Brachmann-de Lange syndrome and congenital heart disease.
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De Lange Syndrome↗
Biomedical subjects
N Okamoto
Publications and source records attributed to N Okamoto.
Administration of IL-4 prevents autoimmune diabetes but enhances pancreatic insulitis in NOD mice.
The present study demonstrated that the administration of recombinant interleukin-4 (rIL-4) prevented overt diabetes in nonobese diabetic (NOD) mice whose T cells produced relatively low amounts of IL-4. However, massive insulitis was observed in rIL-4-treated NOD mice. The flow cytometric analysis of islet-infiltrating T cells revealed that the number of CD45RBlowCD4+ T cells was significantly increased by in vivo administration of rIL-4. By measuring the cytokine production of splenic T cells after stimulation, it was shown that CD45RBlowCD4+ T cells predominantly produced IL-4 and IL-10 but produced less IL-2 and interferon-gamma (IFN-gamma). A semiquantitative reverse-transcriptase polymerase chain reaction assay revealed a higher expression of IL-4 and IL-10 mRNA and an apparent decrease in IFN-gamma mRNA in the islets of NOD mice which were administered rIL-4. These results suggested that autoreactive CD45RBlowCD4+ T helper 2 (Th2)-like cells which developed following rIL-4 administration were predominant in the infiltrate of the islets, and overt diabetes was prevented. On the other hand, when splenocytes from rIL-4-treated NOD mice were transferred to irradiated NOD recipients, along with splenocytes from diabetic NOD mice, all of the recipient mice became diabetic within 8 weeks after transfer. Considered together, a supplement of rIL-4 administered to NOD mice may protect against autoimmune diabetes by facilitating the development of Th2-like autoreactive T cells in the islets.
Animals↗
Cadmium-induced scale deformation in carp (Cyprinus carpio).
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Animals↗
Basic fibroblast growth factor is neither necessary nor sufficient for the development of retinal neovascularization.
Basic fibroblast growth factor (FGF2) is constitutively expressed in the retina and its expression is increased by a number of insults, but its role in the retina is still uncertain. This study was designed to test the hypothesis that altered expression of FGF2 in the retina affects the development of retinal neovascularization. Mice with targeted disruption of the Fgf2 gene had no detectable expression of FGF2 in the retina by Western blot, but retinal vessels were not different in appearance or total area from wild-type mice. When FGF2-deficient mice were compared with wild-type mice in a murine model of oxygen-induced ischemic retinopathy, they developed the same amount of retinal neovascularization. Transgenic mice with a rhodopsin promoter/Fgf2 gene fusion expressed high levels of FGF2 in retinal photoreceptors but developed no retinal neovascularization or other abnormalities of retinal vessels; in the ischemic retinopathy model, they showed no significant difference in the amount of retinal neovascularization compared with wild-type mice. These data indicate that FGF2 expression is not necessary nor sufficient for the development of retinal neovascularization. This suggests that agents that specifically antagonize FGF2 are not likely to be useful adjuncts in the treatment of retinal neovascularization and therapies designed to increase FGF2 expression are not likely to be complicated by retinal neovascularization.
Animals↗
Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model.
Choroidal neovascularization (CNV) is the major cause of severe visual loss in patients with age-related macular degeneration. Laser treatment is helpful for a minority of patients with CNV, and development of new treatments is hampered by a poor understanding of the molecular signals involved. Several lines of evidence have suggested that basic fibroblast growth factor (FGF2) plays a role in stimulating CNV. In this study, we tested this hypothesis using mice with targeted disruption of the FGF2 gene in a newly developed murine model of laser-induced CNV. One week after krypton laser photocoagulation in C57BL/6J mice, 34 of 60 burns (57%) showed fluorescein leakage and 13 of 16 (81%) showed histopathological evidence of CNV. At 2 weeks, CNV was detected in 9 of 10 burns (90%) in which a bubble had been observed at the time of the laser treatment. Electron microscopy showed fenestrated vessels with large lumens within choroidal neovascular lesions. Two weeks after laser-induced rupture of Bruch's membrane, 27 of 36 burns (75%) contained CNV in FGF2-deficient mice compared with 26 of 30 (87%) in wild-type control mice, a difference that is not statistically significant. This study demonstrates that FGF2 is not required for the development of CNV after laser-induced rupture of Bruch's membrane and provides a new model to investigate molecular mechanisms and anti-angiogenic therapy in CNV.
Animals↗
Site-specific lead distribution in scales of lead-administered carp (Cyprinus carpio) by non-destructive SR-XRF analysis.
