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Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 649 records · Page 36Linked to original sources

Amino acid sequence of an inhibitor from the silkworm (Bombyx mori) hemolymph against fungal protease.

A novel protein protease inhibitor (FPI-F) which is highly specific for fungal proteases and subtilisin was isolated from the silkworm hemolymph, and its amino acid sequence was determined by conventional methods. The inhibitor consisted of 55 amino acid residues and had a molecular weight of 6,100. The inhibitor included eight cysteine residues and relatively large amounts of acidic amino acids, but neither alanine, methionine nor tryptophan. The amino acid sequence of FPI-F was not homologous with those of other known protease inhibitors of microbe, plant or animal origin.

Amino Acid Sequence↗

Successful treatment of cytophagic histiocytic panniculitis with modified CHOP-E. Cyclophosphamide, adriamycin, vincristine, predonisone, and etoposide.

A 27-year-old woman developed generalized subcutaneous painful nodules, fever, abnormal liver function, a bleeding tendency, and pancytopenia. Skin biopsies revealed the lobular panniculitis with a morphologically benign histiocytic infiltration with prominent phagocytosis. Leukophagocytosis and erythrophagocytosis were also present in the bone marrow. The diagnosis of cytophagic histiocytic panniculitis was made. The patient received polychemotherapy with cyclophosphamide, Adriamycin, and vincristine on day 1, prednisone on day 1-5 (modified CHOP), with the addition of etoposide (E). This regimen was repeated 8 times every 3 weeks. The patient obtained a complete clinical remission that has lasted almost 2 years after the completion of chemotherapy. Thus we suggest modified CHOP-E chemotherapy for an effective treatment for the aggressive form of cytophagic histiocytic panniculitis.

Adult↗

Semi-quantitative analysis of DNA topoisomerase-I mRNA level using reverse transcription-polymerase chain reaction in cancer cell lines: its relation to cytotoxicity against camptothecin derivative.

Expression of DNA topoisomerase (Topo)-I-mRNA in various cancer cell lines was detected using the reverse transcription-polymerase chain reaction (RT-PCR) method. The cytoplasmic polyadenylated RNA isolated from cancer cell lines was reverse-transcribed and the complementary DNA was amplified by PCR primed with Topo-I specific primers. Fidelity of the amplified sequence was confirmed by restriction endonuclease digestion and Southern blot hybridization. The level of Topo-I mRNA was correlated positively with the cytotoxicity of a Topo-I inhibitor, a camptothecin derivative. This RT-PCR method may be applicable to the assessment of sensitivity of cells to Topo-I targeted drugs, especially when only small quantities of cell samples are available.

Adenocarcinoma↗

Gastric ulcer treatment with intravenous human epidermal growth factor: a double-blind controlled clinical study.

We introduced a double-blind controlled clinical study to compare intravenous human epidermal growth factor (hEGF) to cetraxate hydrochloride (CH), an antiulcer drug, for their healing effect on gastric ulcers. We also prospected an oral use of EGF on the basis of our experimental evidence. In the clinical trial, the rate of ulcer healing within 8 weeks was 77.9% (67/86) in patients receiving 6 micrograms EGF intravenously twice a week, being significantly greater than 51.7% (45/87) in those given CH. Taking together all aspects assessed including the healing rate, pain relief, blood examination and adverse reactions, we judged the hEGF to be a useful and safe anticuler drug. In rats, 50 micrograms/kg mouse EGF (mEGF) and 2% hydroxypropyl cellulose (HPC) or 1.0 g/kg sucralfate given by gastric intubation significantly raised the residual mEGF levels in both gastric luminal content (HPC: x 30; sucralfate: x 300 as high as those in EGF alone) and tissue (HPC: x 60; sucralfate: x 100). In addition, the combined treatments significantly promoted healing of rat gastric ulcers whereas each agent alone had no significant effect as compared with control (saline). This indicated the beneficial effect on ulcers of oral administration of EGF with agents allowing it to remain at high levels in the stomach, whereas most reports suggested less effect of oral EGF on healing of gastroduodenal ulcers. Subsequent to the clinical study, evaluation of oral use of EGF may be expected as the next step in the treatment of ulcers. The experimental evidence above would possibly be a guide for such trial.

Administration, Oral↗

Identification of causative chemicals of allergic contact dermatitis using a combination of patch testing in patients and chemical analysis. Application to cases from industrial rubber products.

