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Biomedical subjects

N Nakachi

Publications and source records attributed to N Nakachi.

12 recordsLinked to original sources
PubMed2000

Delta 9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma, IL-12, and IL-12 receptor beta 2 responses to Legionella pneumophila infection.

The marijuana cannabinoid, delta 9-tetrahydrocannabinol (THC), suppresses immunity to Legionella pneumophila and development of Th1 activity and cell-mediated immunity. In the current study, THC effects on cytokines regulating the development of Th1 cells were examined. BALB/c mice showed significant increases in serum IL-12 and IFN-gamma within hours of infection; however, the levels of these Th1-promoting cytokines as well as resistance to a challenge infection were suppressed by THC (8 mg/kg) injected 18 h before priming. The Th2-promoting cytokine, IL-4, was increased within hours of a Legionella infection and was further increased by THC treatment. These results suggested that THC injection suppressed the cytokine environment promoting Th1 immunity. In additional experiments, THC pretreatment and infection of IL-4 knockout mice showed that serum IL-12 and IFN-gamma were suppressed equally in both knockout and normal mice. This suggested that the drug-induced increase in IL-4 was not responsible for the decreases in serum IL-12 and IFN-gamma. However, THC treatment was shown to suppress the expression of IL-12 receptor beta 2 mRNA, indicating that, in addition to suppression of IL-12, THC injection suppressed the expression of IL-12 receptors. Finally, the role of cannabinoid receptors in Th1-promoting cytokine suppression was examined, and results with receptor antagonists showed that both cannabinoid receptors 1 and 2 were involved. It is suggested that suppression of Th1 immunity to Legionella is not due to an increase in IL-4 production but to a decrease in IFN-gamma and IL-12. Furthermore, both types of cannabinoid receptors are involved.

Animals↗
PubMed2000

Helicobacter pylori infection of human gastric epithelial cells induces IL-8 and TNFalpha, but not TGFbeta1 mRNA.

Helicobacter pylori (Hp) infection causes gastric ulcers and gastric carcinomas. The mechanisms of these diseases are not known but Hp induction of cytokines is believed to be involved. However, the profile as well as the involvement of cytokines induced by Hp infection is less clear. In the present study, steady state levels of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNFalpha) and TGFbeta1 mRNA of human gastric epithelial cell lines Kato III, AGS and NCI-87N in response to Hp infection were investigated. The cell cultures were infected with Hp for up to 18 h. Total RNA was extracted and analyzed by reverse transcription-PCR. The three cell lines tested expressed low constitutive levels of mRNA for IL-8 and TNFalpha. The mRNA levels of IL-8 quickly increased within 2 h in all three cells tested and reached a peak at 4 h following infection with Hp. In contrast, the levels of TNFalpha after Hp infection increased in only Kato III cells. The other cells, AGS and NCI-87N, responded with minimum increases after Hp infection. The TGFbeta1 mRNA was constitutively expressed in both AGS and NCI-87N cells, but Kato III cells expressed only low levels prior to infection. The Hp infection did not increase the levels of TGFbeta1 mRNA as well as TGFbeta1 secretion in all cells tested. These results indicate that the cytokine response to Hp infection differs according to the cells studied and the response may be linked somewhat to TGF levels of gastric cells.

Cell Line↗
PubMed2000

Differential effects of virulent versus avirulent Legionella pneumophila on chemokine gene expression in murine alveolar macrophages determined by cDNA expression array technique.

The cDNA expression array technique is a powerful tool to determine, at one time from many genes, specific gene messages modulated by infection. In the present study, we identified genes modulated in response to virulent versus avirulent Legionella pneumophila infection of the alveolar macrophage cell line MH-S by the cDNA expression array technique. Many macrophage genes were found to be modulated after 5 h of in vitro infection with L. pneumophila. In particular, it was found that the monocyte chemotactic protein 3 (MCP-3) gene expression was significantly induced by infection with virulent L. pneumophila but not with avirulent L. pneumophila. In contrast, other chemokine genes, such as macrophage inflammatory protein (MIP) 1alpha, were induced by both virulent and avirulent L. pneumophila. Reverse transcription (RT)-PCR assay of total RNA isolated from macrophages infected with the bacteria for 5 or 24 h confirmed the differential induction of the chemokine genes by virulent versus avirulent L. pneumophila. Thus, the cDNA expression array technique readily revealed differential induction by L. pneumophila infection of select chemokine genes of macrophages from more than 1,100 genes. These results also indicate that certain chemokine genes may be selectively induced by virulent bacteria.

