Biomedical subjects

T Akaike

Publications and source records attributed to T Akaike.

At least 235 records · Page 13Linked to original sources

PubMed1990

Inactivation of chemotactic activity of C5a by the serratial 56-kilodalton protease.

The effects of the 56-kilodalton protease (56K protease) from Serratia marcescens on complement-derived chemotactic activity were examined. Fresh human serum was incubated with zymosan to produce C5a. This activated serum was then incubated with various concentrations of 56K protease, and the chemotactic activity of mouse peritoneal exudate polymorphonuclear leukocytes (PMN) and macrophages was evaluated. A significant dose-dependent decrease of chemotactic activity was observed after protease treatment. Furthermore, treatment of human recombinant C5a with 56K protease at a dose of 1.0 microgram/ml resulted in a complete loss of chemotactic activity. When the living bacteria of the virulent strain, which produced about 10 times more protease than did the less virulent strain, were injected intraperitoneally into mice, the magnitude of infiltration of polymorphonuclear leukocytes into the peritoneal cavity was much lower than that caused by the less virulent strain. Because complement-dependent chemotactic activity is an initial response to bacterial infection, these results suggest indirect pathogenic functions of serratial proteases that suppress chemotactic activity.

Blood Bactericidal Activity↗

PubMed1990

Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice.

We evaluated various biochemical parameters in influenza virus-infected mice and focused on adenosine catabolism in the supernatant of bronchoalveolar lavage fluid (s-BALF), lung tissue, and serum (plasma). The activities of adenosine deaminase (ADA) and xanthine oxidase (XO), which generates O2-, were elevated in the s-BALF, lung tissue homogenate, and serum (plasma). The elevations were most remarkable in s-BALF and in lung tissue: We found a 170-fold increase in ADA activity and a 400-fold increase in XO activity as measured per volume of alveolar lavage fluid. The ratio of activity of XO to activity of xanthine dehydrogenase in s-BALF increased from 0.15 +/- 0.05 (control; no infection) to 1.06 +/- 0.13 on day 6 after viral infection. Increased levels of various adenosine catabolites (i.e., inosine, hypoxanthine, xanthine, and uric acid) in serum and s-BALF were confirmed. We also identified O2- generation from XO in s-BALF obtained on days 6 and 8 after infection, and the generation of O2- was enhanced remarkably in the presence of adenosine. Lastly, treatment with allopurinol (an inhibitor of XO) and with chemically modified superoxide dismutase (a scavenger of O2-) improved the survival rate of influenza virus-infected mice. These results indicate that generation of oxygen-free radicals by XO, coupled with catabolic supply of hypoxanthine from adenosine catabolism, is a pathogenic principle in influenza virus infection in mice and that a therapeutic approach by elimination of oxygen radicals thus seems possible.

Adenosine↗

PubMed1989

Activation of hageman factor and prekallikrein and generation of kinin by various microbial proteinases.

Activation of the Hageman factor-kallikrein-kinin system by serratial 56-kDa proteinase was previously demonstrated (Matsumoto, K., Yamamoto, T., Kamata, T., and Maeda, H. (1984) J. Biochem. (Tokyo) 96, 739-749; Kamata, R., Yamamoto, T., Matsumoto, K., and Maeda, H. (1985) Infect. Immun. 48, 747-753). To investigate whether the activation of the system is specific for 56-kDa proteinase or is found similarly with other microbial proteinases, 11 proteinases of microbial origins were studied; the 56-kDa proteinase was the control. For in vitro studies, activation of guinea pig Hageman factor and prekallikrein was examined in purified systems as well as in plasma as a zymogen source. Specific antibodies and inhibitors confirmed the activation steps of the cascade. In the in vivo study the enhancement of vascular permeability in guinea pig skin and its sensitivity to inhibitors of activated Hageman factor, plasma kallikrein, or a kininase were examined. The results from the in vivo experiments were consistent with those in vitro. Taking all the data together, we classified the 11 microbial proteinases into three groups as follows: 1) Serratia marcescens 56-, 60-, and 73-kDa proteinases, Pseudomonas aeruginosa alkaline proteinase and elastase, and Aspergillus melleus proteinase (this group activated Hageman factor but not prekallikrein); 2) Vibrio vulnificus proteinase, subtilisin from Bacillus subtilis, and thermolysin from Bacillus stearothermophilus (this group activated both Hageman factor and prekallikrein); 3) Streptomyces caespitosus proteinase and V8 proteinase from Staphylococcus aureus (this group activated neither Hageman factor nor prekallikrein, but generated kinin from high molecular weight kininogen directly).

