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1.
Oral Dis ; 20(7): 700-6, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25360469

RESUMEN

OBJECTIVE: Streptococcus mutans, a major dental caries pathogen, has shown to be associated with the aggravation of cerebral hemorrhage and inflammatory bowel diseases. In this study, we evaluated the effects ofS. mutans on the development of non-alcoholic steatohepatitis (NASH) in a mouse model. MATERIALS AND METHODS: Streptococcus mutans oral strain MT8148 (serotype c) and a blood isolate TW871 (k) were used. C57BL/6J mice (6 weeks old)were fed a high-fat diet for 4 weeks; the test strains or phosphate-buffered saline was then intravenously administered. Mice were euthanized after 8 or 12 weeks. Whole body, extirpated liver, and visceral fat weights were determined, and histopathological evaluations of the liver specimens were performed. RESULTS: Mice infected with TW871 showed significantly greater body and liver weights than those administered MT8148 or phosphate-buffered saline. Histopathological analyses revealed prominent infiltration of inflammatory cells and adipocellular deposition in livers extirpated 8 weeks after an infection with TW871; fibrosis was also observed in livers extirpated after 12 weeks. CONCLUSION: These results suggest that a specific strain of S. mutans could induce NASH.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico/microbiología , Infecciones Estreptocócicas/complicaciones , Streptococcus mutans , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Índice de Severidad de la Enfermedad
2.
Eur J Surg Oncol ; 40(5): 521-528, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24388411

RESUMEN

INTRODUCTION: The drugs and protocols used for hyperthermic intraperitoneal chemotherapy (HIPEC) vary among institutions. Here we show the efficacy of the 3-drug combination of mitomycin C (MMC), 5-fluorouracil (5FU), and oxaliplatin (OHP) in an in vitro simulation of HIPEC and the safety of HIPEC with these drugs during a Phase I study of patients at high risk of developing colorectal peritoneal metastasis. METHODS: To simulate HIPEC, we used HCT116 and WiDr cells to assess the growth inhibitory efficacy of MMC 2 µg/mL, 5FU 200 µg/mL, and OHP 40 µg/mL as single drugs or their combination after an exposure time of 30 min at 37 or 42 °C. In addition, nine patients underwent surgical resection of tumors and HIPEC with MMC, 5FU, and an escalating dose of OHP (90/110/130 mg/m²). Dose-limiting toxicity was monitored. RESULTS: In the simulation, the 3-drug combination showed marked tumor-suppressive effects compared with those from ten times higher dose of OHP 400 µg/mL, with significant augmentation under hyperthermic conditions. No dose-limiting toxicity occurred in the clinical study. Dose escalation was completed at the final level of OHP. CONCLUSIONS: The MMC-5FU-OHP combination showed marked growth inhibition against colorectal cancer cells under hyperthermic conditions in vitro. In the phase I study, the recommended dose of OHP was determined as 130 mg/m² when used with MMC and 5FU; HIPEC using MMC-5FU-OHP appears to be safe and feasible for patients at high risk of colorectal peritoneal metastasis.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Hipertermia Inducida/métodos , Siembra Neoplásica , Neoplasias Peritoneales/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Terapia Combinada , Femenino , Fluorouracilo/administración & dosificación , Células HCT116 , Humanos , Técnicas In Vitro , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias Peritoneales/secundario , Resultado del Tratamiento
3.
Oral Dis ; 20(4): 359-66, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-23679203

RESUMEN

OBJECTIVES: Streptococcus mutans can aggravate colitis in mice. We evaluated the virulence of colitis using type strains as well as blood isolates of several oral streptococcal species. MATERIALS AND METHODS: We investigated the susceptibility of blood isolates of several oral streptococci to phagocytosis, adhesion to and invasion of hepatic cells and interferon-γ secretion. A mouse model of dextran sodium sulphate-induced colitis was used to evaluate bacterial aggravation of colitis. In addition, interferon-γ antibody was administered to mice with prominent aggravation of colitis. RESULTS: In vitro analyses showed that Streptococcus sanguinis ATCC 10556 was a possible virulent strain among type strains of several oral streptococci, and that analysis of blood isolates of S. sanguinis TW289 revealed a potential virulent strain. Intravenous administration of ATCC 10556 and TW289 caused prominent aggravation of dextran sodium sulphate-induced colitis, and histopathological examinations showed that interferon-γ secretion due to infection of hepatic cells caused colitis aggravation. Administration of interferon-γ antibody suppressed TW289-induced colitis. CONCLUSION: These results suggest that some virulent oral streptococcal strains are associated with the aggravation of colitis induced by enhanced secretion of interferon-γ when they invade the bloodstream.


