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Biomedical subjects

I Azuma

Publications and source records attributed to I Azuma.

At least 127 records · Page 7Linked to original sources
PubMed1992

Human immunodeficiency virus type 1 (HIV-1) superinfection of a cell clone converting it from production of defective to infectious HIV-1 is mediated predominantly by CD4 regions other than the major binding site for HIV-1 glycoproteins.

A cell clone, L-2, which produces non-infectious doughnut-shaped human immunodeficiency virus type 1 (HIV-1) particles, was permissive for HIV-1 superinfection, which resulted in the production of infectious particles. The superinfection showed slow kinetics compared with primary HIV-1 infection of M10 cells, the parent of the L-2 cell clone. Inhibition studies on the superinfection of L-2 cells using several CD4-related reagents showed that the CD4 molecule was an essential component of the receptor for superinfection. Strong inhibitory effects were obtained using CD4 peptides such as CD4(68-130), which includes a portion homologous to the immunoglobulin third complementarity-determining region (CDR3), as well as recombinant soluble CD4. In contrast, a CD4(45-60) peptide, which includes most of the CDR2-related region, was not effective, although the Leu-3a monoclonal antibody (MAb), which recognizes a site near the CDR2-related region, did slightly, but significantly, delay the superinfection kinetics. Comparative flow cytometry of L-2 and M10 cells revealed that the cell surface of L-2 cells despite expressing HIV-1 env protein, reacted slightly with OKT4 or anti-CD4(68-130) MAb, but not with Leu-3a or OKT4A MAb. In contrast, no reaction was detected with any of these anti-CD4 MAbs on the surface of another HIV-1 superinfection-resistant cell clone, MOLT-#8IIIB-14, which expresses HIV-1 env proteins but does not produce infectious HIV-1 particles. These results strongly suggest that expression of the CD4 major receptor site for primary HIV-1 infection is preferentially decreased on the surface of L-2 cells, but that the OKT4 epitope and the nearby region corresponding to immunoglobulin CDR3 remain exposed on the cell surface. Consequently, the CD4 CDR3-related region could play a major role as the receptor for the superinfection reported here.

Binding Sites↗
PubMed1992

Arginine deiminase gene of an AIDS-associated mycoplasma, Mycoplasma incognitus.

Recently, we have demonstrated by molecular cloning that a strong immunosuppressive factor derived from Mycoplasma arginini is arginine deiminase. We show here that mycoplasma species identified in many of AIDS patients also bear the arginine deiminase gene. The implication of the arginine deiminase gene detected in AIDS-associated mycoplasma species is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1992

DT-5461, a new synthetic lipid A analogue, inhibits lung and liver metastasis of tumor in mice.

We have investigated the antimetastatic effect of a new synthetic lipid A analogue, of low endotoxicity, DT-5461, against two highly metastatic tumor cell lines, L5178Y-ML25 T-lymphoma and B16-BL6 melanoma cells in mice. Four intermittent i.v. administrations of DT-5461 at intervals of 4 days resulted in a significant inhibition of liver metastasis caused by i.v. injection of L5178Y-ML25 cells and lung metastasis of B16-BL6 cells in the experimental metastasis models. Intraperitoneal and intranasal administrations as well as i.v. administration of DT-5461 were also effective in preventing lung metastasis of the melanoma cells. Multiple administrations of DT-5461 before the surgical excision of primary tumors significantly reduced the number of lung colonies of melanoma cells and primary tumor size. Similarly, this treatment modality after the surgical excision of primary tumors showed a greater reduction of lung tumor colonies as compared with lipopolysaccharide, a synthetic lipid A (No. 506) and its analogue as well as untreated control in the spontaneous lung metastasis model. Furthermore, the group that received DT-5461 after the inoculation of lymphoma or melanoma cells showed significantly enhanced survival rate compared with the untreated control. These results suggested that DT-5461 may be therapeutically useful for the inhibition of tumor metastasis.