Animals↗

PubMed1989

Oxygen radicals in influenza-induced pathogenesis and treatment with pyran polymer-conjugated SOD.

The pathogenicity of influenza virus infection in the mice involves, at least in part, overreaction of the immune responses of the host rather than a direct effect of virus multiplication. Xanthine oxidase, which is responsible for the generation of oxygen free radicals, was elevated in serum and lung tissue of mice infected with influenza virus. To test the theory that oxygen-free radicals are involved in pathogenesis, free radicals were removed by injecting superoxide dismutase (SOD), a specific superoxide radical scavenger, which was conjugated with a pyran copolymer. The conjugate protected mice against a potentially lethal influenza virus infection if administered 5 to 8 days after infection. These findings indicate that oxygen radicals are important in the pathogenesis of influenza virus infection, and that a polymer-conjugated SOD has therapeutic potential for this virus infection and other diseases associated with free radicals.

Animals↗

PubMed1989

Electrophysiological analysis of the trigemino-olivo-cerebellar (crura I and II, lobulus simplex) projection in the rat.

In albino rats the whisker area was electrically stimulated while climbing fiber responses were surveyed in the cerebellar hemisphere on the ipsilateral side. They were identified both deep in the intercrural sulcus, and in the posterior superior fissure. Histological examination has revealed that the response areas extend longitudinally from the dorsal surface of crus II to the ventral surface of crus I in the intercrural sulcus, and from the rostral surface of crus I to the caudal surface of lobulus simplex in the posterior superior fissure. These are supposed to be transmitted through direct trigemino-olivary projections.

Action Potentials↗

PubMed1989

Inactivation of various proteinase inhibitors and the complement system in human plasma by the 56-kilodalton proteinase from Serratia marcescens.

The interaction of the 56-kilodalton (kDa) proteinase from Serratia marcescens with human plasma activated C1 (C1) inhibitor, alpha 2-antiplasmin, and antithrombin III was investigated. The 56-kDa proteinase was not affected by these inhibitors; on the contrary, all the inhibitors were inactivated by the 56-kDa proteinase within 2 to 6 h. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that all three inhibitors showed decreases in molecular weight of approximately 8,000 to 10,000 as a result of proteolytic cleavage by the 56-kDa proteinase. The 56-kDa proteinase also inactivated serum complement within 2 to 6 h. The loss of inhibitory activity caused by the 56-kDa proteinase, together with the effects of endogenous serine proteinases, may facilitate tissue destruction and inflammation.

Complement C1 Inactivator Proteins↗

PubMed1989

Molecular mechanism of complex infection by bacteria and virus analyzed by a model using serratial protease and influenza virus in mice.

We examined the effect of a serratial exoprotease on the pathogenesis of influenza virus infection in mice as a model of complicated respiratory infection by bacteria and virus in humans. The 56-kilodalton (56-kDa) protease from Serratia marcescens was administrated intranasally to mice at a dose of 10, 20, or 40 micrograms from day 0 to day 3 after inoculation of the influenza virus. Administration of the protease resulted in remarkable enhancement of the lethal effect of the virus and enhancement of pathological changes in the lungs. Influenza virus replication, determined by plaque-forming assay, was accelerated by the protease. Namely, we found a 100-fold increase in virus yield by day 2. The 56-kDa protease caused generation of plasmin activity in the lungs. In vitro experiments showed that plasmin greatly enhanced the yield of influenza virus, although the effect of the 56-kDa protease by itself was much lower than that of plasmin. Furthermore, the 56-kDa protease could induce plasmin production indirectly via activation of plasminogen by the Hageman factor-dependent cascade in the in vitro system. We conclude that this major serratial exoprotease has a deleterious effect on mice infected with influenza virus and that this effect seems to result from enhancement of viral growth by indirect acceleration of plasmin generation induced by the protease.

