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Biomedical subjects

H Itakura

Publications and source records attributed to H Itakura.

At least 91 records · Page 5Linked to original sources
PubMed1995

Effects of Platycodon grandiflorum feeding on serum and liver lipid concentrations in rats with diet-induced hyperlipidemia.

To study the effect of Platycodon grandiflorum (P.g.) feeding on serum and liver lipid concentrations, diet-induced hyperlipidemic rats were fed diets containing 5% and 10% P.g. powder for 3 weeks. The P.g. feeding markedly decreased both serum and liver lipid concentrations in hyperlipidemic rats. Especially, 5% P.g. diet significantly decreased the concentrations of total cholesterol and triglycerides in serum and liver as compared with those of the hyperlipidemic control group. Dietary P.g. also induced a reduction in low-density lipoprotein (LDL)-cholesterol as well as an increase in the concentration of high-density lipoprotein (HDL)-cholesterol in serum. Furthermore, the atherogenic index was also low in rats fed P.g. diet. These results indicated that dietary P.g. may have a beneficial effect on preventing hypercholesterolemia and hyperlipidemia.

Alanine Transaminase↗
PubMed1995

Polymorphism and Distribution of Apo(a).

Several apo(a) isoforms, controlled by a series of alleles Lp(a)F, Lp(a)B, Lp(a)S1, Lp(a)S2, Lp(a)S3, Lp(a)S4 and null, were found in 470 healthy Japanese by 4% SDS-PAGE and immunoblotting techniques. There was a strong inverse relationship between the apparent molecular weight of apo(a) isoforms and plasma concentrations of Lp(a). Lp(a) in d < 1.006 fraction increased 2-4h after oral fat load. Lp(a) exhibited a marked avidity for triglyceride-rich lipoprotein (TRL), and we suggest that the TRL-bound Lp(a) is the intact Lp(a) derived from serum. We demonstrated that the lipid-free apo(a) does not contain apo B-100 in serum, and has a molecular mass of ca 200 kDa. The free apo(a) level in normal subjects was 1.75 mg/dl (as Lp(a)) and was no different from the level in CAD patients.

Coronary Disease↗
PubMed1995

[Clinical investigation of renal pelvic and ureteral cancer with special reference to adjuvant chemotherapy].

Clinical investigation of 93 patients with histologically confirmed renal pelvic and ureteral cancer were performed. These patients consisted of 55 males and 38 females with a mean age of 64.8 years. There were 61 cases of renal pelvic cancer, 55 cases of ureteral cancer and 23 with cancers of both sites. Thirty-four cases were associated with bladder cancer and 41 of 82 patients had multiple tumors. The overall 5-year survival rate was 46.0%. 5-year survival of stages pTa, pT1, pT2, pT3, and pT4, was 93.3%, 71.8%, 37.5%, 30.4% and 10.5%, respectively. In this report, we evaluated various prognostic factors according to the survival rate. Sex, age, tumor localization, multiplicity, associated bladder cancer and concomitance of CIS had no influence on survival. In the ABC analysis, the B group showed a tendency for a poor prognosis. However it may be explained from the fact that the B group contained more patients at advanced stages than the other groups. Tumor grade, tumor stage, pV factor and pL factor had a significant effect on survivals. But tumor grade, pV and pL factors were closely related to the tumor stage. Thus the stage was thought to be the most important factor in the prognosis of upper urinary tract cancer. Different surgical procedures and irradiation also did not affect the prognosis of the patients with the same degree of invasion. Chemotherapy for all stages had no effect on survivals compared with non-chemotherapeutic group. However only for pT3 and higher stage cases, cisplatin-based chemotherapy improved the prognosis compared with patients not given chemotherapy. In conclusion, chemotherapy containing cisplatin should be considered for treatment of high stage upper urinary tract cancer.

Aged↗
PubMed1995

Determination of mRNA levels of cholesterol biosynthesis enzymes and LDL receptor using ribonuclease protection assay.

