Assuntos
Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVE: Gene expression is related to the pathogenesis of periodontitis and plays a crucial role in local tissue destruction and disease susceptibility. The aims of the present study were to identify the expression of specific genes and biological pathways in periodontitis-affected gingival tissue using microarray and quantitative real-time RT-PCR analyses. MATERIAL AND METHODS: Healthy and periodontitis-affected gingival tissues were taken from three patients with severe chronic periodontitis. Total RNAs from six gingival tissue samples were used for microarray analyses. Data-mining analyses, such as comparisons, gene ontology and pathway analyses, were performed and biological pathways with a significant role in periodontitis were identified. In addition, quantitative real-time RT-PCR analysis was performed on samples obtained from 14 patients with chronic periodontitis and from 14 healthy individuals in order to confirm the results of the pathway analysis. RESULTS: Comparison analyses found 15 up-regulated and 13 down-regulated genes (all of which showed a change of more than twofold in expression levels) in periodontitis-affected gingival tissues. Pathway analysis identified 15 up-regulated biological pathways, including leukocyte transendothelial migration, and five down-regulated pathways, including cell communication. Quantitative real-time RT-PCR verified that five genes in the leukocyte transendothelial migration pathway were significantly up-regulated, and four genes in the cell communication pathway were significantly down-regulated, which was consistent with pathway analysis. CONCLUSION: We identified up-regulated genes (ITGB-2, MMP-2, CXCL-12, CXCR-4 and Rac-2) and down-regulated genes (connexin, DSG-1, DSC-1 and nestin) in periodontitis-affected gingival tissues; these genes may be related to the stimulation of leukocyte transendothelial migration and to the the impairment of cell-to-cell communication in periodontitis.
Assuntos
Periodontite Crônica/imunologia , Expressão Gênica/genética , Gengiva/imunologia , Leucócitos/imunologia , Migração Transendotelial e Transepitelial/imunologia , Adulto , Antígenos CD18/genética , Comunicação Celular/imunologia , Quimiocina CXCL12/genética , Quimiotaxia de Leucócito/imunologia , Periodontite Crônica/patologia , Conexinas/genética , Desmocolinas/genética , Desmogleína 1/genética , Regulação para Baixo/genética , Células Endoteliais/imunologia , Células Endoteliais/patologia , Feminino , Regulação da Expressão Gênica/genética , Gengiva/patologia , Humanos , Proteínas de Filamentos Intermediários/genética , Masculino , Metaloproteinase 2 da Matriz/genética , Análise em Microsséries , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Nestina , RNA/genética , Receptores CXCR4/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima/genética , Proteínas rac de Ligação ao GTP/genética , Proteína RAC2 de Ligação ao GTPRESUMO
The contribution of radiology to brain tumor research is unknown. We sought to determine how the proportion of neuro-oncologic publications generated by radiology departments has changed and if there is an association with NIH funding levels. Therefore we searched The National Library of Medicine's PubMed database for all articles published on brain neoplasms from 1996 to 2007. Country and department of origin and NIH grant support were noted for each article. Approximately 10% of brain tumor publications originated from radiology departments, ranking third among medical specialties. NIH funding for this research grew from less than 20% in 1996 to more than 50% in 2007. Overall NIH funding levels rose approximately 2.5 fold during this time. The U.S. was the dominant producer of brain tumor publications, and the gap between the U.S. and the rest of the world grew over the study period. Thus a substantial proportion of brain tumor publications originate from radiology departments, and the percentage of this research that is funded by the NIH has grown significantly during a period of increasing NIH budgets.
Assuntos
Pesquisa Biomédica/economia , Pesquisa Biomédica/tendências , Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , National Institutes of Health (U.S.) , Apoio à Pesquisa como Assunto/economia , Apoio à Pesquisa como Assunto/tendências , American Recovery and Reinvestment Act/economia , American Recovery and Reinvestment Act/tendências , Neoplasias Encefálicas/mortalidade , Orçamentos/tendências , Causas de Morte , Comparação Transcultural , Estudos Transversais , Financiamento Governamental/economia , Financiamento Governamental/tendências , Previsões , Glioblastoma/mortalidade , Humanos , Editoração/tendências , Radiografia , Taxa de Sobrevida , Estados UnidosRESUMO
Alpha2 integrin on fibroblasts is reported to play an important role in the induction of drug-induced gingival overgrowth, which is characterized by excessive accumulation of type I collagen in gingival connective tissue. Silent polymorphism 807 T/C within the alpha2 integrin gene is associated with high/low alpha2 integrin expression. The aim of this study was to test the hypothesis that expression of alpha2 integrin 807 T/C polymorphism correlates with drug-induced gingival overgrowth. A case-control study comparing 136 subjects taking calcium channel blockers (72 with vs. 64 without drug-induced gingival overgrowth) demonstrated that the frequency of the +807 C allele was significantly higher in the case group than in the controls (odds ratio, 3.61; 95% confidence interval, 2.14 - 6.10; P < 0.05). The present findings suggest that the alpha2 +807 C allele is one of the genetic risk factors for drug-induced gingival overgrowth.
