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Biomedical subjects

M Tsuji

Publications and source records attributed to M Tsuji.

At least 235 records · Page 13Linked to original sources

Growth factors as mediators of androgen action during the development of the male urogenital tract.

Studies on the developing prostate and SV suggest that androgens act via mesenchymal AR to elicit synthesis and secretion of various autocrine and paracrine factors that regulate epithelial and stromal growth and differentiation. Clearly, the global regulation of epithelial growth and ductal branching morphogenesis is a complex multifactorial process involving the interplay of many diffusible factors (both positive and negative regulators), extracellular matrix molecules, cell-surface receptors for growth factors, receptors for extracellular matrix molecules, and matrix-degrading enzymes. Future progress will certainly be dependent upon the utilization of appropriate, biologically relevant models to examine the respective roles of various growth factors in the growth and development of androgen target organs.

Androgens↗

Evaluation of G-to-A substitution in the apolipoprotein A-I gene promoter as a determinant of high-density lipoprotein cholesterol level in subjects with and without cholesteryl ester transfer protein deficiency.

The effect of a polymorphism, guanine (G) to adenine (A) substitution in the promoter of apolipoprotein A-I gene at a position 78 bp upstream of the transcription initiation site, on the serum high-density lipoprotein (HDL)-cholesterol level was studied in 168 Japanese subjects with HDL-cholesterol levels ranging from 26 to 171 mg/dl. Considering the significant effect of cholesteryl ester transfer protein (CETP) on the HDL-cholesterol level and the common occurrence of its deficiency, we performed statistical analyses separately for two groups: one without CETP deficiency (n = 126) and the other with CETP deficiency (n = 42). In the group without CETP deficiency, in which the numbers of G/G, G/A, and A/A genotypes were 92 (73.0%), 28 (22.2%), and 6 (4.8%), respectively, the frequency of the A allele in the subjects with HDL-cholesterol levels of > or = 70 mg/dl did not differ from subjects with HDL-cholesterol levels of < or = 69 mg/dl, irrespective of gender: 0.154 and 0.145 in males, and 0.182 and 0.174 in females, respectively, for the > or = 70 mg/dl and < or = 69 mg/dl groups. Additionally, the HDL-cholesterol levels for the subjects with the G/G genotype did not differ from those for the subjects with the A allele: 64 +/- 22, 58 +/- 14, 77 +/- 14 and 62 +/- 16 mg/dl, respectively, for the G/G, G/A, A/A, and G/A + A/A in males, and 72 +/- 18, 74 +/- 24, 63 +/- 4, and 73 +/- 23 mg/dl in females. For the group with CETP deficiency, in which the numbers of G/G and G/A + A/A genotypes were 25 (59.5%) and 17 (40.5%), the HDL-cholesterol levels also did not differ: 98 +/- 24 mg/dl and 99 +/- 30 mg/dl, respectively, for the G/G and G/A + A/A genotypes. Thus, there is no evidence that the polymorphism has any effect on serum HDL-cholesterol levels regardless of CETP status. We conclude that the G-to-A substitution in the promoter of apolipoprotein A-I gene does not significantly alter serum HDL-cholesterol level.

Adult↗

Serum from Theileria sergenti-infected cattle accelerates the clearance of bovine erythrocytes in SCID mice.

Anemia is a major clinical sign of Japanese bovine theileriosis caused by Theileria sergenti. To investigate the possible factors causing anemia in cattle, we developed a clearance test for bovine erythrocytes (Bo-RBC) in severe combined immunodeficient (SCID) mice. Clearance of Bo-RBC in the SCID mice was significantly accelerated when the mice were inoculated with a serum sample obtained from an infected calf during a highly parasitized phase but not when they were injected with a serum sample obtained during the convalescence phase. Acceleration of the clearance of Bo-RBC was also observed in mice treated with merozoite extract. Furthermore, the clearance of Bo-RBC that had been treated with merozoite extract was accelerated. A significant hemolytic activity in infected serum (highly parasitized phase) was observed. Activities sufficient to accelerate the clearance of Bo-RBC in SCID mice and to induce in vitro hemolysis of Bo-RBC were also observed with a merozoite extract from T. sergenti. The results suggest a possible linkage between the in vitro hemolysis of Bo-RBC and the acceleration of Bo-RBC clearance in SCID mice.

