Pilot study of oral tolerance to keyhole limpet hemocyanin in humans: down-regulation of KLH-reactive precursor-cell frequency.
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Administration, Oral↗
Biomedical subjects
M Matsui
Publications and source records attributed to M Matsui.
A new transgenic mouse mutagenesis test system using Spi- and 6-thioguanine selections.
A new transgenic mouse mutagenesis test system has been developed for the efficient detection of point mutations and deletion mutations in vivo. The mice carry lambda EG10 DNA as a transgene. When the rescued phages are infected into Escherichia coli YG6020-expressing Cre recombinase, the phage DNA is converted into plasmid pYG142 carrying the chloramphenicol-resistance gene and the gpt gene of E. coli. The gpt mutants can be positively detected as colonies arising on plates containing chloramphenicol and 6-thioguanine. The EG10 DNA carries a chi site along with the red and gam genes so that the wild-type phages display Spi- (sensitive to P2 interference) phenotype. Mutant phages lacking both red and gam genes can be positively detected as plaques that grow in P2 lysogens of E. coli. These mutant phages are called lambda Spi-. The spontaneous gpt mutation frequencies of five independent transgenic lines were 1.7 to 3.3 x 10(-5) in bone marrow. When the mice were treated with ethylnitrosourea (single i.p. treatments with 150 mg/kg body weight; killed 7 days after the treatments), mutation frequencies were increased four- to sevenfold over the background in bone marrow. The average rescue efficiencies were more than 200,000 chloramphenicol-resistant colonies per 7.5 micrograms bone marrow DNA per packaging reaction. In contrast to gpt mutation frequencies, spontaneous Spi- mutation frequencies were 1.4 x 10(-6) and 1.1 x 10(-6) in bone marrow and sperm, respectively. No spontaneous Spi- mutants have been detected so far in spleen, although 930,000 phages rescued from untreated mice were screened. In gamma-ray-treated animals, however, induction of Spi- mutations was clearly observed in spleen, at frequencies of 1.4 x 10(-5) (5 Gy), 1.2 x 10(-5) (10 Gy), and 2.0 x 10(-5) (5O Gy). These results suggest that the new transgenic mouse "gpt delta" could be useful for the efficient detection of point mutations and deletion mutations in vivo.
Animals↗
Long-term cryopreserved allogeneic nervous and vascular tissue transfers in monkeys.
Four adult Japanese monkeys were used. Donor tissues were harvested from the radial artery, saphenous vein and median nerve, 10 cm in length, and cryopreserved at -196 degrees C in a stepwise manner for long-term preservation for more than 6 months. After rapid thawing of the tissue, the allogeneic tissue transfer was performed of the radial artery to the radial artery, the saphenous vein to the ulnar artery and the median nerve to the median nerve between male and female monkeys. After one year follow-up, angiography was performed and the transferred tissue was harvested for scanning electron microscopic examination and histological examination. As a result, the allogeneic artery in the radial artery was completely patent with no stenosis, whereas there was obstruction of the allogeneic vein in the ulnar artery. Good axonal recovery of the median nerve was observed on histological examination. The cellular structure of neurovascular tissue can be maintained even after long-term cryopreservation. The antigenicity of tissue may be reduced significantly by being frozen, and cryopreserved allogeneic artery can be transferred successfully without the use of immunosuppressive agents. In this report, clinical aspects and the great potential of allogeneic neurovascular tissue transfer, especially in combination with arterial transfer, using cryopreservation are discussed.
Animals↗
IL-10 suppresses cell surface CD23/Fc epsilon RII expression, not by enhancing soluble CD23 release, but by reducing CD23 mRNA expression in human monocytes.
To examine a possible involvement of interleukin-10 (IL-10) in CD23/Fc epsilon RII expression in human monocytes, effects of IL-10 on the cell surface CD23 expression, soluble CD23 (sCD23) release, and CD23 type b mRNA expression were investigated. IL-10 suppressed IL-4-induced surface CD23 expression on monocytes in a dose-dependent manner, and this effect was completely neutralized by anti-IL-10 antibody. The suppressive effect of IL-10 on surface CD23 expression was not due to enhancement of sCD23 release from the cell surface because no increase in sCD23 in culture supernatant was detected after incubation with IL-10. Instead, the effect of IL-10 seemed to be exerted at the transcriptional level since IL-4-induced expression of CD23 type b mRNA was significantly reduced when IL-10 was present. Although IL-4 induced surface CD23 expression on both monocytes and B cells, the suppressive effect of IL-10 was observed only on monocytes, which underscores different regulatory mechanisms for CD23 expression between the two cell types.
