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Biomedical subjects

R Nakajima

Publications and source records attributed to R Nakajima.

At least 19 recordsLinked to original sources
PubMed1996

Oral application of romurtide, a synthetic muramyl dipeptide derivative, stimulates nonspecific resistance to microbial infections and hematopoiesis in mice.

Romurtide given orally enhanced the nonspecific resistance against microbial infections and hematopoiesis up to the levels achieved by subcutaneous (s.c.) injection of the compound in mice. Oral romurtide conferred protection and, in consequence, enhanced therapeutic efficacy of antibiotics against systemic infections in mice. The leukocytosis followed by the elevations of colony stimulating activity in serum and the colony forming unit of granulocyte-macrophage (c.f.u.-GM) in femoral bone marrow was observed as successive event in mice treated orally with romurtide. To obtain a comparable potency to s.c. injection of the compound at a dose of 0.1 mg per mouse, oral application required doses of 3 and 10 mg per mouse for stimulating the nonspecific resistance to infection and hematopoiesis, respectively.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1996

Gene expression of insulin signal-transduction pathway intermediates is lower in rats fed a beef tallow diet than in rats fed a safflower oil diet.

To elucidate the effects of dietary fatty acid composition on the insulin signaling pathway, we measured the gene expression of the earliest steps in the insulin action pathway in skeletal muscle of rats fed a safflower oil diet or a beef tallow diet. Rats were meal-fed an isoenergetic diet based on either safflower oil or beef tallow for 8 weeks. Both diets provided 45%, 35%, and 20% of energy as fat, carbohydrate, and protein, respectively. Insulin resistance, assessed from the diurnal rhythm of plasma glucose and insulin and the oral glucose tolerance test (OGTT), developed in rats fed a beef tallow diet. Body fat content was greater in rats fed a beef tallow diet versus a safflower oil diet. The level of insulin receptor mRNA, relative expression of the insulin receptor mRNA isoforms, and receptor protein were not affected by the composition of dietary fatty acids. The abundance of insulin receptor substrate-1 (IRS-1) and phosphatidylinositol (PI) 3-kinase mRNA and protein was significantly lower in rats fed a beef tallow diet versus a safflower oil diet. We conclude that long-term feeding of a high-fat diet with saturated fatty acids induces decrease in IRS-1 and PI 3-kinase mRNA and protein levels, causing insulin resistance in skeletal muscle.

Actins↗
PubMed1996

Identification and characterization of two tandem repeat sequences (TrsB and TrsC) and a retrotransposon (RIRE1) as genome-general sequences in rice.

Three kinds of DNA sequences (here called TrsB, TrsC and RIRE1) have been previously reported to be those repeated in tandem specifically in the wild rice species with FF, CC or EE genome, respectively. To characterize these genome type-specific sequences, we carried out PCR using a pair of primers, which hybridize to a restricted region in the repeating unit sequence and prime DNA synthesis in both directions. Gel electrophoresis and DNA sequencing revealed that PCR using primers for TrsB (or TrsC) amplified the fragments with an integral series of a unit length not only from total DNA of the rice strain with FF (or CC) genome, but also from those of the rice strains with non-FF (or non-CC) genome. TrsB or TrsC was, however, found to be repeated in an extraordinary number of copies in the species with FF or CC genome, respectively, in which the TrsB (or TrsC) sequence has been originally identified. PCR using primers for RIRE1 produced various sizes of fragments from total DNA of the rice strains with EE genome. The fragments, however, showed no progression at interval of the unit length characteristic for tandem repeats. Nucleotide sequencing of the amplified fragments revealed that they were not the sequences repeated in tandem, but were those interspersed as an element having partial homology with the LTR sequences of retrotransposons, Wis-2-1A in wheat and BARE-1 in barley. RIRE1 was present in the rice species with any types of genomes, but in the species with EE genome in an extraordinary number of copies.

Base Sequence↗
PubMed1995

Effects of endurance training on gene expression of insulin signal transduction pathway.

