Biomedical subjects

Yoshitaka Tamura

Publications and source records attributed to Yoshitaka Tamura.

18 recordsLinked to original sources

PubMed2006

Modulation of immunity-related gene expression in small intestines of mice by oral administration of lactoferrin.

Oral administration of lactoferrin (LF), an antimicrobial and immunomodulatory protein, shows a protective effect against infectious diseases, possibly via immunomodulation of the host. Initially, we confirmed an immunomodulatory effect of LF by observing changes in the number of cells in the leukocyte subsets in the peripheral blood and spleens of mice 1 day after oral administration of LF. Then we developed a quantitative reverse transcription-PCR method for 20 immunity-related genes of antimicrobial proteins, pattern recognition receptors, cytokines, and lymphocyte mobilization-related proteins, and we assessed the expression of these genes in the small intestines of mice 2 h after administration of water, bovine serum albumin (BSA), or LF. Expression of the LF gene was lower in mice administered LF than in mice administered water or BSA, implying a negative-feedback control. Expression of gamma interferon (IFN-gamma) and interleukin-10 (IL-10) was lower in both BSA- and LF-administered mice than in water administered mice, suggesting a nonspecific effect of protein ingestion. Expression of NOD2, IFN-beta, and IL-12p40 was higher with LF administration than with water or BSA administration. The expression levels of these three genes were correlated. This study indicated that oral administration of LF modulates the small intestinal expression of genes closely related to the host defense in a specific or a nonspecific manner.

Administration, Oral↗

PubMed2006

16-MDCT aortography with a low-dose contrast material protocol.

OBJECTIVE: The objective of our study was to evaluate whether a low-dose contrast material (CM) protocol with a saline flush might provide sufficient contrast enhancement in aortoiliac 16-MDCT angiography. SUBJECTS AND METHODS: Forty-five patients were divided into two groups on the basis of the CM (300 mg I/mL) administration protocol: group 1 (23 patients) received 100 mL of CM at 3.0 mL/sec; and group 2 (22 patients), 50 mL of CM at 3.0 mL/sec followed by a 20-mL saline flush at 3.0 mL/sec. All patients underwent 16-MDCT angiography of the entire aortoiliac region. Seven regions of interest (ROIs) were drawn from the ascending aorta (ROI 1) to the external iliac artery (ROI 7). Quantitative analysis was performed by calculating the mean aortoiliac attenuation and the mean difference between the maximum and minimum attenuation values. Vascular enhancement of the renal arteries was visually assessed using 2D and 3D postprocessing techniques. RESULTS: The mean aortoiliac attenuation in group 1 was 314.3 +/- 45.9 H and that in group 2 was 306.1 +/- 35.0 H. The difference was not statistically significant. Adequate mean aortoiliac attenuation was achieved in 95.7% (22/23) and 95.5% (21/22) of patients in groups 1 and 2, respectively. The difference was not statistically significant. The mean difference between the maximum and minimum attenuation values was significantly smaller in group 1 (41.3 +/- 16.8 H) than in group 2 (57.2 +/- 25.3 H). The renal arteries were assessable in all patients in both groups. CONCLUSION: This protocol of 50 mL of CM with a saline flush provides attenuation comparable to that obtained with the 100 mL of CM in aortoiliac 16-MDCT angiography.

Aged↗

PubMed2005

Bovine lactoferrin is effective to suppress Helicobacter pylori colonization in the human stomach: a randomized, double-blind, placebo-controlled study.