Animals↗
PubMed2000

Induction of interleukin-4 (IL-4) by legionella pneumophila infection in BALB/c mice and regulation of tumor necrosis factor alpha, IL-6, and IL-1beta.

Infection of BALB/c mice with a sublethal concentration of Legionella pneumophila causes an acute disease that is resolved by innate immune responses. The infection also initiates the development of adaptive Th1 responses that protect the mice from challenge infections. To study the early responses, cytokines induced during the first 24 h after infection were examined. In the serum, interleukin-12 (IL-12) was detectable by 3 h and peaked at 10 h, while gamma interferon was discernible by 5 h and peaked at 8 h. Similar patterns were observed in ex vivo cultures of splenocytes. A transient IL-4 response was also detected by 3 h postinfection in ex vivo cultures. BALB/c IL-4-deficient mice were more susceptible to L. pneumophila infection than were wild-type mice. The infection induced higher serum levels of acute-phase cytokines (tumor necrosis factor alpha [TNF-alpha], IL-1beta, and IL-6), and reducing TNF-alpha levels with antibodies protected the mice from death. Moreover, the addition of IL-4 to L. pneumophila-infected macrophage cultures suppressed the production of these cytokines. Thus, the lack of IL-4 in the deficient mice resulted in unchecked TNF-alpha production, which appeared to cause the mortality. Monocyte chemoattractant protein-1 (MCP-1), a chemokine that is induced by IL-4 during Listeria monocytogenes infection, was detected at between 2 and 30 h after infection. However, MCP-1 did not appear to be induced by IL-4 or to be required for the TNF-alpha regulation by IL-4. The data suggest that the early increase in IL-4 serves to regulate the mobilization of acute phase cytokines and thus controls the potential harmful effects of these cytokines.

Animals↗
PubMed1997

Seroepidemiological study on hepatitis delta virus infection in the Irabu Islands, Okinawa, Japan.

A seroepidemiological study was performed to clarify the prevalence of hepatitis delta virus (HDV) infection among the general population in the Irabu islands, Okinawa, Japan. Of 2028 healthy people examined who had received their annual health check-up in 1994-95, 195 (9.6%) were positive for hepatitis B surface antigen (HBsAg). Of these 195 HBsAg-positive individuals, 46 (23.6%) showed a positive reaction for antibody to HDV (anti-HDV). The positivity rate of anti-HDV among HBsAg-positive subjects tended to increase with age up to 50-59 years of age. The prevalence of anti-HDV also varied among the seven districts in the islands (0-63.3%). None of the anti-HDV-positive subjects was included in the high risk group for parenterally transmitted diseases. The unusually high prevalence of anti-HDV among HBsAg-positive individuals, particularly in the older age groups, seemed to reflect the natural prevalence or previous HDV infection, rather than a current or imported infection of HDV. Although the great majority of HBsAg-positive subjects with anti-HDV were asymptomatic, abnormally high values of serum transaminases were more frequently seen in these subjects compared with HBsAg-positive subjects without anti-HDV.

Adult↗
PubMed1995

Effects of various dopamine uptake inhibitors on striatal extracellular dopamine levels and behaviours in rats.

