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Biomedical subjects

Y Imai

Publications and source records attributed to Y Imai.

At least 667 records · Page 37Linked to original sources

[An in vivo DNA adduct database for carcinogens: O6-alkylguanine, O4-alkylthymine and 8-hydroxyguanine].

Many carcinogens react with DNA and form critical DNA adducts, such as O6-alkylguanine (O6-AG), O4-alkylthymine (O4-AT), and 8-hydroxyguanine (8-OHG). This study provides a database that can be used for molecular dosimetry of these DNA adducts. A literature survey on DNA binding in vivo was done by the Dialog search from the MEDLINE database. We propose a Critical Covalent Binding Index (CCBI) for the assessment of in vivo DNA binding level (expressed as micro mol chemical bound per mol G or T/mmol chemical administered per kg body weight). The number of records and compounds in parenthesis of O6-AG, O4-AT, and 8-OHG were 245(13), 54(4), 79(15), respectively. Since the CCBI values for N-nitrosamine in target organ were higher than for non-target organ, they may provide a useful index for estimation of target organ site and carcinogenic potency. As a case example, CCBI values for O4-AT from animal data were applied for diethylnitrosamine human exposure estimation by diethylnitrosamine.

Animals↗

[Reoperation after surgical repair of atrioventricular canal defect].

Among 114 survivors who underwent total repair of atrioventricular canal defect between 1981 and 1993, 19 patients underwent reoperation for the occurrence and progression of mitral valve insufficiency (18 patients), thrombosed prosthetic valve (1 patient), and subaortic stenosis (4 patients) on one or two occasions after operation. There were 7 males and 12 females with ages at reoperation ranging from 3 months to 13.8 years (mean, 3.8 years), and was no operative but one late death. At reoperation, reparative procedures involving the readjustment of previously repaired mitral cleft and annuloplasty were successfully achieved in 6 patients who had no additional abnormalities of subvalvar apparatus. Twelve patients, who were associated with additional valvar and subvalvar lesions, needed a prosthetic valve replacement. We emphasized that surgical technique based on precise knowledge of each individual mitral and submitral anatomy is indispensable to achieve good surgical results. When the anatomy involves submitral abnormalities, careful postoperative follow-up should be recommended to take measures of the progression of mitral valve regurgitation.

Adolescent↗

Nitric oxide production from macrophages is regulated by arachidonic acid metabolites.

In activated macrophages the inducible form of the enzyme nitric oxide (NO) synthase generates high amounts of the toxic mediator NO. After 20 h of treatment with LPS rat peritoneal macrophages release 12-16 nmol NO2-/10(5) cells which is detectable in the culture supernatant by the Griess reaction as a measure of NO formation. The addition of aminoguanidine (1 mM), a preferential inhibitor of the inducible NO-synthase, completely abolished NO2-accumulation. Incubation with indomethacin or acetyl-salicylic acid, preferential inhibitors of the cyclooxygenase pathway of the arachidonic acid metabolism, did not influence NO2- levels. Nordihydro-guaiaretic acid (50 microM), a preferential inhibitor of the lipoxygenase pathway, caused strong reduction of NO2- accumulation to 1.9 +/- 0.3 nmol/200 microliter. Simultaneous inhibition of cyclo- and lipoxygenase by BW755c resulted in an intermediate effect (7.3 +/- 1.1 nmol/200 microliter NO2-). These results show that the induction of NO production in activated macrophages is regulated by products of the lipoxygenase-pathway of the arachidonic acid metabolism.

Amino Acid Oxidoreductases↗

Opioid peptide release evoked by noxious stimulation of the hind instep of rats.

Previous studies showed that opioids and opioid peptides modulate vascular reactions such as plasma extravasation and vasodilatation through inhibition of substance P release from peripheral nerve endings of primary afferent fibers, and suggested the existence of endogenous opioid peptide activity related to regulation of inflammatory responses. Here we examined the effect of heat stimulation and antidromic stimulation of primary afferent fibers on the release of immunoreactive opioid peptides into the perfusate of the subcutaneous space in the rat instep. Antidromic stimulation of sectioned sciatic and saphenous nerves did not have any significant effect on the release of Met-enkephalin (Met-EK), while immersion of the hind paw in hot water (47 degrees C) for 30 min caused an increase in Met-EK release into the perfusate. High-pressure liquid chromatography of the perfusate revealed that noxious heat stimulation induced increase in release of Leu-enkephalin (Leu-EK) as well as Met-EK, although the maximal concentration of Leu-EK was less than 16% of that of Met-EK. No beta-endorphin was detected in the perfusate before, during or after heating. We conclude that noxious heat stimulation mainly leads to increase in Met-EK, and that this peptide originates mainly, from peripheral cells containing opioid peptides such as immune cells and/or Merkel cells, not from primary afferent fibers.

