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Masato Suzuki

Publications and source records attributed to Masato Suzuki.

49 records · Page 3Linked to original sources
PubMed2003

Lon, a stress-induced ATP-dependent protease, is critically important for systemic Salmonella enterica serovar typhimurium infection of mice.

Studies on the pathogenesis of Salmonella enterica serovar Typhimurium infections in mice have revealed the presence of two prominent virulence characteristics-the invasion of the nonphagocytic cells to penetrate the intestinal epithelium and the proliferation within host phagocytic cells to cause a systemic spread and the colonization of host organs. We have recently demonstrated that the ATP-dependent Lon protease of S. enterica serovar Typhimurium negatively regulates the efficiency of invasion of epithelial cells and the expression of invasion genes (A. Takaya et al., J. Bacteriol. 184:224-232, 2002). This study was performed to reveal the contribution of the Lon protease to the virulence of S. enterica serovar Typhimurium in mice. Determination of 50% lethal doses for the lon disruption mutant and wild-type strain revealed that the mutant was highly attenuated when administered either orally or intraperitoneally to BALB/c mice. The mutant was also found to be able to reach extraintestinal sites but unable to proliferate efficiently within the spleen and cause lethal systemic disease of mice. Macrophage survival assays revealed that the lon disruption mutant could not survive or proliferate within murine macrophages. In addition, the mutant showed extremely increased susceptibility to hydrogen peroxide, which contributes to the bactericidal capacity of phagocytes. The mutant also showed increased sensitivity to acidic conditions. Taken together, the impaired ability of the lon disruption mutant to survive and grow in macrophages could be due to the enhanced susceptibility to the oxygen-dependent killing mechanism associated with respiratory burst and the low phagosomal pH. These results suggest that the Lon protease is essentially involved in the systemic infection of mice with S. enterica serovar Typhimurium, which can be fatal. Of further interest is the finding that the lon disruption mutant persists in the BALB/c mice for long periods without causing an overwhelming systemic infection.

ATP-Dependent Proteases↗
PubMed2003

Distinct isoforms of protein kinase C are involved in human eosinophil functions induced by platelet-activating factor.

BACKGROUND: Platelet-activating factor (PAF) is a potent stimulator of eosinophils. Recently, treatment with a protein kinase C (PKC) inhibitor which generally inhibits PKC isoforms has been shown to modulate several eosinophil functions in distinct manners, in that PKC inhibition enhanced CD11b expression and cellular adhesion, but inhibited superoxide generation and degranulation in PAF-stimulated human eosinophils. These results suggested that distinct PKC isoforms were likely to be involved in each eosinophil function induced by PAF. We have therefore investigated whether or not the PKC isoforms involved in PAF-induced CD11b expression and superoxide generation were different. METHODS: Human eosinophils prepared from healthy volunteers were treated with PKC inhibitors, bis-indolylmaleimide I (BisI; a general PKC inhibitor), myristoylated PKC inhibitor peptide (myr-psiPKC; a PKCalpha, beta and delta inhibitor) and rottlerin (a PKCdelta inhibitor), followed by stimulation with PAF. CD11b expression was determined using flow cytometry and superoxide generation was evaluated using a cytochrome c reduction assay. RESULTS: BisI treatment led to enhancement of PAF-induced CD11b expression, while myr-psiPKC and rottlerin did not. In contrast, PAF-induced superoxide generation was inhibited by treatment with BisI, myr-psiPKC and rottlerin. CONCLUSIONS: PKCalpha, beta and delta are not involved in PAF-induced CD11b expression, but PKCdelta is involved in the PAF-induced activation of superoxide anion generation.

Acetophenones↗
PubMed2002

Facile preparation of mono-2-O-modified eicosa-O-methylcyclomaltoheptaoses (-beta-cyclodextrins).

Mono-2-O-benzylated eicosa-O-methylcyclomaltoheptaose (-beta-cyclodextrin) was prepared in one pot from cyclomaltoheptaose (beta-cyclodextrin) in 33% isolated yield and quantitatively converted to mono-2-OH-free eicosa-O-methylcyclomaltoheptaose, which is the key compound for further modification. Transformation of this 2-OH group successfully gave several mono-2-O-modified eicosa-O-methylcyclomaltoheptaoses such as the acetate, the N,N-dimethylcarbamate, the N-n-butylcarbamate, the methanesulfonate, and the S-methyldithiocarbonate.