Bovine lactoferrin (bLF) has antibacterial activity against Helicobacter pylori in vitro and is effective to suppress bacterial colonization in mice. The aim of our study was to evaluate the efficacy of orally administered bLF on H. pylori colonization in humans by a randomized, double-blind, placebo-controlled study. Fifty-nine healthy subjects positive for H. pylori infection were recruited. Subjects were randomized into two groups. The bLF group received bLF tablets at a dosage of 200 mg b.i.d. for a period of 12 weeks, and the control group received placebo tablets without bLF. The (13)C-urea breath test (UBT) was performed before, during, and at the end of administration, and again 4 weeks after administration. Positive response was defined as more than 50% decrease of the UBT value at the end of administration. Positive response was observed in 10 of 31 bLF-treated subjects (32.3%) and 1 of 28 control subjects (3.6%), indicating that the rate of positive response in the bLF group was significantly higher than that in the control group (bLF vs. control, P < 0.01). These results suggested that bLF administration is effective to suppress H. pylori colonization.

Adolescent↗

PubMed2005

Effects of orally administered bovine lactoferrin and lactoperoxidase on influenza virus infection in mice.

Milk contains a wide variety of host protective factors against infectious microbes. Among these protective factors, lactoferrin (LF) and lactoperoxidase (LPO) have been reported to exhibit antiviral activities as well as immuno-modulatory effects. In the present study, the effects of orally administered LF and LPO were assessed in a mouse influenza virus infection model. BALB/c mice were intranasally infected with 6.6x10(2) p.f.u. of influenza virus A/PR/8/34(H1N1). Bovine LF or LPO was administered once daily at a dose of 62.5 mg per mouse by gavage, starting 1 day before infection. Mice given LF or LPO showed a significantly lower lung consolidation score on day 6 after infection compared with the control mice that were given water instead. Concurrently, the number of infiltrated leukocytes recovered from bronchoalveolar lavage fluid (BALF) on day 6 was significantly lower in mice given LF or LPO. However, the virus yield in the BALF was not affected by these treatments. The serum level of IL-6, a pro-inflammatory cytokine, positively correlated with the lung consolidation score in each group and was significantly lower on day 6 in the mice given LPO. These results suggest the potential of oral administration of LF or LPO to attenuate pneumonia in influenza-virus-infected mice through the suppression of infiltration of inflammatory cells in the lung.

Administration, Oral↗

PubMed2005

Polymerase chain reaction--restriction fragment length polymorphism analysis of clarithromycin-resistant Helicobacter pylori infection in children using stool sample.

BACKGROUND: To analyze clarithromycin-resistant Helicobacter pylori infection in children, we developed a method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis using stool samples. MATERIALS AND METHODS: Twenty-three children without significant upper abdominal symptoms were included (mean age 7.0 years). Of these, 18 and five were diagnosed as H. pylori-positive and -negative, respectively, by the H. pylori stool antigen test (HpSA). The DNA from the stool samples was purified using the QIAamp DNA Stool Minikit (QIAGEN). The PCR was performed on the purified DNA using oligonucleotide primers designed to amplify the 23S rRNA gene of H. pylori. The PCR products were reacted with restriction enzymes MboII, BceAI, and BsaI to detect mutations A2142G, A2142C, and A2143G, respectively. RESULTS: Sixteen of the 18 HpSA-positive samples were PCR-positive, and all five HpSA-negative samples were PCR-negative. Thus, the PCR had 89% sensitivity and 100% specificity, with 91% accuracy in reference to HpSA. Of the 16 PCR-positive samples, one and four were digested with MboII and BsaI, respectively, indicating 31% prevalence of CAM-resistance. CONCLUSIONS: We conclude that the PCR-RFLP using stool samples is a rapid and reliable method to noninvasively detect clarithromycin-resistant H. pylori infection in children. It may be useful before choosing regimens of H. pylori eradication.

Adolescent↗

PubMed2004

Administration of macrophage colony-stimulating factor mobilized both CD11b+CD11c+ cells and NK1.1+ cells into peripheral blood.

