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Biomedical subjects

N Tsuboi

Publications and source records attributed to N Tsuboi.

At least 19 recordsLinked to original sources

The effect of angiotensin receptor blockade ARB on the regression of left ventricular hypertrophy in hemodialysis patients: comparison between patients with D allele and non-D allele ACE gene polymorphism.

OBJECTIVE: It is revealed that LVH is one of risk factors for the development of cardiac complications in long-term HD patients. Therefore, maneuvers to reduce hypertrophy of cardium are very important for improving life prognosis. Angiotensin II receptor blockade (ARB) could reduce LVH in general populations without renal failure. However, no conclusive data has been available regarding the clinical consequences of ARB administration on the regression of LVH in HD patients. Furthermore, it has not clearly determined if ACE gene polymorphism has a possible influential effect on it. This study is conducted to clarify these issues. SUBJECTS AND METHOD: 32 hypertensive patients on regular HD (male/female: 21/11, mean age: 60.5 years, mean duration of HD: 52.8 months) were studied. Patients were classified into two groups according to the different type of ACE gene polymorphism: cases with D allele (DD/ID; D group: n = 13) and those without (II; non-D group: n = 19). All patients were administered ARB (losartan 50 - 100 mg/day) and echocardiography (UCG) was performed at 6-month-interval regularly until the end of observation (24 months). RESULTS: Before the commencement of ARB, no differences were found between the two groups, neither in mean blood pressure (MBP: D group/non-D group: 120 +/- 13 vs. 115 +/- 14 mmHg) nor in left ventricular mass index (LVMI: D/non-D: 172 +/- 41 vs. 165 +/- 41 g/m2). During the 24r-month follow-up, there were significant and similar reductions in MBP in both groups. In respect to LVMI, a significant reduction of LVMI was found in the D group after six months (p < 0.01 vs. basal) with a final reduction rate (FRR) -26 +/- 13%, whereas in the non-D group it was found at 24 months (p < 0.01 vs. basal) with FRR -11 +/- 16% (p < 0.01 vs. D group). There were significant differences between the two groups at all points (p < 0.05 at 6, 18 and 24 months, p < 0.005 at 12 months, respectively). CONCLUSION: It is indicated that ARB could insert a regression effect on LVH predominantly in patients with D allele ACE polymorphism, due partly to factor (s) independent of its anti-hypertensive effect.

Alleles↗

Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors.

Osteoclast differentiation factor (ODF), a recently identified cytokine of the TNF family, is expressed as a membrane-associated protein in osteoblasts and stromal cells. ODF stimulates the differentiation of osteoclast precursors into osteoclasts in the presence of M-CSF. Here we investigated the effects of LPS on the gene expression of ODF in mouse osteoblasts and an osteoblast cell line and found that LPS increased the ODF mRNA level. A specific inhibitor of extracellular signal-regulated kinase or protein kinase C inhibited this up-regulation, indicating that extracellular signal-regulated kinase and protein kinase C activation was involved. A protein synthesis inhibitor, cycloheximide, rather enhanced the LPS-mediated increase of ODF mRNA, and both a neutralizing Ab of TNF-alpha and a specific inhibitor of PGE synthesis failed to block the ODF mRNA increase by native LPS. Thus, LPS directly induced ODF mRNA. Mouse osteoblasts and an osteoblast cell line constitutively expressed Toll-like receptor (TLR) 2 and 4, which are known as putative LPS receptors. ODF mRNA increases in response to synthetic lipid A were defective in primary osteoblasts from C3H/HeJ mice that contain a nonfunctional mutation in the TLR4 gene, suggesting that TLR4 plays an essential role in the process. Altogether, our results indicate that ODF gene expression is directly increased in osteoblasts by LPS treatment via TLR, and this pathway may play an important role in the pathogenesis of LPS-mediated bone disorders, such as periodontitis.

Animals↗

Measurement of ethylene emission from Japanese red pine (Pinus densiflora) under field conditions in NOx-polluted areas.

