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T Umekawa

Publications and source records attributed to T Umekawa.

At least 19 recordsLinked to original sources
PubMed2004

Effects of growth hormone (GH) on mRNA levels of uncoupling proteins 1, 2, and 3 in brown and white adipose tissues and skeletal muscle in obese mice.

We have investigated whether GH treatment influences the expression of UCP1, 2 and 3 mRNA in a KK-Ay obese mouse model. KK-Ay mice (n = 10) and C57Bl/6J control mice (n = 10) were injected subcutaneously with human GH (1.0 mg/kg/day and 3.5 mg/kg/day) for 10 days, and compared with mice injected with physical saline. The KK-Ay obese mice weighed significantly less (p < 0.01 : 1.0 mg/kg/day, p < 0.05 : 3.5 mg/kg/day) and had smaller inguinal subcutaneous and perimetric white adipose tissue (WAT) pads (p < 0.05 : 3.5 mg/kg/day), but increased skeletal muscle weight (p < 0.05). The brown adipose tissue (BAT) weight did not change significantly. Not only plasma free fatty acid and glucose levels but also plasma insulin levels decreased. The reduced HOMA-IR (homeostasis model assessment-insulin resistance) values suggested that insulin resistance was improved by GH treatment. UCP1 mRNA levels increased after the 3.5 mg GH treatment by 2.8-fold (p < 0.01 vs. saline controls) and 2.0-fold (p < 0.05 vs. 1 mg GH treatment) in BAT, and by 6.0-fold in subcutaneous WAT (p < 0.05 vs. controls). UCP2 mRNA levels increased 2.2-fold (p < 0.05 vs. control) and 2.1-fold (p < 0.05 vs. 1 mg GH treatment) in BAT, and 2.0-fold (p < 0.05 vs. controls) in skeletal muscle. One mg GH administration also stimulated UCP1 mRNA expression by 2.5-fold (p < 0.05 vs. controls) and UCP3 mRNA expression by 2.8-fold (p < 0.05 vs. controls) in the muscle. On the other hand, lean mice showed no significant difference in body composition or plasma parameters. UCP1, 2 and 3 mRNA expression in lean mice did not show any significant change after treatment with GH. We conclude that GH treatment increased mRNA levels for not only UCP1, but also UCP 2 and 3 in BAT, WAT and muscle in a KK-Ay obese mouse model. These findings suggest that GH-induced thermogenesis may contribute to the reduction in WAT and energy expenditure.

Adipose Tissue↗
PubMed2003

Salvage chemotherapy with a combination of irinotecan hydrochloride and mitomycin C in platinum- and paclitaxel-resistant epithelial ovarian cancer: case reports.

INTRODUCTION: The efficacy and toxicity of salvage chemotherapy with a combination of irinotecan hydrochloride (CPT-11) and mitomycin C (MMC) for platinum-and paclitaxel-resistant epithelial ovarian cancer are reported. CASE REPORT: Three consecutive patients with platinum- and paclitaxel- resistant epithelial ovarian cancer were treated with 120 mg/m2 of CPT-11 (days 1 and 15) and 7 mg/m2 of MMC (days 1 and 15) every four weeks. In all three cases partial responses were achieved and overall survivals were 17 months or longer. Most of the adverse side-effects were manageable. CONCLUSIONS: This regimen could be administered even in heavily pretreated patients with platinum- and paclitaxel- resistance. Phase I and II studies are needed to confirm the feasibility of this treatment. The efficacy of most salvage treatments for platinum- and paclitaxel-resistant epithelial ovarian cancer is disappointing, and our cases might be of interest from the perspective of treating platinum- and paclitaxel-resistant ovarian cancer.

Aged↗
PubMed2002

Influence of urinary sialic acid on calcium oxalate crystal formation.

Using seed crystal method, whole-urine method, and scanning electron microscopy, the inhibitory effects of sialic acid and osteopontin (OPN) on aggregation/growth of CaOx crystals were investigated. Using the seed crystal method, sialic acid showed an inhibitory effect on CaOx crystal aggregation/growth in a concentration-dependent manner, but almost no effect was observed using the whole-urine method. OPN showed an inhibitory effect on aggregation/growth in both experimental systems. The inhibitory effect of asialo-OPN on aggregation/growth was approximately 20% lower than that of OPN in the experiment using the seed crystal method and approximately 15% lower in the experiment using the whole-urine method. Scanning electron microscopy showed that OPN and sialic acid inhibit the aggregation of CaOx crystals. The above findings show that sialic acid accounts for about 15-20% of the involvement of OPN in CaOx crystallization.

