Assignment of IkappaB kinase beta (IKBKB) to human chromosome band 8p12-->p11 by in situ hybridization.
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Chromosome Banding↗
Biomedical subjects
M Mihara
Publications and source records attributed to M Mihara.
Pleomorphic adenoma of the salivary glands: correlation between gallium-67 uptake and histopathological components.
UNLABELLED: We correlated 67Ga uptake and histopathological findings in pleomorphic adenomas of the salivary glands. METHODS: Sixty-two pleomorphic adenomas of the salivary glands were visually graded by degree of 67Ga uptake as negative, weakly positive or strongly positive in comparison to uptake in the nasal cavity. These adenomas were re-examined pathologically and classified as epithelial, intermediate or mesenchymal type according to their dominant histological components. The pathological presence of marginal invasion or associated sialoadenitis was also re-examined. RESULTS: Eighteen adenomas were classified as strongly positive, eight as weakly positive and 36 as negative. Nine (50%) of the 18 strongly positive adenomas were of the epithelial type and the other nine (50%) strongly positive adenomas were of the intermediate type. While none of the strongly positive adenomas were of the mesenchymal type, 27 (75%) of the 36 negative adenomas were of the mesenchymal type. Six (75%) of the eight weakly positive adenomas were of the intermediate type. About half of the adenomas showed marginal invasion regardless of the grade of 67Ga uptake. None of the strongly positive adenomas were associated with sialoadenitis. CONCLUSION: The epithelial component of pleomorphic adenomas may be responsible for 67Ga uptake. The presence of marginal invasion or associated sialoadenitis has little relation to 67Ga uptake in pleomorphic adenomas.
Adenoma, Pleomorphic↗
[Continuous intraportal chemotherapy for prevention of metachronous hepatic metastasis in colorectal cancer].
Fifty-five colorectal cancer patients who had continuous intraportal chemotherapy between 1990 and 1993 (treated group) and 130 colorectal cancer patients who did not have portal chemotherapy between 1982 and 1993 (untreated group) were studied to clarify the effects of continuous intraportal chemotherapy on the prognosis. After a catheter was placed in the portal vein through the right gastroepiploic vein at the time of radical operation, 10 mg of MMC was continuously infused for 4 hours at operation and 500 mg/day of 5-FU was continuously infused for 7 days postoperatively. The toxicities of this therapy were not serious. The five-year survival rate was 65.3% in the treated group and 65.6% in the untreated group. The five-year disease-free survival rate was 69.8% in the treated group and 58.6% in the untreated group, with no significant difference. In stage II patients, however, the five-year disease-free survival rate in the treated group was slightly higher than in the untreated group (90.0% vs 70.3%, p = 0.073), and the rate of hepatic recurrence in the treated group was significantly lower than in the untreated group. These results suggest that continuous intraportal chemotherapy may prevent metachronous hepatic metastases in stage II colorectal cancer patients.
Aged↗
Overexpression of N-acetylglucosaminyltransferase III disrupts the tyrosine phosphorylation of Trk with resultant signaling dysfunction in PC12 cells treated with nerve growth factor.
beta-1,4-N-Acetylglucosaminyltransferase III (GnT-III: EC 2.4.1.144) is a pivotal glycosyltransferase which participates in branch formation by catalysis of the synthesis of a bisecting GlcNAc structure in N-glycans. These structures are thought to be one of the unique features of the N-glycans of neural tissues. To examine the intracellullar role of GnT-III expression and its product in neural cells, its gene was overexpressed in rat pheochromocytoma PC12 cells which normally express a low level of GnT-III. In the GnT-III gene-transfected cells, lectin blot analysis showed that some glycoproteins showed increased levels of bisecting GlcNAc structures. Following treatment with nerve growth factor (NGF) the control cells showed neurite outgrowth for differentiation whereas the transfectants showed no morphological response or change in the rate of cell growth. Transient tyrosine phosphorylation of the Trk/NGF receptor was detected at 5-15 min after NGF treatment in control cells, but not detected in the GnT-III gene-transfected cells despite the intact binding of NGF to the cells. Moreover the dimerization of Trk with NGF treatment was not induced in the GnT-III transfectant as compared with the dimerization seen in control cells. These results indicate that overexpression of GnT-III gene in PC12 cells affects some functions of glycoprotein receptors such as Trk by alteration of N-glycan structures, and results in changes in the intracellular signaling pathway of tyrosine phosphorylation modified by NGF.
