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Biomedical subjects

M Terada

Publications and source records attributed to M Terada.

At least 163 records · Page 9Linked to original sources
PubMed1998

Mouse NK1.1+ cytotoxic T cells can be generated by IL-2 exposure from lymphocytes which express an intermediate level of T cell receptor.

NK-like T cells which express the NK1.1 molecule and CD3 (or TCR) of intermediate level (CD3int or TCRint cells) were recently demonstrated to be present in various immune organs, and to have NK-like cytotoxic activity against NK target cells. In this study, we investigated whether NK1.1- T cells could express NK1.1. We found that NK1.1+ TCRint cells were much more abundant in the liver (20%) than in the spleen (2%). When hepatic and splenic mononuclear cells (MNCs) were cultured either in the absence of IL-2 or in the presence of CD3/TCR cross-linking, the original NK1.1+ TCRint cells disappeared. However, when they were cultured in the presence of a high dose of IL-2 for 4 days, a new type of NK1.1+ T cell was formed to the extent of approximately 15-20%, and the liver and spleen contained similar percentages of this new type of NK1.1+ T cells. The phenotypes of the original and the new type of NK1.1+ T cells were clearly distinct. The freshly obtained NK1.1+ TCRint cells consisted of double-negative (DN) CD4-CD8- cells and single-positive (SP) CD4+ cells, whereas the new type of NK1.1+ T cells predominantly consisted of DN CD4-CD8- cells and SP CD8+ cells and expressed a high level of CD3 (CD3high or TCRhigh cells). When NK1.1- cells or IL-2 receptor beta-chain (IL-2Rbeta)- cells were isolated from the liver and spleen, and cultured in the presence of IL-2 for 4 days, NK1.1+ T cells were generated from NK1.1- cells, but not from IL-2Rbeta- cells. Our results suggested that the NK1.1- cells, but not IL-2Rbeta- cells, contained the precursor of IL-2-stimulated NK1.1+ TCRhigh cells. When purified NK1.1- IL-2Rbeta+ TCRint cells were cultured in the presence of IL-2 for 4 days, approximately 10% of the cells became NK1.1+ TCRhigh cells. Approximately 60% of the purified NK1.1+ TCRint cells lost NK1.1 expression. The IL-2-stimulated NK1.1+ TCRhigh cells that had arisen from NK1.1- TCRint cells exerted an NK cell-like cytotoxic activity similar to that of the original NK1.1+ T cells. Thus, NK1.1- TCRint cells could express NK1.1 and exert NK-like cytotoxic activity regardless of their origin. It appears that NK1.1+ TCRhigh cells can only be induced through an IL-2-stimulation pathway but not via CD3/TCR cross-linking.

Animals↗
PubMed1998

Growth-inhibitory effect of a high glucose concentration on osteoblast-like cells.

Impaired bone formation resulting from a decline of osteoblast activity has been implicated in the pathogenesis of diabetic osteopenia. We examined the effects of high glucose concentration alone, independent of insulin deficiency, on the growth of a human osteoblast-like cell line (MG-63). Sustained exposure to high glucose for 7 days inhibited cell growth in a concentration-dependent manner up to 49.5 mmol/L, as compared with cells cultured with a normal glucose concentration (5.5 mmol/L) or a high mannitol concentration (an iso-osmolar control). Glucose (49.5 mmol/L) attenuated the increment either in DNA content or in [3H]thymidine incorporation induced by insulin-like growth factor I (IGF-I). The IGF-I-induced increase of ornithine decarboxylase (ODC) activity, which plays an important role in cell growth, was also attenuated. The half-life of ODC protein was not shortened by the high glucose culture, but the intracellular content of putrescine (an end product of ODC) was significantly decreased. These changes did not occur in the high mannitol culture, strongly suggesting a specific effect of glucose. In summary, our observations suggest that a high glucose concentration significantly impairs the proliferative response of osteoblastic cells to IGF-I and that the defective cell function caused by sustained exposure to high glucose levels might contribute to impaired bone formation in patients with diabetic osteopenia.

Acetyltransferases↗
PubMed1998

Elevated serum level of thioredoxin in patients with hepatocellular carcinoma.

