological effects in a hitherto unsuspected variety of tissues. The generation of angiotensin in tissue requires the local presence of its high molecular weight precursor angiotensinogen and is best tested by investigating angiotensinogen gene expression. A quantitative solution hybridization assay for rapid and sensitive measurement of angiotensinogen mRNA was therefore established to study the extrahepatic expression of the angiotensinogen gene. We used a 714 bases BamHI angiotensinogen cDNA fragment cloned into vector pSPT18 and developed a sensitive and rapid assay with a detection limit of 0.5 pg RNA. Quantification of angiotensinogen mRNA from male Sprague-Dawley rats resulted in the following tissue levels (n = 10 for all tissues, except pituitary where n = 5), was expressed as fg mRNA per microgram total RNA, in descending order: liver (9950), hypothalamus (6050), midbrain (4450), brainstem (3950), total brain (2325), aorta (625), kidney (338), adrenal gland (170), and heart atrium (140). The high sensitivity of the assay in addition also allowed for the first time measurement of angiotensinogen mRNA in the low gene expression tissues pituitary (70), heart ventricle (30), and testis (30). This assay will allow detailed studies on the regulation of tissue angiotensinogen and the pathophysiological role of the tissue renin angiotensin systems.


Assuntos
Angiotensinogênio/genética , Aorta/metabolismo , Encéfalo/metabolismo , Rim/metabolismo , RNA Mensageiro/análise , Glândulas Suprarrenais/metabolismo , Angiotensinogênio/biossíntese , Animais , Northern Blotting , Regulação da Expressão Gênica , Masculino , Miocárdio/metabolismo , Hibridização de Ácido Nucleico , Hipófise/metabolismo , Ratos , Ratos Endogâmicos , Testículo/metabolismo
19.
Anticancer Res ; 17(1B): 689-94, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9066603

RESUMO

Although curative surgery is desirable in patients with gastric cancer, tumors adjacent to the esophagogastric and/or gastroduodenal junctions present surgeons with some difficulty in estimating whether or not the lesion has infiltrated beyond the surgical margin. We report herein a retrospective analysis with respect to the clinicopathologic features of the primary lesion and margin positivity for tumor cells. Between 1982 and 1993, 861 gastric cancer patients underwent gastrectomy in our clinics. Of these, 340 had early cancer and the remaining 521 advanced cancer. Cancer infiltration at the surgical margin was determined macroscopically in the fresh resected specimen; re-resection was carried out immediately for positive cases and, subsequently, a rapid histologic examination at the newly-incised edge was carried out intraoperatively. Of the 340 patients with early cancer. 15 (4.4%) had a positive surgical margin which was directly resected successfully. Of the 521 patients with advanced cancer, 73 (14%) had a positive surgical margin and 28 of them had a microscopically negative surgical edge after re-resection; however, 8 others had a positive result at the newly-excised edge after re-resection, and the remaining 37 could not undergo re-resection because of their poor general condition and/or because the tumor had spread to other sites. The positive rate for the final surgical margin was 5.2% (45/861 patients). All of the patients with a positive margin and early cancer had a superficial or excavative type lesion, and 76.7% (56/73 patients) of those with advanced cancer had Borrmann's III or IV type lesion. These findings suggest that in such patients with a tumor adjacent to the esophagogastric and/or gastroduodenal junctions, particular attention should be paid to Borrmann's III or IV lesions in advanced cancer and to superficial or excavated type lesions in early cancer in order to reduce the frequency of positive surgical margin. Additionally, an immediate histologic examination after re-resection is extremely important.


Assuntos
Adenocarcinoma/patologia , Neoplasias Gástricas/patologia , Estômago/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Reoperação , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
20.
Anticancer Res ; 14(3B): 1405-8, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8067713

RESUMO

From 1980 to 1991, Japanese patients aged over 49 years with gastric cancer underwent gastric resection in our hospitals. For various studies, two groups, 35 patients over 79 years (advanced age group) and 884 patients aged 50-79 years (mature age group) were prepared. A retrospective study was done with special reference to clinicopathological features and the prognosis. There were no differences in clinicopathological characteristics between the two groups, except for operative procedures and the size, histology and vascular involvement of the primary tumor. The survival rate for the advanced age group was higher than that for the mature age group, with a significant difference at p = 0.00556. However, the postoperative morbidity rate was 48.6% in the advanced age group compared with 5.1% in the mature age group. The most frequent complications were respiratory-related, that is, atelectasis, pneumonia or aspiration pneumonia. Based on these data, advanced age is not a contraindication for resection of a gastric cancer, but patients with serious pulmonary and/or cardiac diseases would not be candidates.


Assuntos
Neoplasias Gástricas/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
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