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Biomedical subjects

A Fukushima

Publications and source records attributed to A Fukushima.

At least 19 recordsLinked to original sources

Interleukin 10 and transforming growth factor beta contribute to the development of experimentally induced allergic conjunctivitis in mice during the effector phase.

AIM: To investigate the involvement of interleukin (IL)10 and transforming growth factor (TGF) beta in the development of experimentally induced allergic conjunctivitis in mice. METHODS: Balb/c mice were actively sensitised with ragweed in alum, and then challenged with ragweed in eye drops after 10 days. 24 h later, the conjunctivas, spleens and blood were collected for histological and cytokine expression analyses, proliferation and cytokine production assays and measurement of immunoglobulin (Ig) levels. Mice developing experimentally induced allergic conjunctivitis were injected intraperitoneally with 200 microg of anti-IL10 or anti-TGF beta antibodies at 0, 2, 4, 6 and 8 days (induction phase treatment) or 500 microg of antibodies 2 h before ragweed challenge (effector phase treatment). Normal rat IgG was used for control injections. RESULTS: Treatment with either anti-IL10 or anti-TGF beta antibodies during the induction phase did not affect eosinophil infiltration into the conjunctiva. By contrast, treatment with either antibody during the effector phase suppressed infiltration. During the effector phase, treatment with anti-TGF beta antibody, but not the anti-IL10 antibody, markedly up regulated proliferation and Th2 cytokine production by splenocytes. IL1alpha levels in the conjunctiva were reduced after treatment with either antibody; in addition, eotaxin and tumour necrosis factor alpha levels were reduced after treatment with antibody to TGF beta. CONCLUSIONS: IL10 and TGF beta do not have immunosuppressive roles in the development of experimentally induced allergic conjunctivitis. Rather, they augment the infiltration of eosinophils into the conjunctiva during the effector phase of experimentally induced allergic conjunctivitis.

Adoptive Transfer↗

Involvement of programmed death-ligand 2 (PD-L2) in the development of experimental allergic conjunctivitis in mice.

BACKGROUND/AIM: Involvement of programmed death-1 (PD-1) and its ligands has been demonstrated in experimental allergic airway disease. Here, the authors aimed to examine whether PD-1 and its ligands are involved in the development of experimental allergic conjunctivitis (EC) in mice. METHODS: EC was induced in Balb/c mice by active immunisation with short ragweed pollen (RW) in alum. 10 days later (day 10), the mice were challenged with eye drops containing RW. 24 hours after the challenge, conjunctivas, spleens, and sera were harvested for histological analysis, cytokine assays, and measurement of RW specific Ig levels. The actively immunised mice were treated with anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies (Abs), or normal rat immunoglobulin G (nrIgG) during either the induction (day 0, 2, 4, 6, and 8) or the effector (2 hours before RW challenge on day 10) phase. RESULTS: Ab treatment during the induction phase did not affect eosinophil infiltration although immune responses were modulated. In contrast, treatment with anti-PD-L2 Ab, but not anti-PD-1 or anti-PD-L1 Ab, during the effector phase significantly increased eosinophil infiltration into the conjunctiva without affecting systemic immune responses. CONCLUSIONS: Similar to allergic airway inflammation, PD-L2 is involved in the development of EC during the effector phase but not the induction phase.

Ambrosia↗

Inflammatory reaction following cataract surgery and implantation of acrylic intraocular lens in rabbits with endotoxin-induced uveitis.

PURPOSE: To investigate whether inflammatory responses are more severe in uveitic eyes than nonuveitic eyes when acrylic intraocular lens (IOL) is implanted after cataract surgery. METHODS: Clear lens removal (phacoemulsification and aspiration) was conducted and the hydrophobic acrylic IOL (AR40e, AMO) was implanted in adult albino rabbits. Just after the operation, rabbits were divided into two groups. One group (nine rabbits) received intravitreal injection of lipopolysaccharide (LPS, 200 ng/10 microl) into both eyes to induce endotoxin-induced uveitis (EIU) and the other group (nine rabbits) received intravitreal injection of phosphate-buffered saline (PBS, 10 microl) into both eyes as the control. Aqueous humour (AH) and IOLs were harvested 1, 3 , and 7 days after the intravitreal injection. The infiltrating cell number in AH was counted and the protein concentration of AH was measured. IOLs were evaluated morphologically. RESULTS: At 1 day after intravitreal injection, both the infiltrating cell number in AH and protein concentration of AH were significantly higher in the LPS-injected group than in the PBS-injected group. Similarly, more inflammatory cells attached to the surfaces of the IOLs in the LPS-injected group. However, 7 days later, inflammatory reactions subsided and no clear differences in any of the parameters examined were observed between the two groups. CONCLUSIONS: At 7 days after the operation, inflammatory reactions in eyes implanted with the hydrophobic acrylic IOLs were similar in uveitic eyes and nonuveitic eyes. The data suggest that the hydrophobic acrylic IOLs may be suitable for patients with uveitis.