We attempted the phenotypic characterization of peripheral blood (PB) cells after daily administration of macrophage colony-stimulating factor (M-CSF) in mice. The number of CD11b+ cells was increased by M-CSF treatment (2- and 5-day injections). Notably, CD11bbrightCD11cdim, CD11b+CD11c+ and CD11b+CD80+ cells were significantly increased by 2-day treatment of M-CSF. On the other hand, the number of NK1.1+ cells was not changed by the 2-day treatment, but it was significantly increased by the 5-day treatment. However, the numbers of CD3+ and NK1.1+CD3+ cells were not changed by M-CSF treatment. Then, mononuclear cells (MNCs) were separated from the PB of mice treated with saline or M-CSF, and they were incubated with GM-CSF + IL-4 or IL-2. Compared with the saline-treated one (S-MNCs), the MNCs of M-CSF-treated mice (M-MNCs) showed strong proliferation by the GM-CSF + IL-4 stimulation. The MNCs could stimulate proliferation of allo-T cells in the mixed lymphocyte reaction (MLR), especially the M-MNCs showed strong reaction. On the other hand, the stimulation by IL-2 induced strong cell growth of MNCs. And M-CSF treatment enhanced this response. Furthermore, the M-MNCs (stimulated by IL-2 in vitro) exhibited greater cytotoxicity against Yac-1 cells than the S-MNCs. In conclusion, we found that administration of M-CSF mobilized CD11b+, CD11b+CD11c+, CD11b+CD80+, and NK1.1+cells into PB. And the injection of M-CSF facilitates the generation of dendritic and natural killer cells from PB cells in vitro. These results suggest that the mobilized cells may provide for application of immunotherapy.

Animals↗

PubMed2004

Protection against infections by oral lactoferrin: evaluation in animal models.

It has been reported previously that oral administration of lactoferrin (LF) provides some host-protective effects against infections, cancers, and inflammations. In this review, we focus on the effect of oral LF on various infectious diseases and discuss the mechanism as elucidated in animal models. In the case of infections occurring at sites other than the digestive canal, it is unclear whether oral LF is absorbed from the intestine and exerts its protective effect at the site of infection. In preterm human infants, neonatal pigs, and rats with colitis, it was reported that LF is detectable in various body fluids after oral administration. We could not detect the transport of oral bovine LF into the blood of adult rats without gastrointestinal illness using several techniques, suggesting that there is an extremely low level of transport of LF, if any. Orally administered LF may act at the oro-gastro-intestinal mucosa and aid the defense system against infections through a network of mucosal immunity and systemic immunity. Indeed, it is reported that oral LF increases the number of cells in the leukocyte subset and cytokine (IFN-gamma and IL-18) production in the intestinal mucosa of mice. Regarding systemic immunity, we have observed an increase of leukocyte number, cytokine (IFN-gamma, TNF-alpha, IL-12, and IL-18) production, and effector activity of macrophages in response to LF administration in several animal models. These enhanced immune responses may contribute to eradication of the pathogen, resolution of the symptoms, and maintenance of the homeostasis during infectious diseases.

Administration, Oral↗

PubMed2004

Effect of orally administered bovine lactoferrin on the immune response in the oral candidiasis murine model.

Therapeutic activity against oral candidiasis of orally administered bovine lactoferrin (LF), a multifunctional milk protein, was shown in a previous report using an immunosuppressed murine model. In the present study, the influence of orally administered LF on immune responses relevant to this therapeutic effect was examined. Because mice were immunosuppressed with prednisolone 1 day before and 3 days after the infection with Candida, the numbers of peripheral blood leukocytes (PBL) and cervical lymph node (CLN) cells were reduced. LF feeding prevented the reduction in the numbers of PBL on day 1 and CLN cells on days 1, 5 and 6 in the Candida-infected mice. The number of CLN cells of individual mice on days 5 and 6 was inversely correlated with the Candida c.f.u. in the oral cavity. Increased production of IFN-gamma and TNF-alpha by CLN cells stimulated with heat-killed Candida albicans on day 6 was observed in LF-treated mice compared with non-treated mice. Concanavalin A (ConA)-stimulated CLN cells from LF-treated mice also showed a significant increase in the production of IFN-gamma and IL12 on day 5 and a tendency for increased production of IFN-gamma and TNF-alpha on day 6. The levels of cytokine production by ConA-stimulated CLN cells on day 6 were inversely correlated with the Candida c.f.u. in the oral cavity. In conclusion, the alleviation of oral candidiasis by LF feeding in this model may correlate with the enhancement of the number of leukocytes and their cytokine responses in regional lymph nodes against Candida infection.

