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Biomedical subjects

A Nakane

Publications and source records attributed to A Nakane.

At least 19 recordsLinked to original sources
PubMed2004

Buthionine sulfoximine inhibits cytopathic effect and apoptosis induced by infection with human echovirus 9.

We studied the effect of buthionine sulfoximine (BSO) on the replication of an isolate of human echovirus 9 (EV9) and the apoptosis induced by it in GMK cells. One hundred microM BSO markedly inhibited the cytopathic effect (CPE) induced by EV9. BSO also significantly inhibited apoptosis induced by EV9. BSO did not influence replication of EV9 genome, but inhibited virion formation. These results suggest that the inhibition by BSO of CPE and apoptosis induced by EV9 may be associated with the impairment of virion formation. Moreover, apoptosis induced by infections of human poliovirus 3, human coxsackievirus B5, A10 and A16, which, like EV9, belong to the genus Enterovirus, was markedly abolished by BSO. This finding suggests that enteroviral infections cause apoptosis through the activation of a common pathway that can be inhibited by BSO.

Animals↗
PubMed2001

Tubularized incised-plate urethroplasty for secondary hypospadias surgery.

PURPOSE: Reoperation for failed hypospadias has been considered to be seriously bothersome because abundant penile skin does not tend to remain for urethroplasty or for penile shaft skin coverage. In this study, the tubularization of incised urethral plate was employed for those who had no excessive penile skin after failure of hypospadias repair. METHODS: Five patients with hypospadias underwent tubularized incised-plate urethroplasty as salvage surgery. The surgical techniques necessary for the performance of the reoperation were not different from those for the primary repair. The urethral plate was incised sufficiently deeply in its midline from the tip of the glans to the regressed meatus. The incised urethral plate was tubularized without tension over a catheter of an appropriate size. RESULTS: Four of those who underwent secondary tubularized incised-plate urethroplasty were successfully repaired without complications. A urethrocutaneous fistula occurred at the corona in the remaining patient. CONCLUSIONS: The absence of preputial skin in reoperative cases makes tubularized incised-plate urethroplasty the ideal option, although the series was small and postoperative duration is still short. In addition, this procedure can give excellent functional and cosmetic results even in patients who require revisional hypospadias surgery.

Adolescent↗
PubMed2001

The modified Koyanagi repair for severe proximal hypospadias.

OBJECTIVE: To report the method and results of a modified one-stage Koyanagi repair (urethroplasty with a parameatal-based and fully extended circumferential foreskin flap) to preserve the vascularity to the peripheral portion of the neourethra, in the repair of severe hypospadias. PATIENTS AND METHODS: Using a skin-incision line as in the original Koyanagi repair, a circumferential incision is made approximately 5 mm proximal to the corona and the urethral plate incised as for repair of chordee. A U-shaped skin incision is then made surrounding the meatus, extended to the dorsal prepuce for approximately 8 mm and parallel to the first incision. The tissue between the prepuce and dartos is dissected on the dorsal side to fix the prepuce as a neourethra to the dartos and to maintain blood supply. After mobilizing the loop-shaped skin flap through the button-hole of the pedicle, the internal and external sides of the loop are sutured to construct a neourethra. Twenty patients (aged 10 months to 9 years) with severe proximal hypospadias underwent the one-stage modified Koyanagi repair. RESULTS: The repair was successful after the initial procedure in 14 patients, but urethrocutaneous fistulae developed in three and meatal stenosis in three. The overall success rate was thus 70%. CONCLUSIONS: There were fewer complications than reported with the original Koyanagi repair, suggesting that the attempted vascular preservation of the neourethra was effective.

Child↗
PubMed2001

Effect of 6-hydroxydopamine on host resistance against Listeria monocytogenes infection.

