Mite-related allergy and oral tolerance.
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Administration, Oral↗
Biomedical subjects
T Ono
Publications and source records attributed to T Ono.
Immunohistochemical examination of phosphorylated tau in granulovacuolar degeneration granules.
Granulovacuolar degeneration (GVD) and neurofibrillary tangles (NFT) are neuropathological features in Alzheimer's disease (AD). The molecular mechanism of GVD formation remains unknown. Recent immunohistochemical investigations suggested a potential link of NFT to GVD formation. Enzyme histochemical studies and electronmicroscopic findings suggested that GVD is formed through lysosomal autophagy of intraneuronal substances. We recently demonstrated that in non-demented cases NFT was phosphorylated at serines 199, 202 and 422 in paired helical filament (PHF)-tau more than in serine 396, while NFT in AD cases was similarly phosphorylated at these four sites in tau. In this study, we demonstrated immunohistochemically a similar phosphorylation state of tau in GVD granules to that in NFT in both non-demented cases and AD patients by using a mouse monoclonal anti-tau antibody and three phosphorylation site-specific antibodies for PHF-tau, indicating that GVD granules and NFT are composed of similar phosphorylated-tau. However, we could not detect PHF structures within any GVD using electronmicroscopy, indicating that PHF itself is not phagocytized by lysosomes during GVD formation. Therefore, the source of GVD granules might be phosphorylated pre-PHF-tau.
Aged↗
Transient brain ischaemia provokes Ca2+, PIP2 and calpain responses prior to delayed neuronal death in monkeys.
To clarify the mechanism of postischaemic delayed cornu Ammonis (CA)-1 neuronal death, we studied correlations among calpain activation and its subcellular localization, the immunoreactivity of phosphatidylinositol 4,5-bisphosphate (PIP2) and Ca2+ mobilization in the monkey hippocampus by two independent experimental approaches: in vivo transient brain ischaemia and in vitro hypoxia-hypoglycaemia of hippocampal acute slices. The CA-1 sector undergoing 20 min of ischaemia in vivo showed microscopically a small number of neuronal deaths on day 1 and almost global neuronal loss on day 5 after ischaemia. Immediately after ischaemia, CA-1 neurons ultrastructurally showed vacuolation and/or disruption of the lysosomes. Western blotting using antibodies against inactivated or activated mu-calpain demonstrated mu-calpain activation specifically in the CA-1 sector immediately after ischaemia. This finding was confirmed in the perikarya of CA-1 neurons by immunohistochemistry. CA-1 neurons on day 1 showed sustained activation of mu-calpain, and increased immunostaining for inactivated and activated forms of mu- and m-calpains and for PIP2. Activated mu-calpain and PIP2 were found to be localized at the vacuolated lysosomal membrane or endoplasmic reticulum and mitochondrial membrane respectively, by immunoelectron microscopy. Calcium imaging data using hippocampal acute slices showed that hypoxia-hypoglycaemia in vitro provoked intense Ca2+ mobilization with increased PIP2 immunostaining specifically in CA-1 neurons. These data suggest that transient brain ischaemia increases intracellular Ca2+ and PIP2 breakdown, which will activate calpain proteolytic activity. Therefore, we suggest that activated calpain at the lysosomal membrane, with the possible release of biodegrading enzyme, will cause postischaemic CA-1 neuronal death.
Animals↗
Possible origin of murine AIDS (MAIDS) virus: conversion of an endogenous retroviral p12gag sequence to a MAIDS-inducing sequence by frameshift mutations.