Emission of ethylene from the needles of Japanese red pine, Pinus densiflora, was measured in air-polluted areas in Hiroshima, Japan. We applied a suitable protocol to determine the rate of ethylene emission from the excised needles. The influence of excision of needles on ethylene emission was not detected during the first 4 h of incubation at 20 degrees C. Ethylene emissions were low in the unpolluted (clean) areas regardless of the altitude or season. The emission of stress ethylene increased with the atmospheric NO2 concentration, suggesting that atmospheric NOx or related substances induced the higher ethylene emission in the polluted areas (near urban and industrial areas). In all cases, 1-year-old needles emitted significantly larger amounts of ethylene than the current needles. Ethylene emission did not increase evenly in the polluted areas, but the frequency of trees emitting high ethylene increased. Therefore, threshold rates for the baseline ethylene emission were proposed.

Air Pollutants↗

Urothelial mucosal concentration of levofloxacin administered before transurethral resection: Is the mucosal concentration predictable?

BACKGROUND: Although it is an established surgical technique, transurethral resection (TUR) is associated with a certain incidence of postoperative bacteriuria. Assessment was made whether the urothelial mucosal concentration of an antibiotic administered before TUR was high enough to decrease the incidence of urinary tract infection (UTI). Also investigated were factors predicting the organ concentration. METHODS: Forty-nine patients (45 men and four women aged 51-79 years with a median age of 70 years) who underwent TUR between August 1996 and September 1997 were enrolled in the study. Each patient received 200 mg of levofloxacin (LVFX) about two hours before surgery. Blood and bladder urine were collected and urothelial mucosa was harvested at the time of TUR. Then the LVFX concentration in these samples was measured using high-performance liquid chromatography. The association between drug levels, or the ratio to the serum concentration, and factors likely to affect the vascular system that delivers the drug (age, bodyweight, blood pressure, pulse rate, total cholesterol and diabetes mellitus) were investigated. RESULTS: The mean serum drug level was 2.4 microg/mL, and it was 206.4 microg/mL in the urine and 5.7 microg/mL in the urothelial mucosa. The mean ratio of the mucosal to serum concentrations was 2.6. The urinary drug concentration showed no association with any of the factors assessed, while the serum concentration decreased with increasing bodyweight (P = 0.03). As the diastolic blood pressure increased, both the mucosal drug concentration and the mucosa/serum ratio decreased (P < 0.01). When the relationship between the serum and mucosal concentrations was investigated, no correlation was found. However, the mucosa/serum ratio (indicating the transfer of LVFX from the blood) was positively correlated with the mucosal concentration. CONCLUSION: Preoperative administration of LVFX was demonstrated to have potential value for the prophylaxis of UTI after TUR. Both the mucosal concentration and the mucosa/serum ratio were correlated with the diastolic blood pressure. As the diastolic blood pressure seems to be an indicator of the tissue concentration of LVFX, it may be possible to set the optimum dose based on the diastolic pressure.

Aged↗

Ganglioside as an endogenous growth suppressor for glomerular mesangial cells.

BACKGROUND: Glomerular mesangial cells potentially secrete many growth-modulating substances that could regulate mesangial cell proliferation. To date, however, the properties of such factors have not been fully evaluated. METHODS: For that purpose, conditioned medium (CM) from mesangial cells was used for cross-feeding experiments. Cell proliferation was evaluated by 3H-thymidine incorporation assay and direct cell counting. The growth-regulatory molecule was further characterized using biochemical techniques. RESULTS: Cross-feeding this CM to mesangial cells in vitro, despite stimulation with platelet-derived growth factor (PDGF), effectively suppressed the cells' synthesis of DNA in a dose-dependent manner. The inhibitory substance derived from mesangial cells was less than 3 kD in molecular mass, was heat stable, and was insensitive to proteinase K. After neuraminidase digestion, this inhibitory activity was lost. These data indicated that the inhibiting substance bore the typical features of gangliosides, which are multifunctional glycolipids that reside in cell membrane. Gangliosides were abundant in the CM from mesangial cells, as detected by metabolic radiolabeling and thin-layer chromatography (TLC). This result suggested that mesangial cells constitutively shed gangliosides. The growth suppressive activity in the CM was blunted when mesangial cells were pretreated with the ganglioside synthesis inhibitor d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol-HCl (d-threo-PDMP; 20 micromol/L) in accordance with the decreased ganglioside content in cells. Finally, gangliosides isolated from CM of mesangial cells suppressed PDGF-induced DNA synthesis of mesangial cells. CONCLUSIONS: These results suggest that mesangial cells constitutively shed gangliosides that then suppress the division of these cells in an autocrine-like manner.

