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Biomedical subjects

T Teramoto

Publications and source records attributed to T Teramoto.

At least 19 recordsLinked to original sources
PubMed1999

An interaction between human colon carcinoma cells and hepatocytes activates transforming growth factor-beta1 in vitro.

We established in vitro heterotypic co-cultures of a human colon carcinoma cell line, HT-29, and a human hepatocyte line, tPH5CH, using transwells to investigate possible interactions between colon carcinoma cells and hepatocytes during the metastatic process. Co-culture, but not HT-29 conditioned medium, inhibited tPH5CH cell proliferation, and this inhibition was blocked by an anti-TGF-beta1 antibody. Significantly more activated TGF-beta1 was released by co-culture than by each cell line cultured alone, whereas there were no significant differences between the total TGF-beta1 released by the individual cultured cell lines and that released by co-culture. These data indicate that an interaction between human colon carcinoma cells and hepatocytes activates TGF-beta1 in vitro.

Carcinoma↗
PubMed1999

Laparoscopic ileocecal resection for Crohn's disease associated with intestinal stenosis and ileorectal fistula.

Although a complete remission of Crohn's disease can be induced by conservative therapy, surgical treatment is often required for patients with intestinal stenosis or fistulas, for whom minimally invasive laparoscopic surgery appears to be most appropriate. We herein report on a 26-year-old patient with Crohn's disease, who presented with an ileorectal fistula and severe stenosis of the terminal ileum and thus underwent laparoscopic surgery. The ileorectal fistula was divided intracorporeally using an autostapling device. The return to full activity after laparoscopic surgery is earlier than after open surgery, and the former approach is often beneficial for some patients with Crohn's disease. This is the first report of laparoscopic surgery for Crohn's disease associated with ileorectal fistula.

Adult↗
PubMed1999

HGF-mediated apoptosis via p53/bax-independent pathway activating JNK1.

Current studies have indicated both positive and negative roles for the hepatocyte growth factor (HGF)/c-met receptor signaling system in tumor development. Recently, we have shown that HGF has the capacity to induce both growth inhibition and programmed cell death in aflatoxin-transformed (AFLB8) rat liver epithelial cells. Using the same cell line, we have now investigated a potential mechanism for HGF-induced apoptosis. Immunoblot analysis of bcl-2 gene family member (bax, bcl-2, bclX-s/l) expression showed no correlation with HGF treatment, suggesting that HGF-mediated apoptosis is bax independent. Following HGF treatment retinoblastoma protein (pRB) was present in the hypophosphorylated state. HGF treatment increased cyclin A, cyclin G1 and nuclear transcriptional factor (NFkappaB) protein expression. However, electrophoretic mobility shift analysis showed that NFkappaB activity decreased with HGF treatment. Under these apoptotic conditions, c-Jun N-terminal kinase (JNK1) and extracellular signal-regulated kinase (ERK2) were activated with lower level activation of ERK2, while no involvement of phosphatidylinositol-3 kinase was observed. Epidermal growth factor (EGF) was not protective, and actually induced cells to undergo apoptosis to a level similar to that of HGF alone or EGF/HGF in combination. These results suggest the possibility of cross-talk between HGF/c-met and EGF/EGFR signaling pathways, and the involvement of JNK1 induction in HGF-mediated apoptotic cell death.

Aflatoxins↗
PubMed1999

Preventive effect of matrix metalloproteinase inhibitor, R-94138, in combination with mitomycin C or cisplatin on peritoneal dissemination of human gastric cancer cell line TMK-1 in nude mice.

R-94138, a matrix metalloproteinase inhibitor, was examined for the ability to prevent peritoneal dissemination of a human gastric cancer xenograft, TMK-1. When the supernatant of a co-culture of TMK-1 cells and human normal fibroblast cells was subjected to gelatin zymography, it was clear that the protein expression of MMP-2 had been inhibited by R-94138. When TMK-1 was injected intraperitoneally (i.p.) into nude mice at 5 x 10(5) cells/body, the resulting peritoneal dissemination mimicked clinical carcinomatous peritonitis. When the maximum tolerated dose of mitomycin C (MMC) or cisplatin (DDP) was given 12 h after the tumor inoculation, peritoneal dissemination was completely inhibited, while the effect of R-94138 was limited when it was given i.p. at a dose of 20 mg/kg in a schedule of q.d. x 5 starting 12 h after tumor injection. MMC and DDP also suppressed peritoneal dissemination when they were administered 1 week after the tumor inoculation at a single dose of 2 and 3 mg/kg i.p., respectively. R-94138 inhibited peritoneal dissemination when it was administered i.p. at a dose of 30 mg/kg in a schedule of q.d. x 5 starting from 1 week after tumor injection. The combination of MMC and R-94138 increased the preventive effect on peritoneal dissemination. R-94138 seems to be a promising candidate to prevent peritoneal dissemination of gastric cancer.

