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Biomedical subjects

T Iijima

Publications and source records attributed to T Iijima.

At least 235 records · Page 13Linked to original sources

Osteoclasts in normal and adjuvant arthritis bone tissues express the mRNA for both type I and II interleukin-1 receptors.

Osteoclasts are known to play a crucial role in both physiologic and pathologic bone resorption. Moreover, it is generally agreed that IL-1 has powerful effects on osteoclastic bone resorption, although the precise cellular sites and mechanisms by which IL-1 mediates osteoclastic bone resorption remain unclear. In particular, it is still controversial whether osteoclasts can respond to IL-1 directly. The expression of mRNA for type I IL-1 receptor (IL-1RI) and type II IL-1 receptor (IL-1RII) in osteoclasts was investigated in normal and inflammatory bone tissues by in situ hybridization to determine whether osteoclasts are the target cells for IL-1 and to elucidate the mechanism by which IL-1 induces osteoclastic bone resorption. For this study, normal tibiae were obtained from newborn, young, and adult mice and rats, and inflammatory bone tissues with bone destruction were obtained from adjuvant arthritis rat models. The results showed that (a) both IL-1 receptors (IL-1RI and -II) mRNA were expressed by osteoclasts in all tissue sections of normal tibiae; (b) at the stage of the adjuvant arthritis studied, the IL-1RI mRNA was the most predominant message in osteoclasts present in the area with serious cartilage and bone destruction, whereas the expression level of IL-1RII mRNA in these osteoclasts was weak; and (c) both IL-1RI and -II mRNA were expressed by osteoblasts, as well as by osteocytes localized in the osteoid. In addition, these messages were also expressed by chondrocytes, but the signals were not detected in the chondrocytes in the zones of hypertrophy and provisional calcification. Our present study demonstrates for the first time that mouse and rat osteoclasts express IL-1RI and -II mRNA, which suggest that a primary effect of IL-1 on osteoclasts may be one of the mechanisms by which IL-1 mediates normal bone remodeling and pathologic bone resorption in chronic inflammatory diseases.

Animals↗

Induction of endometrial adenocarcinomas by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine to aged Donryu rats showing spontaneously persistent estrus.

Induction of endometrial adenocarcinomas by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) to aged rats was examined. Donryu rats showing spontaneously persistent estrus were given a single intra-uterine administration of ENNG (20 mg/kg) at 10 months (44 weeks) of age. At the termination of the experiment (week 34 after the ENNG-treatment), 22% and 13% incidences of endometrial adenocarcinomas were observed in the experimental and control groups, respectively, the difference being without significance. No variation was found in the endocrine environment between experimental and non carcinogen-treated control animals throughout the experimental period. These results show that ENNG-treatment alone is not sufficient in aged rats for high induction of endometrial carcinomas. Comparison of the data with those from our previous studies, in which ENNG was given at a young age (10 weeks of age), indicates that young rats may be more sensitive than their old counterparts.

Adenocarcinoma↗

Determination of the photoaffinity-labeled site on the ligand-binding domain of retinoic acid receptor alpha.

The ligand-binding domain of human retinoic acid receptor alpha (hRAR alpha) was photoaffinity-labeled with a fluorescent retinoid, ADAM-3, by the use of a recombinant fused protein constructed from a maltose-binding protein and the E/F-domain of hRAR alpha (MBP-RAR alpha/E), which was expressed in E. coli. The labeled site was identified as Arg-589 (this corresponds to amino acid residue 385 of hRAR alpha) or a residue in its vicinity.

Affinity Labels↗

Modulation of cytosolic Ca2+ concentration by thapsigargin and cyclopiazonic acid in human aortic endothelial cells.

To clarify the agonist-induced Ca2+ entry mechanism, effects of thapsigargin and cyclopiazonic acid, selective inhibitors of endoplasmic reticulum Ca(2+)-ATPase, on intracellular free Ca2+ concentration ([Ca2+]i) were studied in cultured human aortic endothelial cells loaded with the fluorescent Ca2+ indicator fura-2. Thapsigargin (1-1000 nM) and cyclopiazonic acid (0.1-100 microM) produced a biphasic change in [Ca2+]i, which consisted of a transient peak elevation followed by a long-lasting decline of [Ca2+]i in a concentration-dependent manner. In the presence of thapsigargin or cyclopiazonic acid, the rapid transient elevation of [Ca2+]i elicited by histamine was attenuated in a time-dependent manner. The slow declining phase of the response to thapsigargin and cyclopiazonic acid was completely eliminated by removal of extracellular Ca2+, and it was also prevented by reduction of the extracellular Cl- concentration to 40 mM or by the Cl- channel blocker N-phenylanthranilic acid. These findings suggest that the initial transient rising phase and the slow declining phase of [Ca2+]i in response to thapsigargin and cyclopiazonic acid reflect a blockade of Ca2+ uptake into the endoplasmic reticulum and the Cl(-)-sensitive Ca2+ entry activated by the depletion of agonist-sensitive intracellular Ca2+ stores, respectively, in human aortic endothelial cells.

