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1.
Oral Dis ; 20(7): 700-6, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25360469

ABSTRACT

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.


Subject(s)
Non-alcoholic Fatty Liver Disease/microbiology , Streptococcal Infections/complications , Streptococcus mutans , Animals , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , Severity of Illness Index
2.
Eur J Surg Oncol ; 40(5): 521-528, 2014 May.
Article in English | MEDLINE | ID: mdl-24388411

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Hyperthermia, Induced/methods , Neoplasm Seeding , Peritoneal Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Combined Modality Therapy , Female , Fluorouracil/administration & dosage , HCT116 Cells , Humans , In Vitro Techniques , Infusions, Parenteral , Male , Middle Aged , Mitomycin/administration & dosage , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Peritoneal Neoplasms/secondary , Treatment Outcome
3.
Oral Dis ; 20(4): 359-66, 2014 May.
Article in English | MEDLINE | ID: mdl-23679203

ABSTRACT

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.


Subject(s)
Colitis, Ulcerative/microbiology , Streptococcus/pathogenicity , Animals , Disease Progression , Inflammatory Bowel Diseases/microbiology , Mice , Mice, Inbred C57BL , Mouth/microbiology , Streptococcus/isolation & purification
4.
Arch Oral Biol ; 58(11): 1627-34, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24112728

ABSTRACT

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.


Subject(s)
Adhesins, Bacterial/immunology , Bacterial Adhesion/immunology , Collagen/immunology , Endocarditis, Bacterial/microbiology , Mouth/microbiology , Streptococcus mutans/pathogenicity , Adhesins, Bacterial/metabolism , Collagen/metabolism , Culture Techniques , Endocarditis, Bacterial/immunology , Humans , Microscopy, Confocal , Protein Binding/genetics , Protein Binding/immunology , Reverse Transcriptase Polymerase Chain Reaction , Streptococcus mutans/classification , Streptococcus mutans/immunology , Virulence
5.
Oral Dis ; 19(4): 387-93, 2013 May.
Article in English | MEDLINE | ID: mdl-22998492

ABSTRACT

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.


Subject(s)
Adhesins, Bacterial/metabolism , Carrier Proteins/metabolism , Collagen/metabolism , Endocarditis, Bacterial/microbiology , Streptococcal Infections/microbiology , Streptococcus mutans/chemistry , Adhesins, Bacterial/genetics , Adult , Aged , Aortic Valve/microbiology , Bacterial Adhesion , Carrier Proteins/genetics , DNA, Bacterial , Endocarditis, Bacterial/metabolism , Endothelial Cells/microbiology , Female , Human Umbilical Vein Endothelial Cells/microbiology , Humans , Male , Middle Aged , Mitral Valve/microbiology , Protein Binding , Streptococcal Infections/metabolism
6.
Mol Oral Microbiol ; 27(4): 308-23, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22759315

ABSTRACT

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.


Subject(s)
Adhesins, Bacterial/chemistry , Collagen Type I/metabolism , Endocarditis, Bacterial/microbiology , Protein Binding , Streptococcus mutans/chemistry , Adolescent , Adult , Aged , Aged, 80 and over , Base Sequence , Child , Child, Preschool , Female , Finland , Gene Knockout Techniques , Genes, Bacterial , Humans , Japan , Male , Middle Aged , Saliva/microbiology , Serotyping , Streptococcus mutans/classification , Thailand , Transformation, Bacterial , Virulence/genetics , Young Adult
7.
Arch Oral Biol ; 57(9): 1183-8, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22417880

ABSTRACT

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.


Subject(s)
Dental Plaque/microbiology , Gram-Negative Bacteria/isolation & purification , Periodontal Diseases/microbiology , Pets/microbiology , Aggregatibacter actinomycetemcomitans/isolation & purification , Animals , Bacteroides/isolation & purification , Campylobacter rectus/isolation & purification , Capnocytophaga/isolation & purification , Dogs , Eikenella corrodens/isolation & purification , Female , Humans , Male , Periodontal Diseases/veterinary , Porphyromonas/isolation & purification , Porphyromonas gingivalis/isolation & purification , Prevotella intermedia/isolation & purification , Prevotella nigrescens/isolation & purification , Treponema denticola/isolation & purification , Zoonoses/microbiology
8.
Oral Dis ; 17(4): 370-8, 2011 May.
Article in English | MEDLINE | ID: mdl-21029263

ABSTRACT

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.