Recent studies have shown that immunocompetent cells bear receptors of neuropeptides and neurotransmitters and that these ligands play roles in the immune response. In this study, the role of the sympathetic nervous system in host resistance against Listeria monocytogenes infection was investigated in mice pretreated with 6-hydroxydopamine (6-OHDA), which destroys sympathetic nerve termini. The norepinephrine contents of the plasma and spleens were significantly lower in 6-OHDA-treated mice than in vehicle-treated mice. The 50% lethal dose of L. monocytogenes was about 20 times higher for 6-OHDA-treated mice than for vehicle-treated mice. Chemical sympathectomy by 6-OHDA upregulated interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) production in enriched dendritic cell cultures and gamma interferon (IFN-gamma) and TNF-alpha production in spleen cell cultures, whereas chemical sympathectomy had no apparent effect on phagocytic activities, listericidal activities, and nitric oxide production in peritoneal exudate cells and splenic macrophages. Augmentation of host resistance against L. monocytogenes infection by 6-OHDA was abrogated in IFN-gamma(-/-) or TNF-alpha(-/-) mice, suggesting that upregulation of IFN-gamma, IL-12, and TNF-alpha production may be involved in 6-OHDA-mediated augmentation of antilisterial resistance. Furthermore, adoptive transfer of spleen cells immune to L. monocytogenes from 6-OHDA-treated mice resulted in untreated naive recipients that had a high level of resistance against L. monocytogenes infection. These results suggest that the sympathetic nervous system may modulate host resistance against L. monocytogenes infection through regulation of production of IFN-gamma, IL-12, and TNF-alpha, which are critical in antilisterial resistance.

Adoptive Transfer↗
PubMed2001

Interference between host resistance to Listeria monocytogenes infection and ovalbumin-induced allergic responses in mice.

Listeria monocytogenes promotes the induction of the T-helper 1 (Th1) cell response, while ovalbumin (OVA) induces a Th2 cell response and allergic reactions, such as airway hyperreactivity and immunoglobulin E (IgE) production. When mice were immunized with OVA on day 7 after L. monocytogenes infection, eosinophilia in bronchoalveolar lavage and the production of total IgE, OVA-specific IgE, interleukin-4 (IL-4), and IL-5 in the circulation were markedly suppressed. Cytokine responses, including IL-4, IL-5, IL-10, IL-13, and gamma interferon, to OVA were decreased in the spleen cell cultures obtained from OVA-immunized mice that had been infected with L. monocytogenes. Conversely, when OVA-immunized mice were infected with L. monocytogenes, conversion from the nonlethal infection to the lethal infection occurred. Host resistance to L. monocytogenes infection in OVA-immunized mice was enhanced by the administration of anti-IL-10 monoclonal antibody. The present study indicates that striking interference is observed between Th1-inducing L. monocytogenes infection and Th2-driven OVA-induced airway hyperreactivity.

Animals↗
PubMed2001

Disruption of the genes for ClpXP protease in Salmonella enterica serovar Typhimurium results in persistent infection in mice, and development of persistence requires endogenous gamma interferon and tumor necrosis factor alpha.

The enteric pathogen Salmonella enterica serovar Typhimurium, similar to other facultative intracellular pathogens, has been shown to respond to the hostile conditions inside macrophages of the host organism by producing a set of stress proteins that are also induced by various environmental stresses. The stress-induced ClpXP protease is a member of the ATP-dependent proteases, which are known to be responsible for more than 90% of all proteolysis in Escherichia coli. To investigate the contribution of the ClpXP protease to the virulence of serovar Typhimurium we initially cloned the clpP and clpX operon from the pathogenic strain serovar Typhimurium chi3306 and then created insertional mutations in the clpP and/or clpX gene. The Delta clpP and Delta clpX mutants were used to inoculate BALB/c mice by either the intraperitoneal or the oral route and found to be limited in their ability to colonize organs of the lymphatic system and to cause systemic disease in the host. A variety of experiments were performed to determine the possible reasons for the loss of virulence. An oxygen-dependent killing assay using hydrogen peroxide and paraquat (a superoxide anion generator) and a serum killing assay using murine serum demonstrated that all of the serovar Typhimurium Delta clpP and Delta clpX mutants were as resistant to these killing mechanisms as the wild-type strain. On the other hand, the macrophage survival assay revealed that all these mutants were more sensitive to the intracellular environment than the wild-type strain and were unable to grow or survive within peritoneal macrophages of BALB/c mice. In addition, it was revealed that the serovar Typhimurium ClpXP-depleted mutant was not completely cleared but found to persist at low levels within spleens and livers of mice. Interferon gamma-deficient mice and tumor necrosis factor alpha-deficient mice failed to survive the attenuated serovar Typhimurium infections, suggesting that both endogenous cytokines are essential for regulation of persistent infection with serovar Typhimurium.