Aorta↗

Interleukin-10 selectively inhibits osteoclastogenesis by inhibiting differentiation of osteoclast progenitors into preosteoclast-like cells in rat bone marrow culture system.

Recombinant human interleukin-10 (hIL-10) inhibited the formation of osteoclast-like multinucleated cells in rat whole bone marrow cultures. The effect of hIL-10 on the process of osteoclast formation was further examined, since the process of osteoclast formation includes the proliferation and the differentiation of osteoclast progenitors into mononuclear preosteoclasts and the fusion of preosteoclasts into multinucleated osteoclasts. In the nonadherent bone marrow cell culture system, which was free of stromal cells and formed preosteoclast-like cells, hIL-10 significantly inhibited the formation of preosteoclast-like cells even at a very low concentration (0.5 U/ml). The strong inhibition appeared even after treatment with hIL-10 for only the first 24 h of the culture. However, hIL-10 did not affect the fusion process of preosteoclast-like cells to form osteoclast-like multinucleated cells in the rat coculture system of preosteoclast-like cells with primary osteoblasts. Furthermore, hIL-10 completely inhibited the colony formation induced by granulocyte macrophage colony-stimulating factor (GM-CSF). These findings suggest that the inhibition of osteoclastogenesis by hIL-10 started at the early stage of the differentiation of osteoclast progenitors to preosteoclasts.

Animals↗

Surgical treatment of extra-abdominal desmoid tumours (aggressive fibromatoses).

Extra-abdominal desmoid tumours (EADT) are benign lesions but difficult to cure because of their infiltrative nature and tendency to recur. Among many treatments recommended in the past, wide excision has been successful, even in difficult cases. We have analyzed retrospectively 41 cases of histologically confirmed EADTs. A total of 98 operations were performed on these patients: 29 wide excisions on 22 patients, 52 intra-lesional excisions with wide margins on 16 patients, and 17 incomplete excisions on 3 patients. One patient, with intra-pelvic lesions, died of a massive haemorrhage 3 days after surgery. Forty patients were followed from between 3 and 29 years. One, who had a multicentric EADT for 21 years, died from the disease. The significant factors concerning local recurrence after wide procedures were an unsatisfactory initial wide local excision, disease affecting 4 or more muscles and the invasive nature of the recurrences. We recommend wide local excision of these tumours in all anatomical areas that allow this procedure. When major nerves and vessels are involved, we recommend an intralesional excision with wide margins in order to preserve limb function. Radiation therapy should be confined to cases in which wide local procedures are not feasible. Overall, 37 of our patients (90%) were cured of the disease, 2 had their disease controlled, and 2 died.

Adolescent↗

Effect of extracorporeal life support on cerebral blood flow, metabolism and electrophysiology in normothermic cats.

OBJECTIVE: Recently, extracorporeal life support (ECLS) by venoarterial bypass perfusion has been recommended for the treatment of refractory respiratory and/or cardiac failure but the safety of this application for the brain is not yet established. Therefore, the effects of normothermic ECLS on cerebral blood flow, metabolism and electrophysiology were studied in cats with total arrest of cardiopulmonary circulation. DESIGN: An extracorporeal circulation (ECC) system, consisting of a roller pump, a membrane oxygenator and a heat exchanger, was connected to the circulation of cat by cannulae inserted via the jugular vein and femoral vessels. After 2 h ECLS brains were frozen in situ and investigated for changes in regional metabolism. MEASUREMENTS AND RESULTS: During 2 h ECC hematocrit declined from 37 +/- 7% to 21 +/- 10% (means +/- SD, p < 0.05), cerebral blood flow decreased to 73 +/- 14% of control (p < 0.05) and cerebral oxygen delivery to 46 +/- 13% of control (p < 0.05) although arterial blood pressure and bypass flow rate did not change. Plasma lactate increased from 0.8 +/- 0.3 to 9.2 +/- 4.2 mumol/ml (p < 0.05), and brain tissue lactate from 2.3 +/- 0.9 to 10.6 +/- 2.7 mumol/g (p < 0.05). Hematocrit correlated positively with cerebral oxygen delivery (r = 0.86, p < 0.001). CONCLUSIONS: These data demonstrate that ECLS is associated with reduced cerebral oxygen delivery and may cause brain hypoxia despite normal blood pressure. This complication may contribute to the high incidence of neurological disturbances after prolonged ECLS.

