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Biomedical subjects

T Teramoto

Publications and source records attributed to T Teramoto.

At least 145 records · Page 8Linked to original sources

Stable expression of the neuronal BI (class A) calcium channel in baby hamster kidney cells.

Plasmids containing the BI (alpha 1) cDNA with the dihydrofolate reductase (DHFR) gene, skeletal muscle alpha 2-subunit cDNA with the neo marker gene, and beta-subunit cDNA were co-transfected into baby hamster kidney (BHK) cells. BHK cells lack endogenous calcium channel activity. Twenty percent of the methotrexate (MTX) and G418 resistant clones were found to express calcium channel activity using the patch-clamp technique. A single clone, BHKBI147, demonstrated stable electrophysiological characteristics over 20 passages. Ca2+ currents of the BI channel in BHKBI147 cells were largely blocked by a specific P-type blocker, omega-AgaIVA, with an IC50 of 150 nM. Unlike the BI channel, Ca2+ currents of cardiac L-type channels expressed in BHK cells were completely blocked by the L-type antagonist, nifedipine, with an IC50 of 56 nM.

Animals↗

p53 gene abnormalities are closely related to hepatoviral infections and occur at a late stage of hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) accumulates a mutation of the p53 gene with a common substitution of nucleotide in a particular site. It is hypothesized that infection of hepatitis B virus (HBV) or exposure to aflatoxins could induce it. In Japan, the concentration of aflatoxins in the environment is low; however, infection of HBV and/or hepatitis C virus (HCV) is frequently seen in patients with HCC. The purpose of our studies was to determine whether these hepatoviral factors influence p53 alterations. In our results, p53 abnormalities, which were composed of loss of heterozygosity (LOH) and/or point mutation, were shown in 39% of patients. We postulated that they occurred at late stages in tumor growth based on the following two results. LOH analysis on p53 showed that most of the tumor nodule consisted of two phenotypes, LOH and non-LOH cancer cells. The p53 abnormalities correlated with the grade of cancer cell atypia which advanced with tumor growth. HBV and HCV infections were identified by polymerase chain reaction using DNA extracted from cancerous and noncancerous regions of the liver. By these methods, the patients who had been infected with either HBV or HCV showed an incidence of p53 abnormalities (45%) higher than those infected by neither (13%). However, the detection rate of these viruses was lower in the HCC region (33%) than that in the noncancerous region (56%) in cases with mutated p53. The low rate of HCV detection (22%) in the HCC region with altered p53 was attributable to these different viral detection rates. There was a difference in pattern of p53 mutational changes in patients depending upon whether they were infected by HBV or by HCV. Two of three HBV-infected patients had a transversional change of nucleotide at the G:C site to T:A. However, in cases with HCV, four of eight patients had a transitional change of nucleotide of p53. These results showed that HBV and HCV infections affect carcinogenic pathways causing p53 abnormalities independently.

Adolescent↗

Detection of serum IgG antibody against Helicobacter pylori from childhood in a Japanese population.

Epidemiological evidence has shown that seropositivity for Helicobacter pylori in the stomach is positively correlated with the incidence of gastric cancer. In this study, we investigated serum IgG antibody against H. pylori in asymptomatic Japanese subjects by an enzyme-linked immunoassay (ELISA) method (Serion, Wuerzburg, Germany). We noted two characteristics: (1) Seropositivity was seen in 41% of individuals aged less than 1 year, and in 9% of those aged 1-2 years, indicating the possibility that IgG antibody in infancy is derived from the mother. (2) Seropositivity was seen in 35% of individuals aged 15-19 years compared to 70% in those aged 20-24 years, indicating the spread of H. pylori infection with age.

Adolescent↗

An ultrastructural study of extracellular fibrillar components of developing mouse mandibular condyle with special reference to type VI collagen.

