Suppression of antigen-antibody reaction in xenotransplantation.
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ABO Blood-Group System↗
Biomedical subjects
S Hayashi
Publications and source records attributed to S Hayashi.
Early introduction of HMG-CoA reductase inhibitors could prevent the incidence of transplant coronary artery disease.
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Adolescent↗
Modulation of lung local immune responses by oral administration of a herbal medicine Sho-saiko-to.
Sho-saiko-to (SST), a Chinese/Japanese herbal medicine (Kampo medicine) widely used to treat chronic hepatitis in Japan, is known to modulate immune responses, and thus its immunomodulating activity may be responsible for its bi-directional effects on the lungs as therapeutic efficacy in various lung diseases and involvement in development of interstitial pneumonia. We administered SST to BALB/c mice orally and examined the lung tissue levels of pro/anti-inflammatory cytokines, interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and the effects of SST on acute lung injury induced by instillation of lipopolysaccharide (LPS) or IL-1. Although SST had no effect on lung TNF-alpha or IL-1beta level, it increased IL-6. Investigation of active fractions of SST suggested that multiple ingredients were supposed to be responsible for IL-6-inducing activity. Liquiritigenin, a metabolite of liquiritin which is one of the major ingredients in SST enhanced in vitro IL-6 production in anti-CD3 monoclonal antibody (anti-CD3 mAb)-stimulated lung mononuclear cells in a cell-type specific and dose-dependent manner. SST suppressed LPS-induced lung injury at the later phase when lung leak was evident while being ineffective on initial neutrophil sequestration to the lung in these models. These findings suggest that SST modulates lung inflammation by regulating local immune response.
Administration, Oral↗
Significance of transporter associated with antigen processing gene polymorphism in living related renal transplantation.
The HLA class I and class II mediated antigen presentation plays a major role in the initiation of immune response and the development of acute rejection after transplantation. The purpose of this study was to examine whether MHC-encoded antigen processing (TAP1, TAP2, LMP2, DMA and DMB) gene polymorphisms were associated with the incidence and the severity of acute rejection after renal transplantation. We studied a selected population of 112 pairs of donors and recipients who underwent living-related renal transplantation. They were divided into 3 groups: rejection-free (Group A, n = 51), steroid-sensitive rejection (Group B, n = 31) and steroid-resistant rejection (Group C, n = 30). The frequency of TAP2*0103 (41.2%) was significantly higher in the donors of Group A than that of Group B (12.9%, p = 0.0070, pc = 0.0280) or Group C (16. 7%, p = 0.0225, pc = 0.0900). No significant difference was observed in the allelic frequencies of the TAP1, LMP2, DMA, and DMB genes in the donors or recipients among Groups A, B, and C. This result supported the idea that the TAP2 gene polymorphism might be functionally related to antigen presentation. It also suggested that donor's antigen presenting cells with the TAP2*0103 allele would have the attenuated efficacy in the presentation of allospecific antigens to recipient's T cells.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
International telemicroscopy with a 3 MV ultrahigh voltage electron microscope.
The ability for remote microscope operation via a network connection was added recently to the ultrahigh voltage electron microscope (UHVEM) in Osaka University, and used successfully for the observation of thick biological samples across the Pacific Ocean by researchers at the National Center for Microscopy and Imaging Research (NCMIR) at the University of California San Diego. High-quality images at video rate were transferred by a satellite link and control signals were transmitted by an ISDN connecting the workstations at both sites. Most microscope functions operated from the console of the UHVEM were replicated on the graphical user interface of the remote workstation. By clicking on icons or in boxes in the display window with a mouse, the researcher could operate the UHVEM from the remote-site. The total delay time for sending images and returning control signals was about 0.7 s, which did not interfere significantly with the smooth operation of the instrument. Researchers at the remote site were able to record images on film in the microscope which were later sent to San Diego.
Animals↗
Monoclonal antibodies to plasma high density lipoprotein (HDL) of eel (Anguilla japonica).
