RESUMO
At the Mainz Microtron MAMI, the first high-resolution pion spectroscopy from decays of strange systems was performed by electron scattering off a (9)Be target in order to study the Λ binding energy of light hypernuclei. Positively charged kaons were detected by a short-orbit spectrometer with a broad momentum acceptance at 0° forward angles with respect to the beam, efficiently tagging the production of strangeness in the target nucleus. Coincidentally, negatively charged decay pions were detected by two independent high-resolution spectrometers. About 10(3) pionic weak decays of hyperfragments and hyperons were observed. The pion momentum distribution shows a monochromatic peak at pπ≈133 MeV/c, corresponding to the unique signature for the two-body decay of hyperhydrogen Λ(4)Hâ(4)He+π(-), stopped inside the target. Its Λ binding energy was determined to be BΛ=2.12±0.01 (stat)±0.09 (syst)MeV with respect to the (3)H+Λ mass.
RESUMO
BACKGROUND AND STUDY AIMS: Carbon dioxide (CO2) insufflation is expected to be safe and effective in endoscopic submucosal dissection (ESD) as well as in other endoscopic procedures. The present study aimed to clarify the usefulness and safety of CO2 insufflation in gastric ESD. PATIENTS AND METHODS: A total of 102 consecutive patients were randomly assigned to CO2 insufflation (CO2 group, n = 54) or air insufflation (Air group, n = 48). Abdominal pain and distension were chronologically recorded on a 100-mm visual analog scale (VAS). The volume of residual gas in the digestive tract was measured by computed tomography performed immediately after ESD. RESULTS: Abdominal pain on a 100-mm VAS in the CO2 vs. Air group was 4 vs. 3 immediately after ESD, 4 vs. 4 one hour after the procedure, 3 vs. 3 three hours after the procedure, and 1 vs. 4 the next morning, showing no difference between the groups. In addition, there was no difference in abdominal distension on the 100-mm VAS over the time course of the study. The volume of residual gas in the digestive tract in the CO2 group was significantly smaller than that in the Air group (643 mL vs. 1037 mL, P < 0.001). The dose of sedative drugs did not differ between the groups. Neither the incidences of complications nor clinical courses differed between the groups. CONCLUSIONS: Compared with air insufflation, CO2 insufflation during gastric ESD significantly reduced the volume of residual gas in the digestive tract but not the VAS score of abdominal pain and distension.
Assuntos
Dióxido de Carbono , Gases , Mucosa Gástrica/cirurgia , Insuflação/métodos , Neoplasias Gástricas/cirurgia , Dor Abdominal/etiologia , Idoso , Idoso de 80 Anos ou mais , Ar , Dióxido de Carbono/efeitos adversos , Dissecação , Método Duplo-Cego , Feminino , Gases/efeitos adversos , Gastroscopia , Humanos , Insuflação/efeitos adversos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/etiologia , Fatores de TempoRESUMO
The effect of a variety of cell death-inducing reagents on the release of herpes simplex virus type 1 (HSV-1) was examined. Ionomycin was found to increase the release of HSV-1, whereas no significant increase was observed by the treatment with TNF-alpha, anti-Fas antibody, C2-ceramide, sphingosine, H-7, tyrphostin and camptothecin. Ionomycin induced an immediate early peak and a subsequent long-lasting elevation of intracellular Ca(2+) concentration ([Ca(2+)]i). In the absence of extracellular Ca(2+), ionomycin neither elevated [Ca(2+)]i nor increased the release of HSV-1 from the infected cells, indicating that Ca(2+) influx play an important role in the release of HSV-1. Studies with trypan blue and annexin V staining revealed that the ionomycin-induced alteration of [Ca(2+)]i was accompanied by cell death of the infected cells. Disintegration of cell membrane, cytoplasmic vacuole formation and the leakage of virus particles from the cell surface were observed by electron microscopy. These results indicate that Ca(2+)-dependent cell death showing necrotic alteration is responsible for the enhanced release of HSV-1. The data also give some initial insights into the functional importance of cell death during the late stages of HSV-1 infection.