Animals↗
PubMed1992

Differences in chemotaxis to fibronectin in weakly and highly metastatic tumor cells.

We have examined the chemotactic ability of tumor cell lines with different metastatic potential to plasma fibronectin in Transwell chamber assay. Human renal carcinoma cells with highly metastatic potential, SN12 C-2, chemotactically migrated to fibronectin (10 micrograms/ml) about three-fold more strongly than weakly metastatic SN12 C-4 cells. Similarly, murine melanoma B16-BL6 cells (highly metastatic) showed higher motility to soluble fibronectin in comparison with weakly metastatic B16-F1 cells. Anti-VLA-alpha 3 and beta 1 antibodies potently blocked the chemotaxis of both highly and weakly metastatic cells (SN12 C-2 and C-4) to fibronectin. This implies that the migration of both C-2 and C-4 cells to fibronectin is basically mediated by VLA-3 receptor. In contrast, the anti-VLA-alpha 5 antibody and RGDS peptide significantly inhibited the chemotaxis of SN12 C-2 cells to fibronectin, but did not affect weakly metastatic SN12 C-4 cells. These results suggest that the chemotactic ability to fibronectin positively correlates with the metastatic potential in SN12 and B16 cell lines, and that VLA-5 receptor is concerned in the motility of highly metastatic SN12 C-2 cells to soluble fibronectin.

Antibodies, Monoclonal↗
PubMed1992

Elevated gene expression of argininosuccinate synthetase in peripheral lymphocytes from systemic lupus erythematosus (SLE) patients.

Argininosuccinate synthetase (ASS) is a rate-limiting enzyme of urea cycle and functions primarily in the liver, whereas ASS activity is hardly detected in normal lymphocytes. In this study, we examined the level of ASS gene expression in peripheral blood lymphocytes (PBL) from human SLE patients by amplification of reverse-transcribed mRNA using the polymerase chain reaction. We have demonstrated that (a) approximately 40% of SLE patients exhibited 2.5 to 5 times higher expression of ASS gene in PBL than those of healthy PBL and (b) the elevation of ASS gene expression of PBL significantly correlates with the active pathogenesis of SLE patients according to the criteria of Japanese Ministry of Health and Welfare (p < 0.001 by student's two-tailed t-test). Thus, it is suggested that ASS gene expression is a promising marker of hyperactivated lymphocytes uniquely generated in patients with systemic autoimmune disease.

Animals↗
PubMed1992

Theileria sergenti proliferates in SCID mice with bovine erythrocyte transfusion.

The unavailability of in vitro or in vivo experimental systems has been the major factor hampering the progress of research studies on Theileria sergenti, causative agent of theileriosis, a major disease of cattle in Japan. We report the first successful propagation of T. sergenti in SCID mice into which uninfected bovine erythrocytes (Bo-RBC) were supplied periodically. The infectivity of T. sergenti proliferated in an SCID mouse was ascertained by successful transfer of infection into another SCID mouse into which uninfected Bo-RBC were supplied periodically.

Animals↗
PubMed1991

Recombinant human granulocyte colony-stimulating factor inhibits the metastasis of hematogenous and non-hematogenous tumors in mice.

We studied the effects of in vivo administrations of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the metastasis of murine hematogenous and non-hematogenous tumors in spontaneous and experimental metastasis models. Spontaneous lung metastasis caused by intra-footpad injections of B16-BL6 melanoma and Lewis-lung-carcinoma (3LL) cells were inhibited by intravenous (i.v.) and subcutaneous (s.c.) injections of rhG-CSF after excision of the primary tumors. Recombinant hG-CSF significantly inhibited liver metastasis when administered i.v. after i.v. injection of L5178Y-ML25 T-lymphoma cells. Multiple i.v. administration of rhG-CSF after the tumor inoculation prolonged the survival times of mice inoculated i.v. with L5178Y-ML25 lymphoma cells. Recombinant hG-CSF did not directly affect the growth of B16-BL6 and L5178Y-ML25 cells in vitro. During the administration periods, both i.v. and s.c. injections of rhG-CSF increased the number of total white blood cells (WBC) in peripheral blood to approximately 3 times the normal level in normal and tumor-bearing mice. We also found that the administration of rhG-CSF stimulates neutrophils to become cytostatic against these tumor cells. Our results indicate that the injection of rhG-CSF is effective in inhibiting lung and liver metastases by activating neutrophils and increasing cell number.

