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Biomedical subjects

J Iida

Publications and source records attributed to J Iida.

At least 55 records · Page 3Linked to original sources

Adhesion of committed human hematopoietic progenitors to synthetic peptides from the C-terminal heparin-binding domain of fibronectin: cooperation between the integrin alpha 4 beta 1 and the CD44 adhesion receptor.

Close interaction of human hematopoietic progenitors with the bone marrow microenvironment is important for the ordered progression of human hematopoiesis. Progenitor cell adhesion to stroma has a complex molecular basis, involving various cell-extracellular matrix and cell-cell interactions. We have previously shown that adhesion of colony-forming cells (CFC) to fibronectin, present in stromal extracellular matrix, involves multiple sites, including two heparin-binding synthetic peptides (FN-C/H I and FN-C/H II) and the alpha 4 beta 1 integrin-binding peptide CS1. These synthetic peptides are located in close proximity in the type III repeat 14 and the immediately adjacent type IIIcs region of fibronectin. In the current study, we evaluate receptors expressed by CFC responsible for their adhesion to fibronectin. We show that the alpha 4 beta 1 integrin mediates adhesion to CFC to the peptides FN-C/H I and CS1. Adhesion of CFC to fibronectin is also mediated by proteoglycans, because removal of cell surface chondroitin-sulfate proteoglycans resulted in decreased adhesion of CFC to FN-C/ I and FN-C/H II. The core protein of this proteoglycan was identified by immunoprecipitation as a 90-kD member of the CD44 group of adhesion molecules. Interestingly, although the proteoglycan core protein failed to adhere to FN-C/H II affinity columns, anti-CD44 monoclonal antibodies blocked CFC adhesion to FN-C/H II, indicating that these monoclonal antibodies may interfere with core protein-mediated intracellular signalling. Finally, we show that CD44 and alpha 4 beta 1 may cooperate in establishing progenitor adhesion, because anti-CD44 antibodies potentiated the adhesion-inhibitory effects of suboptimal concentrations of anti-alpha 4 or anti-beta 1 monoclonal antibodies. These results provide a working model for progenitor cell recognition of fibronectin (and possibly the marrow micro-environment) in which the coordinated action of integrins and cell surface proteoglycans is necessary for cell adhesion. This model can now be used to study the complex relationship between progenitor cell adhesion and the regulation of their proliferation and differentiation.

Amino Acid Sequence↗

Human neuroblastoma growth inhibitory factor (h-NGIF), derived from human astrocytoma conditioned medium, has neurotrophic properties.

Investigations on the general characteristics of human astrocytoma cell line NAC-1 revealed neuroblastoma growth inhibitory activity in conditioned medium. Neuroblastoma growth inhibitory factor (NGIF) was partially purified by Econo Q, Econo CM, and Superose 12 column chromatography. The protein is weakly basic with an estimated M(r) of 120,000, possibly having an M(r) 60,000 dimeric structure. NGIF inhibits the growth of human neuroblastoma cell lines but has no effect on morphology nor does it produce any change in the growth of human glioblastoma cell lines. Interestingly, NGIF appears to promote survival and neurite outgrowth of embryonal rat cortical neurons. These neurotrophic properties suggest a role for NGIF in the development of the nervous system.

Animals↗

Investigations of mental health of school teachers for the mentally retarded and staff members in social welfare facilities for the mentally retarded: using a Japanese version of the General Health Questionnaire (GHQ).

The mental health of 70 school teachers for the mentally retarded, 60 direct care staff in social welfare facilities for the mentally retarded, 124 nurses and 369 general office workers was investigated by means of General Health Questionnaire (GHQ). The results were: 1) The incidence of mental unhealthiness was 44.6% among staff serving the mentally retarded, tending to be higher than among nurses, and significantly higher than among general office workers. 2) Among staff serving the mentally retarded, females tended to be more mentally unhealthy than males; among school teachers for the mentally retarded, the incidence among females was significantly higher than among males. 3) As to the incidence by age and experience, among staff serving the mentally retarded, the younger the age and the shorter the experience, the higher the incidence of mental unhealthiness.

Adult↗

Purification and characterization of arginine amidinohydrolase from Bacillus brevis TT02-8.