Asunto(s)
Colitis Ulcerosa/microbiología , Streptococcus/patogenicidad , Animales , Progresión de la Enfermedad , Enfermedades Inflamatorias del Intestino/microbiología , Ratones , Ratones Endogámicos C57BL , Boca/microbiología , Streptococcus/aislamiento & purificación
4.
Arch Oral Biol ; 58(11): 1627-34, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24112728

RESUMEN

OBJECTIVE: Streptococcus mutans, an aetiologic agent of dental caries, is a pathogen for infective endocarditis (IE). We investigated strains that express collagen-binding proteins (CBPs) with further classification based on expression of the 190-kDa protein antigen (PA). METHOD: Zeta-potential values of strains TW871 (CBP+/PA+) and MT8148 (CBP-/PA+), and their respective PA-defective mutant strains TW871PD (CBP+/PA-) and MT8148PD (CBP-/PA-), were analysed, as were their adhesion to and invasion of human umbilical vein endothelial cells (HUVECs). The distribution of strains from the oral cavities of 200 healthy individuals was analysed for CBP and/or PA expression and the strains were characterised for their adhesion and invasion properties. RESULTS: TW871PD and MT8148PD showed significantly lower zeta-potential values than TW871 and MT8148, respectively. Collagen-binding rates were significantly higher for TW871PD than for TW871 but nearly negligible for MT8148 and MT8148PD. The adhesion and invasion rates of HUVECs were significantly higher for TW871PD than for TW871 and significantly higher for TW871 than for MT8148 and MT8148PD. The prevalence of CBP+ strains was ~10% and ~3% in the case of CBP+/PA- strains. Analyses of 200 clinical strains showed the CBP+/PA- group to have higher adhesion and invasion rates than other groups. CONCLUSIONS: CBP+/PA- S. mutans strains, despite their low distribution frequency, may be highly virulent for infective endocarditis.


Asunto(s)
Adhesinas Bacterianas/inmunología , Adhesión Bacteriana/inmunología , Colágeno/inmunología , Endocarditis Bacteriana/microbiología , Boca/microbiología , Streptococcus mutans/patogenicidad , Adhesinas Bacterianas/metabolismo , Colágeno/metabolismo , Técnicas de Cultivo , Endocarditis Bacteriana/inmunología , Humanos , Microscopía Confocal , Unión Proteica/genética , Unión Proteica/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Streptococcus mutans/clasificación , Streptococcus mutans/inmunología , Virulencia
5.
Oral Dis ; 19(4): 387-93, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-22998492

RESUMEN

OBJECTIVE: Streptococcus mutans, a major pathogen of dental caries, is considered to be one of the causative agents of infective endocarditis (IE). Two types of cell surface collagen-binding proteins, Cnm and Cbm, have been identified in the organism. The aim of the present study was to analyze these proteins as possible etiologic factors for IE. MATERIALS AND METHODS: The binding activities of S. mutans strains to collagen types I, III, and IV were analyzed relative to the presence of Cnm and Cbm, as were their adhesion and invasion properties with human umbilical vein endothelial cells (HUVEC). In addition, distributions of the genes encoding Cnm and Cbm in S. mutans-positive heart valve specimens extirpated from IE and non-IE patients were analyzed by PCR. RESULTS: Most of the Cbm-positive strains showed higher levels of binding to type I collagen as well as higher rates of adhesion and invasion with HUVEC as compared to the Cnm-positive strains. Furthermore, the gene encoding Cbm was detected significantly more frequently in heart valve specimens from IE patients than from non-IE patients. CONCLUSIONS: These results suggest that the collagen-binding protein Cbm of S. mutans may be one of the potential important factor associated with the pathogenesis of IE.


