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Biomedical subjects

Hideyuki Kobayashi

Publications and source records attributed to Hideyuki Kobayashi.

61 records · Page 4Linked to original sources
PubMed2002

Antiproteinuric effects of combined antihypertensive therapies in patients with overt type 2 diabetic nephropathy.

Combined antihypertensive therapy plays a crucial role in achieving targeted blood pressure reductions and renoprotection. We therefore compared the antihypertensive and antiproteinuric effects of combined therapy with either a calcium channel blocker (CCB) plus an angiotensin II receptor blocker (ARB) or an angiotensin converting enzyme inhibitor (ACE-I) plus an ARB in patients with type 2 diabetes mellitus complicated by overt nephropathy and mild to moderate hypertension. After a 12-week dietary control period, diabetic patients with mildly to moderately impaired renal function were randomly assigned to either a CCB (amlodipine 5 mg once daily) or an ACE-I (temocapril 2 mg once daily) for 12 weeks (monotherapy period). Both groups then received add-on therapy with an ARB (candesartan 4 mg once daily) for an additional 12 weeks. During the monotherapy period, blood pressure was decreased equally well in both groups. Daily urinary protein excretion remained unchanged in the CCB-treated group (control period, 4.0 +/- 1.8 g/day vs. CCB period, 4.1 +/- 1.9 g/day; ns; n = 8), but decreased in the ACE-I-treated group (control period, 4.3 +/- 1.8 g/day vs. ACE-I period, 3.5 +/- 1.7 g/day; p < 0.05; n = 9). After the combined therapy period, blood pressure was decreased to the same degree in both groups. Although ARB plus CCB significantly reduced urinary protein excretion (to 3.5 +/- 1.5 g/day; p < 0.05 vs. control period; n = 8), a more profound reduction was achieved with ARB plus ACE-I (to 2.6 +/- 1.3 g/day; p < 0.01 vs. control period; n = 9). Monotherapy with the ACE-I increased the serum potassium concentration, and this elevation was sustained after addition of the ARB. In contrast, the serum potassium concentration was not influenced by monotherapy with the CCB, but was significantly increased after addition of the ARB. A decreased hematocrit was observed in the ARB plus ACE-I group. The present study suggests that combined antihypertensive therapy with either a CCB plus an ARB or an ACE-I plus an ARB exerts an antiproteinuric effect in patients with type 2 diabetic nephropathy with mildly impaired renal function. Although the latter combination had a more profound effect, it was associated with an increased serum potassium concentration and worsening of renal anemia. Thus, the combination of a CCB and an ARB should be the first line antihypertensive therapy in those with overt diabetic nephropathy. The long-term efficacy of these combined antihypertensive therapies will need to be further addressed in a future study.

Aged↗
PubMed2002

A possible mechanism of NK cell-lineage granular lymphocyte proliferative disorder (NK-GLPD) in a patient with chronic active Epstein-Barr virus infection (CAEBV) and severe hypersensitivity to mosquito bites (SHMB).

We report the case of a young female patient with chronic active Epstein-Barr virus infection (CAEBV) and severe hypersensitivity to mosquito bites (SHMB). She showed a marked increase of NK cell population in peripheral blood. The NK cell population was suggested to be infected with EBV, and to be oligoclonal by Southern blotting using an EBV genome terminal-repeat probe. The NK cells aberrantly expressed CD25, a high affinity receptor for IL-2, and showed an augmented in vitro proliferative response to IL-2. Moreover, they also showed enhanced expression of both Fas-ligand and Bcl-2, and resistance to in vitro Fas-induced apoptotic cell death (Fas-ACD). Taken together, these observations suggested that both the augmentation of proliferative response to IL-2 and the decrease in Fas-ACD may cause NK cell lineage granular lymphocyte proliferative disorder (NK-GLPD) in patients with CAEBV and SHMB.

Adolescent↗
PubMed2002

Antigen induced arthritis (AIA) can be transferred by bone marrow transplantation: evidence that interleukin 6 is essential for induction of AIA.

OBJECTIVE: To investigate the role of bone marrow cells (BMC) in the induction of antigen induced arthritis (AIA), the expression of 3 major proinflammatory cytokines, interleukin 1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6, was examined in the bone marrow (BM) of mice with AIA. We also examined whether AIA could be transferred by bone marrow transplantation (BMT). METHODS: Expression of IL-1beta, TNF-alpha, and IL-6 in BMC was assessed by immunohistochemistry throughout the course of AIA. BMT experiments were performed using 2 different mouse genotypes, wild type (IL-6+/+) and IL-6 deficient (IL-6-/-) mice, as a donor. The gradation of AIA was evaluated histologically. RESULTS: IL-6 was highly expressed in the BM at induction as well as during progression of AIA, while TNF-alpha showed a marginal expression, and no significant expression of IL-1beta was detected throughout the course of AIA. In BMT experiments, all irradiated IL-6+/+ mice developed typical AIA by transplantation of BMC from immunized IL-6+/+ mice, whereas almost no irradiated IL- 6+/+ mice transplanted with BMC from the immunized IL-6-/- mice developed definite arthritis. CONCLUSION: These results suggest that BMC play a critical role and IL-6 is a key cytokine for the induction and progression of AIA. There may be clinical benefits in the blockade of IL-6 and BMT in the treatment of rheumatoid arthritis.

