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T Teramoto

Publications and source records attributed to T Teramoto.

At least 127 records · Page 7Linked to original sources

Two types of calcium channels sensitive to omega-agatoxin- TK in cultured rat hippocampal neurones.

We characterized the electrophysiological properties of calcium channels in cultured rat hippocampal neurones using omega-agatoxin-TK (omega-Aga-TK) and compared them with those of the P-type channel and the BI (alpha 1A) channel which resembles the Q-type channel. Two types of omega-Aga-TK-sensitive calcium channels were detected in hippocampal neurones. The first type showed slow inactivation, high sensitivity to omega-Aga-TK and low reversibility from omega-Aga-TK-induced block, resembling the P-type channel. The second type showed fast inactivation, low sensitivity to omega-Aga-TK and high reversibility from omega-Aga-TK-induced block. These results suggest that the second type of calcium channel (Q-type-like) plays a prominent role in the hippocampal synaptic transmission.

Agatoxins↗

Isolation and characterization of a peptide isomerase from funnel web spider venom.

A novel peptide isomerase was purified from the venom of funnel web spider, Agelenopsis aperta. The complete primary structure of the isomerase has been established by sequence analyses of polypeptide chains, assignments of disulfide bridges, carbohydrate analyses, and mass spectrometry of sugar chains. The isomerase was found to be a 29-kDa polypeptide that consists of an 18-residue light chain and a 243-residue heavy chain connected by a single disulfide bridge. The heavy chain contains three intramolecular disulfide bridges and one N-linked oligosaccharide chain with a simple trimannosyl core structure. A sequence homology search showed a significant similarity of the enzyme with serine proteases, particularly around a putative catalytic triad of the isomerase. The isomerase specifically interconverts the configuration of Ser46 of a 48-amino-acid peptide, omega-agatoxin-TK, and the conversion rate from L-Ser to D-Ser was approximately two times faster than the reverse reaction.

Amino Acid Isomerases↗

Clinical efficacy of fluvastatin for hyperlipidemia in Japanese patients.

The objective of the study was to evaluate the efficacy and safety of fluvastatin in patients with hypercholesterolemia, including heterozygous familial hypercholesterolemia, in a 1-year study (a 12-week open assessment, followed by 40 weeks of active treatment). Of the 337 patients enrolled in the study, the effects of fluvastatin were analyzed in 296 patients at baseline and at 12 weeks. Of these, 265 were receiving 20 mg/day fluvastatin at week 12 and in 20 patients the dose had been increased to 30 mg/day; 11 patients violated the dosing protocol. A total of 229 patients continued into the 40-week, long-term phase, and 212 patients were analyzed at baseline and after 24 and 52 weeks. At the end of treatment, 153 evaluable patients were still taking 20 mg/day fluvastatin, 1 was taking 10 mg/day, and 48 patients were taking 30 mg/day, and 10 were taking 40 mg/day. In the 20 mg/day fluvastatin group, low density lipoprotein cholesterol (LDL-C) levels decreased by 24.1% at week 12 and by 29.3% at week 52. In those patients requiring the higher doses, the corresponding reductions in LDL-C were 20.2% (week 12) and 26.7% (week 52). Total cholesterol was also reduced at week 12 by 17.0% (20 mg/day) and 15.7% (20-30 mg/day), and at week 52 by 20.4% (< or = 20 mg/day) and 19.2% (> or = 30 mg/day). Throughout the study, fluvastatin was generally well tolerated and no serious clinical adverse events were observed. In conclusion, long-term treatment of hypercholesterolemia with fluvastatin at dosages of 20-40 mg daily can be considered both safe and effective.

Anticholesteremic Agents↗

Alteration of expression in integrin beta 1-subunit correlates with invasion and metastasis in colorectal cancer.

We have investigated the expression of the integrin beta 1 subunit in 51 colorectal cancer tissues using immunoblotting and have determined the relationship between expression and clinical stage. In comparison with normal mucosa the pre-beta-subunit (the precursor of beta 1-subunit) was increased in 15 cases and decreased in two cases, and expression of the beta 1-subunit was decreased in two cases. These alterations of expression of the beta 1-subunit were significantly correlated with lymph node metastasis and depth of invasion (P < 0.01). These results suggest that integrin plays an important role in the invasion and metastasis of colorectal cancer.

Colorectal Neoplasms↗

Expression of sialyl Lewis(a) as a new prognostic factor for patients with advanced colorectal carcinoma.