Acetates↗
PubMed2002

Dynamic-enhanced MRI predicts metastatic potential of invasive ductal breast cancer.

BACKGROUND: Dynamic magnetic resonance imaging (MRI) has improved the detection of breast malignancies. The method is based on estimating the velocity of contrast enhancement taking into account increased angiogenesis in tumor. Microvessel density correlates with breast carcinoma metastasis. Thus, we hypothesized that contrast enhancement on MRI correlates with metastasis in breast cancer patients. The present study attempts to clarify the quantitative assessment of dynamic data, and examines the correlation between MRI enhancement and breast carcinoma metastasis. METHODS: The subjects consisted of 31 patients with invasive ductal breast cancer. Twenty patients were disease free for five years (group A), and eleven patients suffered from metastatic disease at distant sites concurrently or postoperatively (group B). Dynamic MRI was performed preoperatively using a 1.5T system in all cases. Using the dynamic data, the signal intensity (SI)ratio and SI index were determined and analyzed retrospectively taking into account the presence of distant metastases. RESULTS: The values of the SI ratio were 2.2+/-0.7 in group A and 2.3+/-0.4 in group B, respectively, with no significant difference seen between the groups. The SI index value was significantly higher in group B (28.5+/-32.8) than in group A (10.3+/-5.5, p<0.05). CONCLUSIONS: The current series suggests that the SI index could distinguish patients with high risk of distant metastasis from disease free patients, preoperatively. If a suitable borderline value were established, the quantitative dynamic parameter determined by MRI may be useful for predicting the prognosis of breast cancer patients.

Adult↗
PubMed2002

The first isolation of Nocardia nova from an HIV-1 infected individual in Japan.

Nocardia species are opportunistic pathogens of immunocompromised patients. We report a case of Nocardia nova infection complicating Pneumocystis carinii pneumonia (PCP) in an HIV-1 infected individual. A 27-year-old man with hemophilia A was admitted on October 17, 2000, with fever and dyspnea. CD4 cell counts were 5/microl on admission. Prophylaxis against PCP was administered by inhalation of pentamidine isethionate because he was allergic to sulfamethoxazole-trimethoprim (SMZ-TMP). He was diagnosed with PCP from chest X-ray and bronchoalveolar lavage. The sputum obtained for culture on admission was positive for Gram-positive branching rods; the organism was later identified as Nocardia nova. He died from respiratory failure on November 7, 2000. Although PCP might be a principal factor in respiratory failure, this case shows the need to consider pulmonary nocardiosis as a cause of respiratory illness in patients with advanced HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Disseminated coccidioidomycosis with intra- and paravertebral abscesses.

We report a case of paravertebral and intravertebral abscesses caused by Coccidioides immitis in a Japanese man. The patient had lived in Arizona, United States, for 5 years, and suffered from overt disease after coming back to Japan. Culture of pus from the paravertebral abscess revealed Coccidioides immitis, and a diagnosis of disseminated coccidioidomycosis was made. Fluconazole (600 mg/day), taken orally, was started, and the abscesses surrounding the vertebral bodies disappeared after 2 years of treatment. The abscess in the vertebral bodies also responded to treatment, but a small lesion was still left in the 10th vertebral body after 2 years of treatment. Coccidioidomycosis is a fungal infection that is endemic in the southwestern United States and in Central and South America. Although coccidioidomycosis causes self-limiting flu-like illness or pneumonia, a small proportion of the infections progress to disseminated diseases. Because the incidence of coccidioidomycosis is increasing year by year, physicians not only in endemic but also in nonendemic areas have to consider coccidioidomycosis as one of the differential diagnoses when they examine patients from endemic areas.

Abscess↗
PubMed2002

Nuclear morphometric analysis of T2 lesions of the rectum--a simple, reproducible method for predicting malignancy potential.