We designed a rapid method for determining mRNA content of cholesterol biosynthesis enzymes and LDL receptor (LDLR) using a ribonuclease protection assay (RPA). 32P-labeled cRNA fragments for genes of human LDLR and the enzymes HMG-CoA synthase (HMGS), HMG-CoA reductase (HMGR), mevalonate kinase (MK), farnesyl pyrophosphate synthase (FPPS), and squalene synthase (SQS) were prepared by in vitro transcription. Total RNA prepared from HepG2 cells was hybridized with the cRNA probe and the hybridized mRNA was determined under protection from RNase digestion. Probe content used in this assay was excess in determining the desired mRNA in total RNA, and surplus probes were completely digested using RNase under standard conditions. When cells were cultured in DMEM supplemented with 10% fetal calf serum (FCS), mRNA levels of FPPS, SQS, and LDLR were about 4- to 7-fold higher than those of HMGS, HMGR, and MK. On incubation with DMEM supplemented with 10% lipoprotein-deficient serum (LPDS) for 8 h, all messenger RNA levels increased 1.5- to 3.5-fold. In addition, when the HMG-CoA reductase inhibitor compactin was added to 10% LPDS-DMEM, these levels increased even further and the change in mRNA level seemed to differ between the enzymes and LDLR. From these results, we conclude that RPA is a useful method for determining the very small amount of mRNA level of cholesterol biosynthesis enzymes and LDLR in the cell.

Base Sequence↗
PubMed1994

Sterol mediated regulation of SREBP-1a,1b,1c and SREBP-2 in cultured human cells.

Under conditions of cholesterol depletion and SREBP-1 accumulation, changes in the levels of sterol regulatory element binding protein(s) (SREBPs) and sterol regulated gene mRNA were studied in Hep G2 cells by RNase protection assay. Cholesterol depletion increased the expression of mRNAs for cholesterol biosynthetic enzymes and low density lipoprotein (LDL) receptor. mRNAs levels for SREBP-1c and SREBP-2 were also increased by the cholesterol depletion. In contrast, levels for SREBP-1a and 1b (1a/b) mRNA increased transiently and then decreased. To examine the effect of SREBP-1 accumulation, Hep G2 cells were incubated with a SREBP-1 degradation inhibitor, N-acetyl-leucyl-leucyl-norleucinal (ALLN). The ALLN treatment increased the LDL receptor mRNA significantly, and also increased mRNA levels for HMG-CoA reductase, SREBP-1a/b and SREBP-2. The mRNA level for squalene synthase was not changed, and for SREBP-1c was decreased by the treatment. In conclusion, the regulation of differential expression of SREBP mRNA may be involved in sterol mediated regulation of gene expression. Moreover, the regulation of the SREBP-1 level may be a critical step in the regulation of sterol mediated LDL receptor expression.

Amino Acid Sequence↗
PubMed1994

Stabilization of interleukin-2 receptor alpha chain mRNA by HTLV-1 Rex in mouse L cells: lower amounts of Rex do not stabilize the mRNA.

T cell growth factor receptor, interleukin-2 receptor alpha chain (IL-2R alpha) is constitutively expressed on human T-cell leukemia virus type-1 (HTLV-1) infected T cells. We have established L cell lines which express both IL-2R alpha and the Rex protein of HTLV-1. We found that IL-1R alpha mRNA is stabilized in a cell line, Ltk/1-2a, which expresses a high amount of the Rex protein. In the presence of lower amounts of Rex, stabilization of the mRNA was not observed. These results may well explain the mechanism by which most of the lymphocytes infected with HTLV-1 escape from malignant transformation.

Animals↗
PubMed1994

A clinicpathological study of hepatocellular carcinoma in Nagasaki, south-western Japan: the association of hepatitis B and C viruses.

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in Japan as well as Southeast Asia and Africa. On 89 patients with HCC in the Nagasaki City area were performed serological examinations and histopathological studies. The number of HBsAg positive and anti-HCV positive was three (3%), HBsAg positive and anti-HCV negative 21 (24%), HBsAg negative and anti-HCV positive 58 (65%) and HBsAg negative and anti-HCV negative seven (8%). These results strongly suggest that HCV infection is a more important factor in the development of HCC than HBV infection. The HBsAg negative and anti-HCV positive group showed a higher mean age and a higher male to female ratio than the HBsAg positive and anti-HCV negative group. Histological examinations showed no differences between these two groups. In addition, all cases were complicated with chronic hepatitis (CH) or liver cirrhosis (LC) in adjacent liver tissue. These findings suggest that CH and LC seem to play an important role in the pathogenesis of HCC.