Acetamides↗
PubMed1999

[Experimental studies on the penetration into the human stratum corneum of the dermatophyte].

We present results on the experimental penetration of Trichophyton mentagrophytes and T. rubrum under designated condition of humidity into human stratum corneum obtained from a healthy human heelregion. When mycelia were applied to the surface side of stratum corneum and then incubated at 100 % humidity, T. mentagrophytes and T. rubrum were observed in the stratum corneum on day 1 and day 1.5, respectively. At 95% humidity, T. mentagrophytes and T. rubrum penetrated on day 1.5 and day 4, and at 90% humidity, they penetrated on day 3 and day 7, respectively. At less than 85% humidity, no fungal elements of either strain were observed in stratum corneum for up to 7 days. These datasuggest that at least 90% humidity is necessary for these two fungi to penetrate into stratum corneum within a few days. However, when T. mentagrophytes was applied to the cutting side of the stratum corneum and thenincubated at more than 70% humidity, the mycelia were able to penetrate within a day. The same results were obtained when T. rubrum was applied on the cutting side and incubated at 95 and 100% humidity. T. rubrum was also able to penetrate into the stratum corneum within several days at 70 and 80% humidity. These results may indicate that not only persistent moisture but also minor injuries of stratum corneum are the most important factors in the development of tinea pedis.

Culture Techniques↗
PubMed1999

Dihydropyrimidine dehydrogenase activity and messenger RNA level may be related to the antitumor effect of 5-fluorouracil on human tumor xenografts in nude mice.

We investigated the correlation between tumor sensitivity to 5-fluorouracil (5-FU) and the enzymatic activity and mRNA levels of thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) using human tumor xenografts in nude mice. Three gastric carcinoma xenografts (SC-1-NU, St-4, and H-111), two colon carcinoma xenografts (Co-4 and Col-3-JCK), one pancreatic carcinoma xenograft (PAN-3-JCK), and one breast carcinoma xenograft (MX-1) were inoculated into nude mice. When the resultant tumors reached 100-300 mg, 5-FU was administered i.p. at a dose of 60 mg/kg in a schedule of three times every 4 days, and the antitumor activity of 5-FU was evaluated as the relative mean tumor weight in treated mice compared to control mice. Xenografts were also inoculated into untreated nude mice. When tumors weighed 200-300 mg, tumor tissues were resected for measurement of tumoral TS and DPD. TS and DPD activities were detected by the TS-binding assay and a radioenzymatic assay, respectively. mRNA levels were measured by semiquantitative reverse transcription-PCR, with glyceraldehyde-3-phosphate dehydrogenase coamplified as an internal standard. TS and DPD activities ranged from 84.7 to 775.5 fmol/mg protein and from not detectable to 79.7 pmol/min/mg protein, respectively. TS and DPD mRNA levels ranged from 0.51 to 9.90 and from not detectable to 0.93, respectively. The enzymatic activities of TS and DPD were correlated with observed mRNA levels. DPD levels were significantly correlated with 5-FU sensitivity, with high DPD activity and high DPD mRNA level resulting in low sensitivity to 5-FU. In contrast, no correlation between TS level and 5-FU sensitivity was observed. Tumoral DPD activity and DPD mRNA level may be useful indicators in predicting the antitumor activity of 5-FU.

Animals↗
PubMed1998

Single tottering mutations responsible for the neuropathic phenotype of the P-type calcium channel.

