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Hiromichi Suzuki

Publications and source records attributed to Hiromichi Suzuki.

At least 19 recordsLinked to original sources
PubMed2025

Carbonic Anhydrase Inhibition Sensitizes Group 3 Medulloblastoma to Radiotherapy.

UNLABELLED: Group 3 (G3) medulloblastoma constitutes the most aggressive molecular subgroup, and nearly all patients present with metastases upon recurrence. Treatment for newly diagnosed medulloblastoma relies on a combination of maximal safe surgical resection, followed by chemotherapy and ionizing radiation, and no therapies have been shown to confer a survival benefit at the time of recurrence. Given the limited therapeutic options available for patients with medulloblastoma, especially at recurrence, and the incomplete understanding of the molecular mechanisms underlying resistance to treatment, we sought to uncover actionable targets and biomarkers that could help refine patient selection and treatment of newly diagnosed medulloblastoma to reduce the risk of recurrence. In clinically relevant mouse models of G3 medulloblastoma, CT-guided fractionated radiotherapy extended overall survival and induced the clonal selection of radioresistant subpopulations of tumor cells that drove medulloblastoma recurrence. Comparison of recurrent tumors with treatment-naïve newly diagnosed tumors revealed a gene expression signature that was found to be a biomarker of radioresistance and poor prognosis. This prognostic gene signature was shown to be subgroup specific in a large patient cohort. Recurrent tumors had elevated expression of carbonic anhydrase 4, and genetic and pharmacologic modulation of carbonic anhydrase 4 could promote or reduce resistance to radiotherapy. These data suggest that the FDA-approved carbonic anhydrase inhibitor acetazolamide may be a useful radiosensitizer to improve the efficacy of the treatment of newly diagnosed G3 medulloblastoma that could reduce the risk of tumor recurrence and improve survival in pediatric patients. SIGNIFICANCE: G3 medulloblastoma features a prognostic subgroup-specific gene expression signature and can be targeted with a carbonic anhydrase inhibitor to enhance radiosensitivity, reducing the risk of recurrence and improving survival.

Medulloblastoma↗
PubMed2007

Key role of insulin resistance in vascular injury among hemodialysis patients.

Insulin resistance prevails not only among diabetic patients but also among hypertensive and obese patients. The relationship between insulin resistance and cardiovascular diseases was investigated in hemodialysis (HD) patients. Eighty-one maintenance HD patients were enrolled. The homeostasis model assessment of insulin resistance (HOMA-IR) method was used to assess insulin resistance. The relationship of HOMA-IR with cardiovascular and all-cause events was assessed. Compared with nondiabetic patients (n = 55), diabetic patients (n = 26) showed higher HOMA-IR (2.5 +/- 0.3 vs 1.4 +/- 0.2, P < .05), lower ankle-brachial pressure index (ABI, 0.85 +/- 0.09 vs 1.12 +/- 0.02, P < .01), and shorter HD duration (3 +/- 1 vs 9 +/- 1 years, P < .01), although their body mass index was similar (22.3 +/- 0.5 vs 21.5 +/- 0.4 kg/m(2)). Nondiabetic patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (n = 36) had lower HOMA-IR (1.2 +/- 0.2 vs 1.8 +/- 0.4, P < .05) and higher ABI (1.18 +/- 0.02 vs 1.02 +/- 0.05, P < .01) than those without (n = 17). Cardiovascular events were less common in HD patients with normal HOMA-IR (P < .05) or ABI (P < .01). Our data indicate that 69% of diabetic and 27% of nondiabetic patients have HOMA-IR greater than 1.6, implying reduced insulin sensitivity in HD patients. The present results provide evidence that angiotensin inhibition improves insulin resistance, possibly preventing vascular injury in HD patients. Finally, our findings suggest that insulin resistance is prognostic of cardiovascular events in HD patients.

Aged↗
PubMed2006

Impact of selectin gene polymorphisms on rapid progression to end-stage renal disease in patients with IgA nephropathy.