The murine AIDS (MAIDS) virus has a unique sequence in its p12gag region, which is responsible for MAIDS development. A transcript hybridizing with this sequence is expressed in normal C57BL/6 mice. The transcript, designated Edv, has been previously cloned and sequenced (Y. Kubo, Y. Nakagawa, K. Kakimi, H. Matsui, K. Higo, L. Wang, H. Kobayashi, T. Hirama, and A. Ishimoto, J. Gen. Virol. 75:881-888, 1994). Compared with the nucleotide sequence of the helper LP-BM5 ecotropic virus, the pathogenic replication-defective MAIDS virus has a 16-bp deletion and a 1-bp insertion in the 5' and 3' regions of the p12gag sequence, respectively, and the Edv transcript contains only a 3-bp deletion. Therefore, the amino acid sequence of the defective MAIDS virus p12gag region is not homologous to that of the helper virus and the Edv transcript because of the frameshift. To determine whether the amino acid sequence resulting from the frameshift is critical for MAIDS development, we constructed chimeric viruses that contained the p12gag regions of the helper virus and the Edv transcript, respectively, with and without the same frame as the defective MAIDS virus by the artificial frameshift mutations. The mutant viruses with the frameshift mutations induced MAIDS in inoculated mice, but the viruses without the mutations did not. These results suggested that the MAIDS virus was generated by frameshift mutations in the p12gag region of Edv or a related sequence.
Animals↗
Intron retention generates a novel isoform of the murine vitamin D receptor that acts in a dominant negative way on the vitamin D signaling pathway.
We identified and characterized a novel rat vitamin D receptor isoform (rVDR1), which retains intron 8 of the canonical VDR (rVDR0) during alternative splicing. In this isoform protein directed by the stop codon in this newly identified exon, a part of the ligand binding domain (86 amino acids) is truncated at the C-terminal end but contains 19 extra amino acids. The rVDR1 transcript was expressed at a level 1/15 to 1/20 of that of rVDR0 in the kidney and intestine in adult rats but not in embryos. The recombinant rVDR1 protein showed no ligand binding activity. Homo- and heterodimers of the recombinant rVDR0 and rVDR1 proteins bound to a consensus vitamin D response element (VDRE) but not to consensus response elements for thyroid hormone and retinoic acid. However, unlike rVDR0, rVDR1 did not form a heterodimeric complex with RXR on the VDRE. A transient expression assay showed that this isoform acted as a dominant negative receptor against rVDR0 transactivation. Interestingly, the dominant negative activities of rVDR1 differed among VDREs. Thus, the present study indicates that this new VDR isoform negatively modulates the vitamin D signaling pathway, through a particular set of target genes.
Alternative Splicing↗
Intraglomerular deposition of intact cross-linked fibrin in IgA nephropathy and Henoch-Schönlein purpura nephritis.
To investigate the significance of intraglomerular coagulation and fibrinolysis in IgA nephropathy (IgA-N) and Henoch-Schönlein purpura nephritis (HSPN), the distribution of intact cross-linked fibrin (XFb) modulated by plasmin activity was examined in 25 patients with IgA-N and in 12 with HSPN. In addition to the conventional method detecting fibrin-related antigen (FRA) with an antibody against fibrinogen, the enhanced intensity of immunoreactivity of cross-linked FRA (KL-FRA) using the monoclonal antibody DD3B6/22 after plasmin exposure was evaluated to assess intraglomerular deposition of intact XFb. Also, intraglomerular invasion of macrophages was detected using the monoclonal antibody KP1 against CD68. Sixteen of a total of 37 specimens (43%) showed increased intensity of XL-FRA staining after plasmin treatment which is considered to reflect the distribution of intact XFb. Increases in the intensity of XL-FRA staining were observed mainly in mesangium and partially along glomerular capillary loops and also in a few cases in the crescents. The incidence (67%) of increases in XL-FRA staining after plasmin exposure in HSPN specimens was significantly higher than that in IgA-N specimens (32%; p < 0.05). In the group positive for XL-FRA after plasmin exposure, the numbers of macrophages per glomerulus were significantly higher (n = 15; mean +/- SD = 1.6 +/- 0.9) than in the negative group (n = 6; 0.5 +/- 0.6; p < 0.01). In HSPN, the number of macrophages per glomerulus (n = 8; 1.9 +/- 1.0) was higher than that in IgA-N (n = 13; 0.9 +/- 0.9; p < 0.05). Based on these results, we conclude that XFb is often produced and distributed in intact form in the glomeruli both in IgA-N and HSPN, associated with a relatively low intraglomerular plasmin activity, and that intraglomerular coagulation may progress in accordance with macrophage infiltration, especially in HSPN.