Alternative splicing of insulin receptor mRNA and gene expression of insulin receptor, IRS-1 and MAP kinase isoforms were examined in skeletal muscle of trained and sedentary rats. Adult male Sprague-Dawley rats were trained for 9 weeks on a treadmill: 30 m/min at 6 degrees incline, 90 min/day, 5 days/week. Endurance training increased insulin receptor mRNA level without change in alternative splicing of insulin receptor mRNA in skeletal muscle. The levels of IRS-1 and MAP kinase (ERKI) mRNA were significantly higher in trained rats than sedentary rats. Our findings provide the first evidence that gene expression of insulin receptor and postreceptor signal transduction pathway is enhanced by endurance training, without affecting alternative splicing of insulin receptor isoforms.

Alternative Splicing↗
PubMed1995

In vitro and in vivo antifungal activities of DU-6859a, a fluoroquinolone, in combination with amphotericin B and fluconazole against pathogenic fungi.

DU-6859a is an investigational fluoroquinolone agent with potent bactericidal activity, but by itself it has no antifungal activity. When combined with amphotericin B (AmB), however, DU-6859a clearly enhanced the in vitro antifungal activity of AmB against Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, and Cryptococcus neoformans in microdilution checkerboard studies. Positive interactions of DU-6859a with AmB against Aspergillus fumigatus were dependent on the medium used; yeast nitrogen base supplemented with amino acids, ammonium sulfate, and 1% glucose was better for demonstrating synergism, while in RPMI 1640 medium, unexpected antagonism between the drugs occurred against three of the strains tested. In combination with fluconazole (Flu), DU-6859a increased the activity of Flu against C. albicans both in synthetic amino acid medium fungal and in supplemented yeast nitrogen base. An in vitro time-kill study revealed that DU-6859a combined with AmB significantly suppressed the regrowth of C. albicans compared with the suppression brought about by AmB used alone in a concentration-dependent fashion. Furthermore, in a model of C. albicans infection in mice, the fungal load in infected kidneys was significantly less in mice given the combination treatment of DU-6859a plus either AmB or Flu, and thus, the combination treatment resulted in prolonged survival of infected mice compared with treatment with either antifungal alone. The prolonged survival in mice given the combined treatment was also observed in mice with A. fumigatus infection, indicating that DU-6859a potentiated the actions of the antifungal agents in vivo as well as in vitro.

Amphotericin B↗
PubMed1995

Suppression of cytokines in mice by protein A-V antigen fusion peptide and restoration of synthesis by active immunization.

It is established that an approximately 70-kb Lcr plasmid enables Yersinia pestis, the causative agent of bubonic plague, to multiply in focal necrotic lesions within visceral organs of mice by preventing net synthesis of the cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), thereby minimizing inflammation (Lcr+). Rabbit antiserum raised against cloned staphylococcal protein A-V antigen fusion peptide (PAV) is known to passively immunize mice against 10 minimum lethal doses of intravenously injected Lcr+ cells of Y. pestis. In this study, injected PAV suppressed TNF-alpha and IFN-gamma in mice challenged with avirulent V antigen-deficient Y. pestis (lcrV or Lcr-) and promoted survival in vivo of these isolates as well as salmonellae and Listeria monocytogenes (with which the outcome was lethal). Active immunization of mice with PAV protected against 1,000 minimum lethal doses of intravenously injected Lcr+ cells of Y. pestis and Yersinia pseudotuberculosis but not Yersinia enterocolitica. The progressive necrosis provoked by Lcr+ cells of Y. pestis in visceral organs of nonimmunized mice was replaced after active immunization with PAV by massive infiltration of neutrophils and mononuclear cells (which generated protective granulomas indistinguishable from those formed against avirulent Lcr- mutants in nonimmunized mice). Distinct multiple abscesses typical of Lcr+ cells of Y. pseudotuberculosis were prevented by similar immunization. Significant synthesis of TNF-alpha and IFN-gamma occurred in spleens of mice actively immunized with PAV after challenge with Lcr+ cells of Y. pestis. These findings suggest that V antigen contributes to disease by suppressing the normal inflammatory response.