Animals↗

PubMed1989

[Usefulness of serum adenosine deaminase activity in the early diagnosis of Mycoplasma pneumonia].

It is sometimes difficult to clinically diagnose mycoplasma pneumonia at an early stage before the rise of titer of antibody to Mycoplasma pneumoniae. Mycoplasma pneumonia may be related with T-lymphocyte activity, and its inflammatory process is different from that of bacterial pneumonia. Adenosine deaminase (ADA) activity is a predominant T-lymphocyte enzyme, and its plasma activity is high in diseases in which cellular immunity is stimulated. In this study, we have investigated 31 cases with pneumonia (11 cases of mycoplasma pneumonia and 20 cases of bacterial pneumonia) within 10 days after onset to evaluate the usefulness of ADA measurement in the diagnosis of mycoplasma pneumonia. Serum ADA activity in the group of mycoplasma pneumonia was 32.1 +/- 12.0 U/l (63.9-18.8 U/l), that of non-mycoplasma pneumonia 12.5 +/- 3.3 (4.6-18.6) U/l, and that of normal control 14.0 +/- 3.4 (6.3-19.3) U/l. ADA activity of the group of mycoplasma pneumonia was significantly higher than those of non-mycoplasma pneumonia and normal control (p less than 0.001). This results suggest that serum ADA activity in patients with acute pneumonia may be useful for the early diagnosis of mycoplasma pneumonia.

Adenosine Deaminase↗

PubMed1988

Electrophysiological analysis of the trigemino-tecto-olivo-cerebellar (crus II) projection in the rat.

In albino rats the whisker area was electrically stimulated while climbing fiber responses were surveyed in the cerebellar cortex of the tecto-olivo-recipient zone in the medial region of crus II. Climbing fiber responses were evoked by the vibrissal stimulation only in the medial portion of the zone. Based both on lesion experiments of the superior colliculus and on recording multiunit potentials in the inferior olive it is suggested that the trigeminal climbing fiber responses are evoked via the superior colliculus.

Afferent Pathways↗

PubMed1988

Streptococcus acidominimus infections in a human.

We described the first case of pneumonia, pericarditis and meningitis due to Streptococcus acidominimus, who had no underlying disease. The organism is very rarely obtained in clinical bacteriology. The identifying characteristics of this isolate were discussed. There are no reports in which this organism caused such complicated human infection as this case in the English literature.

Adult↗

PubMed1988

Deferoxamine mesylate inhibits bacterial growth in vivo.

Iron is one of the essential element for bacterial growth. To study the effect of chelation of iron on bacterial growth, 17 different strains of bacteria were cultured in chocolate-agar medium in the presence or absence of deferoxamine methylate (DM), a potent chelating agent for iron. A fairly low concentration of DM (10 mg/ml) in the culture medium markedly inhibited the growth rates of the three bacterial strains, B. catarrhalis, N. meningiditis and N. gonorrhoeae. In vivo effect of DM was also tested in mice that were intraperitoneally inoculated with a lethal number of N. meningiditis (2 x 10(8)/animal). After 40 h of inoculation, more than 90% of the control animals died for acute peritonitis. In contrast, animals which were intraperitoneally administered with DM showed a marked resistance to the inoculated bacteria without showing toxic effects of the agent: less than 30% of animals died of acute peritonitis caused by infection within 40 h. The results suggest that, in addition to the currently used antibiotics. DM might also be an useful therapeutic agent for treatment of bacterial infection.

Animals↗

PubMed1987

Electrophysiological analysis of the tecto-olivo-cerebellar (lobulus simplex) projection in the rat.