Recent genetic and molecular biological analyses have revealed many forms of inherited channelopathies. Homozygous ataxic mice, tottering (tg) and leaner (tgla) mice, have mutations in the P/Q-type Ca2+ channel alpha1A subunit gene. Although their clinical phenotypes, histological changes, and locations of gene mutations are known, it remains unclear what phenotypes the mutant Ca2+ channels manifest, or whether the altered channel properties are the primary consequence of the mutations. To address these questions, we have characterized the electrophysiological properties of Ca2+ channels in cerebellar Purkinje cells, where the P-type is the dominant Ca2+ channel, dissociated from the normal, tg, and tgla mice, and compared them with the properties of the wild-type and mutant alpha1A channels recombinantly expressed with the alpha2 and beta subunits in baby hamster kidney cells. The most striking feature of Ca2+ channel currents of mutant Purkinje cells was a marked reduction in current density, being reduced to approximately 60 and approximately 40% of control in tg and tgla mice, respectively, without changes of cell size. The Ca2+ channel currents in the tg Purkinje cells showed a relative increase in non-inactivating component in voltage-dependent inactivation. Besides the same change, those of the tgla mice showed a more distinct change in voltage dependence of activation and inactivation, being shifted in the depolarizing direction by approximately 10 mV, with a broader voltage dependence of inactivation. In the recombinant expression system, the tg channel with a missense mutation (P601L) and one form of the two possible tgla aberrant splicing products, tgla (short) channel, showed a significant reduction in current density, while the other form of the tgla channels, tgla (long), had a current density comparable to the normal control. On the other hand, the shift in voltage dependence of activation and inactivation was observed only for the tgla (long) channel. Comparison of properties of the native and recombinant mutant channels suggests that single tottering mutations are directly responsible for the neuropathic phenotypes of reduction in current density and deviations in gating behavior, which lead to neuronal death and cerebellar atrophy.

Animals↗
PubMed1998

Induction of p53 and Bax during TGF-beta 1 initiated apoptosis in rat liver epithelial cells.

The relationship between transforming growth factor-beta1 (TGF-beta1) induced growth arrest and apoptosis in rat liver derived epithelial (RLE) cells was analyzed. TGF-beta1 treatment of RLE cells induced both cell cycle arrest and apoptosis. However, pretreatment of the cells with either dexamethasone or cyclohexamide suppressed TGF-beta1 induced apoptosis, without preventing the cell cycle arrest. Both p53 and Bax were subsequently shown to be overexpressed during the TGF-beta1 induced apoptosis. Furthermore, it was revealed that cycloheximide suppressed expression of both p53 and Bax. In contrast, dexamethasone treatment prevented Bax expression alone. Treatment of RLE cells with several growth factors either alone or in combination was ineffective in counteracting TGF-beta1 induced apoptosis. In additon, we show that TGF-alpha also induced both p53 and Bax expressions and augmented TGF-beta-induced apoptosis. Thus, p53 and Bax are likely to be key factors in TGF-beta1 induced apoptosis in RLE cells.

Animals↗
PubMed1998

Silent nucleotide substitution in the sterol 27-hydroxylase gene (CYP 27) leads to alternative pre-mRNA splicing by activating a cryptic 5' splice site at the mutant codon in cerebrotendinous xanthomatosis patients.

A functionally silent nucleotide substitution of the sterol 27-hydroxylase gene (CYP 27), identified in two families with cerebrotendinous xanthomatosis (CTX), was confirmed to cause alternative pre-mRNA splicing of the gene. Full-length RT-PCR analysis of the CYP 27 gene in a patient from one of the CTX families revealed one major and an additional faint band. Sequence analysis of the cloned RT-PCR product showed three species of cDNA: 3' terminal 13 bp of exon 2 deleted cDNA, exon 2 skipped cDNA, and full-length cDNA with a functionally silent G to T mutation at codon 112 (GGG 112Gly to GGT 112Gly). Only a single base change was identified by genomic DNA sequence analysis of the CYP 27 gene in the patient: T replaced G at the third position of codon 112, 13 bp upstream from the 3' terminus of exon 2. Transfection of constructed minigenes, with or without the mutation, confirmed that this silent mutation resulted in alternative pre-mRNA splicing by activating a cryptic 5' splice site around the mutant codon. The mutation was also identified in two patients from another CTX family, with a compound heterozygous pattern of A for G substitution at codon 372, a mutation reported previously by our group. The results elucidate a novel molecular basis for the CTX and suggest the significance of a silent nucleotide substitution with regard to pre-RNA splicing.

Alternative Splicing↗
PubMed1998

Molecular basis of selective IgG2 deficiency. The mutated membrane-bound form of gamma2 heavy chain caused complete IGG2 deficiency in two Japanese siblings.

Patients with IgG2 deficiency have recurrent sinopulmonary infections caused by Pneumococcus and Hemophilus. Hereditary and selective IgG2 deficiency was suspected in two Japanese siblings whose serum IgG2 levels were under detection limits, while other serum levels of immunoglobulin subclasses were within normal ranges. Expression level of spontaneous germline Cgamma2 transcript was normal, but that of the spontaneous mature Cgamma2 transcript was greatly decreased in the patients' PBMCs, suggesting the presence of a defect at or after the class switch to Cgamma2. We sequenced the Cgamma2 gene region, and in both patients a homozygous one-base insertion (1793insG) was present in exon 4 of the Cgamma2 gene, just upstream from the alternative splice site for M exons. The mutant membrane-bound gamma2 heavy chain loses the transmembrane domain and the evolutionarily conserved cytoplasmic domain. Considering several lines of evidence showing that intact expression of the membrane-bound heavy chain is essential for a normal response of B cells and production of secreted immunoglobulin in mice, we concluded that 1793insG is responsible for selective and complete IgG2 deficiency in these two siblings. This is the first documentation of a mutation in human selective IgG2 deficiency.