Animals↗
PubMed1994

Physical mapping of the 5S ribosomal RNA genes on rice chromosome 11.

One 5S ribosomal RNA gene (5S rDNA) locus was localized on chromosome 11 of japonica rice by in situ hybridization. The biotinylated DNA probe used was prepared by direct cloning and direct labeling methods, and the locus was localized to the proximal region of the short arm of chromosome 11 (11p1.1) by imaging methods. The distance between the signal site and the centromere is 4.0 arbitrary units, where the total length of the short arm is 43.3 units. The 5SrDNA locus physically identified and mapped in rice was designated as 5SRrn. The position of the 5S rDNA locus reported here differs from that in indica rice; possible reasons for this difference are discussed. DNA sequences of 5S rDNA are also reported.

Base Sequence↗
PubMed1994

Passive immunity to yersiniae mediated by anti-recombinant V antigen and protein A-V antigen fusion peptide.

LcrV (V antigen), a known unstable 37.3-kDa monomeric peptide encoded on the ca. 70-kb Lcr plasmid of Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica, has been implicated as a regulator of the low-calcium response, virulence factor, and protective antigen. In this study, lcrV of Y. pestis was cloned into protease-deficient Escherichia coli BL21. The resulting recombinant V antigen underwent marked degradation from the C-terminal end during purification, yielding major peptides of 36, 35, 34, and 32 to 29 kDa. Rabbit gamma globulin raised against this mixture of cleavage products provided significant protection against 10 minimum lethal doses of Y. pestis (P < 0.01) and Y. pseudotuberculosis (P < 0.02). To both stabilize V antigen and facilitate its purification, plasmid pPAV13 was constructed so as to encode a fusion of lcrV and the structural gene for protein A (i.e., all but the first 67 N-terminal amino acids of V antigen plus the signal sequence and immunoglobulin G-binding domains but not the cell wall-associated region of protein A). The resulting fusion peptide, termed PAV, could be purified to homogeneity in one step by immunoglobulin G affinity chromatography and was stable thereafter. Rabbit polyclonal gamma globulin directed against PAV provided excellent passive immunity against 10 minimum lethal doses of Y. pestis (P < 0.005) and Y. pseudotuberculosis (P < 0.005) but was ineffective against Y. enterocolitica. Protection failed after absorption with excess PAV, cloned whole V antigen, or a large (31.5-kDa) truncated derivative of the latter but was retained (P < 0.005) upon similar absorption with a smaller (19.3-kDa) truncated variant, indicating that at least one protective epitope resides internally between amino acids 168 and 275.

Animals↗
PubMed1994

Preparation and taste of certain glycosides of flavanones and of dihydrochalcones.

The 7-O-[2-O-(alpha-L-Rhamnopyranosyl)-beta-L-quinovoside] of naringenin and of hesperetin, and their dihydrochalcone (DHC) derivatives were synthesized by the method of Koenigs-Knorr (Ag2CO3 and quinoline). The reaction of TMS ethers of naringenin and of hesperetin with each of the alpha-acetofluoro derivatives of D-glucose, L-rhamnose, 2-O-(alpha-L-rhamnopyranosyl)-L-rhamnose, and 2-O-(alpha-L-rhamnopyranosyl)-D-glucose (neohesperidose), using boron trifluoride etherate as an activator, yielded coupling products which, after deprotection, gave naringenin 4'-O-beta-D-glucoside, naringenin 4'-O-alpha-L-rhamnoside, naringenin 4'-O-[2-O-(alpha-L-rhamnopyranosyl)-alpha-L-rhamnoside], hesperetin 3'-O-[2-O-(alpha-L-rhamnopyranosyl)-alpha-L-rhamnoside], and naringenin 4'-O-beta-neohesperidoside, respectively. Catalytic hydrogenation of these flavanones gave the corresponding DHC derivatives. Hesperetin DHC 4'-O-[2-O-(alpha-L-rhamnopyranosyl-beta-L-quinovoside] was 300 times sweeter than sucrose, while the other compounds were bitter or tasteless.