Calcium Oxalate↗
PubMed2001

The effect of osteopontin immobilized collagen granules in the seed crystal method.

Osteopontin (OPN) is a urinary protein which inhibits calcium oxalate (CaOx) crystal growth in the seed crystal system. The aim of this study was to evaluate the effects of OPN immobilized on collagen granules (CG) for CaOx crystal growth and aggregation in this system. OPN-immobilized CG showed a 30% decrease in inhibitory activity compared with non-OPN-immobilized CG. Scanning electron microscopy revealed that 1) OPN-immobilized CG showed more marked aggregation and adhesion of seed crystals (smaller than 0.5 microm in diameter) than non-OPN-immobilized CG, 2) the amount of adherent large type crystals (2-3 microm in diameter) did not differ between OPN immobilized and non-OPN-immobilized CG. In conclusion, immobilized OPN promotes aggregation and adhesion of CaOx crystals smaller than 0.5 microm on CG. These observations suggest that crystal adhesion to immobilized OPN plays a role in the retention of crystals in the kidney.

Calcium Oxalate↗
PubMed2001

Beta 3-adrenergic agonist up-regulates uncoupling proteins 2 and 3 in skeletal muscle of the mouse.

Chronic stimulation of the beta3-adrenergic receptor (AR) in obese animals resulted in a reduced adiposity associated with an increased expression of thermogenic uncoupling protein (UCP)1 in adipose tissues. In this study, the mRNA expression of newly cloned UCP isoforms (UCP2 and UCP3) were examined in obese yellow KK and C57BL control mice. UCP2 mRNA was found in all tissues examined, with higher levels in adipose tissues and skeletal muscle of the obese mice. UCP3 mRNA was expressed in skeletal muscle, heart and brown adipose tissue similarly in the two mouse strains. Daily injection of a selective beta3-adrenergic agonist, CL316,243 (0.1 mg/kg), for 10 days resulted in a marked reduction of white fat pad weight and 1.8-4.8-fold increase in the mRNA levels of UCP2 and UCP3 in skeletal muscle of obese mice. No noticeable change in the UCP2 and 3 mRNA levels was found in brown and white adipose tissues. It was also found that CL316,243 injection produced a marked and sustained elevation of the plasma free fatty acid level. These results, together with our previous findings of the fatty acid-induced UCP expression in a myocyte cell line in vitro, suggest that the beta3-AR agonist-induced UCP expression in skeletal muscle may be mediated through the elevated plasma free fatty acids. It was also suggested that anti-obesity effect of beta3-AR agonists is attributable to increased thermogenesis not only by UCP1 but also by UCP2 and UCP3.

Adipose Tissue, Brown↗
PubMed2000

Effect of ethyl icosapentate on urinary calcium and oxalate excretion.

BACKGROUND: The effect of ethyl icosapentate (EPA-E) on urinary calcium and oxalic acid excretion was examined to evaluate whether EPA-E is useful in the prevention of calcium-containing urinary stones. METHODS: For 6 months, urine was measured daily from 40 calcium-containing urinary stone producers at an outpatient clinic, before and after the administration of 1800 mg/day EPA-E. The urine was measured for volume, urea nitrogen, creatinine, calcium, magnesium, phosphorus, uric acid, oxalic acid and citric acid. Serum total cholesterol and triglyceride were also measured. RESULTS: Urinary calcium excretion was not reduced in any of the patients or particular hypercalciuric groups, nor did the level of calcium change. However, nine of the 25 hypercalciuric patients experienced a significant urinary calcium reduction to the normal calciuric level (a reduction of approximately 44%). It is not known why these particular patients experienced a reduction. Urinary oxalic acid did not change, whether hypercalciuria was present or not. CONCLUSIONS: These findings suggest that EPA-E is not particularly effective in reducing urinary calcium excretion in the hypercalciuric patients, but it needs future investigation because some patients experienced significant urinary calcium reduction.

