Search PubMed⌕ Search

Biomedical subjects

T Yamamura

Publications and source records attributed to T Yamamura.

At least 91 records · Page 5Linked to original sources
PubMed1999

Characterization of apolipoprotein E7 (Glu(244)-->Lys, Glu(245)--->Lys), a mutant apolipoprotein E associated with hyperlipidemia and atherosclerosis.

Previously, a mutant apolipoprotein (apo) E, apolipoprotein E7 (Glu(244)-->Lys, Glu(245)--->Lys), has been identified in association with hyperlipidemia and atherosclerosis. To investigate the effects of its structural changes on lipoprotein metabolisms and its correlation with atherosclerosis, we characterized this mutant apoE with respect to its receptor-binding, heparin-binding, and lipoprotein association. In a competitive binding assay, apoE7. dimyristoylphosphatidylcholine displayed a defective binding to the low density lipoprotein (LDL) receptor. The concentration of apoE7 required for 50% displacement of (125)I-labeled LDL was 0.223 microg/ml, while that for apoE3 was 0.048 microg/ml. ApoE7 possesses only 23% of normal binding activity. To investigate the lipoprotein preference of apoE7, we determined the relative amounts of apoE7 in plasma lipoprotein fractions obtained by ultracentrifugation or gel filtration. Like human apoE4, apoE7 was preferentially associated with the very low density lipoproteins (VLDL). For determination of heparin-binding activity, apoVLDL was applied to a heparin-Sepharose affinity column and the bound materials were eluted with a salt gradient. The apoE7 was eluted at a higher NaCl concentration (157 mm) than apoE3 (126 mm), indicating that this mutant has a higher affinity for heparin than does apoE3. While the reduced receptor-binding activity indicates delayed clearance of the triglyceride-rich lipoproteins, the preferential association of apoE7 with larger-size lipoproteins and the stronger interaction with heparin may compensate, to some extent, for the delayed clearance of triglyceride-rich lipoproteins. The strong interaction with proteoglycans in the arterial wall seems to be one of the possible explanations for the association of apoE7 with atherosclerosis.-Yamamura, T., L-M. Dong, and A. Yamamoto. Characterization of apolipoprotein E7 (Glu(244)-->Lys, Glu(245)--->Lys), a mutant apolipoprotein E associated with hyperlipidemia and atherosclerosis.

Apolipoprotein E3↗
PubMed1998

Discovery of IRL 3461: a novel and potent endothelin antagonist with balanced ETA/ETB affinity.

IRL 3461, N-butanesulfonyl-[N-(3,5-dimethylbenzoyl)-N-methyl-3-[4-(5-+ ++isoxazolyl) -phenyl]-alanyl]-(L)-valineamide, a potent and bifunctional (ETA + ETB) [Ki(ETA) = 1.8 nM, Ki(ETB) = 1.2 nM] antagonist was discovered by structural modification of IRL 2500, an ETB selective antagonist. IRL 3461 was found to be stable on incubation with human, rat, mouse, and guinea pig plasmas.

Animals↗
PubMed1998

Acquisition of secretion of transforming growth factor-beta 1 leads to autonomous suppression of scavenger receptor activity in a monocyte-macrophage cell line, THP-1.

Macrophage cells derived from the human monocytic leukemia cell line, THP-1, accumulate esterified cholesterol when cultivated in the presence of acetylated low density lipoprotein (Ac-LDL) through scavenger receptors (ScR). In the present study, we isolated a subtype of THP-1 cells that failed to accumulate esterified cholesterol when cultivated in the presence of Ac-LDL. The cells had negligible amounts of cell association and degradation of Ac-LDL compared with the parent THP-1 cells. The subtype THP-1 cells did not express ScR mRNA as well as that of lipoprotein lipase. In contrast, the expression of apolipoprotein E mRNA was greater than that found in parent THP-1 cells. The culture medium of subtype THP-1 cells treated with 12-O-tetradecanoylphorbol-13-acetate inhibited the uptake of Ac-LDL and the expression of ScR in parent THP-1 cells. After a 48-h incubation in the culture medium containing 12-O-tetradecanoylphorbol-13-acetate, the culture medium of differentiated subtype THP-1 cells contained 6.9 ng/ml transforming growth factor (TGF)-beta 1, while that of parent THP-1 cells secreted below detection level, which was less than 3 ng/ml. This inhibitory effect of the conditioned medium on the expression of ScR in parent THP-1 cells was abolished by pretreatment of the culture medium with anti-TGF-beta 1 antibodies. Parent THP-1 cells expressed as much TGF-beta 1 mRNA as sTHP-1 cells after stimulation of differentiation. Although the precursor forms of TGF-beta 1 that were synthesized in both parent and subtype THP-1 cells were of similar size and were expressed at similar levels, latent TGF-beta 1-binding protein, which is necessary for the secretion of TGF-beta 1, could only be co-immunoprecipitated with anti-TGF-beta 1 antibody from subtype THP-1 cells. This suggests that subtype THP-1 cells secrete TGF-beta 1 into the medium by forming a functional complex with the latent TGF-beta 1-binding protein. We conclude that subtype THP-1 cells could not take up Ac-LDL because ScR was inhibited (leading to a loss of function) caused by the secreted TGF-beta 1.