B-Lymphocytes↗
Human calcitonin has the same inhibitory effect on osteoclastic bone resorption by human giant cell tumor cells as salmon calcitonin.
Human calcitonin (hCT) has been reported to have a less hypocalcemizing effect on rats and to have a lower binding affinity for the receptor of mouse osteoclasts than salmon CT(sCT). In this study we comparatively examined the effect of hCT and sCT on osteoclastic bone-resorbing activity of unfractionated cells obtained from human giant cell tumor of bone and from rabbit and mouse long bones. We found that hCT had the same inhibitory effect as sCT on the bone-resorbing activity of human and rabbit osteoclastic cells, but a different one on that of mouse cells. These results indicate that the activity of drugs should be assayed using human cells if possible.
Animals↗
Occurrence of Borrelia garinii oculo-neuroborreliosis in Japan.
We report a 64-year-old Japanese man with oculo-neuroborreliosis. His clinical features consisted of polyarthralgia, keratoconjunctivitis, chorioretinitis, optic neuritis, confusion, and polyradiculitis. Assay of antibodies to Borrelia species detected IgG-antibody to B. garinii in both serum and CSF. Progressive declining of serum IgG antibody titer against Borrelia garinii, in parallel with clinical improvement, was observed after administration of ceftriaxone.
Aged↗
Inducible osteonecrosis in a rabbit serum sickness model: deposition of immune complexes in bone marrow.
We established inducible osteonecrosis in a rabbit serum sickness model. Osteonecrosis with marrow necrosis could be induced by the intravenous injection of horse serum in two doses separated in time by a period of three weeks. In this model, osteonecrosis could be successfully produced in rabbit femoral metaphysis. The incidence of marrow necrosis was 45% (9 of 20 rabbits) and trabecular necrosis occurred in 6 of 20 rabbits (30%) at 7 days after the second injection of the horse serum. In bone marrow of the femoral metaphysis, extravasation of erythrocytes and the formation of micro-thrombi in arterioles were often observed in an early stage of the present model and both findings correlate well each other (p = 0.0001). Immune complexes could be demonstrated using immunohistochemistry in bone marrow of the femoral metaphysis as well as in glomeruli of the kidney. Extravasation of erythrocytes in bone marrow of the femoral metaphysis was observed in 8 of 12 (67%) cases with immune complex deposition in the sinusoidal space of the femoral metaphysis and in 12 of 21 (57%) cases with immune complex deposition in glomeruli of the kidney. Immune complex deposition both in the sinusoidal space of femoral bone marrow (p = 0.0385) and in glomeruli of the kidney (p = 0.0209) closely related to extravasation of erythrocytes and microthrombi in arterioles in the early stage of this model. Early microcirculatory injury (extravasation of erythrocytes and microthrombi in arterioles) adjacent to osteonecrosis could be induced by immune complex deposition in femoral bone marrow and might be predictable characteristics for the inducible osteonecrosis in the present serum sickness model. The important findings in this study were that early microcirculatory injury was closely related to the deposition of immune complexes in femoral bone marrow, and that early microcirculatory injury associated with immune complex deposition was located close to osteonecrotic regions.
Animals↗
Case report: hepatic adenoma with nodule-in-nodule appearance: CT and MR findings.
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Adenoma, Liver Cell↗
A point mutation in HLA-A*0201 results in failure to bind the TAP complex and to present virus-derived peptides to CTL.
Mutating the HLA-A*0201 heavy chain from threonine to lysine at position 134 (T134K) results in a molecule that presents exogenous peptide, but cannot present endogenously derived antigen. This is reflected in diminished cell surface expression and altered intracellular trafficking of T134K. The failure of T134K to present endogenous antigen can be overcome by using an ER targeting sequence, suggesting that the antigen presentation defect is restricted to TAP-dependent peptide loading. The ability of T134K to load peptide in a TAP-dependent manner is dramatically reduced compared with HLA-A*0201. By coimmunoprecipitation there is no detectable association of the T134K molecule with the TAP complex. Thus, T134K selectively affects TAP association and peptide loading, suggesting a requirement for the direct interaction of MHC class I heavy chain and the TAP complex for efficient presentation of endogenous antigen.
ATP-Binding Cassette Transporters↗
Regionally-targeted mutagenesis by metabolically-activated steviol: DNA sequence analysis of steviol-induced mutants of guanine phosphoribosyltransferase (gpt) gene of Salmonella typhimurium TM677.