Six week-old female mice (Balb/c) injected intraperitonealy with 50 micrograms of eel high density lipoprotein (HDL) emulsified with equal volume of adjuvant three times every two weeks. Three weeks after the third injection, hyperimmunized mice were boosted by injection of 100 micrograms of HDL. After 5 days, the best responding mouse to injected HDL was sacrificed, and spleen cells were fused with mouse myeloma cells (Sp2/O-Ag14), and hybridomas were cultured in a selection medium. Monoclonal antibodies specific to apolipoprotein A-I or A-II (apoA-I or apoA-II) of HDL were obtained by cloning and recloning the hybridomas. Eighteen monoclonal antibodies specific to apoA-I and/or apoApII were isolated. Antibodies in the culture medium were purified by a HiTrap Protein G or an eel-HDL column. These purified antibodies belong to the subclass IgG1. The monoclonal antibodies specific to eel apoA-I and apoA-II secreted by clone 10D12 and 2G3, respectively, interact with serum proteins of some fish species such as red-sea bream and carp. The anti-eel apoA-I antibody of 10D12 did not bind to serum proteins of rat, rabbit, and chicken, while the anti-eel apoA-II of 2G3 antibody did.
Amino Acid Sequence↗
Prenatal exposure to diethylstilbestrol decreases the number of estrogen receptor alpha-containing neurons innervating the ovary in rat celiac ganglion.
Recently, we reported that, in rats, transplacental exposure to diethylstilbestrol, a potent synthetic estrogen, decreases the density of the ovarian sympathetic nerve network compared to that in control rats not exposed to diethylstilbestrol. To clarify the mechanism of the decrease in the density, we performed a series of experiments using rats prenatally exposed to diethylstilbestrol and unexposed control rats. First, a retrograde tract tracer, Fast Blue, was microinjected into the ovaries of both groups of rats at four months of age, and the number of Fast Blue-positive neurons in the celiac ganglion was counted. The number of neurons in the ganglion was smaller in diethylstilbestrol-exposed rats than in the controls. Second, double labeling of the neurons with antibody against estrogen receptor alpha and Fast Blue in the celiac ganglion was carried out in both groups of rats. The results showed that estrogen receptor alpha-containing neurons in the ganglion innervated the ovary, and their number was decreased selectively by prenatal diethylstilbestrol exposure. Finally, a decrease in the celiac ganglion volume in rats prenatally exposed to diethylstilbestrol was also detected on day 23 of gestation, as compared to the volume in the control rats. From these observations, we propose that prenatal exposure to diethylstilbestrol can induce a loss of estrogen receptor alpha-containing neurons innervating the ovary during development, resulting in paucity of the neural network in the ovary.
Amidines↗
Liquid chromatographic determination of urinary 6beta-hydroxycortisol to assess cytochrome p-450 3A activity in HIV positive pregnant women.
Assessing the activity of CYP3A4 is important for predicting the pharmacokinetic behavior of protease inhibitors in HIV positive patients, especially in pregnant women. The endogenous hormonal ratio of 6beta-hydroxycortisol (beta-OHF) to cortisol (F) in the urine is an index for metabolic enzyme activity of cytochrome p-450 (CYP) 3A4. Because the ratio is a unique way to assess the enzyme activity without using any exogenous probes for this isozyme, it is practical for use in pregnant women. In this paper, we describe a method using high performance liquid chromatography (HPLC) for 6beta-OHF in urine from pregnant women to estimate the ratio of 6beta-OHF/F. Urinary 6beta-OHF was measured by using C18-cartridge solid phase extraction and isocratic HPLC. Aliquots (1 ml) of urine samples spiked with internal standard, 6beta-hydroxyprednisolone (6beta-OHPSL), were alkalinized with NaOH, then applied to C18-cartridges, which were washed with water and hexane and eluted with ethyl acetate. After the effluents were dried and reconstituted in 10% acetonitrile, the samples were analyzed by HPLC using an isocratic mobile phase (acetic acid/acetonitrile/50 mM potassium dihydrogenphosphate: 0.2/9/90.8; v/v) and ultraviolet detection at 245 nm. The recoveries of 6beta-OHF from C18 cartridges were 93.2 and 93.9% when the authentic 6beta-OHF was added to the urine sample at the concentration of 50 and 300 ng/ml, respectively. Intra- and inter-day variations estimated at concentrations of 113-674 ng/ml were 2.9-5.6 and 4.9-8.1%, respectively. The method was applied to morning urine samples collected from HIV-positive pregnant women managed with protease inhibitor containing anti-retroviral regimens.
