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Biomedical subjects

T Itoh

Publications and source records attributed to T Itoh.

At least 235 records · Page 13Linked to original sources

Differential effect of antiallergic drugs on IgE-mediated cutaneous reaction in passively sensitized mice.

We investigated the effect of several antiallergic agents on murine IgE-mediated biphasic cutaneous reaction. Mice were passively sensitized by an intravenous injection of monoclonal anti-dinitrophenol (anti-DNP) IgE antibody. Skin reaction was elicited by an epicutaneous challenge of dinitrofluorobenzene (DNFB) and occurred biphasically with immediate-phase response (IPR) and late-phase response (LPR) at 1 and 24 h, respectively. Classical histamine H1 receptor antagonists and some chemical mediator-release inhibitors, such as diphenhydramine and terfenadine, inhibited IPR, but not LPR. In contrast, leukotriene B(4) (LTB(4)) receptor antagonist (ONO-4057) inhibited LPR only. Antagonists for LTC(4), D(4), E(4) receptor (ONO-1078) and platelet-activating factor (PAF) receptor (Y-24180) significantly inhibited both IPR and LPR, similarly to prednisolone. We recently found that a third-phase inflammatory reaction with marked infiltration of eosinophils (named very-late-phase response; vLPR), which is supposed to be a more important reaction in allergic diseases, was induced, peaking at day 8 following IPR and LPR in this model. The effect of these drugs on the triphasic skin reaction can be scored based on efficacy against IPR / LPR / vLPR; +/+/+ (prednisolone, a PAF receptor antagonist Y-24180, cyclosporin A and FK-506), +/-/- (diphenhydramine), +/+/- (azelastine and LT receptor antagonist ONO-1078), and -/+/+ (an LTB(4) receptor antagonist ONO-4057). Thus the inhibitory effect on vLPR as well as LPR may relate to the inhibition of eosinophil function mediated by LTB(4) and PAF and/or T cells. These findings may provide the basis for a treatment modality using various antiallergic agents in allergic disease.

Animals↗

Long-term administration of oral low-dose topoisomerase II inhibitors, MST-16 and VP-16, for refractory or relapsed non-Hodgkin's lymphoma.

It is known that the topoisomerase II inhibitors, MST-16 (sobuzoxane) and VP-16 (etoposide), are effective for the treatment of lymphoma. Five patients with refractory or relapsed non-Hodgkin's lymphoma (NHL) were treated with a combination of oral MST-16 and VP-16 over a long period. Two patients had severely refractory NHL. The remaining 3 patients could not be treated with intensive chemotherapy because of severe organ dysfunction or a poor hematopoietic reserve. All 5 are alive and well after MST-16 and VP-16 treatment. MST-16 and VP-16 are effective for NHL when intensive chemotherapy is ineffective or contraindicated.

Administration, Oral↗

Orally administered lactoferrin exerts an antimetastatic effect and enhances production of IL-18 in the intestinal epithelium.

The effects of oral administration of bovine lactoferrin (bLF) and its hydrolysate on the lung colonization by colon 26 carcinoma were investigated. At doses of 100 or 300 mg/kg/day for seven successive days, bLFs demonstrated a significant inhibitory effect on experimental metastasis, which indicated effectiveness before and after tumor implantation. Oral administration of bLFs augmented CD4+, CD8+, and asialoGM1+ cells in the spleen and peripheral blood. Their cytotoxic activities against Yac-1 and colon 26 carcinoma were enhanced by bLF. In the small intestinal epithelium, CD4+ and CD8+ cells were markedly increased, and, simultaneously, enhanced production of interleukin-18 (IL-18) was confirmed in the intestinal epithelial cells. In this model, intravenous injection of murine IL-18 showed significant inhibition of the lung colonization by colon 26 carcinoma. These results suggested that inhibition of experimental metastasis by oral administration of bLF and pepsin hydrolysate of bLF might be due to enhanced cellular immunity, presumably mediated by enhanced IL-18 production in the intestinal epithelium.

Administration, Oral↗

Cleavage of S-S bond by nitric oxide (NO) in the presence of oxygen: a disproportionation reaction of two disulfides.

Disulfide bond was cleaved by a catalytic amount of nitric oxide in the presence of oxygen, which was confirmed by experiments employing two symmetrical disulfides. The reaction resulted in the formation of unsymmetrical disulfides in nearly 50% yields. The steric hindrance of alkyl disulfide slowed the reaction rate, and an electron-donating group on the aryl disulfide promoted the reaction. The substituent and S-nitrosothiol effects suggested that the reaction was initialized with an oxidative process by NO+.