Assuntos
Cálcio/metabolismo , Herpesvirus Humano 1/fisiologia , Cálcio/farmacologia , Inibidores de Caspase , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Ionomicina/farmacologia , Tapsigargina/farmacologia , Fatores de TempoRESUMO
Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental and skeletal anomalies, palmo-plantar pits, odontogenic keratocysts, ectopic calcification, and occurrence of various types of tumors including basal cell carcinoma. Recent evidence has indicated that the human homologue of a Drosophila segment polarity gene, PTCH, is a NBCCS susceptibility gene. In the study presented here, we detected two novel mutations of the PTCH gene, I805X/2395delC and Y93X/C297A, in two unrelated Japanese patients. Early protection of the skin from the sunlight is important to the prevention of BCC development in NBCCS patients. Genetic analysis of the PTCH gene is essential for the early, definitive diagnosis of NBCCS, especially before the expression of clinical manifestations is complete.
Assuntos
Síndrome do Nevo Basocelular/genética , Mutação em Linhagem Germinativa , Proteínas de Membrana/genética , Adulto , Sequência de Bases/genética , Deleção de Genes , Humanos , Masculino , Dados de Sequência Molecular , Receptores Patched , Receptor Patched-1 , Linhagem , Receptores de Superfície CelularRESUMO
The proliferation of mouse submandibular gland carcinoma YT-12 cells was stimulated by endothelial cell growth factor (ECGF)/bovine brain-derived acidic fibroblast growth factor (aFGF) and recombinant human aFGF. To determine whether aFGF was capable of modifying salivary gland carcinogenesis, the effect of brain-derived aFGF was examined in vivo. Mice in Groups 1 and 2 were injected with 9,10-dimethyl-1,2-benzanthracene (DMBA) into the left submandibular gland, and then Group 1 mice received bovine brain-derived aFGF and Group 2 mice received vehicle subcutaneously for 10 weeks. Group 3 and 4 mice received either bovine brain-derived aFGF or vehicle only. Sixteen weeks after the start of the experiment, the incidence of submandibular gland carcinomas in Group 1 was significantly greater than that in Group 2. Immunohistochemical study indicated that ducts in the normal submandibular glands and carcinomas showed positive staining with anti-aFGF antibody. Immunoblot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the expression of aFGF in these tissues. FGF receptor (FGFR)-1 and FGFR-4 were detectable in the mouse submandibular glands and carcinomas. These findings suggest that bovine brain-derived aFGF stimulates the proliferation of submandibular gland carcinoma cells and promotes mouse submandibular gland carcinogenesis.
Assuntos
Carcinoma/induzido quimicamente , Fator 1 de Crescimento de Fibroblastos/farmacologia , Neoplasias da Glândula Submandibular/induzido quimicamente , 9,10-Dimetil-1,2-benzantraceno , Idoso , Animais , Carcinoma/metabolismo , Bovinos , Divisão Celular/efeitos dos fármacos , Feminino , Humanos , Immunoblotting , Camundongos , Camundongos Endogâmicos ICR , Fosforilação , RNA Mensageiro/análise , Receptores de Fatores de Crescimento de Fibroblastos/biossíntese , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Glândula Submandibular/metabolismo , Neoplasias da Glândula Submandibular/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo , Tirosina/metabolismoRESUMO
A morphological change induced by syn- herpes simplex virus type 1 (HSV-1), polykaryocyte formation, was enhanced by treatment with 12-O-tetradecanoyl phorbol 13-acetate (TPA) in A431 cells. TPA treatment decreased the number of stress fibers, but led to the development of spike-like filopodia and actin-containing long projections. Similar reorganization of actin filaments was observed in HSV-1-induced polykaryocytes. The actin filament-disrupting drug cytochalasin D, but not the microtubule-disrupting drug nocodazole, inhibited the effect of TPA on polykaryocyte formation, indicating that the actin microfilament system plays a key role in this event. HSV-1 glycoprotein D (gD) was present in the cytoplasm of HSV-1-infected cells and gD gene-transfected cells; its expression became prominent at long cell projections in the presence of TPA. These findings suggest that the reorganization of actin filaments and cell motility are associated with the enhancing effect of TPA on HSV-1-induced polykaryocyte formation.
Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Movimento Celular , Células Gigantes/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Citoesqueleto de Actina/ultraestrutura , Fusão Celular , Citocalasina D/farmacologia , Inibidores Enzimáticos/farmacologia , Imunofluorescência , Células Gigantes/ultraestrutura , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 1/fisiologia , Humanos , Nocodazol/farmacologia , Proteína Quinase C/antagonistas & inibidores , Transfecção , Células Tumorais Cultivadas , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Replicação ViralRESUMO
We describe a 25-year-old woman who had mental nerve neuropathy. The symptom was attributed to herpes simplex virus infection, which appeared as herpetic gingivostomatitis 4 days after the extraction of the lower third molar. This case suggests that herpes simplex virus can infect the inferior alveolar nerve through an extraction wound and can induce mental nerve neuropathy.
Assuntos
Doenças dos Nervos Cranianos/virologia , Nervo Mandibular , Estomatite Herpética/complicações , Extração Dentária/efeitos adversos , Adulto , Queixo/inervação , Feminino , Humanos , Dente Serotino/cirurgiaRESUMO
This study investigated whether epidermal growth factor (EGF) administration was capable of modifying salivary gland carcinogenesis. Two groups of mice were given 1 mg of 9,10-dimethyl-1,2-benzanthracene (DMBA) into the left submandibular gland, and then Group 1 mice received 2 microg of EGF and Group 2 mice received vehicle subcutaneously for 8 weeks. Mice in two other groups, 3 and 4, received either EGF or vehicle alone. Twelve weeks after the start of the experiment, the incidences of submandibular gland carcinomas in Groups 1 and 2 were 39% and 58%, respectively, although this difference was not statistically significant. Duct- and cyst-like structures and carcinomas in the left submandibular glands were weakly stained by anti-EGF receptor (EGFR) antibody. Immunoblot and reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed the expression of EGFR in the submandibular glands and carcinomas. However, EGFR was undetectable in YT cells that were derived from a submandibular gland undifferentiated carcinoma of a Group 2 mouse. These findings indicate that EGF does not promote tumor induction in mouse salivary gland carcinogenesis. This may be ascribed in part to the low expression level of EGFR in tumor cells.
Assuntos
Carcinógenos/farmacologia , Carcinoma/induzido quimicamente , Fator de Crescimento Epidérmico/farmacologia , Neoplasias da Glândula Submandibular/induzido quimicamente , 9,10-Dimetil-1,2-benzantraceno/administração & dosagem , 9,10-Dimetil-1,2-benzantraceno/efeitos adversos , Animais , Carcinógenos/administração & dosagem , Carcinógenos/efeitos adversos , Carcinoma/genética , Fator de Crescimento Epidérmico/administração & dosagem , Receptores ErbB/análise , Receptores ErbB/genética , Feminino , Imunofluorescência , Regulação Neoplásica da Expressão Gênica , Immunoblotting , Incidência , Injeções , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Camundongos Nus , Transplante de Neoplasias , Veículos Farmacêuticos , Reação em Cadeia da Polimerase , Ductos Salivares/efeitos dos fármacos , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/metabolismo , Neoplasias da Glândula Submandibular/genética , Células Tumorais CultivadasRESUMO
The effect of protein tyrosine kinase (PTK) inhibitors on the replication of herpes simplex virus (HSV) was examined. Tyrphostins AG17, AG213, AG490, and AG555, and herbimycin A all inhibited the plaque formation of HSV type 1 (HSV-1) in Vero cells, but AG17, AG490, and AG555 exhibited a more selective antiviral effect. In the presence of 0.4 microM AG17, the virus production 24 h after infection was decreased to 7.7% of the untreated control level. Even if the treatment was started 12 h after the initiation of infection, the viral titer was reduced by 82.4%, compared with the untreated control level. In HSV-1-infected cells ICPs 6, 17/18, 19/20, and 25 were tyrosine-phosphorylated proteins. The synthesis and phosphorylation of these proteins were inhibited by AG17, and suppression of ICP 19/20, which were identified as the UL47 gene products, was the greatest. In contrast, the in vitro autophosphorylation of viral proteins was not affected by this PTK inhibitor. These results indicate that tyrphostin may represent a novel class of inhibitors of HSV-1, and that the viral proteins which have phosphorylated tyrosine residues and are suppressed by AG17 most significantly are the products of the UL47 gene, the tegument proteins VP13/14.