Adult↗
PubMed1999

Localization and inhibitory activity of alpha(2)HS-glycoprotein in the kidney.

alpha(2)HS-Glycoprotein (HS), a crystal surface binding substance extracted from human urine, is considered to be one of the urinary macromolecular inhibitors in urolithiasis. In the present study, reverse transcription-polymerase chain reaction was used to examine HS mRNA expression, and immunohistochemical staining was used to reveal its localization in the human kidney. The inhibitory effects of recombinant human HS and native human HS on calcium oxalate crystal growth were examined in a seed crystal system. HS mRNA was found to be expressed in the human kidney, and it was located in the epithelial cells of distal and proximal renal tubular cells. However, neither recombinant HS nor native HS had an inhibitory effect on crystals in the protein concentration of urine of healthy humans. HS in the urine, therefore, does not seem to be a potent inhibitor in stone formation.

Blood Proteins↗
PubMed1999

Nicotine induces uncoupling protein 1 in white adipose tissue of obese mice.

OBJECTIVE: To test the hypothesis that nicotine not only activates uncoupling protein1 (UCP1) in brown adipose tissue (BAT), but also induces UCP1 in white adipose tissue (WAT), which contributes to the mitigation of obesity in obese mice. DESIGN: Weights of the whole body, the gastrocnemius muscle, interscapular BAT and subcutaneous and retroperitoneal WAT, food intake and the mRNA and protein of UCP1 in these tissues were measured and immunohistochemistry using antiserum against UCP1 was also performed in obese yellow KK mice treated with nicotine for 6 months and control mice treated with physiological saline. RESULTS: Obese mice treated with nicotine for 6 months, compared with those injected with saline, weighed significantly less (P < 0.01) and had smaller subcutaneous and retroperitoneal WAT pads (P < 0.01), while obese mice that received nicotine ate less (P < 0.05) than those injected with saline. In mice treated with nicotine, the mRNA and protein of UCP1 was detected not only in BAT, but also in subcutaneous and retroperitoneal WATs. Immunohistochemically, the BAT of obese mice contained large lipid droplets and appeared rather WAT-like, but changed to typical brown adipocytes after nicotine treatment. The fat pads of nicotine-treated mice contained many multilocular cells that were positive for UCP1. CONCLUSION: Nicotine not only activates UCP1 in BAT, but also induces UCP1 in WAT and decreases food intake, which contributes to the mitigation of obesity.

Adipocytes↗
PubMed1999

Inhibitory effects of female sex hormones on urinary stone formation in rats.

BACKGROUND: The effects of female sex hormones on urinary stone formation are not known. This study was conducted to investigate the effects of these hormones on stone formation by using an ethylene glycol (EG) and vitamin D-induced rat urolithiasis model. METHODS: Adult female Wistar rats were fed the same diet for four weeks and were then divided into four groups (N = 10 each). One group was administered 0.5 ml of olive oil three times per week for four weeks as a control. The other three groups were administered 0. 5 microg of vitamin D3 and 0.5 ml of 5% EG three times per week for four weeks. The rats in two of these three groups were oophorectomized, and the rats of the remaining group underwent a sham operation on the day before the start of the four-week treatment period. One of the two oophorectomized groups was then administered a supplementation of female sex hormones (0.1 mg of estrogen and 2.5 mg of progesterone 3 times per week for 4 weeks). On the first day of the fifth week of the experimental period, the degree of crystal deposition was determined histologically, and the calcium content in renal tissue was measured. We also investigated the level of osteopontin (OPN) mRNA in renal tissues by Northern blot analysis. OPN is a matrix protein thought to be a promoter of stone formation. RESULTS: The urinary oxalate excretion, crystal deposition and calcium content in renal tissue and the expression of OPN-mRNA were greater in the oophorectomized rats compared with the controls, and the same parameters were inhibited by the female sex hormone supplementation. CONCLUSIONS: These results suggest that female sex hormones can inhibit renal crystal deposition in EG-treated rats by suppressing the urinary oxalate excretion and the expression of OPN.

Animals↗
PubMed1999

Interaction between osteopontin on madin darby canine kidney cell membrane and calcium oxalate crystal.