Asunto(s)
Adhesinas Bacterianas/metabolismo , Proteínas Portadoras/metabolismo , Colágeno/metabolismo , Endocarditis Bacteriana/microbiología , Infecciones Estreptocócicas/microbiología , Streptococcus mutans/química , Adhesinas Bacterianas/genética , Adulto , Anciano , Válvula Aórtica/microbiología , Adhesión Bacteriana , Proteínas Portadoras/genética , ADN Bacteriano , Endocarditis Bacteriana/metabolismo , Células Endoteliales/microbiología , Femenino , Células Endoteliales de la Vena Umbilical Humana/microbiología , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/microbiología , Unión Proteica , Infecciones Estreptocócicas/metabolismo
6.
Mol Oral Microbiol ; 27(4): 308-23, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22759315

RESUMEN

Streptococcus mutans, a major pathogen of dental caries, is occasionally isolated from the blood of patients with infective endocarditis. Bacterial attachment of exposed collagen tissue in the impaired endothelium is an important step in the onset of infective endocarditis. In our previous studies, some S. mutans strains were shown to possess collagen-binding activities and most of them had an approximately 120-kDa cell-surface collagen-binding protein called Cnm. However, several strains without Cnm proteins show collagen-binding properties. In the present study, another collagen-binding protein, Cbm, was characterized and its coding gene cbm was sequenced in these strains. The amino acid alignment in the putative collagen-binding domain of Cbm was shown to have approximately 80% identity and 90% similarity to the comparable region of Cnm. Cbm-deficient isogenic mutant strains constructed by insertional inactivation of the cbm gene, lacked collagen-binding properties, which were recovered in the complemented mutant. Analyses of a large number of clinical isolates from Japan, Thailand and Finland revealed that cbm-positive strains were present in all of these countries and that cnm-positive and cbm-positive strains were detected in the oral cavity of approximately 10 and 2% of systemically healthy subjects, respectively. In addition, cnm-positive strains were predominantly identified in the serotype f group, whereas cbm-positive strains were frequently detected in serotype k. These results suggest that Cbm as well as Cnm are major cell surface proteins of S. mutans associated with binding to type I collagen and predominantly identified in serotype k strains.


Asunto(s)
Adhesinas Bacterianas/química , Colágeno Tipo I/metabolismo , Endocarditis Bacteriana/microbiología , Unión Proteica , Streptococcus mutans/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Niño , Preescolar , Femenino , Finlandia , Técnicas de Inactivación de Genes , Genes Bacterianos , Humanos , Japón , Masculino , Persona de Mediana Edad , Saliva/microbiología , Serotipificación , Streptococcus mutans/clasificación , Tailandia , Transformación Bacteriana , Virulencia/genética , Adulto Joven
7.
Arch Oral Biol ; 57(9): 1183-8, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22417880

RESUMEN

OBJECTIVE: Presently, a large number of individuals consider their companion animals as family members and have close contact with them in daily life. The purpose of the present study was to analyze the distribution of periodontopathic bacterial species in oral specimens taken from dogs and their owners. DESIGN: Dental plaque specimens were collected from 66 dogs and 81 members of 64 families who came to an animal clinic or dog training school in Okayama, Japan, in 2011. Bacterial DNA was extracted from each specimen and PCR analyses using primers specific for 11 periodontopathic species, Porphyromonas gingivalis, Porphyromonas gulae, Treponema denticola, Tannerella forsythia, Capnocytophaga ochracea, Capnocytophaga sputigena, Prevotella intermedia, Prevotella nigrescens, Aggregatibacter actinomycetemcomitans, Campylobacter rectus, and Eikenella corrodens were performed. RESULTS: P. gulae (71.2%), T. forsythia (77.3%), and C. rectus (66.7%) were frequently found in the dogs, whereas the detection rates of those species in humans were less frequent at 16.0%, 30.9%, and 21.0%, respectively. P. gulae was identified in 13 human subjects and each of their dogs was also positive for the species. Furthermore, E. corrodens and T. denticola in specimens obtained from dogs were correlated with their presence in specimens from owners who had close contact with them. CONCLUSIONS: These results suggest that several periodontopathic species could be transmitted between humans and their companion dogs, though the distribution of periodontopathic species in both is generally different.


Asunto(s)
Placa Dental/microbiología , Bacterias Gramnegativas/aislamiento & purificación , Enfermedades Periodontales/microbiología , Mascotas/microbiología , Aggregatibacter actinomycetemcomitans/aislamiento & purificación , Animales , Bacteroides/aislamiento & purificación , Campylobacter rectus/aislamiento & purificación , Capnocytophaga/aislamiento & purificación , Perros , Eikenella corrodens/aislamiento & purificación , Femenino , Humanos , Masculino , Enfermedades Periodontales/veterinaria , Porphyromonas/aislamiento & purificación , Porphyromonas gingivalis/aislamiento & purificación , Prevotella intermedia/aislamiento & purificación , Prevotella nigrescens/aislamiento & purificación , Treponema denticola/aislamiento & purificación , Zoonosis/microbiología
8.
Oral Dis ; 17(4): 370-8, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21029263