BACKGROUND: Using computerized nuclear morphometry, we searched for common, objective parameters for use in predicting potential malignancy of primary T2 tumors of the rectum. METHODS: In 119 surgically resected T2 rectal cancers, the following parameters of the cancer cell nuclei were microscopically measured: mean nuclear area (NA), mean perimeter (PM), largest-to-smallest diameter ratios (LS), circularity factor (CF), and coefficient of variation of nuclear area (NACV). The calculated parameters were retrospectively analyzed and compared with patients' outcome. RESULTS: NA, PM, and NACV correlated with recurrence. NA and NACV were significantly associated with disease-free survival. High NACV correlated with lymph node metastasis. In node-negative cases, high NACV correlated with recurrence and tended to be associated with poor prognosis. CONCLUSIONS: These findings suggest that computerized morphometry is useful for predicting malignancy potential of T2 lesions of the rectum.

Adult↗
PubMed2002

Cellular adhesion is required for effector functions of human eosinophils via G-protein coupled receptors.

BACKGROUND: Eosinophils play an important role in the pathogenesis of allergic diseases. Chemoattractants, including platelet-activating factor (PAF) and complement component 5a (C5a), induce eosinophil infiltration and promote eosinophil effector functions. OBJECTIVE: To compare eosinophil degranulation and superoxide anion (O2-) generation induced by various chemoattractants, and to elucidate the role of cellular adhesion on these effector functions. METHODS: Human eosinophils were stimulated with PAF, C5a, eotaxin, or leukotriene B4 (LTB4). O2- generation was assayed by a chemiluminescence method using a Cypridina luciferin analog as the amplifier. Degranulation and adhesion were measured by quantitating eosinophil protein X by radioimmunoassay. Expression of CD11b on eosinophils was measured by flow cytometry. RESULTS: PAF and C5a induced significant degranulation and O2- generation from eosinophils. In contrast, the potency of eotaxin or LTB4 for these functions was much less. PAF and C5a also significantly enhanced eosinophil adhesion, whereas eotaxin and LTB4 did not. CD11b expression on eosinophils was enhanced by all four stimulants, and the order of potency to induce CD11b expression was C5a > PAF > eotaxin > LTB4. CONCLUSIONS: The potency of PAF and C5a for inducing effector function in eosinophils was greater than that of eotaxin or LTB4. The magnitude of the effector function was consistent with the degree of eosinophil adherence induced by each stimulant. These results suggest that effector functions of eosinophils which are mediated through G-protein coupled receptors are dependent on cellular adhesion.

Cell Adhesion↗
PubMed2002

Fenoterol inhibits superoxide anion generation by human polymorphonuclear leukocytes via beta-adrenoceptor-dependent and -independent mechanisms.

BACKGROUND: Beta2-adrenoceptor agonists, used widely as bronchodilator in treating bronchial asthma, may have anti-inflammatory activity. OBJECTIVE: We examined whether various widely prescribed beta2-adrenoceptor agonists differ in anti-inflammatory mechanisms. METHODS: We investigated effects of these drugs on superoxide anion generation by stimulated human polymorphonuclear leukocytes in vitro using chemiluminescence. RESULTS: At high concentrations, fenoterol significantly inhibited both N-formylmethionyl-leucyl-phenylalanine- and phorbol myristate acetate-induced superoxide generation by neutrophils. In contrast, salbutamol or procaterol partially inhibited generation with the former stimulus but not the latter. Inhibition by salbutamol or procaterol was completely reversed by either propranolol, a nonselective beta-adrenoceptor antagonist, or ICI-118551, a beta2-adrenoceptor-selective antagonist. In contrast, the effect of fenoterol at concentrations exceeding 10(-6) M against superoxide generation with the former stimulus was only partially reversed by antagonists, and the effect of high concentrations of fenoterol against generation with the latter stimulus was not reversed. No drugs scavenged superoxide at the highest concentration used (10(-5) M). CONCLUSIONS: Fenoterol at high concentrations has an inhibitory effect on superoxide generation that includes a component not mediated via beta2-adrenoceptors. Direct inhibition at or downstream from protein kinase C may be involved.