Assuntos
Crescimento Excessivo da Gengiva/induzido quimicamente , Integrina alfa2/genética , Polimorfismo Genético/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Estudos de Casos e Controles , Criança , Citosina , Feminino , Fibroblastos/imunologia , Frequência do Gene , Crescimento Excessivo da Gengiva/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , TiminaRESUMO
Spontaneous hemorrhage is a rare complication of lupus. We describe a 36-year old female with lupus who suffered spontaneous, nontraumatic hemorrhage from branches of the splenic artery with massive blood loss while being treated for a lupus flare. We compare this to the two other reported cases of similar lupus-associated splenic artery hemorrhage documented in the literature, both of which had significant pre-existing hemorrhagic risk factors. Spontaneous, nontraumatic hemorrhage of the splenic artery in the absence of risk factors, and in a patient with secondary antiphospholipid syndrome, has been previously undescribed in lupus.
Assuntos
Síndrome Antifosfolipídica/etiologia , Hemorragia/etiologia , Lúpus Eritematoso Sistêmico/complicações , Esplenopatias/etiologia , Adulto , Feminino , Hemorragia/diagnóstico , Humanos , Esplenopatias/diagnósticoRESUMO
A battery of mouse monoclonal antibodies (mAbs) reactive with porcine peripheral blood (PB) leukocytes was generated. Among the mAbs, 6F10 was found to react probably with cluster of differentiation (CD)8 alpha-chain, while 7G3 and 3E12 were found to recognize gammadelta T-cells, as revealed by two-color flow cytometric and immunoprecipitation studies. 7G3 was shown to react with the constant (C) region of the T-cell receptor (TCR) delta-chain by the following facts: (1) 7G3 immunoprecipitated full-length TCR delta-chain protein fused with glutathione S-transferase (GST) produced by Esherichia coli and (2) 7G3 reacted with TCR delta-chain expressing Cos-7 cells transfected with either full-length or N-terminal deleted mutant cDNA, but did not react with Cos-7 cells transfected with C-terminal deleted mutant TCR delta-chain cDNA. All three mAbs produced high-quality immunostaining results on frozen sections, revealing a distinct distribution of gammadelta T-cells and CD8(+) cells. This report precisely characterizes mAbs against porcine TCR for the first time, facilitating molecular biological investigations of the porcine immune system.
Assuntos
Anticorpos Monoclonais/imunologia , Linfócitos/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Suínos/imunologia , Sequência de Aminoácidos , Animais , Citometria de Fluxo , Imuno-Histoquímica , Imunoprecipitação , Dados de Sequência Molecular , Receptores de Antígenos de Linfócitos T gama-delta/análise , Receptores de Antígenos de Linfócitos T gama-delta/genéticaRESUMO
OBJECTIVE: In an attempt to clarify the megakaryo-specific regulatory mechanism of GPV gene transcription, we characterized the 5'-flanking region of the mouse GPV gene. MATERIALS AND METHODS: The promotor activity of a -481/+22 5'-fragment of the mouse GPV gene was examined in normal mouse bone marrow cells (BMC) and various human cell lines using two distinct reporter gene assay systems, luciferase and green fluorescence protein (GFP). RESULTS: When a DNA construct consisting of this fragment and a GFP reporter gene were transiently expressed in thrombopoietin-supported mouse BMC culture, GFP was identified only in megakaryocytes. The same construct expressed high levels of GFP in the human megakaryocytic Dami line. When assessed by dual luciferase assay, the full -481/+22 fragment could drive variable promoter activity in human as well as mouse megakaryocytic lines but did not work in non-megakaryocytic cells. Sufficient transcriptional activation of this fragment was restricted to the cells expressing apparent GPV mRNA. A deletion and point mutation study indicated that GATA and Ets motifs, typical cis-acting elements for platelet-specific genes, located of -75 and -46, respectively, were essential for promoter function. CONCLUSION: The GPV promoter has the general characteristics found in platelet-specific genes, and the mechanism for megakaryocyte-specific, maturation-dependent regulation of GPV gene transcription is highly conserved between mouse and human. Analysis of GPV transcription mechanism utilizing human lines as well as BMC should provide new information on the final maturational process of megakaryocytes.