Animals↗

The short-term effects of terazosin in Japanese men with benign prostatic hyperplasia.

We evaluated the short-term efficacy of terazosin for treating symptomatic benign prostatic hyperplasia (BPH). Thirty men, aged 52 to 83 years (mean: 69.2 years) complaining of obstructive urinary symptoms due to BPH who had not received any prior treatment for their symptoms were orally administered 2 mg/day of terazosin. Symptoms (the total IPSS and the obstructive and irritative symptom scores) and objective parameters (peak flow rate [Qmax] and prostatic volume) were evaluated before treatment and after 1, 2, and 4 weeks of treatment. The mean total IPSS and the mean symptom scores for weak stream and nocturia were significantly decreased after only 1 week of treatment, while the mean scores for emptying, frequency, and urgency were significantly decreased after 2 weeks of treatment. However, the mean scores for intermittency and hesitancy did not decrease significantly at any time during treatment. Regarding objective parameters, the mean Qmax was significantly improved after 1 week of treatment, but the mean prostatic volume remained almost unchanged after 4 weeks. In conclusion, short-term terazosin therapy not only improved Qmax but also alleviated symptoms including irritative symptoms.

Adrenergic alpha-Antagonists↗

Anti-apolipoprotein A-I autoantibody: characterization of monoclonal autoantibodies from patients with systemic lupus erythematosus.

OBJECTIVE: The autoantibody to apolipoprotein A-I (apoA-I), a major constituent of high density lipoproteins (HDL), has been detected in sera of patients with systemic lupus erythematosus (SLE). We established a series of monoclonal anti-apoA-I antibodies (MAAI) from 2 patients with SLE and report the reactivities of MAAI with oxidized HDL, anionic substances, and blood coagulation factors. METHODS: Peripheral blood B cells from patients with SLE were immortalized by Epstein-Barr virus, and B cells secreting anti-apoA-I antibodies (AAI) were fused with mouse myeloma cells. Six MAAI reactive with human apoA-I in both ELISA and immunoblotting analysis were established. The reactivities of MAAI with HDL, ssDNA and dsDNA, phospholipids such as cardiolipin (CL), and coagulation factors were examined by ELISA. RESULTS: Although all MAAI bound effectively to apoA-I after the protein had been denatured and transferred to the filter membrane (in immunoblotting analyses), they bound less effectively to apoA-I present in HDL. Both oxidation of HDL in the presence of Mn2+ and an association of apoA-I with autoxidized trilinolein strongly enhanced the binding of MAAI to apoA-I, suggesting that MAAI recognize a defined region of apoA-I, which is exposed upon interacting with oxidatively modified lipids. MAAI showed a functional heterogeneity in their cross-reactivity with self-components: some MAAI were shown to cross-react with anionic substances such as CL and ssDNA, and one MAAI was shown to bind effectively to thrombin. CONCLUSION: We identified a novel family of AAI that shows preferential binding to apoA-I in oxidatively modified HDL. These AAI are composed of antibodies with heterogeneous cross-reactivities to various self-components such as anionic phospholipids, ssDNA, and thrombin.

Antibodies, Monoclonal↗

[Usefulness of power Doppler ultrasound in a patient with renal cell carcinoma in the wall of a simple renal cyst].

We present a case of renal cell carcinoma in the wall of a simple renal cyst. A 54-year-old man visited our hospital with a complaint of right back pain. Ultrasound study revealed right hydronephrosis, a ureteral stone, and a 9 x 8 cm renal cyst, with a tumor, 2 cm in diameter, in the cyst wall. Power Doppler Ultrasound and enhanced computed tomography demonstrated hypervascularity of the tumor. Clinically, he was diagnosed as renal cell carcinoma and nephrectomy was performed. Pathological findings of the tumor showed clear cell carcinoma in the wall of a simple renal cyst. Twelve months after the nephrectomy, he was free from recurrence.

Carcinoma, Renal Cell↗

Evaluation of left ventricular function using electrocardiographically gated myocardial SPECT with (123)I-labeled fatty acid analog.