3 cases of allergic contact dermatitis from industrial rubber products were investigated using a combination of patch testing in patients and chemical analysis of causative rubber products by gas chromatography (GC), GC-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). Our studies revealed N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), a typical rubber allergen, as a causative chemical in a case from a brand of heavy-duty rubber gloves and a case from a black rubber ring for car manufacture, and zinc ethylphenyldithiocarbamate (ZEPC), a dithiocarbamate (DTC)-type accelerator, as a causative chemical in a case from a brand of rubber work gloves: both IPPD and ZEPC, which showed positive patch test reactions, were confirmed in the extracts of the causative rubber products by GC, GC-MS and/or HPLC.

Adult↗

Identification of causative chemicals of allergic contact dermatitis using a combination of patch testing in patients and chemical analysis. Application to cases from rubber footwear.

5 cases of allergic contact dermatitis from rubber footwear were investigated by a combination of patch testing in patients and chemical analysis of causative rubber products. Our studies revealed 2-mercaptobenzothiazole (MBT) and benzothiazyl disulfide (MBTS) (typical allergenic accelerators) as causative chemicals in 3 cases from children's rubber shoes, ladies' rubber boots and ladies' canvas shoes. These 3 patients reacted to mercaptobenzothiazole-type accelerators including MBT and MBTS. MBT and MBTS were determined in each item of causative footwear by chemical analysis, including extraction by shaking with acetone-chloroform (1:1) mixture at room temperature and determination using reversed-phase high-performance liquid chromatography (RP-HPLC). Subsequently, we identified styrenated phenol (SP), a newly found allergenic antioxidant, as a causative chemical in a case from ladies' canvas shoes. The patient reacted to SP but not to MBT and MBTS, though SP, MBT and MBTS were determined in the causative shoes by gas chromatography (GC), GC-mass spectrometry (GC-MS) and HPLC. We also identified p-tert-butylphenol-formaldehyde resin (PTBP-F-R), (a known allergenic adhesive ingredient) as a causative chemical in a case from ladies' sneakers. The patient reacted to PTBP-F-R but not to p-tert-butylphenol (PTBP), MBT and MBTS. These 4 compounds were determined in the causative sneakers by GC, GC-MS and HPLC. Thus, our studies revealed that not only known allergens, such as MBT, MBTS and PTBP-F-R, but also a newly found one, such as SP, were important causes of allergic contact dermatitis from rubber footwear.

Adhesives↗

Identification of causative chemicals of allergic contact dermatitis using a combination of patch testing in patients and chemical analysis. Application to cases from rubber gloves.

5 cases of allergic contact dermatitis from rubber gloves were investigated by our recommended procedures using a combination of patch testing in patients and chemical analysis of causative rubber products by gas chromatography (GC) and high-performance liquid chromatography (HPLC). We previously confirmed that zinc ethylphenyldithiocarbamate (ZEPC), a dithiocarbamae-type accelerator (DTC), was causative in a case of allergic contact dermatitis from rubber work gloves. Subsequently, we have clarified that DTCs such as zinc dimethyldithiocarbamate (ZDMC), zinc diethyldithiocarbamate (ZDEC) and zinc dibutyldithiocarbamate (ZDBC) and amines such as dimethylamine (DMA), diethylamine (DEA) and piperidine (PIP) were also causative in cases from surgical rubber gloves. Thus, our investigative studies revealed that, although thiurams have been taken much more notice of as allergenic compounds than their corresponding DTCs and amines, not only DTCs such as ZDMC, ZDEC, ZDBC and ZEPC, but also amines such as DMA, DEA and PIP were noteworthy causative candidates of allergic contact dermatitis from rubber gloves.

Adult↗

A protease activation mutant, MVCES1, as a safe and potent live vaccine derived from currently prevailing Sendai virus.

Sendai virus fresh isolates were shown to be antigenically different from the prototype Fushimi strain that had long been passaged in embryonated chicken eggs. Phylogenetic analysis of the hemagglutinin-neuraminidase genes also revealed the difference between these two virus groups. Both trypsin-resistant and elastase-sensitive mutations were additionally introduced to an LLC-MK2-cell-adapted and attenuated mutant derived from one of the fresh isolates. This protease activation mutant (MVCES1) showed the same antigenicity as the fresh isolates, and as a result of a single cycle of growth in lungs, it could confer better protection on mice against challenge infection with the currently prevailing Sendai virus than TR-5, which is a trypsin-resistant mutant derived from the Fushimi strain. The eligibility of MVCES1 as an attenuated live vaccine of Sendai virus is discussed.