Assuntos
Antivirais/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Simplexvirus/fisiologia , Tirfostinas , Proteínas Virais/metabolismo , Replicação Viral/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Benzoquinonas , Catecóis/farmacologia , Chlorocebus aethiops , Inibidores Enzimáticos/farmacologia , Lactamas Macrocíclicas , Dados de Sequência Molecular , Nitrilas/farmacologia , Fenóis/farmacologia , Fosforilação/efeitos dos fármacos , Quinonas/farmacologia , Rifabutina/análogos & derivados , Simplexvirus/metabolismo , Células Vero , Proteínas Virais de Fusão/análise , Proteínas Virais/biossínteseRESUMO
The chemopreventive effect of oral and intraperitoneal (i.p.) administration of hexamethylene bisacetamide (HMBA) on 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced tumour formation in hamster cheek pouches was investigated. Male Syrian hamsters were treated by painting both cheek pouches with a 0.5% solution of DMBA twice weekly for 11 weeks. In addition to DMBA application, Group 1 hamsters were given 1% HMBA continuously in the drinking water and Group 2 hamsters received i.p. injection of HMBA at a dose of 500 mg/kg three times per week during the experiment. Group 3 animals received DMBA application alone. Thirteen weeks after the start of the experiment, the numbers of cheek pouch tumours and tumour volume were significantly decreased by oral but not i.p. administration of HMBA. Low levels of HMBA were detected in the plasma of the hamsters which were given 1% HMBA in drinking water. These results indicate that oral administration of HMBA can act as a chemopreventive agent against hamster cheek pouch tumorigenesis.
Assuntos
Acetamidas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Bucais/prevenção & controle , 9,10-Dimetil-1,2-benzantraceno , Acetamidas/sangue , Acetamidas/farmacologia , Administração Oral , Animais , Antineoplásicos/sangue , Antineoplásicos/farmacologia , Peso Corporal/efeitos dos fármacos , Cricetinae , Injeções Intraperitoneais , Masculino , Mesocricetus , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/patologia , Neoplasias Experimentais/sangue , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/prevenção & controle , Tamanho do Órgão/efeitos dos fármacosRESUMO
To determine whether testosterone administration was capable of modifying salivary gland carcinogenesis, female mice were given 1 mg of 9,10-dimethyl-1,2-benzanthracene (DMBA) into the left submandibular gland and then Group 1 mice received 5 mg of testosterone propionate and Group 2 mice received vehicle, olive oil, subcutaneously for 8 weeks. Twelve weeks after the start of the experiment, the weight of the left submandibular gland of the Group 2 mice was greater than that of the Group 1 mice. The incidences of submandibular gland carcinoma in Groups 1 and 2 were 41% (12/29) and 57% (17/30), respectively. Epidermal growth factor (EGF) levels of the left submandibular gland were significantly higher in Group 1 as compared with Group 2. These findings indicate that testosterone increases the production of EGF in the DMBA-injected submandibular gland, but does not promote the development of submandibular gland carcinoma.
Assuntos
Fator de Crescimento Epidérmico/biossíntese , Neoplasias da Glândula Submandibular/metabolismo , Glândula Submandibular/efeitos dos fármacos , Testosterona/farmacologia , 9,10-Dimetil-1,2-benzantraceno , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/metabolismo , Animais , Carcinoma/induzido quimicamente , Carcinoma/metabolismo , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/metabolismo , Feminino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Neoplasias da Glândula Submandibular/induzido quimicamenteRESUMO
To determine whether the local administration of 9,10-dimethyl-1,2-benzanthracene (DMBA) into the hamster maxillary sinus induced carcinoma at the injected site, hamsters were injected with 30 microliters of 0.5% solution of DMBA in dimethyl sulfoxide (DMSO) through the infraorbital foramen into the maxillary sinus once weekly for 10 weeks (Group 2). Another group of hamsters (Group 1) received similar injections of 30 microliters of DMSO only. In a third group of animals (Group 3), a roll of oxycellulose was inserted into the maxillary sinus and 40 microliters of a 2% solution of DMBA in DMSO was injected once. Sinonasal carcinomas were demonstrated in 73% (8/11) of the hamsters in Group 2 and sarcomas were shown in 73% (8/11) of the hamsters in Group 3, as well as some carcinomas. No tumors were seen in the Group 1 hamsters. Histologic examination revealed squamous cell carcinomas arising from the surface epithelium and submucous glands of the nasal cavity and maxillary sinus. These findings indicate that the intrasinal administration of a 0.5% solution of DMBA in DMSO is a reliable method for inducing maxillary sinus cancer.
