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Biomedical subjects

Tatsuo Hosoya

Publications and source records attributed to Tatsuo Hosoya.

At least 37 records · Page 2Linked to original sources

5-hydroxytryptamine synthesis in HL-1 cells and neonatal rat cardiocytes.

Some reports showed that serotonergic system might have existed and that 5-hydroxytryptamine (5-HT) was detected in the hamster heart. The source of 5-HT in the heart, however, remains to be fully elucidated. So the present study was designed to define serotonergic system and to clarify which cell could produce 5-HT in the heart. As a result, 5-HT was detected in homogenates of HL-1 cardiomyocytes by high performance liquid chromatography with fluorescence detection, but not in those of neonatal rat non-cardiomyocytes (NMCs). And TPH and AADC mRNAs were expressed in HL-1 cardiomyocytes and neonatal rat cardiomyocytes (MCs), not in NMCs. mRNAs of 5-HT(2A) receptor were detected in both MCs and NMCs, and those of 5-HT(2B) receptor in NMCs. These findings definitively demonstrate that 5-HT is secreted from the myocytes of the heart and strongly implied that 5-HT might play a certain role in cardiac physiology.

Animals↗

Human mesenchymal stem cells in rodent whole-embryo culture are reprogrammed to contribute to kidney tissues.

The use of stem cells has enabled the successful generation of simple organs. However, anatomically complicated organs such as the kidney have proven more refractory to stem-cell-based regenerative techniques. Given the limits of allogenic organ transplantation, an ultimate therapeutic solution is to establish self-organs from autologous stem cells and transplant them as syngrafts back into donor patients. To this end, we have striven to establish an in vitro organ factory to build up complex organ structures from autologous adult stem cells by using the kidney as a target organ. Cultivation of human mesenchymal stem cells in growing rodent embryos enables their differentiation within a spatially and temporally appropriate developmental milieu, facilitating the first step of nephrogenesis. We show that a combination of whole-embryo culture, followed by organ culture, encourages exogenous human mesenchymal stem cells to differentiate and contribute to functional complex structures of the new kidney.

Animals↗

Correction of CAPD catheter displacement using alpha-replacement method.

BACKGROUND: Malposition of the tip of a continuous ambulatory peritoneal dialysis (CAPD) catheter may impede a dialysis, and an invasive method, such as open or laparoscopic surgery, is necessary to correct its position. The alpha-replacement method is a nonsurgical procedure; however, the reported clinical experience has been limited. We thus reviewed our 19 cases to clarify the efficacy of this method. METHOD: The alpha-replacement method was used in 19 patients [mean age, 50 +/- 14 years old; male/female ratio, 13/6; duration of catheter insertion, 23.7 +/- 23.9 months; total, 29 times in 19 patients (once in 13 patients, twice in 3, three times in 2, four times in 1 patient)]. All patients received a swan-neck J-type catheter. The procedure was carried out by using a special guidewire within 1-2 weeks after dislocation of the tips. RESULTS: The procedure was successfully performed 22 times in 14 patients (success rate, 78% in each performance). Required time was only 5-10 min in most successful cases. No evident complications were encountered in any case. CONCLUSIONS: The alpha-replacement method for a displaced CAPD catheter proved to be effective and safe.

Adult↗

Calcium channel blocker versus angiotensin II receptor blocker in autosomal dominant polycystic kidney disease.