In vivo central effects of some dopamine uptake inhibitors were evaluated in both brain microdialysis and behavioural studies in rats, and compared with their in vitro affinities to dopamine uptake sites. IC50 values of GBR12909 (1-[2- bis(4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl)piperazine), diclofensine, mazindol, amfonelic acid and nomifensine for inhibiting 1 nM [3H]GBR12935 (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine) binding to rat striatal membrane were 7.0, 36, 81, 187 and 290 nM, respectively. In the brain microdialysis study, dopamine levels in the striatal dialysates were increased to 16.3- (GBR12909), 14.1- (nomifensine), 4.8- (diclofensine) and 1.9-fold (amfonelic acid) the respective basal levels 40-60 min after i.p. administration (0.1 mmol/kg) and thereafter decreased slowly but remained at the elevated levels for a further 3 h, while mazindol gradually increased dopamine levels though less pronouncedly than others (1.7-fold 200 min after administration). Remarkable and comparable stereotyped behaviours (licking and forepaw treading) were continuously observed at least for 3 h after administration of GBR12909, nomifensine and amfonelic acid, while stereotypies induced by diclofensine and mazindol were moderate and marginal, respectively. In vivo potencies of dopamine uptake inhibitors to increase the extracellular dopamine levels in the striatum tended to correlate with their in vitro affinities to dopamine uptake sites except in the case of nomifensine, and correlated significantly with their potencies to induce stereotyped behaviours except in the case of amfonelic acid. Based on these findings, pharmacological characteristics of these dopamine uptake inhibitors are discussed.

Animals↗
PubMed1995

Ca(2+)-dependent enhancement of [3H]dopamine uptake in rat striatum: possible involvement of calmodulin-dependent kinases.

We studied effects of Ca2+ in the incubation medium on [3H]dopamine ([3H]DA) uptake by rat striatal synaptosomes. Both the duration of the preincubation period with Ca2+ (0-30 min) and Ca2+ concentration (0-10 mM) in Krebs-Ringer medium affected [3H]DA uptake by the synaptosomes. The increase was maximal at a concentration of 1 mM Ca2+ after a 10-min preincubation (2.4 times larger than the uptake measured without preincubation), which reflected an increase in Vmax of the [3H]DA uptake process. On the other hand, [3H]DA uptake decreased rapidly after addition of ionomycin in the presence of 1 mM Ca2+. The Ca(2+)-dependent enhancement of the uptake was still maintained after washing synaptosomes with Ca(2+)-free medium following preincubation with 1 mM Ca2+. Protein kinase C inhibitors did not affect apparently Ca(2+)-dependent enhancement of the uptake, whereas 1(-)[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L- tyrosyl]-4-phenylpiperazine (KN-62; a Ca2+/calmodulin-dependent kinase II inhibitor) and wortmannin (a myosin light chain kinase inhibitor) significantly reduced it. Inhibitory effects of KN-62 and wortmannin appeared to be additive. N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7; a calmodulin antagonist) also remarkably inhibited the enhancement. These results suggest that Ca(2+)-dependent enhancement of [3H]DA uptake is mediated by activation of calmodulin-dependent protein kinases.

Animals↗
PubMed1995

[Increase in extracellular levels of serotonin and amino acids in the rat brain following cyanide-induced energy failure].

We studied the effects of ATP depletion on neurotransmitter release in the rat brain using the microdialysis method. Ringer's solution containing 2 mM sodium cyanide (NaCN) was perfused into the hippocampus and striatum for 60 min via a microdialysis probe, and changes in serotonin (5-HT) and amino acids (glutamate, aspartate and taurine) levels in dialysates were investigated. NaCN perfusion induced a transient 3.9-fold increase in 5-HT levels in the hippocampal dialysate. Amino acid levels in dialysates also increased during NaCN perfusion, but differently in the striatum and hippocampus (glutamate: 1.3- and 2.4-fold, taurine: 2.3- and 1.3-fold, respectively). Perfusion of Ca(2+)-free Ringer's solution remarkably suppressed the NaCN-induced increase in 5-HT but not the increases in amino acid levels. Depolarization by 100 mM KCl perfusion could induce increases in 5-HT and amino acids in dialysates at 3 hr after NaCN perfusion similarly with that of control. These findings indicate that the sensitivity of nerve terminals to energy failure are different between neurons containing different neurotransmitters and also between brain regions, and suggest that this regionally different sensitivity of amino acid neurons might be involved in the underlying mechanism of the localized vulnerability to transient ischemia.

Adenosine Triphosphate↗