Animals↗

L-type Ca channel block by highly hydrophilic dihydropyridines in single ventricular cells of guinea-pig hearts.

Blocking of L-type Ca channels by highly hydrophilic dihydropyridines, NKY-722 and KV-1360, was investigated in single ventricular cells of guinea-pig hearts using the whole-cell voltage clamp technique. At a holding potential of -30 mV, NKY-722 (1-100 nM) decreased the amplitude of the L-type Ca channel current (ICa) in a concentration-dependent manner. NKY-722 did not change the time constants of the decay of ICa. In the presence of NKY-722 (1 microM), the steady-state inactivation curve was shifted toward a more negative potential (by -33.0 +/- 2.0 mV) without changing its slope factor. The use-dependent block was elicited at a pulse frequency of 3.3 Hz or more. Even after washing out the drug at -80 mV for 20 min, ICa inhibited by NKY-722 (100 nM) at -30 mV was scarcely recovered when the membrane potential was clamped back to -30 mV. A permanently charged compound KV-1360 (0.1-1 microM), a quaternary amine derivative of NKY-722, hardly affected ICa by intracellular and extracellular application. These results suggest that, in spite of the high degree of ionization (91% in the charged form at pH 7.4), the mode of the L-type Ca channel block by NKY-722 is quite similar to that by lipophilic dihydropyridines. Consequently, the neutral form of NKY-722 is the active compound and this reaches the dihydropyridine receptor by "membranous approach".

Animals↗

Euthyroid Graves' disease showing no thyroid abnormalities except positive thyroid-stimulating antibody (TSAb): two case reports.

We report two cases of euthyroid Graves' disease in women who had ophthalmopathy without previous history of hyperthyroidism. Enlargement of extraocular muscles was observed by magnetic resonance imaging (MRI). The patients had no thyroid enlargement and their serum concentrations of free T4, free T3, and TSH were normal. The sera were negative for antithyroid microsomal and thyrogobulin antibodies, and anti-TSH receptor antibodies measured by radioreceptor assay. T3 suppression test results were normal. Only thyroid-stimulating antibody (TSAb) measured by sensitive bioassay was positive. These findings indicate that sensitive TSAb is the most useful laboratory test in the diagnosis of euthyroid Graves' disease.

Adult↗

A case of repeated painless thyroiditis followed by Graves' disease.

A fifty-year-old woman was admitted to our hospital because of palpitation and general fatigue. She had received hemithyroidectomy for thyroid papillary adenocarcinoma at 28 years of age. She had experienced episodes of repeated painless thyroiditis five times over the last 12 years. At her sixth episode of thyrotoxicosis, she was suspected to have Graves' disease and admitted to our hospital. Laboratory findings revealed thyrotoxicosis with positive thyroid stimulating antibody and high radioactive iodine uptake, i.e. Graves' disease. Painless thyroiditis often relapses but rarely develops into Graves' disease. This is a rare case in which repeated painless thyroiditis was followed by Graves' disease. The relation between painless thyroiditis and Graves' disease is discussed.

Female↗

[Analysis of functional architecture of the brain by optical recording methods].

To date, our understanding of the elaborate mechanism that governs the information processing of neural tissue or the brain is based mainly on data obtained from single-electrode recordings in vivo or in vitro. The refinement of electrophysiological techniques has advanced our knowledge about neural information processing, but clearly, we are still far from complete and coherent understanding of these brain functions. Although conventional approaches have provided the bulk of our knowledge about neural information processing, there is clearly a need for research tools that are better suited to investigate the detailed properties of individual neurons on the one hand and allow for studying the interactions between large numbers of neurons on the other hand. The use of optical recording methods with voltage-sensitive dyes (extrinsic optical signal recording) seems to be one of the most promising ways to attack the above problems. This approach allows to record the neural activity at many sites simultaneously and thus provides spatio-temporal information about the flow of electrical activity in a given preparation. The optical recording without using voltage-sensitive dyes, intrinsic optical signal recording, is also useful to detect the neural activity in the brain. The signal is thought to be originated from the metabolic change of the brain tissue which is associated with the change in neural activity. We compared the both activity mapping obtained with extrinsic signals and intrinsic signals. This kind of trial seems to be useful not only for understanding the origin of the metabolic signal, but also for treating the data obtained with PET or functional MRI.