Carbohydrate Sequence↗
PubMed1993

Alterations of the p53 tumor suppressor gene and its association with activation of the c-K-ras-2 protooncogene in premalignant and malignant lesions of the human uterine endometrium.

We previously reported (T. Enomoto et al., Cancer Res., 50: 6139-6145, 1990; T. Enomoto et al., Cancer Res., 51: 5308-5314, 1991) a significant frequency of activating point mutations in codon 12 of the c-K-ras-2 protooncogene in endometrial adenocarcinoma and its premalignant precursor lesions (series 1 and 2). To reveal the role of the p53 tumor suppressor gene in the development of endometrial adenocarcinoma and to study the association of p53 alterations with K-ras activation, an additional 28 endometrial adenocarcinomas and an additional 11 premalignant atypical uterine hyperplasias (series 3), as well as 12 cases of endometrial adenocarcinoma (10 having K- or N-ras activation) and 2 cases of atypical hyperplasia from series 1 and 2, were screened for the presence of p53 alterations. Allelic loss, recognized at the polymorphic site in codon 72 of the p53 gene, was detected in 6 of 19 (32%) informative cases of endometrial adenocarcinoma and 1 of 4 (25%) informative cases of endometrial atypical hyperplasia by restriction fragment length polymorphism analysis and by single-strand conformation polymorphism analysis of polymerase chain reaction (PCR)-amplified DNA fragments. Mutations in the highly conserved regions of the p53 gene were detected by single-strand conformation polymorphism analysis of PCR-amplified DNA fragments. Mutations were found in 9 of 40 (23%) endometrial adenocarcinomas and 1 of 13 (8%) atypical hyperplasias that were studied. Mutations in p53 were significantly more frequently found in clinical grade 3 (G3) cancers (6 of 14, 43%) than in G1-G2 cancers (3 of 26, 12%) (P = 0.033). Mutations were subsequently confirmed by direct sequencing. Single missense base substitutions were detected in 6 cases of endometrial carcinoma and in one case of atypical hyperplasia. Deletions of a single base and of 2 bases were each detected in single cases of endometrial carcinoma, and a single base insertion was found in a third case. Point mutations in K-ras were also identified in tumors of series 3 by direct sequencing of PCR-amplified DNA fragments of exons 1 and 2. Point mutations in codons 12 and 13 in K-ras were detected by direct sequencing of PCR-amplified DNA in 7 of 28 adenocarcinomas in series 3, but none were found in exon 2 (codons 59.63. The spectrum of point mutations in p53 in endometrial adenocarcinomas was almost identical to what we found in K-ras in series 1 and 2 and in series 3, suggesting the possible role of a mutagen that might be responsible for mutations in both K-ras and p53.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1993

Minimum alveolar concentration of sevoflurane in elderly patients.

We have determined the minimum alveolar concentration (MAC) for sevoflurane in elderly patients (mean age 71.4 yr). MAC was found to be 1.48 (SEM 0.08)%, which is smaller than the values for children and adults. The magnitude of the change in MAC with age is similar to that for halothane and isoflurane. The calculated anesthetic ED95 for preventing 95% of patients from moving was 1.98%.

Age Factors↗
PubMed1993

Association between virulence of Yersinia pestis and suppression of gamma interferon and tumor necrosis factor alpha.