Steviol is the aglycone of stevioside, a non-caloric sugar substitute commonly used in Japan. Steviol strongly induces mutations at the guanine phosphoribosyltransferase gene (gpt) of Salmonella typhimurium TM677 when the metabolic activation system (S9 mix) is present. However, it is completely negative in the reverse mutation assays using Escherichia coli WP2uvrA/pKM101 or S.typhimurium TA strains. In order to characterize the mutations induced by metabolically-activated steviol, the chromosomal gpt alleles of 24 induced (ST clones) and 16 spontaneous mutants (SP clones) of S.typhimurium TM677 were sequenced and the mutation spectra were compared. About 40% of the mutations of ST clones (nine out of 24) were localized in the region between nucleotides 280 and 330 from the starting codon ATG, whereas no mutations of SP clones were found in that region. The mutations identified in the region included transitions (three clones), transversions (four clones), a duplication and a deletion. There were no other marked differences between ST and SP clones: base-change mutations were dominant over frameshifts and deletions (ST clones, 20 versus three; SP clones, 16 versus two) and base change mutations occurred more frequently at G:C pairs rather than at A:T pairs (ST clones, 15 versus five; SP clones, 12 versus four). The possibility that metabolically-activated steviol gives pause to DNA synthesis around nucleotide 280, thereby stimulating the duplication, deletion and untargeted mutagenesis in the defined region of the gpt gene is discussed.
Amino Acid Sequence↗
Evaluation of the genotoxicity of stevioside and steviol using six in vitro and one in vivo mutagenicity assays.
Stevioside, a constituent of Stevia rebaudiana, is commonly used as a non-caloric sugar substitute in Japan. The genetic toxicities of stevioside and its aglycone, steviol, were examined with seven mutagenicity tests using bacteria (reverse mutation assay, forward mutation assay, umu test and rec assay), cultured mammalian cells (chromosomal aberration test and gene mutation assay) and mice (micronucleus test). Stevioside was not mutagenic in any of the assays examined. The aglycone, steviol, however, produced dose-related positive responses in some mutagenicity tests, i.e. the forward mutation assay using Salmonella typhimurium TM677, the chromosomal aberration test using Chinese hamster lung fibroblast cell line (CHL) and the gene mutation assay using CHL. Metabolic activation systems containing 9000 g supernatant fraction (S9) of liver homogenates prepared from polychlorinated biphenyl or phenobarbital plus 5,6-benzoflavone-pretreated rats were required for mutagenesis and clastogenesis. Steviol was weakly positive in the umu test using S.typhimurium TA1535/pSK1002 either with or without the metabolic activation system. Steviol, even in the presence of the S9 activation system, was negative in other assays, i.e. the reverse mutation assays using S.typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and Escherichia coli WP2 uvrA/pKM101 and the rec-assay using Bacillus subtilis. Steviol was negative in the mouse micronucleus test. The genotoxic risk of steviol to humans is discussed.
Animals↗
Assignment of two hydroxysteroid sulfotransferase genes (St1 and St2) to rat chromosome bands 1q21.3-->q22.1 by in situ hybridization.
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Animals↗
Cholestane glycosides from Solanum abutiloides.
From the roots of Solanum abutiloides, glycosides of 26-hydroxy- and 26-aminocholestane were obtained and their structures were characterized. Both of them were regarded as key intermediates in the biogenesis of steroidal alkaloids.
Carbohydrate Sequence↗
Development of in vitro matured/fertilized bovine embryos in a chemically defined medium: influence of oxygen concentration in the gas atmosphere.
The influence of oxygen concentrations in the gas atmosphere on the development of IVM/IVF bovine embryos was determined by culturing them in a microdrop of modified synthetic oviduct fluid medium supplemented with amino acids, insulin and PVA (mSOFai). After removing the cumulus cells at 18 hr post-insemination, presumptive zygotes were cultured in mSOFai for 104-106 hr under 5% CO2 with various O2 concentrations (2.5 to 20%). Reduced O2 (5-10%) improved the development to the morula stage, and 5% O2 gave the highest development. In the next experiment, morulae obtained after 102-104 hr of culture, were further cultured for 50 hr in mSOFai with 2mM glucose under 5 and 20% O2. An increase in the mean cell number in blastocysts, but not in the frequency of blastocysts, was observed under 5% O2. In the third experiment, zygotes were cultured for 152-154 hr in mSOFai under 5 and 20% O2, or cocultured with bovine oviduct epithelial cells in TCM199 + 10% FCS under 5% CO2 in air. Percentage of blastocysts for mSOFai in 5% O2 doubled to that for 20% O2, and was similar to that for coculture. Moreover, mean cell number in the blastocysts for mSOFai in 5% O2 was significantly higher than that for coculture. Results demonstrate that oxygen concentration critically affects embryonic development through zygotes to blastocysts, and suggest that around 5% 02 is optimal. It also indicates that bovine zygotes can be cultured up to the blastocyst stage using a chemically defined medium with rates similar to those of a conventional coculture system.
