Biomedical subjects

Hiroko Sato

Publications and source records attributed to Hiroko Sato.

At least 19 recordsLinked to original sources

PubMed2006

Jagged1-selective notch signaling induces smooth muscle differentiation via a RBP-Jkappa-dependent pathway.

The Notch signaling pathway plays a crucial role in specifying cellular fates by interaction between cellular neighbors; however, the molecular mechanism underlying smooth muscle cell (SMC) differentiation by Notch signaling has not been well characterized. Here we demonstrate that Jagged1-Notch signaling promotes SMC differentiation from mesenchymal cells. Overexpression of the Notch intracellular domain, an activated form of Notch, up-regulates the expression of multiple SMC marker genes including SMC-myosin heavy chain (Sm-mhc) in mesenchymal 10T1/2 cells, but not in non-mesenchymal cells. Physiological Notch stimulation by its ligand Jagged1, but not Dll4, directly induces Sm-mhc expression in 10T1/2 cells without de novo protein synthesis, indicative of a ligand-selective effect. Jagged1-induced expression of SM-MHC was blocked bygamma-secretase inhibitor, N-(N-(3,5-difluorophenyl)-l-alanyl)-S-phenylglycine t-butyl ester, which impedes Notch signaling. Using Rbp-jkappa-deficient cells and site-specific mutagenesis of the SM-MHC gene, we show that such an induction is independent of the myocardin-serum response factor-CArG complex, but absolutely dependent on RBP-Jkappa, a major mediator of Notch signaling, and its cognate binding sequence. Of importance, Notch signaling and myocardin synergistically activate SM-MHC gene expression. Taken together, these data suggest that the Jagged1-Notch pathway constitutes an instructive signal for SMC differentiation through an RBP-Jkappa-dependent mechanism and augments gene expression mediated by the myocardin-SRF-CArG complex. Given that Notch pathway components are expressed in vascular SMC during normal development and disease, Notch signaling is likely to play a pivotal role in such situations to modulate the vascular smooth muscle cell phenotype.

Adenoviridae↗

PubMed2006

The elevated level of circulating matrix metalloproteinase-9 in patients with abdominal aortic aneurysms decreased to levels equal to those of healthy controls after an aortic repair.

Matrix metalloproteinase-9 (MMP-9) is abundantly expressed in abdominal aortic aneurysms (AAAs), and it is considered to play a pivotal role in aneurysmal formation. Elevated circulating concentrations of MMP-9 have been reported in patients with AAA, but the influence of an operation on circulating MMP-9 is unclear. Therefore, to clarify the influence of an operation on circulating MMP-9 levels and to determine the role of MMP-9 in the progression of AAA, we measured serum MMP-9 levels in patients before and after AAA repair. Blood samples were obtained from 53 patients with AAA; 22 patients underwent AAA operations, including 17 patients with arterial occlusive disease (AOD), and nine normal control subjects. Serum MMP-9 levels were determined by an enzyme-linked immunosorbent assay. The serum MMP-9 concentration was significantly higher in AAA patients (622.0 +/- 400.2 ng/mL) than in either AOD patients (284.3 +/- 151.4 ng/mL) or healthy controls (280.8 +/- 165.5 ng/mL) (p < 0.001). The mean serum MMP-9 levels in patients undergoing surgery for AAA (268.1 +/- 215.9 ng/mL) was significantly lower than that in AAA patients (p < 0.01). Among the 10 patients whose sera were obtained preoperatively and postoperatively, the serum MMP-9 concentration fell significantly after the patients underwent the operation (p = 0.004). No significant difference was identified in serum MMP-9 concentrations among AOD patients, controls, and postoperative patients. These studies suggest that MMP-9 plays a pivotal role in aneurysm formation, and the circulating MMP-9 level is thus considered to reflect the biological behavior of the aneurysm.

Aged↗

PubMed2006

Genetic exchange of the S2 and S3 subunits in pertussis toxin.