Thioredoxin (TRX) is known to contain an active site with a redox-active disulfide and has various biological activities. The objective of the present study was to investigate whether circulating TRX levels are elevated in patients with chronic hepatitis (CH) or liver cirrhosis (LC) and hepatocellular carcinoma (HCC). An anti-TRX monoclonal antibody and polyclonal antibodies that specifically recognize TRX, were generated and used for the development of an ELISA system to measure TRX levels in human serum. The geometric mean and its 95% confidence interval of serum level of TRX in healthy volunteers was 81.75 ng/ml (74.60-89.59 ng/ml). The serum level of TRX in LC/CH patients without HCC was 80.87 ng/ml (69.66-93.88 ng/ml). The value was not statistically different from that in serum from normal volunteers (p=0.69). In contrast, the serum level of TRX in patients with HCC was 147.35 ng/ml (125.53-172.96 ng/ml), which was significantly higher when compared with the level in serum of normal volunteers (p<0.001) and in serum of LC/CH patients without HCC (p<0.001). In four patients with HCC, the initially high level of serum TRX (>150 ng/ml) decreased below 150 ng/ml after surgical removal of the tumor. The data reported herein revealed that patients with HCC had a significantly elevated serum level of TRX, suggesting that measurement of serum of TRX might be a useful clinical parameter when HCC is suspected.

Adult↗
PubMed1998

In vivo malignant phenotype of hst-1-transfected cells regulated by paracrine endothelial cell growth stimulation by HST-1.

The hst-1 gene product, one of the fibroblast growth factor family proteins, has transforming and angiogenic activities. The BALB/c 3T3 cell line was transfected with an expression vector harboring human hst-1 cDNA and the malignant properties of two stably transfected clones, TC-1 and TC-2, were examined. The stimulating activity of TC-1-conditioned medium for endothelial cell DNA synthesis was approximately four times stronger than that of TC-2-conditioned medium and correlated with hst-1 mRNA expression levels. Other than endothelial cell growth stimulation, these two clones had similar typical in vitro transformed properties, with identical doubling times and morphological changes. When nude mice were injected s.c. with these clones, TC-1 cells revealed faster tumor formation and growth, compared to TC-2 cells which had less potential to promote endothelial cell growth. Furthermore, the life span of mice injected i.v. with TC-1 cells was shorter than those with TC-2 cells, resulting from progressive tumor growth in the lungs. This advanced malignant in vivo behavior of TC-1 cells may be mediated by the high angiogenic potential of TC-1 cells secreting larger amounts of HST-1 compared to TC-2 cells, suggesting that angiogenesis contributes to malignant progression of tumors.

Journal Article↗
PubMed1998

Expression and activity of cyclin-dependent kinase 5/p35 in adult rat peripheral nervous system.

In spite of the clarification in the temporal and spatial expression pattern of a cyclin-dependent kinase (Cdk) 5 and its neuron-specific activator, p35, in the CNS, it remains to be elucidated in the PNS. In addition, it is not known whether Cdk5 activity exists in the PNS. Therefore, we have examined their expression and activity in the PNS by immunoblot analysis, immunohistochemistry, and in vitro kinase assay. Immunoblot analysis indicated the expression of Cdk5 and p35 proteins in dorsal root ganglion (DRG) and sciatic nerve alike in the CNS. By immunohistochemistry, both proteins were shown to be present in the cell body and axon (sciatic nerve) of both DRG neurons and anterior horn cells. A co-immunoprecipitation study indicated the in vivo association between Cdk5 and p35 in both DRG and sciatic nerve. However, Cdk5 kinase activity was found only in DRG, but not in sciatic nerve. These results suggest that Cdk5 kinase activity exists and functions physiologically in the PNS and may be regulated by unknown mechanisms other than the availability of p35 as reported in developing brains.

Animals↗
PubMed1998

Experimental chemical carcinogenesis in the stomach and colon.

Experimental chemical carcinogenesis in the digestive tract is reviewed, mainly on the basis of information obtained in the laboratories of the National Cancer Center Research Institute. It is generally accepted that cancer is the outcome of DNA damage, resulting in mutation, loss, amplification and recombination of genes. Gastric cancer is no exception. It was shown very early that cancer of the glandular stomach can be produced in rats by administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a widely used mutagen. However, this depends on the genotype. Whereas the ACI rat is susceptible to MNNG, the Buffalo rat is resistant and this is a dominantly inherited trait. Genes responsible for the sensitivity to gastric cancer induction are at present under investigation by linkage analysis of rat genome markers. With regard to cancer in humans, our finding that cooked proteinaceous foods can give rise to a series of heterocyclic amines (HCAs) is of major significance. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the most abundant, causes colon cancers in male rats, whereas in females it induces breast cancers. The colon cancers induced by PhIP feature a deletion of G as represented by 5-GGGA-3-->5-GGA-3 in the Apc gene, resulting in a truncated Apc molecule. Microsatellite mutations have also been found in PhIP-induced colon tumors, as in human hereditary non-polyposis colorectal cancer cases. Similarly to the case of gastric cancer production by MNNG, there is a genetic component and F344 rats are more susceptible to PhIP colon carcinogenesis than the ACI/N strain and the gene responsible is being sought. Since carcinogenesis proceeds with accumulation of genetic alteration, often involving genomic instability, exposure to any kind of carcinogenic substances, either xeno- or autobiotics, needs to be reduced as far as possible, taking account of inconvenience at the individual and socio-economical levels.