By utilizing non-destructive synchrotron radiation-excited X-ray fluorescence (SR-XRF), we observed the distribution of lead (Pb) in both ontogenic and regenerating scales of lead-administrated carp, Cyprinus carpio. The fish in the Pb-administered group were fed pellets containing 1 mg/g of Pb at a rate of 1.5% body weight per day for 30 days. In the ontogenic scales, Pb was highly accumulated near the basal edge of the scale and the accumulated amount decreased toward the focus of the scale. On the other hand, in the regenerating scales, high accumulation was observed near the basal edge and the accumulated amount remained high toward the focus. The present results of Pb accumulation correspond well with the region which is calcifying in the ontogenic and regenerating scales, and indicate that the distributions of Pb show when and how long Pb was administered.
Animals↗
Comparison of ciliary sulcus fixation techniques for posterior chamber intraocular lenses.
OBJECTIVE: To anatomically and histologically evaluate suturing techniques for sulcus fixation of posterior chamber intraocular lenses. SETTING: Kitano Hospital, Osaka, Japan. METHODS: The reproducibility of three suturing techniques (perpendicular to the eye wall; parallel to the iris; midway between perpendicular to the eye wall and parallel to the iris) were evaluated in a postmortem eye. Histologic sections of another eye and ultrasound biomicroscopy (UBM) images of 21 normal eyes were evaluated to determine the safety zone for the needle to avoid damaging adjacent structures. RESULTS: The ciliary sulcus was completely penetrated in the three techniques in 100, 40, and 70% of cases, respectively. The histologic sections and the UBM images showed that when sutures were placed perpendicular to the eye wall, there was the possibility of postoperative angle closure and suturing parallel to the iris might damage adjacent structures because of a narrow safety zone. CONCLUSIONS: The needle should penetrate obliquely, as in the technique in which the suturing is midway between perpendicular to the eye wall and parallel to the iris. This technique provides better reproducibility and causes less damage to adjacent tissue.
Ciliary Body↗
Homozygous missense mutation (band 3 Fukuoka: G130R): a mild form of hereditary spherocytosis with near-normal band 3 content and minimal changes of membrane ultrastructure despite moderate protein 4.2 deficiency.
The characteristics of phenotypic expression were studied in a Japanese family with hereditary spherocytosis and an extremely rare homozygous missense mutation of the band 3 gene (band 3 Fukuoka: G130R). The homozygous unsplenectomized proband was a 29-year-old male with compensated haemolytic anaemia (red cell count 4.21 x 10(12)/l, reticulocytes 278 x 10(9)/l, and indirect bilirubin 44 micromol/l). His red cell band 3 (B3) protein demonstrated a 9.3% reduction and his protein 4.2 (P4.2) level was substantially reduced (45.0%), compared to normal subjects. P4.2 protein was composed mostly of a wild type (72 kD) with a trace of 68 kD peptide. The binding properties of the mutated B3 to normal P4.2 were significantly impaired, which probably resulted in the substantial reduction of P4.2 in this proband, since no abnormalities were detected on the P4.2 gene. Electron microscopy (EM) using the freeze-fracture method demonstrated a mild decrease in intramembrane particles (IMPs) of near-normal size (8 nm in diameter) with no substantial increases in their oligomerization. Their distribution on the membrane P face was almost normal, although most of the IMPs could represent the homozygously mutated B3 protein. EM (quick-freeze deep-etching method) disclosed a skeletal network of near-normal size and size distribution of the skeletal units, suggesting that the mutated B3 protein itself did not have much effect on the skeletal network in situ. Therefore the reduced P4.2 content (45% of that of normal subjects), which remained on the red cell membrane of this proband, appeared to be nearly sufficient for maintaining the normal structure of the skeletal network and IMPs in situ, contrary to the marked abnormalities in both IMPs and the skeletal network in complete P4.2 deficiencies.
Adult↗
Role of p300, a transcriptional coactivator, in signalling of TGF-beta.
BACKGROUND: Smad proteins are novel transcriptional regulators mediating the signalling of the transforming growth factor-beta (TGF-beta) superfamily. Coactivators such as p300/CBP promote transactivation by various transcription factors through a direct interaction with them. Adenoviral oncoprotein E1A, which binds p300, was shown to inhibit the signalling of TGF-beta. These findings raise the possibility that p300 may be involved in TGF-beta signalling. RESULTS: We investigated whether p300 is involved in transactivation by Smads. p300 enhanced the Smad-induced transactivation of p3TP-Lux, a TGF-beta responsive reporter. E1A inhibited this enhancement, and the inhibition required its ability to bind p300/CBP. p300 and Smad3, as well as Smad2, interacted in vivo in a ligand-dependent manner. The binding region in Smad3 was its C-terminal half that was previously shown to possess an intrinsic transactivation activity. The binding region in p300 was mapped to its C-terminal 678 amino acids. The minimal Smad2/3-interacting region, as well as the rest of the p300, inhibited the transactivation of p3TP-Lux in a dominant-negative fashion. CONCLUSION: p300 interacted with Smad2 and Smad3 in a ligand-dependent manner, and enhanced the transactivation by Smads. Our results present the molecular basis of the transactivation by Smad proteins.