RESUMEN

OBJECTIVE: Porphyromonas gingivalis was recently shown to cause intimal hyperplasia in a mouse model by a novel cholesterol-independent mechanism, suggesting to be a pathogen-specific feature of cardiovascular diseases. The aim of this study was to characterize the clinical and histopathological features of aortic aneurysms in cardiovascular disease patients harboring oral P. gingivalis. SUBJECT AND METHODS: Aortic aneurysm specimens were collected from 76 Japanese patients who underwent surgery, of whom dental plaque specimens were also collected from 31 patients. Bacterial DNA was extracted from each specimen to detect P. gingivalis by polymerase chain reaction. Histopathological analyses of the aortic aneurysm specimens, including immunohistochemical staining for embryonic myosin heavy chain isoform (SMemb) and S100 calcium-binding protein A9 (S100A9), were also performed. RESULTS: The number of aneurysms occurring in the distal aorta was significantly higher in subjects positive for P. gingivalis in dental plaque compared with those who were negative. The expressions of S100A9 and SMemb were also significantly greater in the subjects positive for P. gingivalis in dental plaque. On the other hand, there were no significant differences in adipocellular accumulation between the groups. CONCLUSIONS: These results suggest that aortic aneurysms in patients harboring oral P. gingivalis have greater expression of S100A9 and proliferative smooth muscle cells, which was different from the present patients without oral P. gingivalis.


Asunto(s)
Aneurisma de la Aorta/patología , Enfermedades Cardiovasculares/patología , Placa Dental/microbiología , Porphyromonas gingivalis/aislamiento & purificación , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta/microbiología , Aneurisma de la Aorta Abdominal/microbiología , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Torácica/microbiología , Aneurisma de la Aorta Torácica/patología , Calgranulina B/análisis , Enfermedades Cardiovasculares/microbiología , Proliferación Celular , ADN Bacteriano/análisis , Dilatación Patológica/patología , Femenino , Proteínas Fimbrias/genética , Humanos , Hiperplasia , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/patología , Cadenas Pesadas de Miosina/análisis , Pili Sexual/genética , Reacción en Cadena de la Polimerasa , Porphyromonas gingivalis/genética , Isoformas de Proteínas/análisis
9.
Arch Oral Biol ; 55(6): 410-6, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20398892

RESUMEN

OBJECTIVE: Streptococcus mutans is a major pathogen of dental caries and occasionally isolated from the blood of patients with infective endocarditis, though the association of its cell-surface glucosyltransferases (GTFB, GTFC, and GTFD) with pathogenicity for infective endocarditis remains to be elucidated. In this study, we investigated the contribution of S. mutans GTFs to platelet aggregation and analysed GTF expression profiles in a large number of clinical oral isolates. DESIGN: The platelet aggregation properties of GTF-defective isogenic mutant strains constructed from S. mutans reference strain MT8148 were evaluated using whole blood and platelet-rich plasma (PRP) taken from mice, as well as human PRP. In addition, GTF expression profiles for 396 S. mutans strains isolated from the oral cavities of 396 subjects were analysed by western blotting using antisera specific for each GTF. RESULTS: The platelet aggregation activities of the GTF-defective isogenic mutants were significantly lower than that of MT8148 when added to a large number of cells. Western blotting revealed no strains without GTF expression, though six strains had alterations of GTFB and GTFC as compared to MT8148. PCR analyses indicated that the gtfB-gtfC region length was approximately 4.5 kb shorter in those strains as compared to MT8148. These were designated as "GTFBC-fusion" strains and they demonstrated lower levels of platelet aggregation. CONCLUSIONS: Our findings indicate that GTFs are associated with platelet aggregation. Although the clinical detection frequency of S. mutans strains with altered expressions is extremely low, GTFBC-fusion strains have activities similar to GTF-defective mutant strains.