Adenomatous Polyposis Coli↗
PubMed1998

Living related liver transplantation in adults.

OBJECTIVE: To evaluate the outcome of living related liver transplantation (LRLT) in adult patients and to assess graft size disparity and graft regeneration. SUMMARY BACKGROUND DATA: Although LRLT has been accepted as an optional life-saving procedure for pediatric patients with end-stage liver disease, the feasibility of LRLT for adult patients has not been reported with reference to a clinical series. METHODS: Adult-to-adult LRLT was performed using whole left lobar grafts in 13 patients (5 with primary biliary cirrhosis, 6 with familial amyloid polyneuropathy, 1 with biliary atresia, and 1 with citrullinemia). The 13 donors comprised 5 husbands, 3 sons, 2 sisters, 2 fathers, and 1 mother. The ratio of the graft volume to standard liver volume (GV/SV ratio) was calculated for use as a parameter of graft size disparity. RESULTS: Although the liver graft was markedly small for size (GV/SV ratio 32%-59% at the time of LRLT), none of the 13 patients developed postoperative liver failure. Eleven of the patients are still alive and well with satisfactory graft function 2 to 35 months after LRLT. Graft liver volume increased rapidly after LRLT and approximated the standard liver volume with time. CONCLUSIONS: Our LRLT program for adult patients has produced good results. LRLT in adults can be indicated for selected donor-recipient combinations.

Adult↗
PubMed1998

Singly dehydroxylated A-ring analogues of 19-nor-1alpha,25-dihydroxyvitamin D3 and 19-nor-22-oxa-1alpha,25-dihydroxyvitamin D3: novel vitamin D3 analogues with potent transcriptional activity but extremely low affinity for vitamin D receptor.

1Alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] mediates its biological activities through specific binding to the nuclear vitamin D receptor (VDR). The VDR, bound to 1alpha,25(OH)2D3, forms a heterodimer with a nuclear accessory factor, retinoid X receptor (RXR), and the complex subsequently binds to specific nucleotide sequences or a vitamin D-responsive element (VDRE) to induce gene transcriptions. Thus, an ideal analogue of 1alpha,25(OH)2D3 for therapeutic applications has been considered to be one which has a high binding affinity for VDR, thus forming a stable VDR/RXR complex, and binding strongly to VDRE. By contrast, we report here evidence contrary to this hypothesis. Several singly dehydroxylated A-ring analogues of 19-nor-1alpha,25-dihydroxyvitamin D3 and 19-nor-22-oxa-1alpha,25-dihydroxyvitamin D3, all of which have an extremely low binding affinity for VDR, and some of which lack the 1alpha-hydroxyl group that is considered to be essential for VDR-mediated gene expression, have greater or equivalent potencies to 1alpha,25(OH)2D3 for inhibiting the proliferation and inducing the differentiation of HL-60 cells, as well as inducing the transactivation of a luciferase reporter gene combining a rat 25-hydroxyvitamin D3 24-hydroxylase gene promoter containing two VDREs. The present findings open interesting possibilities as to the role of the VDR in the genomic action of 1alpha,25(OH)2D3 and the development of new 19-nor-analogues of 1alpha,25(OH)2D3.

Animals↗
PubMed1998

Glycated hemoglobin levels and their correlation with atherosclerotic risk factors in a Japanese population--the Jichi Medical School Cohort Study 1993-1995.

We conducted a large population-based study to assess levels of glycated hemoglobin A1c (HbA1c) and to evaluate the correlation between HbA1c and other cardiovascular risk factors in Japan. A total of 910 men and 1,890 women aged 30-69 years participated in the Jichi Medical School Cohort Study (1993-95). Mean HbA1c was 5.61% in men and 5.49% in women. HbA1c levels were significantly correlated with levels of triglycerides, fibrinogen, and factor VII, and inversely correlated with high-density lipoprotein (HDL)-cholesterol level in both sexes. Lipoprotein(a) was inversely correlated in men. Blood pressure, body mass index (BMI), and total cholesterol were significantly associated with HbA1c in women. After adjusting for significant variables in univariate analyses, fibrinogen and factor VII remained as significant correlates in men, and BMI and total cholesterol in women. The authors conclude that HbA1c level is correlated not only with classical cardiovascular risk factors, but also with fibrinogen and factor VII. Our results suggest that HbA1c could be an alternative to blood glucose in evaluating atherosclerotic risk in a large-sized population study.

Adult↗
PubMed1998

Effects of amorphous and polymorphs of PF1022A, a new antinematode drug, on Angiostrongylus costaricensis in mice.