Animals↗
Antirheumatic agents: novel methotrexate derivatives bearing a benzoxazine or benzothiazine moiety.
Novel methotrexate (MTX) derivatives bearing dihydro-2H-1,4-benzothiazine or dihydro-2H-1,4-benzoxazine were synthesized and tested for in vitro antiproliferative activities against human synovial cells (hSC) and human peripheral blood mononuclear cells (hPBMC) obtained from patients with rheumatoid arthritis and healthy volunteers, respectively. In vivo antiarthritic activities of these derivatives were also evaluated in a rat adjuvant arthritis model. N-[[4-[(2,4-Diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzothiazin-7-yl]carbonyl]-L-glutamic acid (3c) exhibited more potent antiproliferative activities in hSC and hPBMC than MTX in vitro. Antiproliferative activities of N-[[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzoxazin-7-yl]carbonyl]-L-homoglutamic acid (3b) and N-[[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzothiazin-7-yl]carbonyl]-L-homoglutamic acid (3d) (MX-68) were comparable to that of MTX in these in vitro assays. Compounds 3b,d (MX-68) significantly suppressed progression of the adjuvant arthritis in a dose-dependent manner ranging from 0.5 to 2.5 mg/kg (po). In addition, 3d (MX-68) completely suppressed this progression at the dose of 2.5 mg/kg (po). Importantly, 3d (MX-68) having benzothiazine and homoglutamate, as expected, did not undergo polyglutamation, a process which may be responsible for the associated side effects of MTX. These results suggest that 3d (MX-68) is a potent and safe candidate antirheumatic agent, absent of the side effects of MTX.
Animals↗
Preventive effect of a novel antifolate, MX-68, in murine systemic lupus erythematosus (SLE).
We evaluated the preventive effects of a novel nonpolyglutamatable antifolate, MX-68, on two experimental murine models of systemic lupus erythematosus (SLE); NZBxNZW F1 (BWF1) mice and chronic graft-versus-host disease (GVHD) mice, in comparison with classical antifolate methotrexate (MTX). The oral administration of 2 mg/kg MX-68, three times a week from 12 to 40 or 60 weeks of age, significantly delayed the onset of proteinuria and prolonged the life-span of BWF1 mice. The elevation of serum blood urea nitrogen (BUN) and cholesterol levels resulting from the development of lupus nephritis was also inhibited. However, MX-68 did not suppress the increase of serum anti-DNA or anti-TNP antibodies or total IgG isotype (IgG1, IgG2 and IgG3) levels. In chronic GVHD mice, MX-68 given three times a week from the day of first cell injection, for 9 weeks, dose-dependently delayed the appearance of proteinuria. The elevation of BUN and cholesterol levels was also inhibited. Furthermore, in the 4 mg/kg MX-68 group, the production of IgG anti-DNA and anti-TNP antibodies was significantly inhibited, but this was not observed in the 2 mg/kg MX-68 and the 4 mg/kg MTX groups. These beneficial effects of MX-68 were much greater than those of MTX in both models. These results suggest that MX-68 might be a more useful drug for the treatment of SLE.
2-Aminoadipic Acid↗
Involvement of caspases in apoptosis induced by ultraviolet B irradiation in A431 human epithelioid tumor cells.
Six hours after ultraviolet B (UVB) irradiation (11.6 mJ/cm2), the viability of A431 cells decreased, and, at the same time, fragmentation of genomic DNA into nucleosomal units was observed. Z-Asp-CH2-DCB (100 microM), an inhibitor of interleukin-1 beta-converting enzyme (caspase-1) and caspase-1-like proteases, markedly inhibited UVB-induced cell death and DNA fragmentation. Both YVAD-CMK, an inhibitor of caspase-1, and DEVD-CHO, an inhibitor of caspase-3, moderately inhibited the UVB-induced cell death. A combination of YVAD-CMK and DEVD-CHO acted additionally in inhibiting cell death. These observations suggest strongly the cooperative involvement of caspases in the apoptosis induced in A431 cells by UVB.
Amino Acid Chloromethyl Ketones↗
Rudimentary meningocele of the scalp.