Amino Acid Sequence↗
PubMed1998

Selective antitumor activity of MKT-077, a delocalized lipophilic cation, on normal cells and cancer cells in vitro.

BACKGROUND AND OBJECTIVES: 1-Ethyl-2-¿[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4-+ ++oxothiazolidin-2-ylidenemethyl¿pyridium chloride (MKT-077, formerly known as FJ776), a delocalized lipophilic cation, is known to accumulate in the mitochondria, according to the negative potential inside the mitochondria, and exert its cytotoxicity. METHODS: The single-cell suspensions of human cancer cell lines, human spleen cells, and fresh cancer specimens obtained from patients with gastric carcinoma were used for the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. RESULTS: The antitumor activity of MKT-077 was dose and concentration related, and 50% inhibitory concentrations (IC50) ranged from 1.7 to 14.3 microg/ml, with a mean +/- standard deviation (SD) of 8.4 +/- 4.6 microg/ml. The IC50 of fresh surgical spleen-cell specimens ranged from 0.34 microg/ml to >100 microg/ml in a 48 h incubation, with a mean +/- SD of 66.5 +/- 37.7 microg/ml. When the antitumor activity of MKT-077 was compared between gastric cancer cells and spleen cells obtained from the same patient, the concentration-dependent antitumor activity of this agent was obvious in the cancer cells, while no significant cytotoxicity was observed in the spleen cells. The fresh surgical specimens of gastric cancer showed higher sensitivity to MKT-077 than did spleen cells at a concentration of 30 microg/ml, with a statistically significant difference at P < 0.05. CONCLUSIONS: The selective antitumor activity of MKT-077 was confirmed using fresh surgical specimens and warrants further investigation.

Antineoplastic Agents↗
PubMed1998

Ataxia-telangiectasia in the Japanese population: identification of R1917X, W2491R, R2909G, IVS33+2T-->A, and 7883del5, the latter two being relatively common mutations.

We analyzed the data regarding six Japanese ataxia-telangiectasia (A-T) patients from four unrelated families, at the DNA level, to search for possible common mutations in the Japanese population. Among eight mutant alleles in the four families, c. 4612del165 (exon 33 skipping) was identified in two alleles, and c. 5749A to T (R1917X), c. 7471T to C (W2491R), c.7883de15, and c. 8725A to G (R2909G) were identified in one allele each. We found no mutations in the other two alleles. The IVS33 + 2T-->A mutation was identified at the genomic level as the cause of exon 33 skipping. We also identified the IVS33 + 2T-->A mutation in a Japanese patient ATL105 who was previously found to be a homozygote of c. 4612del165. W2491R and R2909G mutations were not detected in more than 100 control Japanese alleles. The latter is located in a highly conserved PI-3 kinase domain and is a completely conserved residue among ATM-related proteins. Taken together with previously documented mutations in five other Japanese A-T patients, IVS33 + 2T-->A and 7883del5 were identified in four and five alleles, respectively, in a total of 18 mutant alleles of Japanese A-T patients. These results suggest that these two mutations are relatively common mutations in the Japanese population.

Adolescent↗
PubMed1998

A new approach to dynamic graciloplasty.

The reestablishment of anal function by transposition of the gracilis muscle, combined with the implantation of electrodes and a neuromuscular stimulator (dynamic graciloplasty), has recently been developed. With this method, the transposed muscle maintains contraction by electrical stimulation to maintain neoanal pressure without fatigue. It is necessary to convert the fatigue-prone gracilis muscle to fatigue-resistant muscle by long-term electrical stimulation (conditioning). In most patients receiving dynamic graciloplasty, the conditioning is accomplished after the transposition. However, conditioning before graciloplasty should reduce the risk of ischemia in the transposed muscle after the graciloplasty and improve the outcome. This new sequence of procedures is described, in combination with J-pouch construction, in a patient who required abdominoperineal excision of the rectum for lower rectal cancer. The graciloplasty was performed after conditioning of the gracilis muscle in situ; the conditioning did not cause the patient discomfort and resulted in good anal function.