Bordetella pertussis, the causative agent of whooping cough, produces a complex hetero-oligomeric exotoxin, named pertussis toxin (PTX), which is responsible for several of the clinical manifestations associated with whooping cough. The toxin is composed of five dissimilar subunits, named S1 through S5 and arranged in a hexameric structure with a 1S1:1S2:1S3:2S4:1S5 stoichiometry. Although S2 and S3 share 70% amino acid identity, these two subunits were previously thought not to be able to substitute for each other in toxin assembly/secretion and the biological activities of PTX. Here, we show that toxin analogues containing two S3 subunits and lacking S2 (PTXdeltaS2), or containing two S2 subunits and lacking S3 (PTXdeltaS3), can be produced, assembled and secreted by B. pertussis strains, in which the S2-encoding cistron or the S3-coding cistrons have been inactivated by internal in-frame deletions that avoid downstream effects. In fact, PTXdeltaS3 was produced in higher amounts in the bacterial culture supernatants than natural PTX, whereas PTXdeltaS2 was produced in lower amounts than PTX. The action of the toxin analogues on the clustering of Chinese Hamster Ovary cells was also affected differentially by the S2-S3 substitution. These toxin analogues constitute thus interesting probes for the study of cellular functions, in particular immune cell functions, for which natural PTX has already shown its usefulness.

Amino Acid Sequence↗

PubMed2005

Tead proteins activate the Foxa2 enhancer in the node in cooperation with a second factor.

The cell population and the activity of the organizer change during the course of development. We addressed the mechanism of mouse node development via an analysis of the node/notochord enhancer (NE) of Foxa2. We first identified the core element (CE) of the enhancer, which in multimeric form drives gene expression in the node. The CE was activated in Wnt/beta-catenin-treated P19 cells with a time lag, and this activation was dependent on two separate sequence motifs within the CE. These same motifs were also required for enhancer activity in transgenic embryos. We identified the Tead family of transcription factors as binding proteins for the 3' motif. Teads and their co-factor YAP65 activated the CE in P19 cells, and binding of Tead to CE was essential for enhancer activity. Inhibition of Tead activity by repressor-modified Tead compromised NE enhancer activation and notochord development in transgenic mouse embryos. Furthermore, manipulation of Tead activity in zebrafish embryos led to altered expression of foxa2 in the embryonic shield. These results suggest that Tead activates the Foxa2 enhancer core element in the mouse node in cooperation with a second factor that binds to the 5' element, and that a similar mechanism also operates in the zebrafish shield.

Animals↗

PubMed2005

HERP1 inhibits myocardin-induced vascular smooth muscle cell differentiation by interfering with SRF binding to CArG box.

OBJECTIVE: Myocardin is a coactivator of serum response factor (SRF) required for vascular smooth muscle cell (VSMC) differentiation. HERP1 is a transcriptional repressor, which is abundantly expressed in vascular system and is known to function as a target gene of Notch. However, the role of HERP1 in the pathogenesis of vascular lesions remains unknown. The present study characterizes the expression of HERP1 in normal and diseased vessels, and tests the hypothesis that HERP1 inhibits SRF/myocardin-dependent SMC gene expression. METHODS AND RESULTS: Immunohistochemistry revealed that HERP1 and myocardin expression was localized to SMC in the neointima of balloon-injured rat aorta and in human coronary atherosclerotic lesions. Expression of both HERP1 and myocardin was elevated in cultured VSMCs compared with medial SMC. Overexpressed HERP1 inhibited the myocardin-induced SMC marker gene expression in 10T1/2 cells. HERP1 protein interfered with the SRF/CArG-box interaction in vivo and in vitro. Immunoprecipitation assays showed that HERP1 physically interacts with SRF. CONCLUSIONS: HERP1 expression was associated with the SMC proliferation and dedifferentiation in vitro and in vivo. HERP1 may play a role in promoting the phenotypic modulation of VSMCs during vascular injury and atherosclerotic process by interfering with SRF binding to CArG-box through physical association between HERP1 and SRF.

Adult↗

PubMed2005

Glucose-6-phosphate dehydrogenase (G6PD) mutations in Cambodia: G6PD Viangchan (871G>A) is the most common variant in the Cambodian population.

We conducted a survey of malaria diagnoses and glucose-6-phosphate dehydrogenase (G6PD) testing in remote areas of Cambodia. Blood specimens from 670 people were collected by the finger-prick method. Of these people, 24.9% were found to have malaria, and 7.0% of people were G6PD deficient. In the Khmer, the largest ethnical population in Cambodia, the G6PD deficiency rate of males was 12.6% (25/199) whereas the rates in the minorities of the Tum Pun and the Cha Ray were 1.1% (1/93) and 3.2% (2/63), respectively. Of the G6PD-deficient subjects, 97.9% (46/47) were G6PD Viangchan (871G>A), and only one case (2.1%) was G6PD Union (1360C>T). Since G6PD Mahidol (487G>A) is common in Myanmar according to our previous study, the current finding suggests that the Cambodian population is derived from homogeneous ancestries and is different from the Myanmar population. All G6PD Viangchan cases were linked to two other mutations of 1311C>T and IVS-11 nt93T>C in the G6PD gene.