Acute Disease↗

Spiral computed tomography for biliary dilatation.

Spiral computed tomography (SCT), which consists of rapid volumetric data acquisition and planar image display, was performed on 12 patients with biliary dilatation after excisional procedure. The technique was evaluated for image quality and impact on clinical practice. All patients safely underwent SCT scanning after intravenous cholangiography (IVC) without any sedations. In 11 of 12 patients reliable biliary images were obtained and three-dimensional (3D) reconstruction images of the biliary system with bilioenteric anastomosis were generally of diagnostic quality even in young children. As a consequence, IVC-SCT technique appears to have the potential for improving the efficacy and safety of diagnostic CT in investigation of the biliary system. In particular, this technique may be useful for detecting bilioenteric anastomotic conditions in follow-up studies of pediatric patients with biliary dilatation.

Adolescent↗

Effects of a highly selective nonpeptide delta opioid receptor agonist, TAN-67, on morphine-induced antinociception in mice.

The effects of a potent and highly selective nonpeptide delta opioid receptor agonist, 2- methyl-4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha- octahydroquinolino [2,3,3,-g] isoquinoline (TAN-67), on morphine-induced antinociception were examined using the warm-plate (51 degrees C) method. When a peptide delta 1 opioid receptor agonist, [D-Pen2, Pen5]enkephalin (DPDPE), was co-administered with i.c.v. morphine, low-dose morphine-induced antinociception was significantly increased. In contrast, i.c.v. co-administration of a peptide delta 2 opioid receptor agonist, [D-Ala2]deltorphin II (DELT), with morphine did not affect the morphine-induced antinociception. When morphine and TAN-67 were co-administered i.c.v., low-dose morphine-induced antinociception was significantly increased. Moreover, when TAN-67 and morphine were co-administered s.c., the morphine dose-response curve shifted to the left and the ED50 value of morphine decreased. These effects DPDPE and TAN-67 were antagonized by the delta opioid receptor antagonist naltrindole (NTI) and the delta 1 opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) not by the delta 2 opioid receptor antagonist naltriben (NTB). Moreover, the mu opioid receptor antagonist beta-FNA also antagonized the effects of DPDPE and TAN-67. These results suggest that the effect of TAN-67 may result from the activation of central delta 1 opioid receptors, since the effect of TAN-67 was antagonized by NTI and BNTX, but not NTB. Furthermore, since pretreatment with beta-FNA also antagonized the effects of both DPDPE and TAN-67, a beta-FNA-sensitive site, i.e. a mu-delta complex site, may play an important role in the modulation of morphine-induced antinociception.

Analgesics↗

Effect of naltrindole on the development of physical dependence on morphine in mice: a behavioral and biochemical study.

The effect of pretreatment with a delta opioid receptor antagonist, naltrindole (NTI), on the development of physical dependence on morphine was investigated in mice. Several withdrawal signs, an increase in cortical noradrenaline (NA) turnover and a decrease in dopamine (DA) turnover in the limbic forebrain were observed following naloxone challenge in morphine-dependent mice. Pretreatment with NTI (0.3-5 mg/kg, s.c.) during chronic morphine treatment dose-dependently suppressed the behavioral and biochemical changes after withdrawal. The blocking effects of NTI suggest that delta opioid receptors may play a significant role in modulating the development of physical dependence on morphine.

Animals↗

A sulfated chitin, SCM-chitin III, inhibits the clearance of human erythrocytes from the blood circulation in erythrocyte-transfused SCID mice.