Animals↗
PubMed1991

Chemical synthesis and biological activities of 6,6'-di-O-mycoloyl-beta,beta- and -alpha,beta-trehalose.

6,6'Di-O-mycoloyl-beta,beta-trehalose (beta,beta-TDM) and 6,6'-di-O-mycoloyl-alpha,beta-trehalose (alpha,beta-TDM) were synthesized and their toxicity and ability to activate peritoneal macrophages in situ were examined in mice, in comparison with 6,6'-di-O-mycoloyl-alpha,alpha-trehalose (TDM). Both beta,beta-TDM and alpha,beta-TDM caused a decrease in body weight two days after injection, however the weights reverted to a normal level. No deaths were caused by either analog. On the other hand, TDM showed potent toxicity, causing decrease in body weight and death of all animals injected. Beta,beta-TDM and alpha,beta-TDM were effective in the in situ activation of mouse peritoneal macrophages.

Animals↗
PubMed1991

Inhibition of tumor-induced angiogenesis by sulfated chitin derivatives.

The effect of antimetastatic sulfated chitin derivatives (SCM-chitin III) on angiogenesis induced by B16-BL6 cells was examined in syngeneic mice. SCM-chitin III caused a marked decrease of the number of vessels toward tumor mass (angiogenic response) without affecting the tumor cell growth when coinjected with tumor cells (on day 0), or injected into tumor site on day 1 or 3 after tumor inoculation. In contrast, carboxymethyl chitin as well as heparin had no effect. Invasion of endothelial cells through reconstituted basement membrane (Matrigel) toward tumor-conditioned media was significantly inhibited by SCM-chitin III in a Transwell chamber assay. SCM-chitin III also inhibited the haptotactic migration of endothelial cells to fibronectin-substrate, but did not inhibit the chemotactic activity in tumor conditioned media in vitro. SCM-chitin III did not directly affect the viability and the growth of tumor cells and endothelial cells in vitro. These results suggest that inhibition of lung tumor metastasis by SCM-chitin III may in part be due to the inhibition of tumor-associated angiogenesis.

Animals↗
PubMed1991

Effect of bunazosin hydrochloride on intraocular pressure and aqueous humor dynamics in normotensive human eyes.

We investigated the effects of topical administration of bunazosin hydrochloride, a new selective alpha 1-adrenergic antagonist, on intraocular pressure and aqueous humor dynamics in normal human eyes. In the single-dose study, all concentrations of bunazosin (0.025%, 0.05%, 0.1%, and 0.2%) significantly lowered intraocular pressure in a concentration-dependent manner. Administration of multiple doses of 0.1% bunazosin revealed no occurrence of tachyphylaxis after 1 week. Single application of 0.1% bunazosin had no significant influence on aqueous flow rate, tonographic outflow facility, or episcleral venous pressure, suggesting that bunazosin reduces intraocular pressure by increasing uveoscleral outflow. Aqueous protein concentration was found to be unaltered by bunazosin, indicating that blood-aqueous barrier permeability to protein molecules remained unchanged. We conclude that bunazosin may be a possible new antiglaucoma agent with a mechanism of action different from those currently in use for treating ocular hypertension.

Administration, Topical↗
PubMed1991

Effects of prostaglandin D2 and its analogue, BW245C, on intraocular pressure in humans.