A bacterial arginase was purified to homogeneity from a strain of Bacillus brevis. The native enzyme, with an estimated MW of 143,000, migrated on SDS-PAGE as a single polypeptide of estimated MW of 33,000. The enzyme, highly specific to L-arginine, showed the maximum activity at pH 11.0 in the presence of Mn2+ ions and the pI was 4.8 by isoelectric focusing. The enzyme activity was increased significantly by the addition of Mn2+, Ni2+, or Co2+ ions, and inhibited potently by chemicals such as HgCl2, N-bromosuccinimide, or glutathione. The Kms for L-arginine and L-canavanine were 0.69 and 22.2 mM, respectively. The enzyme was inhibited competitively by gamma-guanidinobutyric acid, and non-competitively by L-lysine, L-ornithine, creatine, blasticidin S, and edeine B1. Analysis of the N-terminal amino acid sequence of the purified bacterial enzyme found 33-36% homologies with the Agrobacterium, yeast, rat, and human enzymes.

Amino Acid Sequence↗

[A case of aspergillosis presenting marked granulomatous pachymeningitis].

The authors report a rare case of intracranial aspergillosis presenting marked granulomatous pachymeningitis. A 58-year-old male who had a three-year history of diabetes and chronic bronchitis was referred to us because of progressive left hemiparesis and dysarthria. Postcontrast CT scan showed a ring-enhancing lesion with marked perifocal edema in the right parietal lobe, and right subdural enhancing mass. MR image revealed hypertrophic dura mater in the right convexity. On June 9, 1992, partial removal of the intra-axial cystic mass and granulomatous dura mater was performed. A number of characteristic aspergillus hyphae were recognized in the resected cyst and granulomatous dura mater. Postoperatively, the patient was treated with amphotericin-B and fluconazole. But granulomatous pachymeningitis became progressively enlarged and eventually created a large mass effect again. On January 23, 1993, the patient died of pneumonia. Cerebral aspergillosis is getting common but preoperative diagnosis is still difficult because of its causing several clinical features such as brain abscess, granuloma, intracerebral hemorrhage, cerebral infarction, meningitis, and encephalitis. Several comments were made about the pathogenesis of these features, and the necessity of early diagnosis and treatment was emphasized.

Aspergillosis↗

Stimulation of host-defense mechanism with synthetic adjuvants and recombinant cytokines against viral infection in mice.

The efficacy of synthetic immunoadjuvants and recombinant cytokines for the potentiation of host-resistance against virus infection was investigated using mouse models infected with Sendai virus and herpes simplex type 1 virus (HSV). The synthetic MDP derivative, MDP-Lys(L18), and recombinant cytokines, IL-1 beta, IFN-gamma, G-CSF and GM-CSF were shown to be effective for the stimulation of nonspecific protection against Sendai virus infection in mice. Both MDP-Lys(L18) and GM-CSF were effective for the protection against HSV infection in cyclophosphamide (CY)-treated mice. B30-MDP was suggested to be useful as an immunoadjuvant for the potentiation of antigenicity of recombinant or component vaccines.

Acetylmuramyl-Alanyl-Isoglutamine↗

Coordinate role for cell surface chondroitin sulfate proteoglycan and alpha 4 beta 1 integrin in mediating melanoma cell adhesion to fibronectin.

Cellular recognition and adhesion to the extracellular matrix (ECM) has a complex molecular basis, involving both integrins and cell surface proteoglycans (PG). The current studies have used specific inhibitors of chondroitin sulfate proteoglycan (CSPG) synthesis along with anti-alpha 4 integrin subunit monoclonal antibodies to demonstrate that human melanoma cell adhesion to an A-chain derived, 33-kD carboxyl-terminal heparin binding fragment of human plasma fibronectin (FN) involves both cell surface CSPG and alpha 4 beta 1 integrin. A direct role for cell surface CSPG in mediating melanoma cell adhesion to this FN fragment was demonstrated by the identification of a cationic synthetic peptide, termed FN-C/H-III, within the fragment. FN-C/H-III is located close to the amino terminal end of the fragment, representing residues #1721-1736 of intact FN. FN-C/H-III binds CSPG directly, can inhibit CSPG binding to the fragment, and promotes melanoma cell adhesion by a CSPG-dependent, alpha 4 beta 1 integrin-independent mechanism. A scrambled version of FN-C/H-III does not inhibit CSPG binding or cell adhesion to the fragment or to FN-C/H-III, indicating that the primary sequence of FN-C/H-III is important for its biological properties. Previous studies have identified three other synthetic peptides from within this 33-kD FN fragment that promote cell adhesion by an arginyl-glycyl-aspartic acid (RGD) independent mechanism. Two of these synthetic peptides (FN-C/H-I and FN-C/H-II) bind heparin and promote cell adhesion, implicating cell surface PG in mediating cellular recognition of these two peptides. Additionally, a third synthetic peptide, CS1, is located in close proximity to FN-C/H-I and FN-C/H-II and it promotes cell adhesion by an alpha 4 beta 1 integrin-dependent mechanism. In contrast to FN-C/H-III, cellular recognition of these three peptides involved contributions from both CSPG and alpha 4 integrin subunits. Of particular importance are observations demonstrating that CS1-mediated melanoma cell adhesion could be inhibited by interfering with CSPG synthesis or expression. Since CS1 does not bind CSPG, the results suggest that CSPG may modify the function and/or activity of alpha 4 beta 1 integrin on the surface of human melanoma cells. Together, these results support a model in which the PG and integrin binding sites within the 33-kD fragment may act in concert to focus these two cell adhesion receptors into close proximity on the cell surface, thereby influencing initial cellular recognition events that contribute to melanoma cell adhesion on this fragment.

