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Biomedical subjects

M Kimoto

Publications and source records attributed to M Kimoto.

At least 73 records · Page 4Linked to original sources
PubMed1998

Staging and treatment for patients with pancreatic cancer. How small is an early pancreatic cancer?

To determine the tumor size that constitutes early pancreatic cancer, we reviewed and analyzed the English-language and Japanese literature (a total of 25 publications) on small pancreatic cancers less than 2 cm in diameter and/or stage 1 cancers. Reports on in situ carcinoma and intraductal carcinoma of the pancreas were also evaluated. The results were: (1) A total of 302 cases of small pancreatic cancer less than 2 cm in diameter reported at separate institutions were pooled from 15 reports. The rates for patients in stage I and those with no lymph node metastasis averaged 41.7% and 57.9%, respectively. The 5-year postoperative cumulative survival rate (5Y-PCR) was less than 50% in almost all these reports. Similar data were shown in the 7 collective reviews. (2) Another 33 cases of small pancreatic cancer of 1 cm or less in diameter were collected from three reports. The rates for stage I tumor and 5Y-PCR at one institution with two reports were 100% and 100% and the rates in the other report were 85% and 78%, respectively. (3) Twelve cases of in situ carcinoma and intraductal carcinoma of the pancreas were collected from four reports. All of the patients were stage I and were alive with no evidence of tumor recurrence for periods ranging from 6 to 78 months. Small pancreatic cancer less than 1 cm in diameter is better viewed as an early pancreatic cancer, and in situ carcinoma and intraductal carcinoma of the pancreas with minimal invasion to the pancreatic parenchyma may be defined as early pancreatic cancer, regardless of size.

Carcinoma↗
PubMed1998

Fosfomycin, an antibiotic, possessed TGF-beta-like immunoregulatory activities.

The regulatory effects of fosfomycin (FOM) were correlated closely with the multifunction of TGF-beta in the modulation of immune responses in vivo and in vitro. LPS-induced polyclonal IgM and IgG antibody responses were depressed at 3 days after the initial culture and subsequently enhanced at day 10 by FOM or TGF-beta. Neither FOM nor TGF-beta inhibited LPS-induced IgA antibody responses, whereas dexamethasone (DX) reduced polyclonal IgM, IgG and IgA antibody responses wholly. The suppression of antibody responses and Mv1Lu cell proliferation induced by FOM or TGF-beta was partly overcome with soluble TFG-beta receptors (sRIII). Oral, i.v. and i.p. administration of FOM exhibited similar enhanced SRBC-specific antibody responses to that seen after oral administration of TGF-beta. The addition of FOM and latent TGF-beta inhibited the proliferation of Mv1Lu cells, but FOM did not lead to an increase in plasmin activities, which convert latent to active TGF-beta, and further the expression of TGF-beta receptors on the cell surface. In addition, FOM failed to enhance TGF-beta secretion. These findings suggest that immunomodulation of FOM results in increased sensitivity of cells to TGF-beta.

Adjuvants, Immunologic↗
PubMed1998

Autoreactive CD4- CD8- alpha beta T cells to vaccinate adjuvant arthritis.

Studies suggested that experimental autoimmune diseases can effectively be prevented and treated by application of normal autoreactive T cells or autoreactive T cells in an attenuated form. In this study, several autoreactive CD4- CD8- T-cell clones (A2, A6, and A13 cells) were isolated for the first time from the draining lymph nodes of Lewis rats with adjuvant arthritis (AA). Surprisingly, intraperitoneal inoculation with A13 cells, but not A2 or A6 cells protected rats from AA both clinically and histologically. It was demonstrated that A13 cells were CD4- CD8- alpha beta T cells, and showed proliferative responses to irradiated syngeneic spleen cells (antigen-presenting cells; APC). Interestingly, A13 cells proliferated against concanavalin A (Con A) and staphylococcal enterotoxin B (SEB), but did not show any proliferation to Mycobacterium tuberculosis (Mt), or its 65 000 MW heat-shock protein (HSP). Rats protected from AA by inoculation with A13 cells showed a specific anti-idiotypic delayed-type hypersensitivity reaction compared with other autoreactive T cells (A2 or A6 cells). These findings demonstrate that AA can be suppressed by autoreactive CD4- CD8- alpha beta T cells, and these cells may be used as therapeutic agents in experimental autoimmunity.

Adoptive Transfer↗
PubMed1998

Peptide-binding motifs of the mixed haplotype Abetaz/Aalphad major histocompatibility complex class II molecule: a restriction element for auto-reactive T cells in (NZBxNZW)F1 mice.