BACKGROUND: Although hypertension is commonly found in patients with autosomal dominant polycystic kidney disease (ADPKD), there is no consensus about which antihypertensive agents are most appropriate. The effects of calcium channel blockers (CCB) and angiotensin II receptor blockers (ARB) on blood pressure and renoprotection were compared in hypertensive patients with ADPKD. METHODS: We randomly assigned 49 participants to CCB amlodipine-based (2.5-10 mg/day) or ARB candesartan-based (2-8 mg/day) regimens. Twenty-five patients (13 males and 12 females) received amlodipine, and 24 patients (13 males and 11 females) received candesartan. This was followed up for 36 months. RESULTS: Baseline characteristics were similar, and blood pressure was well controlled in both groups throughout the study period. Six out of 25 (24.0%) amlodipine and 1 out of 24 (4.2%) candesartan patients were terminated from the protocol due to a twofold increase in serum creatinine and/or decrease in creatinine clearance (Ccr) to half of the baseline. The renal event-free survival rate was significant (p < 0.05, Breslow-Gehan-Wilcoxon test). Serum creatinine was higher in the amlodipine group than in the candesartan group at 24 and 36 months (p < 0.05). The decrease in Ccr at 36 months was larger in the amlodipine group than in the candesartan group (DeltaCcr: -20.9 +/- 13.1 vs. -4.8 +/- 13.8 ml/min, p < 0.01). Urinary protein excretion was significantly lower in the candesartan group than in the amlodipine group at 36 months. Urinary albumin excretion was significantly lower in the candesartan group than in the amlodipine group at 12, 24 and 36 months. CONCLUSIONS: The renoprotective effect of candesartan is considered more favorable than amlodipine in the treatment of ADPKD. This is independent of the antihypertensive effect per se.

Adult↗

Morning blood pressure predicts hypertensive organ damage in patients with renal diseases: effect of intensive antihypertensive therapy in patients with diabetic nephropathy.

Blood pressure (BP) measured at home early in the morning (HBP) has been recognized as a useful predictor for organ damage and has been viewed as an important therapeutic target in patients with hypertension. The present study was aimed to determine whether this notion holds true in patients with progressive renal disease. The study enrolled patients with mild to moderate renal impairment. They were all directed to record self-measured HBP to evaluate the adequacy of BP control. In addition to the conventional antihypertensive therapy, intensive treatment to more efficiently reduce elevated morning HBP was applied, especially in patients with diabetic nephropathy. The results were as follows: 1) The status of BP control assessed using HBP and office/clinic BP (OBP) shows predominance of morning hypertension. The prevalence of patients with well-controlled systolic HBP was 38%, those with poorly-controlled HBP 30%, masked hypertension 20% and white coat hypertension 12%. 2) Early morning systolic HBP in diabetics was significantly higher than that in non-diabetics. However, when evaluated on systolic OBP, both groups were comparable.3)Logistic regression analysis showed that the predictive variables to explain morning hypertension (more than 130 mmHg and increased systolic HBP) were age, amount of daily urinary protein excretion and left ventricular mass index (LVMI).4)Following conventional therapy, intensive antihypertensive therapy consisting of calcium channel blockers (CCB) and/or diuretics given in the morning, and angiotensin receptor blockers (ARB) given in the evening, together with alpha1-blockers given at bedtime, efficaciously reduced elevated HBP in the morning. This result was associated with significant reduction in daily urinary protein excretion and in serum plasminogen-activator inhibitor (PAI-1) concentration. The present study indicates that, regardless of ongoing conventional antihypertensive therapy, the majority of patients with renal disease had morning hypertension, suggesting that these patients are at a higher risk for cardiovascular disease. For the purpose of improving morning hypertension, intensive treatments with combined CCB, ARB and alpha1-blockers could have substantial benefit on the morbidity and prognosis in patients with diabetic nephropathy.

Aged↗

Frequency of gouty arthritis in patients with end-stage renal disease in Japan.

OBJECTIVE: The purpose of this study was to investigate gouty arthritis in Japanese patients with end-stage renal disease (ESRD). METHODS: Questionnaires plus patient interviews and reviews of medical records were used to investigate gouty arthritis in 493 Japanese patients with ESRD receiving maintenance dialysis. RESULTS: The frequency of gouty arthritis was 4.1% for female patients and 15.4% for male patients greater than 2 years before the start of dialysis, and 0.6% for female patients and 7.7% for male patients less than 2 years before the start of dialysis. After the start of dialysis the frequency was 3.4% for the first 2 years and 1.2% thereafter in male patients, but no gouty arthritis appeared in female patients. Although the annual number of gouty attacks was 2.0+/-4.2 greater than 2 years before the start of dialysis, and 1.9+/-6.6 less than 2 years before the start of dialysis, the annual number of attacks decreased significantly after the start of dialysis to 0.2+/-0.7 in the first 2 years and 0.1+/-0.6 thereafter. CONCLUSIONS: The frequency of gouty arthritis in Japanese patients with ESRD is similar to that of patients with hyperuricemia in the general population and it is decreased slightly before dialysis; however, the frequency decreases markedly after dialysis.