Amino Acid Sequence↗

Bulimia nervosa in a pair of male monozygotic twins.

This is a report of a pair of male monozygotic twins meeting the DSM-III-R criteria for bulimia nervosa. At the age of 15, both brothers began to diet and suffered from bulimia. They were admitted to psychiatric hospitals and separated. After admission, their clinical course dramatically changed. The differences in their clinical courses and endocrinological data are suggestive as to the roles of environmental and hereditary factors in the etiology of bulimia nervosa.

Adolescent↗

Changes in the microvasculature after mechanical pressure on the hamster cheek pouch.

The reaction of the microvasculature in the periodontal ligament to mechanical pressure is considered a very important phenomenon with respect to the biological background to orthodontic tooth movement. For clarification of the microvascular reaction to mechanical pressure, an experimental model that incorporated a hamster cheek pouch was established. This in vivo model solves some of the problems of other experimental models of the microvasculature of the periodontal ligament. Blood plasma permeation in this model was examined by means of a blue dye (pontamine sky blue), and histological observation was performed by light and transmission electron microscopy. Increased vascular permeability was observed within 30 min after removal of the mechanical stimulation. The threshold weight resulting in dye leakage was between 1 and 5 g applied for 60 min. From the histological observations, some large gaps between the endothelial cells in venules were found, while most basement membranes remained undisturbed. These observations suggest that the plasma leakage was due to mild traumatic injury to the endothelial cells. Both leukocytes and platelets were observed in the gaps between the endothelial cells in the venule. These types of microvascular reactions to mechanical pressure could initiate tissue changes in the periodontal ligament during orthodontic tooth movement.

Animals↗

Tumor cell adhesive mechanisms and their relationship to metastasis.

Despite recent advances in the diagnosis and therapy of many forms of cancer, metastasis remains the major cause of death in cancer patients. As tumors progress they become increasingly heterogeneous, giving rise to aggressive subpopulations of tumor cells that subsequently invade local tissues, the lymphatics, and the circulatory system. This invasive behavior can ultimately lead to the widespread dissemination and metastasis of the primary tumor. In hematogenous metastasis, emboli consisting of tumor cells, host cells, platelets, and fibrin are transported to distant sites where they arrest in the microvasculature prior to extravasation. It is well accepted that tumor cell adhesion plays a fundamental role in many of the stages of the metastatic process. Tumor cell interactions with extracellular matrix components of tissue, tissue boundaries (basement membranes), or cell adhesion-promoting components of plasma; influence tumor cell motility, invasiveness, and many other important aspects of the metastatic tumor cell phenotype. Tumor cell adhesion also has a rate-limiting influence at various stages within the metastatic process, such as tumor cell arrest and extravasation. In addition, the ability of the immune system to recognize and successfully eradicated tumors is also highly dependent on the adhesion of activated lymphocytes to target tumor cells. Despite the rapid accumulation of information on the molecular basis of cell adhesion, our understanding of the relationship between tumor cell adhesion and hematogenous metastasis per se is fragmented and incomplete. Nevertheless, clear progress has been made, both in understanding the molecular basis of tumor cell adhesion and its relationship to the biology of tumor metastasis. New and exciting directions have been identified that are likely to yield direct benefits in developing new therapeutic or diagnostic approaches for malignant neoplasms. Our purpose is to briefly review the molecular basis of tumor cell adhesion from the standpoint of many of the receptors involved as well as their putative ligands. The relationship between specific tumor cell adhesion events and the formation of metastatic lesions is also addressed.

Animals↗

Prophylactic activity of dihydroheptaprenol, a synthetic polyprenol derivative, against Sendai virus infection in mice.