Amino Acid Sequence↗

Gastric epithelial damage induced by local ischemia-reperfusion with or without exogenous acid.

We evaluated the damage to the gastric epithelium produced by local ischemia-reperfusion (IR) with or without luminal perfusion with 0.1 N HCl. Local gastric ischemia was induced by clamping the left gastric artery. Use of radioactive microsphere technique revealed a significant reduction in blood flow induced only in the corpus (67% reduction). Because no measurable gross lesion was observed in this model, the blood-to-lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA) served as an index of epithelial damage. In the absence of exogenous acid, the histological damage was minimum and could not be quantified. However, a significant increase in 51Cr-EDTA clearance was observed shortly after reperfusion in a manner that depended on the duration of ischemia. This increase in clearance reached a maximum approximately 10 min after reperfusion and returned rapidly toward control levels within 40-50 min after reperfusion. In the presence of exogenous acid, EDTA clearance increased significantly during ischemia, increased further during reperfusion, and did not recover for at least 60 min after reperfusion. The acid infused after reperfusion (no acid before reperfusion) did not significantly aggravate the mucosal damage that followed reperfusion. However, the acid infused before reperfusion (no acid after reperfusion) showed an effect on EDTA clearance similar to that induced by continuous acid perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗

Epidermal growth factor attenuates jejunal mucosal injury induced by oleic acid: role of mucus.

Epidermal growth factor (EGF) is present in biliary, pancreatic, and Brunner's gland secretions. The aim of the present study was to assess the effects of EGF on lipid-induced mucosal injury. The proximal jejunum of anesthetized rats was cannulated for perfusion of the lumen with emulsified oleic acid (40 mM oleic acid in 20 mM sodium taurocholate; pH 6.0). Mucosal epithelial integrity was monitored by measuring the blood-to-lumen clearance of 51Cr-labeled EDTA. Perfusion of the lumen with emulsified lipid increased EDTA clearance. Addition of EGF (0.5 ng/ml) to the lipid emulsion ameliorated the lipid-induced increase in EDTA clearance. Perfusion of the lumen with EGF alone stimulated mucus secretion from goblet cells. This effect of EGF was abolished by atropine. In addition, in atropinized animals there was 1) an exaggeration of the lipid-induced injury and 2) a loss of the protective effect of EGF. Our findings provide evidence supporting the hypothesis that EGF provides protection against lipid-induced mucosal injury, in part, by stimulating mucus production.

Animals↗

Autoimmune myocarditis induced in mice by cardiac C-protein. Cloning of complementary DNA encoding murine cardiac C-protein and partial characterization of the antigenic peptides.

Autoimmune myocarditis is considered to play a major role in the pathogenesis of dilated cardiomyopathy. A new autoimmune myocarditis model was attained by repeated immunization using murine cardiac C-protein with the immunological adjuvant, Klebsiella pneumoniae O3 lipopolysaccharide. For further analysis of a pathological epitope, the cDNA encoding C-protein was isolated; a fusion protein encoded by part of this cDNA induced myocarditis in SMA mice as well as in three other strains: DBA/1J (H-2q), O20/A (H-2pz1), and SJL (H-2s). The nucleotide sequence and its deduced amino acid analysis revealed that this protein had immunoglobulin-like and fibronectin-like repeats. This study provides a new animal model of autoimmune myocarditis which may shed light on the pathogenesis of dilated cardiomyopathy.

Adult↗

Studies on thermophile products. XI. Biological effect of antigen presenting inhibitor, isofatty acid-containing phosphatidylethanolamine, on mouse macrophages.