Disulfides↗

Dose and dose-rate effects of X rays and fission neutrons on lymphocyte apoptosis in p53(+/+) and p53(-/-) mice.

Following the exposure of mice to X rays or fission neutrons, the frequency (F) of apoptosis was measured after 4 h, and the weight loss or lymphocyte content loss in the thymus and spleen was measured after 24 h. In p53(+/+) mice, F increased linearly with the dose (D (Gy)) and the induced rate per Gy of F (detected by TUNEL staining) was 0.05 and 0.23 for X rays and fission neutrons, respectively. Therefore, the RBE of fission neutrons was 4.6 for apoptosis induction. This indicates that radiation-induced apoptosis is mostly due to double strand breaks (DSBs) in DNA because we previously obtained almost the same RBE value of fission neutrons for the induction of crossover mutations in Drosophila melanogaster, which arise from the recombinational repair of DSBs. In p53(+/+) mice, decreases in the organ weight and the lymphocyte content were observed for the thymus and the spleen 24 h after X-irradiation. These atrophic changes in the thymus and the spleen quantitatively corresponded to the total apoptotic cell deaths occurring in them. However, in p53(-/-) mice, no vigorous apoptosis was induced after X-irradiation, and hyperplastic changes in the weight and the lymphocyte content appeared in the thymus and the spleen 24 h after X-irradiation. In p53(+/+) mice, there was no difference in the induced rate per Gy of reduction in the surviving fraction of lymphocytes between acute (0.4 Gy/min) and chronic (3 mGy/min) gamma-irradiations. Namely, radiation-induced apoptosis in lymphocytes is a dose-rate independent event.

Animals↗

Primary amino acid and DNA sequences of gassericin T, a lactacin F-family bacteriocin produced by Lactobacillus gasseri SBT2055.

A broad-spectral bacteriocin, named gassericin T, produced by Lactobacillus gasseri SBT 2055 (from human feces) was isolated to homogeneity from the culture supernatant by hydrophobic chromatography. By SDS-PAGE and in situ activity assay, the purified gassericin T migrated as a single band with bacteriocin activity and molecular size of 5,400. A 2.9-kbp HindIII-HindIII fragment of chromosome DNA was hybridized with the oligonucleotide probe designed from the partial N-terminal amino acid sequence of gassericin T and was cloned. Six ORFs including the structural gene of gassericin T were deduced by computer analysis and the data bases. The structural gene of gassericin T (gatA) was identified as the fourth ORF, which encoded a protein composed of 75 amino acids that included the GG motif of the cleavage site. Chemical sequencing analysis of the complete amino acid sequence showed that gassericin T (57 amino acids) had a disulfide bond in the molecule and no modified amino acid residues, making it a class II bacteriocin. The gassericin T had 60% sequence similarity to mature LafA (57 amino acids, lactacin F, bacteriocins produced by L. johnsonii VPI11088), and the sequences around the processing site and C-terminal area were well conserved. The fifth ORF was designated as gatX, encoded as a peptide composed of 65 amino acids containing the GG motif of the putative cleavage site, however mature GatX and its antibacterial activity were not detected in the culture supernatant. GatX has higher similarity with LafX than with lactobin A (50 amino acids) belonging to the first lactacin F-family. These results indicated that gassericin T belongs to the hydrophobic class II bacteriocins and the most vicinal lactacin F-family.

Amino Acid Sequence↗

Efficient isolation and long-term viability of bovine small preantral follicles in vitro.

A comparison of isolation techniques for small preantral follicles (30-70 microm) from bovine ovaries using a mechanical method with a grating device or collagenase treatment was performed. The mean number (157.0) of intact follicles per ovary isolated by the mechanical method was significantly greater (P < 0.05) than that (26.0) of follicles isolated by the enzymatic method. Isolated morphologically normal follicles (MNF) were cultured for up to 30 d either in control cultures (non-coculture) or in coculture with bovine ovary mesenchymal cells (BOM), fetal bovine skin fibroblasts (FBF), and/or bovine granulosa cells (BGC). In control cultures, most of the follicles degenerated and only a few MNF (1.2%) were present after 30 d in culture. In contrast, the cocultures with BOM, FBF, and BGC resulted in 50.7, 46.6, and 21.4% viable MNF, respectively. Trypan blue and Hoechst 33258 staining were used for a quick and sensitive assessment of oocyte and granulosa cell viability during follicle isolation and culture in vitro. After 30 d, percentages of viable follicles in coculture with BOM (18.6%) and FBF (17.1%) were significantly greater than those of follicles in the control cultures (0%) or in coculture with BGC (10.0%). There was a gradual increase in the average diameter of the MNF during culture. The mean diameter of the follicles increased by 15.4 and 30.0% in coculture with BOM and FBF, respectively, by day 30. In conclusion, small bovine preantral follicles were efficiently isolated using a mechanical method that utilizes a grating device, and could be maintained for up to 30 d in the presence of mesenchymal cell cocultures such as BOM and FBF. This in vitro culture system that supports long-term survival of bovine preantral follicles should be beneficial for studying follicle growth and development.