OBJECTIVE: It is evident that leukocyte infiltration plays an important role in the pathogenesis of IgA nephropathy (IgAN). Selectin is one of the key adhesion molecules involved in leukocyte infiltration. Recent studies demonstrated a significant association between the selectin gene polymorphisms and susceptibility to IgAN. However, the impact of selectin gene polymorphisms on the progression to end-stage renal disease (ESRD) has not been studied. PATIENTS AND METHODS: To evaluate the influence of the selectin gene polymorphisms on the progression of IgAN, we designed specific primers for PCR genotyping and analyzed the association of selectin gene polymorphisms with the declining rate in renal function to its ESRD. RESULTS: A total of 61 hemodialysis patients were enrolled in the study. The mean age at renal biopsy was 33.0+/-13.3 years old, and the mean age at the start of hemodialysis was 41.2+/-13.8 years old. The mean interval between the time points of renal biopsy and the start of hemodialysis was 8.2+/-6.5 years (ranging from 0 to 33 years). The interval was significantly longer in IgAN patients with a homoallele of C in C1402T, C1402/C1402, of the E-selectin gene, or a homoallele of C in C712T, C712/C712, of the L-selectin gene compared to others. The haplotype, which is a combination of C1402/C1402 and C712/C712, is able to distinguish the group that is at least a better prognosis than the severest prognostic one. CONCLUSION: This study provides a possible association between the selectin gene polymorphisms and the rapid progression to ESRD in IgAN patients.

Adult↗
PubMed2006

Clinical response is associated with elevated plasma interleukin-1 receptor antagonist during selective granulocyte and monocyte apheresis in patients with ulcerative colitis.

Depletion of granulocytes and monocytes (GM) by selective apheresis (GMA) with an Adacolumn exerts an anti-inflammatory effect in patients with ulcerative colitis (UC) or rheumatoid arthritis. However, the mechanism of the anti-inflammatory effect of GMA is not fully understood yet. We investigated the effect of GMA on the plasma concentration of interleukin-1 receptor antagonist (IL-1ra), a potent anti-inflammatory cytokine. Twenty-six patients with active UC received GMA at one session per week for 5 consecutive weeks. Clinical response was defined as Deltaclinical activity index (DeltaCAI=CAI at entry - CAI at post)>or=4, while clinical remission was defined as CAI<or=4. Twenty-one of twenty-six patients (80.8%) responded to GMA. In the first session, plasma from responder patients showed a significant (P < 0.01) increase in IL-1ra in the Adacolumn outflow. In contrast, there was no change in IL-1ra in nonresponders. In conclusion, release of IL-1ra during GMA might be one mechanism of clinical efficacy associated with this therapy.

Adolescent↗
PubMed2006

A five-year comparison of the renal protective effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with non-diabetic nephropathy.

OBJECTIVE: Evidence suggests that the effectiveness of angiotensin-converting enzyme (ACE) inhibition diminishes with time, resulting in increasing angiotensin II levels, the action of which can be inhibited by the addition of an angiotensin receptor blocker (ARB). In the present study, the renal protective effects of ACE inhibitors and ARBs were compared over a five-year period in a prospective, randomized, open-blind study in 68 nondiabetic Japanese patients with elevated serum creatinine levels. PATIENTS AND METHODS: Japanese patients with renal insufficiency were randomly assigned to receive either an ACE inhibitor (benazepril 1.25 to 5 mg daily or trandolapril 0.5 to 4 mg daily) or ARB (candesartan 2 to 8 mg daily or losartan 25 to 100 mg daily) at the Kidney Disease Center at Saitama Medical School Hospital. The primary study endpoint was a change in glomerular filtration rate (GFR) between the baseline value and the last available value obtained during the five-year treatment period, as estimated by the Cockcraft-Gault equation. Secondary endpoints included the annual changes in GFR, serum creatinine level, urinary protein excretion, and blood pressure, as well as the rate of development of endstage renal disease. RESULTS: There were no significant differences in the primary endpoint between the two groups. However, after 4 years, the decline in GFR in patients treated with ARBs was significantly greater than that seen in patients treated with an ACE inhibitor (p<0.05). Furthermore, the rate of introduction of dialysis therapy was also significantly greater in the ARB-treated patients (52.7% in ACE inhibitor and 81.2% in ARB group at year 5. p<0.01). CONCLUSION: While our data suggested that ARB, like ACE, treatment might slow the progression of renal dysfunction, it also pointed to the necessity to be alerted to the progression to endstage renal disease with longterm medication.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Characterization of extracellular RNAs produced by the marine photosynthetic bacterium Rhodovulum sulfidophilum.