We recently reported that the addition of the protein osteopontin (OPN) resulted in an increase in the deposition of calcium oxalate (CaOx) crystals on the surface of Madin Darby canine kidney (MDCK) cells. To determine the degree to which this increased deposition is caused by OPN, we investigated the extent to which the CaOx crystal deposition produced by the expression of OPN at the cell surface was suppressed by 4 different methods prior to the determination of the level of CaOx crystal binding. MDCK cells (2 x 10(6) cells/well) were cultured to a confluent state, and the binding of OPN to the cellular surface was then inhibited by adding one of the following 4 substances: human OPN polyclonal antibody, thrombin, cyclic Arg-Gly-Asp (RGD) peptides and tunicamycin. The cells were cultured for 24 h. We then used a fluorescent antibody technique with an OPN polyclonal antibody to determined whether the expression of OPN at the cell surface was inhibited, and we measured the degree of CaOx crystal deposition using the isotope (45)Ca. The degree of CaOx crystal deposition was inhibited by 80% or more in the antibody-treated group, by 50-80% in the thrombin-treated group, by 60-80% in the cyclic RGD-treated group, and by 50-60% in the tunicamycin-treated group. These results suggest that OPN in the extracellular matrix is the main cause of CaOx crystal deposition on the surface of MDCK cells.

Animals↗
PubMed1999

Trp64Arg mutation of beta3-adrenoceptor gene deteriorates lipolysis induced by beta3-adrenoceptor agonist in human omental adipocytes.

The recently described variant of the human beta3-adrenergic receptor (AR) gene located mainly in visceral adipocytes is associated with earlier onset of NIDDM, abdominal obesity, insulin resistance, and an increased capacity to gain weight. We investigated whether lipolysis in human omental adipocytes induced by a potent and selective human beta3-AR agonist (L-755,507) was affected by the Trp64Arg mutation of the beta3-adrenoceptor, using 18 omental fat samples obtained during total hysterectomy. The Trp64Arg mutation was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Arg64 homozygous (n = 4) had a lower median effective concentration (EC50) and lower responsiveness compared with wild-type (n = 8) (EC50: -6.55 +/- 0.21 vs. -7.53 +/- 0.35 log mol/l, P = 0.007; responsiveness: 3.48 +/- 0.32 vs. 5.76 +/- 0.36 micromol x 10(5) cells(-1) x 90 min(-1), P = 0.014, respectively), although there was no difference in lipolysis induced by isoproterenol or CGP12177. Trp64Arg heterozygous (n = 6) also had a significantly lower EC50 and lower responsiveness (EC50: -6.18 +/- 0.09 log mol/l; responsiveness: 4.17 +/- 0.33 micromol x 10(5) cells(-1) x 90 min(-1)). We concluded that the Trp64Arg mutation of the beta3-AR gene is associated with lower lipolytic activities.

Adipose Tissue↗
PubMed1999

[Structural characteristics of osteopontin for calcium oxalate crystal].

BACKGROUND: I investigated which structural segment of osteopontin (OPN), a matrix component of urinary stones, is significantly related to the formation of urinary stones. METHODS: I prepared several kinds of OPNs under various conditions and compared the effects of these OPNs on calcium oxalate (CaOx) crystal using RI counts obtained by the seed crystal method and diluted urine method. Furthermore, I performed scanning electron microscopic (SEM) observation of CaOx crystals used in these experiments and evaluated the effects of OPN based on morphological changes in CaOx crystals. The following OPNs were used in this study: human recombinant OPN (rOPN), human native OPN (nOPN) purified from human milk, denatured OPN (dOPN) obtained by adding organic solvent during the course of nOPN purification, and asiaro OPN (aOPN) obtained by removing sialic acid after enzymatic digestion of nOPN. RESULTS: When the effects of OPNs (15 micrograms/ml) were evaluated by the seed crystal method, the following inhibitory activities were observed: nOPN (82%), aOPN (56%), dOPN (49%) and rOPN (15%). When the effects of OPNs (150 micrograms/ml) were evaluated by the undiluted urine method, the following inhibitory activities were observed: nOPN (38%), aOPN (27%), dOPN (21%) and rOPN (0%). Furthermore, using nOPN, I performed SEM observation of CaOx crystals and found that nOPN mainly inhibited CaOx crystal aggregation. CONCLUSION: Since the inhibitory activity of nOPN was observed not only in the seed crystal method, but also in the undiluted urine method, it was suggested that nOPN may play an important role in the living body during the course of urinary stone formation. Moreover, the inhibitory activity of OPN was not due to its primary structure, but it was closely related to its higher-order structure and side chains including sialic acid. Furthermore, it was clarified that the inhibitory activity of OPN mainly resulted from inhibition of CaOx crystal aggregation rather than growth inhibition in these crystals.

Calcium Oxalate↗