Assuntos
Megacariócitos/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Regiões Promotoras Genéticas , Animais , Sequência Consenso , Proteínas de Ligação a DNA/genética , Fatores de Ligação de DNA Eritroide Específicos , Feminino , Humanos , Camundongos , Proteínas Nucleares/genética , Complexo Glicoproteico GPIb-IX de Plaquetas/fisiologia , Proteína Proto-Oncogênica c-ets-2 , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-ets , Proteínas Repressoras/genética , Transativadores/genética , Fatores de Transcrição/genética , Transcrição Gênica , Transfecção , Dedos de Zinco/genéticaRESUMO
The mouse- and rat-platelet-specific hamster monoclonal antibody (MAb) 1C2, previously found to react with a thrombin-sensitive 74-kD glycoprotein, was now shown to recognize platelet glycoprotein V (GPV, CD42d). 1C2 reacted with NIH-3T3 cells in which recombinant mouse or rat GPV was expressed. Both 1C2 and 4A5, another mouse-platelet-specific rat MAb, immunoprecipitated GVP, although they recognized different epitopes. Side-by-side comparison confirmed that 1C2 as well as RPM.9, a MAb against rat GPV, recognized the same rat platelet molecule. In a mouse bone marrow culture, 1C2+ megakaryocytes emerged from CD41 (GPIIb)+1C2- megakaryocytes. Because 1C2+ megakaryocytes exhibited higher DNA ploidy distribution than CD41+ cells, GPV likely appears in the late stage of megakaryocyte maturation. This study established 1C2 as a MAb against mouse and rat GPV, namely CD42d, and as useful tool to study rodent megakaryopoiesis.
Assuntos
Anticorpos Monoclonais/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas/imunologia , Animais , Especificidade de Anticorpos , Biomarcadores/análise , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Técnicas de Cultura de Células , Diferenciação Celular/imunologia , Cricetinae , Mapeamento de Epitopos , Megacariócitos/citologia , Megacariócitos/imunologia , Camundongos , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , RatosRESUMO
We investigated the effect of thiamphenicol plus lincomycin (TP + LCM) and thiamphenicol plus tylosin (TP + TS) combinations using checker board method on the growth of Pasteurella (P.) multocida, P. haemolytica and Mycoplasma (M.) bovis by calculating the fractional inhibitory concentration index (FIC index). The results showed that the FIC indexes of the TP + LCM combination for P. multocida, P. haemolytica and M. bovis were 0.36 +/- 0.10, 0.72 +/- 0.09 and 0.81 +/- 0.18, respectively. The FIC indexes of the TP + TS combination for P. multocida, P. haemolytica, and M. bovis were 0.79 +/- 0.20, 0.66 +/- 0.11 and 0.32 +/- 0.14, respectively. Thus, these combinations are assumed to have a more synergistic or additive effect on bacteria growth than a single antimicrobial agent.
Assuntos
Antibacterianos/farmacologia , Doenças dos Bovinos , Quimioterapia Combinada/farmacologia , Infecções por Mycoplasma/veterinária , Mycoplasma/efeitos dos fármacos , Mucosa Nasal/microbiologia , Infecções por Pasteurella/veterinária , Infecções Respiratórias/veterinária , Animais , Bovinos , Sinergismo Farmacológico , Lincomicina/farmacologia , Mannheimia haemolytica/efeitos dos fármacos , Mannheimia haemolytica/crescimento & desenvolvimento , Mannheimia haemolytica/isolamento & purificação , Testes de Sensibilidade Microbiana , Mycoplasma/crescimento & desenvolvimento , Mycoplasma/isolamento & purificação , Infecções por Mycoplasma/microbiologia , Infecções por Pasteurella/microbiologia , Pasteurella multocida/efeitos dos fármacos , Pasteurella multocida/crescimento & desenvolvimento , Pasteurella multocida/isolamento & purificação , Infecções Respiratórias/microbiologia , Tianfenicol/farmacologia , Tilosina/farmacologiaRESUMO
To characterize intracellular Ca2+ stores, the Ca(2+)-releasing effects of caffeine, carbachol and inositol 1,4,5-trisphosphate (IP3) were compared by measuring the drug-induced tension development in beta-escin-skinned longitudinal smooth muscle of guinea-pig ileum. Caffeine (20 mM), carbachol (10 or 100 microM) or IP3 (40 microM), applied after loading Ca2+ within intracellular stores, produced a transient rise in tension in a Ca(2+)-free solution. This change in tension occurred in response to release of Ca2+ from the stores. The effect of either caffeine or carbachol was markedly reduced or abolished after preceding application of the other drug. IP3 was without effect when applied subsequently to caffeine. The effects of carbachol and IP3 were abolished after combined treatment with ryanodine (30 microM) and caffeine (20 mM) which causes functional removal of caffeine-releasable Ca2+ stores, but not after combined treatment with ryanodine (30 microM) and carbachol (10 microM). The results suggest that caffeine, carbachol and IP3 all act on common Ca2+ stores to release Ca2+.