Adenovirus E1A Proteins↗
Results of a qualitative and field study using the WHOQOL instrument for cancer patients.
The main purpose of the study was to evaluate quality of life (QOL) among cancer patients using the WHOQOL-100 instrument and to see if any significant differences were seen in cancer stages, treatment status and prognosis. This study consisted of two parts; qualitative and quantitative. For the qualitative study, two focus groups were conducted by medical professionals to establish the applicability of the WHOQOL instrument in evaluating the QOL of cancer patients, but most participants were negative about using a generic instrument such as WHOQOL. For the quantitative study, 197 cancer patients (average age 55.86) from eight medical centers using the WHOQOL instrument, in addition to each patient's information sheet filled in by their own physicians, were analyzed. The average overall QOL score was 3.39. There was high reliability (Cronbach's alpha = 0.9685) and a high correlation between the psychological and the environmental domains (r = 0.7021), the physical domain and the level of independence (r = 0.6031) and social relations and the environment (r = 0.6856) and between health conditions perceived by patients and QOL scores. In addition, differences by gender, treatments and cancer sites were also found to be significantly different at the 5% significance level. The results indicated that the WHOQOL core instrument was sensitive enough to evaluate the QOL of cancer patients.
Adult↗
Intractable diarrhea with serious tetany in "CATCH 22".
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Abnormalities, Multiple↗
Identification of a human heavy chain antibody fragment directed against human platelet alloantigen 1a by phage display library.
The human platelet alloantigen HPA-1a (PlA1) is responsible for most cases of post-transfusion purpura and neonatal alloimmune thrombocytopenia in the Caucasian population. HPA-1a and HPA-1b are two allelic forms of the platelet membrane glycoprotein IIIa (GPIIIa) gene that differ by a single amino acid. In this report, we describe the development of a recombinant heavy chain antibody fragment capable of distinguishing between the homozygous forms of HPA-1a and HPA-1b. This antibody fragment was isolated from the lymphocytes of an immunized individual through the use of a phage display library system. The recombinant antibody fragment reacted with human platelet lysates from HPA-1a homozygous donors, the HPA-1a form of recombinant N-terminal GPIIIa and intact HPA-1a platelets, but did not react with platelet lysate from HPA-1b homozygous donors, reduced HPA-1a form of platelet GPIIIa or other platelet glycoproteins. This HPA-1a specific human antibody fragment works well in common laboratory assays such as ELISA and flow cytometry, which can assist in identifying HPA-1b homozygous individuals who are known to have a higher risk for developing neonatal alloimmmune thrombocytopenia and post-transfusion purpura. Thus, selection of recombinant antibody fragment using phage display offers a promising alternative to hybridoma technology for the production of human antibodies against human alloantigens and holds potential as a technique in therapeutic applications.
Antibody Specificity↗
[Evaluation of home-oxygen-therapy for old tuberculosis cases, especially emphasis on the medical support for more comfortable life].
We investigated the home-oxygen-therapy (HOT) for old tuberculosis patients. Tuberculosis cases are 100 of 296 all home-oxygen-therapy during the period from Aug. 1986 to Dec. 1997. 36 dead cases of these 100 were evaluated. Average period for HOT was 988 days (32.9 months). The mean rate of home stay was 78.9%. HOT is very useful for supporting comfortable home stay life. Our Medical respiratory Care (MRC) system is consist of primary education on HOT start, respiratory rehabilitation, mass education, annual rehabilitation trip and home nursing. Our MRC team is consist of 2 doctors, 12 nurses, 3 physical therapists, a dietician, a pharmacist and a medical clerk. We consider that it's important to support more comfortable life of the patients with chronic respiratory distress syndrome due to old tuberculosis.
Aged↗
Evolution of neovascularization in mice with overexpression of vascular endothelial growth factor in photoreceptors.