BACKGROUND: Sialyl Lewis(a) antigen (SLA) is considered to be a cancer-associated carbohydrate antigen. METHODS: A total of 309 surgically resected primary colorectal cancer specimens and 501 associated metastases to regional lymph nodes were analyzed immunohistochemically using a monoclonal antibody (NS19-9) recognizing SLA. The specimens were obtained from 1981 to 1988 at the Department of Surgery, Keio University School of Medicine (Tokyo, Japan). RESULTS: Sialyl Lewis(a) antigen expression was detected in 75.4% (233/309) of the primary tumors and in 78.5% (99/126) of the metastases to regional lymph nodes. Significantly stronger expression was noted in the regional lymph node metastases than in the primary lesions (P = 4.5E-7). Sialyl Lewis(a) antigen expression in the primary tumors correlated significantly with regional lymph node metastasis (P < 0.005), recurrence (P < 0.005), and postoperative survival (P < 0.001) as determined by univariate analysis. Sialyl Lewis(a) antigen expression in the regional lymph node metastases also correlated strongly with recurrence (P < 0.005) and survival (P < 0.01). As determined by multivariate analysis, SLA expression in the primary tumor correlated strongly with recurrence (P = 3.0E-6) and survival (P = 6.9E-3). CONCLUSIONS: Sialyl Lewis(a) antigen expression in primary tumors and metastases to regional lymph nodes is a useful marker for evaluating tumor aggressiveness and prognosis in patients with advanced colorectal cancer.

Aged↗

K-ras gene mutations in early colorectal cancer ... flat elevated vs polyp-forming cancer....

K-ras gene mutations in early colorectal cancer were detected by two-step sensitive polymerase chain reaction (PCR) and enzyme digestion method. Early colorectal cancer was classified into flat elevated cancer or polyp-forming cancer according to morphology and presence of adenomatous components. A total of 60 paraffin-embedded tissue specimens from patients with early colorectal cancer were analysed. K-ras codon 12 mutations were detected in 23.3% (7/30) of flat elevated cancer and 63.3% (19/30) of polyp-forming cancer. The incidence of K-ras codon 12 mutations in flat elevated cancer was significantly lower than in polyp-forming cancer (P < 0.01). These data suggested that K-ras gene mutations may be correlated with morphology or clinical features in flat elevated cancer, and that flat elevated cancer may originate from a pathway different from adenoma-carcinoma sequence.

Base Sequence↗

Clinical significance of epidermal growth factor (EGF), EGF receptor, and c-erbB-2 in human gastric cancer.

The EGF stimulation system for growth regulation is implicated in normal and neoplastic cell proliferation. The role of EGF, the EGF receptor, and c-erbB-2 in human gastric cancer is reviewed on the basis of several reports, which have been mainly oriented toward their clinical significance. EGF has been shown immunohistochemically to be present in 26% of gastric cancers (n = 395). The presence of EGF in gastric cancer is correlated with the degree of gastric wall invasion and lymph node metastasis. The 5-year survival of patients with EGF-positive tumors is worse than that of patients with EGF-negative tumors. The presence of EGF in human gastric cancer may therefore represent a higher malignant potential. Fifteen percent of gastric cancers (n = 352) were also shown to be positive for both EGF and the EGF receptor immunohistochemically, and the simultaneous occurrence of EGF and the EGF receptor suggests that these tumors grow in an autocrine fashion. Tumors exhibiting EGF and the EGF receptor simultaneously show a greater degree of local invasion and lymph node metastasis. Increased expression of EGF receptor protein in gastric cancer appears to be related to biologic aggressiveness, although gene amplification has occurred only to a small extent. Twelve percent of gastric cancers (n = 486) were found to be positive for c-erbB-2. This type of tumor has a frequent metastasis, and patients with c-erbB-2-positive cancer have a poorer prognosis than those with c-erbB-2-negative tumors. Selective blockade of the EGF receptor and c-erbB-2 from their ligands with monoclonal antibodies (MoAbs) inhibits the growth of human gastric cancer xenografts. These MoAbs may therefore be effective antitumor agents against gastric cancer showing overexpression of EGF receptors or c-erbB-2.

Epidermal Growth Factor↗

p53 gene mutations in early colorectal carcinoma. De novo vs. adenoma-carcinoma sequence.

p53 gene mutations in early and advanced colorectal cancer were detected by PCR-SSCP analysis. Early colorectal cancer was classified into de novo cancer and polyp-forming cancer, respectively, according to morphology and presence of adenomatous components. A total of 94 paraffin-embedded tissue specimens from patients with colorectal cancer were analysed. p53 gene mutations were detected in 40.0% (12/30) of de novo cancer, 36.7% (11/30) of polyp-forming cancer, and 44% (15/34) of advanced cancer. p53 mutations were detected at a high frequency in both types of early colorectal cancer as well as in advanced cancer. No correlations were found between p53 mutations and clinicopathological data. Our data suggest that the p53 gene mutations occurred in the early colorectal cancer stage of carcinogenesis regardless of the pathway.

Adenoma↗

Conversion of the rabbit gracilis muscle for transposition as a neoanal sphincter by electrical stimulation.