Adult↗
Synthesis and biological activity of alpha-methylene-gamma-lactones as new aroma chemicals.
Seven kinds of alpha-methylene-gamma-lactones with an alkyl group at the C-4 position were synthesized according to a previously described method, with yields of 28-34%. These alpha-methylene-gamma-lactones had characteristic and unique odors. All alpha-methylene-gamma-lactones added a roast-like odor to materials. The antimicrobial effects of alpha-methylene-gamma-lactones were investigated by using a paper disk diffusion method. The results showed the alpha-methylene-gamma-lactones inhibited the growth of three bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas fluorescens) and two fungi (Saccharomyces cerevisiae and Aspergillus niger). In particular, alpha-methylene-gamma-undecalactone and alpha-methylene-gamma-dodecalactone exhibited potent inhibition of the growth of these microorganisms compared to butyl p-hydroxybenzoate as standard antibiotic. The umu test revealed that the alpha-methylene-gamma-lactones suppressed the SOS-inducing activity of three mutagens, furylfuramide, UV irradiation, and Trp-P-1, respectively. The antimicrobial effects and the suppressive effects of SOS induction by alpha-methylene-gamma-lactones had a tendency to intensify as the number of carbons in the side chain increased.
Alkanes↗
Changes in pulmonary histology and exfoliated bronchoalveolar cells induced by in vivo introduction of the tumor necrosis factor-alpha gene.
An inflammatory cytokine, tumor necrosis factor (TNF)-alpha, has been implicated in the pathogenesis of inflammatory lung diseases such as interstitial pneumonia (IP). To clarify the role of the inflammatory cytokine in the pathogenesis of lung inflammation, we introduced a murine TNF-alpha gene into murine lungs by the hemagglutinating virus of Japan (HVJ)-liposome method. Seven days after the TNF-alpha gene introduction resulted in marked cellular infiltration of alveoli, and mild histological change was observed 28 days after the gene introduction. Electron microscopic analysis revealed minimal deposition of collagen fibrils. Analysis of the BAL revealed that the total cell number was markedly increased 3 and 7 days after the gene introduction, and more than 90% of the cells were macrophages. The increase in the cell number was returned to below the normal level 28 days after the gene introduction. During the development of IP, TNF-alpha may regulate pathologic change of the pulmonary interstitium and alveolar cells.
Animals↗
Lack of antibody production against Hanganutziu-Deicher (H-D) antigens with N-glycolylneuraminic acid in patients with porcine exposure history.
The significance of non-alphagalactosyl antigens remains unclear in pig-to-primate xenotransplantation. Hanganutziu-Deicher (H-D) antigens with terminal N-glycolylneuraminic acid (NeuGc) are widely expressed on endothelial cells of mammalian species, with the exception of humans. As baboons and monkeys also express H-D antigens, a pig-to-non-human primate experimental model cannot resolve the question of whether H-D antigens can elicit a potent humoral response in human recipients. The purpose of this study was to elucidate the clinical significance of H-D antigens by examining the sera from patients who have been previously exposed to porcine tissue. After the digestion of porcine aortic endothelial cells (PAEC) by neuraminidase, NeuGc and N-acetylneuraminic acid (NeuAc) were quantitated by HPLC. IgG and IgM antibody levels against H-D antigens were measured by NeuGc-GM3-coated ELISA plates in the sera of patients who had undergone ex vivo kidney perfusion 1 to 3 weeks and 2 years previously (n=2) or had been injected with fetal porcine islets 2 months previously (n= 10). HPLC determined that 9.7x 10(7) NeuAc and 6.3x 10(7) NeuGc residues per cell were released from PAEC by neuraminidase, while 25.7x 10(7) NeuAc and an undetectable level of NeuGc were released from human aortic endothelial cells (HAEC). No significant elevation of IgG or IgM antibody levels against NeuGc-GM3 was observed in sera from patients with a history of porcine exposure. Considering the active production of antibody against the foreign galactosyl antigens after pig-to-human xenotransplantation, some production of antibodies against the equally foreign H-D antigens would be expected, because large amounts of NeuGc terminated saccharides are present in the pig endothelial cell surface. However, no production of antibodies directed to H-D antigens could be found in patients exposed to porcine tissue. Further studies are warranted to explain why H-D antigens do not elicit a significant antibody production.