In albino rats the deep layers of the superior colliculus were stimulated, and climbing fiber responses of Purkinje cells were explored in the medial region of the lobulus simplex. They were identified in a strip (ca. 0.7-1.0 mm wide) in the most medial region of folium b. In the tectorecipient zone of the medial accessory olive antidromically evoked potentials from the lobulus simplex were recorded laterally to those from lobule VII. Evidence is presented that climbing fibers innervating the zone in the lobulus simplex are axon collaterals of the inferior olivary neurons which project to crus II.

Action Potentials↗

PubMed1986

Differential localization of inferior olivary neurons projecting to the tecto-olivo-recipient zones of lobule VII or crus II in the rat cerebellum.

In albino rats antidromically evoked potentials by stimulation of the cerebellar cortices of lobule VII or crus II were surveyed in the tectorecipient zone of subnucleus c in the medial accessory olive. Those from lobule VII were localized in the medial region, while those from crus II in the lateral region of the tectorecipient zone. The results confirm the tecto-olivo-cerebellar (lobule VII and crus II) projections via different inferior olivary neurons.

Animals↗

PubMed1986

Electrophysiological analysis of the tecto-olivo-cerebellar (crus II) projection in the rat.

In albino rats the superior colliculus was stimulated and evoked potentials were explored in the cerebellar hemisphere including the paramedian lobule, and crura I and II. Climbing fiber responses were identified in a strip (ca. 1 mm wide) in the medial region of crus II, extending to both folia a and b. In the tectorecipient zone in subnucleus c of the medial accessory olive, antidromically evoked potentials from crus II were recorded lateral to those from lobule VII. Evidence is presented that inferior olivary neurons projecting to crus II are different from those projecting to lobule VII.

Animals↗

PubMed1986

Spatial distribution of evoked potentials in the inferior olivary nucleus by stimulation of the visual afferents in the rat.

Visual pathways (optic disc, optic nerve and pretectal regions) were electrically stimulated and evoked potentials were explored throughout the inferior olive in the anesthetized rat. Responsive areas were identified as the caudal half of the dorsal cap, nucleus beta and the most caudal region of subnucleus c of the medial accessory olive. No field potentials were identified in the rostral half of the dorsal cap, its ventrolateral outgrowth or the dorsomedial cell column. Contralateral retinal afferents were only effective all over the responsive areas.

Animals↗

PubMed1985

Electrophysiological analysis of the tecto-olivocerebellar (lobule VII) projection in the rat.

In albino rats the superior colliculus was stimulated and its evoked potentials were explored throughout the posterior vermis of the cerebellum. Climbing fiber responses were identified only in lobule VII, ipsilaterally 1.2-1.6 mm wide. In the medial accessory olive, subnucleus c, in the contralateral side both antidromically evoked potentials from lobule VII and orthodromically evoked potentials from the superior colliculus were recorded. This evidence suggests that they are tecto-olivocerebellar projections.

Animals↗

PubMed1985

Lobular distribution of visual climbing fiber responses in the cerebellum.

The visual pathway was electrically stimulated at the optic disc, optic nerve and pretectal region in the albino rat. Field potentials of climbing fiber activation of Purkinje cells were explored in a large area of the cerebellum, and obtained in flocculus and posterior vermis. The responses in the posterior vermis were identified in the medial region of lobules VIa-c, VIII, IX, and the dorsal region of lobule X of Larsell. No response was obtained in lobule VII.

Animals↗

PubMed1984

Separation of macrophages from mouse peritoneal exudate cells with substrata coated with chemically modified collagens.

A cell-separation technique was designed on the basis of specific interaction between macrophages and chemically modified collagens in the presence of serum. When unseparated mouse peritoneal exudate cells containing approximately 50% macrophages and 50% lymphocytes were incubated in dishes coated with unmodified and chemically modified collagens, only macrophages adhered more rapidly and in greater numbers to succinylated and methylated collagen than to unmodified collagen. The adherent macrophages could be easily detached from the substrata by divalent cation chelating agents. The purity and recovery of macrophages separated by this method were approximately 92-94% and 41-48%, respectively.

Animals↗