Subject(s)
Aortic Aneurysm/pathology , Cardiovascular Diseases/pathology , Dental Plaque/microbiology , Porphyromonas gingivalis/isolation & purification , Aged , Aged, 80 and over , Aortic Aneurysm/microbiology , Aortic Aneurysm, Abdominal/microbiology , Aortic Aneurysm, Abdominal/pathology , Aortic Aneurysm, Thoracic/microbiology , Aortic Aneurysm, Thoracic/pathology , Calgranulin B/analysis , Cardiovascular Diseases/microbiology , Cell Proliferation , DNA, Bacterial/analysis , Dilatation, Pathologic/pathology , Female , Fimbriae Proteins/genetics , Humans , Hyperplasia , Immunohistochemistry , Male , Middle Aged , Muscle, Smooth, Vascular/pathology , Myosin Heavy Chains/analysis , Pili, Sex/genetics , Polymerase Chain Reaction , Porphyromonas gingivalis/genetics , Protein Isoforms/analysis
9.
Arch Oral Biol ; 55(6): 410-6, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20398892

ABSTRACT

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.


Subject(s)
Glycosyltransferases/deficiency , Platelet Aggregation , Streptococcus mutans/enzymology , Adult , Analysis of Variance , Animals , Blood/microbiology , Gene Expression , Glycosyltransferases/biosynthesis , Glycosyltransferases/genetics , Humans , Male , Mice , Mice, Inbred ICR , Mouth/microbiology , Platelet-Rich Plasma/microbiology , Species Specificity , Streptococcus mutans/physiology
10.
Arch Oral Biol ; 55(1): 34-9, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20005510

ABSTRACT

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.


Subject(s)
Adhesins, Bacterial/genetics , Carrier Proteins/genetics , Collagen/metabolism , Streptococcus mutans/genetics , Blotting, Southern , Dental Caries/microbiology , Finland , Gene Expression Regulation, Bacterial/physiology , Glucans/metabolism , Humans , Japan , Polymerase Chain Reaction , Protein Binding/genetics , Saliva/microbiology , Streptococcus mutans/isolation & purification , Streptococcus mutans/pathogenicity , Thailand
11.
Transplant Proc ; 41(1): 425-8, 2009.
Article in English | MEDLINE | ID: mdl-19249571

ABSTRACT

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.


Subject(s)
Cell Transplantation/methods , Gastric Mucosa/physiology , Hepatocytes/cytology , Hepatocytes/transplantation , Animals , Hepatectomy , Liver Failure/surgery , Male , Rats , Rats, Inbred Lew , Stomach , Transplantation, Homologous/methods
12.
Med Arh ; 56(3): 127-9, 2002.
Article in Croatian | MEDLINE | ID: mdl-12378855

ABSTRACT

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).


Subject(s)
Ethanol/pharmacology , Muscle, Smooth/drug effects , Respiratory Distress Syndrome, Newborn/physiopathology , Trachea/drug effects , Gestational Age , Humans , In Vitro Techniques , Infant, Newborn , Muscle Contraction/drug effects , Muscle, Smooth/physiopathology , Trachea/physiopathology
13.
Biomed Pharmacother ; 56(2): 93-9, 2002 Mar.
Article in English | MEDLINE | ID: mdl-12000141

ABSTRACT

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.


Subject(s)
Boron Neutron Capture Therapy/methods , Boron/administration & dosage , Boron/therapeutic use , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Liposomes/administration & dosage , Cell Division , Gamma Rays , Humans , Isotopes/administration & dosage , Isotopes/therapeutic use , Liposomes/chemistry , Neutrons , Solutions , Tumor Cells, Cultured
14.
Transplantation ; 72(11): 1803-7, 2001 Dec 15.
Article in English | MEDLINE | ID: mdl-11740392

ABSTRACT

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.