Recently, we have developed a SCID mouse model in which circulating red blood cells (RBC) are entirely substituted with RBCs from other animals like bovine (Bo) or human (Hu). The relatively short life time, especially of Hu-RBCs, in the SCID mouse, however, is a major obstacle in this model. The present study was performed to examine whether a low-toxic sulfated chitin, carboxymethyl chitin III (SCM-chitin III), which has heparin-like structures in the molecule (heparinoid), could inhibit the Hu-RBC clearance in RBC-transfused SCID mice. When Hu-RBCs were transfused simultaneously with SCM-chitin III, their life time in the blood circulation was prolonged significantly. Sulfated chitosan (S-chitosan) showed only a weak decelerating activity on the clearance of Hu-RBCs. Carboxymethyl chitin (CM-chitin), which was used as an unsulfated control compound, had no effect on the Hu-RBC clearance. Another sulfated polysaccharide, dextran sulfate, though this showed some adverse effects, such as anti-coagulant and anti-platelet aggregation, also exhibited a potent decelerating activity on Hu-RBC clearance. Clearance deceleration by these sulfated polysaccharides was primarily attributable to the inhibition of RBC uptake by cultured macrophages.

Animals↗

dinP, a new gene in Escherichia coli, whose product shows similarities to UmuC and its homologues.

A new gene, designated dinP, was found during E. coli genomic sequencing around the 5.5 min region. Its coding region is preceded by a sequence similar to the consensus binding sequence for LexA, the so-called SOS box sequence. The amino acid sequence of DinP (351 amino acid residues) has a strong similarity to the C. elegans hypothetical protein F22B7.6 and weaker similarities to the UmuC homologues in E. coli and Salmonella typhimurium and also to REV1 of Saccharomyces cerevisiae. Another SOS operon (dinJ1 and dinJ2 genes) found in this region is also described.

Amino Acid Sequence↗

Establishment of a SCID mouse model having circulating human red blood cells and a possible growth of Plasmodium falciparum in the mouse.

Our previous study has demonstrated that repeated transfusions of bovine red blood cells (RBCs) into SCID mice resulted in a complete substitution of their circulating RBCs. Identical experiments with human (Hu) RBCs, however, gave rise to a poor RBC-substitution because of the rapid elimination of Hu-RBCs from the circulation of SCID mice. Search for substances to decelerate the Hu-RBC clearance picked up some effective polysaccharides, such as sulfated chitin and mannan, but they were not effective enough to achieve a high level of Hu-RBC-substitution. In the present study, we found that Hu-serum significantly extended the lifetime of Hu-RBC in SCID mice and that repeated transfusions of the mice with Hu-RBCs, in combination with Hu-serum administration, resulted in an almost complete substitution of their circulating RBCs. An Hu-RBC-substituted SCID mouse inoculated with Plasmodium falciparum had a parasitemia persisting for two weeks, indicating a possible growth of this parasite in the mouse. Thus, this report gave the first demonstration of a complete substitution of the circulating RBCs in SCID mice with Hu-RBCs and of a successful P. falciparum infection in the mice.

Animals↗

Clearance of Theileria sergenti-infected bovine red blood cells in severe combined immune deficiency mice.

Clearance of Theileria sergenti-infected bovine red blood cells (Bo-RBCs) from the blood circulation of severe combined immune deficiency (SCID) mice was studied to help understand the mechanisms of anemia developing in cattle infected with T. sergenti. For the clearance test, Bo-RBC samples having 2%, 58%, and 76% parasitemia and, as a control, parasite-free Bo-RBCs were prepared in the Bo-RBC-SCID mouse model. The T. sergenti-infected Bo-RBCs and the uninfected control Bo-RBCs were separately labeled with two, green and red, fluorescent dyes, mixed together, and injected intravenously into SCID mice. The blood samples collected at various time points were observed under a fluorescent microscope, and the numbers of green and red fluorescing RBCs were counted differentially to determine the clearance rates of T. sergenti-infected and uninfected Bo-RBCs. This test clearly demonstrated that the Bo-RBC samples having higher parasitemias were cleared faster from the blood circulation of SCID mice. The results suggest that the intravascular clearance system in SCID mice may have a mechanism by which T. sergenti-parasitized and non-parasitized Bo-RBCs are recognized and cleared differentially.

