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Biomedical subjects

Y Aoyama

Publications and source records attributed to Y Aoyama.

At least 37 records · Page 2Linked to original sources

Expression of metallothionein in the liver and kidney of rats is influenced by excess dietary histidine.

It is well known that excess dietary histidine induces the metabolic changes in copper and zinc. Therefore, this study was carried out to clarify whether excess dietary histidine alters the gene expressions of metallothionein-1 and metallothionein-2 in the liver and kidney. Male rats were fed the control (ad libitum and pair-fed) or histidine-excess (50 g of L-histidine per kg of diet) diet for 0, 1 and 3 days. The levels of liver metallothionein-1 and metallothionein-2 mRNA were markedly lower in the rats fed the histidine-excess diet as compared to those of the control (ad libitum and pair-fed) diet, when fed for 1 or 3 days. The levels of renal metallothionein-1 and metallothionein-2 mRNA in the rats fed the histidine-excess diet were higher or tended to be higher as compared with the rats fed the control (ad libitum and pair-fed) diet when fed for 1 or 3 days, respectively. At the same time, hepatic copper content was decreased and renal zinc content was increased by dietary histidine. It thus appears, that such a response on the level of liver metallothionein mRNA might be related to the contents of liver copper, but of kidney metallothionein mRNA might be due to the content of zinc.

Animals↗

Primary refractoriness to platelet transfusion caused by Nak(a) antibody alone.

BACKGROUND AND OBJECTIVES: Anti-Nak(a), a platelet-specific antibody, occasionally causes platelet-transfusion refractoriness (PTR) together with human leucocyte antigen (HLA) antibodies. Anti-Nak(a) usually appears after frequent platelet transfusions or pregnancy. We report the first case of PTR caused by anti-Nak(a) alone. MATERIALS AND METHODS: A 19-year-old male patient with testicular tumour showed PTR when receiving his first transfusion of platelets. Screening for platelet antigens and platelet antibodies revealed that he had type I CD36 (Nak(a)) deficiency and that anti-Nak(a), but not anti-HLA, was present before he received his first transfusion. RESULTS: The transfusion of Nak(a)-negative, but HLA non-selected, platelets was effective in raising the platelet count. CONCLUSION: Clinically significant Nak(a) antibody was present as naturally occurring antibody in a platelet glycoprotein IV (CD36)-negative non-transfused male patient.

Adult↗

Ingestion of insoluble dietary fibre increased zinc and iron absorption and restored growth rate and zinc absorption suppressed by dietary phytate in rats.

We examined the effects of ingestion of five types of insoluble fibre on growth and Zn absorption in rats fed a marginally Zn-deficient diet (6.75 mg (0.103 mmol) Zn/kg diet) with or without added sodium phytate (12.6 mmol/kg diet). The types of insoluble fibre tested were corn husks, watermelon skin, yam-bean root (Pachyrhizus erosus) and pineapple core, and cellulose was used as a control (100 g/kg diet). Body-weight gain in the cellulose groups was suppressed by 57 % by feeding phytate. Body-weight gain in phytate-fed rats was 80 % greater in the watermelon skin fibre and yam-bean root fibre group than that in the cellulose group. Zn absorption ratio in the cellulose groups was lowered by 46 and 70 % in the first (days 7-10) and second (days 16-19) measurement periods with feeding phytate. In the rats fed the phytate-containing diets, Zn absorption ratio in the watermelon skin, yam-bean root and pineapple core fibre groups was 140, 80 and 54 % higher respectively than that in the cellulose group, in the second period. Fe absorption was not suppressed by phytate, however, feeding of these three types of fibre promoted Fe absorption in rats fed phytate-free diets. The concentration of soluble Zn in the caecal contents in the watermelon skin fibre or yam-bean root fibre groups was identical to that in the control group in spite of a higher short-chain fatty acid concentration and lower pH in the caecum. These findings indicate that ingestion of these types of insoluble fibre recovered the growth and Zn absorption suppressed by feeding a high level of phytate, and factors other than caecal fermentation may also be involved in this effect of insoluble fibre.

Animals↗

The amino acid residues affecting the activity and azole susceptibility of rat CYP51 (sterol 14-demethylase P450).