The localization of type VI collagen was examined from birth to 8 weeks of age. Immunohistochemical staining with anti-type VI collagen antibody was strongly positive in the hypertrophic zone and moderately positive in the fibrous zone and the outer periphery of the proliferative zone, but negative in the inner area of the proliferative zone and mature zone. After ATP treatment, type VI collagen periodic fibrils with about 80-nm intervals were frequently observed but only in the fibrous zone. They occurred mainly in the superficial area of this zone, where striated collagen fibrils were sparse, while a few were noted in the inner area, where bundles of collagen fibrils were abundant. From these distributional differences of both components, a subzonation of the fibrous zone into superficial and inner area is suggested. Moreover, with ATP treatment there were fewer type VI collagen periodic fibrils formed with increasing age (8 weeks). Testicular hyaluronidase digestion before ATP treatment facilitated the formation of periodic fibrils, in all the ages examined, in the intercellular space and around the fibroblastic cells. The interaction of type VI collagen with other components such as collagen fibrils, glycosaminoglycans or proteoglycans may play a part in maintaining the structural integrity of extracellular matrix in the mouse mandibular condyle.

Adenosine Triphosphate↗

Effect of chylomicron remnants on apolipoprotein E synthesis in HepG2 cells.

The effect of chylomicron remnants (CM-R) on apolipoprotein (apo) E synthesis by HepG2 cells was studied. The accumulation rate of apo E in the medium was increased in cells incubated with CM-R (chylo-cells) compared with that in the control cells. However, the abundance of apo E mRNA was not greater in chylo-cells than in control cells. The time course of apo E accumulation in the medium showed that apo E increased in the chylo-cells linearly up to 24 hours, whereas it increased in the control cells linearly only up to 6 hours, when it reached a plateau. The results suggest that the secretion rate of apo E was not affected by incubation with CM-R, but that uptake of the newly secreted apo E by the cells may be depressed by incubation with CM-R. Autoradiography of newly synthesized apo E showed that chylo-cells produced much more "larger" apo E than did the control cells. Two-dimensional electrophoresis of the apo E newly synthesized by the chylo-cells showed that the larger apo E was slightly acidic even after treatment with neuraminidase. Pulse-chase labeling of apo E showed that the larger apo E was secreted by both control and chylo-cells equally and that the larger apo E was converted to regular apo E in the medium more effectively in control cells than in chylo-cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins E↗

Effect of starving and refeeding on lipid metabolism in suncus.

We have previously reported that fatty liver is easily induced in a novel experimental animal, Suncus murinus (suncus) by withholding food, and that apolipoprotein B (apo B) is not actively synthesized in the liver. In the present paper we describe the effect of starving and refeeding on lipid and lipoprotein metabolism in suncus, in order to explore the mechanisms of induction of fatty liver by starving and of its improvement by refeeding. Starvation induced increase in triglyceride content and decrease in glycogen content of the liver. Although the glycogen content returned to the level before starvation at 12 h after refeeding, the triglyceride content decreased gradually but did not reach the prestarvation level even at 24 h after refeeding in suncus. Plasma lipids, glucose, and insulin levels were decreased by starvation and returned to the levels before starvation between 8 and 24 h after refeeding. On the other hand, the plasma levels of free fatty acid and ketone bodies were elevated significantly by starvation and decreased rapidly by refeeding. These responses to starvation and refeeding, except for the change in hepatic triglyceride, are in common with other experimental animals, suggesting that there are no abnormalities in glucose metabolism or in fatty acid metabolism in suncus. In conclusion, the fatty liver induced by starvation in suncus may be caused by impaired triglyceride transport out of the liver, for which apolipoprotein B is mostly responsible, as reported previously.

Animals↗

Deficiency of acyl CoA cholesterol acyl transferase activity in suncus liver.

We reported previously that apolipoprotein B is not actively secreted from suncus liver. In the present study we have investigated the hepatic cholesterol metabolism, which plays a critical role in the secretion of apo B. We found that the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in suncus liver is high and that acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity is almost absent in contrast to rats. As a result, the hepatic content of cholesterol ester, upon which apoprotein B secretion partly depends, is very low in suncus. The deficiency of ACAT activity may cause the defect in active secretion of apoprotein B-containing lipoproteins in suncus.

Animals↗

Long-term results of the anterior cervical spondylodesis.

