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Biomedical subjects

M Sekiya

Publications and source records attributed to M Sekiya.

At least 37 records · Page 2Linked to original sources

DNA vaccination by mecA sequence evokes an antibacterial immune response against methicillin-resistant Staphylococcus aureus.

More than 90% of methicillin-resistant Staphylococcus aureus (MRSA) isolates produce a penicillin-binding protein PBP2' (or PBP2a) with low affinity for beta-lactam antibiotics. PBP2' is encoded by the mecA gene, a foreign gene integrated into the chromosome of methicillin-susceptible S. aureus (MSSA). DNA vaccination by injection of transgene-expressing plasmids has been demonstrated to elicit an immune response against transgene-encoded protein. We hypothesized that the application of DNA vaccination with the mecA sequence would elicit protective immunity against MRSA. This immunity was evoked by injection of a mecA-expressing plasmid into BALB/c mice. Anti-PBP2' antibody was detected in the sera obtained from the DNA-vaccinated mice. These sera produced a five-fold increase in phagocytosis of MRSA compared with sera from mice treated with control plasmid. However, there was no difference in phagocytosis of MSSA among these groups. In addition, the in-vivo antibacterial effect of DNA vaccination was demonstrated in mice infected with MRSA. Eight days after iv inoculation of 10(8) cfu of MRSA into mice, the number of bacteria in the kidneys obtained from mice vaccinated with mecA-expressing plasmid (1.48 +/- 0.27 x 10(5) cfu/mg kidney; n = 18) was significantly lower than that from mice vaccinated with negative control plasmid (3.59 +/- 0.57 x 10(5) cfu/mg kidney; n = 17) (P < 0.02) or that from sham-treated mice (3. 43 +/- 0.66 x 10(5) cfu/mg kidney; n = 9) (P < 0.02). Interestingly, PBP2' was found in both the bacterial membrane fraction and the supernatant, thus being accessible to serum antibodies. Together these observations indicate that PBP2' or the mecA sequence may be eligible as a candidate molecule for vaccination against MRSA.

Animals↗

Effect of insulin resistance on left ventricular hypertrophy and dysfunction in essential hypertension.

BACKGROUND: In hypertensive patients, the relationships between glucose tolerance and left ventricular hypertrophy (LVH) and left ventricular diastolic function (LVDF) have been described in several reports. OBJECTIVE: In this study, we examined the relationships between insulin resistance and LVH and LVDF in hypertensive patients from the therapeutic perspective. METHODS AND RESULTS: The study participants were essential hypertensive patients with impaired glucose tolerance (IGT-HT, n = 26), hypertensive patients with normal glucose tolerance (NGT-HT, n = 39), and normotensive control individuals (n = 18). Insulin resistance was evaluated by the insulin suppression test by use of the steady-state plasma glucose (SSPG) level. Left ventricular mass index (LVMI) and LVDF, which was determined by the E:A ratio, were estimated by echocardiography. Temocapril, an angiotensin-converting enzyme inhibitor, was administered in an open, non-randomized manner with a mean dose of 2.8+/-0.2 mg/ day, and the mean administration period was 18 weeks. The systolic and diastolic blood pressure, the LVMI, and the SSPG level were significantly higher in the hypertensive patients than in the control individuals. The mean systolic and diastolic blood pressures were significantly decreased by treatment with Temocapril. Before treatment, stepwise regression analysis showed that SSPG is an independent predictor for LVMI and LVDF. After treatment, the changes in LVMI (D-LVMI; %) (-15.1+/-1.5), the changes in LVDF (D-E:A; %) (-38.2+/-4.1), and the changes in insulin resistance (D-SSPG; %) (-13.7+/-1.7) were significantly higher in the IGT-HT group than in the NGT-HT group (-11.4+/-1.1, -18.1+/-1.7, -9.4+/-1.4, respectively), and the D-SSPG was an independent predictor for D-LVMI and D-E :A. CONCLUSIONS: The results of this study indicate that insulin resistance is an important factor affecting LVH and LVDF.

