The histopathological characteristics of the newly formed blood vessels in the atherosclerotic intima of human coronary arteries examined three-dimensionally and light microscopically using serial sections were as follows : (1) the vascular density in atherosclerotic intimas significantly correlated with the degree of luminal stenosis, (2) the neovascularization was prominent in the intimas showing chronic inflammatory infiltrate, formation of granulation tissue or atheromatous change, while decreased in the extensively hyalinized and calcified intimas, and (3) the intimal vasculature originated mainly from the adventitia and partly from the proper coronary lumen. These findings support the hypothesis that the arteriointimal angiogenesis represents an essential and coincidental response to arterial injuries occurring in atherosclerotic process.
In vivo introduction of human VEGF mRNA into rabbit carotid arteries using HVJ-liposome method induced the prominent angiomatoid proliferation of endothelial cells in thickened intima due to fibromuscular hyperplasia. Thus, the interventional suppression of intimal neovascularization by gene therapy may be an effective therapy for the restenosis following PTCA in the futural perspectives.

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Although Interleukin-1 (IL-1) is the key mediator of rheumatoid arthritis, the mechanisms underlying the breakdown of cartilage and inhibition of proteoglycan synthesis have not been clear. We presented here the involvement of superoxide anion in IL-1-induced cartilage breakdown. We also demonstrated that nitric oxide plays an important role in IL-1-induced inhibition of proteoglycan synthesis.
These data suggest the significance of gas mediator in the joint destruction of rheumatoid arthritis.

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Active NADPH oxidase of neutrophils is found on the membrane as an enzyme complex, composed of membrane integrated cytochrome b558 (gp91 and p22 subunits), and two cytosolic factors (p47 and p67) . Recently, we radioactively identified a third cytosolic factor, p40, as a molecule which associates with p67. However, there is no evidence to functionally relate it to the NADPH oxidase system.
In this study, we raised antibodies against either the C-or N-terminal polypeptide of p40 as well as against the C-terminal polypeptide of p67 to examine the mode of interaction between p40 and p67 in a complex unit. The antibody against the C-terminus of p67 was able to coimmunoprecipitate p40 in conjunction with p67. Interestingly, however, antibody against the C-terminus of p40 completely dissociated the p67 molecule from the p40-p67 complex unit, despite their tight association, whereas that against the N-terminus of p40 had absolutely no dissociation effect. Similar results were found regarding their effects on the O^-₂-generating ability of cytosol potentiated with myristic acid in a cell free activation system, i.e., its inhibition with the antibody for the C-terminus but not with that for the N-terminus of p40.
These results are first demonstration that p40 is virtually involved in the activation process of NADPH oxidase through its C-terminal, but not its N-terminal, association with p67.

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To investigate the relationship of serum and urine levels of hyaluronic acid (HA) in rheumatoid arthritis (RA) patients to aging, joint destruction and clinical parameters, we measured HA levels by HA binding protein assay in 92 patients and 128 healthy controls.
Serum and urine levels of HA in healthy controls were elevated with aging over 70 years old. Serum and urine levels of HA in RA patients were elevated compared with those in 30 to 83 years old healthy controls (P<0.001) . There was no significant correlation between serum and urine HA in RA patients (r=0.018) . Serum levels of HA in stage III and IV in Steinbrocker's classification were significantly elevated compared with those in stage I (P<0.001) . Serum levels of HA did not show a significant correlation with inflammatory markers, including ESR (r=0.194, P=0.064), CRP level (r =0.202, P=0.053), WBC count (r=0.042, P=0.688) and IgG level (r=-0.081, P=0.445) .
These results suggest that the elevation of serum HA levels might be one of the evidences for premature senescence in RA patients.

