Biomedical subjects

T Teramoto

Publications and source records attributed to T Teramoto.

At least 271 records · Page 15Linked to original sources

PubMedDate not supplied

Reduced interferon-gamma production and mutations of the interleukin-12 receptor beta(2) chain gene in atopic subjects.

BACKGROUND: The atopic patient has a predisposition to selective synthesis of IgE antibodies to common environmental antigens. IgE production is upregulated by interleukin-4 (IL-4) and downregulated by interferon-gamma (IFN-gamma). IL-12 is a cytokine that induces IFN-gamma production. The signal of IL-12 is transduced through the IL-12 receptor (IL-12R) and Stat4. METHODS: We examined IFN-gamma production in peripheral blood mononuclear cells (PBMCs) following stimulation with IL-12 or phytohemagglutinin (PHA) in healthy controls and atopic patients. Moreover, sequences of the IL-12R beta(2) chain gene were analyzed. RESULTS: The serum IgE levels were negatively correlated (p < 0.001) with IFN-gamma production. In 24 out of 75 atopic patients, IFN-gamma production in PBMCs following stimulation with IL-12 was under the detection limit, but PHA stimulation elicited detectable IFN-gamma production. Sequence analysis of the cDNA of IL-12R beta(2) revealed three kinds of distinct genetic mutations (2496 del 91, 1577 A to G and 2799 A to G) in 10 unrelated subjects of the 24 whose IFN-gamma production following IL-12 stimulation was under the detection limit. PBMCs cultured with IL-12 and PHA in these 10 subjects showed decreased tyrosine phosphorylation of Stat4. CONCLUSIONS: The results of our study indicate that atopic diseases are caused, in part, by impairment of the IL-12 signal cascade, which downregulates IgE production, and that the mutation of the IL-12R beta(2) chain gene is one of the causative genes for atopy.

Cells, Cultured↗

PubMedDate not supplied

The effects of combination therapy with niceritrol and pravastatin on hyperlipidaemia.

In the present study, we evaluated the effects of combination therapy with niceritrol and pravastatin in patients with hyperlipidaemia. A total of 62 patients with hyperlipidaemia, defined as total cholesterol levels above 220 mg/dl or triglyceride levels above 150 mg/dl, were recruited. Patients were divided into two groups: Group N received initial therapy with niceritrol 750-1500 mg/day, and those in Group P, pravastatin 10 mg/day. After 8 weeks, pravastatin 10 mg/day was added to the Group N treatment regimen for a further 8 weeks, while patients in Group P were given niceritrol 750-1500 mg/day in addition to pravastatin for 8 weeks. After the 8-week combination therapy study period, total cholesterol levels were 209.6 mg/dl in Group N and 220.7 mg/dl in Group P. Decreased triglyceride and lipoprotein(a) levels and increased high-density lipoprotein cholesterol levels, neither of which were achieved by pravastatin administration alone, were achieved with the combination of pravastatin and niceritrol. We conclude that when a single lipid-lowering drug fails to show therapeutic value, attempting combination therapy with a nicotinic acid preparation and a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) is worthwhile.

Cholesterol↗

PubMedDate not supplied

Interferon gamma increases the antitumor activity of mitomycin C against human colon cancer cells in vitro and in vivo.

A combined antitumor activity of mitomycin C (MMC) and interferon gamma-1a (IFN-gamma) was evaluated to be synergistic by the 3-(4, 5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide assay and human tumor xenografts/severe combined immunodeficient (SCID) mouse system using colon cancer cell lines. The experimental metastasis of WiDr cells in SCID mouse was inhibited by MMC and IFN-gamma with their synergism. Intracellular uptake of MMC in WiDr cells in vitro was significantly increased by IFN-gamma, suggesting the mode of synergism of these agents. This model may also partly explain the antitumor activity of combined MMC, 5-fluorouracil and interleukin-2 treatment on hepatic metastasis of colon cancer.

Animals↗

PubMedDate not supplied

Combined antitumour activity of mitomycin C, 5-fluorouracil and interleukin-2 against human colon cancer cells.

