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K Yoshimoto

Publications and source records attributed to K Yoshimoto.

257 records · Page 15Linked to original sources

Anti-obesity and anti-diabetic effects of mazindol in yellow KK mice: its activating effect on brown adipose tissue thermogenesis.

1. The anti-obesity and anti-diabetic effects of mazindol were evaluated in obese diabetic yellow KK mice and C57Bl control mice. 2. The study compound was fed through a gastric tube at a rate of 1 or 2 mg/kg per day (0.01 mol/L HCl as control) for 2 weeks. The following parameters were compared in treated and control animals: bodyweight, food intake, white adipose tissue (WAT) weight, brown adipose tissue (BAT) weight and its thermogenesis, noradrenaline (NA) turnover, blood glucose and serum insulin levels and glucose transporter 4 (GLUT4). 3. Furthermore, bodyweight loss of mice pair-fed the same amount of food as the mazindol-treated mice for 2 weeks was measured. 4. Mazindol significantly decreased food intake and significantly increased guanosine-5'-diphosphate-binding in BAT mitochondria and NA turnover in BAT in both yellow KK and C57Bl groups. The amounts of WAT in subcutaneous, mesenteric and retroperitoneal regions and bodyweights were significantly decreased in both groups. Bodyweight loss in mice pair fed with the mazindol-treated groups was approximately 70% compared with that in the mazindol-treated groups. Furthermore, mazindol decreased the levels of blood glucose and serum insulin during the glucose overloading test in yellow KK mice, but it did not influence the GLUT4 protein concentration in WAT and muscle. 5. These observations suggest that mazindol possesses both an anti-obesity action, due to the inhibition of appetite as well as the activation of BAT thermogenesis via increased NA turnover in BAT, and an anti-diabetic action. Consequently, mazindol may be useful for the treatment of obesity as well as non-insulin-dependent diabetes mellitus in obese persons.

Adipose Tissue↗

Distinct expression of CCR1 and CCR5 in glomerular and interstitial lesions of human glomerular diseases.

We investigated the presence of CCR1- and CCR5-positive cells immunohistochemically in the kidneys of 38 patients with several renal diseases, including 13 crescentic glomerulonephritis patients. In addition, we determined cell phenotypes of CCR1- and CCR5-positive cells using a dual immunostaining technique. Urinary levels of their ligands, for CCR1 and CCR5; macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and regulated upon activation in normal T cells expressed and secreted (RANTES) were evaluated by enzyme-linked immunosorbent assay. CCR1- and CCR5-positive cells were detected in both glomeruli and interstitium of the diseased kidneys. Using a dual immunostaining technique, these positive cells were CD68-positive macrophages (MPhi) and CD3-positive T cells. The number of CCR1-positive cells in glomeruli was correlated with urinary levels of MIP-1alpha. The number of CCR1-positive cells in the interstitium was correlated with both urinary MIP-1alpha and RANTES levels. CCR1-positive cells in the interstitium remained after glucocorticoid therapy, most of which were MPhi, and were correlated with the intensity of interstitial fibrosis and tubular atrophy. Glomerular CCR5-positive cells were well correlated with extracapillary lesions and urinary MIP-1alpha levels, while interstitial CCR5-positive cells, mainly CD3-positive T cells, were correlated with interstitial lesions and urinary RANTES levels. Renal CCR5-positive cells were dramatically decreased during convalescence induced by glucocorticoids. These results suggest that chemokine receptor signaling may be pivotal for human renal diseases through the recruitment and activation of MPhi and T cells; CCR5-positive cells may participate in glomerular lesions including extracapillary lesions via MIP-1alpha and in interstitial lesions via RANTES. CCR1 may be involved in interstitial lesions in resolving phase after glucocorticoid therapy.

Adolescent↗

Primary choroid plexus carcinoma producing carbohydrate antigen 19-9.

An autopsy case of primary choroid plexus adenocarcinoma arising in a 40-year-old female, who was associated with a high serum level of a carbohydrate antigen 19-9 (CA19-9), is herein presented. After a subtotal removal of a tumor in the left lateral ventricle, the serum level of CA19-9 decreased rapidly, and immunohistochemical examinations of tumor tissue specimens obtained at surgery revealed intense reactivity for CA19-9. The present case may be the first example in which a primary choroid plexus carcinoma was shown to produce CA19-9.

Adult↗

Anomalous pancreaticobiliary ductal junction without bile duct dilatation in gallbladder cancer.

BACKGROUND/AIMS: Anomalous pancreaticobiliary junction is a rare anomaly but is a risk factor for primary carcinoma of the gallbladder. To define the relationship between anomalous pancreaticobiliary junction, especially if it is not associated with common bile duct dilatation, and gallbladder carcinoma, we retrospectively reviewed data of 126 patients with gallbladder carcinoma. METHODOLOGY: All these patients had undergone direct cholangiography either by endoscopic retrograde cholangiopancreaticography or percutaneous transhepatic cholangiography. RESULTS: Among 126 patients with gallbladder cancer, 23 patients (18.3%) exhibited anomalous pancreaticobiliary junction. Patients with anomalous pancreaticobiliary junction were younger (mean age: 54 +/- 9.1 years) than patients without anomalous pancreaticobiliary junction (mean age: 65 +/- 9.7 years). The incidence of gallstones in patients with anomalous pancreaticobiliary junction (17%) was significantly lower than in those without this anomaly (64%) (P < 0.01). Among the 23 patients with anomalous pancreaticobiliary junction, 12 patients (52%) had no bile duct dilatation and, 11 patients (48%) had bile duct dilatation in the form of fusiform or cylindrical dilatation. However, no cases with severe cystic dilatation were found. Patients of anomalous pancreaticobiliary junction without common bile duct dilatation had more advanced disease and poor prognosis than those with common bile duct dilatation. CONCLUSIONS: The present study revealed that gallbladder cancer in the patients of anomalous pancreaticobiliary junction without common bile duct dilatation was diagnosed at advanced stage and the prognosis was very poor. Therefore, if a minor abnormality is detected in the wall of acalculous gallbladder on ultrasonography, direct cholangiography should be done to exclude this anomaly.

Adult↗

6R-L-erythro-5,6,7,8-tetrahydrobiopterin is involved in brain vulnerability of senescence-accelerated mouse during the processes of aging.

The effects of age on the dopamine (DA) turnover and 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4), a cofactor for monooxygenases, were investigated in the striatum and midbrain of the senescence accelerated mouse (SAM) at 6, 12 and 15 months old. 6R-BH4 and DA levels were decreased significantly in the striatum of 15-month-old SAM-P/1 (senescence accelerated prone) mice. At 12 months old, DA level was decreased significantly in the striatum of SAM-P/1 compared with SAM-R/1 (senescence accelerated resistant) mice. The reduction of striatal DA level was shown to be related to the depletion of 6R-BH4 in the striatum during the processes of aging. Age-related decreases in striatal dopamine function occurred in SAM-P/1 mice earlier than in the SAM-R/1 mice. The striatal [DOPAC]/[DA] ratio, as the index of DA turnover, was increased significantly in the 15-month-old SAM-P/1 mice. On the other hand, the DA, 6R-BH4 levels and the ratio of [DOPAC]/[DA] did not show any changes in the midbrain of SAM-P/1 and SAM-R/1 during the processes of aging. It was suggested that brain vulnerability with aging may be associated with the levels of 6R-BH4.

3,4-Dihydroxyphenylacetic Acid↗