A rudimentary meningocele, a variant of primary cutaneous meningioma, was seen on the scalp of a 9-month-old Japanese boy. Clinically, the lesion on the left parietal area was round, about 1.6 cm in diameter, alopecic, and slightly elevated. Histologically, the lesion, located from the dermis to the subcutis, consisted of scattered foci of meningothelial cells, an anastomosing network of empty spaces with psammoma bodies and collagen bodies, and small vessels. Immunohistochemically, the meningothelial cells were positive for vimentin and desmin. Ultrastructurally, they had elongated cytoplasmic processes, intermediate filaments in the cytoplasm, and desmosomal junctions.
Humans↗
Lymphocytoma cutis induced by cobalt.
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Cobalt↗
Thermal injury induces both necrosis and apoptosis in rat skin.
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Animals↗
A novel antifolate, MX-68, inhibits the development of autoimmune disease in MRL/lpr mice.
We compared a novel unpolyglutamable antifolate, MX-68, with polyglutamable antifolate, methotrexate (MTX), for treatment of an autoimmune kidney disease which develops spontaneously in MRL/Mp-lpr/lpr (MRL/lpr) mice. Oral administration of either MX-68 or MTX was commenced in 8-week-old female mice and continued 3 times a week until they reached 30 weeks of age. MX-68 delayed the onset of proteinuria and prolonged life span dose-dependently. Furthermore, it suppressed the elevation of serum blood urea nitrogen and cholesterol levels. MX-68 was as effective as MTX at ameliorating events which accompany the development of lupus nephritis, despite that MX-68 did not undergo polyglutamation. These ameliorative effects of MX-68 and MTX did not occur via inhibition of either autoantibody production or cell proliferation. Neither compound suppressed age-dependent elevation of immune complexes or antibodies for single-stranded DNA and TNP in serum nor did they influence the associated enlargement of lymph nodes and spleen. We conclude that MX-68 is beneficial for the treatment of autoimmune kidney disease in mice and may be useful for other related diseases such as systemic lupus erythematosus.
2-Aminoadipic Acid↗
Immunosuppressive properties of MX-68, a novel unpolyglutamatable antifolate.
MX-68 is a novel unpolyglutamatable antifolate. We here reported the in vitro and in vivo immunosuppressive properties of MX-68 compared with a polyglutamatable antifolate, methotrexate (MTX). MX-68 showed potent suppressive effects on mitogen-induced mouse splenic lymphocyte proliferation as well as immunoglobulin production from LPS-stimulated mouse splenic B cells. In in vivo studies, MX-68 significantly suppressed antigen-specific antibody production of both T cell-dependent antigen and T cell-independent antigen. Moreover, MX-68 inhibited a sheep red blood cell (SRBC)-induced delayed-type hypersensitivity (DTH) reaction by administration starting from the day of antigen immunization, but did not suppress the effector phase of the DTH reaction. MTX showed suppressive activities similar to MX-68 in all experiments. Interestingly, although MX-68 demonstrated somewhat stronger suppressive effects than MTX in vivo, the results from in vitro studies were reversed. These results suggest that polyglutamation is not always required to suppress immune responses and that MX-68 is a slightly stronger immunosuppressive drug than MTX in mice.
2-Aminoadipic Acid↗
Antirheumatic agents. III. Novel methotrexate derivatives bearing an indoline ring and a modified ornithine or glutamic acid.
The synthesis, biological profile and structure-activity relationship of various methotrexate (MTX) derivatives bearing an indoline ring are described. In particular, Nb-(3-carboxyphenyl)-N alpha-[1-[(2,4-diaminopteridin-6-yl)-methyl] indoline-5-ylcarbonyl]-L-glutamine (3d), compared to MTX, exhibited an enhanced anti-proliferative effect on human peripheral blood mononuclear cells obtained from healthy volunteers.
Antirheumatic Agents↗
[Comparative study of sustained-release in theophylline (Slobid, Theolong, Theodur) by pharmacokinetics].
