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H Itakura

Publications and source records attributed to H Itakura.

At least 109 records · Page 6Linked to original sources

Apolipoproteins and lipoprotein receptors in glomeruli in human kidney diseases.

This study offers morphological evidence of the involvement of lipid abnormalities in human glomerular injury. Renal biopsy tissues from patients with several types of glomerular diseases were immunocytochemically examined using antibodies to apolipoproteins (apo) A-I, B-100, and E, and antibodies to low density lipoprotein (LDL) receptors and scavenger receptors. Immunofluorescent staining showed the predominant deposition of apo B and apo E in the mesangial area in mesangial proliferative types of glomerulonephritis; the distribution and staining intensity of these apolipoproteins correlated with the grade of mesangial proliferation and proteinuria, but were independent of plasma lipid levels. Immunoelectron microscopy revealed that apo B and apo E were distributed in droplets within glomerular epithelial and mesangial cells or in a granular pattern in the expanded mesangial matrix. Apo A-I was mainly localized in the visceral epithelial cells of normal human kidneys. Staining for apo A-I was increased in the glomerular epithelial cells of nephritic kidneys, compared to the pattern in normal human kidneys, and was decreased in the sclerosed areas of glomeruli. An immunogold technique revealed the expression of LDL receptors on the surface membranes of glomerular mesangial and epithelial cells. Dual immunofluorescent staining showed that apo B and LDL receptors were occasionally co-localized in nephritic glomeruli. Scavenger receptor was detected on the plasma membranes of mesangial and visceral epithelial cells. The glomerular expression of scavenger receptor was increased in glomeruli with marked mesangial proliferation. In addition, the expression of this receptor was intense in monocytes/macrophages occasionally infiltrating the glomeruli. Our present findings indicate that in human nephritic kidneys, glomerular epithelial and mesangial cells express both LDL receptors and scavenger receptors. The accumulation of apolipoproteins, whether receptor-mediated or mediated by other mechanisms, can occur independently of plasma lipid levels, and may be associated with mesangial expansion and proteinuria.

Apolipoproteins↗

Cholera toxin inhibits lethal hit stage of natural killer cell-mediated cytotoxicity.

Cytolytic process which was affected by cholera toxin (CT) resulting in the loss of natural killer (NK) cell activity was analyzed. Conjugate formation assay, membrane phospholipid methylation assay and serine esterase (granzyme A) release assay were used to determine the stage of the CT-induced inhibition of NK cell-mediated cytotoxicity. A human NK cell line YT cell-mediated cytotoxicity was completely abolished by CT pretreatment or addition of CT to the assay system. The conjugate formation assay revealed that the binding between YT cells and target cells was not affected by CT. The defined triggering stage which is coupled with membrane phospholipid methylation was not affected by CT treatment, either. On the other hand, the lethal hit stage which is represented by serine esterase (SE) release was completely inhibited by CT treatment of YT cells. Therefore, CT inhibits the stage after binding and triggering--i.e., lethal hit stage of NK cell-mediated cytotoxicity. The results also suggest that there exists a CT-sensitive negative cytotoxic signal transduction pathway as well as usual positive signal transduction pathway and these pathways might cross talk each other in the NK cell cytotoxic process.

Cholera Toxin↗

B-cell antigen marker expression in nasopharyngeal carcinoma.

Immunohistochemical analysis was carried out to examine the characteristics of nasopharyngeal carcinoma (NPC) using 38 biopsy cases obtained from southern China. These cases were divided into 3 groups according to their predominant pattern associated with cell and tissue differentiation which is based on World Health Organization (WHO) classification as follows: 6 cases of squamous cell carcinoma (16%), 25 cases of differentiated non-keratinizing carcinoma (66%), 7 cases of undifferentiated carcinoma (18%). All tumor tissues reacted with MB-1, but they did not react with L26 (CD20), 4KB5 (CD45R), MT-1, and leukocyte common antigen (LCA). Keratin and epithelial membrane antigen (EMA) as epithelial markers focally stained NPC tissues in all cases. Carcinoembryonic antigen (CEA)-positive staining was detected in 7 (28%) of the 25 cases of differentiated non-keratinizing carcinoma and in 3 (43%) of the 7 cases of undifferentiated carcinoma; thus, of 38 cases, 10 (26%) were CEA-positive. On the other hand, squamous cell carcinoma cases did not react with CEA. These NPC tissues did not react with S-100 protein, alpha-1-antichymotrypsin (ACT), lysozyme, vimentin, and desmin. Therefore, it is concluded that some cases of NPC are difficult to distinguish from malignant lymphoma. In certain cases, NPC may be distinguished from malignant lymphoma, using immunohistochemical methods for the detection of MB-1, keratin, EMA, and LCA. Specifically, this evidence suggests that MB-1 may be useful as a tumor marker of NPC. Moreover, the CEA reaction to NPC may be related to the cell differentiation.