UNLABELLED: Electrocardiographically (ECG) gated myocardial SPECT with (99m)Tc-tetrofosmin has been used widely to assess left ventricular (LV) function. However, the accuracy of variables using ECG gated myocardial SPECT with beta-methyl-p-(123)I-iodophenylpentadecanoic acid (BMIPP) has not been well defined. METHODS: Thirty-six patients (29 men, 7 women; mean age, 61.6 +/- 15.6 y) with ischemic heart disease underwent ECG gated myocardial SPECT with (123)I-BMIPP and with (99m)Tc-tetrofosmin and left ventriculography (LVG) within 1 wk. LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) were determined on gated SPECT using commercially available software for automatic data analysis. These volume-related items on LVG were calculated with an area-length method and were estimated by 2 independent observers to evaluate interobserver validity. The regional wall motion with these methods was assessed visually. RESULTS: LVEF was 41.1% +/- 12.5% on gated SPECT with (123)I-BMIPP, 44.5% +/- 13.1% on gated SPECT with (99m)Tc-tetrofosmin, and 46.0% +/- 12.7% on LVG. Global LV function and regional wall motion between both gated SPECT procedures had excellent correlation (LVEF, r = 0.943; LVEDV, r = 0.934; LVESV, r = 0.952; regional wall motion, kappa = 0.92). However, the correlations of global LV function and regional wall motion between each gated SPECT and LVG were significantly lower. Gated SPECT with (123)I-BMIPP showed the same interobserver validity as gated SPECT with (99m)Tc-tetrofosmin. CONCLUSION: Gated SPECT with (123)I-BMIPP provides high accuracy with regard to LV function and is sufficiently applicable for use in clinical SPECT. This technique can simultaneously reveal myocardial fatty acid metabolism and LV function, which may be useful to evaluate various cardiac diseases.

Electrocardiography↗

High-frequency endoluminal ultrasonography for staging transitional cell carcinoma of the bladder.

OBJECTIVES: To assess the feasibility and limitations of endoluminal ultrasound (ELUS) for clinical staging of bladder tumors. METHODS: From 1998 to 1999, 32 patients with transitional cell carcinoma of the bladder were evaluated by high-frequency ELUS using miniature ultrasound transducers (20 MHz, 5.1F or 7.2F) before transurethral resection. Clinical staging using ELUS was compared with the results of pathologic staging. RESULTS: Seventeen (94%) of the 18 patients with superficial tumors on ELUS were confirmed by pathologic examination to have Stage pTa (n = 12) or Stage pT1 (n = 5) disease, and 11 (63%) of the 14 patients with muscle-invasive tumors on ELUS were confirmed by pathologic evaluation to have Stage pT2a (n = 2) or Stage pT2b (n = 9) disease. In all of the misdiagnosed patients, the tumor lacked a well-defined base and was larger than 2 cm in size. It was difficult to distinguish between Stage Ta and Stage T1 tumors because of the limited resolution of ELUS and between Stage T2a and Stage T2b tumors because of its low penetration. CONCLUSIONS: ELUS using a high-frequency (20 MHz), miniature ultrasound transducer is able to distinguish superficial tumors from those with muscle invasion. However, the lack of penetration of the sonographic beam places major limitations on the evaluation of the depth of the invasion in large (greater than 2 cm) tumors with a broad base.

Adult↗

Antiarrhythmic efficacy of dipyridamole in treatment of reperfusion arrhythmias : evidence for cAMP-mediated triggered activity as a mechanism responsible for reperfusion arrhythmias.