The effects of topically applied prostaglandin (PG) D2 and BW245C, a potent PGD2 agonist, on intraocular pressure (IOP) were studied in normotensive human volunteers. Doses of 5 and 10 micrograms PGD2 induced a mean reduction in IOP of 0.8 and 1 mmHg, respectively. At a dose of 50 micrograms, hypotension was preceded by initial hypertension (4 mmHg at 0.5 h) and the magnitude of the mean IOP reduction during the hypotensive phase was 1.1 mmHg. The application of BW245C (2.5 micrograms) induced an IOP change similar to that observed following treatment with 50 micrograms PGD2. Side effects caused by these compounds included conjunctival hyperemia, itching, and foreign-body and mild burning sensations. However, miosis and signs of intraocular inflammation were not observed. These results indicate that although PGD2 and BW245C are effective in reducing human IOP, their clinical usefulness as anti-glaucoma drugs may be limited by the extraocular side effects.

Administration, Topical↗
PubMed1991

Inhibitory effect of fibronectin and its recombinant polypeptides on the adhesion of metastatic melanoma cells to laminin.

We have utilized recombinant fibronectin fragments with cell-binding domain (C-274), heparin-binding domain (H-271) or CS1 peptide in type III connecting segment (IIICS) and their fusion polypeptides such as CH-296 (containing C-274, H-271 and CS1), CH-271 (containing C-274 and H-271) and C-CS1 (containing C-274 and CS1) to investigate the mechanism of the fibronectin-mediated inhibitory effect on tumor cell adhesion to laminin as well as fibronectin. These fragments retained cell adhesion-promoting and/or heparin-binding properties when they were immobilized on a surface. Pretreatment of tumor cells with CH-296 or CH-271 suppressed cell adhesion to both laminin and fibronectin. H-271 at the high concentration of 500 micrograms/ml slightly inhibited cell adhesion to laminin (but not to fibronectin), whereas C-274, C-CS1 or a mixture of C-274, H-271 and CS1 (similar molar ratio to CH-296) inhibited cell adhesion to fibronectin but not to laminin. On the other hand, tumor cell adhesion to laminin-substrate was also inhibited by heparin or heparan sulfate, which were able to bind to laminin, suggesting that heparin-like molecules on the cell surface may be included among the laminin receptors. These results indicated that the co-presence of cell- and heparin-binding domains of fibronectin may be required for the fibronectin-mediated inhibitory effect on tumor cell adhesion to laminin, and that the interaction of the heparin-binding domain of fibronectin with the cell surface leads to the inhibition of the cell adhesion to laminin.

Amino Acid Sequence↗
PubMed1991

Recombinant fusion polypeptide with cell- and heparin-binding domains of fibronectin inhibits liver metastasis of L5178Y-ML25 lymphoma cells.

We have investigated the effect of recombinant polypeptides with cell-binding domain (C-274) or with heparin-binding domain (H-271) and their fusion polypeptide (CH-271) on liver metastasis of murine lymphoid tumor. The polypeptides containing heparin-binding domain, H-271 and CH-271, were able to inhibit liver metastasis when co-injected i.v. with L5178Y-ML25 T-lymphoma cells, while C-274 with cell-binding domain showed much weaker antimetastatic activity. Treatment with H-271 or CH-271 substantially prolonged the survival time of mice injected i.v. with L5178Y-ML25 cells. CH-271, containing cell- and heparin-binding domains, was more antimetastatic than H-271. The reason why CH-271 was more effective in inhibiting liver metastasis than H-271 can not be explained in terms of a difference in the stability in the circulation or in the molecular size of the polypeptide. The polypeptides used in this study did not affect the tumor cell growth or viability in vitro. CH-271 was found to be still active in inhibiting liver metastasis even when natural killer cells or macrophages were removed from this system. Furthermore, multiple administrations of CH-271 after tumor implantation effectively inhibited liver metastasis and enhanced the survival rate as compared with H-271, C-274 and untreated control. Thus, the fusion of H-271 with C-274 (i.e. CH-271) augments the antimetastatic property of H-271, possibly through the interaction between tumor cells and the heparin-binding domain of fibronectin.