Cambodia↗

PubMed2005

Mitochondrial reactive oxygen species and c-Src play a critical role in hypoxic response in vascular smooth muscle cells.

OBJECTIVE: Thickened atherosclerotic plaques are prone to be hypoxic because of poor perfusion. In this study, we tested (a) whether reactive oxygen species (ROS) and c-Src play roles in hypoxic induction of HIF-1alpha protein and PAI-1 gene expression in the rabbit aortic smooth muscle cell line C2/2 cells and primary cultures of rat aortic smooth muscle cells, and (b) how mitochondria act on the hypoxia-induced signaling mechanism. METHODS AND RESULTS: Hypoxic exposure of C2/2 cells increased H2O2 generation, c-Src phosphorylation, HIF-1alpha protein expression, and PAI-1 gene expression. Catalase, a scavenger of H2O2, inhibited the hypoxia-induced ROS generation and PAI-1 gene expression. Src kinase inhibitors PP1 and PP2 inhibited hypoxia-induced HIF-1alpha protein and PAI-1 gene expression. Ablation of mitochondrial respiration by rotenone abolished hypoxia-induced ROS generation, c-Src phosphorylation, HIF-1alpha protein expression, and PAI-1 gene expression. CONCLUSION: Induction of HIF-1alpha protein and PAI-1 gene expression in response to hypoxia was regulated by ROS production and c-Src activation in vascular smooth muscle cells. Mitochondria linked the hypoxic signal to c-Src, which in turn led to HIF-1alpha protein and PAI-1 gene expression. These results provide evidence that hypoxia induces the ROS-mediated and c-Src-dependent signaling cascades which are closely associated with angiogenesis and thrombosis in atherosclerotic vasculature.

Androstadienes↗

PubMed2005

Beneficial effect of complementary alternative medicine on lymphedema with rheumatoid arthritis.

Lymphedema of the limbs can be an added complication in a small number of rheumatoid arthritis cases, becoming a long-standing problem even when there is good control of inflammatory joint disease. In the present article, we describe a patient with RA who developed lymph-edema of the forearms successfully treated with TJ-48 (Juzentaihoto) as a complementary alternative medicine (CAM). This kind of edema does not seem to show any consistent relationship with the severity of arthritis in the literature surveyed. In contrast, lymphedema in this case improved in parallel with RA disease activity. We discuss the utility of CAM treatments and review the literature.

Journal Article↗

PubMed2005

A novel mechanism of autolysis in Helicobacter pylori: possible involvement of peptidergic substances.

BACKGROUND: Helicobacter pylori survival in a hostile acidic environment is known to be caused by its production of urease, which is not released by known secretion pathways. It has been proposed that H. pylori cells undergo spontaneous autolysis during cultivation and that urease becomes surface-associated only concomitant with bacterial autolysis. The aim of this study was to elucidate mechanisms by which H. pylori cells undergo autolysis during cultivation. MATERIALS AND METHODS: Autolysis of H. pylori KZ109 cells was estimated by measuring the turbidity of the culture, by detection of cytoplasmic protein release into the culture supernatant and by scanning electron microscopic observation of H. pylori cells during cultivation. An autolysis-inducing factor (AIF) was partially purified from the culture supernatant by a partition method using ethyl acetate. RESULTS: Bacterial turbidity of KZ109 cells was drastically decreased after late-log phase accompanying release of urease and HspB into the extracellular space. Concomitantly, cell lytic activity was detected in the culture supernatant. Scanning electron microscopic observation suggested that partially purified AIF induced cell lysis. It was also shown that the AIF is different from other autolytic enzymes or substances so far reported. CONCLUSIONS: This study demonstrated the presence of the peptidergic autolytic substances in the culture supernatant of H. pylori KZ109 cells. The results of this study should be useful for further studies aimed at elucidation of the strategy of survival of H. pylori in the gastric environment and elucidation of the mechanisms of pathogenesis induced by H. pylori.