Animals↗
PubMed2002

Enhanced local production of osteopontin in rheumatoid joints.

OBJECTIVE: To investigate the involvement of osteopontin (OPN) in the pathogenesis of rheumatoid arthritis (RA), localization and production of OPN were examined in patients with RA. METHODS: Localization of OPN in the rheumatoid synovium was examined by immunohistochemistry. In vitro OPN production by cultured synovial cells from patients with RA (n = 5) and with osteoarthritis (OA) (n = 5) was assessed by ELISA. OPN concentrations in plasma and synovium were quantified in patients with RA (n = 23) by 2 distinct ELISA systems to measure both thrombin cleaved and non-cleaved OPN. The same experiments were done in patients with OA (n = 15) and healthy volunteers (n = 10) as a control. RESULTS: OPN was highly detected by immunohistochemistry predominantly in the RA synovial lining cells, while less and scattered OPN was detected in OA synovial tissues. ELISA revealed that cultured RA synovial cells secreted significantly more OPN than OA cells. ELISA also showed a marked increase of OPN levels in synovial fluid (SF) of patients with RA and with OA compared to the control plasma OPN levels, although OPN levels were not increased in RA and OA plasma compared to healthy controls. SF OPN levels of patients with RA were significantly higher than those of patients with OA, and correlated with serum C-reactive protein levels. The ratios of thrombin cleaved versus non-cleaved OPN were significantly increased in RA plasma and SF compared with OA plasma and SF and plasma from healthy controls. CONCLUSION: Our results revealed enhanced local production of OPN in rheumatoid joints, suggesting involvement of OPN in the pathogenesis of RA.

Adult↗
PubMed2002

[Combined chemoendocrine therapy using adriamycin, cyclophosphamide and high dose toremifene in patients with recurrent breast cancer].

We studied a new chemoendocrine therapy against recurrent breast cancer in order to evaluate its efficacy and toxicity. Sixteen eligible patients were treated with the therapy consisting of adriamycin/cyclophosphamide (AC) plus toremifene (TOR). Adriamycin (20 mg/m2) was administered intravenously on days 1 and 8, and cyclophosphamide (100 mg/body) was given orally on days 1 to 14 every 4 weeks. TOR (120 mg/day) was given orally daily. The median age of the patients was 52 years; 6 were premenopausal and 10 postmenopausal. As post-operative adjuvant therapy, anthracycline chemotherapy and tamoxifen were given to 4 and 9 patients, respectively. AC therapy was administered for 8.5 cycles (median). Four complete responses (25%), 8 partial responses (37.5%), 4 no change (25%) (including 2 long NC), and 2 progressive disease (12.5%) were obtained, for an overall response rate of 62.5%. The median duration of time to progression and survival were 13.2 months (0.7-30.4 months) and 22.8 months (13.7-44.8 + months), respectively. The frequent toxicities were leukopenia, nausea/vomiting, and alopecia, but these were clinically well tolerated. Our results suggest that the addition of high dose TOR to AC therapy is useful in the treatment of recurrent breast cancer.

Administration, Oral↗
PubMed2000

Localization of olfactomedin-related glycoprotein isoform (BMZ) in the golgi apparatus of glomerular podocytes in rat kidneys.

Agene encoding olfactomedin-related glycoprotein was isolated from rat glomerulus despite its prior identification as a neuron-specific gene. The mRNA expression was remarkably intense in renal glomerulus and brain and faint in the lung and eye among rat systemic organs. Although the brain contained four mRNA variants (AMY, AMZ, BMY, and BMZ) transcribed from a single gene, the glomerulus, lung, and eye expressed only two variants (BMZ and BMY). The glycoprotein was intensely immunolocalized in glomerular podocytes and neurons by using an antibody against synthetic peptide of the M region, but weak in endothelial cells of the kidney and lung. Bronchiolar epithelial cells in the lung, and ciliary, corneal, and iris epithelial cells in the eye were also stained. Immunogold electron microscopy revealed selective localization of olfactomedin-related glycoprotein at the Golgi apparatus in podocytes. In glomerular culture, the staining was also intense at a juxtanuclear region in synaptopodin-positive epithelial cells of irregular shape (phenotypic feature of podocytes), whereas it was weak in synaptopodin-negative ones of cobblestone-like appearance (phenotypic feature of parietal epithelial cells of Bowman's capsule). Interestingly, Western blot analysis identified an intense band corresponding to BMZ isoform and another faint band corresponding to BMY isoform in the glomerulus, whereas the intensity of these two bands were nearly equal in the lung and eye. In the brain, four bands corresponding to four isoforms were observed apparently. Computer sequence analysis predicted coiled-coil structures in the secondary structure of the glycoprotein similar to those in Golgi autoantigens, suggesting significant roles in the unique functions of the Golgi apparatus in rat podocytes and neurons.

Amino Acid Sequence↗