Adult↗

Relationship between insulin resistance and cardiac sympathetic nervous function in essential hypertension.

BACKGROUND: It has been suggested that hyperinsulinemia and insulin resistance participate in the pathogenesis of hypertension, in part by activating sympathetic activity. OBJECTIVE: We aimed to examine the relationship between insulin resistance and cardiac sympathetic nervous function in patients with essential hypertension using 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy. METHODS AND RESULTS: Twenty-eight patients (18 men) with essential hypertension and 11 (seven men) control individuals with a mean age of 55.8+/-3.3 years were recruited. Patients with diabetes mellitus, congestive heart failure or coronary artery disease were excluded from this study. To evaluate insulin resistance, we used steady-state plasma glucose (SSPG; mg/dl) levels measured by the SSPG method. To evaluate cardiac sympathetic nervous function, we calculated the heart-to-mediastinum ratio from the delayed MIBG image (H:M-D) and the mean washout rate (WOR, %). There were significant differences (P<0.01) in SSPG, H:M-D and WOR between the essential hypertension and control individual groups (125 versus 103 mg/dl, 2.2 versus 2.4, and 32 versus 23%, respectively). Stepwise regression analysis showed that SSPG and plasma norepinephrine level are independent predictors for the cardiac sympathetic nervous function obtained from MIBG scintigraphy. CONCLUSIONS: These findings indicate that insulin resistance is significantly related to activation of the cardiac sympathetic nervous function associated with left ventricular hypertrophy in patients with essential hypertension.

3-Iodobenzylguanidine↗

[A case of elderly onset sarcoidosis].

Although sarcoidosis is generally considered a disease of young and middle aged adults, there have been a certain number of cases among elderly. However it is unknown whether sarcoidosis in the elderly is recurrence of prior disease or initial onset at old ages. We present a 77-year-old woman with sarcoidosis the onset of which was considered to be in the last 6 months prior to the initial diagnosis. The patient was admitted to our hospital for further evaluation of bilateral hilar and mediastinal lymphadenopathy (BHL) and uveitis. BHL was not present in a chest radiograph taken 6 months prior to the admission. A clinical diagnosis of sarcoidosis was made by elevated serum angiotensin converting enzyme (ACE) and lysozyme (24.9 IU/L and 18.2 micrograms/ml, respectively), negative tuberculin skin test, concomitant presence of uveitis, and a high proportion of lymphocytes (33.2%) in bronchoalveolar lavage fluid with an elevated CD4/CD8 ratio (24.5). This is a noteworthy case of sarcoidosis in which we could confirm elderly onset of the disease.

Age of Onset↗

[Intralobar pulmonary sequestration presenting increased serum CEA, CA 19-9, and CA 125, and associated with asymptomatic pulmonary aspergillosis].

A 44-year-old woman was admitted to our hospital for further evaluation of a consolidated shadow in the left lower lobe and the evaluation of serum tumor markers (CEA 46.3 ng/ml, CA 19-9 1911 U/ml, and CA 125 103 U/ml). Chest computed tomography revealed an irregular shaped, low density mass shadow in the left S10 region, suggesting the diagnosis of pulmonary sequestration or bronchial atresia. However digital subtraction angiography failed to demonstrate an anomalous feeding artery. We could not rule out the possibility that a malignant lesion was included in the consolidated shadow. A left thoracotomy revealed an intralobar pulmonary sequestration of the left lower lobe. Hyphae of aspergillus were found in the lumen of the cystic bronchus of the resected lung. Immunohistochemical studies showed strong expression of CEA, CA 19-9, and CA 125 by bronchial epithelia in the pulmonary sequenstration. The serum values of tumor markers returned to their normal ranges after surgery.

Adult↗

[Administration of docetaxel in cases of recurrent breast carcinoma with malignant pleural effusion controlled by intrapleural administration of OK-432].