Aged↗

[Antihypertensive therapy for refractory morning hypertension in patients on peritoneal dialysis].

Due to excessive salt and water retention, hypertension often becomes refractory in patients undergoing peritoneal dialysis (PD). Management of high blood pressure (BP) appears to be of particular importance in such patients because of its substantial impact on the patients' prognosis. However, attempts to control hypertension in PD patients have not been successful in most cases. In this regard, the present study aimed to address the adequacy of current antihypertensive therapy for PD patients. A new antihypertensive strategy expected to improve the outcome was tested on the assumption that treatment with either angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) in the evening together with alpha1-blocker at bed time and long-acting Ca channel blocker (CCB) in the morning might ameliorate BP control associated with morning hypertension. Enrolled in the present study were 40 patients whose BP was evaluated by both office and home measurement. Due to an emerging concern about morning hypertension, home BP measured early in the morning was used for the analysis. Each patient was categorized into the following four groups in accordance with office and home BP: well-controlled, poorly-controlled, white-coat and masked (opposite to white-coat), hypertension. After the observation period, 28 patients with refractory hypertension were allocated to intensive antihypertensive therapy in which ARB or ACE-I previously prescribed in the morning or daytime was shifted to the night. In addition, alpha1-blocker was given at bed time. Furthermore, long-acting CCB and diuretics were shifted to the morning. The patients were then followed up for 4-6 months. The results were as follows: 1) Of the total number of 40 PD patients, systolic hypertension was noted in 50% of cases by office BP and in 80% by home BP. The former was less frequent than the latter (p=0.0047, n=40). Similarly, diastolic hypertension was noted in 20% by office BP and in 45% by home BP. The former was less frequent than the latter (p=0.0045, n=40 by McNemar's analysis). The distribution of BP control categories was well-controlled in 11%, poorly-controlled in 42%, masked hypertension in 39% and white-coat hypertension in 8% when determined by systolic BP. The distribution was well-controlled in 45%, poorly-controlled in 13%, masked hypertension in 34% and white-coat hypertension in 8% of cases when determined by diastolic BP. 2) In 28 patients subjected to the intensive therapy, the control category of systolic BP was changed from 11 to 37% in well-controlled cases, from 42 to 30% in poorly-controlled cases, from 39 to 26% in masked hypertension cases and from 8 to 7% in white-coat hypertension cases. The shift in categories in both poorly-controlled and masked hypertension cases to the better category (well-controlled), was statistically significant (p=0.001, by Wilcoxon's signed rank test). Similarly, the control category of diastolic BP was changed from 45 to 43% in well-controlled cases, from 13 to 15% in poorly-controlled cases, from 34 to 32% in masked hypertension cases and from 8 to 10% in white-coat hypertension cases. There was a tendency for the prevalence of poorly-controlled and masked hypertension to improve to the well-controlled category in response to intensive therapy (p=0.0625, by Wilcoxon's signed rank test). 3) The plasma concentration of plasminogen activator inhibitor (PAI-1)/tissue plasminogen activator (t-PA) complex (total PAI-1 complex) was significantly decreased after intensive therapy (17.3+/-7.8 ng/ml vs. 13.5+/-4.6 ng/ml, n=28, p<0.01 by paired t-test). In contrast, the plasma concentration of t-PA was unchanged even after intensive therapy (4.8+/-3.9 ng/ml vs. 6.2+/-2.9 ng/ml, n=28, ns). These data suggest that home BP obtained in the morning is a useful measure for evaluating morning hypertension in PD patients, most of whom have refractory hypertension categorized as either poorly-controlled or masked hypertension. Intensive treatment with ACE-I/ARB given in the evening along with alpha1-blocker at bed time combined with a diuretic and/or long-acting CCB in the morning is efficacious in controlling the BP of patients with refractory hypertension in PD patients. The link between the reduction in plasma total PAI-1 levels and the intensive therapy may suggest that this therapeutic strategy could prevent thrombotic events associated with morning hypertension in patients on PD.