BACKGROUND: Intracellular calcium overload is believed to play an important role in development of reperfusion arrhythmias. Dipyridamole, an inhibitor of cellular uptake of adenosine, may prevent or terminate reperfusion arrhythmias by reducing intracellular calcium overload. METHODS AND RESULTS: First, we tested for a preventive effect of dipyridamole. Sixty-one patients who underwent primary PTCA for treatment of acute anterior wall myocardial infarction were enrolled in this prospective study. Patients were divided into dipyridamole (DP) and nondipyridamole (non-DP) groups. The 2 groups had similar baseline characteristics. In the DP group, dipyridamole 0.5 mg/kg was infused intravenously for 3 minutes immediately before reperfusion during primary PTCA. Arrhythmias after reperfusion were analyzed from continuous ECG recordings. None of the patients in the DP group (n=23) had accelerated idioventricular rhythms (AIVR) or ventricular tachycardia (VT). In contrast, 7 (18.4%) had AIVR and 3 (7.9%) had VT in the non-DP group (n=38; P<0.01). Second, we tested for a termination effect of dipyridamole. Dipyridamole 0.5 mg/kg was infused intravenously while continuous ECG recordings were obtained in 9 patients who had either sustained AIVR (n=7) or sustained VT (n=2) after reperfusion of occluded coronary artery. Arrhythmias were terminated in all patients. CONCLUSIONS: These results indicate that administration of dipyridamole can prevent and terminate reperfusion arrhythmias such as AIVR and VT. cAMP-mediated triggered activity may, at least in part, be responsible for reperfusion-induced AIVR and VT.

Adenosine↗

Comparative study of lymphocyte-suppressive potency between prednisolone and methylprednisolone in rheumatoid arthritis.

We compared lymphocyte-suppressive potencies of prednisolone and methylprednisolone in rheumatoid arthritis (RA). IC(50)s of the glucocorticoids (GCs) on concanavalin A-induced blastogenesis of peripheral-blood mononuclear cells (PBMCs) from 44 RA patients and 30 healthy subjects were estimated in vitro, and differences in the IC(50)s of the two GCs were evaluated. The mean (+/-SD) IC(50)s for prednisolone and methylprednisolone on PBMC-blastogenesis of RA were 17.2+/-17.1 and 12.6+/-18.4 ng/ml, respectively, and no significant differences were observed between prednisolone-IC(50) and methylprednisolone-IC(50). In contrast, the mean IC(50)s of prednisolone and methylprednisolone on healthy PBMCs were 19.4+/-22. 4 and 3.7+/-3.9 ng/ml, respectively, and thus methylprednisolone potency was significantly higher than prednisolone potency (p<0.01). Methylprednisolone potency against PBMCs in RA patients exhibiting a high level of rheumatoid factor (RF) (>20 IU/ml) and the rheumatoid arthritis particle-agglutination value (RAPA) (>80) was significantly higher than that of patients exhibiting a lower level of RF or RAPA (p<0.05). In prednisolone-IC(50), however, such differences between the two patient-subgroups were not observed. Unlike reported cases of renal transplantation and healthy subjects, there was no difference in the lymphocyte-suppressive potencies for both prednisolone and methylprednisolone on RA-PBMCs. However, PBMCs from RA patients exhibiting high levels of RF or RAPA are more sensitive to methylprednisolone rather than prednisolone.

Aged↗

Post-voiding repeated renal ultrasonography for slight hydronephrosis detected during screening for asymptomatic microhematuria.

BACKGROUND: There is not a well established method for further screening of asymptomatic microhematuria found through annual health examinations. However, it is apparent that a large number of examiners are using ultrasonography for screening. When slight hydronephrosis is found through screening, it is difficult to determine whether further examinations, such as intravenous pyelography (IVP), should be performed. In this paper, we discuss the usefulness of post-voiding repeated renal ultrasonography, which was applied to 57 patients with slight hydronephrosis found in a screening. METHODS: Ultrasonography in the kidney and the urinary bladder at the ultrasound laboratory of Toma Hospital was carried out on a total of 1906 patients with asymptomatic microhematuria, which was found by routine annual health examination, from January 1996 to December 1998. Slight hydronephrosis was found in 57 (14 males and 43 females) of 1906 patients and post-voiding repeated renal ultrasonography was carried out on all patients. RESULTS: Slight hydronephrosis had disappeared and IVP was avoided in 22 (38.6%) of 57 patients. Of 35 cases in which slight hydronephrosis persisted after urination, there were no abnormalities on IVP in 32 patients, while abnormalities were found in three patients. Two of these had ureteropelvic junction stenosis and the remaining one had a ureteral stone. CONCLUSION: The results of this study indicate that post-voiding repeated renal ultrasonography is useful for avoiding unnecessary further examination to determine whether upper urinary tract obstruction exists, when slight hydronephrosis is observed upon screening by simultaneous renal and urinary bladder ultrasonography for asymptomatic microhematuria.

Female↗