To re-establish anal function in fecally incontinent patients it may be feasible to transpose the gracilis muscle around the anal canal, using electrical stimulation to trigger contraction. However, because the fast-twitching gracilis muscle is incapable of prolonged contraction without fatigue, it is necessary to convert it to a slow-twitching, fatigue-resistant muscle. We demonstrated this conversion by longterm electrical stimulation at low frequencies using a rabbit model. The nerve to the gracilis muscle was continuously stimulated at 2 Hz, 5 Hz, and 10 Hz for 2, 4, or 6 weeks. In the 6-week conditioning group, the percentage of type I fibers, identified by ATPase staining, increased as the conditioning frequency became higher, but the twitch contraction speed reduced with conditioning at a frequency of more than 5 Hz. The fatigue resistance improved by conditioning at 10 Hz, and conversion occurred in 6 weeks. Thus, we concluded that conditioning at 10 Hz for 6 weeks can convert rabbit gracilis muscle to a slow-twitching, fatigue-resistant muscle suitable for use as a neoanal sphincter.

Anal Canal↗

Type VI collagen periodic fibrils in the synovium of the mouse temporomandibular joint.

Immunohistochemical staining with anti-type VI collagen antibody was strongly positive in the intimal layer and moderately positive in the subsynovium. After treatment with 20 mM ATP, numerous structures with a periodicity of 100 +/- 10 nm (type VI collagen fibrils) appeared around the synovial cells. As the periodic dark bands were stained by ruthenium red, proteoglycan(s) or glycosaminoglycan(s) were probably associated with the type VI collagen fibrils. When the tissue was digested with testicular hyaluronidase before ATP treatment, the periodic fibrils were not found, and only a filamentous network of 100-nm interval was seen around the cells. Thus, type VI collagen is abundant in the synovium of the mouse mandibular joint and is associated with proteoglycans or glycosaminoglycans, which might have a role in its formation.

Animals↗

Dual modulation by l-leucovorin and recombinant human interferon alpha 2a of 5-fluorouracil antitumor activity against the human colon carcinoma xenograft Co-4.

We investigated the dual modulation by l-leucovorin (LV) and recombinant human interferon-alpha 2a (IFN-alpha 2a) of 5-fluorouracil (5-FU) antitumor activity against human colon carcinoma cells (Co-4) using a nude mouse system. 5-FU was administered intraperitoneally (IP) at 10 or 90 mg/kg. 5-FU (10 mg/kg) was administered daily for 10 days, and 90 mg/kg was administered once. LV was administered IP 1 and 0 h before 5-FU treatment at 200 mg/kg. IFN-alpha 2a was administered subcutaneously (SC) daily for 14 days at 60,000 IU/mouse. When 5-FU was administered at 10 or 90 mg/kg with these two modulators, the antitumor effect was increased significantly, with T/C ratios of 18.1 and 6.1, respectively. These modulatory effects were assessed as synergistic, without associated severe side effects or death during the experimental period. LV augmented the antitumor activity of 5-FU through increment of thymidylate synthetase (TS) inhibition, and IFN-alpha 2a showed a modulatory effect in elevating the intratumoral concentration of fluorouridine without change in TS inhibition. These results suggest that 5-FU antitumor activity against human colon carcinoma could be significantly potentiated without severe side effects by these two modulators, which possess different modes of action.

Animals↗

Defect in assembly process of very-low-density lipoprotein in suncus liver: an animal model of fatty liver.

We previously showed that fatty liver was easily induced in suncus by starvation and that the plasma level of apolipoprotein B (apo B) was very low. There are three possible explanations for the low level of apo B in the animals: low synthetic rate, low secretion rate, and rapid catabolism in the circulation of apo B. We measured post-heparin lipolytic activity (lipoprotein lipase activity), which plays a key role in the catabolism of apo B-containing lipoprotein, VLDL, and found no difference between rats and suncus. We also investigated the hepatic synthetic rate of apo B by liver perfusion studies. Newly synthesized apo B in the suncus liver was detected by immunoprecipitation and found to amount to 12.5% of that in rats. The secretion rate of VLDL in suncus, which was estimated by intravenous injection of Triton WR1339, was 13.8% of that in rats. These two results suggest that there is no major defect in the secretory process. We separated Golgi apparatus from rat and suncus livers, and found much fewer lipoprotein particles in suncus than in rat Golgi apparatus. This evidence suggests that there is no defect in the lipolytic process or hepatic secretory process of apo B-containing lipoprotein, VLDL, but there may be a defect in the assembly process of VLDL and/or in the synthetic process of apo B in suncus. Such a defect may be one of the reasons for starvation-induced fatty liver in suncus.