From 1974 to 1992, anterior cervical spondylodesis was performed in 163 patients of cervical spondylotic myelopathy, cervical spondylotic radiculopathy, traumatic spinal injury, ossification of the posterior longitudinal ligament, or cervical spondylitis. Forty-five of these patients were followed for more than 4 years. To analyze the long-term results of anterior cervical spondylodesis, a radiological examination was performed in these 45 patients and magnetic resonance imaging was conducted in 41 of them. Postoperative spondylotic changes were observed radiologically in 23 (51.1%) of the 45 patients. Anterior bony spur was more frequently observed than posterior bony spur in these postoperative spondylotic changes. Postoperative canal stenosis caused by the bulging of the discs and the ligamentum flavum was frequently demonstrated with hypo- or isointense signal on T2-weighted images by magnetic resonance imaging in patients followed long term after surgery and in patients with malalignment of the cervical spine due to kyphosis of the fused vertebrae and multisegmental fusion. Neurological improvement was less in patients with bulge of the discs and the ligamentum flavum seen in magnetic resonance imaging than in patients without it. The bulge of the ligamentum flavum was histopathologically defined as hypertrophy of the ligament.

Adolescent↗

[Structure and function of apolipoproteins].

Plasma lipoproteins are macromolecular complexes that transport hydrophobic lipids, cholesteryl ester, and triglycerides, in their cores. Regulation of the plasma levels of the major lipoproteins, very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) is complex, but the rate of secretion of these lipoproteins, and their accompanying apolipoproteins, are clearly key factors in this process. Apo B is the major apolipoprotein of VLDL and LDL, and plays a key role in assembling VLDL as well as in LDL receptor mediated catabolism of LDL. Apo E is the major apolipoprotein of chylomicron remnant and mediates the recognition by remnant receptor, VLDL receptor as well as LDL receptor. Apo A-I and apo C II are well known as activators of LCAT and LPL, respectively. The purpose of this article is to summarize the current information available concerning the relationship between the structure and function of apolipoproteins.

Amino Acid Sequence↗

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

We investigated the utility of intraoperative peritoneal lavage smears and gastric wall brushing smears for diagnosis of peritoneal dissemination and serosal involvement during gastric cancer surgery. One hundred fifty-three patients with gastric cancer were examined; 138 who underwent gastric resection and 15 who did not. The incidence of cancer cell positivity determined by these methods was 8.0% in resected cases, and 80.0% in unresected cases. According to macroscopic serosal invasion, the incidence of positive cytology was 0% for S0, 15.4% for S1, 13.0% for S2, and 38.7% for S3. According to microscopic wall invasion, the incidence of positivity was 0% for m and sm, 6.3% for mp, 0% for ss, and 22.2% for se and si. In terms of macroscopic peritoneal dissemination, the incidence of positivity was 2.6% for P0, 28.6% for P1, 42.9% for P2, and 90.0% for P3. These results suggest that peritoneal lavage smears and gastric wall brushing smears are useful for predicting the spread of peritoneal dissemination. Thus, further study of intraoperative fast-smear cytology seems warranted.

Gastrectomy↗

[Treatment for peritoneal dissemination of gastric cancer by intraperitoneal administration of CDDP through Infuse-a-Port].

This report describes the effect of intraperitoneal administration of CDDP for the treatment of peritoneal dissemination (P) in 20 patients with gastric cancer. Eight patients after palliative resection, 4 after non-resection and 8 with recurrent cancer were given 25 mg of CDDP through a reservoir (Infuse-A-Port) implanted in the abdominal wall once a week. Simultaneously, 400 mg/body/day of UFT and 2 mg/body/week of Lentinan were administered. Twelve of the patients died of disease at 6-19 months (median 7 months), but 8 have survived 3 to 15 months (median 6 months). Complete and partial responses were obtained in 7 of the 8 patients with recurrence (88%) for malignant ascites. No patient showed any toxicity from treatment. All patients receive the treatment in the outpatient clinic after discharge, and 17 patients have shown a long hospital-free survival.