Animals↗

No effect of RU 486 (mifepristone) on hepatocellular tumorigenesis in orchiectomized male mice induced by 3'-methyl-4-dimethylaminoazobenzene.

Effects of RU 486 (mifepristone) on hepatocellular tumorigenesis in orchiectomized male mice induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) were investigated. Male mice that had been treated with 3'-Me-DAB neonatally were orchiectomized at one month of age, and injected daily with vehicle only or RU 486 at 0.2 or 0.4 mg/day thereafter. In the liver of orchiectomized males injected with vehicle only, adenomatous nodules developed at incidences of 16.2 and 38.5% at 9 and 12 months of age, respectively, but no carcinomas developed at these ages. Injections of RU 486 at 0.2 or 0.4 mg/day neither affect incidences of adenomatous nodules in the liver, their numbers per mouse, and their areas, nor promote the development of carcinomas. The present results suggest that the long term administration of RU 486 has no effects on hepatocellular tumorigenesis.

Animals↗

Correlation between serum prolactin levels and hepatocellular tumorigenesis induced by 3'-methyl-4-dimethylaminoazobenzene in mice.

Ovariectomy at 1 month of age promotes development of hepatocellular adenomatous nodules in female C57BL/6 x DS-F1 mice treated neonatally with 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). Implantation of oestradiol-17 beta (E2) pellets at 1 month of age suppresses nodule development. Since E2 increases serum levels of prolactin, high serum levels of prolactin in mice that have received implants of E2 pellets may play a role in the suppression of hepatocellular tumorigenesis. Therefore, to investigate the role of prolactin in hepatocellular tumorigenesis, we examined development of adenomatous nodules in female mice that had been treated neonatally with 3'-Me-DAB and had undergone ovariectomy at 1 month of age, under various serum levels of prolactin. Treatment of these mice with perphenazine (dopamine antagonist) from 6 months of age or transplantation of pituitary glands under the renal capsule at 6 months of age markedly increased serum levels of prolactin and significantly suppressed the incidence of adenomatous nodules at 12 months of age. Implantation of E2 pellets at 1 month of age increased serum levels of prolactin to a greater extent and further decreased the incidence of adenomatous nodules. Treatment of mice that had received implants of E2 pellets at 1 month of age with bromocriptine (dopamine agonist) from 6 months of age decreased serum levels of prolactin, and was accompanied by an increase in the incidence of nodules. The present results showed that an increase in serum levels of prolactin was accompanied by a decrease in incidence of liver tumours induced by 3'-Me-DAB in mice, suggesting a suppressive effect of prolactin on liver tumorigenesis in mice. Thus, it is possible that the suppressive effect of oestrogen on liver tumorigenesis in mice is mediated, at least in part, by prolactin.

Adenoma↗

Molecular cloning and sequencing of a cDNA encoding alanine-glyoxylate aminotransferase 2 from rat kidney.

Alanine-glyoxylate aminotransferase (AGT) 2 is a pyridoxal 5'-phosphate dependent, mitochondrial enzyme which, in the rat, is expressed at a high level in the kidney. The amino acid sequences of nine tryptic and seven CNBr peptides of the rat kidney AGT2 were determined. Three overlapping cDNAs encoding the AGT2 were cloned on the basis of its partial amino acid sequences by means of a polymerase chain reaction-based approach involving rat kidney poly(A)+ RNA. The complete cDNA sequence comprised 1,919 bases, and contained a 1,536-base open reading frame which encodes a polypeptide of 512 amino acid residues with a putative presequence consisting of 39 amino acid residues at the amino terminus, giving a precursor protein with a molecular mass of 57,150 Da. The sequence of AGT2 exhibits significant homology with neither peroxisomal AGT1 from human liver nor mitochondrial AGT1 from rat liver. However, the sequence of AGT2 exhibited 30.8, 29.2, and 27.1% identity with those of Escherichia coli 4-aminobutyrate aminotransferase, rat ornithine aminotransferase, and Pseudomonas cepacia 2,2-dialkylglycine decarboxylase, respectively. The active site sequences were also well conserved among these aminotransferases. AGT2, thus, is more similar to the other aminotransferases than to AGT1. The results suggest that the rat kidney AGT2 may play a biological role in amino acid metabolism distinct from that of AGT1.