Adenosine Triphosphatases↗
PubMed2001

Molecular cloning and characterization of the fructooligosaccharide-producing beta-fructofuranosidase gene from Aspergillus niger ATCC 20611.

The fopA gene encoding a fructooligosaccharide-producing beta-fructofuranosidase was isolated from Aspergillus niger ATCC 20611. The primary structure deduced from the nucleotide sequence showed considerable similarity to those of two other beta-fructofuranosidases from A. niger, but the fopA gene product had several amino acid insertions and an extra C-terminal polypeptide consisting of 38 amino acids that could not be found in the two others. We could successfully express the fopA gene in S. cerevisiae and the fopA gene product obtained from the culture supernatant of the S. cerevisiae transformant had similar characteristics to the beta-fructofuranosidase purified from A. niger ATCC 20611. However, we could not detect any beta-fructofuranosidase activity in either the culture supernatant or cell lysate when the C-terminal truncated fopA gene product by 38 amino acids was used to transform S. cerevisiae. In western analysis of those samples, there was no protein product that is cross-reacted with anti-beta-fructofuranosidase antibody. These results suggested that the C-terminal region of the fopA gene product consisting of 38 amino acids was essential for the enzyme production.

Amino Acid Sequence↗
PubMed2001

Analysis of the epitopes on staphylococcal enterotoxin A responsible for emetic activity.

To identify which region of staphylococcal enterotoxin A (SEA) is responsible for the emetic activity, twelve synthetic peptides corresponding to the entire SEA amino acid sequence and their respective anti-peptide antibodies were prepared and tested. The anti-peptide antibodies were tested for neutralization of SEA-induced emesis in Suncus murinus (Shrew mouse). The results indicate that SEA-induced emesis was neutralized by the mixture of three anti-peptide antibodies to A-7 (corresponding to amino acid residues 121-140), A-8 (141-160) and A-9 (160-180). These findings suggest that the regions corresponding to residues 121-180 may be the epitopes responsible for the emetic activity of SEA.

Animals↗
PubMed2000

Congenital urethrocutaneous fistula.

BACKGROUND: A 3-year-old boy visited our hospital for aberrance of urination. He had a fistula on his ventral penile shaft. Our diagnosis was congenital urethrocutaneous fistula. METHODS/RESULTS: We performed one-stage repair transverse preputial onlay island flap urethroplasty. Postoperatively, the patient was voiding comfortably with no recurrence of fistula. CONCLUSIONS: Congenital urethrocutaneous fistula is rare. Eighteen cases of congenital urethrocutaneous fistula have been reported previously. We consider the etiology of congenital urethrocutaneous fistula as a deficiency of the urethral plate and fusion of urethral folds.

Child, Preschool↗
PubMed2000

Anaerobic bacterial extracts influence production of matrix metalloproteinases and their inhibitors by human dental pulp cells.

The role of human dental pulp (HDP) cells in extracellular matrix degradation in pulpitis is still unclear. In this study, the effects of sonicated bacterial extracts (SBEs) from Prevotella intermedia, Fusobacterium nucleatum, Porphyromonas endodontalis, and Porphyromonas gingivalis on the balance between the production of matrix metalloproteinases (MMPs) and that of their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] by HDP cells were examined. HDP cells were treated with SBEs, and their culture media were later harvested. MMP activities and TIMP concentrations were determined by use of independent measurement strategies and sensitive ELISAs. The production of MMP-1 and MMP-2 was accelerated by all SBE. On the other hand, TIMP-1 production was slightly elevated; and TIMP-2 production was markedly inhibited by all of the extracts. SBEs derived from these anaerobic bacteria seemed to affect the acceleration of extracellular matrix degradation activity by HDP cells. These findings suggest that HDP cells stimulated by bacterial byproducts may be involved in the pathogenesis of pulpitis.

Bacteria, Anaerobic↗
PubMed2000

Roles of endogenous cytokines in liver apoptosis of mice in lethal Listeria monocytogenes infection.