Assuntos
Cafeína/farmacologia , Cálcio/metabolismo , Carbacol/farmacologia , Músculo Liso/efeitos dos fármacos , Animais , Escina/farmacologia , Cobaias , Íleo/efeitos dos fármacos , Íleo/metabolismo , Técnicas In Vitro , Inositol 1,4,5-Trifosfato/metabolismo , Masculino , Músculo Liso/metabolismo , Rianodina/farmacologiaRESUMO
The effects of exoenzyme C3 of Clostridium botulinum on Ca(2+)- and drug-induced tension developments were investigated in beta-escin skinned smooth muscle of guinea pig ileum to test the involvement of a small G-protein in the regulation of myofilament Ca2+ sensitivity. C3 is known to ADP-ribosylate the rho p21 family of small G-proteins. Treatment with C3 (0.35 microgram/ml, for 30 min) shifted the pCa-tension curve rightward along the Ca2+ concentration axis, indicating a decrease in Ca2+ sensitivity of the contractile elements. The inhibitory effect of C3 was not preserved after treatment with GDP beta S (1 mM), an antagonist of GTP for the binding to G-proteins. Stimulation of muscarinic receptors with carbachol (CCh, 100 microM) shifted the pCa-tension curve leftward, indicating Ca2+ sensitization of tension development. The Ca(2+)-sensitizing effect of CCh was not observed after C3 treatment. When GTP gamma S (10 microM), an activator of G-proteins, was applied at a plateau of tension development produced by a moderate concentration of Ca2+, further increase in tension was elicited and the effect of GTP gamma S was inhibited by C3 treatment. The results suggest the possible involvement of a rho p21-like small G-protein in the regulation of Ca2+ sensitivity of smooth muscle myofilaments.
Assuntos
Cálcio/metabolismo , Complemento C3/farmacologia , Proteínas de Ligação ao GTP/fisiologia , Músculo Liso/fisiologia , Animais , Carbacol , Guanosina Trifosfato , Cobaias , Íleo/fisiologia , Masculino , Contração MuscularRESUMO
The effects of trimebutine on Ca2+ release and modulation of Ca2+ sensitivity of contractile elements induced by carbachol (CCh) were investigated using a tension measuring method in beta-escin-treated skinned smooth muscle of the longitudinal muscle layer of guinea pig ileum. Trimebutine (10-100 microM) concentration-dependently inhibited tension development brought about by Ca2+ release from intracellular stores induced by CCh (10 microM), but did not affect those induced by inositol 1,4,5-trisphosphate (IP3, 25 microM) or caffeine (5 mM). The inhibitory effect was reversible. Trimebutine (100 microM) neither altered the Ca2+ sensitivity of the contractile elements nor affected the effects of GTP gamma S (50 microM) and CCh (100 microM) in potentiating Ca2+ sensitivity of the contractile elements after the Ca2+ storage function had been eliminated by A23187. These results suggest that trimebutine inhibits CCh-induced Ca2+ release by acting at some point during the coupling of muscarinic receptors through a G-protein to phospholipase C and thus reducing the accumulation of IP3.