Alanine Transaminase↗

Murine epidermal V gamma 5/V delta 1-T-cell receptor+ T cells respond to B-cell lines and lipopolysaccharides.

The V gamma 5/V delta 1(+)-T-cell receptor (TCR)-bearing T-cell clone, 2CBET-3, was generated from C57BL/6 mice. Upon stimulation, 2CBET-3 cells produce interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha, but not IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, macrophage colony-stimulating factor, or interferon-gamma. These cells were evaluated for their ability to be stimulated by a variety of murine cell lines, including fibroblasts, trophoblasts, melanoma cells, embryonic carcinomas, B-cell lymphomas, mastocytoma cells, and keratinocytes. The human B-lymphoma cell line, Daudi, also was included in these studies. We found that 2CBET-3 cells produced cytokines up to several hundredfold above the control levels in response to the B-cell lines, Daudi, and A20/2J, but not to the B-cell line 439.4.2. After fixation with glutaraldehyde, Daudi and A20/2J continued to stimulate this gamma delta T-cell line. 2CBET-3 cells also responded to the keratinocyte line PAM212, but not to another, XB-2. When lipopolysaccharides (LPS) from Escherichia coli or S. typhimurium were added to 2CBET-3 cells in the presence of A20/2J cells, 2CBET-3 cells responded with increased cytokine production compared with the cytokine production in the presence of A20/2J cells alone. 2CBET-3 cells by themselves did not respond to LPS alone or to supernatants from A20/2J cells incubated with LPS. Unlike 2CBET-3, the epidermal T-cell hybridoma 70BET-49, expressing a V gamma 5/V delta 1-TCR identical to that of 2CBET-3, did not respond to A20/2J cells in the presence or absence of LPS, suggesting a requirement for molecules other than the TCR for V gamma 5/V delta 1-TCR+ T-cell stimulation by the B-cell lines and by LPS. This unique reactivity of gamma delta-TCR+ cells is different from that of alpha beta-TCR+ cells and may reflect a functional specialization of gamma delta-TCR+ cells in the response to bacterial infections.

Animals↗

Anerythremic form of acute erythremic myelosis (Di Guglielmo's syndrome) causing hepatosplenomegaly due to the infiltration of hemoglobin-bearing blast cells: an autopsy case.

An autopsy case of a 42 year old man with the anerythremic form of acute erythremic myelosis (Di Guglielmo's syndrome) is reported. The patient was admitted because of a 1 month history of fatigue and fever. Physical examination showed hepatosplenomegaly. Laboratory data showed leukopenia, mild normocytic anemia, and high levels of serum lactate dehydrogenase and vitamin B12. Bone marrow aspirate revealed an elevated number of erythroblasts, with dyserythropoiesis (E/M = 3.7). After admission, thrombocytopenia progressed rapidly, but blast cells were not seen in the peripheral blood throughout the clinical course. On the 56th hospital day, the patient died of pneumonia. At autopsy, the spleen weighed 550 g and the liver 1800 g. Histologically, the white and red pulps of the spleen and the portal region and sinusoid of the liver were diffusely infiltrated by blast cells that were positive for anti-hemoglobin (Hb) antibody on immunoperoxidase staining. The bone marrow, the lymph nodes, the adrenal glands, the pancreas, and the heart were also infiltrated by the blast cells. This was thus considered to be a rare case of the anerythremic form of acute erythremic myelosis (Di Guglielmo's syndrome), the findings showing that Hb immunoperoxidase staining is useful for the diagnosis of this condition.

