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Biomedical subjects

T Umekawa

Publications and source records attributed to T Umekawa.

At least 73 records · Page 4Linked to original sources

Probucol prevents the progression of fatty liver in MSG obese mice.

We investigated the effect of Probucol in preventing fatty liver in monosodium-L-glutamate (MSG) treated obese mice and control mice fed a high fat diet. MSG mice became significantly obese 9 weeks after birth with higher levels of serum blood glucose, total cholesterol, HDL-cholesterol, GPT, and cholinesterase, and had greater triglyceride contents in their livers relative to control mice. Morphologically, MSG obese mice also had a marked fatty liver. Administration of Probucol mixed with the high fat diet for 2 weeks significantly decreased the serum levels of total cholesterol and HDL-cholesterol, and liver triglyceride contents in both MSG and control mice. Morphologically, the livers were less fatty after Probucol treatment. These results suggest that Probucol prevents the development of fatty liver, and in addition reduces hypercholesterolemia.

Animals↗

A case of primary hyperparathyroidism that had been treated under a diagnosis of depression for 10 years.

A 66 year old man who had been treated under a diagnosis of depression for 10 years was referred to the Kyoto Prefectural University of Medicine, Kyoto because of general fatigue and appetite loss. The patient was diagnosed as having primary hyperparathyroidism (PHPT) based on the increased parathyroid hormone (PTH) and serum calcium levels. Computed tomography revealed solitary adenoma of parathyroid gland. The resection of this solitary adenoma improved the PTH and serum calcium concentrations to normal ranges, which resulted in an improvement in his depressive state. This case suggests that ionic calcium levels contribute to the mental symptoms associated with PHPT. As PHPT is curable, the possibility of PHPT should be taken into account when patients have depressive symptoms.

Aged↗

Clinical efficiency of type-IV collagen in extracorporeal shock wave lithotripsy.

We previously reported a patient who developed anti-glomerular basement membrane antibody-induced glomerulonephritis (GBM-GN) after extracorporeal shock wave lithotripsy (ESWL). To determine whether ESWL causes anti-GBM antibody production thereby inducing GBM-GN, we measured serum levels of type-IV collagen (the most major component of GBM) before and after ESWL. Serum samples were obtained from 13 patients with renal stones and 15 with ureteral stones. The serum type-IV collagen level was determined by a radioimmunoassay method. No significant changes were observed in the type-IV collagen level after ESWL in each patient group. Type-IV collagen was abundant in the GBM but was not released into the blood after ESWL. Therefore, in patients with urinary tract stones, it is not likely that type-IV collagen, a hidden antigen in the renal glomeruli, is exposed or released into the blood after ESWL, resulting in autoantibody production and GBM-GN.

Adult↗

Osteopontin mRNA in the kidney on an experimental rat model of renal stone formation without renal failure.

We had sequenced a cDNA of calcium oxalate urinary stone protein extracted with 0.1 M EDTA. cDNA sequences showed complete homology between urinary stone protein and human osteopontin (OPN, bone sialoprotein I). In the present study, we investigated the expression of OPN mRNA in the rat kidney in an experimental model of renal stone formation using glyoxylic acid and 1,25-dihydroxyvitamin D3 (D3). In the renal stone formation model with and without renal failure, OPN mRNA was shown to be localized by in situ hybridization using an OPN cRNA probe mainly in the distal convoluted tubule of the kidney, and was enhanced compared with the normal control which was sporadically positive. By Northern blot analysis, the expression of OPN mRNA was shown to be increased by about 5.2-fold in the renal stone formation model and 2.3-fold in D3-administered rats compared with controls. However, no change in the expression of OPN mRNA was observed in an acute renal failure model induced by gentamicin or in rats administered glycoxylic acid alone. Therefore, the promotion of OPN mRNA expression was intrinsic to this stone formation model, and not secondary to acute renal failure because of obstruction by microcrystals in the renal tubules or gentamicin.

Acute Kidney Injury↗

Treatment of mesothelioma of the tunica vaginalis testis.