Acrylic Resins↗

Spin-torque diode effect in magnetic tunnel junctions.

There is currently much interest in the development of 'spintronic' devices, in which harnessing the spins of electrons (rather than just their charges) is anticipated to provide new functionalities that go beyond those possible with conventional electronic devices. One widely studied example of an effect that has its roots in the electron's spin degree of freedom is the torque exerted by a spin-polarized electric current on the spin moment of a nanometre-scale magnet. This torque causes the magnetic moment to rotate at potentially useful frequencies. Here we report a very different phenomenon that is also based on the interplay between spin dynamics and spin-dependent transport, and which arises from unusual diode behaviour. We show that the application of a small radio-frequency alternating current to a nanometre-scale magnetic tunnel junction can generate a measurable direct-current (d.c.) voltage across the device when the frequency is resonant with the spin oscillations that arise from the spin-torque effect: at resonance (which can be tuned by an external magnetic field), the structure exhibits different resistance states depending on the direction of the current. This behaviour is markedly different from that of a conventional semiconductor diode, and could form the basis of a nanometre-scale radio-frequency detector in telecommunication circuits.

Journal Article↗

Monitoring of T-cell repertoire was useful for predicting graft-versus-host disease prognosis in a patient with chronic myelogeneous leukemia after allogeneic bone marrow transplantation.

We analyzed 24 T-cell receptor (TCR)beta chain subfamilies (Vbeta) and the chimerism of a patient with chronic myelogeneous leukemia who underwent allogeneic bone marrow transplantation (allo-BMT). The patient developed liver dysfunction at day 19 leading to worsening of his condition. He died on day 91 of hepatic failure. Complete donor chimerism was observed after day 19. The average complexity score of TCR-Vbeta, which was low on day 19 (5.50), because much lower on day 82 (3.77). The average value of normal volunteers is 7.69. Neither immunosuppressive therapy nor antiviral therapy was effective to treat his hepatic dysfunction. A liver specimen at autopsy showed necrotic tissue with invasion of lymphocytes under the endothelial cells of the bile ducts. These findings suggest that the liver dysfunction was due to graft-versus-host disease (GVHD). Careful monitoring of chimerism and TCR-Vbeta complexity may help to predict the prognosis of GVHD after allogeneic BMT.

Adult↗

Exertion of the suppressive effects of IFN-gamma on experimental immune mediated blepharoconjunctivitis in Brown Norway rats during the induction phase but not the effector phase.

BACKGROUND/AIMS: Interferon gamma (IFN-gamma) knockout mice exhibit severe allergic conjunctivitis (AC), indicating that IFN-gamma regulates the development of AC. The authors examined whether this inhibitory effect of IFN-gamma is exerted during the induction or effector phase of experimental AC. METHODS: Experimental immune mediated blepharoconjunctivitis (EC) was induced in Brown Norway (BN) rats, using ovalbumin (OVA) as the antigen. To investigate the role of IFN-gamma in the induction phase, EC was induced by active immunisation and IFN-gamma (10 micro g/time, total 70 micro g), or phosphate buffered saline (PBS) as a control, was injected intraperitoneally every other day from the day of immunisation. The rats were challenged with OVA eye drops 13 days after immunisation, and 24 hours later, the eyes were harvested for histology. To examine the effects of IFN-gamma in the effector phase, OVA specific T cells were transferred into syngeneic rats and IFN-gamma (10 micro g/time, total 50 micro g) or PBS was injected each day after the transfer until induction of EC 4 days later with an OVA challenge. To investigate the role of endogenous IFN-gamma during the effector phase, an anti-IFN-gamma monoclonal antibody (3 mg/time) was injected on days 3 and 4. RESULTS: Injection of IFN-gamma into actively immunised rats suppressed eosinophilic infiltration but not infiltration of mononuclear cells. In contrast, neither IFN-gamma nor anti-IFN-gamma affected EC in passively immunised rats. CONCLUSION: IFN-gamma is a suppressive cytokine for the development of EC and exerts this suppressive effect during the induction phase.