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Despite aerosol inhalation therapy plays a key role in the treatment of bronchial diseases, the devices for the treatment are not necessarily satisfactory. The present study was designed for the comparative functional assessment of our newly developed device with one of marketed devices, Spinhaler.
In order to evaluate them precisely and objectively, we assembled new two detection systems. One was for the detection of spouting amount, and another for pressure drop, or airway resistance. With regard to distribution of powder, we followed FDA requirement, using cascade impactor. Thus, we assessed these two devices from view points of these three functions, i. e. distribution, spouting and pressure drop, or airway resistance.
As the study results, the spouting and distribution functions of Spinhaler were found poor. The spouting amount of Spinhaler was unstable and varied from 0 % to 100 %, mostly 30 to 50 %. Sometimes its needle did not puncture the capsule at all. Spinhaler took one second at the fastest but usually took more than ten seconds to complete its spouting.
On the contrary, Jethaler spouted out always more than 90 % of the powder and completed spouting within 0.1 second. Collection of the most appropriate particle size for inhalation to bronchi, from 1.1 up to 7 micro meter, with Jethaler was larger by 30 to 50 % than that with Spinhaler. The application of unique control mechanism of air stream enabled us to develop this device for dry powder inhalation. This new device weighs only 30 grams and is handy.

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To investigate whether the nitric oxide (NO) is involved in the myocardial damage in acute myocardial infarction (AMI), ventricular myocardial tissue of autopsied cases with myocardial infarction was examined by immunohistochemical staining with anti-inducible NO synthase (iNOS) and anti-nitrotyrosine antibody.
The damaged residual myocardium were positively stained with anti-iNOS antibody and anti -nitrotyrosine antibody in AMI. These findings were not obtained in the myocardial tissue of patients who died shortly in the early stage when myocardial cells reveal contraction band necrosis with minimal inflammatory cell infiltration. And also they were not obtained in patients with old myocardial infarction.
Since iNOS development accompanied by cell infiltration was noted in the damaged myocardium and nitrotyrosine was also disclosed in the same area, it is suggested that not only NO but also peroxynitrite is involved in myocardial damage in AMI.

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A gene encoding the variable regions of the heavy and light chains of a mouse monoclonal antibody H2, which specifically reacts with human liver cells, was cloned in a phagemid vector. Anti-idiotypic antibody was produced by immunizing the original mouse antibody with various absorptions. The cloned phage specifically reacted with this anti-idiotypic antibody, and the reaction between the cloned phage and anti-idiotypic antibody was specifically blocked by the original antibody. The soluble protein, expressed as a fusion protein, was detected as a 30 kDa single band on sodium dodecyl sulfate polyacrylamide gel electrophoresis. This protein was demonstrated to bind specifically to an anti H2 idiotypic antibody by Western blot analysis.
The sera of patients with various diseases were assayed using this anti-idiotypic antibody and sandwich enzyme-linked immunosorbent assay. Only the sera of patients with chronic liver diseases highly reacted and this binding was specifically attenuated by the cloned soluble protein. This liverspecific idiotype-bearing antibody detected in the serum of a patient with chronic hepatitis C could be purified and this antibody mediated antibody-dependent cytotoxicity against a hepatocyte derived cell line Chang in vitro.
These findings suggest that a human antibody that reacts with human liver cells, can be detected in patients with chronic liver diseases and can contribute to the liver cell damage.

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Lipopolysaccharides (LPS) from periodontal pathogens, Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Actinobacillus actinomycetemcomitans (Aa) were tested for their ability to induce the production of interleukin-1β (IL-1β) in human monocytes. Pg-LPS induced IL-1β production in a serum dependent manner. IL-1β production induced by 1.0-10 ng/ml of each LPS was the following order, E. coli-LPS>Aa-LPS>Pg-LPS>Pi-LPS. The IL-1β production by each LPS was abolished by the preincubation of LPS with polymyxin B and was blocked by anti-CD14 antibody, indicating that human monocytes utilized CD14 to recognize every LPS. IL-1β production by the cells stimulated with E. coli- or Aa-LPS (0.1-10 ng/ml) was blocked by the preincubation of the cells with LA-14-PP (100 ng/ml) but IL-1β response induced by Pg- or Pi-LPS was not.
These results suggest that to respond to Pg- or Pi-LPS, monocytes utilize a class of signaling molecule (transducer) that is not blocked by LA-14-PP.

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