We report a rare case of malignant mesothelioma of the tunica vaginalis testis. A 67-year-old man was hospitalized with a complaint of swelling on the right side of the scrotal contents. Right high orchiectomy was performed, and the pathological examination revealed malignant mesothelioma of the tunica vaginalis testis. The surgery was thought to have been radical, but 4 months postoperation, local recurrence in the inguinal skin and distant metastasis in the para-aortic lymph node were found. The tumors were treated by surgical resection and radiation therapy. Two months after the second treatment, multiple lung metastasis and a second local recurrence in the inguinal skin were found. High-dose chemotherapy with cisplatin and doxorubicin was performed, but no change was confirmed after 4 weeks. The disease progressed, resulting in death within 8 months of diagnosis. The response of mesothelioma to chemotherapy is thought to be poor histologically as indicated by this case and previously reported cases, so initial radical surgery and adjuvant procedures soon after diagnosis are necessary to achieve cure.

Aged↗

Acromegalic gigantism with low serum level of growth hormone and elevated serum insulin-like growth factor-I.

In a case of acromegalic gigantism with hyperprolactinemia is reported, the basal serum growth hormone (GH) levels ranged from 1.2 to 1.9 ng/ml. Serum GH response to either insulin-induced hypoglycemia or GH-releasing hormone was blunted. Frequent blood sampling showed non-pulsatile GH secretion. Serum prolactin and insulin-like growth factor-I (IGF-I) levels were elevated. After unsuccessful surgery, bromocriptine treatment normalized serum prolactin without affecting serum GH and IGF-I levels. Combined administration of octreotide with bromocriptine reduced serum GH and IGF-I levels. In this case, non-pulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-I and cause clinical acromegalic gigantism.

Acromegaly↗

[Influence of genetic factors on family history of upper urinary stones].

The family history between patients with upper urinary tract stones and healthy subjects was compared to evaluate the possible involvement of genetic factors in obtaining information through a questionnaire. The patients showed a significantly more marked history than the healthy subjects (p < 0.001). In particular, recurrent stone formers showed a significantly more marked history than single stone formers (p < 0.05). Compared with the healthy subjects, a more marked family history was observed in the parents, brothers and sisters, and children, but not in the spouse (p < 0.05-0.005). However, the family history was not affected by consanguineous marriage. A more marked family history was observed in patients with upper urinary tract stones, suggesting the involvement of genetic factors in the development of upper urinary tract stones. In particular, genetic factors seem to be more closely involved in recurrent stone formers.

Adult↗

Expression of osteopontin messenger RNA in the rat kidney on experimental model of renal stone.

We investigated the expression of osteopontin (OPN) messenger (m) RNA in the rat kidney under the experimental models of several conditions that are considered to be risk factors of human renal stones. In the renal stone formation model administrated glyoxylic acid and 1,25-dihydroxyvitamin D3, pyelonephritis model and hydronephrosis model the expression of OPN mRNA in the distal convoluted tubule of the kidney was enhanced compared with the control which was sporadically positive utilizing in situ hybridization and northern blot analysis. The expression of OPN mRNA was markedly inhibited in the renal stone formation model by concominant administration of estradiol and/or progesterone.

Animals↗

Thermogenic, anti-obesity effects of bofu-tsusho-san in MSG-obese mice.

OBJECTIVE: To investigate the hypothesis that anti-obesity action of bofu-tsusho-san (TJ-62) works via activating the brown adipose tissue thermogenesis and inhibiting the phosphodiesterase activity. DESIGN: MSG obese mice and lean controls were fed a diet including 1.4% or 4.7% TJ-62 of weight of food for 8 weeks. Another group of MSG obese mice were fed with 1-ephedrine (1-E) + d-pseudoephedrine (d-PE) of equivalent amounts as contained in TJ-62 (4.7%) for 8 weeks. Yet another group of MSG obese mice were further supplemented with Glycyrrhizae Radix (GR) extract + Forsythiae Fructus (FF) extract + Schizonepetae Spica (SS) extract (that inhibited phosphodiesterase activity) of amounts contained in TJ-62 (4.7%) for 8 weeks. MEASUREMENTS: The following were measured: The concentration of ephedrine and its congeners in TJ-62; the inhibitory effect of TJ-62 on phosphodiesterase activity; body weight; food intake; retroperitoneal white adipose tissue (RWAT) weight; interscapular brown adipose tissue (IBAT) weight; mitochondrial protein content in IBAT; cytochrome c oxidase activity in IBAT; guanosine-5'-diphosphate (GDP) binding in IBAT mitochondria. RESULTS: One gram of TJ-62 contained 3.33 mg of 1-E and 0.73 mg of d-PE. One mg of TJ-62 was equivalent to 2.5 mg of caffeine in the inhibitory effect on phosphodiesterase activity. After feeding with TJ-62, GDP binding was significantly increased in a dose dependent manner. Body weight and RWAT weight decreased in both MSG obese mice and lean controls. Food intake was not changed by TJ-62. Feeding with 1-E + d-PE produced responses of about 70% of those of TJ-62. These responses were, furthermore, enhanced by the addition of the three extracts to the levels that were similar to those produced by TJ-62. CONCLUSION: Bofu-tsusho-san (TJ-62) works via activating the BAT thermogenesis and inhibiting the phosphodiesterase activity in mice.