Various bacterial pathogens have been identified as mediators of apoptosis. Apoptosis reportedly shows both detrimental and beneficial effects on biological functions. We studied the role of liver apoptosis in lethal Listeria monocytogenes infection and the regulation of apoptosis by endogenous cytokines during infection. Apoptosis was observed in the spleen but not in the liver of infected mice, whereas the induction of liver necrosis was evident by rising levels of serum aminotransferases in these animals. Apoptosis was detected in the liver of L. monocytogenes-infected mice which had been treated with monoclonal antibody (mAb) against tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6), or in TNF-alpha(-/-) mice, but not in gamma- interferon (IFN-gamma)(-/-) mice or mice which had been treated with mAb against IL-4 or IL-10. Augmentation of liver apoptosis in mice treated with mAb against TNF-alpha or IL-6 or in TNF-alpha(-/-) mice correlated with the increase in bacterial numbers in the organ, while no augmentation of apoptosis was observed in the liver of IFN-gamma(-/-) mice irrespective of the marked increase in bacterial numbers in the organs, indicating that augmentation of liver apoptosis may not be merely due to the increase in bacterial growth in the organs. These results suggest that TNF-alpha and IL-6 may play an important role in protecting the liver from apoptosis in lethal L. monocytogenes infection.

Animals↗
PubMed2000

Effect of a matrix metalloproteinase inhibitor on host resistance against Listeria monocytogenes infection.

Hydroxy acid-based matrix metalloproteinase (MMP) inhibitors have been shown to inhibit tumor infiltration and growth, endotoxin shock, and acute graft-versus-host disease. Blockade of the release of soluble tumor necrosis factor-alpha (TNF-alpha) and CD95 ligand (CD95L; FasL) from cell-associated forms is reportedly involved in the mechanism of the drug effect. We investigated the effect of a MMP inhibitor, KB-R7785, on host resistance against Listeria monocytogenes infection, in which TNF-alpha is essentially required for the defense, in mice. The administration of KB-R7785 exacerbated listeriosis, while the drug prevented lethal shock induced by lipopolysaccharide and D-galactosamine. KB-R7785 inhibited soluble TNF-alpha production in spleen cell cultures stimulated by heat-killed L. monocytogenes and the drug treatment reduced serum TNF-alpha levels in infected mice, whereas the compound was ineffective on the modulation of interferon-gamma and interleukin-10 production. The effect of KB-R7785 was considered to be dependent on TNF-alpha because the drug failed to affect L. monocytogenes infection in anti-TNF-alpha monoclonal antibody-treated mice and TNF-alpha knockout mice. Anti-CD95L monoclonal antibody was also ineffective on the infection. These results suggest that induction of infectious diseases, to which TNF-alpha is critical in host resistance, should be considered in MMP inhibitor-treated hosts.

Animals↗
PubMed2000

Interleukin-4 and interleukin-10 are involved in host resistance to Staphylococcus aureus infection through regulation of gamma interferon.

Our previous study showed that gamma interferon (IFN-gamma), a T-helper 1 (Th1)-type cytokine, plays a detrimental role in Staphylococcus aureus infection in mice. In this study, the role of Th2-type cytokines such as interleukin-4 (IL-4) and IL-10 in S. aureus infection was investigated. IL-10 mRNA was induced in parallel with IFN-gamma in the spleens and kidneys of mice during S. aureus infection, whereas IL-4 mRNA was induced in the spleens but not in the kidneys of these animals. Spleen cells obtained from S. aureus-infected mice produced lower titers of IFN-gamma and higher titers of IL-4 and IL-10 in response to heat-killed S. aureus than did those from uninfected mice. Administration of anti-IL-4 monoclonal antibody (MAb) or anti-IL-10 MAb inhibited the elimination of S. aureus cells from the kidneys of mice. IFN-gamma mRNA expression was enhanced in the spleens of anti-IL-4 MAb- or anti-IL-10 MAb-treated mice and also in the kidneys of anti-IL-4 MAb-treated animals. Next, we evaluated the role of IFN-gamma in S. aureus infection in IFN-gamma(-/-) mice. An increase in survival rates, a decrease in bacterial numbers in the kidneys, and an amelioration of histologic abnormalities in these organs were observed in IFN-gamma(-/-) mice compared with those in IFN-gamma(+/+) mice. Administration of MAb against IL-4 or IL-10 failed to affect bacterial growth in the spleens and kidneys of IFN-gamma(-/-) mice irrespective of the expression of Th2 response. These results suggest that S. aureus infection induced a Th2 response and that IL-4 and IL-10 might play a protective role through the regulation of IFN-gamma in S. aureus infection.