Animals↗

mu opiate receptor: cDNA cloning and expression.

mu opiate receptors recognize morphine with high affinity. A 2.1-kb rat brain cDNA whose predicted translation product displays 63% identity with recently described delta and kappa opiate receptor sequences was identified through polymerase chain reaction and cDNA homology approaches. This cDNA recognizes a 10.5-kb mRNA that is expressed in thalamic neurons. COS-cell expression confers naloxonazine-, Na(+)-, and GTP-sensitive binding of mu but not delta or kappa opioid ligands. Expressing cells bind morphine, [D-Ala2,N-methyl-Phe4,glyol5]enkephalin (DAMGO), and [D-Ala2,D-Leu5]enkephalin (DADLE) with nanomolar or subnanomolar affinities, defining a mu opiate receptor that avidly recognizes analgesic and euphoric opiate drugs and opioid peptides.

Amino Acid Sequence↗

Tissue-specific distribution and age-dependent increase of human CD11b+ T cells.

Distribution of CD11b Ag, a member of the leukocyte integrin (beta 2 integrin) family, on human T cells is not well characterized. We investigated in this study the tissue distribution and age-related alteration of human CD11b+ T cells. Significant proportions of CD11b+ cells were found in T cells from adult peripheral blood (18-58 yr) (20%), liver (32%), and spleen (16%), but were rarely observed in those from thymus, lymph nodes, intraepithelial lymphocytes, lamina propria lymphocytes, and lung. In contrast, percentages of CD28+ T cells, a counter population of CD11b+ T cells, were highest in lymph nodes (91%), modest in intraepithelial lymphocytes (82%), lamina propria lymphocytes (77%), PBL (77%), spleen (73%) and lower in thymus (62%), lung (60%) and liver (56%). The CD11b+ T cells from peripheral blood gradually increased with age, whereas the CD28+ T cells showed an age-dependent decrease. Namely, the percentages of CD11b+ T cells were 6% in newborns (cord blood), 15% in young adults (18 to 22 yr), 25% in middleaged adults (45 to 58 yr), and 27% in aged adults (72 to 86 yr), whereas those of CD28+ T cells were 96%, 83%, 72%, and 71%, respectively. Proportions of CD11b+ T cells in TCR-gamma delta+ or CD8+ T cells were, respectively, higher than those in TCR-alpha beta+ or CD4+ T cells. Age-dependent increase of CD11b+ T cells in CD8+ T cells was more obvious than that of CD4+ T cells. Furthermore, CD11b+ CD28+ T cells increased in the peripheral blood only of aged adults. The percentage of CD11b+ CD28+ T cells in TCR-gamma delta+ T cells was highest in young adults (25%), whereas that in CD4+ T cells was highest in aged adults (15%). CD11b+ CD28+ T cells expressed much potent IFN-gamma, IL-2, and IL-4 at mRNA level than CD28+ CD11b- T cells or CD11b+ CD28- T cells, and had potential cytotoxic activity. Roles of CD11b+ T cells in vivo were discussed.

Adolescent↗

Interleukin-2 enhances the viability of primary cultured rat neocortical neurons.

We determined the neurotrophic activity of interleukin-2 (IL-2) on primary cultured neocortical neurons from embryonic rat brain. IL-2 clearly enhanced the viability of cultured neurons in a dose-dependent manner. The neurotrophic effect of IL-2 was completely neutralized by IL-2 antibody. Furthermore, expression of IL-2 receptor mRNA was more pronounced in neurons than in other cultured cells such as astroglia and microglia. These results strongly suggest that IL-2 plays certain roles in the central nervous system as a neurotrophic factor.

Animals↗

[A case of bilateral aldosterone-producing adrenal adenomas].

A 43-year-old female was admitted to our hospital for high blood pressure control. She showed hypokalemia with increased urinary potassium excretion, high plasma aldosterone concentration (33.9ng/dl, normal range; 2-12ng/dl) and reduced plasma renin activity (trace, normal range; 0.83-5ng/ml/hr). Bilateral adrenal tumors were revealed by abdominal computed tomography, and left adrenalectomy and right partial adrenalectomy were performed. Cytochromes p-450 and other enzymes involved in aldosterone synthesis were found predominantly in the tumor portions but not in the zona glomerulosa of the attached adrenals, which histopathologically showed paradoxical hyperplasia. This was a rare case of bilateral aldosterone-producing adrenal adenomas, which we could differentiate from idiopathic hyperaldosteronism by employing immunohistochemical analysis of steroidogenic enzymes.

Adenoma↗

Clinical features of autosomal dominant retinitis pigmentosa with rhodopsin gene codon 17 mutation and retinal neovascularization in a Japanese patient.

