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Biomedical subjects

O Sakai

Publications and source records attributed to O Sakai.

At least 19 recordsLinked to original sources
PubMed2002

Clinical effect of intravenous calcitriol administration on secondary hyperparathyroidism. A double-blind study among 4 doses.

BACKGROUND/AIMS: Although the PTH-suppressive effect of intravenous calcitriol has already been demonstrated by various studies, the precise dose-response to calcitriol has not been fully determined for uremic secondary hyperparathyroidism (2HPT). In order to investigate in detail the dose-response of intravenous calcitriol and the adequate initial dose against 2HPT, a randomized prospective double-blind study was conducted. METHOD: One-hundred and sixty-two patients with 2HPT undergoing hemodialysis three times per week were randomly assigned to four calcitriol (Ro21-5535) treatment groups, 0 (placebo), 1, 1.5 or 2 microg. Calcitriol or placebo was given intravenously after each dialysis for 12 weeks under double-blind conditions. RESULTS: Calcitriol dose-dependently reduced both intact-PTH and high-sensitivity assay mid-terminal (HS)-PTH levels. The rate of per-week change in intact-PTH was 0.0% in the placebo group, -7.8% in the 1-microg group, -18.9% in the 1.5-microg group and -24.1% in the 2-microg group. Calcitriol dose-dependently increased the rate of increase in serum Ca adjusted by albumin level. The per-week increases in adjusted serum Ca were -0.01, 0.08, 0.23 and 0.35 mg/dl in the placebo, 1-, 1.5- and 2-microg groups, respectively. Although the degree of PTH suppression was correlated with the adjusted serum Ca increase, by-patients investigation revealed that the number of patients with suppression of PTH despite of no or slight elevation of adjusted serum Ca level was largest in the 1-microg group among the three calcitriol groups. CONCLUSION: Intravenous calcitriol was found to have a clear dose-dependent effect on PTH reduction in patients with 2HPT, and the appropriate initial dose of this agent was determined to be 1 microg per dialysis session.

Adult↗
PubMed2001

Tunneling through a quantum dot in local spin singlet-triplet crossover region with Kondo effect.

Tunneling conductance through a quantum dot is calculated around the local spin singlet-triplet crossover region including the Kondo effect. The calculation is carried out using the numerical renormalization group method. When the potential on the dot deepens, two electrons filling a lower energy orbital redistribute to gain Hund's coupling energy. This redistribution induces a bump in the conductance between the Coulomb peaks. The Kondo temperature on the bump is high due to the fluctuation on the singlet-triplet crossover region. The behaviors agree well with recent experiment.

Journal Article↗
PubMed2000

Lymph node pathology. Benign proliferative, lymphoma, and metastatic disease.

The evaluation of cervical lymph nodes is one of the main indications for performing CT and MR imaging of the neck. Imaging may be done for evaluation of an unknown neck mass, but more commonly the neck is imaged to evaluate potential metastasis from a known mucosal malignancy. CT and MR imaging characteristics of both malignant and nonmalignant nodal diseases are reviewed and the differential diagnosis of nodal pathologies for specific imaging findings are discussed. A recently proposed imaging-based nodal classification for metastatic nodal diseases from head and neck cancer is also described.

Calcinosis↗
PubMed2000

Synthesis and aldose reductase inhibitory activities of novel N-nitromethylsulfonanilide derivatives.

A novel series of 14 N-nitromethylsulfonanilide derivatives were synthesized and evaluated for their ability to inhibit recombinant aldose reductase. Computational docking simulations provided a good explanation for the observed structure-activity relationships. Kinetic analysis of (2-fluoro-5-methyl-N-methyl)-N-nitromethylsulfonanilide, 11, one of the most potent compounds in this series with an IC50 = 0.35 M, showed uncompetitive inhibition. Subsequent in vitro culture studies of rat lenses with 11 indicated that this series of aldose reductase inhibitors are effective in either preventing or retarding sugar cataract formation associated with diabetes.

Aldehyde Reductase↗
PubMed2000

Dedifferentiated chondrosarcoma of the larynx.