Assuntos
Cálcio/metabolismo , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Trimebutina/farmacologia , Animais , Cafeína/farmacologia , Calcimicina/farmacologia , Cálcio/farmacologia , Carbacol/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Eletrofisiologia , Escina/farmacologia , Proteínas de Ligação ao GTP/metabolismo , Guanosina 5'-O-(3-Tiotrifosfato)/farmacologia , Cobaias , Íleo/efeitos dos fármacos , Técnicas In Vitro , Inositol 1,4,5-Trifosfato/farmacologia , Masculino , Músculo Liso/metabolismo , Receptores Muscarínicos/efeitos dos fármacos , Receptores Muscarínicos/metabolismo , Fosfolipases Tipo C/metabolismoRESUMO
To characterize the calcium (Ca2+)-releasing effects of histamine and GTP gamma S, the drug-induced tension developments were measured in beta-escin-treated skinned longitudinal smooth muscle of guinea pig ileum. Intracellular Ca2+ stores were loaded with Ca2+ by incubating the muscle for 10 min in a Ca(2+)-containing solution. Histamine (10-100 microM), applied after Ca(2+)-loading, produced a transient rise in tension. The effect of histamine was not preserved after treatment with 20 mM caffeine, a Ca(2+)-store releaser. The effect of histamine was potentiated by GTP; inhibited by GDP beta S, an antagonist of GTP for binding to G-proteins; or heparin, an antagonist of inositol 1,4,5-trisphosphate (IP3) for binding to its receptor; and mimicked by IP3. When GTP gamma S (20 microM) was applied and continued to be present for 15 min, a transient rise in tension followed by a small, sustained rise in tension was elicited. The effect of GTP gamma S was completely inhibited by GDP beta S. The initial, transient component of the biphasic GTP gamma S response was abolished or markedly inhibited after treatment with caffeine, heparin or the calcium ionophore A23187. The present results suggest that histamine and GTP gamma S cause a release of Ca2+ from caffeine-sensitive stores which is mediated by IP3 formed through a G-protein-coupled mechanism. The GTP gamma S-induced Ca2+ release is not considered to involve such an IP3-independent process as described in chemically-skinned arterial muscle.
Assuntos
Cálcio/metabolismo , Guanosina 5'-O-(3-Tiotrifosfato)/farmacologia , Histamina/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Animais , Escina , Guanosina Trifosfato/farmacologia , Cobaias , Heparina/farmacologia , Íleo/efeitos dos fármacos , Técnicas In Vitro , Masculino , Músculo Liso/metabolismoRESUMO
Reported is a rare case of a multiple peripheral pulmonary carcinoids showing a diffuse lung disease synchronously associated with a sigmoid colon cancer. An abnormal chest shadow was detected in a 75-year-old male by X ray during a periodic health examination. After admission to hospital for a more thorough examination he was found to have a sigmoid colon cancer. A CT scan of his chest suggested sarcoidosis, but the results of a bronchofiberscopic examination appeared normal. Subsequently, a TBLB specimen revealed typical carcinoid tumors. Thus, the diagnosis of diffuse multiple peripheral carcinoids was made. A surgical resection of the sigmoid colon cancer was performed successfully, but five months later, the patient died of acute pneumonia. An autopsy was not permitted. Also discussed are multiple pulmonary carcinoids and a double cancer.
Assuntos
Adenocarcinoma/patologia , Tumor Carcinoide/patologia , Neoplasias Pulmonares/patologia , Neoplasias Primárias Múltiplas , Neoplasias do Colo Sigmoide/patologia , Adenocarcinoma/cirurgia , Idoso , Biópsia , Tumor Carcinoide/diagnóstico por imagem , Humanos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Radiografia Torácica , Neoplasias do Colo Sigmoide/cirurgiaRESUMO
Hypoplastic-hypocalcified enamel of all permanent teeth and dysplasia of finger- and toe-nails were found in a 17-year-old Japanese male. Physical examination revealed no remarkable changes in skin, hair, sweat glands, bones, etc. Family history revealed the same abnormalities of teeth and nails in his mother's brother. A review of the literature concerning ectodermal dysplasia syndromes failed to reveal a combination of hypoplastic-hypocalcified enamel and dysplastic nails without changes in any other ectodermal tissues.
Assuntos
Hipoplasia do Esmalte Dentário/patologia , Displasia Ectodérmica/patologia , Unhas Malformadas , Adolescente , Humanos , MasculinoRESUMO
A case of osseous hyperplasia under the pontics of fixed partial dentures in right and left mandibular first molar regions is presented. Radiographs showed hemispherical radio-opacities on the alveolar ridges. Histologic examination revealed the lesions were composed of a dense mass of mature bone with well-developed lamellae and haversian systems, viable osteocytes in lacunae and a few marrow spaces filled with loose fibrous connective tissue. The review of the literature showed osseous hyperplasia under the pontic of a fixed partial denture has been seen only in the mandibular molar or premolar regions, but no conclusion about its etiology was made.