Docetaxel is an anti-tumor agent which promotes the congregation and stabilization of microtubules, there by preventing cell division. It is reported to have anti-tumor activity against breast or non-small cell lung carcinomas which have been resistant to other anti-tumor agents. On the other hand, it causes peripheral edema and effusion in the pleural or peritoneal cavities. Thus, pleural or peritoneal effusions, which require drainage have been considered to be contraindications for the administration of docetaxel. OK-432 is an agent which causes adhesion by evoking a local inflammatory reaction. We experienced two cases of recurrent breast carcinoma with malignant pleural effusion. We successfully managed their pleural effusion with the intrapleural administration of OK-432. Thereafter, we safely administered docetaxel, and obtained good outcomes. The present paper also discussed the synergistic action between these agents.

Adenocarcinoma↗

Prognostic value of dipyridamole-thallium myocardial scintigraphy in patients with Kawasaki disease.

BACKGROUND: Although coronary artery lesions are critical complications of Kawasaki disease, their long-term outcome is still unclear. It is sometimes difficult to monitor progressive changes from aneurysms to stenotic lesions because coronary angiography (CAG) cannot be repeated very often, especially in infants. Our prospective study was designed to evaluate the prognostic value of dipyridamole-thallium single-photon-emission CT (SPECT) in the long-term follow-up of patients with Kawasaki disease. METHODS AND RESULTS: Of 459 consecutive patients with Kawasaki disease, coronary aneurysms were detected in 90 cases by echocardiography during the acute stage. After paired studies of selective CAG and SPECT were conducted, all patients were followed up and monitored for the occurrence of any cardiac events for > or =8 years. During the follow-up interval, there were 15 cardiac events (1 death, 5 infarctions, 2 coronary artery bypass graft operations, and 7 occurrences of unstable angina). Of patients who had some event, thallium redistribution was found on SPECT in 14 (93%, P<0.001). Of the various clinical and scintigraphic image variables, the presence of thallium redistribution was the best multivariate independent predictor of a late cardiac event (chi2=57.8, P<0.0001). The number of aneurysms detected on CAG added minimal statistical improvement to the model (chi2=1.9, P=0.0009). CONCLUSIONS: Dipyridamole-thallium SPECT is safely performed and is useful and important for risk stratification in the long-term follow-up of patients with Kawasaki disease.

Age of Onset↗

Effects of probucol and cilostazol alone and in combination on frequency of poststenting restenosis.

The present study was conducted to assess the preventive effect of combined treatment with probucol, an antioxidant, and cilostazol, a phosphodiesterase inhibitor, against poststenting restenosis. Study patients were randomized to 4 modality groups 1 week before stenting: control, probucol (500 mg/day), cilostazol (200 mg/day), and probucol plus cilostazol. Treatment on these modalities was conducted from 5 prestent days until the poststenting follow-up evaluation (6 poststenting months). All patients received aspirin (81 mg/day). The efficacy of each modality against restenosis was evaluated in a total 126 patients with 165 coronary arterial lesions, using a quantitative method. The decrease in luminal diameter at the poststenting follow-up was 1.04 +/- 0.57 mm for controls, 0.88 +/- 0.82 mm for those taking probucol, 0.61 +/- 0.59 mm for those taking cilostazol (p <0.05 vs control), and 0.40 +/- 0.52 mm (p <0.01 vs control) for the combined treatment group. Restenosis rate per segment was 31.7% for controls, 16.7% for the probucol group, 12.5% for the cilostazol group (p <0.05 vs control), and 9.5% for the combined treatment group (p <0.05 vs the control). Neither mortality, myocardial infarction, stent thrombosis, or coronary bypass surgery, nor any serious complications were observed in the combined treatment group. Combined treatment with probucol and cilostazol has thus proved safe and effective in preventing acute poststenting complications and suppressing chronic restenosis.

Adult↗

Very low-dose cyclosporin treatment of steroid-resistant interstitial pneumonitis associated with Sjögren's syndrome.