A 74-year-old man with a history of a chondroid lesion of the larynx noted an enlarging neck mass. Axial CT showed a large expansile lesion arising from the left thyroid cartilage. Multiple rings and arcs with relatively intact cortex indicated a chondroid lesion. Irregularity of the anterolateral margin abutted a prominent soft-tissue component. The specimen obtained from fine needle aspiration was suggestive of a malignant fibrous histiocytoma. After further resection, the final diagnosis was dedifferentiated chondrosarcoma. A new soft-tissue component or rapid growth of the mass can be indicative of a diagnosis of dedifferentiated chondrosarcoma.

Aged↗
PubMed2000

Persistent stapedial artery: CT findings.

CT of a patient with conductive hearing loss showed a small vascular structure leaving the carotid canal and passing through the stapes to join the facial nerve canal. The small bony channel paralleled the anterior tympanic segment of the facial nerve, continuing beyond the geniculate ganglion into the middle cranial fossa. Otoendoscopic photography documented the presence of a persistent stapedial artery.

Angiography↗
PubMed1999

Significance of mesangial expression of alpha-smooth muscle actin in the progression of IgA nephropathy.

To determine whether phenotypic modulation of mesangial and interstitial cells correlated with the long-term prognosis of IgA nephropathy (IgAN), we analyzed retrospectively 27 patients with IgAN whose creatinine clearance at the time of renal biopsy was normal. The patients were subdivided into two groups according to the course of renal function during follow-up. Thirteen patients maintained normal renal function for more than 15 years (stable group), and 14 progressed to end-stage renal disease (ESRD group). The score of mesangial cell cellularity in the ESRD group was significantly higher than in the stable group. Immunohistochemistry localized alpha-smooth muscle actin (alpha-SMA) in renal mesangial cells of approximately half these patients. Macrophages localized predominantly in the mesangial area in patients with mesangial expression of alpha-SMA, which was associated with the expression of macrophage-colony-stimulating factor. Noteworthily, the score of mesangial alpha-SMA expression and the incidence of patients with mesangial expression of alpha-SMA at the time of renal biopsy were markedly higher in the ESRD group than in the stable group. However, there was no significant difference in both the score of interstitial alpha-SMA expression and the incidence of patients with interstitial expression of alpha-SMA between these two groups. These results suggest that macrophages recruited into the mesangium may induce phenotypic modulation of mesangial cells and that mesangial alpha-SMA expression predicts a progressive decline in renal function in patients with IgAN.

Actins↗
PubMed1999

Bone marrow transplantation attenuates murine IgA nephropathy: role of a stem cell disorder.

BACKGROUND: The pathogenesis of IgA nephropathy is still obscure. The aim of this study was to investigate whether the fundamental pathogenesis of IgA nephropathy lies in bone marrow stem cells (BMCs). METHODS: We used donors of two different strains for bone marrow transplantation (BMT) into mice with a high content of serum IgA (ddY strain, HIGA mice), a murine model of IgA nephropathy. One group (B6-->HIGA, N = 5) received BMCs of C57BL/6j (B6) mice, and the other (HIGA-->HIGA, N = 8) were reconstituted with BMCs of HIGA mice. RESULTS: Twenty-six weeks after BMT, in B6-->HIGA mice, mesangial deposits of IgA and C3 were statistically milder than those in HIGA-->HIGA mice. Light microscopic observations disclosed that glomerular sclerosis and mesangial matrix expansion in B6-->HIGA mice were decreased compared with those in HIGA-->HIGA mice. These B6-->HIGA mice also excreted less urinary albumin than HIGA-->HIGA mice. Furthermore, serum levels of IgA in B6-->HIGA mice were markedly lower than those in HIGA-->HIGA mice. Size analysis of serum IgA revealed that macromolecular IgA were notably lower in B6-->HIGA mice than in HIGA-->HIGA mice. CONCLUSIONS: Our results suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells, and that BMT from normal donors can attenuate glomerular lesions in HIGA mice. This approach may offer a new avenue to study the pathogenesis of IgA nephropathy.

Age Factors↗
PubMed1999

A heart-specific increase in cardiotrophin-1 gene expression precedes the establishment of ventricular hypertrophy in genetically hypertensive rats.