Adipose Tissue↗

Anti-obesity and anti-diabetic effects of CL 316,243, a highly specific beta 3-adrenoceptor agonist, in yellow KK mice.

The anti-obesity and anti-diabetic effects of CL 316,243, a highly specific beta 3-adrenoceptor agonist (beta 1: beta 2: beta 3 = 0:1:100,000), were evaluated in obese diabetic yellow KK mice and C57Bl control mice. The study compound was fed through a gastric tube at a rate of 0.1 mg/kg/day for 2 weeks. The following parameters were compared in the treated and control animals given distilled water: brown adipose tissue thermogenesis, resting metabolic rate, insulin receptors in adipocytes, and blood glucose and serum insulin levels during a glucose overloading test. CL 316,243 significantly increased brown adipose tissue thermogenesis and resting metabolic rate in both yellow KK mice and C57Bl controls. The amount of white adipose tissue decreased, although food intake was not affected. The effects contributed to the mitigation of obesity in yellow KK mice. CL 316,243 also increased the concentration of insulin receptors and decreased the levels of serum insulin and blood glucose during the glucose overloading test in yellow KK mice. These observations suggest that CL 316,243 possesses anti-obesity and anti-diabetic effects and consequently may be useful for treating obesity as well as non-insulin-dependent diabetes mellitus in obese persons, without causing excessive side effects.

Animals↗

Effect of nicotine on sympathetic nervous system activity of mice subjected to immobilization stress.

We tested the hypothesis that nicotine possesses an antistress action by measuring the turnover of norepinephrine (NE), a reliable indicator of sympathetic nervous system activity, in the interscapular brown adipose tissue (IBAT) and heart of mice treated with nicotine injections, immobilization stress, or nicotine + immobilization stress, vs. untreated controls. Nicotine enhanced the sympathetic activity in the IBAT and heart, and induced a loss of body weight. Immobilization-related stress accelerated sympathetic activity in the IBAT and heart more strongly than did nicotine loading alone. Pretreatment with nicotine suppressed the sympathetic activity induced by immobilization stress to the same extent as that observed after administering nicotine alone. Thus, these results appeared to support our hypothesis.

Adipose Tissue, Brown↗

Production of anti-glomerular basement membrane antibody after extracorporeal shock wave lithotripsy.

We report a case of acute renal failure occurring about 90 days after extracorporeal shock wave lithotripsy (ESWL) for a right renal stone. On left renal needle biopsy, immunofluorescence demonstrated linear fixation of IgG and C3 along the glomerular basement membrane (GBM). Serum circulating antitype IV collagen NC1 domain antibody was detected after ESWL, while it was not detected in the serum taken before ESWL. Based on these findings, the diagnose of anti-GBM antibody-mediated glomerulonephritis was made. Circulating antibodies against several GBM components (type IV collagen NC1 domain, laminin, fibronectin and heparan sulfate proteoglycan) was consistently negative in 9 randomly selected patients who underwent ESWL for renal stones. These findings suggest that the production of these autoantibodies associated with irradiation of shock waves to the kidney was not frequent, but, after ESWL, patients deserve close follow-up.

Acute Kidney Injury↗

Effect of CL 316,243, a novel beta 3-adrenoceptor agonist, on insulin secretion in perfused mouse pancreas.

In order to clarify the insulin-release mechanism of beta 3-adrenoceptor agonist, we examined the effect of CL 316,243, a highly specific beta 3-adrenoceptor agonist having a relative potency of beta 1:beta 2:beta 3 = 0:1:100,000, on insulin secretion in perfused mouse pancreas. The application of 0.2 mM and 0.5 mM CL 316,243 produced significant insulin secretion from within 1 min, which lasted until 2 min after its withdrawal. DL-propranolol and ICI 118551 at 0.2 mM partially inhibited the insulin secretion induced by the 0.2 mM CL 316,243, but 0.2 mM metoprolol had no effect on the insulin release produced by 0.2 mM CL 316,243. We conclude that beta 3-adrenoceptor agonist stimulates insulin secretion via beta 3-action in the perfused mouse pancreas.

