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Biomedical subjects

H Iijima

Publications and source records attributed to H Iijima.

At least 217 records · Page 12Linked to original sources

Modification of amino acids and bovine pancreatic ribonuclease A by kethoxal.

Kethoxal (3-ethoxy-2-ketobutanal) reacts with the guanidino group of Nalpha-acetylarginine to produce four derivatives, reactive to periodate, stable at pH 7, with 15% reverting to arginine on acid hydrolysis. Other amino acids with blocked alpha-amino groups do not react, except the epsilon-amino of lysine (slowly). The pK of the mixed Kethoxal-Nalpha-acetylarginine derivatives is 5.8-6.1. Kethoxal reacts at neutral pH with arginyl residues of bovine pancreatic ribonuclease A. In the presence of an active-site ligand, arginine-39 and arginine-85 react at about equal rates. The loss of enzymic activity at pH 7 is proportional to the combined loss of these residues. The enzymic activity toward RNA is 20-25% of that of native RNAase at pH 7, and 90-100% at pH 5. In the absence of an active site ligand, arginine-10 is also modified with the loss of almost all enzymic activity, although arginine-10 is not an active-site residue. Arginine-33 is unreactive. Kethoxal-modified RNAase undergoes cross-linking in solution at pH 7 or in the freeze-dried state, Incubation at pH 9 in the presence of homoarginine results in partial regeneration of arginyl residues and activity at pH 7. Kethoxal modification of arginines-39 and -85 appears to raise the pK of lysine-41 by about 1 unit, as indicated ty the pH dependence of arylation by 2-carboxy-4,6-dinitrochlorobenzene. The claims of Patthy and Smith (J. Biol, Chem. (1975) 250, 565-569), and of Takahashi (J. Biol. Chem. (1968) 243, 6171-6179) that arginine-39 is a more important functional residue than is arginine-85 are questioned.

Aldehydes↗

Mucosal immune network in the gut for the control of infectious diseases.

The common mucosal immune system (CMIS) consists of an integrated cross-communication pathway of lymphoid tissues made up of inductive and effector sites for host protection against pathogenic microorganisms. Major effector molecules of the CMIS include IgA antibodies and cytokines, chemokines and their corresponding receptors. Secretory IgA (S-IgA), the major immunoglobulin, is induced by gut-associated lymphoreticular tissue (GALT)-derived B cells with the help of Th1- and Th2-type CD4(+) T lymphocytes. Cytotoxic T lymphocytes (CTLs) in the mucosal epithelium, a subpopulation of intraepithelial lymphocytes (IELs), also help maintain the mucosal barrier. The CMIS is unique in that it can provide both positive and negative signals for the induction and regulation of immune responses in both the mucosal and systemic compartments after oral or nasal antigen exposure. Prevention of infection through mucosal surfaces can be achieved by the CMIS through connections between inductive (e.g. GALT) and effector tissues. When vaccine antigens are enterically administered together with mucosal adjuvants [e.g. cholera toxin (CT), heat-labile toxin produced by Escherichia coli (LT) and IL-12], antigen-specific Th1/Th2 and IgA B cell responses are induced simultaneously in the mucosal effector compartment. Since these antigen-specific immune responses are not generated by oral vaccine without mucosal adjuvant, safe and effective adjuvants for the induction of antigen-specific S-IgA and CTL responses are essential for the development of mucosal vaccines for protection against infectious diseases. Finally, recent findings suggest the presence of a CMIS-independent IgA induction pathway, which also must be considered in the development of mucosal vaccines.

Animals↗

Detection of HIV-RNA in aqueous humor and subretinal fluid in an HIV carrier with rhegmatogenous retinal detachment.