Fibrin↗
24R,25-dihydroxyvitamin D3 promotes bone formation without causing excessive resorption in hypophosphatemic mice.
To clarify the differences in the action of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and 24,25-(OH)2D3 in hypophosphatemic (Hyp) mice, a model for familial X-linked hypophosphatemic rickets in humans, we carried out histomorphometric examinations of the effects of these agents in the lumbar vertebra of these mice. The Hyp mice received 1-1000 micrograms/kg.day 24,25-(OH)2D3, 0.01-0.1 micrograms/kg.day 1,25.(OH)2D3, or vehicle alone given daily for 28 days by ip injection. Histomorphometrically, 1,25-(OH)2D3 and 24,25-(OH)2D3 showed similar effects on bone formation. The parameters of bone formation, mineralized bone volume/bone volume, mineral apposition rate, and bone formation rate/bone surface, were improved to a similar extent in a dose-dependent manner by 1,25-(OH)2D3 and 24,25-(OH)2D3, but there were remarkable differences in the indexes of the bone resorption between these two metabolites. In 24,25-(OH)2D3-treated Hyp mice, osteoclast number/bone perimeter and osteoclast surface/bone surface, the parameters of bone resorption, increased to control levels and did not change according to the dose of 24,25-(OH)2D3. However, in 1,25-(OH)2D3-treated Hyp mice, these values increased remarkably, exceeding the control level. That is, 24,25-(OH)2D3 normalized bone resorption in the rachitic mice, whereas 1,25-(OH)2D3 caused excessive stimulation of bone resorption. This qualitative difference between the two compounds contributes to the superior effects exerted by 24,25-(OH)2D3 in improving the bone lesion in Hyp mice. At doses from 1-1000 micrograms/kg.day, 24,25-(OH)2D3 had dose-dependent effects in increasing bone formation without promoting excessive bone resorption, as shown by histomorphometric analysis.
24,25-Dihydroxyvitamin D 3↗
Growth hormone (GH) treatment of GH-deficient children increases serum levels of insulin-like growth factors (IGFs), IGF-binding protein-3 and -5, and bone alkaline phosphatase isoenzyme.
To investigate the contribution of the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) to the regulation of bone growth in 10 GH-deficient Japanese children receiving recombinant GH therapy, we determined the percent increase from pretreatment levels of serum IGF-I, IGF-II, IGFBP-3, IGFBP-5, and bone-specific alkaline phosphatase isoenzyme (B-ALP). For 10 children between 6-13 yr of age, serum IGF-I and IGF-II were increased after 1 month of treatment by 53% and 7%, respectively; after 12 months of therapy, IGF levels remained elevated at 51% and 17%, respectively. Serum IGFBP-3 and IGFBP-5 were also increased after 1 month of GH therapy by 17% and 13% respectively; after 12 months of therapy, they remained elevated at 22% and 15%, respectively. After 12 months of treatment, the bone formation marker B-ALP was also elevated to 23% greater than pretreatment levels. The elevation of IGF-I induced by GH was significantly correlated with the increases in IGFBP-3 (r = 0.735; P < 0.0001) and IGFBP-5 (r = 0.795; P < 0.0001), and the elevation of B-ALP was also significantly positively correlated with the increases in IGF-I, IGF-II, IGFBP-3, and IGFBP-5 (r = 0.544, P < 0.0001; r = 0.268, P = 0.0399; r = 0.414, P = 0.0010; and r = 0.500, P < 0.0001, respectively). Our data are consistent with the anabolic effect on bone growth of GH treatment being mediated by IGF-II, IGFBP-3, and IGFBP-5 as well as by IGF-I. This is the first evidence that GH treatment increases IGF-II in GH-deficient children. This finding was probably the result of application of a valid assay that measures IGF-II without interference of IGFBPs.
Adolescent↗
Effect of NaN3 on oxygen-dependent lethality of UV-A in Escherichia coli mutants lacking active oxygen-defence and DNA-repair systems.