Animals↗

Role of acyl coenzyme A cholesterol acyltransferase in intrahepatic processing of apo B-lipoprotein in suncus.

We have previously shown that fatty liver was easily induced in suncus by starvation and that the plasma level of apolipoprotein B (apoB) was very low. We also previously reported that a defect in the assembling process of apo B-containing lipoprotein (very low density lipoprotein, VLDL) may be one of the reasons for the low level of plasma apo B and for induction of fatty liver by starvation in suncus. We also found that hepatic acyl coenzyme A cholesterol acyltransferase (ACAT) activity is very low in the animals, resulting in decreased cholesteryl ester contents in the liver. A deficiency of cholesteryl ester in suncus liver may be one of the reasons for the defect in the assembling process of VLDL. In this study, we investigated the effect of cholesterol-feeding, which induces an increase in triglyceride and cholesteryl ester of the liver as a consequence of the induction of both intestinal and hepatic ACAT activities, on the secretion of VLDL. Although the basal ACAT activity of intestinal mucosa was high, cholesterol-feeding did not induce either an increase in plasma lipid or an increase in intestinal ACAT activities in suncus. The hepatic secretion rate of VLDL was estimated by treatment with Triton WR1339, which is well known to inhibit the catabolism of VLDL. Cholesterol-feeding caused a slight increase in hepatic triglyceride and cholesteryl ester but no increase either in the secretion rate of VLDL or in hepatic ACAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunohistochemical and biochemical detection of low density lipoprotein receptors in cultured rat mesangial cells.

The expression of low density lipoprotein (LDL) receptors by cultured rat mesangial cells was demonstrated using immunohistochemical and biochemical methods. Using a mouse monoclonal anti-human LDL receptor antibody, the immunofluorescence technique was applied to cultured mesangial cells and showed granular staining. Immunoblotting analysis of the membrane fraction of cultured mesangial cells showed a single band with a protein of approximately 130,000 molecular weight. In addition, [125I]LDL binding and the uptake of [125I]LDL by cultured mesangial cells were studied. Binding and uptake both reached an equilibrium after about 30 min of incubation. A 50% reduction in [125I]LDL (20 micrograms protein/ml) binding and uptake occurred when unlabelled LDL was added to cultures at 20-40 micrograms protein/ml. Addition of high density lipoprotein without apoE to the culture medium did not induce competitive inhibition of [125I]LDL binding and uptake by mesangial cells. These findings suggest that cultured mesangial cells have the capacity to express an LDL receptor that regulates the cellular uptake of LDL.

Animals↗

[Prognostic evaluation of peritoneal lavage smears and gastric wall brushing smears in gastric cancer surgery].

We investigated the correlation of intraoperative peritoneal lavage smear and gastric wall brushing smear cytology with macroscopic and histologic findings and prognosis, in 216 patients with gastric cancer. Some 196 of these patients underwent gastric resection and 20 did not. The incidence of positive cancer cells determined by these methods was significantly correlated with gastric resection, tumor invasion, and peritoneal dissemination. Among patients without macroscopic peritoneal dissemination, four were found to have positive peritoneal lavage smears or gastric wall brushing smears, respectively. The prognosis of these patients did not differ from that of patients with metastases to the adjacent peritoneum but not the distant peritoneum. These results suggest that peritoneal lavage smears and gastric wall brushing smears are useful for predicting the peritoneal cancer dissemination. Therefore we intend to target patients with no peritoneal metastases (Po) showing positive peritoneal cytology for intensive treatment.

Female↗

[Study of hepatocellular carcinoma type C by quantitation of serum HCV-RNA using branched DNA probe assay].

Serum HCV-RNA levels were determined by newly developed branched DNA probe (bDNA) assay in 87 patients with hepatocellular carcinoma (HCC), compared with 73 patients with chronic hepatitis active and 30 patients with liver cirrhosis. Patients with decompensated liver cirrhosis (LC-d) had a significant lower viremia (mean 3.2Meg.eq./ml, bDNA positive rate; 40%) than chronic hepatitis active (18.0; 64%) and compensated LC (LC-c, 17.9; 80%) (p < 0.05). Those data indicates that HCV replication may decrease as progression of LC. In contrast, there was no difference between the levels of HCC with LC-c (8.2; 85%) and LC-d (6.1; 89%), and their positive rate of bDNA assay were significantly higher than LC-d without HCC (p < 0.01). Therefore, patients undergoing LC in whom serum HCV-RNA sustained high level may correspond to the high risk group of HCC. In HCC of heavy drinker, serum HCV-RNA levels (11.3; 91%) were significantly higher than the levels (4.6; 79%) of HCC without heavy drink (p < 0.05). The result indicates that heavy drink may induced an increase in HCV replication.

Carcinoma, Hepatocellular↗

[Chylomicron].

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Chylomicrons↗