We previously showed that the mixed haplotype Abetaz/Aalphad major histocompatibility complex (MHC) class II molecules function as restricting element for autoreactive T-cell clones derived from autoimmune prone (NZBxNZW)F1 (B/WF1) mice. Subsequent analysis revealed that some of these Abetaz/Aalphad-restricted autoreactive T-cell clones were pathogenic upon transfer to pre-autoimmune B/WF1 mice. In this paper, we analysed the peptide-binding motif of Abetaz/Aalphad class II molecules. Amino acid-sequencing analysis of peptides eluted from purified Abetaz/Aalphad molecules revealed several sequences, including one that corresponds to murine l-plastin 588-601. Synthetic 18-mer l-plastin 588-605 peptide (SMARKIGARVYALPEDLV, as described by the amino acid single letter code) was demonstrated to bind to Abetaz/Aalphad MHC class II molecules on transfectant B lymphoma cells (TAbetaz). A competitive binding inhibition assay using truncation peptides revealed the core sequence for binding resides in 591Arg to 601Pro. Binding inhibition assay using substitution peptides, each having substitution to the other 19 residues at positions from 590Ala to 601Pro, revealed four major anchor sites 592Lys (p1), 594Gly (p3), 595Ala (p4), 597Val (p6) and one minor anchor site 600Leu (p9). Positively charged residues are not allowed at p3 and negatively charged residues are not allowed at p4 and p6. Relatively large hydrophobic residues (Leu, Ile) are not tolerated at p3 and p4. Met and Trp are not tolerated at p6. Based on these findings, the characteristics of peptides recognized by autoreactive T cells in B/WF1 mice are discussed.

Animals↗
PubMed1998

Augmentation of natural killer cell activity in mice by oral administration of transforming growth factor-beta.

The latent form of transforming growth factor-beta (TGF-beta) in human milk and platelets was converted to the active form when conscious, pylorus-ligated mice were given human milk and platelets by intragastric intubation. Oral administration of TGF-beta exerted enhancing effects on the natural killer (NK)-cell activities in spleen and liver. Augmentation of NK-cell activities in spleen was observed for 7 days after oral administration of TGF-beta. TGF-beta at concentrations of 5 and 20 ng produced the greatest augmentation of NK-cell activities in spleen. However, NK-cell activities in spleen were unaffected when TGF-beta was given intravenously. Interleukin (IL)-12 production in spleen was enhanced by oral administration of TGF-beta, but not by intravenous administration of TGF-beta. These findings suggest that large amounts of TGF-beta in human milk are involved in early antiviral protection through the augmentation of NK-cell activities.

Administration, Oral↗
PubMed1998

Quantitative analysis of Gly m Bd 28K in soybean products by a sandwich enzyme-linked immunosorbent assay.

A sandwich enzyme-linked immunosorbent assay for the soybean allergen, which consists of a monoclonal antibody (D4) as the fixing (first) antibody and another peroxidase-conjugated monoclonal antibody (C5) as the second, has been developed. Both D4 and C5 monoclonal antibodies strongly bound to the guanidine/HCl-denatured allergen, Gly m Bd 28K. Therefore the samples used in the present experiment were extracted with sodium phosphate buffer (pH 8.0) containing 6 M guanidine and 10 mM 2-mercaptoethanol, then completely dialyzed against phosphate-buffered saline (PBS). The dialyzed samples were subjected to the assay. Various soybean products were observed to contain the allergen at high concentrations, such as soybean protein isolate (SPI), tofu, kori-dofu, and yuba, but its content in soy milk and abura-age were found to be low. In fermented products such as natto, soy sauce, and miso, and even in the processed foods with soybean protein isolate (SPI), the allergen was not detected. These results were also confirmed by an immunoblotting technique with D4.

Allergens↗
PubMed1998

[Sequential chemotherapy with methotrexate and 5-fluorouracil for advanced gastric cancer].