Adjuvants, Immunologic↗

PubMed2004

Oral lactoferrin prevents body weight loss and increases cytokine responses during herpes simplex virus type 1 infection of mice.

Lactoferrin (LF), a multifunctional milk protein, is known to inhibit in vitro infection by viruses such as herpes simplex virus type 1 (HSV-1). We evaluated the influence of LF feeding on the HSV-1 cutaneous infection of mice. Bovine LF was administered to mice and, after 10 d, the mice were infected with HSV-1. LF administration did not affect the viral clearance in the skin, but inhibited the appearance of skin lesions. LF prevented body weight loss and the decrease of splenocyte number associated with HSV-1 infection. LF increased the serum interleukin (IL)-18 level and splenocyte production of interferon-gamma and IL-12. These results suggest that LF feeding was not effective for eradication of the virus, but may contribute to the maintenance of homeostasis and the concomitant increases of cytokine responses during HSV-1 infection.

Administration, Oral↗

PubMed2004

No detectable transfer of dietary lactoferrin or its functional fragments to portal blood in healthy adult rats.

We investigated the transfer of dietary bovine lactoferrin (LF) and its functional lactoferricin (LFcin) B-containing fragments to the portal blood of healthy adult rats by using several techniques. After a single administration of (125)I-labeled LF, radioactive bands were detected in autoradioluminograms of the portal blood, but similar bands were also observed after the administration of [(125)I]NaI. Although ovalbumin was detected by ELISA at 3-18 ng/ml in the portal blood plasma after an overnight administration, no LF was detected (< or =1.5 ng/ml). The antibody-captured ovalbumin fragments, but not the LF fragments, were detected in the plasma by surface-enhanced laser desorption/ionization affinity mass spectrometry (SELDI affinity MS). We finally attempted to detect the LFcin B-containing fragments by SELDI affinity MS with on-chip LFcin B-conversion, but could not detect them (< or =1 ng/ml) in the portal blood after the LF ingestion. The level of LF or its functional fragments transferred to the portal blood was therefore extremely low, if any.

Aging↗

PubMed2004

The characteristics of people requesting HIV antibody tests at public health centers in Japan.

BACKGROUND: The epidemiologic features of those who requested to undergo the human immunodeficiency virus (HIV) antibody test at public health centers in Japan are still ambiguous, although as a group, they are probably at a high risk to be infected. METHODS: Between April 2001 and March 2002, 14,900 persons visited 131 public health centers that cooperated with this study in relation to the HIV antibody tests. A questionnaire was given to 8,972 persons who agreed to participate in the survey and 5,079 (56.6%) returned the form. Excluding those filled out by persons whose true intent in undergoing the test was the diagnosis of hepatitis C, 4,102 questionnaires were analyzed, individual characteristics examined, and first time visitors and repeaters were compared to assess their behavior and the reasons for of undergoing the test. RESULTS: There were 2,515 (61.3%) males and 1,587 (38.7%) females. The largest age group was composed of 25 to 29 year-olds. Repeaters accounted for 27.2% of all the males and 21.3% of all the females. Their main reason for undergoing the test was anxiety about having contracted an HIV infection through sexual contact with a person of the opposite sex. The proportion of those having sexual contact with males was significantly higher among male repeaters (14.1%) than first timers (8.0%). Among females, the proportion of those who had experience of sexual contact with many and unspecified males was significantly higher for repeaters (39.6%) than first timers (27.3%). CONCLUSION: It was evident from this study that repeaters exist among those who seek to be examined for possible contraction of HIV: they are characterized by risk-taking behavior in contracting an HIV infection through sexual contact.