Asunto(s)
Glicosiltransferasas/deficiencia , Agregación Plaquetaria , Streptococcus mutans/enzimología , Adulto , Análisis de Varianza , Animales , Sangre/microbiología , Expresión Génica , Glicosiltransferasas/biosíntesis , Glicosiltransferasas/genética , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Boca/microbiología , Plasma Rico en Plaquetas/microbiología , Especificidad de la Especie , Streptococcus mutans/fisiología
10.
Arch Oral Biol ; 55(1): 34-9, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20005510

RESUMEN

OBJECTIVE: Streptococcus mutans, known to be a major pathogen of dental caries, is also considered to cause infective endocarditis. Its 120-kDa Cnm protein binds to type I collagen, which may be a potential virulence factor. In this study, we characterized S. mutans clinical strains focusing on the cnm gene encoding Cnm. DESIGN: A total of 528 S. mutans strains isolated from Japanese, Finnish, and Thai subjects were investigated. Using molecular techniques, the distribution frequency of cnm-positive strains and location of the inserted cnm were analyzed. Furthermore, isogenic mutant strains were constructed by inactivation of the cnm gene, then their biological properties of collagen-binding and glucan-binding were evaluated. Southern hybridization of the genes encoding glucan-binding proteins was also performed. RESULTS: The distribution frequency of cnm-positive strains from Thai subjects was 12%, similar to that previously reported for Japanese and Finnish subjects. Furthermore, the location of insertion of cnm was the same in all cnm-positive clinical isolates. As for the cnm-inactivated mutant strains constructed from 28 clinical isolates, their collagen-binding activity was negligible. In addition, glucan-binding activity in the cnm-positive clinical isolates was significantly reduced and corresponded to a lack of gbpA encoding glucan-binding protein A. CONCLUSIONS: Our results indicate that strains with cnm genes, the most crucial factor for the collagen-binding property of S. mutans, are detectable at similar frequencies over several different geographic locations. In addition, the common properties of these strains are a high level of collagen-binding activity and tendency for a low level of glucan-binding activity.


Asunto(s)
Adhesinas Bacterianas/genética , Proteínas Portadoras/genética , Colágeno/metabolismo , Streptococcus mutans/genética , Southern Blotting , Caries Dental/microbiología , Finlandia , Regulación Bacteriana de la Expresión Génica/fisiología , Glucanos/metabolismo , Humanos , Japón , Reacción en Cadena de la Polimerasa , Unión Proteica/genética , Saliva/microbiología , Streptococcus mutans/aislamiento & purificación , Streptococcus mutans/patogenicidad , Tailandia
11.
Transplant Proc ; 41(1): 425-8, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19249571

RESUMEN

To establish a safe repeatable method for hepatocyte transplantation avoiding serious complications, such as portal thrombosis in the case of the intraportal route of transplantation, we attempted liver cell transplantation into the submucosal layer of the stomach wall. Hepatocytes were isolated from the Lewis rats by a two-step collagenase perfusion method. The final hepatocyte suspension containing 2 x 10(7) viable hepatocytes in 1 mL of 0.2% collagen gel solution. Recipient rats underwent 20% partial hepatectomy and the hepatocyte suspension (2 x 10(7) cells) was injected into the submucosal layer of the anterior wall of the stomach. Rats were humanely killed and histologically examined at days 1, 3, 7, 30, or 180. Most transplanted hepatocytes remained in the submucosal layer until day 7. The surviving hepatocytes were arranged in clusters in the submucosa on day 30; 5-bromo-2'-deoxy-uridine (BrdU)-positive cells were observed. Also, the function of glycogen storage was detected by Periodic acid-Schiff (PAS) reactions on days 7, 30, and 180. The transplanted hepatocytes proliferated, reconstructing liver tissue-like structures in the gastric submucosa on day 180. The gastric submucosa is easily, repeatedly accessible by the gastro-endoscope. Thus, these results suggest that the gastric submucosa is a possible site for safe repetitions hepatocyte transplantation using endoscopic injection.


Asunto(s)
Trasplante de Células/métodos , Mucosa Gástrica/fisiología , Hepatocitos/citología , Hepatocitos/trasplante , Animales , Hepatectomía , Fallo Hepático/cirugía , Masculino , Ratas , Ratas Endogámicas Lew , Estómago , Trasplante Homólogo/métodos
12.
Med Arh ; 56(3): 127-9, 2002.
Artículo en Croata | MEDLINE | ID: mdl-12378855

RESUMEN

The aim of this paper was the registration of the answers of the smooth musculature of the trachea at the different concentrations of ethanol, at the gestationary weeks of the newborns with the respiratory distress syndrome. In vitro examination was worked at the nonhuman preparations of the trachea of the newborns at autopsy material, the same material of the trachea and the lungs is fixed on 10% puferized formaline for the pathomorphologic examinations (RDS). The incubation of the preparation is performed on the water bath with Kreps solution, with the constant aerozation (O2 95% and CO2 5%). The answers are registered by means of the Transducer Statham UC2 at higher canal written physiography Watanabe HSE 6600. The preparations are treated with various concentrations of ethanol 96% (0.2 ml, 0.5 ml and 1.0 ml). From the received results we came to the conclusion that the effect of ethanol in the various concentrations at the smooth musculature of the trachea in the newborns with RDS, is demonstrated the contractile or the relaxing effect without statistic significance in various gestational weeks (p > 0.05).