Aged↗
PubMed1994

[Apolipoprotein B].

The gene encoding human apo B has been mapped to the short arm of chromosome 2 in the p23-p24 region. The apo B gene extends over 43 kb and is composed of 29 exons and 28 introns. Both apo B 100 and apo B 48 were encoded by the same gene. All intestinal cDNA clones contained a single C to T base substitution in the codon CAA encoding Gln2153 in apo B 100 cDNA, resulting in a translational stop. In human intestinal cells, apo B mRNA is recognized by a specific enzyme that modifies cytosine 6666 to a uracil, introducing a stop codon. Recently, a human apo B mRNA editing protein was cloned. The cDNA sequence predicts a translation product of 236-aa residues. The human apo B mRNA editing protein is a cytidine deaminase and exists as a homodimer. Familial hypobetalipoproteinemia can be caused by mutations in the apoB gene that interfere with the translation of a full-length apo B molecule. Frequently, a truncated apo B molecule can be detected in the plasma lipoproteins of familial hypobetalipoproteinemia. Abetalipoproteinemia is caused by defect of the gene encoding the large subunit of a microsomal triglyceride transfer protein.

Apolipoproteins B↗
PubMed1994

[Regulation of gene expression by cholesterol and macrophage scavenger receptor].

Cellular cholesterol level is strictly regulated by the synthesis and the incorporation of cholesterol. Cholesterol synthetic enzymes and lipoprotein receptors are regulated mainly at the transcriptional level. Recently, sterol regulatory element binding proteins (SREBPs) which induce LDL receptor expression, were cloned and the mechanism of sterol-mediated gene regulation was proposed. Cholesterol synthesizing enzymes such as HMG-CoA reductase, farnesyl pyrophosphate synthase and squalene synthase are also regulated by the cellular cholesterol level, but it is suggested that SREBPs are not play critical role in their regulation. Scavenger receptors also uptake cholesterol into macrophage, but the receptors are not regulated by the cellular cholesterol level and this leads to the abnormal accumulation of cholesterol in macrophages.

Alkyl and Aryl Transferases↗
PubMed1993

Structure, organization, and chromosomal mapping of the human macrophage scavenger receptor gene.

Macrophage scavenger receptors (MSR) mediate the binding, internalization, and processing of a wide range of negatively charged macromolecules. Functional MSR are trimers of two C-terminally different subunits that contain six functional domains. We have cloned an 80-kilobase human MSR gene and localized it to band p22 on chromosome 8 by fluorescent in situ hybridization and by genetic linkage using three common restriction fragment length polymorphisms. The 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). The promoter has a 23-base pair inverted repeat with homology to the T cell element. Exon 1 encodes the 5'-untranslated region followed by a 12-kilobase intron which separates the transcription initiation and the translation initiation sites. Exon 2 encodes a cytoplasmic domain, exon 3, a transmembrane domain, exons 4 and 5, an alpha-helical coiled-coil, and exons 6-8, a collagen-like domain. The position of the gap in the coiled coil structure corresponds to the junction of exons 4 and 5. These results show that the human MSR gene consists of a mosaic of exons that encodes the functional domains. Furthermore, the specific arrangement of exons played a role in determining the structural characteristics of functional domains.

Amino Acid Sequence↗
PubMed1993

Charged collagen structure mediates the recognition of negatively charged macromolecules by macrophage scavenger receptors.

Macrophage scavenger receptors mediate the recognition of a wide range of negatively charged macromolecules including modified low density lipoproteins (LDL). Truncated bovine receptors lacking residues 330-342, which include the conserved lysine cluster of a collagen-like domain, were unable to degrade modified LDL in spite of their expression on the cell surface. Substitution of lysine 337 into alanine abolished the acetyl-LDL degradation and binding at 37 degrees C, but did not abolish the 4 degrees C binding. In contrast, substitution of more than 2 lysines in this region are needed to abolish the oxidized LDL degradation and 37 degrees C binding. Based on computational modeling of this domain, we propose that a "charged collagen" structure containing a lysine cluster forms a positively charged groove which specifically interacts with negatively charged ligands.

Amino Acid Sequence↗