Assuntos
9,10-Dimetil-1,2-benzantraceno/efeitos adversos , Carcinoma/induzido quimicamente , Neoplasias do Seio Maxilar/induzido quimicamente , Sarcoma Experimental/induzido quimicamente , 9,10-Dimetil-1,2-benzantraceno/administração & dosagem , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/patologia , Animais , Carcinoma/patologia , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/patologia , Celulose Oxidada , Cricetinae , Dimetil Sulfóxido , Modelos Animais de Doenças , Fibrossarcoma/induzido quimicamente , Fibrossarcoma/patologia , Injeções , Masculino , Neoplasias do Seio Maxilar/patologia , Mesocricetus , Cavidade Nasal/efeitos dos fármacos , Cavidade Nasal/patologia , Neoplasias Nasais/induzido quimicamente , Neoplasias Nasais/patologia , Papiloma/induzido quimicamente , Papiloma/patologia , Rabdomiossarcoma/induzido quimicamente , Rabdomiossarcoma/patologia , Sarcoma Experimental/patologiaRESUMO
Tyrphostins 9 and 47, inhibitors of protein-tyrosine kinase, inhibited the replication of herpes simplex virus type 1 (HSV-1), whereas tyrophostin 1, which does not inhibit protein-tyrosine kinase, did not affect the replication of HSV-1. The inhibitory effect of tyrphostin 9 was more potent than that of tyrphostin 47, and the IC50 of tyrphostin 9 was 40 nM. Sodium orthovanadate, an inhibitor of protein phosphotyrosine phosphatase, increased HSV-1 plaque formation and its effect was partly reversed by tyrphostin 9. The phosphorylation of viral phosphoproteins was decreased by tyrphostin 9 in a dose-dependent manner, but the tyrphostin 9-induced reduction of protein synthesis was not dose-dependent. At the late stage of infection, tyrosine phosphorylation was demonstrated in HSV-1 phosphoproteins. These results indicate that protein-tyrosine kinase is involved in the replication of HSV-1 and that tyrphostin can inhibit the synthesis and post-translational phosphorylation of the viral proteins.
Assuntos
Herpesvirus Humano 1/efeitos dos fármacos , Nitrilas/farmacologia , Fenóis/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Tirfostinas , Replicação Viral/efeitos dos fármacos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Chlorocebus aethiops , Replicação do DNA/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Humanos , Fosforilação , Fosfotirosina , Testes de Precipitina , Proteínas Tirosina Quinases/metabolismo , Tirosina/análogos & derivados , Tirosina/imunologia , Vanadatos/farmacologia , Células Vero , Proteínas Virais/biossíntese , Proteínas Virais/efeitos dos fármacosRESUMO
The effect of local administration of epidermal growth factor (EGF) on 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced tumour formation was investigated in a hamster cheek pouch carcinogenesis model. DMBA-treated hamsters underwent either sialoadenectomy (groups 1 and 2) or a sham operation (groups 3 and 4). Thereafter, EGF (groups 1 and 3) or vehicle (groups 2 and 4) was applied to the cheek pouches for 6 weeks. Fourteen weeks after the beginning of the experiment, the number of cheek pouch tumours was significantly greater in EGF-treated hamsters than in vehicle-treated hamsters, irrespective of whether the submandibular glands had been removed. The number of forestomach tumours, induced by DMBA application to the cheek pouches, was also increased by EGF. These results suggest that EGF applied from the luminal side of the mucosa stimulates tumour formation in the hamster cheek pouch and forestomach.