Carrier Proteins↗
PubMed1998

LDLR Database (second edition): new additions to the database and the software, and results of the first molecular analysis.

Mutations in the LDL receptor gene (LDLR) cause familial hypercholesterolemia (FH), a common autosomal dominant disorder. The LDLR database is a computerized tool that has been developed to provide tools to analyse the numerous mutations that have been identified in the LDLR gene. The second version of the LDLR database contains 140 new entries and the software has been modified to accommodate four new routines. The analysis of the updated data (350 mutations) gives the following informations: (i) 63% of the mutations are missense, and only 20% occur in CpG dinucleotides; (ii) although the mutations are widely distributed throughout the gene, there is an excess of mutations in exons 4 and 9, and a deficit in exons 13 and 15; (iii) the analysis of the distribution of mutations located within the ligand-binding domain shows that 74% of the mutations in this domain affect a conserved amino-acid, and that they are mostly confined in the C-terminal region of the repeats. Conversely, the same analysis in the EGF-like domain shows that 64% of the mutations in this domain affect a non-conserved amino-acid, and, that they are mostly confined in the N-terminal half of the repeats. The database is now accessible on the World Wide Web at http://www.umd.necker.fr

Computer Communication Networks↗
PubMed1998

A novel point mutation in a splice acceptor site of intron 1 of the human low density lipoprotein receptor gene which causes severe hypercholesterolemia: an unexpected absence of exon skipping. Mutations in brief no. 139. Online.

Familial hypercholesterolemia (FH) is a genetic disorder caused by mutations in the low density lipoprotein (LDL)-receptor gene. We found a new mutation in the splice acceptor site of intron 1 of the LDL receptor gene, which is designated as 68-1 G->C according to the nomenclature suggested by Beaudet and Tsui (1993), in a Japanese FH homozygote. She was born from consanguineous marriage and has this mutation as a true homozygous form. Her cultured fibroblasts showed no LDL receptor protein synthesis. This mutation caused activation of a cryptic splice acceptor side in the downstream exon 2, leading to frameshift and appearance of premature in-frame stop codon. The mutation was detected by Dde I restriction enzyme. The identical mutation was not found among 24 patients with homozygous and 120 patients with heterozygous FH. The mutation was very rare among the Japanese population.

Alternative Splicing↗
PubMed1998

Usefulness of bipolar scissors for total colectomy.

PURPOSE: Total colectomy is frequently used in colorectal surgery. We evaluated the usefulness of bipolar scissors in this operation. METHODS: Twenty patients with ulcerative colitis underwent total colectomy at Hyogo College Hospital. Bipolar scissors were used in ten randomly chosen colectomies. The resected major vessels of the colonic mesentery were stained by hematoxylin and eosin. The bursting pressure of the artery weld was measured with a water-filled, open-tip catheter. RESULTS: Both number of ligations and operating time were reduced by use of bipolar scissors. The cut edge of the major artery was occluded by the weld created, with a mean bursting pressure of 213 (range, 175-250) mmHg. CONCLUSION: Use of bipolar scissors was safe and had the advantage of shortening the operating time by decreasing the number of clamping and ligating procedures.

Adolescent↗
PubMed1998

Early local recurrence of rectal cancer showing extremely rapid growth after curative surgery: report of a case.

We report herein the case of a 59-year-old woman who developed a local recurrence of rectal cancer which showed extremely rapid growth. The patient had undergone a curative low anterior resection with total mesoexcision, and was discharged on postoperative day 25 after an uneventful recovery. However, 2 months after the operation, she developed bleeding from the rectum during defecation, the quantity of which gradually increased. A colonoscopy performed during the fifth postoperative month revealed a circular tumor at the suture line. The tumor was unresectable because it had firmly invaded not only the sacrum, but also the right ureter. Despite the administration of 5-fluorouracil and leucovorin, the patient died of cancer 18 months after her initial surgery. Considering that local recurrence of rectal cancer does not usually occur within 1 year after surgery, this case is unusual because the local recurrence developed very early and showed extremely rapid growth, occupying the entire lumen of the rectum by the time it was detected by colonoscopy during the fifth postoperative month.

Colonoscopy↗
PubMed1998

The effects of oestrogen on osteocalcin production by human periodontal ligament cells.