Sequential chemotherapy with methotrexate and 5-fluorouracil (MTX/5-FU) for advanced gastric cancer was given 29 patients. The procedure consisted of weekly MTX 100 mg/m2 (i.v.) followed three hours later by 5-FU 600 mg/m2 (i.v.) with leucovorin rescue on each of the following two days. Nine of 28 patients (32.1%) showed partial response to this treatment. Response rates were 28.6% in the 21 cases with poorly differentiated adenocarcinoma and 42.9% in the 7 cases with well- or moderately-differentiated adenocarcinoma. This procedure was especially effective for primary lesions (PR 9/20: 45%) and lymphnode metastases (CR 4 + PR 4, 8/17: 47.1%). Side effects were mild leukopenia and G-I symptoms such as nausea, diarrhea and loss of appetite, except in 1 patient who died of severe myelosuppression with sepsis. We concluded that sequential MTX/5-FU therapy is fairly effective and the adjuvant chemotherapy of choice for advanced or recurrent gastric cancer with not only poorly differentiated adenocarcinoma but also well- or moderately-differentiated adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Differential display cloning of a novel rat cDNA (RNB6) that shows high expression in the neonatal brain revealed a member of Ena/VASP family.

We have used the differential display method to identify genes that control the neural cell development in CNS. Screening of the differential display bands that showed higher expression at neonate than at adult age enabled us to identify a novel rat cDNA (RNB6) coding for a protein of 393 amino acid residues. Database search revealed this gene as a rat homologue of the murine EVL, a member of Ena/VASP protein family that is implicated to be involved in the control of cell motility through actin filament assembly by their GP5 motifs. Although the precise characterization of EVL was not reported, our Northern blot and immunoblot analyses demonstrated that RNB6 expression in the brain gradually increases during embryonic development, reaches maximum at postnatal day 1 and decreases thereafter. Studies of tissue distribution revealed the expression of RNB6 not only in the brain but also in the spleen, thymus and testis. Histochemical analyses showed that RNB6 protein is mainly expressed in neurons and may be expressed in neural fibers. Our analyses suggest that RNB6 is critically involved in the development of CNS probably through the control of neural cell motility and/or including neuronal fiber extension.

Amino Acid Sequence↗
PubMed1997

Cloning and sequencing of cDNA encoding NG,NG-dimethylarginine dimethylaminohydrolase from rat kidney.

Three cDNA clones encoding NG,NG-dimethylarginine dimethylamino-hydrolase (EC 3.5.3.18) have been isolated from a rat kidney lambda gt11 library using a probe prepared by PCR on the basis of partially determined amino-acid sequences of the enzyme. The sequence analyses of the cDNAs established that the 3008 bp cDNA contains 855 bp open reading frame encoding 285 amino acids (M(r) 31414), 3'-flanking region (1722 bp) and 5'-flanking region (431 bp). The amino-acid sequences of all the peptides isolated from the purified enzyme were shown to be included in the deduced amino-acid sequence. Northern blotting analyses showed that the mRNA (4 kb) is ubiquitously expressed in various rat tissues.

Amidohydrolases↗
PubMed1997

Analysis of Vbeta4 T cell receptor CDR3 repertoire in BALB/c and (NZB x NZW)F1 mice.

To examine the unique TCR repertoire in auto-immune-prone (NZB x NZW)F1 (B/WF1) mice, we analysed the Vbeta4 CDR3 region of TCRbeta chain in spleens of young (1 month old) and aged (6 month old) BALB/c and B/WF1 mice. Total RNA from spleens was used for cDNA synthesis and TCRVbeta4 PCR products were cloned and sequenced. Young B/WF1 mice showed high frequency (38.5%) of anionic amino acid residues at position beta100 in TCRVbeta4 chain compared to that (19.0%) in young BALB/c mice. Aged BALB/c mice and B/WF1 mice showed increase of frequency (38.1 and 51.9%, respectively) of anionic residues at beta100. These results indicate that Vbeta4-T cells that have anionic residues at beta100 in CDR3 region of TCRbeta chain increase with age in normal mice. Auto-immune prone mice show high frequency of anionic residues at beta100 in TCRVbeta4 chain even at the age of 1 month. These T cells may interact with cationic self-antigen(s) and might contribute to the onset and/or the progression of systemic autoimmunity in concert with other genetic elements in B/WF1 mice.

Amino Acid Sequence↗
PubMed1997

Colocalization of demethylating enzymes and NOS and functional effects of methylarginines in rat kidney.