Aged↗

[Interstitial pneumonia and nephritis with Sjögren's syndrome: successful treatment with corticosteroid therapy].

A Sixty eight-year-old man complained of shortness of breath on exercise since the spring of 2001. An abnormal lung shadow was pointed out on chest X-ray and progression of renal dysfunction and high gamma globulinemia were detected out on blood examination. He was admitted to the Department of Respiratory Disease in our hospital in March 2003, because of bilateral lower lung interstitial shadow, severe anemia (Hb 7.9 g/dl), and renal dysfunction (S-Cr 1.9 mg/dl). He was found to have hypergammaglobulinemia (IgG 2,997 mg/dl), positive RO/SS-A antigen, high serum KL-6 level (2,050 U/ml), and increased urinary excretion of beta2-microglobulin (beta2MG). Both Gum test and Schirmer test results were positive. Lip biopsy showed cell infiltration to the salivary glands and he was diagnosed as having Sjogren's syndrome. Renal biopsy showed diffuse interstitial cell infiltration and a Trans Bronchoscopic Lung Biopsy (TBLB) showed fibrotic thickness and lymphocyte infiltration in the alveolar septum. Accordingly, he was diagnosed as having Sjögren's syndrome complicated with both interstitial nephritis and interstitial pneumonitis. He was treated by high-dose corticosteroid therapy and anticoagulant heparin. His laboratory data showed that both serum KL-6 and urinary beta2MG were reduced. Chest CT showed remarkable improvement of the interstitial shadow. A second renal biopsy performed at ten weeks after the beginning of treatment showed remarkable improvement of the interstitial cell infiltration. This is a rare case of Sjögren's syndrome complicated with interstitial nephritis and interstitial pneumonitis, treated successfully with high-dose corticosteroid therapy. Both complications showed immediate improvement with high-dose corticosteroid therapy, suggesting that early steroid therapy is effective for both complications.

Aged↗

[Syndrome of inappropriate ADH secretion (SIADH) induced by pramipexole in a patient with Parkinson's disease].

An 85-year-old woman with Parkinson's disease was admitted to our hospital to conduct a further work-up for progressive gait disturbance. She had been on medications for the disease for more than a decade prior to admission. In order to improve her condition, she was newly administered pramipexole, a dopamine agonist, from day 3 in addition to the preceding anti-Parkinson's therapy. However, on day 10, her consciousness level was rapidly deteriorated into delirium(JCS II-10), which was not accompanied by neurological signs and symptoms. Laboratory tests showed severe hyponatoremia with relatively increased urinary sodium excretion, and severe low serum osmolarity with an increased urinary osmolarity. Brain CT and brain MRI showed no specific abnormalities except for those related to aging. Blood concentration of ADH measured at the onset was substantially higher(39.5 pg/ml) than normal (0.3-3.5 pg/ml under normal osmolarity). Diseases causing hyponatremia, such as liver cirrhosis, congestive heart failure, hypotonic dehydration, and malignancy-associated inappropriate ADH secretion (SIADH), were all excluded. Under the suspicion of SIADH due to pramipexole, the drug was discontinued and as a result, her consciousness level improved rapidly together with a prompt reduction in ADH level (9.2 pg/ml). To the best of our knowledge, the present case is the first that demonstrates pramipexole-induced SIADH. Since pramipexole is classified as a dopaminergic receptor agonist, this case may provide new insight into a link between ADH and the dopaminergic receptor in the central nervous system.

Aged↗

[Estimation of glomerular filtration rate by inulin clearance: comparison with creatinine clearance].