Combined treatment of interleukin-2 (IL-2), 5-fluorouracil (5-FU) and mitomycin C (MMC) is reported to be effective against hepatic metastasis of colon carcinoma. To clarify this modality, we investigated lymphokine activated killer (LAK) activity of human peripheral lymphocytes on colon cancer cell lines by 51Cr release assay. LAK activity against Colo 205 cells by untreated lymphocytes was 12%, which increased to 25% upon the addition of 5-FU, but remained unchanged upon the addition of MMC. The combined antitumour activity of MMC or 5-FU with or without LAK-supernatant was evaluated by MTT assay; antitumour activity of MMC was increased by the addition of LAK-supernatant. The concentration of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) was increased in LAK-supernatant, and the antitumour activity of combined IFN-gamma and MMC was synergistic. The mechanism of this therapy seemed to be associated with both increased LAK activity by 5-FU and increased antitumour activity of MMC with IFN-gamma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Chemosensitivity test is useful in evaluating the appropriate adjuvant cancer chemotherapy for stage III non-scirrhous and scirrhous gastric cancers.

A total of 183 cases with gastric cancer was retrospectively analyzed in terms of their chemosensitivity as determined by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay and their survival rates after surgery. After the patients were stratified into scirrhous or non-scirrhous carcinoma groups, they were tested for stage III or IV gastric cancer. In these four cohorts, the patients were categorized into sensitive and insensitive groups determined by the MTT assay. The sensitive group was treated with at least one drug that had been shown to be effective in the MTT assay, and the insensitive group was given a drug that had been shown to be ineffective in the MTT assay. In stage III gastric cancer, the sensitive group showed a favorable survival compared to the insensitive group in scirrhous and non-scirrhous carcinoma, while this difference was diminished in stage IV gastric cancer. There were no survival benefits in the sensitive group in stage III gastric cancer, when they were not treated with adjuvant cancer chemotherapy. These results suggested that MTT assay would be useful in evaluating the appropriate adjuvant cancer chemotherapy for stage III scirrhous and non-scirrhous gastric cancer.

Adenocarcinoma, Scirrhous↗

PubMedDate not supplied

Time-course study of the levels of urinary leukotriene E4, serum thromboxane B2 and serum eosinophil cationic protein in spontaneous asthma attacks in five children.

Leukotrienes thromboxanes, and eosinophil cationic protein (ECP) are chemical mediators involved in airway inflammation. We investigated time courses of urinary leukotriene E4 (LTE4), serum thromboxane B2 (TXB2) and serum ECP, together with blood eosinophil count during asthmatic attacks in five children. Just after the onset of an asthma attack, urinary LTE4 levels reflected the severity of the attack and decreased during the course of clinical improvement with various therapies; however, they did not change in the course of an attack in one of five patients. The other parameters showed less or no significant relation to clinical severity and improvements. Since LTE4 is a stable product from total cysteinyl leukotrienes, it appears to be one of important mediators in most asthma attacks in children. This study suggests that LTE4 is a useful marker for monitoring severity and improvement of spontaneous attacks of asthma.

Antibody Specificity↗

PubMedDate not supplied

Thymidylate synthetase and dihydropyrimidine dehydrogenase levels in gastric cancer.

The measurement of thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) enzymatic activities and mRNA levels in tumors may be useful in predicting tumor sensitivity to 5-fluorouracil (5-FU). Forty-one patients with advanced gastric cancer gave informed consent and were enrolled in this study. Biopsy specimens of gastric cancer were obtained preoperatively through gastrofiberscopy and used to determine TS and DPD mRNA levels. We also measured TS and DPD enzymatic activities and mRNA levels in surgically resected gastric cancer samples, as well as in adjacent normal gastric mucosa. TS and DPD activities were measured using the TS-binding assay and a radioenzymatic assay, respectively, while mRNA levels were measured by semi-quantitative reverse transcription-PCR (RT-PCR) co-amplified with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard. In resected tumor specimens, TS and DPD activities ranged from 7.1 to 176.6 fmol/mg protein and from 3.6 to 99.8 pmol/min/mg protein, respectively, while TS and DPD mRNA levels ranged from 0.50 to 21.12 and from 0.014 to 7:22, respectively. There were no significant correlations between TS/DPD levels and other clinicopathological factors, except for low DPD mRNA levels in undifferentiated carcinoma. Both TS activity and mRNA levels were significantly higher in tumor tissues compared to normal adjacent mucosa. In contrast, there was no significant difference between tumoral and non-tumoral DPD activity, although tumor tissue showed significantly lower DPD mRNA levels than non-tumoral tissue. High tumoral TS mRNA levels in preoperative biopsy specimens from patients with stage III/IV was associated with poor survival outcome after surgery compared with patients with low tumoral TS mRNA levels. In contrast, DPD levels had no influence on prognosis. We conclude that high tumoral TS levels and low tumoral DPD mRNA may indicate the selective cytotoxicity of 5-FU on gastric cancer, and that tumoral TS mRNA levels may be a prognostic factor for patients with stage III/IV gastric cancer.