A new fraction, Fr. 8-A, which consists of a phosphatidylethanolamine with C14:0-C18:0 isofatty acids was obtained from Bacillus stearothermophilus UBT8038. The fraction inhibited major histocompatibility complex class II (Ia) antigen expression and antigen presentation on mouse macrophages. The effect of Fr.8-A on macrophage functions related to antigen presentation was investigated. Fr. 8-A increased arachidonate release, prostaglandin (PG) E2 release and nitrite production from peritoneal macrophages. It increased further the levels of PGE2, nitrite and tumor necrosis factor in the culture supernatant of the macrophages induced by the supernatant from concanavalin A-stimulated spleen cell cultures. Fr. 8-A augmented the activity of peritoneal macrophages to suppress Con A-stimulated T cell proliferation. Addition of either indomethacin or Ng-methyl-L-arginine had no effect on the augmentation of suppressor macrophage activity or the inhibition of antigen presentation by Fr. 8-A, while simultaneous addition of both inhibitors abrogated the effect of the fraction. These results indicate that Fr. 8-A inhibits Ia expression and antigen presentation, and augments suppressor macrophage activity at least partly via the activation of both cyclooxygenase and nitric oxide synthase pathways.

Animals↗

Pharmacological activity of chemically modified subfragment from human serum IgG. XI. Increment of tumor necrosis factor (TNF) activity in mouse sera by carboxamide-methylated light chain.

Intravenous administration of the carboxamide-methylated light chain (G1L) from human serum IgG induced tumor necrosis factor (TNF), one of the inflammatory cytokines, in the serum of mice. Human serum IgG, however, showed no induction of TNF in the serum. G1L showed a potent anti-inflammatory effect in carrageenin-induced paw edema, and the anti-inflammatory effect of G1L was significantly blocked by the concomitant administration of anti-TNF antiserum, but TNF alone had no anti-inflammatory effect.

Animals↗

Studies on pharmacological activation of human immunoglobulin G by chemical modification and active subfragments. XII. Effect of carboxamidemethylated Fc fragment (CM-Fc) from human immunoglobulin G on mixed lymphocyte reaction.

The effect of carboxamidemethylated Fc fragment (CM-Fc) from human serum immunoglobulin G on mixed lymphocyte reaction (MLR) was studied. CM-Fc enhanced the MLR response when added at the start of cultivation, but suppressed the response when added 48 h after onset of cultivation. The Fc fragment had no effect. CM-Fc elevated the levels of interleukin-1 and tumor necrosis factor when added at the start of splenocyte cultivation, and somewhat did so when added 48 h after onset of cultivation. These elevations caused the induction of prostaglandin E2 in MLR culture supernatant. The suppression of MLR by CM-Fc was abrogated by the addition of indomethacin. We considered that CM-Fc regulated the immune response being affected to the function of macrophages.

Animals↗

Studies on pharmacological activation of human immunoglobulin G by chemical modification and active subfragments. XIII. Effect of carboxamidemethylated Fc fragment (CM-Fc) on type II collagen-induced arthritis in DBA/1J mice.

The effect of carboxamidemethylated Fc fragment (CM-Fc) from human immunoglobulin G (IgG) on type II collagen (C II)-induced arthritis (CIA) in DBA/1J mice was studied. CM-Fc suppressed the development of CIA while Fc fragment did not. CM-Fc inhibited the increase in serum anti-C II IgG. CM-Fc suppressed C II-induced delayed type hypersensitivity (DTH) in DBA/1J mice. Moreover, the C II-induced proliferation of splenocytes from mice immunized with C II was suppressed by the administration of CM-Fc. Following an analysis of the lymphocyte population, a decreased percentage of B220+ cells and ratio of L3T4+/Ly-2+ cells was observed in lymph nodes of CM-Fc administered mice as compared with those of control group. These results suggest that CM-Fc inhibits CIA by regulating lymphocyte function.

Animals↗

Studies on thermophile products. VIII. Isolation of Bacillus stearothermophilus UBT8038, a component that inhibits antigen presentation on mouse macrophages.

We have found a new compound from thermophile extracts which inhibits antigen presentation on mouse macrophages. The substance inhibits the expression of the class II major histocompatibility molecule (Ia). It was extracted from Bacillus stearothermophilus UBT8038 and purified by silica gel column chromatography. The isolated inhibitor, Fr. 8-A, was a phosphatidylethanolamine with isofatty acids and chemically different from any of the natural or synthetic products which have been reported to modify Ia expression. Fraction 8-A inhibits Ia expression by mouse peritoneal macrophages induced by the supernatant from concanavalin A stimulated spleen cell cultures in a dose-dependent fashion over the range 0.1-10 micrograms/ml. This fraction also exhibited inhibitory effects on antigen presentation by splenic macrophages in vitro and on the mixed leukocyte reaction. The present results show that Fr. 8-A has a unique inhibitory effect on antigen presenting cells.

Animals↗