Inulin clearance (Cin) is widely believed to be the gold standard of the glomerular filtration rate (GFR). However, in Japan, Cin has not been officially recognized by the Ministry of Health, Labour and Welfare of Japan for clinical use. Creatinine clearance (Ccr) has been used to estimate the renal function of patients, but there have been many studies in which Ccr estimates were GFR falsely high because the metabolism and tubular excretion of creatinine widely varied according to the pathophysiological state of the patient. In the present study, we determined Cin and Ccr simultaneously in 116 adult patients with renal diseases and diabetic mellitus. The clearance study was performed by the modified Wesson's method. The inulin preparation was FFI-1010 (Fuji Yakuhin Co. Ltd.). Inulin in serum and urine was determined by the newly devised enzymatic assay (Toyobo Co. Ltd.), which is specific for inulin. The mean Cin was 35.0 +/- 14.4 ml/min/1.73 m2. The mean Ccr(the enzyme assay) was 63.6 +/- 24.1 ml/min/1.73 m2 and that of the kinetic Jaffe assay was 55.3 +/- 19.3 ml/min/1.73 m2. Mean Ccr/Cin was 1.93 +/- 0.73, 1.69 +/- 0.62, respectively. This ratio was significantly different(p < 0.05) in the degree of reduction of Cin, with values of 2.07 +/- 0.82 (Cin < 40 ml/min/1.73 m2) and 1.64 +/- 0.32(40 < Cin < 80 ml/min/1.73 m2), respectively. Only 8 patients were classified into the same degree of reduced renal function (the Guideline of Japanese Society of Nephrology). The findings of this study suggest that the GFR determined by Ccr could misjudge the renal function of patient and delay the administration of proper treatment of the patient. Introduction of Cin into the clinical field is necessary to avoid this delay.

Acute Disease↗

[Dialysis as bridge therapy for renal transplantation: single center experience, a comparison of hemodialysis and continuous ambulatory peritoneal dialysis].

BACKGROUND: Kidney transplantation is the most ideal treatment in renal replacement therapy for patients with end-stage renal disease. However, the prevalence of transplantation is extremely low and most patients with ESRD should continue dialysis for their whole life. Recently, high transposition rate of renal transplantation from peritoneal dialysis (PD) was reported, however, it was unclear whether a difference in dialytic modality can influence the outcome. Therefore, we evaluated the influence of dialytic modality on the rate of kidney transplantation and outcome in our single center. METHODS: Forty-two kidney transplants were carried among 1,573 dialysis patients from the years 1986 to 2004 in our center. Transposition rates from two modalities (HD and PD) and graft survival were compared. The incidence of acute rejection episode, complications after receiving transplantations, and coexisting diseases were also evaluated between the two modalities prior to transplantation. RESULT: The number of patients who received HD was larger than PD (HD 77.1%, PD 22.9%, respectively). Forty-two patients undergoing dialytic therapy received a living-donor kidney transplantation. Overall graft survival was 92% at 5 years and 75% at 10 years. Among these cases, dialytic modality prior to transplantation was 57.1% in HD, and 42.9% in PD. The transfer rate from PD to transplantation was significantly (p = 0.0036) higher (4.7%) than that of HD (1.9%). The reason for the high transfer rate of PD patients might be cooperation with their family and the provision of relevant information by nephrologists during PD. There were no differences between the two modalities prior to transplantation in the graft survival rate, incidence of acute rejection, and complications before and after transplantation. CONCLUSION: Difference in pretransplant dialysis modality did not affect the outcomes, however, the transfer rate from PD was significantly higher than from HD. Accordingly, PD is useful compared to HD as bridge therapy for kidney transplantation from the high feasibility of living-donor kidney transplantation.

Adult↗

Effects of SCH27899 (Ziracin), an oligosaccharide everninomicin antibiotic, on urate kinetics in humans.

OBJECTIVE: Intravenous administration of an everninomicin antibiotic, SCH27899 (Ziracin), in healthy subjects caused a marked decrease in serum urate by increasing its urinary excretion, as well as an increase in serum bilirubin in a dose-dependent manner. To clarify the underlying mechanism, a crossover study and an in vitro study were conducted. METHODS: Crossover study was performed in nine healthy male volunteers over three periods by administering SCH27899 (1-h i.v. infusion of 3 mg/kg) alone, probenecid (2000 mg, p.o.) alone and their combination. Also, an in vitro experiment was conducted using rat brush-border membrane vesicles to elucidate the effect of SCH27899 on urate transport across renal tubular epithelium. RESULTS: SCH27899 alone and probenecid alone showed a uricosuric, serum urate-lowering effect, and, when given in combination, the effects on serum urate appeared to be additive, as indicated in the earlier phase, prior to the peaks of respective drug effects. Serum and urinary concentrations of SCH27899 were not influenced by the co-administration of probenecid. Serum bilirubin was also significantly increased by both SCH27899 alone and in combination with probenecid. The SCH27899-probenecid combination additive effect on serum bilirubin did not reach significance. SCH27899, probenecid and losartan, an angiotensin-II-receptor antagonist possessing a uricosuric effect, significantly inhibited (14)C-urate uptake into the vesicles, which was dependent on the pH gradient across the membrane; whereas, vancomycin did not. CONCLUSION: It is concluded that SCH27899 itself contributes, at least in part, to a uricosuric effect following i.v. infusion. However, some metabolite(s) may also contribute to this, since the degree of urate-uptake inhibition by SCH27899 was less than probenecid and losartan, and the serum urate-lowering effect was delayed and prolonged compared with the time profile of serum concentration.