Adoptive Transfer↗

Structural analyses of the UTF1 gene encoding a transcriptional coactivator expressed in pluripotent embryonic stem cells.

The UTF1 is a transcriptional coactivator expressed mainly in pluripotent embryonic stem cells. Here, we have isolated a genomic DNA fragment carrying the UTF1 gene and found that the gene contains two exons interrupted by a short intron. The gene possesses four GC boxes, but no TATA box in the 5'-flanking region. This is reminiscent of a housekeeping gene type promoter and the functional relevance of these motifs is confirmed by the transient transfection analyses. As to the gene product, our analyses have led to the identification of two different species. One of them corresponds to the full-length protein, while the other is produced by utilizing the second methionine codon for the translation initiation. The oligo-capping analyses reveal multiple transcription start sites. Interestingly, some of them are localized downstream of the first methionine codon, indicating that such transcripts produce a protein starting from the second methionine codon. Chromosomal mapping analyses locate the gene at 7F5, the syntenic region of the human chromosome (10q26) where the human UTF1 gene is located.

Amino Acid Sequence↗

Crystallization process of transparent conductive oxides Zn(k)In2O(k+3).

Crystallization process of the homologous compounds Zn(k)In2O(k+3) from the coprecipitants was examined by XAFS spectroscopy and X ray diffractometry. Interesting crystallization behavior could be observed. Though zinc oxide already crystallized as the wurtzite-type ZnO at 573K, indium oxide remained amorphous. Subsequently bixbyite-type In2O3 appeared at 873K for k=5 and 7 and at below 773K for the other k-members, respectively. The InO distance in the amorphous In2O3 was a little shorted than that in the bixbyite-type In2O3 by 0.06-7A. The distance remained constant but abruptly increased to that observed in the bixbyite-type In2O3 in accordance with the progress of crystallization. Then the distance gradually decreased and converged to ca. 2.12A at the temperature range of 1173-1373K, due to the reaction between In2O3 and ZnO to form the homologous compound.

Journal Article↗

Skewed abrogation of tolerance to a neo self-antigen in double-transgenic mice coexpressing the antigen with interleukin-1beta or interferon-gamma.

Transgenic (Tg) mice expressing hen egg lysozyme (HEL) under the control of the alphaA-crystallin promoter exhibit tolerance to HEL by both their T- and B-cell compartments. Here, we show that double-Tg mice, coexpressing HEL with either interleukin-1beta or interferon (IFN)-gamma, demonstrated unresponsiveness to HEL by their T-cell compartment, but most of them developed antibodies against HEL following a challenge with the antigen. The abrogation of humoral tolerance was more pronounced in the HEL/IL-1 double-Tg mice than in the HEL/IFN-gamma mice. Unlike their controls, double-Tg mice exhibited remarkable levels of variability in their antibody levels. The skewed abrogation of tolerance in the double-Tg mice is proposed to be due to the cytokines' capacity to rescue from clonal deletion small numbers of T cells, which provide help to antibody producing B cells. This notion is supported by the finding that adoptive transfer of small numbers of Th1 or Th2 cells into HEL-Tg mice made possible antibody production similar to that seen in the double-Tg mice.

Adoptive Transfer↗

A monoclonal antibody-based ELISA for the analysis of the insecticide flucythrinate in environmental and crop samples.

A competitive enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of the insecticide flucythrinate in environmental and food samples. Two types of haptens, the acid moiety that is the hydrolyzed product of flucythrinate, and the carboxylated propyl derivative of the alcohol moiety, were used to prepare monoclonal antibodies (MAbs). Five MAbs, which raised against the former hapten, were reactive with flucythrinate. Among them, MAb F1A27-4 showed the highest activity toward flucythrinate, and did not cross-react with other pyrethroids such as cycloprothrin, fenvalerate, fluvalinate, etofenprox and silafluofen. The assay conditions of indirect competitive ELISA with MAb F1A27-4 were studied to optimize the detection of flucythrinate in environmental and food samples. Incubation at 4 degrees C in the assay buffer, pH 8, with 300 mM sodium chloride improved the sensitivity. The addition of rabbit serum albumin or rabbit antiserum and the presence of 50 ml litre-1 of methanol reduced matrix effects of the samples. Under optimized conditions, the ELISA detected flucythrinate spiked in water, soil, and extracts of apple and tea samples down to 10 mg litre-1, 0.2 mg litre-1, 0.3 mg litre-1 and 0.3 mg litre-1, respectively. The mean recovery and CV ranged from 91% to 120% and from 5% to 12%, respectively. The ELISA results in apple samples correlated well with those from LC-MS analysis (r2 = 0.99, n = 12).