The marine photosynthetic bacterium Rhodovulum sulfidophilum produces extracellular nucleic acids that are involved in its flocculation. These were found to be produced concomitantly with cell growth. The RNA fraction of these extracellular nucleic acids was subjected to cDNA analysis by applying a micro RNA cloning method and found to contain mainly fully mature-sized tRNAs and fragments of 16S and 23S rRNAs. Analyses of modified bases and genes of the RNAs revealed no structural difference between the intracellular and extracellular RNAs. This is the first report of structural analyses of bacterial extracellular RNAs.

Base Sequence↗
PubMed2006

Hypoalbuminemia is an important risk factor of hypotension during hemodialysis.

Hypotension during hemodialysis (HD) is an important problem in patients on HD. To investigate the risk factors that contribute to the hypotension during HD, we compared background factors of hypotensive (HP) patients during HD. Among 58 patients undergoing HD in Tamura Memorial Hospital, 12 patients could not continue full HD because of hypotension. We compared the data of ultrafiltration volume, cardiothoracic ratio (CTR), total protein (TP), serum albumin, blood urea nitrogen (BUN), serum creatinine, total cholesterol (TC), hemoglobin (Hb), blood glucose (BS), brain natriuretic peptide (BNP), and cardiac function between HP patients (HP group; n=12) and sex- and age-matched control patients (NP group; n=12). There were no significant differences of age, sex, and duration of HD between the 2 groups. Cardiothoracic ratio is bigger and BNP is higher in the HP group compared with the NP group (CTR: HP 55.8+/-2.9% vs. NP 47.7+/-1.1%, p=0.0165; BNP: HP 602+/-171 vs. NP 147+/-38, p=0.0167). Serum albumin in the HP group is significantly lower compared with the NP group (HP 3.2+/-0.1 g/dL vs. NP 3.5+/-0.1 g/dL, p=0.0130). However, there were no significant differences of ultrafiltration rate (UFR), BS, TC, Hb, and cardiac function between the 2 groups. There is a significant negative correlation between changes of systolic blood pressure (delta systolic blood pressure) and serum albumin in these patients (r=-0.598, p=0.0016). From these data, we conclude that hypoalbuminemia is a major risk factor of hypotension during HD.

Aged↗
PubMed2006

Valsartan cardio-renal protection in patients undergoing coronary angiography complicated with chronic renal insufficiency (VAL-CARP) trial: rationale and design.

BACKGROUND: Despite an increase in the frequency of coronary angiography (CAG) in Japan, the exact incidence of contrast-induced nephropathy (CIN) remains unknown in the Japanese population, especially in patients with chronic renal insufficiency. In addition, the nature of pharmacological interventions that would benefit the patients before or after procedures such as coronary bypass graft (CABG) and percutaneous coronary intervention (PCI) has not been fully investigated. METHODS: In the trial 500 patients with renal insufficiency (defined as a glomerular filtration rate (GFR) of between 89 and 30 ml . min(-1) . (1.73 m(-2)) following CAG will be randomly assigned to receive either valsartan, an angiotensin receptor blocker or angiotensin converting enzyme (ACE) inhibitor plus valsartan.1 The primary end-point is a change in the GFR of patients, which will be followed up for 3 years, including following CABG surgery or PCI. The incidence of cardiac events as well as the adverse effects of pharmacological intervention will be evaluated. In addition, the incidence of renal artery stenosis at the time of CAG will be reported also; however, the patients with renal artery stenosis will be excluded from the present study. CONCLUSION: The present study will provide data on: 1) the exact incidence and course of renal function of CIN after CAG; and 2) the comparative therapeutic benefit of pharmacological intervention with valsartan alone or with valsartan and an ACE inhibitor in combination in patients with coexisting coronary artery diseases and chronic renal insufficiency, regardless of whether they receive CABG or PCI. In addition to these studies, an estimate of the incidence of renal artery stenosis in these patients will be demonstrated.