Subject(s)
Ischemia/pathology , Liver Circulation , Mitochondria, Liver/metabolism , Proto-Oncogene Proteins c-bcl-2 , Proto-Oncogene Proteins/metabolism , Reperfusion Injury/pathology , Taurochenodeoxycholic Acid/pharmacology , Animals , Aspartate Aminotransferases/blood , Biological Transport/drug effects , Blotting, Western , Cytoprotection , Gene Expression , In Situ Nick-End Labeling , Liver/drug effects , Liver/pathology , Male , Proto-Oncogene Proteins/genetics , Rats , Rats, Sprague-Dawley , bcl-2-Associated X Protein
15.
Gan To Kagaku Ryoho ; 28(11): 1591-4, 2001 Oct.
Article in Japanese | MEDLINE | ID: mdl-11707987

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular/surgery , Electrocoagulation/methods , Liver Neoplasms/surgery , Magnetic Resonance Imaging , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/pathology , Microwaves/therapeutic use
16.
Gan To Kagaku Ryoho ; 27(6): 909-13, 2000 Jun.
Article in Japanese | MEDLINE | ID: mdl-10897220

ABSTRACT

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.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/secondary , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Liver Neoplasms/secondary , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Adenocarcinoma/surgery , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Drug Administration Schedule , Fluorouracil/administration & dosage , Gastrectomy , Humans , Infusions, Intravenous , Liver Neoplasms/drug therapy , Male , Neoadjuvant Therapy , Stomach Neoplasms/surgery
17.
Int J STD AIDS ; 11(6): 406-9, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10872915

ABSTRACT

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.


Subject(s)
HIV Infections/transmission , Health Knowledge, Attitudes, Practice , Infectious Disease Transmission, Vertical , Adolescent , Adult , Female , HIV Infections/prevention & control , HIV Infections/psychology , Hospitals, Maternity , Humans , Logistic Models , Middle Aged , Pregnancy , Prenatal Care , Surveys and Questionnaires , Thailand/epidemiology
18.
Biochem Biophys Res Commun ; 272(3): 808-15, 2000 Jun 16.
Article in English | MEDLINE | ID: mdl-10860835

ABSTRACT

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.


Subject(s)
Carbonic Anhydrases/genetics , Oncogene Protein pp60(v-src)/metabolism , Promoter Regions, Genetic/genetics , Transcriptional Activation/genetics , ras Proteins/metabolism , Animals , Cell Line , Enzyme Activation , Genes, Dominant/genetics , Genes, Reporter/genetics , Humans , Mice , Mutation/genetics , Oncogene Protein pp60(v-src)/genetics , Organ Specificity , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-fyn , Rats , Response Elements/genetics , Signal Transduction , Transfection , Tumor Cells, Cultured , ras Proteins/genetics
19.
Surg Today ; 30(5): 432-4, 2000.
Article in English | MEDLINE | ID: mdl-10819479

ABSTRACT

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.


Subject(s)
Adenocarcinoma/diagnosis , Colonic Neoplasms/diagnosis , Neoplasms, Multiple Primary/diagnosis , Stomach Neoplasms/diagnosis , Adenocarcinoma/surgery , Biopsy, Needle , Colectomy/methods , Colonic Neoplasms/surgery , Fatal Outcome , Follow-Up Studies , Gastrectomy/methods , Gastroscopy , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasms, Multiple Primary/surgery , Palliative Care , Stomach Neoplasms/surgery , Tomography, X-Ray Computed
20.
Surg Today ; 30(5): 458-61, 2000.
Article in English | MEDLINE | ID: mdl-10819487

ABSTRACT

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.


Subject(s)
Peritonitis, Tuberculous/diagnosis , Peritonitis/microbiology , Adult , Antitubercular Agents/administration & dosage , Biopsy , Follow-Up Studies , Humans , Laparotomy , Male , Peritoneum/pathology , Peritonitis/diagnosis , Peritonitis/drug therapy , Peritonitis, Tuberculous/drug therapy , Tomography, X-Ray Computed , Treatment Outcome
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