The amino acid residues affecting the function of rat sterol 14-demethylase P450 (CYP51) were examined by means of point mutation. Forty-five mutants with respect to 27 amino acid sites were constructed and expressed in Escherichia coli. Substitution of highly conserved Y131, E369, R372, or R382 decreased the expression of CYP51 protein, indicating some structural importance of these residues. Substitution of H314, T315, or S316 caused considerable effects on the catalytic activity, and T315 was identified as the "conserved threonine" of CYP51. H314 was important for maintenance of the activity of CYP51 and was a characteristic residue of this P450, because the position corresponding to this residue is occupied by an acidic amino acid in most other P450 species. A144 was identified as a residue affecting the interaction of CYP51 with ketoconazole. Substitution of A144 with I, which occupies the corresponding position in fungal CYP51, enhanced the ketoconazole susceptibility of rat CYP51 with little change in the catalytic activity, indicating an important role of this residue in determination of the ketoconazole susceptibility of CYP51. Alteration of the catalytic activity was caused by the substitution at some other sites, whereas substitution of a few highly conserved amino acids caused little alteration of the activity of CYP51.

Amino Acid Substitution↗

Gonadotropin-dependent expression of sterol 14-demethylase P450 (CYP51) in rat ovaries and its contribution to the production of a meiosis-activating steroid.

Immunohistochemical analysis showed that sterol 14-demethylase P450 (CYP51) is expressed in mature follicles and corpus lutea of rat ovaries. In follicles, CYP51 is expressed in granulosa and theca cells but not in oocytes. The ovarian CYP51 activity of hypophysectomized rats is very low and induced by pregnant mares' serum gonadotropin (PMSG) treatment together with ovarian growth. The expression of CYP51 first increases in growing follicles and then appears in the corpus lutea after luteinization. The former event may be due to the follicular-stimulating hormone action of PMSG, and the latter may be caused by the luteinizing hormone effect of PMSG. Sterol analysis indicated that the product of the CYP51-mediated lanosterol 14-demethylation, 4,4-dimethylcholesta-8,14,24-trienol, which has been identified as a meiosis-activating steroid (MAS) in mammals [Byskov et al. (1995) Nature 374, 559-562], accumulates (about 10 pmol/mg of ovary) in mature rat ovaries, and the content is enough to activate the resumption of meiosis. These lines of evidence suggest that the expression of ovarian CYP51 is dependent on gonadotropins, and ovarian CYP51 activity is enough for accumulating MAS. Serum insulin does not affect the ovarian CYP51 level, although it is essential for hepatic CYP51 expression. These findings indicate that expression of CYP51 is regulated differently among organs.

Animals↗

Bacterial translocation in neonatal rats: the relation between intestinal flora, translocated bacteria, and influence of milk.

BACKGROUND: A high incidence of bacterial translocation in neonates results not only from immaturity of host-defense functions, but also from the dominant colonization of aerobic bacteria in the intestine. Bacterial colonization develops differently among breast-fed, formula-fed, premature, and full-term infants. The purpose of this study was to examine the incidence of bacterial translocation and to identify the translocated bacterial species, relating these findings to the intestinal microflora and to the type of feeding in neonatal rats. METHODS: Animals were divided into three groups: breast-fed normal pups (MR group), formula-fed pups fed via an intragastric cannula implanted esophageally (AR group), and breast-fed pups after the removal of the cannula (Sham group). Artificial rearing was achieved using a machine feeding system. Culture and identification of the bacteria in the intestine, mesenteric lymph nodes, liver, portal blood, and lungs were made using a simplified version of Mitsuoka's method. RESULTS: At 14 days of age, the dominant bacteria in the feces of the MR and Sham Groups were Enterobacteriaceae, Lactobacillus, and Enterococcus, but Enterobacteriaceae and Clostridium were significantly more common in the AR group than in the MR group. The dominant bacteria in the mesenteric lymph nodes were Enterobacteriaceae, Lactobacillus, and Staphylococcus. The extent of systemic bacterial translocation decreased earlier in the Sham group than in the AR group. CONCLUSIONS: The frequency with which species of bacteria were cultured from mesenteric lymph nodes and other peripheral sites did not mirror the composition of the intestinal flora. Among the translocated bacteria, Staphylococcus may be especially hard to recognize and difficult for the host-defense systems to destroy. Breast-feeding inhibited systemic bacterial translocation in the suckling period of the rat.

Animal Feed↗

Surfactant protein D (SP-D) and systemic scleroderma (SSc).