Adenocarcinoma↗
PubMed1998

Peptide N- and P/Q-type Ca2+ blockers inhibit stimulant-induced hyperactivity in mice.

omega-Conotoxin GVIA and omega-agatoxin IVA are specific peptide blockers of N- and P/Q-type calcium channel, respectively. Effects of their intracerebroventricular injection (1-3 pmol/mouse) on psychostimulant-induced hyperactivity were investigated in mice. omega-Conotoxin GVIA antagonized methylphenidate-, methamphetamine- and phencyclidine-induced hyperactivity in a dose-dependent manner. omega-Agatoxin IVA blocked methylphenidate-induced but not methamphetamine- or phencyclidine-induced hyperactivity. Neither peptides showed any effect on apomorphine-induced hyperactivity or spontaneous activity, suggesting that the inhibitory effects on psychostimulant-induced hyperactivity are not due to dopamine receptor blockage or nonspecific behavioral depression. Antagonism of calcium channels, particularly N-type, may ameliorate activation of the dopaminergic system induced by increased dopamine release.

Animals↗
PubMed1998

Serum IgE level is negatively correlated with the ability of peripheral mononuclear cells to produce interferon gamma (IFNgamma): evidence of reduced expression of IFNgamma mRNA in atopic patients.

BACKGROUND: In patients with atopic diseases such as bronchial asthma and atopic dermatitis, an elevated serum IgE level is common. Several studies showed that interleukin-4(IL-4) and interferon-gamma (IFNgamma) are important for regulation of IgE production. OBJECTIVES: The study was designed to examine the pathogenesis of an elevated serum IgE level at the production levels of TH1-type and TH2-type cytokines. METHODS: The production of interleukin-2 (IL-2), IL-4, interleukin-5 (IL-5) and IFNgamma by peripheral blood mononuclear cells (PBMCs) stimulated with phytohemagglutinin (PHA) was analysed in 20 individuals with various serum IgE levels. The amount of IFNgamma mRNA in the stimulated PBMCs was analysed using a quantitative polymerase chain reaction method. RESULTS: Cytokine production was analysed simply as a function of serum IgE level. The serum IgE level was negatively correlated with the amount of IFNgamma secreted by PBMCs (n = 20, R = -0.724, P<0.005) when logarithmically transformed data were analysed, but were not or were only weakly correlated with those of IL-4, IL-2, or IL-5 secreted by these cells (n = 20). For investigation of the cause of reduced IFNgamma production in individuals whose serum IgE level are high, the amount of IFNgamma mRNA was determined. The levels of IFNgamma mRNA expression in the stimulated PBMCs correlated well with the amount of IFNgamma secreted by the PBMCs (n = 8, R = 0.947, P < 0.001). CONCLUSIONS: Reduced IFNgamma production ability due to reduced IFNgamma mRNA expression in PBMCs is associated with an elevated serum IgE level in atopic patients.

Adolescent↗
PubMed1998

Reduced interferon gamma production by antigen-stimulated cord blood mononuclear cells is a risk factor of allergic disorders--6-year follow-up study.

BACKGROUND: It is not sufficient to predict 'high allergic risk newborns' on the basis of increased IgE concentrations of cord blood alone, because a raised cord blood IgE concentration is specific but not sensitive in the prediction of the development of allergic disorders. Warner et al. have reported that interferon gamma (IFN-gamma) production by allergen-triggered cord blood cells is a predictor of atopic eczema, based on the 1-year follow-up study. OBJECTIVE: We examined whether IFN-gamma production by antigen-stimulated cord blood mononuclear cells (CBMCs) is a risk factor of allergic disorders, based on the 6-year follow-up study. METHODS: The relationships among cord blood IgE concentrations, IFN-gamma and interleukin-2 (IL-2) productions by antigen-stimulated CBMCs, and the development of allergic disorders in 21 infants for 6 years were investigated. RESULTS: Atopic dermatitis, atopic dermatitis and allergic rhinitis, or atopic dermatitis and bronchial asthma developed in seven of 21 subjects. The maximal IFN-gamma concentration in culture supernatants of ovalbumin (OA) or bovine serum albumin (BSA) stimulated CBMCs in infants who developed allergic disorders was significantly lower (P < 0.01) than that in infants who did not develop any allergic disorders. In contrast, the maximal IL-2 concentration in culture supernatants of OA- or BSA-stimulated CBMCs in infants who developed allergic disorders was not lower than in infants who did not develop any allergic disorders. Moreover, the IFN-gamma concentrations were negatively correlated with cord blood IgE concentrations. CONCLUSION: Reduced IFN-gamma production by antigen-stimulated CBMCs is a risk factor of allergic disorders.

Antigens↗