Bacterial Proteins↗

PubMed2004

c-Src and hydrogen peroxide mediate transforming growth factor-beta1-induced smooth muscle cell-gene expression in 10T1/2 cells.

OBJECTIVE: Transforming growth factor-beta1 (TGF-beta1) controls the expression of numerous genes, including smooth muscle cell (SMC)-specific genes and extracellular matrix protein genes. Here we investigated whether c-Src plays a role in TGF-beta1 signaling in mouse embryonic fibroblast C3H10T1/2 cells. METHODS AND RESULTS: TGF-beta1 induction of the SMC contractile protein SM22alpha gene expression was inhibited by PP1 (an inhibitor of Src family kinases) or by C-terminal Src kinase (a negative regulator of c-Src). Induction of SM22alpha by TGF-beta1 was markedly attenuated in SYF cells (c-Src(-), Yes(-), and Fyn(-)) compared with Src(++) cells (c-Src(++), Yes(-), and Fyn(-)). PP1 also inhibited the TGF-beta1-induced expression of serum response factor (SRF), a transcription factor regulating the SMC marker gene expression. Confocal immunofluorescence analysis showed that TGF-beta1 stimulates production of hydrogen peroxide. Antioxidants such as catalase or NAD(P)H oxidase inhibitors such as apocynin inhibited the TGF-beta1-induced expression of SM22alpha. Furthermore, we demonstrate that TGF-beta1 induction of the plasminogen activator inhibitor-1 (PAI-1) gene, which is known to be dependent on Smad but not on SRF, is inhibited by PP1 and apocynin. CONCLUSIONS: Our results suggest that TGF-beta1 activates c-Src and generates hydrogen peroxide through NAD(P)H oxidase, and these signaling pathways lead to the activation of specific sets of genes, including SM22alpha and PAI-1. TGF-beta1 controls the expression of numerous genes, including SM22alpha and PAI-1. We investigated whether c-Src plays a role in TGF-beta1 signaling. TGF-beta1 induction of such genes was significantly reduced in Src family tyrosine kinase-deficient cells, and Csk and pharmacological inhibitors for Src family kinases or antioxidants inhibit the effects of TGF-beta1. These results indicate that c-Src and hydrogen peroxide are required for TGF-beta1 signaling.

Acetophenones↗

PubMed2004

The diphtheria and pertussis components of diphtheria-tetanus toxoids-pertussis vaccine should be genetically inactivated mutant toxins.

Replacement of cellular with acellular pertussis (aP) vaccines has considerably reduced the systemic reactions observed with diphtheria-tetanus toxoids-pertussis vaccine but has not eliminated the extensive swelling (sometimes involving an entire limb) observed after the fifth injection of diphtheria-tetanus toxoids-aP (DTaP) vaccine. This local reaction, which is likely an Arthus hypersensitivity reaction caused by high levels of antibodies reacting with DTaP vaccine, could discourage its use in adults, who serve as the major reservoir of pertussis for infants. That a critical level of antibodies to pertussis toxin is both essential and sufficient to prevent infection with Bordetella pertussis is derived from data from animal and clinical studies, including data showing the similarities between the immunity induced by diphtheria and pertussis toxoids. The genetically inactivated diphtheria and pertussis mutant toxins are more immunogenic and, therefore, induce comparable levels of antitoxin at lower protein levels than do the formalin-treated native toxins. Replacement of the diphtheria and aP components with these improved antigens will reduce the amount of protein in DTaP vaccine and, most likely, the incidence and severity of local reactions in teenagers and adults.

Adult↗

PubMed2004

Overshoot and oscillation in surface tension of gelatin solutions.

The experimental data of the surface tension of aqueous gelatin solution reported by Sato and Ueberreiter [H. Sato, K. Ueberreiter, Macromol. Chem. 180 (1979) 829; H. Sato, K. Ueberreiter, Macromol. Chem. 180 (1979) 1107; H. Sato, K. Ueberreiter, ACS Polym. Preprints 20 (1979) 907] were analyzed with a theory of adsorption kinetics with time delay. It is found that the observed overshoot and oscillation of the surface tension are well explained by the present theory. The delay time and the rate constants of adsorption and desorption of gelatin molecules onto the air/gelatin solution interface have been evaluated.