2-Chloroadenosine↗
PubMed1991

Inhibitory effect of antimetastatic fusion polypeptide of human fibronectin on tumor cell adhesion to extracellular matrices.

We investigated the inhibitory mechanism of liver metastasis by using recombinant fragments with cell- and/or heparin-binding domains (C-274, H-271 or the fusion fragment CH-271). Intravenous co-injection of L5178Y-ML25 cells with CH-271 was more effective for the inhibition of liver metastasis than C-274, H-271 or C-274 + H-271. Reduction of the arrest and retention of the radiolabeled tumor cells in the liver of mice was found when CH-271 was co-injected with tumor cells. L5178Y-ML25 cells adhered both concentration- and time-dependently to the substrates precoated with fibronectin, laminin and reconstituted basement membrane, Matrigel. The tumor cell adhesions to the substrates were inhibited in the presence of CH-271. The tumor cell interaction with CH-271-substrate was inhibited by heparin, and monoclonal antibodies (IST-1 or IST-2) against the heparin-binding domain of fibronectin. However, monoclonal antibodies against the cell-binding domain failed to block the interaction. Similarly, CH-271-mediated antimetastatic activity was also inhibited by the treatment of CH-271 with IST-1 before the co-injection with tumor cells, whereas monoclonal antibody against the cell-binding domain had no effect. Thus, the antimetastatic effect of CH-271 fusion fragment on liver metastasis of L5178Y-ML25 cells may be partly due to interference with the adhesive interaction of tumor cells with extracellular matrix or basement membrane components by a heparin-binding domain-dependent mechanism.

Animals↗
PubMed1991

Molecular properties of poly(RGD) and its binding capacities to metastatic melanoma cells.

We examined the binding capacity of anti-metastatic polypeptide containing repetitive Arg-Gly-Asp(RGD) sequence derived from cell binding site of fibronectin, poly(RGD), to the surface of tumor cells. Poly(RGD) competitively inhibited the binding of radiolabeled fibronectin to the cell surface more potently than oligo(RGD) or RGD tripeptide on a molar basis. Compared on a weight basis to oligo(RGD) or RGD peptide, poly(RGD) was more active than the oligo- and monomeric peptide at inhibiting tumor cell adhesion to immobilized fibronectin. The secondary structure of poly(RGD) was predicted to be a beta-turn from the data of CD spectra and its amino acid sequence. These findings suggest that poly(RGD)-mediated inhibition of cell adhesion is due to its potent binding capacity to fibronectin receptors on cell surface probably through its conformational properties.

Animals↗
PubMed1991

[A follow-up study of pupillary dynamics in patients with ocular hypertension and primary open angle glaucoma].

The authors previously reported light reflex abnormalities and adrenergic supersensitivity to topical epinephrine (DPE; dipivalyl epinephrine) of the pupils in patients with ocular hypertension (OH) and those with primary open angle glaucoma (POAG). In this investigation, we attempted to reconfirm pupillary light reflex abnormalities we reported previously, and to investigate the relationship between the normotensive effect of 0.1% DPE and the pupillary light reflex abnormalities in OHs and POAGs. A total of 11 OHs and 11 POAGs under good oculotensive control with neither mydriatics nor miotics were examined. They were measured by an open-loop photically stimulated infrared videopupilogram, and were neurologically diagnosed by comparing the simulated patterns of the light reflex made by topical autonomic agents. When we considered the progress of the stage of POAG, both OHs and POAGs showed satisfactory reproducibility of pupillary light reflex abnormalities. Other cases in which light reflexes altered, showed worsening of the visual field deficit, which was prominent when OHs developed into POAG. OHs with significant reduction of intraocular pressure (IOP) after topical administration of 0.1% DPE showed various kinds of abnormal pupillary light reflexes. On the contrary, cases with little reduction of IOP after 0.1% DPE instillation showed normal pupillary light reflexes in OHs and afferent pupillary defect on POAGs.

Adult↗