Aged↗

PubMedDate not supplied

Immunoblot analysis for laboratory diagnosis of ataxia-telangiectasia: use of Epstein-Barr virus-transformed or phytohemagglutinin-stimulated lymphoblasts for detection of ATM protein.

Ataxia-telangiectasia (A-T) is a genetic disorder characterized by a progressive ataxia, immunodeficiency, neurological abnormalities, hypersensitivity to ionizing radiation, and predisposition to cancer. The gene responsible for A-T (ATM) has been cloned and shown to code for a 350 kDa polypeptide containing 3,056 amino acid residues. Detection of ATM mutations for laboratory diagnosis of A-T is laborious and not practical, unless there are common mutations in a population. We describe here immunoblot analysis for the detection of ATM in seven Japanese A-T patients from five families and in controls using ATM3BA antibody. ATM protein was routinely and clearly detected in Epstein-Barr virus (EBV)-transformed or phytohemagglutinin (PHA)-stimulated lymphoblasts from controls. However, it could not be detected consistently in unstimulated peripheral blood mononuclear cells (PBMCs) from controls. We also detected ATM protein in control fibroblasts, but the background was relatively higher than in control lymphoblasts. ATM protein was not detected or dramatically decreased in EBV-transformed lymphoblasts from all seven patients tested and in fibroblasts from one patient. Immunoblot analysis using EBV-transformed or PHA-stimulated lymphoblasts represents a useful approach for laboratory diagnosis for A-T. The latter is especially preferable since it takes only 3 days to obtain sufficient cells for analysis.

Adult↗

PubMedDate not supplied

Orthotopic reconstitution of human small-cell lung carcinoma after intravenous transplantation in SCID mice.

We have constructed an orthotopically reconstituted model of human small-cell lung carcinoma (SCLC) by intravenous transplantation in severe combined immunodeficient (SCID) mice. Two human SCLC xenografts, H-69 and Lu-130, were disaggregated and injected through the tail vein of SCID mice. Human SCLCs were orthotopically reconstituted with multi-focal lung tumor growth in all SCID mice after intravenous injection of 5 x 10(6) tumor cells per mouse. The heart and liver were also seeded with actively growing SCLC. This orthotopic reconstitution model of human SCLC in SCID mice should be useful for further studies on the biological behavior and treatment of human SCLC.

Animals↗

PubMedDate not supplied

Chemosensitivity testing of clinical gastrointestinal cancers using histoculture and the MTT end-point.

Three-dimensional histoculture with the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) end-point was utilized for chemosensitivity testing of 100 clinical gastrointestinal cancers and the results were compared with those obtained with cell-suspension culture with the MTT end-point. Of the 100 surgical specimens, 91 were evaluable using histoculture assay and 66 were evaluable using the cell-suspension assay. When the assay results were compared with historical frequency of clinical response to chemotherapy, the results of the histoculture assay showed a closer correlation than those of the cell-suspension assay. Therefore, the histoculture assay seems to have a higher evaluability rate and a closer correlation with clinical chemosensitivity of gastrointestinal cancers than the cell-suspension assay.

Antineoplastic Agents↗

PubMedDate not supplied

Recombinant human interferon alpha-2a increases the antitumor activity of 5-fluorouracil on human colon carcinoma xenograft Co-4 without any change in 5-FU pharmacokinetics.

We investigated the modulating effect of recombinant human interferon alpha-2a (IFN-alpha) on the antitumor activity of 5-fluorouracil (5-FU) against a human colon carcinoma xenograft (Co-4) in nude mice with reference to changes in the pharmacokinetic pattern of 5-FU. Mice bearing Co-4 received 5-FU ip at a dose of 90 mg/kg once with or without IFN-alpha, which was administered sc at a dose of 60.000 IU/mouse daily for 7 days before 5-FU treatment. When the area under the curve (AUC) and peak plasma concentration (Cmax) of 5-FU with or without IFN-alpha were measured as pharmacokinetic parameters, the pharmacokinetics of 5-FU was not changed by IFN-alpha administration. This result suggests that the modulating effect of IFN-alpha on 5-FU does not involve augmentation of 5-FU pharmacokinetic parameters.