The effect of a chemically synthesized polyprenol derivative, dihydroheptaprenol (DHP), on the non-specific resistance of mice to Sendai virus infection was investigated. The mice that received 200 micrograms of DHP intranasally twice, at 3 days and 1 day before the infection, showed a significant protection against Sendai virus infection. Treatment of mice twice even with as much as 2000 micrograms of DHP through the subcutaneous route, however, had no protective effect against infection. Excess interferon and tumour necrosis factor production in intranasally DHP-treated mice was seen 1 day after the infection when compared with Sendai virus alone controls or with DHP alone controls. Variance analysis of these findings indicates a prophylactic activity of DHP in pulmonary viral infections.

Administration, Intranasal↗

Tracheostomy--the horizontal tracheal incision.

The complication rate after emergency tracheostomy is two to five times greater than after elective procedures. One of the main causes of the high risk of complications in emergency tracheostomy appears to be the amount of time required to open the trachea. Therefore, simple and fast procedures are mandatory. We have developed a new procedure as follows: A horizontal skin incision is performed. Strap muscles are dissected and retracted laterally. A transverse cut between tracheal rings below the thyroid isthmus is performed up to membranous portion of the trachea. The cut ends of the trachea remain open naturally because of the elasticity of the trachea. Skin and tracheal cut-ends are then joined by interrupted sutures. We have used this procedure during the past three years and have not experienced any major complications. This demonstrates the clear advantage and the more physiological nature of the procedure over various other incisions of the tracheal wall.

Adult↗

Inhibition of the metastasis of murine malignant melanoma by synthetic polymeric peptides containing core sequences of cell-adhesive molecules.

We investigated that the antimetastatic and antiadhesive activities of peptides based on Arg-Gly-Asp adhesive signal in fibronectin could be augmented by their polymerization. Poly(Arg-Gly-Asp), which consists of a repetitive sequence of Arg-Gly-Asp, inhibited lung metastases in C57BL/6 mice more effectively than Arg-Gly-Asp tripeptide was able to do, when coinjected or separately injected with B16-BL6 cells. The adhesion of tumor cells to fibronectin was specifically inhibited by adding poly(Arg-Gly-Asp) but not unrelated peptides. In contrast, poly(Arg, Gly, Asp), in which three amino acids are randomly arranged, showed neither inhibition of lung metastases nor any adhesive ability to attach to tumor cells. The inhibitory effect of polymeric peptides containing the Arg-Gly-Asp sequence on lung metastases decreased according to the decreasing repeat units of the Arg-Gly-Asp core sequence. Polymeric peptides with Arg-Gly-Asp entrapped within the liposome membranes also caused a remarkable reduction of metastatic colonies. In a spontaneous metastasis model, multiple i.v. administrations of poly(Arg-Gly-Asp) after tumor inoculation caused the significant reduction of metastatic colonies in the lung but did not affect the growth (size) of primary tumor. We found that the polymerization (multivalency) of the Arg-Gly-Asp core sequence was able to augment the inhibition of tumor lung metastases in experimental and spontaneous metastasis models as well as the cell-adhesive property more effectively than a monovalent unit of Arg-Gly-Asp peptide.

Amino Acid Sequence↗

Induction of an endogenous tumor necrosis factor in mice by murine recombinant interferon-gamma combined with a lipid A subunit analog (GLA-60) of low toxicity.

We have investigated the endogenous production of a serum cytotoxic factor when recombinant interferon-gamma (rIFN-gamma) is combined with synthetic lipid A subunit analogs of low toxicity (GLA compounds). The cytotoxic activity of the serum was measured by the crystal violet staining method with L929 cells as a target. Intravenous administration of rIFN-gamma followed by intravenous administration of lipopolysaccharide induced the endogenous production of a cytotoxic factor in the serum. The priming effect of rIFN-gamma appeared immediately and persisted for approximately 20 h after the injection. Administration of lipopolysaccharide as a trigger enhanced the production of the cytotoxic factor in the serum maximally 2 h after the injection. The cytotoxic activity in the serum was completely inhibited by anti-(mouse tumor necrosis factor) (TNF) antibody. A synthetic lipid A subunit analog (GLA-60), which is much less toxic in its endotoxin activities than lipopolysaccharide or synthetic lipid A (compound 506), induced the endogenous production of serum TNF in rIFN-gamma-primed mice. GLA-60 entrapped within liposomes induced the production of serum TNF in rIFN-gamma-primed mice more effectively than GLA-60 solubilized in phosphate-buffered saline. Intravenous or intranasal administrations of rIFN-gamma followed by intranasal administration of GLA-60 produced TNF in the lung washing fluid but not in the serum, indicating that TNF production can be induced locally rather than systemically by the alteration of the administration route of the primer and trigger. These results indicate that GLA-60, a lipid A subunit analog of low toxicity, is a beneficial triggering agent in the production of endogenous TNF, as well as having other immunopharmacological properties, and may provide a basis for cancer (metastases) treatment as a result of its ability to induce endogenous TNF.