Animals↗
Comparative study of theefficacy of removal of anti-ABO and anti-gal antibodies by double filtration plasmapheresis.
Successful clinical ABO-incompatible renal transplantation has been achieved by the removal of anti-A or anti-B antibodies using double filtration plasmapheresis (DFPP). We have compared changes in the levels of anti-donor antibodies and the histopathology of the renal grafts following human ABO-incompatible allotransplantation and pig-to-baboon xenotransplantation using pretransplant DFPP. DFPP was performed on days 6, -4, -2 and -1 before the ABO-incompatible transplants (n=25) and on days -2 and 0 (immediately before reperfusion) in the xenotransplants (n=4). In two baboons (XenoTx Group I) the extent of antibody removal was comparable to that in the ABO-incompatible patients, and an even greater level of removal was achieved in another two baboons (XenoTx Group II). Anti-A and anti-B and anti-pig IgM and IgG antibodies were measured by flow cytometry. All clinical ABO-incompatible renal grafts are functioning, except two which were lost from recurrence of the original disease or from chronic rejection. Three other grafts underwent humoral rejection episodes, which were successfully treated. DFPP reduced the mean anti-A/B IgM and IgG antibody levels to 8% and 13% of pretreatment levels, respectively. After kidney transplantation, they were maintained at 37% and 46% of pre-DFPP level. No antibody binding to the transplanted kidney was detected at any time (1 h to 2 yr) after ABO-incompatible allotransplantation. In contrast, in XenoTx Group I, the same extent of antibody removal (90%) prevented hyperacute rejection, but the two grafts were rejected on days 6 and 7, respectively, from acute vascular rejection. In XenoTx Group II, the additional DFPP that was required to deplete the remaining 10% of anti-pig antibody was poorly tolerated and the two baboons died 4 h and 2 days, respectively, after renal transplantation. Although anti-pig IgM antibodies were reduced to 2% of pre-treatment level, IgM and C3 binding were detected in the graft as early as 1 h posttransplantation. These data suggest that the concentration of xeno-antigen epitopes expressed on pig organs may need to be reduced by genetic engineering to the much lower level of blood group A/B antigens on human kidneys if discordant xenotransplantation is to be successful.
ABO Blood-Group System↗
p38 MAP kinase regulates TNF alpha-, IL-1 alpha- and PAF-induced RANTES and GM-CSF production by human bronchial epithelial cells.
BACKGROUND: RANTES and granulocyte macrophage-colony stimulating factor (GM-CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen-activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase in RANTES and GM-CSF production in human bronchial epithelial cells (BECs) has not yet been determined. OBJECTIVE: In the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kinase activation in tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha and platelet-activating factor (PAF)-stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM-CSF expression in order to clarify the intracellular signal regulating RANTES and GM-CSF production by human BECs. RESULTS: The results showed that TNF alpha, IL-1 alpha and PAF induced serine phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SB 203580 inhibited p38 MAP kinase activity and RANTES and GM-CSF production by TNF alpha-, IL-1 alpha- or PAF-stimulated human BECs. CONCLUSIONS: These results indicate that p38 MAP kinase plays an important role in TNF alpha-, IL-1 alpha- or PAF-activated signalling pathway which regulates RANTES and GM-CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway.
Animals↗
Oocyte activation induced by spermatids and the spermatozoa.