Asunto(s)
Etanol/farmacología , Músculo Liso/efectos de los fármacos , Síndrome de Dificultad Respiratoria del Recién Nacido/fisiopatología , Tráquea/efectos de los fármacos , Edad Gestacional , Humanos , Técnicas In Vitro , Recién Nacido , Contracción Muscular/efectos de los fármacos , Músculo Liso/fisiopatología , Tráquea/fisiopatología
13.
Biomed Pharmacother ; 56(2): 93-9, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12000141

RESUMEN

Cell destruction in boron neutron capture therapy is effected by nuclear reaction between 10B and thermal neutrons with the release of alpha-particles (4He) and lithium-7 ions (7Li). 4He kills cells within 10 microm of the site of 4He generation, therefore it is theoretically possible to destroy tumour cells without affecting adjacent healthy tissue, given selective delivery of compounds containing 10B. Liposomes wore prepared by vortex dispersion of solutions containing 10B compounds with dried lipid films and the effects of those compounds on human breast cancer cells in culture were examined after thermal neutral irradiation. [3H]-TdR incorporation by MRKnu/nu-1 cells treated with 10B-containing liposomes showed 40% suppression compared with liposomes without 10B, at 2 x 1012 n/cm2 thermal neutron fluence. Inhibition of tumour cell growth with liposomes prepared with 100 mm 10B-compound was as significant as with those made with 500 ppm 10B solution. The concentration of 10B in liposomes was 76.5 +/- 3.4 microg/mL. Boronated liposomes can thus deliver sufficient 10B atoms to this line of breast cancer cells in culture to effect cytotoxicity and suppression of growth after thermal neutron irradiation.


Asunto(s)
Terapia por Captura de Neutrón de Boro/métodos , Boro/administración & dosificación , Boro/uso terapéutico , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Liposomas/administración & dosificación , División Celular , Rayos gamma , Humanos , Isótopos/administración & dosificación , Isótopos/uso terapéutico , Liposomas/química , Neutrones , Soluciones , Células Tumorales Cultivadas
14.
Transplantation ; 72(11): 1803-7, 2001 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-11740392

RESUMEN

BACKGROUND: Tauroursodeoxycholic acid (TUDC) is a hydrophilic bile acid that has a cytoprotective effect in primary biliary cirrhosis and primary sclerosing cholangitis. TUDC also protects hepatocytes from hydrophobic bile acid-induced apoptosis. The aim of this study was to determine whether TUDC ameliorates hepatocyte apoptosis during ischemia-reperfusion injury. METHODS: We used a rat model of hepatic warm ischemia-reperfusion injury to assess the effects of TUDC. Male Sprague-Dawley rats were subjected to 1 or 2 hr of normothermic ischemia followed by 3 or 6 hr of reperfusion. The treatment group received TUDC (50 mg/kg) by bolus intravenous injection 30 min before initiation of ischemia, whereas the control group received saline only. Blood samples for biochemical analysis were obtained after 6 hr of reperfusion. Liver biopsies for histological assessment were obtained 3 and 6 hr after reperfusion. Hepatocyte apoptosis was determined by terminal dUTP nick-end labeling. The pro-apoptotic protein Bax was quantified at the mRNA and protein level. RESULTS: Treatment with TUDC significantly reduced serum transaminase levels. This was associated with a significant amelioration in the levels of hepatocyte apoptosis in the TUDC-treated group compared with control. Furthermore, Western blot analysis of Bax expression in liver tissue indicated that TUDC inhibited the translocation of Bax from the cytosol to the mitochondria. CONCLUSIONS: TUDC significantly reduced hepatic injury in this model. The beneficial effects of TUDC upon hepatocyte apoptosis were related to the modulation of Bax protein translocation.