Animals↗
PubMed2000

Host resistance to Listeria monocytogenes infection is enhanced but resistance to Staphylococcus aureus infection is reduced in acute graft-versus-host disease in mice.

Acute graft-versus-host disease (GVHD) is characterized by the production of high levels of T helper 1 (Th1)-type cytokines. Bone marrow transplantation from allogeneic C57BL/6 cells to CBF(1) mice produced acute GVHD. Host resistance to Th1-driven Listeria monocytogenes was enhanced, whereas host resistance to Th2-driven Staphylococcus aureus was reduced during acute GVHD. These results suggest that opposite host responses are observed between Th1-driven and Th2-driven bacterial infections in acute GVHD.

Acute Disease↗
PubMed1999

Studies on the functional site on staphylococcal enterotoxin A responsible for production of murine gamma interferon.

To identify the functional region(s) associated with induction of gamma interferon on the staphylococcal enterotoxin A molecule, native staphylococcal enterotoxin A molecules and 12 various synthetic peptides corresponding to different regions of entire staphylococcal enterotoxin A were compared to induce gamma interferon production in murine spleen cells. The native staphylococcal enterotoxin A molecule induced gamma interferon production, whereas all of the 12 synthetic peptides did not. Pre-treatment of the murine spleen cells with synthetic peptide A-9 (corresponding to amino acid residues 161-180) significantly inhibited the staphylococcal enterotoxin A-induced gamma interferon production, whereas those with other synthetic peptides did not. When native staphylococcal enterotoxin A was pre-treated with either anti-staphylococcal enterotoxin A serum or anti-peptide sera, anti-staphylococcal enterotoxin A serum and antisera to peptides A-1 (1-20), A-7 (121-140), A-8 (141-160), A-9 (161-180) and A-10 (181-200) inhibited the staphylococcal enterotoxin A-induced gamma interferon production. From these findings, the amino acid residues 161-180 on the staphylococcal enterotoxin A molecule may be an essential region for murine gamma interferon production. Furthermore, the neutralizing epitopes may be also located on regions of amino acid residues 1-20, 121-140, 141-160 and 181-200 on the staphylococcal enterotoxin A molecule.

Amino Acid Sequence↗
PubMed1999

Endogenous cytokines during a lethal infection with Listeria monocytogenes in mice.

It has been demonstrated that endogenous cytokines including gamma interferon (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) play protective roles but that IL-4 and IL-10 play detrimental roles in nonlethal Listeria monocytogenes infection in mice. In this paper, we studied the roles of endogenous cytokines in a lethal infection with L. monocytogenes in mice. TNF-alpha and IL-6 titres in the bloodstreams, spleens and livers paralleled bacterial numbers in the organs, and both these cytokines and the bacterial numbers peaked just before the mice died. The high titres of TNF-alpha notably detected in the circulation in lethal infection were different from those in nonlethal infection. The maximum production of IFN-gamma was observed before the peaks of TNF-alpha and IL-6, and IFN-gamma almost disappeared from the bloodstreams and organs just before the mice died. No notable difference of IFN-gamma titres between lethal infection and nonlethal infection in the specimens obtained from mice was observed. IL-10 was also detected in the bloodstreams earlier than the peaks of TNF-alpha and IL-6 during lethal infection, while IL-4 was never detected in the sera. The administration of monoclonal antibodies (mAbs) against TNF-alpha, IFN-gamma, IL-6, IL-4 or IL-10 failed to rescue mice from lethal L. monocytogenes infection, whereas anti-TNF-alpha mAb and anti-IFN-gamma mAb prevented mice from lethality by high-dose endotoxin shock. These results suggest that lethality in L. monocytogenes infection might not be determined solely by these cytokines.

Animals↗