Adult↗

A case of renal sarcoidosis: a special reference to calcium metabolism as a diagnostic and the therapeutic implications.

Sarcoidosis is a systemic granulomatous disease of unknown etiology and is associated with a wide variety of renal disorders including nephrolithiasis, hypercalciuria, hypercalcemia, nephrocalcinosis, tubular defect, glomerulonephritis, and granulomatous interstitial nephritis. We report a case of renal sarcoidosis in which we could not detect any evidence of extrarenal involvements that was diagnosed by renal biopsy and abnormal calcium metabolism incompatible with chronic renal insufficiency. On laboratory findings, decreased creatinine clearance, proteinuria, hypercalcemia, hypercalciuria, and mildly elevated serum angiotensin-converting enzyme (ACE) were seen. Serum intact parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,alpha-25 vit D) were lower and higher than normal range, respectively, whereas the patient was already in chronic renal insufficiency. He was treated with oral corticosteroid. Serum ACE tended to fall, and 1,alpha-25 vit D level decreased with substantial fall of serum calcium and daily calcium excretion. In contrast, intact PTH increased slowly in accordance with a fall of serum calcium compatible with the level of renal impairment. Creatinine clearance and daily excretion of protein improved. The case reported here may propose that serial measurement of serum level of 1,alpha-25 vit D, calcium level, and magnitude of daily calcium excretion into urine is a simple and meaningful tool to detect the therapeutic response in sarcoidosis with abnormal calcium metabolism.

Anti-Inflammatory Agents↗

Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a recently identified polypeptide that promotes renal phosphate excretion and decreases serum 1,25-dihydroxyvitamin D3 (1,25D) levels. Serum FGF-23 levels are extraordinarily elevated in patients with end-stage renal failure. METHODS: Blood and urine samples were obtained from 62 predialysis patients (age, 51.3 +/- 14.0 years; range, approximately 18 to 76 years; 32 men, 30 women). Serum FGF-23 levels were determined by means of a sandwich enzyme-linked immunosorbent assay system using 2 kinds of monoclonal antibodies that does not detect biologically inactive N-terminal and C-terminal fragments derived from an identified internal cleavage site to date. RESULTS: Serum FGF-23 levels increased with the decrease in creatinine clearance (Ccr). Both intact parathyroid hormone (PTH) and 1-84 PTH levels correlated closely with FGF-23 levels (r2 = 0.857; r2 = 0.860). A negative correlation between serum concentrations of FGF-23 and 1,25D (r2 = 0.255) was found. The maximum tubular reabsorptive rate of phosphate correlated negatively with serum FGF-23 concentrations (r2 = 0.460). However, the amount of daily urinary phosphate excretion was significantly less in patients with a Ccr less than 30 mL/min (<0.50 mL/s; P < 0.01), whereas their circulating FGF-23 levels were significantly greater (P < 0.001). CONCLUSION: Circulating FGF-23 levels increase with the decrease in renal function. FGF-23 is a likely candidate to lead the reduction in serum 1,25D levels. FGF-23 becomes a potential uremic toxin to decrease 1,25D levels when it loses its hypophosphatemic action because of a decreased number of viable nephrons in patients with advanced renal failure. As such, FGF-23 may be an important determinant in the regulation of mineral metabolism with renal insufficiency.

Adolescent↗