Asunto(s)
Isquemia/patología , Circulación Hepática , Mitocondrias Hepáticas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2 , Proteínas Proto-Oncogénicas/metabolismo , Daño por Reperfusión/patología , Ácido Tauroquenodesoxicólico/farmacología , Animales , Aspartato Aminotransferasas/sangre , Transporte Biológico/efectos de los fármacos , Western Blotting , Citoprotección , Expresión Génica , Etiquetado Corte-Fin in Situ , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Proteínas Proto-Oncogénicas/genética , Ratas , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2
15.
Gan To Kagaku Ryoho ; 28(11): 1591-4, 2001 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-11707987

RESUMEN

Fifty-eight patients with hepatic tumor which consisted of 22 hepatocellular carcinomas and 36 metastatic liver tumors were treated by microwave coagulation therapy with MRI navigation. The tumors were located in all segments of liver except S1. In 24 cases among them, the abdominal approach was difficult, because the tumors were located just below the diaphragm. These cases were selected for thoracoscope-assisted microwave ablation under MR-guidance across the diaphragm. All MR data were collected on a vertically oriented open MRI system (0.5 T SIGNA SP/i system: GE Medical Systems). The microwave electrode was introduced into the liver through a 14G needle via a percutaneous puncture with real-time MR image navigation. Microwave ablations at 60 W for 60 seconds were repeated several times depending on the tumor size. MR imaging may be employed as a reliable guide for percutaneous puncture. Moreover, sufficient safety margin could be obtained for hepatic tumor ablation. MR-guided microwave thermoablation therapy is a feasible method of treatment for hepatic tumors.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Electrocoagulación/métodos , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/patología , Microondas/uso terapéutico
16.
Gan To Kagaku Ryoho ; 27(6): 909-13, 2000 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-10897220

RESUMEN

A 68-year-old man who had Borrmann type 4 gastric cancer with multiple liver metastases was admitted to our hospital on October 20, 1998. He was considered nonresectable and placed on neoadjuvant chemotherapy consisting of low-dose CDDP and 5-FU. After 9 weeks of administration, the liver metastases had disappeared on abdominal computed tomography, but the primary lesion had progressed. On May 12, 1999, a total gastrectomy with a partial resection of the transverse colon and resectional biopsy of a white nodule of the liver were performed. This was a non-curative operation because of the peritoneal dissemination. A histopathological examination of the liver nodule revealed that the cancer cells had disappeared. The patient had an uneventful postoperative course and 4 weeks of chemotherapy were added. He remains alive with no symptoms or re-growth of the liver metastatic tumor 4 months after the surgery.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Hepáticas/secundario , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Adenocarcinoma/cirugía , Anciano , Cisplatino/administración & dosificación , Terapia Combinada , Esquema de Medicación , Fluorouracilo/administración & dosificación , Gastrectomía , Humanos , Infusiones Intravenosas , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Terapia Neoadyuvante , Neoplasias Gástricas/cirugía
17.
Biochem Biophys Res Commun ; 272(3): 808-15, 2000 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-10860835

RESUMEN

Carbonic anhydrase II (CAII) catalyzes the reversible hydration of carbon dioxide and plays key roles in acid base homeostasis in mammals. We found that human CAII gene promoter could be activated in human cells such as HeLa and T47D cells when the CAII promoter-luciferase gene was transfected with v-Src and assayed as a reporter of the promoter activity. Kinase negative mutants of Src, in contrast, showed little activation. The activation was completely suppressed with the introduction of a dominant-negative Ras in T47D cells, while no suppression was observed in HeLa cells. Introduction of various kinds of deletions into the CAII promoter revealed two essential regions responsible for this activation. No activation, however, was observed in activated Fyn-transfected human cells or in v-Src-transfected rodent cells. These findings suggest that Src can modulate the human CAII promoter by exerting its tyrosine kinase activity in certain human cells, and that two types of Src signaling pathways, Ras-dependent and -independent, exist in a cell type dependent manner.