Antigens, CD↗

[Structural and function of the human macrophage scavenger receptor].

Macrophage scavenger receptors (MSR) mediate the binding, internalization and processing of the wide range of negatively charged macromolecules. Functional receptors are trimers of two C-terminally different subunit containing 6 functional domains; cytoplasmic, transmembrane, spacer, alpha-helical coiled-coil, collagen-like, type specific domain. The C-terminal region of the collagen-like domain is essential for the ligand recognition of MSR. Human MSR gene consists of 11 exons, and two types of mRNAs are generated by alternative splicing from exon 8 to either exon 9 (type II) or to exons 10 and 11 (type I). Exon 1 encodes the 5' untranslated resion followed by a 12 kb intron which separates the transcription initiation site and the translation initiation site. Exon 2 encodes a cytoplasmic domain; Exon 3, a transmembrane domain; Exons 4 and 5, an alpha-helical coiled-coil; and exon 6 to 8, a collagen-like domain. The MSR gene consists of a mosaic of exons which encode the functional domains. The arrangement of exons helped determine the fine structural characteristics of functional domains.

Arteriosclerosis↗

[Dietary treatment of atherosclerosis].

Dietary treatments for hyperlipidemia, hypertension, diabetes mellitus and obesity are essential for the prevention or management of atherosclerosis. To correct overweight or obesity, restriction of energy intake should be considered. The consumption of fat should be decreased less than 25 percent of total energy. The ratio of saturated fatty acid, monounsaturaled fatty acid and polyunsaturated fatty acid is recommended as 1:1:1. Intake of oily fish should be included in daily meal. The ratio of n-6/n-3 polyunsaturated fatty acid is considered to be beneficial around three or four. Excess intake of simple sugars must be avoided and increase the intake of complex carbohydrate and dietary fibre are recommended.

Adolescent↗

[Hypolipidemia].

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Adult↗

[Structure and function of the scavenger receptor].

The macrophage scavenger receptors are consisted of six domains: cytoplasmic, membrane-spanning, spacer, alpha-helical coiled-coil, collagen-like and a type-specific C-terminal. The collagen-like domain is revealed to have important role for ligand binding. The receptor gene is located on human chromosome 8. The human scavenger gene spans approximately 80 kb and is composed of 11 exons. Two types of scavenger receptor mRNA were shown to result from alternative splicing of exon 9 for type II or 10 and 11 for type I to the common exon 1-8. The scavenger receptor proteins were detected in macrophages of various organs and tissues such as Kupffer cells, alveolar macrophages, macrophages in the spleen and lymph nodes and perivascular macrophages in the brain. In the atheromatous plaques, scavenger receptors may participate progression of foam cells. Elimination and detoxication of endotoxin by macrophage scavenger receptor may suggest the defending function against a wide variety of pathogenic agents.

Amino Acid Sequence↗

Expression of scavenger receptors on renal cell carcinoma cells in vitro.

Messenger RNAs and proteins of scavenger receptor thought to be macrophage specific protein were expressed in renal cell carcinoma (RCC) cells in vitro. Acetyl LDL was taken up into RCC cells and promoted the production of interleukin-6 (IL-6), an in vitro autocrine growth factor to proliferate the cells. These results suggested that RCC cells might have a scavenger pathway which has not yet been demonstrated except for macrophages.

Blotting, Northern↗

Genetic analysis of a Japanese family with normotriglyceridemic abetalipoproteinemia indicates a lack of linkage to the apolipoprotein B gene.

