Biomedical subjects

Takashi Naganawa

Publications and source records attributed to Takashi Naganawa.

4 recordsLinked to original sources

PubMed2005

Effect of neutrophil adhesion on the size of aggregates formed by agonist-activated platelets.

In this study we have investigated the effect of human neutrophil on agonist-induced platelet aggregation by using the laser-light scattering method that can detect a two-phase process, formation of small aggregates followed by large aggregate formation. When nonstimulated neutrophils were added to agonist-stimulated platelet-rich plasma (PRP), the large platelet aggregates were decreased and the small ones were increased by using either collagen, thrombin or ADP as agonist. Scanning-electron microscopic observation showed marked adhesion of neutrophil to aggregated platelets. The supernatant from neutrophils cell lysate (neutrophil supernatant) showed inhibitory effect similar to that with intact neutrophils, suggesting that the inhibitory effect by neutrophils was due to soluble component(s) including proteases released from neutrophils adhered to activated platelets. We have examined the effect of inhibition of a major released protease, elastase. The addition of its potent inhibitor elafin to intact neutrophils or the neutrophil supernatant changed their antiaggregating activity. The treatment of platelets with genistein, an inhibitor of protein tyrosine kinase, decreased agonist-induced large aggregates and increased small ones, suggesting that certain protein tyrosine kinase would be involved in the transition from small to large platelet aggregates. It was also shown that the tyrosine phosphorylation induced by agonist stimulation of several high molecular-weight proteins of platelets was inhibited by coincubation with neutrophils, concurrent with increases in smaller phosphorylated proteins. In washed platelets, coincubation with neutrophils resulted in reduced formation of large aggregates when stimulated with collagen or thrombin and repressed agonist-induced activation of tyrosine protein kinases (Syk, Lyn, Src, and Pyk2), but not thrombin-induced ERK and p38 MAP kinase. These results suggest that the cleavage of platelet membrane glycoproteins at least in part by elastase which was released from neutrophils, is involved in the inhibition of the transition from small to large platelet aggregates.

Adenosine Diphosphate↗

PubMed2004

In vitro susceptibility to tetracycline and fluoroquinolones of Japanese isolates of Coxiella burnetii.

Coxiella burnetii is the agent of the worldwide zoonosis, Q fever. The in vitro susceptibility to tetracycline and fluoroquinolones of Japanese isolates of C. burnetii was evaluated for the first time. The MICs against Japanese isolates were almost the same as the MICs against the foreign reference isolates. The results suggest that the common antibiotics therapy for Q fever used in other countries is also effective for Japanese Q fever patients.

Anti-Bacterial Agents↗

PubMed2003

Cell permeable ROS scavengers, Tiron and Tempol, rescue PC12 cell death caused by pyrogallol or hypoxia/reoxygenation.

The role of superoxide anion (O(2)*-) in neuronal cell injury induced by reactive oxygen species (ROS) was examined in PC12 cells using pyrogallol (1,2,3-benzenetrior), a donor to release O(2)*-. Pyrogallol induced PC12 cell death at concentrations, which evidently increased intracellular O(2)*-, as assessed by O(2)(*-)-sensitive fluorescent precursor hydroethidine (HEt). Caspase inhibitors, Z-VAD-FMK and Z-Asp-CH(2)-DCB, failed to protect cells from injury caused by elevation of intracellular O(2)*-, although these inhibitors had effects on hypoxia- or hydrogen peroxide (H(2)O(2))-induced PC12 cell death. Two known O(2)*- scavengers, Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid) and Tempol (4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxyl) rescued PC12 cells from pyrogallol-induced cell death. Hypoxia/reoxygenation injury of PC12 cells was also blocked by Tiron and Tempol. Further understanding of the underlying mechanism of the protective effects of these radical scavengers reducing intracellular O(2)*- on neuronal cell death may lead to development of new therapeutic treatments for hypoxic/ischemic brain injury.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

PubMed2003

SCID mouse model for lethal Q fever.

Q fever, a worldwide zoonosis caused by Coxiella burnetii, has many manifestations in humans. Endocarditis is the most serious complication of Q fever. Animal models are limited to acute pulmonary or hepatic disease and reproductive disorders. An appropriate experimental animal model for Q fever endocarditis does not yet exist. In this study, severe combined immunodeficient (SCID) mice infected with C. burnetii showed persistent clinical symptoms and died, whereas immunocompetent mice similarly infected became asymptomatic and survived. The SCID mice examined in this study had severe chronic lesions in their primary organs: the heart, lung, spleen, liver, and kidney. The heart lesions of the SCID mice were similar to those in humans with chronic Q fever endocarditis: they had focal calcification and expanded macrophages containing C. burnetii. The 50% lethal dose of C. burnetii in SCID mice was at least 10(8) times less than that in immunocompetent mice. The SCID mouse is highly susceptible to C. burnetii, and the immunodeficiency of the host enhances the severity of Q fever. This animal model could provide a new tool for the study of chronic Q fever and Q fever in immunodeficient hosts.

Animals↗