OBJECTIVE: Cardiotrophin-1 is a cytokine, a novel member of the interleukin-6 superfamily, which is isolated from mouse embryoid bodies. It is known to bind a gp130/ leukemia inhibitory factor (LIF) receptor heterodimer and to induce myocyte hypertrophy. Accumulating evidence indicates that a gp130 signaling pathway is involved in cardiac development and ventricular hypertrophy. METHODS: In order to elucidate the pathophysiologic significance of cardiotrophin-1 in ventricular hypertrophy associated with hypertension, we examined the level of cardiotrophin-1 mRNA in the ventricle of spontaneously hypertensive rats/Izm stroke-prone (SHRSP/Izm) in neonates, and at 4-, 12- and 20-weeks of age by Northern blot analysis. We also examined the gene expression of LIF by Northern blot and reverse transcription-polymerase chain reaction analyses. RESULTS: No significant difference was observed in the level of cardiotrophin-1 mRNA in the ventricle between SHRSP/ Izm and Wistar-Kyoto/Izm (WKY/Izm) neonates. However, the level of cardiotrophin-1 mRNA in the ventricle was significantly augmented in 4-week-old SHRSP/Izm, which did not yet show overt ventricular hypertrophy, and its augmented expression lasted for the duration of the experimental period. The difference in the level of cardiotrophin-1 mRNA between the two strains was most prominent at the age of 4 weeks. This augmented expression of the cardiotrophin-1 gene was not related to the severity of left ventricular hypertrophy. The level of cardiotrophin-1 mRNA in other organs, including the kidney and lung, showed no significant change with aging and was not different between the two strains. After long-term treatment with lisinopril, levels of cardiotrophin-1 mRNA were not changed, although it morphologically prevented the development of left ventricular hypertrophy. LIF mRNA was not detected in any ventricles examined by Northern blot analysis. CONCLUSIONS: The present study demonstrates that the expression of cardiotrophin-1 mRNA is increased in the early stage of ventricular hypertrophy in SHRSP/Izm and it remains elevated after hypertrophy has been established. However, it is unlikely that cardiotrophin-1 plays a mechanistic role in the development and maintenance of left ventricular hypertrophy in SHRSP/Izm. The present study also suggests that cardiotrophin-1, but not LIF, is a possible candidate for natural ligand of a gp130 signaling pathway in the heart.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Evidence suggesting the involvement of hematopoietic stem cells in the pathogenesis of IgA nephropathy.

To investigate the role of hematopoietic stem cells in the pathogenesis of IgA nephropathy, T-cell-depleted bone marrow cells for IgA nephropathy-prone ddY mice were transplanted into C57BL/6j (B6) mice pretreated with cyclophosphamide. In the 12th week after bone marrow transplantation, transplanted bone marrow cells had successfully regenerated. In B6 recipients of T-cell-depleted allogeneic bone marrow cells for ddY mice ([ddy-->B6]), mesangial IgA and C3 deposits were significantly more intense than those in B6 mice receiving syngeneic bone marrow cells of B6 mice ([B6-->B6]). The serum IgA level in [ddY-->B6] mice was higher than that in [B6-->B6] mice. Molecular profile analysis of serum IgA revealed that the serum concentration of macromolecular IgA was increased in [ddY-->B6], but not in [B6-->B6] mice. These data suggest that disorders programmed at the level of BMCs are involved in the pathogenesis of IgA nephropathy by increasing circulating levels of macromolecular IgA.

Animals↗
PubMed1998

Air bubbles in the subclavian or internal jugular veins: a common finding on contrast-enhanced CT.

We investigated the frequency of air bubbles in the subclavian (SCV) or internal jugular (IJV) vein in 200 patients who underwent contrast-enhanced CT of the head and neck. Half the patients were reviewed retrospectively (group 1), while the other half were investigated prospectively after the radiologists who administered the contrast medium were instructed to be careful not to inject even a single air bubble during the procedure (group 2). Air bubbles were observed in the SCV or IJV in 15 of the 100 patients in group 1, while in group 2, there were 4 such patients. Air injection, a common "complication", can be reduced by care during the procedure.

Air↗
PubMed1998

Successful treatment of tumoral calcinosis using CAPD combined with hemodialysis with low-calcium dialysate.