Cyclosporin is known to be effective for both transplantation and a spectrum of immune-mediated diseases. Because this agent also causes severe adverse effects, especially nephrotoxicity, careful monitoring is required for the development of such reactions. Here we report the successful treatment with extremely low-dose cyclosporin (1 mg/kg/day) of a patient who had steroid-resistant interstitial pneumonitis and Sjögren's syndrome.

Cyclosporine↗

Human tumor growth suppression by apoptosis induced with anti-ErbB-2 chimeric monoclonal antibody.

We established an anti-ErbB-2 mouse-human chimeric monoclonal antibody (MoAb), CH401, which was able to kill cancer cells overexpressing the ErbB-2 protein in vitro. The analysis of the killing mechanism indicated that MoAb CH401 might be the first anti-erbB-2 mouse-human chimeric MoAb which can induce the apoptosis of cancer cells, since morphological changes and DNA fragmentation were recognized in MoAb CH401-treated cells. The ErbB-2 receptor appears to have two opposing functions: acting as a receptor both for a growth factor and for an apoptotic factor. Our results indicate that MoAb CH401 treatment may prove to be very useful for cancer therapy.

Animals↗

Chronic ischemic colonic lesion caused by phlebosclerosis with calcification.

We report here two patients in both of whom ileus finally developed and chronic ischemic colonic lesion caused by phlebosclerosis with calcification was diagnosed. We believe that phlebosclerosis is an old-fashioned diagnostic term, but appropriate here because of the remarkable calcification of the sclerotic walls of the colic veins that seems to be one of the most important hallmarks of this previously unrecognized, "new" condition. Phlebosclerosis could be a novel type of ischemic colitis because of its unique clinical presentations, although the pathogenesis of this unusual venopathy remains unknown.

Adult↗

[Markedly decreased uptake with 123I-MIBG myocardial scintigraphy in a case with vasospastic angina].

A 68-year-old female whose myocardial sympathetic function was severely damaged with multi-vessel vasospastic angina is presented. She had no signs of autonomic dysfunction or diabetes mellitus. Myocardial imaging with 123I-MIBG showed extremely diminished uptake, but 201TlCl and 123I-BMIPP SPECT images were almost normal. Coronary arteriography revealed no significant atherosclerotic stenosis, multivessel spasm was observed by provocation test using acetylcholine. The extremely diminished uptake of 123I-MIBG was slightly increased in response to medication and the subsequent improvement of the patient's condition. Markedly decreased uptake with 123I-MIBG myocardial scintigraphy was considered to be due to multi-vessel spastic angina. We believe that this method of imaging study is useful for evaluating the healing stage of myocardial sympathetic dysfunction.

3-Iodobenzylguanidine↗

IFN-gamma upregulates anti-apoptotic gene expression and inhibits apoptosis in IL-3-dependent hematopoietic cells.

IFN-gamma is a cytokine which functions in a wide range of biological activities by inducing a number of early and delayed genes. In murine IL-3-dependent cell lines BAF-B03 and 32D, IFN-gamma upregulated bag-1 and bcl-xL gene expression. These cells revealed prolonged cell survival against IL-3-deprivation by IFN-gamma stimulation. In contrast, human myeloma cell line RPMI8226, despite expression of IFN-gamma receptor, showed neither induction of their expressions nor prolonged cell survival against serum starvation-induced apoptosis by IFN-gamma stimulation. Gene-transfer-mediated overexpression of BAG-1 protein in BAF-B03 cells led to prolonged cell survival against IL-3-deprived apoptosis compared with control BAF-B03 transfectants, indicating that levels of BAG-1 expression are crucial for cell survival in BAF-B03 cells. Taken together, these studies suggest that induction of anti-apoptotic gene expression is a crucial factor for the anti-apoptotic function of IFN-gamma in IL-3-dependent immature hematopoietic cells.

Animals↗

Right hepatectomy for pyogenic liver abscesses with true multiloculation.