Escherichia coli mutants which lack defence systems against such active oxygen forms as OxyR (delta oxyR), superoxide dismutase (SOD) (sodA and sodB) and catalase (katE and katG) are sensitive to UV-A lethality under aerobic conditions, whereas OxyR- and SOD-mutants have resistance under anaerobic conditions and in the presence of sodium azide (NaN3) during irradiation. UV-A induces lipid peroxidation in the delta oxyR mutant, which is suppressed by NaN3. These results suggest that UV-A generates 1O2 or the hydroxyl radical to produce lipid peroxides intracellularly in the delta oxyR mutant and that O2- stress may be generated in the sodAB mutant after 8hr of exposure to UV-A. The sensitivities of such DNA repair-deficient mutants as recA(ind-) and uvrA to UV-A also were examined and compared. These mutants are sensitive to UV-A lethality under aerobic conditions but show only slight resistance under anaerobic conditions or in the presence of NaN3 during irradiation. We conclude that NaN3 protects these mutant cells from oxygen-dependent UV-A lethality.
Azides↗
Major risk factors for atherosclerosis are manifested in experimental Ca-deficiency.
The eggshell is the major source of Ca required during growth of chick embryos. Therefore, chick embryos placed ex ovo for long-term (SL) are rendered severe systemic calcium deficiency. We report here that SL chick embryos express Ca-deficiency related atherogenic disorders, and that in vitro Ca-deficiency induces dedifferentiation, i.e. loss of cell-type specific features and accelerated proliferative activities, in the various types of cultured cells. Systemic blood pressure is significantly higher and an accelerated weight gain of the heart is noted in SL compared to normal embryos (NL) at the incubation Day-14. Plasma cholesterol was lower, while triglyceride and glucose were higher in SL. Varying Ca in the culture medium (FCa, 1.8 mM; HCa, 2.8 mM; Ca/2, 0.9 mM) clearly affected the phenotype of the cultured cardiomyocytes and vascular cells isolated from the chick embryos. The cell number and total DNA were significantly larger and the level of LDH and proliferating cell nuclear antigen (PCNA) was elevated in Ca/2 compared to FCa. On the contrary, the level of CPK and contractile proteins were lowered in Ca/2. Thus, it is indicated that Ca-deficiency induces atherogenic disorders in vivo, and accelerates cell proliferation and decelerates sarcomeric protein expression in vitro. Taken together, it is suggested that the atherogenic, developmental disorders in SL may be the integrated result of the phenotype alteration in the various cell types directly induced by Ca-deficiency.
Animals↗
Soluble intercellular adhesion molecule 1 (ICAM-1) antigen in sera of bronchial asthmatics.
Previous studies have suggested that intercellular adhesion molecule 1 (ICAM-1, CD54) may be involved in the pathogenesis of asthma. In addition, a soluble form of ICAM-1 (sICAM-1) has been detected in increased concentrations in the sera of patients with certain inflammatory conditions. To determine whether bronchial asthma is associated with increased levels of sICAM-1 in serum and to assess the effects of therapy on these levels, the concentrations of sICAM-1 were measured in sera of healthy donors and asthmatic patients. The mean (+/- SD) level of serum sICAM-1 for 60 asthmatic patients (304.0 +/- 82.5 ng/mL) was significantly higher than that for 39 healthy volunteers (260.9 +/- 67.2 ng/mL; p = 0.004). Twenty-two patients considered to have atopic asthma and 24 patients with nonatopic asthma did not differ in their levels of sICAM-1. In 14 patients, serum concentrations of sICAM-1 were higher during asthma attacks than in the same patients during remission (p = 0.035). Serum sICAM-1 levels were lower in nine patients during treatment with oral prednisolone (2.5 to 40 mg/d) than during periods without systemic corticosteroid therapy (p = 0.002). Thus, active bronchial asthma is associated with the presence of increased levels of sICAM-1 in serum, and these levels may be modulated by corticosteroid therapy.