Adult↗

In vitro and in vivo antibacterial activities of S-1090, a new oral cephalosporin.

S-1090, a new oral cephalosporin, was active against selected gram-negative bacteria and methicillin-susceptible clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus warneri, against which it had excellent activity. S-1090 was the most active compound against Streptococcus pyogenes and Streptococcus agalactiae among the agents compared. The in vivo efficacy of S-1090 against systemic and urinary and respiratory tract infections caused by gram-positive and -negative bacteria was superior to that expected from the in vitro and in vivo activities of the agents against which it was compared.

Animals↗

Reduction of cytochrome aa3 measured by near-infrared spectroscopy predicts cerebral energy loss in hypoxic piglets.

Near-infrared spectroscopy is a noninvasive monitoring technique that allows quantitative measurement of changes in cerebral oxygenated Hb (HbO2), deoxygenated Hb (Hb), total Hb, and oxidized cytochrome aa3 (CytO2). Changes in cerebral Hb oxygenation and CytO2 have been measured in human neonates and infants under a variety of conditions. However, the association of these measurements with cerebral high-energy phosphate loss is not known. We studied simultaneous changes in cerebral HbO2, Hb, total Hb, and CytO2 by near-infrared spectroscopy and changes in nucleoside triphosphate (NTP, mostly ATP) and phosphocreatine (PC) concentrations and intracellular pH by in vivo 31P-labeled magnetic resonance spectroscopy. Four-wk-old piglets (n = 8) underwent sequential hypoxic episodes of increasing severity (inspired O2 concentration, 12, 8, 6, 4, and 0%). Animals were anesthetized and mechanically ventilated. At all levels of hypoxia, cerebral HbO2 decreased, and Hb increased. Loss of PC or NTP was not observed until inspired O2 concentration was decreased to less than 12%. With such severe hypoxia, hypotension, intracellular acidosis, and increasingly severe PC and NTP depletions occurred. Decreases in PC and NTP correlated closely with decreased CytO2 and arterial blood pressure (p < 0.0001) but not with changes in HbO2 and Hb. In conclusion, cerebral hypoxemia is readily detected by near-infrared spectroscopy as a decrease in HbO2 and an increase in Hb. However, relative changes in cerebral HbO2 and Hb have low predictive value for cerebral energy failure. Reduction of CytO2 is highly correlated with decreased brain energy state and may indicate impending cellular injury.

Animals↗

Interaction between discriminative stimulus effects of cocaine and morphine.

We recently demonstrated that combining cocaine and morphine could enhance their reinforcing effects which may be mediated by the dopaminergic system. In the present study, the effects of cocaine and morphine on the discriminative stimulus effects of morphine and cocaine, respectively, were examined. Furthermore, dopaminergic mediation in the discriminative stimulus effects of morphine was also examined. Pretreatment with 1.0 or 3.0 mg/kg morphine shifted the dose-response curve for cocaine to the left, and 3.0 mg/kg morphine significantly potentiated the discriminative stimulus effects of cocaine. On the other hand, neither 1.25 nor 2.5 mg/kg cocaine affected the discriminative stimulus effects of morphine. These results suggest that potentiation of the discriminative stimulus effects of cocaine by morphine may reflect the enhancement of reinforcing effects in the combination of cocaine and morphine. Furthermore, neither SCH23390 (D1-receptor antagonist) nor haloperidol (D2-receptor antagonist) affects the discriminative stimulus effects of morphine, while combining these drugs slightly attenuated the effects of morphine. Thus, another neurotransmitter rather than dopamine may play an important role in the discriminative stimulus effects of morphine. Therefore, the discriminative stimulus effects of morphine are apparently not potentiated by cocaine, unlike those of reinforcing effects.

Animals↗