Adrenergic beta-Agonists↗

Anti-obesity effect of CL 316,243, a highly specific beta 3-adrenoceptor agonist, in mice with monosodium-L-glutamate-induced obesity.

The effects of CL 316,243, a highly specific beta 3-adrenoceptor agonist (relative selectivities of 0, 1 and 100,000 for beta 1-, beta 2- and beta 3-receptors, respectively), were evaluated in mice with monosodium L-glutamate (MSG)-induced obesity as well as in control mice injected with physiological saline instead of MSG. Both MSG- and saline-treated mice were divided into three groups and at 8 weeks of age received either CL 316,243 (0.1 or 1.0 mg/kg) or distilled water through a gastric tube for 2 weeks. CL 316,243 not only reduced white adipose tissue mass but also activated brown adipose tissue and systemic metabolism, and hence reduced body mass without affecting food intake. Furthermore, CL 316,243 decreased hyperglycemia and hypertriglyceridemia in MSG-treated mice. However, at the higher dose, CL 316,243 also increased liver triglyceride in MSG-treated mice. These observations suggest that CL 316,243 exerts an anti-obesity effect in mice with MSG-induced obesity and consequently may prove efficacious in the treatment of human obesity.

Adrenergic beta-Agonists↗

The effects of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, on norepinephrine overflow and antidiuresis induced by stimulation of renal nerves in anesthetized dogs.

We examined the involvement of endogenous nitric oxide (NO) in noradrenergic neurotransmission and renal function in anesthetized dogs, by using NG-nitro-L-arginine (NOARG), a NO synthase inhibitor. Renal nerve stimulation (RNS) produced the frequency-dependent increase in the rate of norepinephrine secretion. The low frequency RNS (0.5-2.0 Hz) decreased urine flow and urinary excretion of sodium, without affecting renal hemodynamics. High frequency RNS (2.5-5.0 Hz) caused a more potent antidiuresis and renal vasoconstriction that resulted in reductions in renal blood flow and glomerular filtration rate. Intrarenal arterial infusion of NOARG, at a dose (10 micrograms/kg/min) which had no effect on renal hemodynamics, significantly enhanced the RNS-induced reductions of urine formation and renal vasoconstriction and increments in norepinephrine secretion rate. Qualitatively similar results were observed with a higher dose of NOARG (40 micrograms/kg/min), although this dose did decrease basal levels of renal blood flow and urine flow. Enhancement of NOARG on RNS-induced actions was abolished by the simultaneous administration of L-arginine. Endogenous NO probably has a role as inhibitory modulator of renal noradrenergic neurotransmission.

Amino Acid Oxidoreductases↗

The alpha/beta-adrenergic receptor blocker arotinolol activates the thermogenesis of brown adipose tissue in monosodium-L-glutamate-induced obese mice.

We have found previously that arotinolol, an alpha/beta-adrenergic blocker, increases blood flow in brown adipose tissue (BAT) in a similar extent as BRL 26830A, a beta 3-adrenoceptor agonist. We tested the hypothesis that arotinolol activates thermogenesis in BAT, leading to weight loss in monosodium-L-glutamate-induced (MSG-induced) obese mice and saline-treated controls. Six weeks of standard animal feed (CE-2) containing arotinolol hydrochloride (350 mg/kg CE-2), which reduced mean blood pressure in MSG-treated mice, significantly increased the mitochondrial protein content in BAT, and activated the specific and total binding of guanosine-5'-diphosphate (GDP) in BAT mitochondria, leading to a reduction of obesity in both MSG- and saline-treated mice vs. the control groups fed with CE-2 diet alone. However, six weeks of CE-2 diet containing propranolol hydrochloride (525 mg/kg CE-2) a non-selective beta-blocker, markedly reduced the specific and total binding of GDP in BAT mitochondria, leading to weight gain in both MSG- and saline-treated mice. These findings support the hypothesis, that arotinolol activates BAT thermogenesis, leading to weight loss.

Adipose Tissue↗