Normotriglyceridemic abetalipoproteinemia is a rare familial disorder characterized by an isolated deficiency of apoB-100. We have previously reported a patient with this disease, who had normal apoB-48 but no apoB-100. To elucidate the genetic abnormalities in this family, we studied the linkage of apoB gene using three genetic markers. The proband and her affected brother showed completely different apoB gene alleles, suggesting that the apoB gene itself is not related to this disorder in this family. By contrast, an American case had a point substitution in the apoB gene generating an in-frame stop codon. These results indicate that this disorder can be caused by defect(s) of either an apoB gene or other genes.

Abetalipoproteinemia↗

Flow cytometric DNA analysis of vascular soft tissue tumors, including African endemic-type Kaposi's sarcoma.

Vascular tumors of the soft tissue display a wide spectrum of histologic features and biologic behavior. Flow cytometric DNA analysis was performed on 40 vascular tumors, including nine African endemic-type Kaposi's sarcomas, nine angiosarcomas, seven hemangiopericytomas, six glomus tumors, and nine capillary hemangiomas. Six of the nine angiosarcoma cases (67%) and one of the seven hemangiopericytomas cases (14%) were aneuploid. All benign vascular tumors and Kaposi's sarcomas were diploid. Clinically, five of the six angiosarcoma patients with aneuploidy died within 2 to 28 months, while the remaining patient, who had the smallest tumor (2 x 1 cm), survived more than 4 years after the initial diagnosis was made. All three angiosarcoma patients with diploidy died within 10 to 14 months. One hemangiopericytoma patient with aneuploidy died within 1 month. No cases of benign tumor recurred. These results suggest that most vascular tumors, which generally follow a benign clinical course, were diploid and that the majority of those with a poor outcome were aneuploid. However, flow cytometrically assessed DNA ploidy has no prognostic value in angiosarcomas or hemangiopericytomas.

Adolescent↗

Effects of fish and safflower oil feeding on subcellular glucose transporter distributions in rat adipocytes.

Effects of fish oil feeding on glucose transport systems and cell size in rat adipocytes were examined and compared with those of safflower oil or carbohydrate feeding under isoenergy intake conditions. Glucose transport activity was assessed by measuring 3-O-methyl-D-glucose transport. The concentration of erythrocyte type glucose transporter (GLUT-1) and muscle/fat type transporter (GLUT-4) was measured by immunoblotting. The amount of each transporter in intact cells was estimated by the amount of transporter and protein of each membrane fraction and by the recovery of marker enzymes. In cells from safflower-fed rats compared with those from carbohydrate-fed rats, insulin-stimulated glucose transport activity per cell decreased to 51% after a 1-wk feeding, and cell size increase became larger with these effects and continued for at least 4 wk. At 1 wk of feeding, GLUT-1 and GLUT-4 per cell in plasma membrane from insulin-treated cells decreased to 62 and 35%, respectively, with concomitant transporter decreases in the low-density microsome fraction. In cells from high-fish oil-fed rats in which two-thirds of safflower oil was replaced by fish oil, when compared with those from safflower oil-fed rats, insulin-stimulated glucose transport activity increased 1.7-fold after 1 wk of feeding with concomitant cellular GLUT-1 and GLUT-4 increases, but its effect declined thereafter. Parallel with this time course, cell size increase was smaller after 1 wk, but this effect also declined thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase↗

Effects of pravastatin sodium alone and in combination with cholestyramine on hepatic, intestinal and adrenal low density lipoprotein receptors in homozygous Watanabe heritable hyperlipidemic rabbits.

Pravastatin sodium (pravastatin), a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was administered alone (50 mg/kg) or in combination with cholestyramine, a bile acid sequestrant resin, at the level of 2% in the diet to homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits for 4 weeks. The low density lipoprotein (LDL)-cholesterol levels were reduced by 29% and 56% with pravastatin alone and the combination treatment, respectively. Hepatic LDL receptor activity was increased by 11.2- and 13.9-fold with pravastatin alone and the combination treatment, respectively. The LDL receptor activity in the untreated homozygous WHHL rabbits was only 2.5% of that in the normal rabbits. mRNA for the LDL receptor in the liver was also increased by 2.1- and 3.4-fold with pravastatin alone and the combination treatment, respectively. On the other hand, mRNA for the LDL receptor in the adrenal gland was not affected by pravastatin and the combination treatment, whereas the mRNA in the intestine was increased in both groups. These results suggest the following: 1) the induction of hepatic LDL receptor activity by the treatment of pravastatin alone or in combination with cholestyramine is the main cause of the reduction of serum cholesterol levels by these treatments even in LDL receptor-deficient animals. 2) The induction of the mRNA for the LDL receptor in the liver and intestine, but not that in the adrenal gland, might be a reflection of the tissue-selective inhibition of cholesterol synthesis by pravastatin.