Animals↗

PubMedDate not supplied

Extended lymphadenectomy and the quality of life in rectal cancer patients.

For a better quality of life in rectal cancer patients, high dose radiotherapy following abdominoperineal resection of the rectum with a pelvic partition is another surgical option replacing extended abdominoperineal resection. In addition to pelvic partition with polyglycolic acid mesh, the tissue expander was inserted into the pelvic cavity to support the intestine upward and the bladder forward. The mean total radiation dosage was 5040 cGy. Between 1989 and 1991, 10 patients were treated according to this method. Out of 10 patients 9 were free of recurrence, and only one had hepatic metastasis. In addition, postoperatively, the average residual urine by this method was 39.1 ml and was statistically different compared to a figure of 200 ml in conventional abdominoperineal resections (p < 0.001, "t"-test). In order to individualize the operative procedures among a variety of surgical options, the molecular biological technique was utilized. In p53 stain analysis of 114 colorectal cancer patients, patients with p53 positive staining reached a higher stage than those with p53 negative staining (p < 0.05, chi 2 analysis). Therefore, we surmised that the positivity of the p53 stain could be one of the factors gauged as an indication of postoperative high-dose radiation. In conclusion, high-dose postoperative radiotherapy was thought to be one of the treatment modalities to improve the survival and quality of life of advanced rectal cancer in selected cases.

Adult↗

PubMedDate not supplied

Recombinant human interferon alpha-2a increases 5-fluorouracil efficacy by elevating fluorouridine concentration in tumor tissue.

The modulating effect of recombinant human interferon alpha (IFN-alpha) on the antitumor efficacy of 5-fluorouracil (5-FU) against human carcinoma cell lines was investigated in vitro and in vivo. 5-FU, fluorouridine (FUR) or fluoro-5'-deoxyuridine (FUdR) were tested against cultured human colon tumor C-1 cells with or without IFN-alpha. The in vitro antitumor activity of 5-FU was enhanced by the addition of IFN-alpha, but IFN-alpha did not increase the effect of FUR or FUdR. The in vivo antitumor activity of 5-FU with or without IFN-alpha was assessed using Co-4, a human colon carcinoma xenograft, in nude mice. Thymidylate synthetase inhibition and concentration of FUR in the treated tumor tissues were concomitantly measured. A synergistic effect of 5-FU and IFN-alpha was observed on Co-4 in nude mice, and this in vivo synergism was obtained without any increment of thymidylate synthetase inhibition or side effects in terms of death rate and body weight loss. The intratumoral concentration of FUR was significantly increased by the addition of IFN-alpha in Co-4 tumor tissue treated with 5-FU. These results suggest that the mechanism of the combined effect of 5-FU and IFN-alpha is not related to enhancement of thymidylate synthetase inhibition, but to an increase of FUR concentration in the target tumor tissue. It is expected that this combination method will be clinically useful for the treatment of advanced colorectal carcinoma.

Animals↗

PubMedDate not supplied

How to convert the rabbit gracilis muscle into a neoanal sphincter.

For reconstruction of anal function in fecally incontinent patients, transposition of the gracilis muscle around the anal canal, with electrical stimulation to maintain contraction, seems practical. But the fast-twitch gracilis muscle is incapable of prolonged contraction without fatigue. Furthermore, the muscle must keep some tension between each stimulus. When the pressure decreases even transiently between stimuli, the neoanus cannot maintain continence. To fulfill these criteria, the neoanal sphincter must be stimulated at a frequency that can induce sufficient summation. We demonstrated that conditioning with long-term electrical stimulation will induce such summation at low frequency. The nerve to the gracilis muscle of rabbits was continuously stimulated at 5 Hz and 10 Hz for 4 to 8 weeks. This conditioning reduced the frequency necessary for summation, and conditioning at 10 Hz for 6 or 8 weeks induced sufficient summation (fusion index [FI] > 90%) at 20 Hz. The muscles conditioned at 10 Hz for 8 weeks showed sufficient summation (FI = 81%) at 15 Hz, a frequency that produced muscle contraction without fatigue, since even unconditioned muscle will remain contracted at 10 Hz without fatigue for 8 weeks. It is concluded that conditioning at 10 Hz for longer than 6 weeks produces enough summation at a low frequency stimulation to permit prolonged contraction.