Animals↗

[Reproducibility of the topographic parameters of the optic disk with the scanning laser tomograph].

The scanning laser tomograph was used to measure the optic disk topography in the left eye of five normal volunteers and five open angle glaucoma patients during the same day. We studied the reproducibility of 7 topographic parameters with the coefficient of variation (CV) and coefficient of reliability (CR) from topographic images of the scanning laser tomograph. The mean CV of the topographic parameters was 8.1 +/- 3.3% (range: 5.3-15.0%) and the mean CR of the topographic parameters was 91.8 +/- 7.6% (range: 78.6-98.4%) in normal eyes. In glaucoma eyes, the mean CV was 7.2 +/- 3.7% (range: 4.4-15.0%) and the mean CR was 84.8 +/- 7.5% (range: 73.4-95.3%), respectively. The results showed that the scanning laser tomograph has good reproducibility for clinical use in optic disk measurements.

Adult↗

Fatal Epstein-Barr virus-associated lymphoproliferative disorder in childhood.

OBJECTIVE: We report five childhood cases of fatal Epstein-Barr virus-associated lymphoproliferative disorder to determine their immunopathologic and immunogenotypic features. DESIGN: Clinicopathologic features are described, using clinical, histologic, immunophenotypic, and genotypic examinations. SETTING: Autopsy cases were performed at Nagoya and Tsukuba university hospitals, Japan. RESULTS: Infiltrating lymphocytes, which were positive for the EBV genome by in situ hybridization, were polymorphic and showed polyclonal immunoglobulin staining in all five cases. Two cases, however, showed genetic clonality of EBV termini. In one case, the clonality was observed only in the spleen, and in the other case, clonal rearrangement of the JH gene was also found. The former case showed none of the morphologic features of neoplasia and presented a morphology similar to virus-associated hemophagocytic syndrome. In the latter case, infiltrating lymphoid cells were much less polymorphous, and nodular masses of the lymphoid cells in colon and lung specimens were observed. CONCLUSION: We suggest that some polyclonal EBV-associated lymphoproliferative disorders develop into polymorphic, but genotypically monoclonal, lymphoproliferative disorders.

Adolescent↗

[Distribution of free amino acids and related compounds in ocular fluids of rat--I. Aging and inherited cataracts].

The distribution of free amino acids and their related compounds has been determined in the aqueous humors of Wistar strain and Ihara cataract f-strain (ICR) aging rats. Taurine was the most abundant amino acid in aqueous humors except in ICR rats of 16 and 70 weeks. It was supposed that the increase of serine and glutamine, and the decrease of aspartate, proline and glycine in aqueous humors were related to aging. There were interesting changes in amino acids related to opacity of lens, concentration of taurine was lower than that of Wistar rats in ICR rats of 4, 16, and 70 weeks, alanine and citrulline increased in Wistar rats and decreased in ICR rats, and histidine increased in ICR rats with aging. The changes in free amino acids in aqueous humors were the greatest in ICR rats, and these data will provide useful clues for the formation of cataract and the transportation of amino acids.

Aging↗

[Postgravid health care and laboratory tests].

Various diseases often occur after delivery but the systemic examinations have not been studied before. Thyroid dysfunction frequently (4.4%) occurs after delivery through an immune rebound mechanism. If postpartum women complain of the symptoms caused by thyrotoxicosis (palpitation, weight loss, increased sweating, finger tremor, fatigue) or hypothyroidism (edema, cold intolerance, hoarseness, sleepiness, fatigue), it is essential to examine thyroid hormones, thyroid stimulating hormone, anti-thyroid microsomal antibody (MCHA) and anti-TSH receptor antibody. To predict who will develop postpartum thyroid dysfunction, the measurement of MCHA during pregnancy is useful because 62% of the subjects with positive MCHA show thyroid dysfunction after delivery. The individuals at high risk of postpartum onset of Graves' thyrotoxicosis can be found early in their pregnancy by the detection of thyroid stimulating antibody (TSAb). Other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, autoimmune hypophysitis and so on, also could develop after delivery. These findings indicate that laboratory tests in the postpartum period are essential to diagnose postpartum onset of autoimmune diseases and the measurement of autoantibodies in early pregnancy is useful for prediction of their onset in the postpartum period.

Autoantibodies↗