Animals↗

Inhibitory effect of apple pectin and culture condensate of Bifidobacterium longum on colorectal tumors induced by 1,2-dimethylhydrazine in transgenic mice harboring human prototype c-Ha-ras genes.

The number and tumor score of colorectal tumors induced by 1,2-dymethylhydrazine in transgenic (Tg) mice carrying human c-Ha-ras genes were significantly reduced by ingestion of apple pectin (AP) or a culture condensate of Bifidobacterium longum (MB) when compared with a control diet. There was no statistical difference in the incidence of colorectal tumors in Tg mice between the AP or MB diet and the control diet. This study demonstrated that Tg mice are a useful tool for screening inhibition of colorectal tumors by functional foods.

1,2-Dimethylhydrazine↗

Decontamination of human xenotransplantable tumor with mouse hepatitis virus by implantation in nude rat: a case report.

A human tumor xenograft contaminated with mouse hepatitis virus (MHV) was implanted in a nude rat in order to decontaminate the tumor line. The decontamination failed in the first trial, but succeeded in the second trial. The difference between the two trials was the duration of implantation of the tumor in the nude rat, i.e., 12 days in the first and 24 days in the second trial. Duration of implantation might be a factor in the decontamination of transplantable tumors infected with MHV by passaging in the nude rat.

Animals↗

Analyses of structure of photoreceptor organelle and blepharismin-associated protein in unicellular eukaryote Blepharisma.

In the ciliated protozoan Blepharisma, step-up photophobic response is believed to be mediated by a novel type of photosensory pigment known as "blepharismins" (BL) that are contained in the pigment granules located just beneath the plasma membrane. We examined the ultrastructure of the pigment granules by freeze-fracture and thin-section electron microscopy and proposed a schematic diagram showing the granules' three-dimensional inner membranous structure. Some of the BL are suggested to be associated with 200 kDa membrane protein. High-pressure liquid chromatography analysis of pigment species associated with 200 kDa protein obtained from blue forms of Blepharisma (oxyblepharisma) revealed that the 200 kDa protein was associated with five types of oxyblepharismin. The fluorescence intensity was increased when the pigments were dissociated from the 200 kDa protein. The result supports the hypothesis that the pigment-200 kDa complex is able to transduce light energy into signals mediating the photobehavior of Blepharisma.

Animals↗

Administration of recombinant bovine tumor necrosis factor-alpha affects intermediary metabolism and insulin and growth hormone secretion in dairy heifers.

Four experiments were conducted to clarify the effect of intravenous (i.v.) administration of recombinant bovine tumor necrosis factor alpha (rbTNF) on selected metabolites and on hormone secretion in Holstein heifers (n = 6; 347.0 kg average BW). In Exp. 1, rbTNF was injected at three dosage levels in a Latin square; 0 (CONT), 2.5 (TNF2.5), or 5.0 (TNF5) microg/kg BW. Plasma glucose and triglyceride concentrations were at first elevated (P < .05) by rbTNF treatment and then were decreased (P < .05) by TNF2.5 and TNF5. Plasma NEFA concentrations were increased (P < .05) in rbTNF-treated groups. The injection of rbTNF resulted in an increase in plasma insulin levels (P < .05 with TNF5) during the period between 2 and 24 h, except for the period between 6 and 8 h, after the treatment. In Exp. 2, 3, and 4, each heifer received i.v. injections of glucose (.625 mM/kg BW) + rbTNF (5 microg/kg) or glucose + saline (10 mL) (Exp. 2), insulin (0.2 U/kg) + rbTNF or insulin + saline (Exp. 3), and GHRH (0.25 microg/kg) + rbTNF or GHRH + saline (Exp. 4) at 1-wk intervals. In Exp. 2, rbTNF inhibited (P < .05) glucose-stimulated insulin secretion during the initial phase. Thereafter, plasma insulin was higher (P < .01) with the glucose + rbTNF treatment than with the glucose + saline treatment. Treatment with rbTNF inhibited the insulin-stimulated glucose utilization (Exp. 3) and GHRH-stimulated GH secretion (Exp. 4) during the initial phase. These results suggest that rbTNF directly and(or) indirectly affects the intermediary metabolism and hormone secretion in Holstein heifers.