The purpose was to investigate the effects of oestradiol on the function of periodontal ligament (PDL) cells by measuring the production of osteocalcin in vitro. Cells were obtained from the healthy periodontal ligament of teeth extracted from two males and two females for orthodontic reasons. Serum-free medium was used when testing the effects of oestradiol on PDL cells. The amount of osteocalcin in the culture medium was analysed by two-step sandwich enzyme immunoassay in the presence or absence of oestradiol. It was shown that oestradiol enhanced the production of osteocalcin by PDL cells in a time- and dose-dependent manner. PDL cells obtained from both male and female donors were affected by oestradiol. It thus appears that oestradiol is one of the factors important for PDL cells to express their function.

Adult↗
PubMed1998

Accumulation of chylomicron remnants in homozygous subjects with familial hypercholesterolaemia.

BACKGROUND: Post-prandial lipoprotein kinetics were investigated in subjects who lack functioning low-density lipoprotein (LDL) receptors [homozygous familial hypercholesterolaemia (FH)]. METHODS: An oral fat load was given, and chylomicron plasma kinetics was determined by monitoring the clearance of triglyceride, retinyl palmitate and apolipoprotein B48, calculated as the area under the curve, for 7.5 h. In addition, the binding and uptake of chylomicron remnants by fibroblasts of FH and control subjects were assessed in vitro. RESULTS: Based on the plasma kinetics of chylomicron triglyceride, retinyl palmitate and apolipoprotein B48 after a lipid meal, chylomicron clearance was found to be substantially delayed compared with normolipidaemic control subjects. Consistent with involvement of the LDL receptor in chylomicron clearance, binding and uptake of chylomicron remnants by fibroblasts of FH subjects was found to be substantially less than in cells from control subjects. CONCLUSION: This study shows that, in addition to LDL, chylomicron metabolism is severely impaired in FH and that the LDL receptor is significantly involved in the clearance of post-prandial lipoproteins. Moreover, this study raises the possibility that in FH, and in other disorders in which LDL receptor expression is reduced, atherogenesis might be a post-prandial disease.

Adolescent↗
PubMed1998

Human pancreatic RNase1-human epidermal growth factor fusion: an entirely human 'immunotoxin analog' with cytotoxic properties against squamous cell carcinomas.

The gene encoding human pancreatic ribonuclease 1 (hpRNasel) was fused with a gene encoding human epidermal growth factor (hEGF). The hybrid human protein was isolated from Escherichia coli inclusion bodies, refolded and purified to homogeneity. The fusion protein competed with 125I-hEGF for binding to hEGF receptors (EGFR) and had ribonucleolytic activities approaching those of hpRNase1. Several conformations having different enzymatic activities could be detected after reversed-phase high-performance liquid chromatographic analysis, the less hydrophobic molecules being the most active. The hybrid protein was specifically cytotoxic to A431, an EGFR overexpressing squamous carcinoma cell line, with an IC50 of approximately 10(-7) M. In contrast, recombinant hpRNase1 had an IC50 higher than 10(-4) M. A mixture of free hEGF and free hpRNasel was not more cytotoxic than hpRNasel alone and no cytotoxicity was detected in EGFR-deficient control cells. Taken together, these data suggest that this construct might be useful for targeted therapy of esophageal, lung and other squamous cell carcinomas and also breast cancers overexpressing EGFR, which correlate with a poor prognosis and cannot be cured by surgery alone. Engineering hybrid molecules with endogenous human proteins for targeted therapy may alleviate the dose-limiting immunogenicity and toxicity of conventional immunotoxins.

Binding, Competitive↗
PubMed1998

Gastroesophageal reflux after distal gastrectomy: possible significance of the angle of His.

OBJECTIVE: We investigated whether the angle of His influences gastroesophageal reflux after distal gastrectomy. METHODS: Thirty-eight patients having distal gastrectomy and 10 controls underwent upper gastroesophageal fluoroscopy to measure the angle of His, and gastroesophageal reflux was assessed by scintigraphy. The association between scintigraphic reflux and the angle of His was then evaluated. RESULTS: In distal gastrectomy patients with and without reflux symptoms, the angle was 108.82 +/- 21.88 degrees and 96.07 +/- 13.25 degrees, respectively; it was 74.14 +/- 10.85 degrees in the controls. The angle was significantly larger in the patients than in the controls (p < 0.01). In addition, the angle in the symptomatic gastrectomy group tended to be larger than in the asymptomatic group. The angle was also significantly larger in patients with a scintigraphic reflux index > or =6% than in those with an index <6% (p < 0.05). CONCLUSIONS: These findings suggest that the angle of His plays a role in reflux after distal gastrectomy and that the severity of reflux may be estimated by measuring this angle.