Acute Disease↗
A randomized crossover study of an oral appliance vs nasal-continuous positive airway pressure in the treatment of mild-moderate obstructive sleep apnea.
STUDY OBJECTIVE: To compare efficacy, side effects, patient compliance, and preference between oral appliance (OA) therapy and nasal-continuous positive airway pressure (N-CPAP) therapy. DESIGN: Randomized, prospective, crossover study. SETTING: University hospital and tertiary sleep referral center. PATIENTS: Twenty-seven unselected patients with mild-moderate obstructive sleep apnea (OSA). INTERVENTIONS: There was a 2-week wash-in and a 2-week wash-out period, and 2 x 4-month treatment periods (OA and N-CPAP). Efficacy, side effects, compliance, and preference were evaluated by a questionnaire and home sleep monitoring. MEASUREMENTS AND RESULTS: Two patients dropped out early in the study and treatment results are presented on the remaining 25 patients. The apnea/hypopnea index was lower with N-CPAP (3.5 +/- 1.6) (mean +/- SD) than with the OA (9.7 +/- 7.3) (p < 0.05). Twelve of the 25 patients who used the OA (48%) were treatment successes (reduction of apnea/hypopnea to <10/h and relief of symptoms), 6 (24%) were compliance failures (unable or unwilling to use the treatment), and 7 (28%) were treatment failures (failure to reduce apnea/hypopnea index to <10/h and/or failure to relieve symptoms). Four people refused to use N-CPAP after using the OA. Thirteen of the 21 patients who used N-CPAP were overall treatment successes (62%), 8 were compliance failures (38%), and there were no treatment failures. Side effects were more common and the patients were less satisfied with N-CPAP (p < 0.005). Seven patients were treatment successes with both treatments, six of these patients preferred OA, and one preferred N-CPAP as a long-term treatment. CONCLUSIONS: We conclude that OA is an effective treatment in some patients with mild-moderate OSA and is associated with fewer side effects and greater patient satisfaction than N-CPAP.
Adult↗
Transfer of male or female primordial germ cells of quail into chick embryonic gonads.
Blood from an individual quail embryo at stages 13-16, when primordial germ cells (PGCs) were in circulation, was taken from its marginal vein and transfused into the marginal vein of a chick embryo at stages 13-16. Both donor and recipient embryos were cultured in vitro until day 8 of development and their sex was determined by morphological and histological observations of the gonads. Sections of recipient gonads were stained immunohistochemically with QCR1 monoclonal antibody positive for quail PGCs but negative for chick PGCs. Donor and recipient embryos were sexed in 17 pairs which included all four sex combinations. Transferred PGCs, either female-derived ZW type or male-derived ZZ type, were observed in the gonads of both sexes of 15 recipient embryos. The population of donor PGCs ranged from 20 to over 2500. In all four sex combinations, there was a higher population in the left than the right gonad of the embryos.
Animals↗
Adult respiratory distress syndrome induced by a Chinese medicine, Kamisyoyo-san.
We report the first case of Kamisyoyo-san-induced adult respiratory distress syndrome (ARDS). A 59-year-old female was given Kamisyoyo-san for treatment of seborrheic dermatitis. She then presented with a respiratory illness having clinical, radiologic and functional characteristics of ARDS. Bronchoalveolar lavage fluid showed an increased number of lymphocytes, neutrophils and eosinophils. The lymphocyte stimulation test with Kamisyoyo-san was positive.
Bupleurum↗
Chromaffin cell survival and host dopaminergic fiber recovery in a patient with Parkinson's disease treated by cografts of adrenal medulla and pretransected peripheral nerve. Case report.
A 55-year-old woman with severe Parkinson's disease was treated by cografting adrenal medulla with pretransected peripheral nerve into the bilateral caudate nuclei. The patient showed modest improvement of her akinesia; this effect persisted for 1 year after transplantation, when she suddenly died from upper gastrointestinal bleeding unrelated to the grafting procedure. At autopsy, a large number of tyrosine hydroxylase-immunoreactive chromaffin cells were observed within the caudate graft sites and a dense network of host dopaminergic fibers was visualized. This autopsy finding is very important for the field of experimental and clinical chromaffin cell grafting because it is the first evidence that cografts using pretransected peripheral nerve might enhance the survival of chromaffin cells and the recovery of host dopaminergic fibers in humans suffering from Parkinson's disease.