AIDS Serodiagnosis↗

PubMed2004

[Lactoferrin].

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Adult↗

PubMed2003

Effects of dietary sphingomyelin on central nervous system myelination in developing rats.

Human milk contains sphingomyelin (SM) as a major component of the phospholipid fraction. Galactosylceramide (cerebroside), a metabolite of sphingolipids, increases along with CNS myelination, and is generally considered a universal marker of myelination in all vertebrates. l-Cycloserine (LCS) is an inhibitor of serine palmitoyltransferase (SPT), a rate-limiting enzyme for sphingolipid biosynthesis that is reported to show increased activity with development of the rat CNS. The present study examined the effects of dietary SM on CNS myelination during development in LCS-treated rats. From 8 d after birth, Wistar rat pups received a daily s.c. injection (100 mg/kg) of LCS. From 17 d after birth, the animals were fed an 810 mg/100g of bovine SM-supplemented diet (SM-LCS group) or a nonsupplemented diet (LCS group). At 28 d after birth, the animals were killed and subjected to biochemical and morphometric analyses. The myelin dry weight, myelin total lipid content, and cerebroside content were significantly lower in the SM-LCS and LCS groups than in a group not treated with LCS (the non-LCS group). However, these levels were significantly higher in the SM-LCS group than in the LCS group. Morphometric analysis of the optic nerve revealed that the axon diameter, nerve fiber diameter, myelin thickness, and g value (used to compare the relative thickness of myelin sheaths around fibers of different diameter) were significantly lower in the LCS group than in the other groups, but were similar in the SM-LCS and non-LCS groups. These findings suggest that dietary SM contributes to CNS myelination in developing rats with experimental inhibition of SPT activity corrected].

Acyltransferases↗

PubMed2003

Lactoferrin feeding augments peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans.

Oral administration of lactoferrin (LF), an innate-defense protein present in exocrine secretions such as milk and in neutrophils, is reported to improve host-protection against infections with microorganisms including pathogenic fungi, possibly due to an immunomodulatory effect. This study aimed to evaluate the effect of bovine LF feeding on peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans. Time course analysis during the 14 days following Candida-priming revealed that LF administration slightly increased the number of peritoneal exudate cells, and significantly enhanced the production of superoxide anion (O2(-)) and nitric oxide (NO) by peritoneal macrophages at day 7. LF administration facilitated NO production and Candida hyphal-growth inhibition by macrophages derived from Candida-primed mice but not non-primed mice, suggesting that the action of LF is dependent on the immune status of the host. LF administration altered the kinetics of cytokines in the peritoneal lavage fluid of Candida-primed mice. Enhancement of cytokine levels by LF was observed for IL-12 at day 5 and IFN-gamma at day 9, but not for TNF-alpha or IL-10. In conclusion, LF feeding augmented the activities of macrophages in a manner dependent on Candida-priming and these effects may be related to enhanced cytokine levels.

Animals↗

PubMed2003

Oral lactoferrin treatment of experimental oral candidiasis in mice.

We assessed the potential of lactoferrin (LF), a multifunctional milk protein, for treatment of oral candidiasis with immunosuppressed mice, which have local symptoms characteristic of oral thrush. Oral administration of bovine LF in drinking water starting 1 day before the infection significantly reduced the number of Candida albicans in the oral cavity and the score of lesions on the tongue on day 7 after the inoculation. The symptomatic effect of LF was confirmed by macroscopic and microscopic observations of the tongue's surface. Similar effects were also observed upon administration of LF pepsin hydrolysate, but not lactoferricin B, an antimicrobial peptide of LF. The anticandidal activity of LF was evident on administration either in drinking water or by intragastric intubation with a stomach tube. These results suggest that the effect of LF in this oral candidiasis model is not due to direct antifungal action. In conclusion, LF could have potential as a food component supporting antifungal drug treatment.