Animals↗

Malignant fibrous histiocytoma of the vagina.

We describe here the case of an 82-year-old woman presenting with a hemorrhagic tumor on the anterior vaginal wall. She was diagnosed with malignant fibrous histiocytoma (MFH) from the findings of cytological analysis of biopsied surface tissue, histopathologic analysis of biopsied tissue, immunohistochemical staining, and electron microscopy. Cytological analysis of the biopsy sample harvested from the tumor surface showed multinucleated giant cells and large atypical cells with rough, granular, chromatin, as well as notable nucleoli. A storiform pattern was observed histopathologically, and immunohistochemical staining confirmed positive reactions to alpha 1-antichymotripsin (alpha 1-ACT), vimentin, and lysosome, but negative reactions to epithelial membrane antigen (EMA), cytokeratin, and alpha-smooth muscle action (alpha-SMA). Electron microscopy showed histiocyte-derived cells with a segmented nucleus with a large groove, pseudopodic cytoplasmic projections, and lysosome-like structures. However, intercellular adhesion factors were not notable, and microvilli were absent. Based on the above findings, a diagnosis of MFH originating from the vaginal wall was made. Because of the patient's advanced age, and, in accordance with her wishes, three courses of cancer chemotherapy, consisting of doxorubicin hydrochloride, fluorouracil, and cisplatin were carried out, without surgery. No reduction in the size of the tumor was seen at follow up, and despite the absence of metastasis and no exacerbation of her general condition, she died suddenly at home 2 years after being discharged.

Aged↗

Chronic docosahexaenoic acid intake enhances expression of the gene for uncoupling protein 3 and affects pleiotropic mRNA levels in skeletal muscle of aged C57BL/6NJcl mice.

Docosahexaenoic acid [DHA, 22:6(n-3)] prevents cardiovascular disease by decreasing obesity. It also prevents cancer and other geriatric diseases. We studied the chronic pleiotropic effects of DHA on transcription including that of mRNAs for uncoupling proteins (UCP). Male and female mice (9 mo old) were fed high (n-6) or high (n-3) fatty acid diets for 4 mo. Compared with controls fed high (n-6) fatty acid diets [high (n-6) group], the livers of male and female mice fed DHA [high (n-3) group] contained six- (P < 0.001) and fivefold (P < 0.001) more DHA, respectively. The high (n-3) group had less white adipose tissue [35.3% in males (P < 0.001) and 27.3% in females (P < 0.001)]. The high (n-3) group expressed more uncoupling protein 3 (UCP3) in the gastrocnemius, 108% higher (P < 0.001) and 104% higher (P < 0.001) in males and females, respectively, than those in the high (n-6) group. However, the prevention of many diseases by DHA is not explained by UCP3. Thus, the gene expression profiles of both high (n-3) and high (n-6) groups were analyzed in skeletal muscle using cDNA expression array. Of 588 genes surveyed in the array, the high (n-3) group showed 12 genes (2%) including those for glucose regulators (e.g., CD38) and tumor suppressors (e.g., CTCF) that were expressed 100-340% more than those of the high (n-6) group. Furthermore, 28 genes (4.8%), including growth factors (e.g., ErbB-2 receptor) and immune regulators (e.g., interleukin-1 beta precursor) were expressed 50-90% less in the high (n-3) group than in the high (n-6) group. These results explain in part the important pleiotropic effects of DHA, which are independent of obesity control by UCP3 suppression.

Aging↗

Mechanism for maintenance of dominant T helper 1 immune responses in Lewis rats.

Lewis rats are prone to T helper (Th) 1 immune responses, whereas Brown Norway (BN) rats are susceptible to Th2 immune responses. Yet, the precise mechanism of induction of the different outcome between these two strains remained elusive. We investigated the expression levels of some cytokines, their receptors and accessory molecules responsible for the polarization of antigen-specific immune response into a predominant Th1 or Th2 profile in Lewis and BN rats. Lymph node (LN) cells collected from rats immunized with short ragweed (RW) were used directly or after stimulation in vitro with RW for 3 days. Expression of cytokines, their receptors and accessory molecules in these LN cells were tested by reverse transcriptase-PCR. Culture supernatant was used for ELISA to detect IL-12 protein. We observed clear differences between these strains in the expression of IL-12p40, which was high in LN cells of Lewis rats even before stimulation in vitro. In addition, a higher amount of IL-12 was present in the culture supernatant in Lewis rats. Upregulation of the expression of IL-12 receptor beta1, beta2, IFN-gamma receptor alpha and beta genes were more prominent in Lewis rats rather than BN rats. Furthermore, attenuated expression of CD40 and CD40 ligand by stimulation in vitro was noted only in BN rats. Changes in expression of these molecules by stimulation as well as higher basal level of IL-12p40 might have led to the activation of Th1 cells in Lewis rats.