Adrenal Medulla↗
Cografting with polymer-encapsulated human nerve growth factor-secreting cells and chromaffin cell survival and behavioral recovery in hemiparkinsonian rats.
Encapsulated cell grafting is one approach for the delivery of neurotransmitters and/or neurotrophic factors to the brain. Baby hamster kidney (BHK) cells were genetically modified to secrete high levels of human nerve growth factor (hNGF). Following polymer encapsulation, these cells were implanted into the left lateral ventricle or the left striatum 1.5 mm away from striatally cografted unencapsulated adrenal medullary chromaffin cells in hemiparkinsonian rats. Although the animals receiving adrenal medulla alone or adrenal medulla with intraventricular hNGF-secreting cell grafting did not show recovery of apomorphine-induced rotational behavior, the animals receiving adrenal medulla with intrastriatal hNGF-secreting cell implants showed a significant recovery of rotational behavior 2 and 4 weeks after transplantation. Histological analysis revealed that in animals receiving adrenal medulla with intraventricular hNGF-secreting cell grafting, the number of tyrosine hydroxylase-immunoreactive (TH-IR) surviving chromaffin cells tended to be higher (approximately five to six times) than in animals receiving adrenal medulla alone; however, this increase did not reach statistical significance. In contrast, in animals receiving adrenal medullary cells together with intrastriatal hNGF-secreting cells, the number of TH-IR surviving chromaffin cells was more than 20 times higher than that in animals receiving adrenal medullary cells alone. Analysis of retrieved capsules revealed that hNGF continued to be released by encapsulated BHK-hNGF cells after 4 weeks in vivo. Moreover, histological analysis confirmed the presence of numerous viable encapsulated BHK-hNGF cells. These results indicate the potential use of intrastriatal implantation of encapsulated hNGF-secreting cells for augmenting the survival of cografted chromaffin cells as well as promoting the functional recovery of hemiparkinsonian rats. These data indicate that this approach may have potential application for treating Parkinson's disease.
Animals↗
[Encapsulated dopamine-secreting cells transplanted into the brain: a possible therapy for Parkinson's disease].
Encapsulation of neurosecretory cells within a semipermeable membrane may possibly isolate the enclosed cells from the host immune system and allow inward diffusion of nutrients and outward diffusion of neurotransmitters. Moreover, the encapsulation procedure may prevent the tumor formation of enclosed cells, when they are derived from tumor cells. In the present study, PC12 cells, a dopaminergic cell line derived from a rat pheochromocytoma, were enclosed within an agarose/poly (styrene sulfonic acid) (agarose/PSSa) mixture and transplanted into the brains of rats (allogeneic transplantation) or guinea pigs (xenogeneic transplantation). Tyrosine hydroxylase (TH) immunoreactive PC12 cells within the microcapsules were observed in all rats and guinea pigs at least up to five weeks after transplantation. PC12 cells were round in shape and of relatively uniform small size. Although PC12 cells occasionally formed cell clusters, the formation of a tumor was not observed. The host reaction to agarose/PSSa microcapsules was minimum. The degree of glial fibrillary acidic protein (GFAP) positive astrocyte density around the microcapsules was similar to that around injection tracks. There was no apparent immunological rejection around the capsules. High-performance liquid chromatography with electrochemical detection (HPLC-EC) showed basal and potassium-evoked release of dopamine from the PC12 cell-enclosed microcapsules in vitro. Although our data is preliminary, we believe that agarose/PSSa microcapsules are promising for producing semipermeable membranes that enable allo-and xenotransplantation of neurosecretory cells into the brain in the absence of systemic immunosuppression. This approach is expected to be applied in Parkinson's disease in the near future.
Adrenal Gland Neoplasms↗
[So-called NK cell lymphoma].
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Adolescent↗