We report the case of 61-year-old woman with cryptogenic liver abscesses who had been profoundly ill with severe upper abdominal pain, impaired consciousness, prostration, continuous high fever secondary to sepsis, and thrombocytopenia (platelets, 1-5 x 10(4)/mm3) since admission. Ultrasonograms and computed tomograms revealed two separate multiloculated lesions in the right lobe of the liver, consistent with the liver abscesses. Immediately after diagnosis, percutaneous abscess drainage was performed under ultrasonographic guidance; however, only a small amount of pus was drained, prompting continuous irrigation of the abscess cavity. Four days later, transcatheter hepatic arterial infusion of antibiotics was attempted. However, the abscesses had enlarged and her general condition had worsened. On hospital day 8, she underwent right hepatectomy because the multiloculated lesions were refractory to drainage. The operation was successful in terms of hepatectomy, although she continued to suffer from sepsis, secondary right subphrenic abscess formation, and prolonged thrombocytopenia with associated coagulation disorders for two months. Examination of multiple cross sections of the resected specimen disclosed that the lesions consisted of aggregations of multiple small locules. There was no communication between the locules and there were true septations, rather than multiloculated lesions with pseudoseptations. The patient has been well for 2 years without recurrent abscess of the liver or any infectious disease.

Drainage↗

Primary adenocarcinoma in the urethrorectal fistula.

A 60-year-old Japanese man was hospitalized because of urinary leakage from the anus on October 3, 1994. Retrograde urethrography detected a fistula between the bulbous urethra and the rectum. Urethrocystoscopy revealed a tumor on the urethrorectal fistula. Tumor biopsy showed a well differentiated adenocarcinoma. Cystourethrectomy with fistulectomy, and ileal conduit urinary diversion were performed. Pathological examination revealed primary adenocarcinoma in the fistula with invasion to the prostatic urethra and bladder wall. The patient showed no evidence of a recurrence as of August, 1996.

Adenocarcinoma↗

Nodular regenerative hyperplasia of the liver in systemic lupus erythematosus. The relationship with anticardiolipin antibody and lupus anticoagulant.

Recent reports have indicated that nodular regenerative hyperplasia (NRH) associated with systemic lupus erythematosus (SLE) is related to anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA). We describe a patient with SLE complicated by NRH, who did not show neither aCL nor LA activity. This case suggests that the pathogenesis of NRH in patients with autoimmune diseases is heterogeneous and not confined to aCL and LA.

Adult↗

Comparison of adenosine triphosphate and dipyridamole in diagnosis by thallium-201 myocardial scintigraphy.

UNLABELLED: We examined whether 201Tl myocardial scintigraphy with intravenous infusion of adenosine triphosphate (ATP) can be substituted for dipyridamole (DIP) in the diagnosis of coronary artery disease CAD). METHODS: The coronary flow reserve (CFR) during intravenous infusion of ATP (0.10-0.20 mg/kg/min) was compared with that during intravenous infusion of DIP (0.56 mg/kg) using a Doppler flow wire in 19 subjects with normal coronary arteries. The highest CFR level was found in the ATP dose range of 0.16-0.20 mg/kg/min. The CFR at the ATP dose of 0.16 mg/kg/min was significantly higher than that during DIP infusion (4.2 versus 3.6) (p < 0.01), for which reason we adopted this dose of ATP. According, 201Tl SPECT in 140 patients with suspected CAD was performed after infusion of 0.16 mg/kg/min of ATP in 70 of them and 0.56 mg/kg of DIP in the 70 others. RESULTS: ATP stress 201Tl SPECT showed no significant difference in sensitivity and accuracy from DIP stress 201Tl SPECT (87.0% versus 82.9, and 87.1% versus 78.6, respectively). Adverse effects occurred at higher frequency when ATP was used, but they were mild and disappeared rapidly after administration was stopped. CONCLUSION: ATP stress 201Tl SPECT is accurate and safe. The optimal ATP regimen for this purpose is considered to be a 5-min infusion at 0.16 mg/kg/min. However, our data in CAD patients suggest that ATP stress 201Tl SPECT is equivalent to DIP stress 201Tl SPECT in the detection of CAD.

Adenosine Triphosphate↗