Amino Acids↗
Thermochemotherapy for cancer of the tongue using magnetic induction hyperthermia (implant heating system: IHS).
A 55-year-old patient with cancer of the tongue (T2N0M0) was treated by thermochemotherapy using interstitial magnetic induction hyperthermia (Implant Heating System: IHS). The patient received 2 courses of hyperthermia, each of which was 45 minutes long. At the same time, the patient received 2 courses of chemotherapy, which included intra-arterial infusion of 100 mg of cisplatin (CDDP) and 25 mg of peplomycin (PEP). The patient showed complete response (CR) to this therapy. To date, 1.5 years after completion of treatment, the patient has shown no recurrence. This therapy, which makes surgery and radiotherapy unnecessary, is promising, because it is expected to improve the quality of life (QOL) of cancer patients.
Antineoplastic Combined Chemotherapy Protocols↗
Recurrent demyelinating transverse myelitis in a high titer HBs-antigen carrier.
A 46-year-old man who was an extremely high titer hepatitis B surface (HBs)-antigen carrier had three attacks of acute demyelinating transverse myelitis associated with signs of meningeal irritation. Each episode showed good response to corticosteroid therapy. The cerebrospinal fluid was characterized by elevated levels of myelin basic protein (MBP) and predominating CD4+CD29+ helper-inducer T cells during the acute stages, and also by persistently positive HBs antigen. There were neither autoantibodies nor evidence of vasculitis. However, circulating immune complexes composed of HBs antigen disappeared after treatment, indicating that immunity to hepatitis B virus played a role in the demyelinative lesion formation in the central nervous system (CNS). In light of the animal studies demonstrating autoimmunity triggered by molecular mimicry between MBP and hepatitis B virus antigens, this patient may serve as a rare example of CNS demyelination in humans with the same autoimmune etiology.
Autoantigens↗
[Vasoactive intestinal contractor (VIC)/mouse ET-2 and VIC receptor: biological activity, gene expression, and specific receptor].
Using molecular biology techniques with the Endothelin (ET) cDNA as a probe, we discovered a novel peptide, vasoactive intestinal contractor (VIC). VIC differed from ET (= ET-1) in 3 amino acid residues. Synthetic VIC had in vivo pressor and in vitro vasoconstrictor activity such as that of ET. Northern blot analysis, however, indicated the VIC gene to be expressed in the intestine. Furthermore, VIC evoked stronger contractile response in ileum than ET. VIC may thus possibly be reasonably classified as a gut peptide. From the cDNA sequence analysis, the mature VIC is predicted to be produced via an intermediate from the deduced prepro VIC.
Amino Acid Sequence↗
[Improvement of ophthalmoplegia by 5-hydroxytryptophan in two cases of progressive supranuclear palsy].
We report two patients with clinically diagnosed progressive supranuclear palsy (PSP): a 69-year-old man and a 73-year-old woman. Both patients showed supranuclear ophthalmoplegia, postural instability, pseudobulbar palsy, and Parkinsonism. In the first patient, we administered L-dopa/carbidopa (300 mg/30 mg/ day), which moderately improved gait disturbance, but exerted no beneficial effects on gaze palsy. Then, we administered amitriptyline, bromocriptine, pergolide, l-threo-DOPS or 5-hydroxytryptophan (5-HTP) in addition to L-dopa/carbidopa. The second patient was treated by the monotherapy of L-dopa/carbidopa, amitriptyline, l-threo-DOPS or 5-HTP. We interposed two to three weeks between administration of each drug. In both patients, amitriptyline (75 mg/day) markedly improved both gait disturbance and horizontal gaze palsy. 5-HTP (600 mg/day) also improved horizontal gaze palsy, but failed to alleviate gait disturbance. The results suggest the involvement of impaired serotonergic system in ophthalmoplegia of PSP.
5-Hydroxytryptophan↗