Adult↗
PubMed2006

Dexamethasone induces connective tissue growth factor expression in renal tubular epithelial cells in a mouse strain-specific manner.

Connective tissue growth factor (CTGF), a downstream mediator of transforming growth factor-beta1, mediates mesangial cell/fibroblast proliferation and extracellular matrix production by renal cells. Here, we show that renal tubular epithelial cells from patients with minimal change nephritic syndrome produced CTGF after glucocorticoid treatment. In addition, the glucocorticoid dexamethasone (DEX) increased CTGF mRNA levels in the kidneys of C57B6 but not SJL mice and produced intermediate CTGF mRNA levels in the kidneys of F1 (C57B6 x SJL) mice, midway between the levels found for parental strains. DEX also increased CTGF mRNA levels in cultured tubular epithelial cells derived from C57B6 (mProx24) but not SJL (MCT) mice via transcriptional up-regulation of CTGF mRNA. Transient transfection experiments using luciferase reporter constructs bearing CTGF promoter fragments revealed that the -897- to -628-bp fragment contained DEX-responsive positive regulatory elements, which were active in mProx24 but not MCT cells. Long-term DEX treatment resulted in fibronectin deposition in the kidneys of C57B6 but not SJL mice, and this effect was inhibited by co-administration of CTGF anti-sense oligodeoxynucleotides. Thus, glucocorticoid-induced renal fibrogenesis seems to be influenced by genetic background, with the critical DEX-responsive elements in the -897- to -628-bp region of the CTGF promoter.

Adolescent↗
PubMed2006

A possible anti-inflammatory role of angiotensin II type 2 receptor in immune-mediated glomerulonephritis during type 1 receptor blockade.

We previously reported that angiotensin II type 1 receptor (AT1R) blockade attenuates renal inflammation/fibrogenesis in immune-mediated glomerulonephritis via angiotensin II type 2 receptor (AT2R). In the present study, further in vivo experiments revealed that AT2R was expressed in tubular epithelial cells of nephritic kidneys in mice, and feedback activation of the renin-angiotensin system during AT1R blockade significantly reduced p-ERK, but not intranuclear nuclear factor-kappaB, levels via AT2R. This led to reduction in mRNA levels of the proinflammatory mediator monocyte chemoattractant protein-1 and overall interstitial inflammation and subsequent fibrogenesis. Specific blockade of ERK expression in tubular epithelium by anti-sense oligodeoxynucleotides also attenuated interstitial inflammation, mimicking the anti-inflammatory action of AT2R in nephritic kidneys. Alternatively, we succeeded in confirming such an AT(2)R function by demonstrating that AT1R blockade did not confer renoprotection in nephritic, AT2R gene-deficient mice. Additional in vitro experiments revealed that AT2R activation did not affect nuclear factor-kappaB activation by tumor necrosis factor-alpha in cultured tubular epithelial cells, although it inhibited ERK phosphorylation, which reduced monocyte chemoattractant protein-1 mRNA levels. These results suggest that feedback activation of AT2Rs in tubular epithelium of nephritic kidneys plays an important role in attenuating interstitial inflammation.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

[E-COST].

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Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Early estimation of high peritoneal permeability can predict poor prognosis for technique survival in patients on peritoneal dialysis.