BACKGROUND: Although human immunodeficiency virus (HIV)-related ocular complexes are commonly observed in acquired immune deficiency syndrome (AIDS) patients, it has not been previously reported that HIV had already invaded the ocular tissues of HIV carriers. CASE: A 56-year-old woman was diagnosed as having rhegmatogenous retinal detachment with a retinal tear in the 6-o'clock position in her right eye. No signs of ocular manifestations except the retinal detachment were observed. A blood examination revealed that she was already infected with HIV-1, and she was categorized as an HIV carrier. OBSERVATIONS: Aqueous humor and subretinal fluid samples were obtained at the time of surgery for rhegmatogenous retinal detachment. Reverse-transcription polymerase chain reaction and Southern blotting at three regions of the HIV, LTR, gag, and env, confirmed the HIV infection in both aqueous humor and subretinal fluid. During the approximately 2-year follow-up after surgery, the patient did not show any signs of retinitis, uveitis, or other ocular manifestations. CONCLUSIONS: This is the first report to reveal that HIV can invade the eye in the early stage of HIV infection. This infection may be related to HIV-related ocular complexes, which suppress the local immunological response.

Aqueous Humor↗

Heat shock protein 70 expression increased in rabbit müller cells in the ischemia-reperfusion model.

Heat shock protein 70 (HSP70) expression in the rabbit retina was evaluated in the ischemia-reperfusion model. Ischemia was induced by increasing the pressure in the anterior chamber, and the retinas were collected 1 or 12 h after reperfusion. HSP70 expression was examined by Western blot, confocal laser scanning microscopy and immunoelectron microscopy. Western blot showed that HSP70 was significantly increased in the retina 12 h after reperfusion, compared with normal control or 1 h after reperfusion. Confocal microscopy demonstrated that HSP70 was constitutive in Müller cells and that its expression was increased 12 h after reperfusion. Electron microscopy showed that glycogen-like granules were significantly decreased with prominent endoplasmic reticulum 1 h after reperfusion. Twelve hours after reperfusion, however, the density of glycogen-like granules was restored, and immunoelectron microscopy indicated that HSP70 was associated with the organelles of the Müller cells. Taken together, these data suggest that HSP70 in Müller cells plays a role in accommodation to stress.

Animals↗

Mechanism of action of the antitumour effect of K18.

K18 is an anticancer drug for oral administration comprising about five molecules of melphalan, an alkylating drug, covalently bonded to human immunoglobulin G. This study measured the in vitro antitumour activity of K18, melphalan and immunoglobulin G on human myeloma cells (RPMI-8226) and the in vivo antitumour effects of K18 and melphalan in BALB/c nude mice bearing human lung cancer cells (LC-10). The relative tumour-inhibitory effect, in vitro, was found to be: immunoglobulin G less than K18 less than melphalan. This activity of K18 was about half the theoretical value indicating that melphalan molecules are not released easily from the conjugate. K18 showed strong antitumour activity in vivo which continued after stopping administration. On the other hand, the effects of melphalan did not continue after administration was stopped. The distribution of [125I] K18 and [14C]melphalan was examined in BALB/c nude mice 14 days after implantation of LC-10 cells. Radioactivity levels in the major organs showed a transient rapid increase followed by a gradual decline. In tumours, [14C]melphalan levels increased transiently and then decreased, whereas [125I]K18 levels persisted following intravenous administration.

Animals↗

A new parameter for assessing the thickness of the retinal nerve fiber layer for glaucoma diagnosis.

PURPOSE: To investigate a new method for assessing the thickness of the retinal nerve fiber layer thickness (NFLT) for glaucoma diagnosis, using scanning laser polarimetry. MATERIAL AND METHODS: Thirty eyes of thirty patients with ocular hypertension or glaucoma were examined using a scanning laser polarimeter. NFL T was measured in each of four 90-degree quadrants; superior (S), temporal (T), inferior (I) and nasal (N) along 1.5-disc diameters concentric from the disc margin. The new parameters S-N (meaning the thickness of the superior nerve fiber layer over the nasal one) etc. were compared with the conventional parameters (S, S/N, etc.). The correlations between these parameters and the mean threshold of the associated visual field test points were included in the comparison. RESULTS: The total thickness (sum of S, I, N and T), N and T did not correlate to the visual field, but S and I did. The new parameters were well correlated to the visual field, S-N giving the best correlation coefficient (rs = O. 782, p < O.0001), and sensitivity and specificity (the area under the receiver operating characteristic curves was 0.91). CONCLUSIONS: The nasal NFLT was the smallest part of individual variation and glaucomatous damage. The new parameters, based on the nasal NFLT, were good evaluators of the changes in glaucoma.

Adult↗