PURPOSE: To determine the earliest changes that occur in the retina after the onset of ectopic expression of vascular endothelial growth factor (VEGF) by photoreceptors in transgenic mice, to characterize the development of neovascularization (NV), and to determine the feasibility of using these mice to test the efficacy of antiangiogenic agents. METHODS: The time course of expression of VEGF transgene mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). Histopathologic changes in the retina were investigated by light and electron microscopy and immunocytochemistry. Standard and confocal fluorescence microscopy and image analysis were used to evaluate NV in retinal whole mounts. RESULTS: VEGF transgene mRNA was first detected in the retina by RT-PCR on postnatal day 6 (P6) and increased over the next several days to reach a constant steady-state level between P14 and P21. Abnormal cells were seen in the outer nuclear layer on P10 and among photoreceptors on P14; by P18 there were cell aggregates in the subretinal space with evidence of lumen formation. The invading cells were demonstrated to be endothelial cells by staining with an endothelial cell-specific lectin. Whole mounts of retinas perfused with fluorescein-labeled dextran showed a similar sequence of events, with sprouts from retinal vessels in the deep capillary bed seen on P14 and vessels reaching the subretinal space by P18. Confocal and standard fluorescence microscopy and changes in the number and area of neovascular lesions in the subretinal space over time measured by image analysis suggest gradual enlargement and coalescence of vascular complexes. The subretinal NV was progressively engulfed by the retinal pigmented epithelium. Invasion of blood vessels from the choroid was not identified in any specimen. CONCLUSIONS: These data support the feasibility of using rhodopsin-VEGF transgenic mice to study tissue-specific aspects of NV in the retina and to test antiangiogenic agents for inhibition of intraretinal and subretinal NV.
Animals↗
[The time course of white retinal arterioles in two cases of antiphospholipid antibody syndrome].
We report two cases of antiphospholipid antibody syndrome with elevated anti-beta 2-glycoprotein I antibodies. Patient 1 had systemic lupus erythematosus (SLE) and was treated with an oral corticosteroid and aspirin. There were foci of sheathed retinal arterioles appearing as white lines in the fundus of both eyes. The sheathed arterioles of the peripheral fundus of the right eye were completely or incompletely occluded. Recanalization occurred during a 10 month follow-up. Patient 2 had hypertension and multiple brain infarction but no association with collagen diseases. Major retinal arterioles showed sheathing. Fluorescein angiography demonstrated progressive occlusion or stenosis of these major arterioles with extensive insufficiency of regional capillary bed circulation. Retinal photocoagulation was applied to both eyes which developed neovascularization. Vitrectomy was performed in the left eye with recurrent vitreous hemorrhage. Antiphospholipid antibody syndrome should be considered in cases of sheathed or white retinal arterioles.
Adult↗
[Evaluation of scanning laser Doppler flowmetry in anesthetized cats].
The aim of this work was to evaluate the reliability of scanning laser Doppler flowmetry (SLDF) developed by Michelson (Heidelberg retina flowmeter) as compared to fundus camera based laser Doppler flowmetry (FLDF). Blood flow was measured on several occasions by SLDF in the optic nerve head (ONH) and in retinal capillaries of the intervascular area (IV A) in four immobilized anesthetized cats. The circulation was stimulated with pure oxygen breathing, and intravenous infusion of noradrenalin or papaverine. Blood flow was also monitored during euthanasia. The two techniques were compared in repeated successful experiments. In the ONH and IV A, mean values of blood flow were 20-1600 (arbitrary units, AU), and 400-1700 AU respectively. The mean coefficient of variance was 9.1% in the ONH and 8.0% in the IV A in five consecutive measurements. The relative change in IV A blood flow between SLDF and FLDF during noradrenalin infusion were similar over time, although the values of the changes were not significantly correlated (n = 15 r = 0. 489 p = 0.064). Papaverine infusion showed various responses in the ONH except one point where FLDF showed an increase in blood flow. During euthanasia, the SLDF revealed an increase in ONH blood flow temporally in some animals, but not in IV A. A Value of 100-200 AU for both ONH and IV A remained even after euthanasia. The FLDF, however, showed a decrease in ONH blood flow with systemic blood pressure. Measurement of IV A blood flow appears more reliable than that of ONH blood flow. The characteristics of SLDF should be considered when we interpret the blood flow value.
Animals↗
Premature aging syndrome with osteosarcoma, cataracts, diabetes mellitus, osteoporosis, erythroid macrocytosis, severe growth and developmental deficiency.
We describe a premature aging disorder in a 15-year-old girl with severe growth and developmental deficiency. Her clinical findings included osteosarcoma, nuclear and subcapsular cataracts, insulin-resistant diabetes mellitus, osteoporosis, epilepsy, foot ulcers, erythroid macrocytosis, and unusual facial appearance. Hyaluronic acid levels in serum and urine were normal. Cultured skin fibroblasts had a normal potential for in vitro growth. This finding represents a new and unique premature aging syndrome.
Abnormalities, Multiple↗