Animals↗

Isolation and structural analysis of antihypertensive peptides that exist naturally in Gouda cheese.

Seven kinds of ripened cheeses (8-mo-aged and 24-mo-aged Gouda, Emmental, Blue, Camembert, Edam, and Havarti) were homogenized with distilled water, and water-soluble peptides were prepared by C-18 hydrophobic chromatography. The inhibitory activity to angiotensin I-converting enzyme and decrease in the systolic blood pressure in spontaneously hypertensive rats were measured before and after oral administration of each peptide sample. The strongest depressive effect in the systolic blood pressure (-24.7 mm Hg) and intensive inhibitory activity to angiotensin I-converting enzyme (75.7%) were detected in the peptides from 8-mo-aged Gouda cheese. Four peptides were isolated by HPLC with reverse-phase and gel filtration modes. Their chemical structures and origins, clarified by combination analyses of protein sequencing, amino acid composition, and mass spectrometry, were as follows: peptide A, Arg-Pro-Lys-His-Pro-Ile-Lys-His-Gln [alpha(s1)-casein (CN), B-8P; f 1-9]; peptide B, Arg-Pro-Lys-His-Pro-Ile-Lys-His-Gln-Gly-Leu-Pro-Gln (alpha(s1)-CN, B-8P; f 1-13); peptide F, Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-Asn (beta-CN, A2-5P; f 60-68); and peptide G, Met-Pro-Phe-Pro-Lys-Tyr-Pro-Val-Gln-Pro-Phe (beta-CN, A2-5P; f 109-119). Peptides A and F, which were chemically synthesized, showed potent angiotensin I-converting enzyme inhibitory activity with little antihypertensive effects.

Amino Acid Sequence↗

Relationship between eradication therapy and clarithromycin-resistant Helicobacter pylori in Japan.

Since clarithromycin is expected to be widely used to treat Helicobacter pylori infection in the near future, it is important to investigate the relationship between resistance to clarithromycin and the regimens of eradication therapy. We investigated: (1) the usefulness of susceptibility tests prior to eradication therapy, and (2) the rate of acquisition of H. pylori resistance to clarithromycin after treatment failure. Drug susceptibility tests to clarithromycin and amoxicillin were conducted by Dry Plate Test or E-test. The subjects in the first part of this study included 112 patients with H. pylori infection who received triple therapy with various combinations of drugs, including clarithromycin. The eradication rate in patients with clarithromycin-susceptible H. pylori was significantly higher than that in patients with clarithromycin-resistant H. pylori. The second part of this study included 21 patients in whom H. pylori was not eradicated by triple therapy and 12 patients in whom H. pylori was not eradicated with dual therapy including clarithromycin. Of the 33 patients showing non-eradication. 90.9% of those treated with dual therapy and 35.7% of those treated with triple therapy acquired secondary resistance of H. pylori to clarithromycin. We conclude that it is important to conduct drug susceptibility tests prior to treatment of H. pylori infection. Since the incidence of acquiring clarithromycin resistance was significantly higher in the patients showing non-eradication, it is important to choose a regimen with a higher eradication rate, such as triple therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

New multifunctional percutaneous transluminal coronary angioplasty catheter device capable of balloon inflation, local drug delivery and coronary perfusion.

A new percutaneous transluminal coronary angioplasty catheter with multiple functions of balloon inflation, local drug delivery and coronary perfusion has been devised. The device consists of an inflatable lumen, a drug delivery lumen, and a perfusion (or guide wire) lumen. A drug can be infused from the port located distal to the inflated balloon during continuous blood perfusion via the perfusion lumen. Fluorescence-labeled heparin and peroxidase administered using the device permeated into denuded vessel tissues during ongoing perfusion and remained there for over 24 hr. This prototype device indicates the potential therapeutic implications of the concepts of the device.

Angioplasty, Balloon, Coronary↗

[Analysis of pulmonary function in leukemia patients after bone marrow transplantation: effects of prior chemotherapy].