NG-monomethylarginine (L-NMA) and asymmetric NG, NG-dimethylarginines (ADMA) are endogenous inhibitors of cellular L-arginine uptake and/or nitric oxide (NO) synthesis that are implicated in renal parenchymal and Dahl salt-sensitive hypertension. Since the L-arginine:(L-NMA + ADMA) ratio determines NO synthase (NOS) activity, we compared the immunohistochemical distribution of NOS with NG, NG-dimethylarginine dimethylaminohydrolase (DDAH), which inactivates dimethylarginines (DMA) and L-NMA by hydrolysis to L-citrulline. Neuronal NOS (nNOS) was expressed predominantly in tubular epithelial cells of macula densa (MD), endothelial NOS (eNOS) in vascular endothelial cells (EC), and inducible NOS (iNOS) quite widely in tubular epithelium, including proximal tubules (PT), thick ascending limbs of Henle (TAL), distal convoluted tubule and intercalated cells (IC) of the collecting duct. Immunostaining for DDAH was present in PT, TAL, MD, and IC, and was also present in the glomerulus, Bowman's capsule, and endothelium of blood vessels. DDAH was detected in small vesicles of TAL and PT by electron microscopic (EM) immunocytochemistry. To study the effects of methylarginines on tubuloglomerular feedback (TGF) response, vehicle or methylarginines (10(-3) M) were added to artificial tubular fluid (ATF) perfused orthogradely from the late PT at 40 nl. min-1 while assessing changes in glomerular capillary pressure from proximal stop flow pressure (PSF). Whereas the maximal TGF responses were unchanged by vehicle (delta TGF 0 +/- 0%) or symmetric DMA (SDMA; +1 +/- 2%, NS), they were enhanced by L-NMA (+22 +/- 4%, P < 0.001) and asymmetric DMA (ADMA; +28 +/- 3%, P < 0.001). Since L-arginine transport can regulate renal epithelial NO generation, methylarginines (10(-3) M) or vehicle were co-perfused orthogradely with [3H]-L-arginine from the late PT and collected at the early distal tubule to study arginine uptake from the perfused loop of Henle. All methylarginines reduced fractional loop [3H] absorption significantly (P < 0.001; vehicle, 84 +/- 6; ADMA, 49 +/- 6; SDMA, 56 +/- 6; L-NMA, 41 +/- 6%). In conclusion, sites of DDAH expression in the vasculature or nephron are all sites of expression of an isoform of NOS. L-NMA, ADMA, and SDMA all inhibit renal tubular L-arginine uptake, whereas L-NMA and ADMA, but not SDMA, enhance TGF responses. Therefore, DDAH may regulate the cellular L-arginine: methylarginine levels in specific renal cells, thereby governing cell-specific L-arginine uptake and NO generation in renal tubular epithelium.

Amidohydrolases↗
PubMed1997

Asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in experimental hypertension.

NG,NG-dimethyl-L-arginine (ADMA) is an endogenously synthesized nitric oxide (NO) synthase inhibitor which has potent pressor/vasoconstrictor effects. Dimethylargininase metabolizes ADMA to L-citrulline and plays a key role in determining the in vivo levels of ADMA. To investigate the role of ADMA in the pathogenesis of hypertension, we measured 24-hour urinary excretion of ADMA (UADMA) and nitrate/nitrite (NOx) in Dahl salt-sensitive hypertensive rats and spontaneously hypertensive rats (SHR). In Dahl salt-resistant rats, high-salt diet (8% NaCl) did not increase blood pressure and increased urinary NOx (P < .01) without changes in UADMA compared with low-salt diet (0.3% NaCl). In contrast, in Dahl salt-sensitive rats, high-salt diet increased blood pressure (P < .01), did not change urinary NOx excretion, and increased UADMA (P < .01). There was a significant (r = .65, P < .01) correlation between UADMA and the level of blood pressure in Dahl salt-sensitive rats. Plasma levels of NOx and ADMA and renal dimethylargininase content were comparable among them. These results may suggest that in Dahl salt-resistant rats, blood pressure is kept constant during high-salt intake, possibly due to the compensatory increased production of NO, and that in Dahl salt-sensitive rats, high-salt intake increases the production of ADMA, attenuates the compensatory increases in NO, and increases blood pressure. These results also suggest that the systemic production of ADMA is not dependent on renal dimethylargininase. SHR had significantly greater urinary NOx excretion (P < .05) and smaller UADMA than Wistar-Kyoto rats (P < .05), and UADMA was inversely correlated with their mean arterial pressure (r =.64, P < .05). In conclusion. ADMA, independently of the renal dimethylargininase content, may play a role in the pathogenesis in Dahl salt-sensitive hypertensive rats but not in SHR.

Amidohydrolases↗
PubMed1997

Purification of characterization of soybean allergen Gly m Bd 28K.