Adult↗
PubMed1998

Scintigraphic assessment of double tract reconstruction after total gastrectomy.

BACKGROUND/AIMS: This study was carried out to evaluate the clinical significance of double tract reconstruction after total gastrectomy. METHODS: 25 patients, 14 with jejunal pouch double tract reconstructions and 11 with rho-double tract reconstructions, were studied. Scintigraphy was used to evaluate duodenal and jejunal passage, and the jejunal/duodenal ratio was calculated. The patients were classified into 3 groups based on this ratio: group A (n = 14) ratio <1; group B (n = 6) ratio 1-2, and group C (n = 5) ratio >2. The reflux score, scintigraphic reflux index, emptying time of the jejunal pouch or rho-limb, and various nutritional parameters were compared between the 3 groups. RESULTS: The emptying time was shortest in group B, but there was no significant difference among the 3 groups in the Sigstad dumping scores. The reflux score, scintigraphic reflux index, and most nutritional parameters also showed no significant differences between the 3 groups. Leakage at the duodenojejunostomy did not occur in any patient. CONCLUSION: Our findings suggest that there was no preferential passage via the duodenum or jejunum after double tract reconstruction. This method is also useful for decompression of the duodenal stump and group B seemed to have the ideal reconstruction on the basis of emptying time.

Adult↗
PubMed1998

A comparison of stapled and hand-sewn anastomoses in Crohn's disease.

Sixty-eight patients with Crohn's disease who underwent intestinal resection were randomly divided into 2 groups: the stapled group (32 patients, 40 anastomoses) with functional end-to-end anastomoses made with linear staplers and with circular stapling anastomoses, and the hand-sewn group (36 patients, 48 anastomoses), with anastomoses achieved by layer-to-layer suturing. There were no significant differences in operative indications, age, sex, blood loss, or length of hospital stay between the groups. The operation times for right hemicolectomy and total colectomy in the stapled group were significantly shorter than those in the hand-sewn group. There were no significant differences in anastomotic dehiscence or recurrence between the stapling and hand-sewn procedures. These results indicate that these stapling techniques, even though producing an everted anastomosis, are not an adverse procedure for Crohn's disease.

Adolescent↗
PubMed1998

Effects of pharmacokinetic modulating chemotherapy using oral UFT and continuous venous 5FU infusion on the prognosis of irradiated rectal carcinomas with p53 overexpression.

We previously found that patients with irradiated rectal carcinomas with p53 overexpression had poor prognoses after radical resection. In the present study, we attempted to improve the prognosis by the introduction of adjuvant chemotherapy. We administered pharmacokinetic modulating chemotherapy, based on the concept that the benefit of a continuous venous 5-fluorouracil (5FU) infusion can be potentiated by low-dose oral UFT, a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4. Forty-two of 107 patients examined between January 1992 and December 1997 with an irradiated rectal carcinoma (39%) showed positive immunohistochemical staining for p53. Among them, 14 patients received adjuvant chemotherapy (CT group). The percentage of highly malignant tumors in the CT group was higher than that in the no-chemotherapy (NCT) group (n=28). However, the rate of cumulative local recurrence in the CT group was 0%, while that in the NCT group was 28.6% (p=0.0392). The distant recurrence rate in the CT group was also significantly lower than that in the NCT group (7.1% vs. 42.9%, p=0.0376). The cumulative 3-year survival rate was 100% in the CT group and 64.3% in the NCT group (p=0.0245). These results suggested that the antitumor property of 5FU enhanced by pharmacokinetic modulation might have a lethal effect on rectal tumors with a loss of the p53-related apoptosis pathway. These preliminary findings are encouraging for the treatment of rectal cancers with possible poor prognosis.

Administration, Oral↗
PubMed1998

[Adjuvant chemotherapy with UFT or UFT with OK-432 to patients with gastric and colorectal cancer. Kanto Adjuvant Study Group].

In Japan, long-term oral therapy with tegafur in combination with immunopotentiators is commonly used as adjuvant therapy after curative resection of gastric or colorectal can for gastric and colorectal cancer. When the outcome was analyzed in terms of the relative performance (R.P.) and the individual dose intensity (I.D.I.) of OK-432, gastric cancer patients with a R.P. of 0.5 or higher tended to have a better survival curve. There were no marked differences in lymphocytes subsets, except that the Leu 7 level at 3 months after gastric cancer resection was significantly higher (p < 0.05) in group B than in group A. Thus, no inhibition of the anticancer effect of UFT was noted during long term combination therapy with UFT and an immunopotentiator as postoperative adjuvant therapy for patients who underwent curative resection of gastric or colorectal cancer. The results suggest that UFT combined with long-term OK-432 maintenance therapy may contribute to improve survival rates in gastric cancer patients.

Adjuvants, Immunologic↗