Successful treatment of tumoral calcinosis using continuous ambulatory peritoneal dialysis (CAPD) combined with hemodialysis is described. A 32-year-old male patient with a 2-year history of CAPD rapidly developed multiple metastatic calcification (tumoral calcinosis) adjacent to his fingers, elbows, and knee joints. Tests showed severe hyperphosphatemia, moderate hypercalcemia, and increased Ca-P product without elevation of intact parathyroid hormone. An enlarged parathyroid gland was not found by echography. In order to rapidly lower the excessive Ca and P levels, a combined therapy with CAPD and vigorous transient hemodialysis using a low-Ca dialysate was performed. In parallel, the patient was given calcitonin, bisphosphonate, and short-term Al to ameliorate the metastatic calcifications more effectively. The result was dramatic with disappearance of the tumoral calcinosis as well as improvement in subjective symptoms within a few months. The present case suggests that combined therapy with hemodialysis and CAPD using a low-Ca dialysate, together with Ca-modulating agents, can be effective in ameliorating tumoral calcinosis in patients on CAPD.

Adult↗
PubMed1998

[A clinical phase III trial of MR-20 in gynecologic nephrotoxicity of cisplatin--a comparative study in MR-20-treated and control patients on cyclical intermittent cisplatin treatment].

UNLABELLED: MR-20 was administered to 52 gynecological cancer patients who presented with nephrotoxicity from cisplatin (CDDP) treatment over 3 courses at 33 institutions throughout Japan during the period from July 1992 through March 1994, in order to study its suppressive effect on the nephrotoxicity as well as its safety; and the results are reported in this paper. METHODS: The efficacy and usefulness of MR-20 were studied by a MR-20-untreated-controlled, non-double-blind manner. An efficacy rate of 72.0% was achieved in the MR-20 group, and 37.0% in the untreated group: MR-20 was significantly more effective for nephrotoxicity than the MR-20-untreated group. Ccr was prevented from significant variations in the MR-20 group, compared with the untreated group. It was considered that MR-20 is a safe drug, and that it is useful in suppressing the nephrotoxicity of CDDP treatment.

Adult↗
PubMed1998

[Reduction of helical artifact using SmartHelical algorithm].

Stair-step artifact is a serious problem in reconstructed images of multiplanar reformation (MPR), surface rendering and maximum-intensity projection (MIP). We developed a new algorithm, SmartHelical Algorithm (SHA), to reduce helical artifacts. SmartHelical Algorithm reduced helical artifacts significantly with slight worsening of longitudinal resolution. Noise was reduced and SNR was increased. SHA reduced stair-step artifact in reconstructed images of MPR, surface rendering and MIP, and improved image quality.

Adult↗
PubMed1997

Enhancement of guanine-nucleotide exchange activity of C3G for Rap1 by the expression of Crk, CrkL, and Grb2.

Crk is an adaptor protein that consists almost entirely of SH2 and SH3 domains. We have previously demonstrated, by using in vivo and in vitro systems, that C3G, which was identified as a Crk SH3 domain-binding guanine nucleotide exchange factor, specifically activates Rap1. C3G also binds to other adaptor proteins, including CrkL and Grb2. In the present study, we analyzed the effect of Crk, CrkL, and Grb2 on the C3G-Rap1 pathway. Expression of Crk, CrkL, and Grb2 with C3G in Cos1 cells significantly increased the ratio of GTP/GDP bound to Rap1. Both the SH2 and SH3 domains of Crk were required for this activity. However, Crk did not stimulate the guanine nucleotide exchange activity of C3G for Rap1 in vitro, suggesting that Crk does not activate C3G by an allosteric mechanism. The requirement of the SH2 domain of Crk for the enhancement of guanine nucleotide exchange activity for Rap1 could be compensated for by the addition of a farnesylation signal to Crk, indicating that Crk enhanced the guanine nucleotide exchange activity of C3G by membrane recruitment of C3G. These results demonstrate that Crk, CrkL, and Grb2 positively modulate the C3G-Rap1 pathway primarily by recruiting C3G to the cell membrane.

Adaptor Proteins, Signal Transducing↗