Animals↗

The application of magnetic cell sorter (MACS) to detect fetal cells in maternal peripheral blood.

OBJECTIVES: The aim of the present study was to investigate the effectiveness of sorting fetal nucleated red blood cells (FNRBC) from maternal peripheral blood, particularly during early gestation periods, by a combination of specific gravity centrifugation and magnetic cell sorter (MACS). METHODS: Without prior knowledge of the gender of the fetus, we determined gender by analyzing a Y-chromosome specific sequence by nested-PCR, using 10 ml of the peripheral blood of healthy primigravida women at different stages of gestation (first trimester: n = 17, second trimester: n = 13, and third trimester: n = 19). The results of this prenatal sex determination were compared to the sex of newborns. RESULTS: The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of the present method during the first trimester were 100, 81.8, 100, and 75%, respectively; during the second trimester, 80, 50, 80, and 50%, respectively; and during the third trimester, 25, 63.6, 53.8, and 33.3%, respectively. CONCLUSION: The results show that this prenatal sex determination method has a highly accurate diagnostic rate during the first trimester, suggesting that it could be developed as a practical, non-invasive prenatal diagnostic technique for use during early gestation periods.

Cell Separation↗

[CT-guided needle biopsy of the lung: factors affecting risk of complications].

PURPOSE: To analyze factors influencing the risk of complications associated with CT-guided percutaneous needle biopsy for lung lesions. MATERIALS AND METHODS: Sixty patients, aged 24-85 years (37 men and 23 women), underwent CT-guided needle biopsy. A definite diagnosis was made in 49 of 60 cases (81.7%), including 38 of 43 malignant lesions (88.4%) and 11 of 17 benign lesions (64.7%). Complications associated with biopsy were observed in 35 patients (58.3%). Major complications included pneumothorax (n = 26) and pulmonary hemorrhage (n = 20). Chest tube placement was needed in 5 (19.2%) of 26 pneumothorax cases (8.3% of all biopsies). RESULTS: The high frequency of pneumothorax (43.3%) in this series had several contributing factors, including the presence of pulmonary emphysema, lesion size, and traversal of aerated lung. Chest tube replacement was necessary more frequently in patients with pulmonary emphysema. The number of pleural passes, location of lesions, and size of needles were not correlated with the incidence of pneumothorax. CONCLUSION: The presence of pulmonary emphysema, lesion size, and traversal of aerated lung are the predominant risk factors for pneumothorax in patients with CT-guided lung biopsy.

Adult↗

Breakdown of tolerance to a neo-self antigen in double transgenic mice in which B cells present the antigen.

Transgenic (Tg) mice expressing a foreign Ag, hen egg lysozyme (HEL), under control of the alphaA-crystallin promoter ("HEL-Tg" mice) develop immunotolerance to HEL attributed to the expression of HEL in their thymus. In this paper we analyzed the immune response in double (Dbl)-Tg mice generated by mating the HEL-Tg mice with Tg mice that express HEL Abs on their B cells ("Ig-Tg" mice). The B cell compartment of the Dbl-Tg mice was unaffected by the HEL presence and was essentially identical to that of the Ig-Tg mice. A partial breakdown of tolerance was seen in the T cell response to HEL of the Dbl-Tg mice, i.e., their lymphocyte proliferative response against HEL was remarkably higher than that of the HEL-Tg mice. T-lymphocytes of both Dbl-Tg and Ig-Tg mice responded to HEL at concentrations drastically lower than those found stimulatory to lymphocytes of the wild-type controls. Cell mixing experiments demonstrated that 1) the lymphocyte response against low concentrations of HEL is due to the exceedingly efficient Ag presenting capacity of the Ab expressing B cells and 2) breakdown of tolerance in Dbl-Tg mice can also be attributed to the APC capacity of B cells, that sensitize in vivo and stimulate in vitro populations of T cells with low affinity toward HEL, assumed to be escapees of thymic deletion. These results thus indicate that T cell tolerance can be partially overcome by the highly potent Ag presenting capacity of Ab expressing B cells.

Animals↗