Administration, Oral↗

PubMed2002

Isolation and identification of DPPH radical scavenging compounds in Kurosu (Japanese unpolished rice vinegar).

Dihydroferulic acid (DFA) and dihydrosinapic acid (DSA) were isolated from Kurosu (unpolished rice vinegar) as the major constituents responsible for Kurosu's radical scavenging activity. The levels of antioxidative activity of DFA and DSA in DPPH radical scavenging were higher than those of their respective structurally related compounds, ferulic acid and sinapic acid. The concentrations of DFA and DSA were low in common rice vinegar (polished rice vinegar), suggesting that Kurosu is more advantageous than rice vinegars as an antioxidative food item. As the concentrations of DFA and DSA were low in unpolished rice, too, these acids are thought to be produced in Kurosu through the process of the fermentation from ferulic acid and sinapic acid, respectively.

Acetic Acid↗

PubMed2002

Effect of lactoferrin feeding on the host antifungal response in guinea-pigs infected or immunised with Trichophyton mentagrophytes.

Earlier studies revealed that oral administration of lactoferrin (LF), a multi-functional milk protein, facilitated curing of dermatophytosis in guinea-pigs and man by an unknown mechanism. The present study aimed to assess the effect of feeding bovine LF on the host antifungal defence systems in guinea-pigs infected or immunised with Trichophyton mentagrophytes, a dermatophytosis-causing fungus. The unbound iron-binding capacity (UIBC) of the plasma of individual animals varied, and plasma with higher UIBC inhibited growth of T. mentagrophytes in vitro. However, LF administration did not enhance plasma UIBC or the anti-T. mentagrophytes activity of plasma in infected or uninfected animals. Phagocytic activity and reactive oxygen (RO) production of blood neutrophil polymorphonuclear leucocytes (PMNLs) were estimated by flow cytometry. LF administration caused no significant effects on phagocytic activity or RO production of neutrophil PMNLs in infected or uninfected animals. The functions of mononuclear cells (MNC) from the spleen were investigated in guinea-pigs immunised with heat-killed T. mentagrophytes conidia. The MNC were cultured with concanavalin A or inactivated T. mentagrophytes. In the bromo-deoxyuridine incorporation assay, the stimulation index was higher for MNC derived from LF-treated animals than for those from control animals. The culture supernates of MNC enhanced the ability of macrophages to kill T. mentagrophytes conidia. Furthermore, stronger augmentation was observed with the culture supernate from LF-treated animals than with that from control animals. In conclusion, LF feeding may potentiate the host antifungal defence systems by modulating MNC function rather than plasma antifungal activity or peripheral blood neutrophil PMNL activity.

Administration, Oral↗

PubMed2002

Increased Staphylococcus-killing activity of an antimicrobial peptide, lactoferricin B, with minocycline and monoacylglycerol.

This study aimed to find antibiotics or other compounds that could increase the antimicrobial activity of an antimicrobial peptide, lactoferricin B (LFcin B), against Staphylococcus aureus, including antibiotic-resistant strains. Among conventional antibiotics, minocycline increased the bactericidal activity of LFcin B against S. aureus, but methicillin, ceftizoxime, and sulfamethoxazole-trimethoprim did not have such an effect. The combination of minocycline and LFcin B had synergistic effects against three antibiotic-resistant strains of S. aureus, according to result of checkerboard analysis. Screening of 33 compounds, including acids and salts, alcohols, amino acids, proteins and peptides, sugar, and lipids, showed that medium-chain monoacylglycerols increased the bactericidal activity of LFcin B against three S. aureus strains. The short-term killing test in water and the killing curve test in growing cultures showed that a combination of LFcin B and monolaurin (a monoacylglycerol with a 12-carbon acyl chain) killed S. aureus more rapidly than either agent alone. These findings may be helpful in the application of antimicrobial peptides in medical or other situations.

Anti-Bacterial Agents↗