It is established that Yersinia pestis, the causative agent of bubonic plague, and enteropathogenic Yersinia pseudotuberculosis and Yersinia enterocolitica share a ca. 70-kb low-calcium response or Lcr plasmid (Lcr+). The latter is known to encode regulatory functions that restrict growth at 37 degrees C in Ca(2+)-deficient medium and virulence factors that are expressed only in vitro within this environment (e.g., certain Yops and V antigen). In this study, gamma interferon (IFN-gamma) was never detected in mice infected with 10 minimum lethal doses (MLD) of Lcr+ cells of Y. pestis, and significant levels of tumor necrosis factor alpha (TNF-alpha) arose only prior to death. Prompt and marked synthesis of these cytokines was observed upon infection with avirulent Lcr- mutants. Treatment of mice with exogenous IFN-gamma plus TNF-alpha inhibited multiplication of Lcr+ yersiniae in vivo, thereby providing protection against challenge with 10 MLD. Administration of both cytokines was required for absolute survival, suggesting a synergistic rather than cumulative interaction. This protective effect entailed cytokine priming as judged by subsequent detection of substantial levels of endogenous IFN-gamma and TNF-alpha. Monospecific anti-V-antigen, known to provide passive immunity against 10 MLD of Lcr+ Y. pestis, permitted significant synthesis of endogenous IFN-gamma and TNF-alpha. These findings demonstrate that Lcr+ yersiniae suppress synthesis of cytokines and suggest that this effect is mediated by one or more Lcr plasmid-encoded virulence factors.

Animals↗
PubMed1992

Blood concentrations of sevoflurane and isoflurane on recovery from anaesthesia.

We studied 16 healthy ASA physical status I patients (aged 13-71 yr for sevoflurane and 22-74 yr for isoflurane) to determine maximum blood concentrations on awakening (MBCawake) from sevoflurane and isoflurane anaesthesia, and determined if age and duration of anaesthesia significantly influenced MBCawake. After operation, the end-tidal concentration of anaesthetics was decreased gradually. During recovery from anaesthesia, patients were asked repeatedly to open their eyes. We obtained blood samples to measure the anaesthetic concentration when patients first opened their eyes. MBCawake of sevoflurane and isoflurane (ml of anaesthetic gas per ml of blood) were 0.40 (SE 0.04)% and 0.53 (0.04)%, respectively. MBCawake values of sevoflurane and isoflurane correlated significantly with age (P < 0.05) but not with duration of anaesthesia. Blood:gas partition coefficients of sevoflurane and isoflurane were 0.65 (SD 0.05) and 1.36 (0.09), respectively. There was no significant correlation between age and blood:gas partition coefficient for sevoflurane and isoflurane. Awakening alveolar concentrations (MACawake) calculated from MBCawake were 0.61 (SE 0.05)% for sevoflurane and 0.39 (0.02)% for isoflurane, and correlated significantly with age. The ratios of awakening alveolar concentration to MAC were reasonably constant--0.33 for sevoflurane and 0.33 for isoflurane.

Adolescent↗
PubMed1992

Synergistic effect of romurtide with ampicillin against pneumococcal pneumonia in mice.

The anti-infective activity of romurtide, a synthetic muramyl dipeptide (MDP) derivative, was evaluated in experimental pneumococcal pneumonia in mice deficient in the third component of complement (C3). The compound was found to be effective against the pneumonia in combination with subcutaneous ampicillin (ABPC). This synergistic effect of romurtide with ABPC was most pronounced when the compound was administered subcutaneously 1 day before infection. Romurtide alone, however, was not effective, irrespective of its treatment timing. Similarly, consecutive treatment with ABPC alone failed to kill pneumococci in the lungs completely, and resultant regrowth of the organisms provoked purulent pneumonia. In contrast, the combination treatment of romurtide with ABPC successfully prevented most of the mice from the purulent pneumonia: the initial infiltration of resident alveolar macrophages and subsequent accumulation of macrophages were observed in the pneumonic foci. In accordance with the occurrence of these cellular responses in the lungs, pneumococci were successfully eliminated from the lungs in mice treated with romurtide in combination with ABPC. Thus, romurtide was suggested to promote recovery of the mice with pneumococcal pneumonia by activating resident and accumulated macrophages in the pneumonic foci to eliminate pneumococci from the lung.

Acetylmuramyl-Alanyl-Isoglutamine↗