We measured serum levels of SP-D in collagen diseases (110 cases) such as systemic scleroderma (SSc), scleroderma spectrum disorders (SSD), systemic lupus erythematodes (SLE), Sjogren syndrome (Sjs), dermatomyositis (DM), rheumatoid arthritis (RA), and dermatitis (DE) (109 cases) as a control. Additionally, we performad a correlation analysis to determine how these levels were related to pulmonary fibrosis and function test (vital capacity, %DLco). The serum levels of SP-D increased in SSc patients with Barnett type III more than in SSc patients with Barnett type I or II, while they increased slightly in SSD (incomplete type of SSc) patients. The differences in these figures were statistically significant between the SSc (SSc & SSD) and non-SSc (SLE, DM, Sjs & RA) groups (p<0.005). The serum levels of SP-D in SSc patients with anti-topoisomerase I antibodies were statistically higher than those in SSc patients with other types of anti-nuclear antibodies. There was a statistically significant correlation between the severity of pulmonary fibrosis and the serum levels of SP-D, and a statistically negative correlation between SP-D levels and vital capacity or %DLco, but there was no proportional correlation with the forced expiatory volume (FEV1.0%). There was no statistical relationship between pre- and post-therapy with photopheresis; however, there was a statistical correlation between the serum levels of SPD and KL-6. In the group of collagen diseases, plasma levels of SP-D were higher than serum levels of SP-D. Patients with SSc possess higher levels of SP-D than do those with other collagen diseases and dermatitis, which may correspond to the severity of pulmonary fibrosis.

Adolescent↗

Nodal gamma/delta T cell lymphoma in complete remission following allogeneic bone marrow transplantation from an HLA-matched unrelated donor.

Gamma/delta T cell lymphoma is very rare, and usually occurs as an extranodal tumor. We describe the case of a 16-year-old Japanese man with an unusual nodal gamma/delta T cell lymphoma with generalized lymphadenopathy and bone marrow involvement. No tumor involvement was observed in the liver, spleen, or nasal cavity. Examination for surface antigens on lymphoma cells revealed a unique phenotype, positive for CD3 and T cell receptor (TCR) gamma/delta, but negative for CD2. Genotypic analysis revealed the tumor to be of monoclonal origin and characterized by TCR gamma-chain gene rearrangement, but there was no rearrangement of the TCR beta-chain gene. Our patient's tumor responded to combination chemotherapy and subsequent allogeneic bone marrow transplantation from an HLA-matched unrelated donor. He has remained well and free of disease for 35 months.

Adolescent↗

Analysis of IL-18 bioactivity and IL-18 mRNA in three patients with adult T-cell leukaemia, acute mixed lineage leukaemia, and acute lymphocytic leukaemia accompanied with high serum IL-18 levels.

Interleukin-18 (IL-18) bioactivity in sera and IL-18 mRNA expression in leukaemia cells of three patients with adult T-cell leukaemia (ATL), acute mixed lineage leukaemia (AMLL) and acute lymphocytic leukaemia (ALL) accompanied with high serum IL-18 levels have been analysed. There was little serum IL-18 bioactivity in the three patients with ATL, AMLL and ALL, while IL-18 mRNA expression was detected in leukaemia cells of all three patients.

Acute Disease↗

Urinary trypsin inhibitor levels in the urine of patients with haematological malignancies.

The urinary trypsin inhibitor (UTI) levels in the urine of patients with various haematological malignancies were determined, using automated latex agglutination immunoturbidimetry. The mean UTI levels in urine in acute non-lymphocytic leukaemia, myelodysplastic syndrome, non-Hodgkin's lymphoma, and multiple myeloma groups were significantly elevated, compared with the normal control group. It was found that the UTI level in urine changed from an elevated value to a normal value with haematological improvement by chemotherapy in a patient with myelodysplastic syndrome included in a previous study. These results suggest tha

Antineoplastic Agents↗

Orotic acid added to casein, but not to egg protein, soy protein, or wheat gluten diets increases 1,2-diacylglycerol levels and lowers superoxide dismutase activities in rat liver.