We made a comparative study of three kinds of sustained-release of theophylline compounds by means of analysis of plasma concentrations. The drugs were Slobid (SB) (Up-john) 11 patients (10 men, 1 woman), Theolong (TL) (Eisai) 22 (10 men, 12 women), Theodur (TD) (Nikken chemicals) 34 (18 men, 16 women), who were hospitalized from January 1989 to November 1994. These patients were given oral theophylline, bid at 9:00 and 21:00, plasma concentration of theophylline was determined at 9:00, 12:00, 15:00, 18:00 and 21:00, after plasma concentration reached a plateau. There were no significant differences as to the zero absorption rate, the moment absorption rate, clearance, but there were significant differences to the half life time (T1/2) of SB (18.9) > TL (13.5) > TD (10.1) (p = 0.0061), mean residence time (MRT) of SB (21.3 hr) > TL (16.7) > TD (15.2) (p = 0.0034), by measurements analysis of variance. These results suggest that these sustained-release drugs have different pharmacokinetics judging from the important indices including Cmax-Cmin, T1/2, V, MRT and Tml/2, and that the best one is the SB, the second is the TL, and the third is the TD for RTC therapy.
Adult↗
[Biweekly CHOP-E chemotherapy for aggressive non-Hodgkin's lymphoma].
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Adult↗
The value of genotypic analysis in the assessment of cutaneous plasmacytomas.
We report a 79-year-old woman with primary cutaneous plasmacytoma in whom polymerase chain reaction (PCR) was used to demonstrate the monoclonality of the tumour. Four years after presentation, further skin lesions occurred and PCR again showed evidence of monoclonality despite the histology being non-specific. The reported frequency of multiple primary cutaneous plasmacytoma is increasing, and the mortality rate of patients with multiple lesions is three times that of those with a solitary lesion. PCR may be a useful technique for assessing such patients at presentation.
Aged↗
Linear focal elastosis associated with striae distensae in an elderly woman.
We report the case of a 73-year-old woman with linear focal elastosis (LFE) associated with striae distensae. Yellow palpable striae were found extending horizontally in the lumbar region. The yellow striae appeared to be joined to striae distensae in the lateral sides of the yellow striae. Striae distensae were also present in regions other than the back but were not associated with yellow striae. Histologic examination of a yellow stria revealed a focal increase in elastic fibers in the dermis. Although there have been some unusual cases of LFE arising in women or in young persons, this disorder still predominantly affects aged men. A fairly uniform feature of LFE is its occurrence on the dorsal skin, suggesting involvement of this specific anatomical site in its pathogenesis. We suspect that LFE usually arises de novo in the skin, although striae distensae may also be a cause of it.
Aged↗
Mechanisms of selenium methylation and toxicity in mice treated with selenocystine.
Mechanisms of selenium methylation and toxicity were investigated in the liver of ICR male mice treated with selenocystine. To elucidate the selenium methylation mechanism, animals received a single oral administration of selenocystine (Se-Cys; 5, 10, 20, 30, 40, or 50 mg/kg). In the liver, both accumulation of total selenium and production of trimethylselenonium (TMSe) as the end-product of methylation were increased by the dose of Se-Cys. A negative correlation was found between production of TMSe and level of S-adenosylmethionine (SAM) as methyl donor. The relationship between Se-Cys toxicity and selenium methylation was determined by giving mice repeated oral administration of Se-Cys (10 or 20 mg/kg) for 10 days. The animals exposed only to the high dose showed a significant rise of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in plasma. Urinary total selenium increased with Se-Cys dose. TMSe content in urine represented 85% of total selenium at the low dose and 25% at the high dose. The potential of Se-methylation and activity of methionine adenosyltransferase, the enzyme responsible for SAM synthesis, and the level of SAM in the liver were determined. The high dose resulted in inactivation of Se-methylation and decrease in SAM level due to the inhibition of methionine adenosyltransferase activity. To learn whether hepatic toxicity is induced by depressing selenium methylation ability, mice were injected intraperitoneally with periodate-oxidized adenosine (100 mumol/kg), a known potent inhibitor of the SAM-dependent methyltransferase, at 30 min before oral treatment of Se-Cys (10, 20, of 50 mg/kg). Liver toxicity induced by selenocystine was enhanced by inhibition of selenium methylation. These results suggest that TMSe was produced by SAM-dependent methyltransferases, which are identical with those involved in the methylation of inorganic selenium compounds such as selenite, in the liver of mice orally administered Se-Cys. Depression of selenium methylation ability resulting from inactivation of methionine adenosyltransferase and Se-methylation via enzymic reaction was also found in mice following repeated oral administration of a toxic dose of Se-Cys. The excess selenides accumulating during the depression of selenium methylation ability may be involved in the liver toxicity caused by Se-Cys.
Adenosine↗