To enhance the bioavailability of PF1022A (cyclo(D-lactyl-L-N-methylleucyl-D-3-phenyllactyl-L-N-met hylleucyl-D-lactyl-L-N-methylleucyl-D-3-phenyllactyl-L-N- methylleucyl)), a newly developed antinematode drug, we examined whether the new drug has polymorphism or not. First, four forms of PF1022A, designated as form alpha, form I, form II and form III of PF1022A, were prepared. By examining physicochemical properties of these forms by various methods including X-ray powder diffractometry and differential scanning calorimetry, it became apparent that PF1022A had one amorphous (form alpha) and three crystalline polymorphic forms, form I, form II and form III. Secondly, a dissolution study was carried out, and form alpha and form III were found to have higher solubility than form I and form II. Thirdly, anti-larval effects of the 4 forms of PF1022A on tissue-dwelling nematode, Angiostrongylus costaricensis, in mice were compared when given orally for 5 successive days at 10 or 40 mg/kg/day. Significant effects were observed in almost all parameters in host mice and worms in the groups treated with form alpha or form III, each at 40 mg/kg, but form I and form II had little effect. The present results suggest that PF1022A has polymorphism and that the form alpha and form III were more effective against tissue-dwelling nematodes than the form I and form II when given orally.

Angiostrongylus↗
PubMed1998

Mepanipyrim induces fatty liver in rats but not in mice and dogs.

Mepanipyrim, a new fungicide, was administered orally to rats, mice and dogs for 13 weeks to clarify its toxic profiles. Hepatotoxicities were observed characteristically in these species with high concentrations of mepanipyrim; more than 200 ppm in rats, more than 1,000 ppm in mice, and more than 50 mg/kg/day in dogs. In rats, obvious fatty vacuolation in the perilobular hepatocytes and changes in the serum-lipid concentrations such as total cholesterol (TC), triglyceride (TG), phospholipid (PL) and non-esterified fatty acid (NEFA) were observed. This fatty liver appeared to be based on the alteration of lipid metabolism. In contrast, no remarkable changes were observed in mice and dogs except for an enhancement of anisonucleosis in mice or a lipofuscin deposition in Kupffer cells and hepatocytes in dogs. It appeared that there were species differences in the hepatotoxicities of mepanipyrim.

Administration, Oral↗
PubMed1998

Effects of mepanipyrim on lipid metabolism in rats.

Our preceding paper reported that mepanipyrim, a new fungicide, induced fatty liver in the rat. This study was undertaken to examine this phenomenon further on hepatic triglyceride (TG) synthesis, on liver and serum lipid concentrations, and on concentration of serum very-low-density lipoprotein (VLDL) in rats fed for 3 weeks on the drug at 4,000 ppm. Mepanipyrim decreased the incorporation of 14C-acetate into hepatic TG, total cholesterol (TC) and total lipids. In addition, mepanipyrim treatment induced a drastic increase in hepatic TG accompanying a decrease in serum TG. Esterified cholesterol (CE), phospholipid (PL) and non-esterified fatty acid (NEFA) also increased in the liver with a concomitant decrease in the serum. The decrease of serum VLDL by mepanipyrim was comparable to the decrease in serum TG. Because hepatic TG is secreted into the blood by forming VLDL, which consists of TG, TC, PL, and apoprotein, the decrease in serum TG would be mainly ascribable to that in serum VLDL. Mepanipyrim also decreased serum concentrations of low-density lipoprotein (LDL) and high-density lipoprotein (HDL), and the relative weights of the epididymal adipose tissue, indicating that a reduction in serum VLDL does not reflect acceleration of serum VLDL dissimulation. These results suggest that the fatty liver induced by mepanipyrim would be due to the inhibition of hepatic VLDL synthesis or its secretion into the blood.

Animals↗
PubMed1998

Neuropathy associated with angioimmunoblastic lymphadenopathy-like T-cell lymphoma.

A 75-year-old woman was admitted because of pain and numbness in the extremities and trunk. She subsequently suffered from lymphadenopathy and spiky fever. The immunohistochemical analysis of the biopsied lymph nodes and sural nerve and electrophysiological examination supported a diagnosis of angioimmunoblastic lymphadenopathy-like T cell lymphoma with polyneuropathy. The infiltrating lymphoma cells of the sural nerve and lymph node shared the same phenotype (CD45RO, CD3, CD30 positive). An increased expression of HLA-DR antigen was observed in endothelial and Schwann cells. Chemotherapy with CHOP-Bleomycin markedly relieved her pain. These findings suggest that a direct lymphocytic infiltration in the nerve may be associated with neuropathy in this case.

Aged↗