Animals↗

Biological activities of synthetic polypeptides containing a repetitive core sequence (Arg-Gly-Asp) of cell adhesion molecules.

A unique polypeptide containing the repeated structure of core sequence from cell adhesion molecules, poly(Arg-Gly-Asp), was successfully prepared by the polymerization procedure with diphenylphosphoryl azide. This polypeptide dramatically inhibited the aggregation of platelets induced by adenosine diphosphate (ADP) or malignant melanoma cells.

Adenosine Diphosphate↗

Inhibition of tumour cell adhesion by anti-metastatic polypeptide containing a repetitive Arg-Gly-Asp sequence.

Anti-cell adhesive activity was examined by the synthetic polypeptide, containing repetitive Arg-Gly-Asp sequence of cell attachment site from fibronectin, poly (Arg-Gly-Asp). The attachment of tumour cells to fibronectin substrate was specifically inhibited by adding poly (Arg-Gly-Asp) in cell surface receptor-mediated and divalent cation-dependent manners, but not by unrelated peptides. In our previous study, the lung metastatic formation of tumour cells was dramatically reduced by intravenous co-injection of anti-cell adhesive poly (Arg-Gly-Asp) with B16-BL6 melanoma cells. These findings suggest that polypeptide-mediated inhibition of pulmonary metastasis is partly due to interference with tumour cell adhesion to the substrates including fibronectin in target organs or tissues.

Amino Acid Sequence↗

Macrophage activation and host augmentation against Sendai or herpes simplex virus (HSV) infections with synthetic polypeptides in mice.

Poly-L-Lys (mean mol. wt; 12,000), poly-L-Arg (5000) and poly-L-Orn were found to activate peritoneal macrophages effectively in vivo in 14 synthetic homo polypeptides. The ability of sequential poly(L-Arg-L-X) (5000) to activate macrophages was less than that of poly-L-Arg. Neither (L-Arg)12 nor (L-Arg)6 by themselves activated macrophages, but poly-D-Arg (5000) did, as also did poly-L-Arg; this suggests that the polycationic character of poly-L-Arg plays a role in the activation of macrophages. The intranasal administration of poly-L-Lys, -L-Arg, -L-Orn, -D-Arg, all of which activated macrophages, augmented host resistance against Sendai virus infection in mice. The protection afforded by poly-L-Arg seemed to depend on its mol. wt: the order of protection was poly-L-Arg greater than (L-Arg)12 greater than (L-Arg)6. The intranasal administration of poly-L-Arg 3 days before the infection was effective, while that 1 day before infection was not. There was no difference between the groups in the titer of interferon produced by the infection of Sendai virus given with poly-L-Arg either 3 days before or 1 day before the infection. The administration of poly-L-Arg 3 days before the infection caused a significant decrease of the virus titer in the lung 6 days after the infection when compared with the control or the mice given 1 day before. The intravenous administration of 2-chloroadenosine (2-Cl-Ade), which is a selective inhibitor of macrophages, into the mice which had received poly-L-Arg intranasally 3 days before the infection caused a significant decrease in the survival rate of the mice, indicating that the macrophages activated with poly-L-Arg are likely to be an important element in affording the protection. Subcutaneous administration of poly-L-Arg revealed protective activity against systematic infection with herpes virus-type 1.

2-Chloroadenosine↗

Effect of N alpha-acetylmuramyl-L-alanyl-D-isoglutaminyl-N epsilon-stearoyl- L-lysine on resistance to herpes simplex virus type-1 infection in cyclophosphamide-treated mice.

The restoration of resistance by N alpha-acetylmuramyl-L-alanyl-D-isoglutaminyl-N epsilon-stearoyl-L-lysine [MDP-Lys(L18)] on herpes simplex virus (HSV) type-1 infection was examined in cyclophosphamide (CY)-treated mice. MDP-Lys(L18) was shown to restore the resistance to HSV infection in CY-treated mice when it was injected either subcutaneously, intravenously, or intraperitoneally before infection. Treatment with MDP-Lys(L18) in CY-treated mice restored impaired activity for inhibiting HSV growth in the liver.

Acetylmuramyl-Alanyl-Isoglutamine↗