Administration, Oral↗

Omega-agatoxin-TK containing D-serine at position 46, but not synthetic omega-[L-Ser46]agatoxin-TK, exerts blockade of P-type calcium channels in cerebellar Purkinje neurons.

omega-Agatoxin-TK (omega-Aga-TK), a 48-amino-acid peptide isolated from the venom of the funnel web spider (Agelenopsis aperta), is a selective and potent inhibitor of P-type calcium channels in the nervous system. We have synthesized a peptide that has the amino acid sequence identified for native omega-Aga-TK. The synthetic omega-Aga-TK, however, showed 80-90-fold less potent inhibition of P-type calcium channels, compared with native omega-Aga-TK. Enantiomer analysis of native omega-Aga-TK revealed D-serine at position 46, and synthetic omega-[D-Ser46]Aga-TK had the same potency as native omega-Aga-TK for blocking P-type calcium channels in cultured cerebellar Purkinje neurons. Two peptide fragments of omega-Aga-TK, namely omega-Aga-TK(1-43) and the carboxyl-terminal peptide fragment omega-Aga-TK(44-48), did not produce any significant inhibition of P-type calcium channels or interfere with the blockade of the channels elicited by native omega-Aga-TK. Molecular dynamics calculations showed that the carboxyl-terminal, six-amino-acid peptide of omega-Aga-TK containing D-Ser46 assumes a different conformation than does the peptide containing L-Ser46. These results suggest that the specific conformation of the carboxyl-terminal region of omega-Aga-TK, particularly the configuration of Ser46, together with a beta-sheet structure formed by four disulfide bonds, might be essential for blockade of P-type calcium channels.

Agatoxins↗

Reconstruction of anal function by transposed gracilis muscle with electrical stimulation: rabbit model.

For the reconstruction of anal function for fecally incontinent patients, it could be practicable to transpose the gracilis muscle around the anal canal, with electrical stimulation to maintain contraction. It is necessary to keep continuous tonus, so tetanic contraction or "summation" would be essential for fecal continence, with a stimulation which permits prolonged contraction. Transposition of the gracilis muscle around the rectum was performed in thirteen Japanese white male rabbits. The muscles of the conditioning group (n = 8) were stimulated at 10 Hz for 6 weeks before the procedure. By stimulation at 15 Hz, a low frequency to permit prolonged contraction, the neoanal pressure increased maximally to 134.2 +/- 55.6 cmH2O (mean +/- s.d.) in the conditioning group, and to 115.0 +/- 37.1 cmH2O in the non-conditioning group (n = 5) (N.S.). But, the basal pressure with stimulation rose 82.3 +/- 12.4% (mean +/- s.d.) of the increase in the conditioning group, while that of the non-conditioning group remained at resting pressure (p < 0.001). The conditioning made it possible for the rabbit's gracilis muscle to create anal pressure with a sufficient rise in the basal pressure at a frequency permitting prolonged contraction.

Anal Canal↗

[Carbohydrate and lipid metabolism in liver cirrhosis].

The liver is of prime importance in carbohydrate and lipid metabolism. Thirty to 60% of the ingested carbohydrates are taken up by the liver, and stored as glycogen. In the fasted state, the liver releases glucose by glycogenolysis and gluconeogenesis. The liver, therefore, acts as a "buffering organ' in carbohydrate metabolism to keep the blood glucose level in a physiological state. In liver cirrhosis, abnormality in carbohydrate metabolism is commonly observed, characterized by hyperinsulinemia and insulin resistance. The liver produces cholesterol, triglyceride, and phospholipid, secretes and uptakes lipoproteins, and discharges cholesterol in the form of bile. In addition, the liver produces important enzymes for lipoprotein metabolism. In consequence, many typical,. features are observed in lipid metabolism in hepatic diseases.

Carbohydrate Metabolism↗

A novel peptide from funnel web spider venom, omega-Aga-TK, selectively blocks, P-type calcium channels.

In the course of purification of omega-Aga-IVA, a specific P-type calcium channel blocker, from the venom of Agelenopsis aperta we discovered a novel peptide. This peptide, named omega-agatoxin Tsukuba (omega-Aga-TK), also blocked P-type channels and was twelve times more abundant in the venom than omega-Aga-IVA. omega-Aga-TK was purified to homogeneity by a two-step reverse-phase HPLC procedure. Its amino acid sequence is 71% identical to that of omega-Aga-IVA. omega-Aga-TK has a negatively charged N-terminus, whereas omega-Aga-IVA has a positively charged one. Electrophysiological data indicate that omega-Aga-TK is a potent and selective inhibitor of P-type channels.

Agatoxins↗