Anal Canal↗

PubMedDate not supplied

Immunochemotherapy prevents human colon cancer metastasis after orthotopic onplantation of histologically-intact tumor tissue in nude mice.

A metastatic model of human colon cancer has been previously established using orthotopic onplantation of histologically intact in tissue nude mice. In this study, effects of immunochemotherapy using OK-432, 5-fluorouracil (5-FU) and mitomycin C (MMC) on Col-2-JCK, a human colon cancer xenograft, were evaluated using this model. When 5-FU and MMC were administered without OK-432, liver metastases were not reduced even at maximum tolerated doses of both drugs, although cecal tumor growth was significantly reduced. On the other hand, when combined with OK-432, both 5-FU and MMC reduced liver metastases with synergistic reduction of cecal tumor growth, demonstrating the potential of combining immunotherapy with chemotherapy against metastases.

Animals↗

PubMedDate not supplied

Early resection of primary orthotopically-growing human colon tumor in nude mouse prevents liver metastasis: further evidence for patient-like hematogenous metastatic route.

We have developed an orthotopic transplant model of human cancer to immunodeficient mice utilizing microsurgical techniques with intact tissue. The resulting transplanted human tumors grow locally and metastasize in a clinical-like pattern. However, there has been no definitive evidence in colon cancer that the human tumors metastasize via hematogenous route in nude mice. In the present study, in order to obtain definitive evidence of physiological spread of the human tumors, the primary tumors were resected 10 days after the initial orthotopic transplantation to the nude mice. The resection prevented metastases from forming, demonstrating that metastases of the human colon cancers occur after 10 days and by physiological and non-seeding mechanisms in the transplanted nude mice.

Animals↗

PubMedDate not supplied

Interferon beta increases antitumor activity of 5-fluorouracil against human colon carcinoma cells in vitro and in vivo.

The modulating effect of human fibroblast-derived interferon beta (IFN-beta) on the antitumor effect of 5-fluorouracil (5-FU) against human colon carcinoma cells in vitro and in vivo was investigated. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay was carried out in vitro using the cultured human colon cancer cell line C-1. IFN-beta at concentrations of 50, 500, 5,000 and 50,000 IU/ml was added to the cultured tumor cells with or without 5-FU at concentrations of 10, 50 and 500 micrograms/ml. The antitumor activity of 5-FU with or without IFN-beta was assessed using Co-4, a human colon carcinoma xenograft in nude mice, with reference to thymidylate synthetase inhibition. IFN-beta was administered subcutaneously daily for 14 days at doses of 6,000, 60,000 and 600,000 IU/mouse. The combined antitumor effect with 5-FU was evaluated by simultaneous intraperitoneal administration of 5-FU at doses of 10 and 20 mg/kg daily for 10 days. The antitumor activity of IFN-beta alone increased in a dose-dependent manner against Co-4 in nude mice, whereas its antitumor activity in vitro against C-1 was limited. The synergistic effect of 5-FU and IFN-beta was observed both in vitro and in vivo, and the in vivo synergism was obtained without any enhancement of thymidylate synthetase inhibition or side effects in terms of death rate and body weight loss. These results suggest that the mechanism of the combined effect of 5-FU and IFN-beta is not related to enhancement of thymidylate synthetase inhibition or the host immune system, since human fibroblastoid IFN-beta is species-specific to humans. The clinical usefulness of this combination method for the treatment of advanced colorectal carcinoma is expected.

Animals↗

PubMedDate not supplied

Adrenal metastasis from hepatocellular carcinoma--report of a case.

A 66-year-old man presented with an epigastric tumor demonstrated by both ultrasonography and computed tomography as hepatocellular carcinoma. He referred himself to a specialist at another hospital who performed transarterial embolization (TAE) of the hepatic artery. But the serum alpha fetoprotein (AFP) concentration gradually rose after the procedure. A right adrenal metastasis was discovered by computed tomography 9 months after his presentation, 8 months after first embolization. When TAE was performed for this metastasis, there was transverse palsy of the lower limb secondary to spinal artery embolization. He returned to our hospital where a right adrenectomy was performed 14 months after his first presentation. The operation was successful and he was discharged 6 weeks later. But he was readmitted in 8 months with an elevated serum AFP concentration and died within 2 weeks. The details of this case are presented, and the indications for resection of adrenal metastasis from hepatocellular carcinoma are discussed.

Adrenal Gland Neoplasms↗