Adrenal Glands↗

Exercise training increases glucose transporter content in skeletal muscles more efficiently from aged obese rats than young lean rats.

Glucose uptake in rat skeletal muscles decreases with age and obesity, but increases with chronic exercise training. The purpose of our study was to determine whether the GLUT4 content in several skeletal muscles from 1-mo-old young, lean rats and 12-mo-old aged, obese rats alters with exercise training. For exercise, a treadmill run of approximately 1 km/day was made for 4 wk by both groups of rats. The concentration of GLUT4 per protein in membrane fraction from several skeletal muscles was measured by immunoblotting. The amount of GLUT4 in the gastrocnemius and white quadriceps from aged rats slightly but significantly decreased to 73% and 78% of that from young rats, respectively. However, no significant difference in GLUT4 amount in the soleus, plantaris, and red quadriceps was observed between young and aged rats. The exercise training resulted in a larger increase in the amount of GLUT4 in each muscle from aged rats than in muscles from young rats. In aged rats, GLUT4 amount increased significantly with exercise training by 30, 33, 41, and 27% in the soleus, plantaris, gastrocnemius, and red quadriceps, respectively, compared with the sedentary controls. However, in young rats, exercise-induced increase of GLUT4 amount was significant only in the plantaris, and the increase was 17%. In exercised aged, obese rats, decreases of body weight, plasma triglyceride levels, and plasma free fatty acid were also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

[Flow cytometric analysis of DNA aneuploidy in adrenal tumors].

Nuclear DNA content of paraffin-embedded tissue from 38 adrenal neoplasms and 9 histologically normal adrenal glands was analyzed using flow cytometry. Histological diagnosis of thirty-eight adrenal neoplasms were 3 adrenocortical carcinomas, 20 adrenocortical adenomas and 15 pheochromocytomas. In 33 cases (87%) of the 38 tumors the determination of DNA ploidy was possible. All 9 control specimens showed DNA diploid pattern in DNA histogram. In adrenocortical neoplasms the incidence of DNA aneuploidy was 0% (0 of 17) in adenomas and 100% (2 of 2) in carcinomas. All 17 adrenocortical adenomas which showed DNA diploid pattern are clinically benign. On the other hand, both 2 cases of adrenocortical carcinoma which showed DNA aneuploidy died within 1 year. These data suggest that DNA aneuploidy may be useful as a prognostic factor in adrenocortical neoplasm. With regard to pheochromocytoma, DNA aneuploidy was detected in 4 of 14 patients (29%). However, all 14 cases were clinically benign. In pheochromocytoma DNA aneuploidy was not found to be correlated with prognosis.

Adenoma↗

[A case of urinary retention due to tuberculous pyometra].

A rare case of urinary retention due to tuberculous pyometra is presented. A 70-year-old woman visited our hospital complaining of dysuria and pollakisuria on January 26, 1990. In spite of medication of cholinergic agents, urinary retention developed on April 6, 1990. Cystoscopy revealed elevation of the urethra and bladder neck. Physical examinations disclosed a child-head-sized tumor in the lower abdomen, which persisted following catheterization. Excretory urogram showed a large retrovesical mass. Chain urethrocystogram revealed anterior dislocation of the bladder neck and the proximal portion of the urethra. CT scan and MRI demonstrated a fluid-filled pelvic mass, which positioned above the vagina and compressed the urinary bladder anteriorly. Total hysterectomy was performed on August 6, 1990. Pathological diagnosis was tuberculous endometritis. Urinary symptoms disappeared immediately after the operation. Postoperative chain urethrocystography revealed complete cure of the dislocation of the bladder neck and urethra. We collected 34 cases of urinary retention due to gynecological disease in Japan, and 110 cases in English literature. Among the frequent diseases were retroverted gravid uterus, prolapse uteri, uterine leiomyomas, ovarian cyst, imperforated hymen and vaginal atresia. The mechanisms of urinary retention in gynecological disease are discussed. No case of urinary retention due to tuberculous pyometra was found in the literature.

Aged↗