Asunto(s)
Anhidrasas Carbónicas/genética , Proteína Oncogénica pp60(v-src)/metabolismo , Regiones Promotoras Genéticas/genética , Activación Transcripcional/genética , Proteínas ras/metabolismo , Animales , Línea Celular , Activación Enzimática , Genes Dominantes/genética , Genes Reporteros/genética , Humanos , Ratones , Mutación/genética , Proteína Oncogénica pp60(v-src)/genética , Especificidad de Órganos , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-fyn , Ratas , Elementos de Respuesta/genética , Transducción de Señal , Transfección , Células Tumorales Cultivadas , Proteínas ras/genética
18.
Int J STD AIDS ; 11(6): 406-9, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10872915

RESUMEN

This study determines the factors which correlate with attitudes towards mother-to-child transmission of HIV in pregnant women. Using a structured questionnaire, 527 pregnant women who visited a hospital to have prenatal checkups were interviewed. The survey items were: sociodemographic characteristics, experiences of pre-test counselling, knowledge of mother-to-child transmission, and attitude towards termination of pregnancy. Results showed that many pregnant women (80%) did not have proper knowledge of the possibility of mother-to-child transmission. Logistic regression analysis also indicates that age and knowledge of the possibility of mother-to-child transmission were the significant determinants of attitudes towards termination of pregnancy. Older women who believe that all the babies of pregnant women with HIV will be infected are most likely to terminate their pregnancy when they are diagnosed as HIV positive. Considering the importance of informed decisions regarding pregnancy, this study must have important implications for future support programmes for HIV-positive pregnant women.


Asunto(s)
Infecciones por VIH/transmisión , Conocimientos, Actitudes y Práctica en Salud , Transmisión Vertical de Enfermedad Infecciosa , Adolescente , Adulto , Femenino , Infecciones por VIH/prevención & control , Infecciones por VIH/psicología , Maternidades , Humanos , Modelos Logísticos , Persona de Mediana Edad , Embarazo , Atención Prenatal , Encuestas y Cuestionarios , Tailandia/epidemiología
19.
Surg Today ; 30(5): 432-4, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10819479

RESUMEN

We report a 48-year-old-man with gastric carcinoma presenting with an unusual extraluminal growth. The patient underwent a barium meal examination and gastrofiberscopy because of progressive anemia over 6 months. These examinations revealed a Borrmann type 3 advanced gastric carcinoma of the greater curvature of the antrum. Biopsies showed moderately differentiated tubular adenocarcinoma. The intraoperative findings showed gastric carcinoma associated with extensive extraluminal invasion into the adjacent organs, i.e., the transverse colon and mesocolon. A palliative distal gastrectomy with a partial resection of the transverse colon was performed because of peritoneal dissemination found in the mesocolon and rectovesical pouch. A histological examination of the specimen confirmed adenocarcinoma which had massively infiltrated the transverse colon and mesocolon. His postoperative course was uneventful. However, he died of peritonitis carcinomatosa 9 months later.


Asunto(s)
Adenocarcinoma/diagnóstico , Neoplasias del Colon/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/cirugía , Biopsia con Aguja , Colectomía/métodos , Neoplasias del Colon/cirugía , Resultado Fatal , Estudios de Seguimiento , Gastrectomía/métodos , Gastroscopía , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Primarias Múltiples/cirugía , Cuidados Paliativos , Neoplasias Gástricas/cirugía , Tomografía Computarizada por Rayos X
20.
Surg Today ; 30(5): 458-61, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10819487

RESUMEN

A case of tuberculous peritonitis, which has been scarcely encountered in clinical practice in recent years, is reported. A 32-year-old man was admitted to our hospital complaining of abdominal fullness, anorexia, and a 15 kg weight loss. His abdomen was distended. There was neither any previous history nor recent contact with tuberculosis. The laboratory data indicated increased C-reactive protein and erythrocyte sedimentation rate, but the white blood cell count was normal. A chest X-ray examination revealed no abnormalities. Abdominal X-ray showed scattered, small-intestinal gas shadows. Abdominal computed tomography scanning revealed a diffuse thickening of the dilated bowel wall, mainly adjacent to the mesentery. After a detailed examination a diagnosis of peritonitis carcinomatosa of unknown origin was suspected, and an exploratory laparotomy was done. Severe adhesions between the parietal peritoneum and the bowel were found. An excisional biopsy specimen was taken from the peritoneum, and a diagnosis of tuberculosis was thus made. Triple therapy with isoniazid, rifampicin, and kanamycin was started, and both the intestinal obstruction and anorexia were thus resolved.


Asunto(s)
Peritonitis Tuberculosa/diagnóstico , Peritonitis/microbiología , Adulto , Antituberculosos/administración & dosificación , Biopsia , Estudios de Seguimiento , Humanos , Laparotomía , Masculino , Peritoneo/patología , Peritonitis/diagnóstico , Peritonitis/tratamiento farmacológico , Peritonitis Tuberculosa/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
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