Adsorption↗

PubMed2004

Homeobox protein Hex facilitates serum responsive factor-mediated activation of the SM22alpha gene transcription in embryonic fibroblasts.

OBJECTIVE: Hex (hematopoietically expressed homeobox), a member of homeobox family of transcription factors, has been implicated in the vascular development because of its expression in hemangioblast, a hypothetical stem cell that gives rise to both angioblasts and hematopoietic lineages. In the present study, we examined the role of Hex in the differentiation of vascular smooth muscle cells. METHODS AND RESULTS: We constructed adenovirus expressing Hex, to which we refer to as AxCA/Hex, and transduced murine embryonic fibroblasts, 10T1/2 cells. Northern blot analyses showed that Hex increased the mRNA levels of smooth muscle alpha-actin and SM22alpha but not of calponin and smooth muscle myosin heavy chain. Transient transfection assays showed that Hex activates the transcription from the SM22alpha promoter in a CArG box-dependent manner. Electrophoretic mobility shift assays demonstrate that Hex is not able to bind to CArG box, but binding of serum responsive factor (SRF) to CArG box is enhanced in AxCA/Hex-transduced cells. Recombinant Hex protein produced by in vitro translation system augmented the binding activity of SRF to CArG box. Immunoprecipitation experiments revealed the physical association between Hex and SRF. CONCLUSIONS: Hex induces transcription of the SM22alpha gene by facilitating the interaction between SRF and its cognate binding site in pluripotent embryonic fibroblasts. This study demonstrates that Hex, a hematopoietically expressed homeobox protein, induces transcription of the SM22alpha gene by facilitating the interaction between SRF and its cognate binding site in embryonic fibroblasts. These findings will provide the clue for understanding the mechanisms by which bone marrow-derived SMC precursor cells undergo differentiation.

Actins↗

PubMed2004

Basic fibroblast growth factor antagonizes transforming growth factor-beta1-induced smooth muscle gene expression through extracellular signal-regulated kinase 1/2 signaling pathway activation.

OBJECTIVE: Transforming growth factor-beta1 (TGFbeta1) and fibroblast growth factor (FGF) families play a pivotal role during vascular development and in the pathogenesis of vascular disease. However, the interaction of intracellular signaling evoked by each of these growth factors is not well understood. The present study was undertaken to examine the molecular mechanisms that mediate the effects of TGFbeta1 and basic FGF (bFGF) on smooth muscle cell (SMC) gene expression. METHODS AND RESULTS: TGFbeta1 induction of SMC gene expression, including smooth muscle protein 22-alpha (SM22alpha) and smooth muscle alpha-actin, was examined in the pluripotent 10T1/2 cells. Marked increase in these mRNA levels by TGFbeta1 was inhibited by c-Src-tyrosine kinase inhibitors and protein synthesis inhibitor cycloheximide. Functional studies with deletion and site-directed mutation analysis of the SM22alpha promoter demonstrated that TGFbeta1 activated the SM22alpha promoter through a CC(A/T-rich)6GG (CArG) box, which serves as a serum response factor (SRF)-binding site. TGFbeta1 increased SRF expression through an increase in transcription of the SRF gene. In the presence of bFGF, TGFbeta1 induction of SMC marker gene expression was significantly attenuated. Transient transfection assays showed that bFGF significantly suppressed induction of the SM22alpha promoter-driven luciferase activity by TGFbeta1, whereas bFGF had no effects on the TGFbeta1-mediated increase in SRF expression and SRF:DNA binding activity. Mitogen-activated protein kinase kinase-1 (MEK1) inhibitor PD98059 abrogated the bFGF-mediated suppression of TGFbeta1-induced SMC gene expression. CONCLUSIONS: Our data suggest that bFGF-induced MEK/extracellular signal-regulated kinase signaling plays an antagonistic role in TGFbeta1-induced SMC gene expression through suppression of the SRF function. These data indicate that opposing effects of bFGF and TGFbeta1 on SMC gene expression control the phenotypic plasticity of SMCs.

Actins↗

PubMed2004

The PAI-1 gene as a direct target of endothelial PAS domain protein-1 in adenocarcinoma A549 cells.