To evaluate the effects of prior chemotherapy on pulmonary function after bone marrow transplantation(BMT), pulmonary function tests were performed prior to and after BMT on 7 acute leukemia (AL) and 13 chronic myelogenous leukemia (CML) patients given with CY (60 mg/kg x 2 days), total body irradiation (3 Gy x 4 days, 10 cGy/min), and CyA plus short-term MTX. No patient had graft-versus-host disease or lung complications. Pulmonary function after BMT did not deteriorate in the AL patients; however, both %Vital Capacity(%VC) and DL/VA decreased significantly in the CML patients (%VC before BMT: 112.1 +/- 11.5%, after BMT: 93.7 +/- 9.4%; DL/VA before BMT: 79.2 +/- 14.6%, after BMT: 54.1 +/- 10.6%). Although prior regimens of busulfan (BU) or interferon (IFN) were equal risk factors for decreased %VC after BMT, decreases in DV/VA were more significant in CML patients who received IFN. CML patients, especially those who have received BU or IFN, should be carefully monitored for pulmonary function to prevent respiratory failure after BMT.

Acute Disease↗

Volume-weighted mean nuclear volume. Is this new prognosticator comparable in different institutions?

OBJECTIVE: To determine whether volume-weighted mean nuclear volume (MNV) obtained at one institution is comparable to that from other institutions. STUDY DESIGN: MNV calculated from histologic slides obtained at three hospitals--Shizuoka Prefectural Hospital (SPH), Shimada Municipal Hospital (SMH) and Shizuoka City Hospital (SCH)--were compared. Between December 1994 and June 1996, transurethral resection of bladder tumor or transurethral resection of the prostate was performed on 37 patients at SPH and 50 patients at SMH; histologic specimens from 40 cases of bladder tumors, 63 cases of normal bladder mucosa, 28 cases of benign prostatic hyperplasia and 1 case of prostate cancer were obtained. A portion of each specimen obtained at SPH or SMH was carried to SCH, and histologic slides were made at SCH using it. Using the remaining position of each specimen, histologic slides were then prepared at each hospital. Estimates of MNV were made from all histologic slides from each hospital, and the differences in MNV between the hospitals were analyzed. In addition, intraobserver and interobserver reproducibility were analyzed using 50 specimens obtained between December 1994 and August 1995. RESULTS: On linear regression analysis, comparison of MNVs calculated from the histologic slides from SPH and SCH and those calculated from SMH and SCH revealed high correlation coefficients (R = .966 and .966, respectively), and the slope of the regression line did not differ significantly from unity. The paired t test also disclosed no significant difference between MNVs calculated at the two hospitals. Furthermore, the correlation coefficients for intraobserver and interobserver reproducibility of MNV estimates were also high (R = .918 and .949, respectively). CONCLUSION: The results of this study indicate that estimates of MNV are comparable in multiple institutions, and we recommend that they be used to support subjective histologic grading.

Cell Nucleus↗

[Evaluation of hematopoiesis by granulocyte elastase after hematopoietic stem cell transplantation].

To evaluate hematopoietic restoration after hematopoietic stem cell transplantation (HSCT), we sequentially monitored the post-HSCT level of granulocyte elastase (GE), a sensitive parameter of qualitative and quantitative changes in granulopoiesis. We compared it with routinely used hematopoietic recovery indices, such as leukocyte and reticulocyte count. We also compared levels of GE in the clinical administration of different colony stimulating factors (granulocyte-colony stimulating factor (G-CSF) versus macrophage-colony stimulating factor (M-CSF) and in different types of hematopoietic stem cell transplantation (allogeneic bone marrow transplantation (BMT) versus autologus peripheral blood stem cell transplantation (PBSCT)). Days to first increase of GE after HSCT were 3.0 and 2.3 days earlier than increase of leukocytes in allo-BMT and auto-PBSCT, respectively. Recovery of highly fluorescent reticulocytes and monocytes were later than recovery of GE. These results indicated that granulopoiesis after transplantation started before the increase in peripheral leucocyte count, and that GE was the earliest indicator of hematopoietic recovery. On the basis of GE level, M-CSF had the same stimulating effect on granulopoiesis as G-CSF. The nadir of GE in PBSCT was significantly higher than that in BMT, indicating continuous granulopoiesis in PBSCT. From these results, we concluded that measurements of GE can be used for the clinical evaluation of myelosuppression by different conditioning regimens as well as of granulopoiesis induced by various cytokines.

Adolescent↗