Adrenergic beta-Agonists↗
PubMed2002

Inhibition of protein kinases A and C demonstrates dual modes of response in human eosinophils stimulated with platelet-activating factor.

BACKGROUND: Platelet-activating factor (PAF) is a potent stimulator of human eosinophils involved in the pathogenesis of allergic diseases. However, intracellular signaling mechanisms in eosinophils involving the PAF receptor are incompletely understood. OBJECTIVE: We sought to determine the roles of protein kinase C (PKC) and cyclic AMP-dependent protein kinase (protein kinase A [PKA]) in signaling pathways of human eosinophils stimulated with PAF. METHODS: After pretreatment with a PKC inhibitor, bisindolylmaleimide I, or a PKA inhibitor, H89, we investigated PAF-evoked functions, such as CD11b expression, cellular adhesion, superoxide anion generation, and degranulation in human eosinophils. RESULTS: Preincubation of eosinophils with bisindolylmaleimide I resulted in enhancement of upregulated CD11b expression and adhesion induced by PAF. H89 pretreatment also enhanced PAF-induced cellular adhesion. Superoxide anion generation and degranulation were suppressed by means of inhibition of either PKC or PKA. CONCLUSION: PKC and PKA negatively regulate PAF-induced CD11b upregulation and cellular adhesion but promote eosinophil effector functions, such as superoxide anion generation and degranulation. PKC and PKA modulate PAF-evoked intracellular signaling of the eosinophil function in distinct ways.

Benzoquinones↗
PubMed2002

The ClpXP ATP-dependent protease regulates flagellum synthesis in Salmonella enterica serovar typhimurium.

The ClpXP protease is a member of the ATP-dependent protease family and plays a dynamic role in the control of availability of regulatory proteins and the breakdown of abnormal and misfolded proteins. The proteolytic activity is rendered by the ClpP component, while the substrate specificity is determined by the ClpX component that has ATPase activity. We describe here a new role of the ClpXP protease in Salmonella enterica serovar Typhimurium in which ClpXP is involved in the regulation of flagellum synthesis. Cells deleted for ClpXP show "hyperflagellate phenotype," exhibit overproduction of the flagellar protein, and show a fourfold increase in the rate of transcription of the fliC encoding flagellar filament. The assay for promoter activity of the genes responsible for expression of the fliC showed that the depletion of ClpXP results in dramatic enhancement of the expression of the fliA encoding sigma factor final sigma(28), leaving the expression level of the flhD master operon lying at the top of the transcription hierarchy of flagellar regulon almost normal. These results suggest that the ClpXP may be responsible for repressing the expression of flagellar regulon through the control of the FlhD/FlhC master regulators at the posttranscriptional and/or posttranslational levels. Proteome analysis of proteins secreted from the mutant cells deficient for flhDC and clpXP genes demonstrated that the DeltaflhD mutation abolished the enhanced effect by DeltaclpXP mutation on the production of flagellar proteins, suggesting that the ClpXP possibly defines a regulatory pathway affecting the expression of flagellar regulon that is dependent on FlhD/FlhC master regulators.

Adenosine Triphosphatases↗
PubMedDate not supplied

Intraoperative cytologic diagnosis of sentinel node metastases in breast cancer.

OBJECTIVE: To clarify the usefulness of imprint cytology for intraoperative investigations of sentinel lymph nodes in breast cancer, comparing the results with those of examinations using frozen and permanent sections. STUDY DESIGN: The material consisted of 303 sentinel lymph nodes from 124 cases of clinically node negative breast cancer. Touch imprint cytologic slides and frozen sections were obtained from the same cut surface of the sentinel nodes. Correlations with the final histopathologic results in paraffin sections were evaluated. RESULTS: The sensitivity, specificity and accuracy of imprint cytology were 70.3%, 99.6% and 96.0%, and those of frozen sections were 83.8%, 100%, 98.0%, respectively. The values were improved when the 2 methods were combined (89.2%, 99.6%, 98.3%), though the concordance between imprint cytology and frozen section was 91.9%. CONCLUSION: Both imprint cytology and frozen section are useful for evaluating sentinel lymph node status in breast cancer. However, the 2 techniques should be combined to improve the diagnostic sensitivity.

Adult↗