At the beginning of continuous ambulatory peritoneal dialysis (CAPD), different patients exhibit large differences in peritoneal permeability. To determine if early estimation of peritoneal permeability can predict the prognosis of CAPD, we used data from a personal dialysis capacity (PDC) study group in Japan to investigate patient and technique survival rates. Based on the data from a previously reported, prospective multicenter study encompassing eight dialysis centers in Japan (Am J Kidney Dis 2002; 40:1045-54), we recalculated patient and technique survival data. We reviewed the records of 139 patients newly initiated on CAPD from January 1995 to December 1999. Peritoneal permeability was estimated by PDC test within the first year after initiation. We divided the patients into paired groups according to several peritoneal permeability variables as calculated by the PDC test (area, plasma loss, and peritoneal creatinine clearance), and we compared patient and technique survival rate between the groups. The mean age of the patients was 49.6 years +/- 14.9 years (standard deviation). The mean pore area of peritoneum was 19,936 +/- 8383 cm/1.73 m2. Estimation of patient survival by the Kaplan-Meier method showed 94.2%, 88.4%, 84.1%, and 79.7% at 1, 2, 3, and 5 years respectively. Estimated technique survival (including death as an endpoint) by the Kaplan-Meier method showed 90.6%, 76.8%, 67.4%, and 54.3% at 1, 2, 3, and 5 years respectively. In the high peritoneal permeability group (high area and high plasma loss), the technique survival at 5 years was significantly lower than in the low peritoneal permeability group [area: 55.9% (high) vs. 72.7% (low), p = 0.0459; plasma loss: 43.3% (high) vs. 62.8% (low), p = 0.0197). We observed no significant difference in patient survival between the high and low peritoneal permeability patients. In the high peritoneal creatinine clearance group, patient and technique survival were both significantly lower than in the high peritoneal creatinine clearance group. Patients with high peritoneal permeability as calculated by the PDC test at the start of PD had a poor prognosis for technique and patient survival on CAPD. We conclude that early estimation of high peritoneal permeability can predict poor outcome for patients on CAPD.

Creatinine↗
PubMed2006

The newly developed calcium antagonist, azelnidipine, increases drain volume in continuous ambulatory peritoneal dialysis patients.

Many patients undergoing continuous ambulatory peritoneal dialysis (CAPD) receive antihypertensive agents, including calcium antagonists, which produce reflex tachycardia through activation of the sympathetic nervous system. Azelnidipine, a newly developed calcium antagonist, has unique characteristics in that it causes less reflex stimulation of the sympathetic nervous system. In the present study, we used a crossover method to compare the effects of amlodipine (5-10 mg daily) and azelnidipine (8-16 mg daily) on drain volume and weekly creatinine clearance in 9 CAPD patients (3 women, 6 men; mean age: 64 +/- 5 years; mean duration of CAPD: 1.8 +/- 0.6 years). Each calcium antagonist was administered for 3 months and then switched for the other. As compared with amlodipine, azelnidipine increased drain volume by 13% +/- 2% (p < 0.05) and weekly creatinine clearance by 12% +/- 2% (p < 0.05). At the same time, we observed no significant differences in blood pressure and urine volume. The increases in drain volume produced by azelnidipine resulted from less activation of the sympathetic nervous system. We therefore suggest that activation of the sympathetic nervous system induced by calcium antagonists may be important in the regulation of drain volume in CAPD patients.

Amlodipine↗
PubMed2006

Efficacy and safety of meropenem plus tobramycin followed by meropenem plus vancomycin for treating peritonitis in patients on continuous ambulatory peritoneal dialysis.

Peritonitis is a serious complication in patients on peritoneal dialysis. We examined the efficacy of MTV therapy [first 7 days: meropenem 0.5 g intravenously (IV) twice daily, plus tobramycin 15 mg intraperitoneally (IP) in every dialysis bag; next 7 days: meropenem 0.5 g IV twice daily, plus vancomycin 8 mg/kg IP in every bag after a 1-g loading dose] on peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), comparing it with the treatment previously recommended by the International Society for Peritoneal Dialysis (combination of first-generation cephalosporins and aminoglycosides). We treated 36 CAPD peritonitis episodes with MTV therapy. Outcome measures were primary response rate at day 14 and relapse rate within 28 days after the start of antibiotic therapy. The primary response rate was 34/36 (94.4%). No patients treated with MTV therapy required catheter removal. We observed no serious side effects in these patients. We conclude that MTV therapy may be an even better choice of treatment for peritonitis in patients on CAPD than was the previous empirical treatment (combination of first-generation cephalosporin and aminoglycosides).

Anti-Bacterial Agents↗