Effects of the dietary addition of orotic acid to a diet containing casein as a sole protein source on lipid levels in the liver and serum, activities of antioxidant enzymes in the liver, and some enzyme activities in serum, were compared with other diets containing egg protein, soy protein, or wheat gluten, respectively. 1. The contents in the liver of each lipid were increased by the addition of orotic acid as compared with those values without it. The orotic acid added to the casein diet caused accumulation of more liver total lipids, triacylglycerol, 1,2-diacylglycerol, and phospholipids than those fed three other diets. 2. The addition of orotic acid to the casein, but not to the other three diets, lowered the activities of liver superoxide dismutase and increased the activities of both serum ornithine carbamoyltransferase and alanine aminotransferase. Thus, the significant increase in serum ornithine carbamoyltransferase activities as the marker of liver lesions may result from the marked accumulation of liver lipids, decreased activities of hepatic superoxide dismutase, and the increased level of hepatic 1,2-diacylglycerol, followed by possibly the increased level of superoxide anion and increased activity of protein kinase C in rats fed the casein diet with orotic acid added.

Alanine Transaminase↗

Improving effect of feeding with a phosphorylated guar gum hydrolysate on calcium absorption impaired by ovariectomy in rats.

We have previously reported that a phosphorylated guar gum hydrolysate (P-GGH) promoted calcium absorption and the accumulation of bone calcium in rats. We now investigate the effect of P-GGH (50 g/kg of diet) on the intestinal calcium absorption and bones of ovariectomized (OVX) rats in comparison with sham-operated rats over a six-week ingestion period. The apparent calcium absorption was decreased by aging and ovariectomy in the rats fed on the control and GGH diets (50 g/kg of diet), but not in the rats fed on the P-GGH diet. The absorption was higher in the P-GGH group than in the GGH and control diet groups in the fourth and sixth weeks after feeding the test diets to OVX rats. Femoral calcium and strength were decreased by OVX in the rats fed on the control and GGH diets, but not in the rats fed on the P-GGH diet. The values of these parameters were higher in the P-GGH group than in either the control or GGH group of OVX rats. The amount of soluble calcium in the ileal contents was higher in the P-GGH group than in the control and GGH groups. These results indicate that P-GGH may be useful for preventing the reduction of intestinal calcium absorption and bone in the condition of estrogen deficiency.

Absorption↗

Different response to choline deficiency of the serum ornithine carbamoyltransferase activity in four strains of rats.

Rats of the Donryu, Wistar, Fischer, and Sprague-Dawley strains were examined for the effects of choline deficiency on liver lipids, serum lipids, and serum ornithine carbamoyltransferase. The liver total lipid, triacylglycerol, cholesterol and phospholipid contents in the choline-deficient rats were significantly higher than those in choline-sufficient rats. The contents of total lipids and phospholipids in the liver of the Wistar and Fischer rats fed on a choline-deficient diet were significantly higher than those of the Donryu and Sprague-Dawley rats. The levels of triacylglycerol, cholesterol and phospholipids in the serum were significantly decreased by feeding with the choline-deficient diet. The serum ornithine carbamoyltransferase activity was increased in the Wistar and Fischer strains by feeding with the choline-deficient diet. The Wistar and Fischer strains were consequently the most sensitive to both lipid accumulation and liver lesions induced by the choline deficiency.

Animals↗

Contractile responses of the basilar artery isolated from rabbits exposed to 8-day head-down tilt.

In the present study, the effects of head-down tilt (HDT) on contractile responses of basilar and popliteal arteries were investigated in vitro. The arteries were isolated from rabbits exposed to 8 d of 45 degrees HDT. Isometric tension and intracellular calcium were measured in an organ bath perfused with physiological salt solution. In the HDT rabbits, contractile response to norepinephrine (NE) was attenuated in the basilar artery, but not in the popliteal artery compared with control rabbits. HDT did not change the responses to either KCl or 5-hydroxytryptamine in both arteries. In the response of basilar artery to NE, the difference in both [Ca(2+)](i) transient and Ca sensitivity between control and HDT rabbits were statistically not significant. The response of the basilar artery to phenylephrine, a selective alpha(1)-adrenergic agonist, was also attenuated by HDT. Treatment with propranolol, a beta-adrenergic blockade, did not affect the response to NE in the basilar arteries isolated from control rabbits, but it significantly enhanced the response in the basilar arteries from HDT rabbits. These results suggest that exposure to 8-d HDT decreases a contractile response of the basilar artery to NE in rabbits. The reduction of NE-induced contraction is probably attributable to both decreased Ca transient and decreased Ca sensitivity, and decreased alpha(1)-adrenoceptor activity and increased beta-adrenoceptor activity seem to be involved in the mechanism.

Animals↗