At least 15 allergenic proteins have been found in soybean using the sera of soybean-sensitive patients with atopic dermatitis [T. Ogawa et al., J. Nutr. Sci. Vitaminol., 35, 555-565 (1991)]. In the present study, a monoclonal antibody (mAb) against Gly m Bd 28K, one of the major allergens of soybean, was prepared, and Gly m Bd 28K was purified from defatted soybean flakes by five purification steps, including immunoaffinity chromatography with the mAb as a ligand. The purified allergen was found to be a glycoprotein with a molecular mass of 26 kDa. During the purification process the allergen was converted to more acidic proteins with the same molecular mass, suggesting that the allergen is unstable. The sugar composition and amino acid sequence of Gly m Bd 28K suggest that the allergen is a new glycoprotein with an Asn-linked sugar moiety. The distribution of the allergen in soybean products was examined by an immunoblotting technique with the mAb.

Allergens↗
PubMed1997

[A case of papillary adenocarcinoma of the stomach with liver metastases and carcinomatous peritonitis treated effectively by methotrexate/5-fluorouracil sequential chemotherapy].

A 54-year-old male was admitted to receive treatment by anticancer drug for advanced gastric cancer with liver metastases and carcinomatous peritonitis. Upper gastrointestinal series showed a Borrmann type 4 gastric cancer occupying the body and antrum, and a pathological diagnosis of papillary adenocarcinoma was made by endoscopic biopsy. Two cycles of neoadjuvant chemotherapy consisting of 5-FU and low-dose CDDP (FP therapy) were given. No effect was observed, so that the next chemotherapy schedule of sequential MTX/5-FU therapy was performed. We adopted the intermediate (MTX: 100 mg/m2 and 5-FU 600 mg/m2 weekly) dose regimen. When six courses of this regimen were completed, the primary lesion of the stomach was decreased to 60% and the metastatic liver tumor to 72%, basel on criteria for the evaluation of clinical effects of solid cancer chemotherapy. However, pylorous stenosis remained, and we performed gastrojejunostomy and biopsy of the regional lymph node to determine the response to the chemotherapy. A pathological examination of lymph node revealed metastatic papillary adenocarcinoma with xanthogranulomatous change, and was judged as an effect showing grade 2. He was discharged and had the outpatient hospital treatment. He died of exacerbation of carcinomatous peritonitis 10 months after his initial admission. The response duration for sequential MTX/5-FU therapy was 4 months. This therapy was usually effective in patients with poorly differentiated adenocarcinoma of the stomach. Our result indicates that this therapy can be effective for not only poorly differentiated adenocarcinoma but also papillary adenocarcinoma of the stomach in an advanced stage.

Adenocarcinoma, Papillary↗
PubMed1996

Molecular cloning of a human RP105 homologue and chromosomal localization of the mouse and human RP105 genes (Ly64 and LY64).

RP105 is a mouse B cell surface molecule that transmits a growth-promoting signal and is implicated in the life/death decision of B cells. RP105 has tandem repeats of a leucine-rich motif in the extracellular domain that is expected to be involved in protein-protein interactions. In the present study, a cDNA clone encoding the human homologue of RP105 was isolated. The amino acid sequence of human RP105 is highly homologous to that of mouse RP105 with 74% identity, and the leucine-rich repeats are well conserved. The expression of the human RP105 transcript was detected in some B cell lines, a histiocytic leukemia cell line, and peripheral blood leukocytes. We also determined the chromosomal locations of the mouse RP105 gene (Ly64 locus) and the human RP105 gene (LY64 locus). Interspecific mouse backcross analysis was used to map the Ly64 locus at the distal region of chromosome 13. The human LY64 locus was localized to 5q12 by fluorescence in situ hybridization, confirming the syntenic relationship between these regions of the mouse and human chromosomes.

Amino Acid Sequence↗
PubMed1996

Cloning and sequencing of cDNA encoding 4-aminobenzoate hydroxylase from Agaricus bisporus.

A cDNA clone encoding 4-aminobenzoate hydroxylase (EC 1.14.13.27) has been isolated using a probe prepared by PCR on the basis of partially determined amino acid sequences of the enzyme. The cDNA contained 1380-base pair open reading frame encoding 460 amino acid residues (M(r) 50974), 14-base pair 5'-untranslated region and 123-base pair 3'-untranslated region including a poly(A) tail of 20 nucleotides. All of the partially determined amino acid sequences were shown to be included in the deduced amino acid sequence. Homology analyses showed that the two regions on the enzyme share other flavoproteins such as salicylate hydroxylase and p-hydroxybenzoate hydroxylase.

Adenosine Diphosphate↗