It has been reported that a sperm factor (SF) found in spermatozoa plays a critical role in fertilization. However, particulars of the oocyte-activating and Ca2+ oscillation (Ca-Os)-inducing abilities of this SF remain unknown. We examined these abilities of spermatids in mouse, hamster and human by a mouse test (injection of spermatids into mouse oocytes). In mice, the round spermatids (ROS), elongated spermatids (ELS) and spermatozoa activated 0%, 93% and 92% of the oocytes, respectively. ROS injection resulted in no Ca-Os (type C). ELS induced a normal oscillation (type A) at 0% and an abnormal oscillation (type B) at 94%. Mouse spermatozoa induced type A Ca-Os at 90%. For mice, oocyte-activating and Ca2+ oscillation-inducing ability arose in different phases of spermiogenesis. We also observed this differential timing for hamster spermatids. Hamster ROS activated 74% of oocyte (ELS: 90%, sperm: 86%). Human ROS activated 64% of oocytes (sperm: 100%), but only 35% of the oocytes showed type A Ca-Os. These results indicate that oocyte activation generally occurs between the ROS and ELS phases, although these phases differ among species. They also indicate that oocyte activation is not necessarily accompanied by Ca-Os. These findings suggest the existence of different thresholds at which the SF induces oocyte activation and Ca2+ oscillation, or of different factors that induce oocyte activation and Ca-Os. We found SF to be clinically impaired in 0.9% of ICSI patients. A combination of artificial oocyte activation and ICSI proved effective with such patients.
Animals↗
Primary progressive aphasia with focal glial tauopathy.
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Aged↗
Sudden death of a 21-year-old female with Williams syndrome showing rare complications.
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Adult↗
Older boys benefit from higher initial prednisolone therapy for nephrotic syndrome. The West Japan Cooperative Study of Kidney Disease in Children.
BACKGROUND: A long course of the initial prednisolone therapy has been shown to be more effective than standard-course therapy in reducing relapse rates in children with idiopathic nephrotic syndrome, but it is commonly accompanied by corticosteroid toxicities. There has been no study on prednisolone dosage for the effective treatment of nephrotic syndrome. METHODS: Sixty-eight children (42 boys and 26 girls) with an initial attack of nephrotic syndrome were randomly allocated into two different long-course treatment groups. Patients in Group 1 received a daily prednisolone dose of 60 mg/m2 for six weeks, followed by an alternate-day dose of 40 mg/m2 for six weeks. Patients in Group 2 had a daily dose of 40 mg/m2 instead of 60 mg/m2. RESULTS: Four children in each group did not respond within six weeks. Group 1 was associated with a significantly earlier response but more frequent corticosteroid toxicities than Group 2. Boys in Group 1 had a higher rate of sustained remission than boys in Group 2 (P = 0.0073), especially boys four years old or more (P = 0.0027), but girls did not show a significant difference (P = 0.863). Boys four years old or more in Group 1 had a course of frequent relapsing less often than those in Group 2 (2 of 13 vs. 6 of 8, P = 0.0075). CONCLUSION: These findings indicate that efficient prednisolone doses may vary between sexes and ages, and that a higher initial prednisolone therapy may be of greater benefit to older boys.
Adolescent↗
Abnormalities of the FHIT gene in human oral carcinogenesis.
The abnormalities of the fragile histidine triad (FHIT) gene in tissue samples of oral squamous cell carcinomas (SCCs) along with several leukoplakias and an erythroplakia were examined to determine whether the FHIT gene is actually a frequent target in vivo for alteration during oral carcinogenesis. Abnormal transcripts of the FHIT gene were found in eight of 15 oral SCCs. Although these abnormal transcripts varied widely, deletion patterns incorporating a deletion of exon 5 were the most common. Loss of heterozygosity (LOH) analysis demonstrated that the abnormal FHIT transcripts found in cancer cells were attributable to abnormalities of the FHIT gene. Abnormal FHIT transcripts were also observed in two of seven premalignant lesions. Interestingly, in the case of one patient with a premalignant lesion showing an abnormal FHIT transcript, subsequent oral SCC developed during a 3-year follow-up period. On the other hand, in the two patients from whom both leukoplakia and SCC samples were taken simultaneously, abnormal FHIT transcripts were found only in the SCCs. Although the functional role of FHIT remains to be clarified, these results suggest that the FHIT alteration is actually involved in carcinogenesis of the oral epithelium.
Acid Anhydride Hydrolases↗