Endothelial PAS domain protein-1 (EPAS1) regulates transcription of the genes encoding erythropoietin and vascular endothelial growth factor, which are important for maintaining oxygen homeostasis. We have previously shown that plasminogen activator inhibitor-1 (PAI-1) gene expression is induced by hypoxia. In this study, we sought to determine whether PAI-1 gene expression is directly regulated by EPAS1 in cancer cells because activities of proteases and their inhibitors are tightly regulated for tumor invasion. Hypoxia increased the PAI-1 mRNA levels in human adenocarcinoma A549 cells. Overexpression of EPAS1 significantly increased the PAI-1 mRNA and protein levels. Transient transfection assays revealed that EPAS1 increased PAI-1 gene transcription through a sequence containing 5'-CACGTACA-3' located at -194 (we refer to it as site HREPAI-1) and GT-box located at -78. Electrophoretic gel mobility shift assays revealed that HREPAI-1 serves as a binding site for EPAS1, and Sp1 constitutively binds to GT-box. In conclusion, PAI-1 expression is induced by EPAS1 through HREPAI-1 and through an Sp1-binding site. These results indicate that the PAI-1 gene is a direct target of EPAS1 and suggest the role of EPAS1 and Sp1 in the hypoxic response of cancer cells.

Adenocarcinoma↗

PubMed2004

Kinetic study on the elastic change of vascular endothelial cells on collagen matrices by atomic force microscopy.

The elasticity of vascular endothelial cells (HUVEC) was measured with an atomic force microscopy (AFM, Olympus), and analyzed by applying the Hertz model, and those data were compared with ones reported by us previously. The latter elasticity data were measured with AFM Instruments (Seiko) on the basis of the Young's modulus of gelatin gel, which was obtained from the measurement with a tensile tester. The elasticity of HUVEC was concluded to depend on the culture period. The elasticity of the cells cultured on type IV collagen for longer than 4 days led to average elasticity values higher than ca. 10(4)Pa. Moreover, the scattered values of elasticity decreased eminently in the AFM measurement of the cells at room temperature. A few cells, however, appeared to adhere long and tensely on matrix, which seems to one of reasons for relatively high elasticity in our previous works. The possibility of such high elasticity was considered to change in cell adhesion, anchoring on matrix during a long culture period.

Cell Adhesion↗

PubMed2004

Nodular scleritis and panuveitis with erythema elevatum diutinum.

PURPOSE: To report a case of nodular scleritis and panuveitis associated with erythema elevatum diutinum, a rare immunocomplex-mediated skin disease. DESIGN: Observational case report. METHODS: A 22-year-old woman who was diagnosed with erythema elevatum diutinum developed nodular scleritis and panuveitis of the right eye. She had experienced peripheral ulcerative keratitis with corneal perforation. RESULTS: All other known causes of nodular scleritis and panuveitis were investigated and ruled out. CONCLUSIONS: Erythema elevatum diutinum should be considered as an underlying systemic disease associated with nodular scleritis and panuveitis as well as peripheral keratitis.

Adult↗

PubMed2004

[A nosocomial outbreak of diarrhea caused by toxin A-negative, toxin B-positive Clostridium difficile in a cancer center hospital].

Between February and July 2001, 15 patients were diagnosed as Clostridium difficile-associated diarrhea in a ward of hematological neoplasm and lung cancer in a cancer center hospital. Of these 15 patients, 10 had malignant lymphoma, and 12 and 11 had exposure to antimicrobial agents and cancer chemotherapy, respectively, before the onset of diarrhea. Toxin A-positive, toxin B-positive (A+ B+) C. difficile was recovered from five patients and the remaining 10 patients suffered from diarrhea caused by toxin A-negative, toxin B-positive (A- B+) strains. All of the 10A- B+ isolates represented an identical banding pattern by PCR ribotyping and classified into one type (two subtypes) by pulsed field gel electrophoresis typing, indicating that a nosocomial outbreak of diarrhea caused by A- B+ C. difficile occurred among the patients hospitalized on this ward. Detection of toxin A in stool specimens by a toxin A detection kit was performed on 14 patients. Although two patients who carried A+ B+ strains were positive for toxin A assay, toxin A detection test was negative in 12 patients including 10 patients with A- B+ C. difficile infection. Diagnosis of C. difficile-associated diarrhea by combination of toxin A assay in feces and culture of C. difficile could successfully lead to recognition of an outbreak caused by A- B+ C. difficile in a cancer center hospital.

Adult↗