A 49-year-old Japanese man had autosomal dominant retinitis pigmentosa with a point mutation in codon 17 of the rhodopsin gene, resulting in a threonine-to-methionine change, and retinal neovascularization in both eyes. Pigmentary degeneration mainly in the inferior area of the fundus, and severe loss in the upper portion of the visual field were observed. Moderately preserved rod and cone functions were demonstrated by electroretinograms. These findings differed from those of Japanese and white patients with autosomal dominant retinitis pigmentosa with a codon 347 mutation and were almost the same as those of white patients with the codon 17 mutation. Our study indicates that phenotypic similarities exist among patients with the same mutation, but of different racial backgrounds. The neovascularization in the right eye diminished over a two-year period in conjunction with the progression of retinal degeneration.

Adaptation, Ocular↗

Sulphation requirement for GlyCAM-1, an endothelial ligand for L-selectin.

L-selectin participates in the initial attachment of leukocytes to the vascular endothelium. On lymphocytes, it mediates binding to high endothelial venules of lymph nodes. As a selectin it functions as a calcium-dependent lectin recognizing carbohydrate-bearing ligands on endothelial cells. Two lymph node ligands for L-selectin have been identified as sulphated glycoproteins of M(r) approximately 50K and approximately 90K, called Sgp50 and Sgp90 (ref. 10). The recently cloned Sgp50 (ref. 12), now designated GlyCAM-1, is a high endothelial venule-associated, mucin-like glycoprotein containing predominantly O-linked carbohydrate chains. Sialylation of GlyCAM-1 is necessary for its ligand activity and a role for fucosylation is suspected. We have used chlorate as a metabolic inhibitor of sulphation, and report here that GlyCAM-1 has an additional requirement for sulphate.

Animals↗

Cell-mediated immune-pancytopenia complicating primary Sjögren's syndrome.

A 64-year-old woman with mild bilateral parotid gland swelling and bilateral lower extremity purpura was admitted for evaluation of xerostomia and pancytopenia. The patient had an increased erythrocyte sedimentation rate, pancytopenia, and positive tests for antibodies to nuclear antigen, SS-A, and SS-B. Impaired cell-mediated immunity was also present. Bone marrow aspiration showed a hypoplastic marrow with an increased percentage of lymphocytes. A positive Schirmer's test and keratoconjunctivitis were also noted. A diagnosis of primary Sjögren's syndrome was made by sialography and histological salivary gland findings. Therapy with prednisolone improved the pancytopenia. Addition of the patient's peripheral blood mononuclear cells to cultures of bone marrow mononuclear cells derived from a healthy volunteer dose dependently inhibited colony formation, including mixed hemopoietic colonies. On the other hand, addition of the patient's serum failed to inhibit colony formation by normal bone marrow mononuclear cells. These results suggested that one of the causes of pancytopenia in primary Sjögren's syndrome might be mediated by the inhibition of mononuclear cells to the hemopoietic progenitors.

Blood Physiological Phenomena↗

Surface-enhanced Raman spectroscopic detection of CO2-(3), SO2-(3), and nucleic acid bases using polyvinyl alcohol film doped with Ag fine particles.

Surface-enhanced Raman scattering (SERS)-active polyvinyl alcohol films doped with Ag particles have been prepared by a counterdiffusion method. SERS spectra of CO2-(3), SO2-(3), and DNA bases have been observed by using the films. The films containing aggregated Ag particles are useful to observe SERS spectra of adsorbates. DNA bases (cytosine, uracil, thymine, guanine, and adenine) can be detected at a level of 10(-8)-10(-9) M by this method.

Adenine↗

Direct demonstration of heterogeneous, sulfated O-linked carbohydrate chains on an endothelial ligand for L-selectin.

We have previously identified endothelial ligands for L-selectin as sialylated, fucosylated and sulfated glycoproteins of approximately 50 kDa and 90 kDa (Sgp50 and Sgp90). In this report, we use the beta elimination reaction to demonstrate directly the presence of sulfated O-linked sugar chains on one of these ligands, after metabolic labeling with radiolabeled sulfate or fucose. All of the sulfated and the majority of the fucosylated O-linked sugar chains were shown to be sialylated by affinity chromatography on a Limax agglutinin column. Analyses by anion exchange and gel permeation chromatography revealed a complexity of sugar chains, which were heterogeneous both in charge and size. Charged groups other than sialic acid appeared to exert a predominant influence on the total charge of the sugar chains. The probable existence of a varying number of sulfate modifications per sugar chain is discussed.

Carbohydrate Conformation↗

Clinical evaluation of plasma des-gamma-carboxy prothrombin as a marker protein of hepatocellular carcinoma in patients with tumors of various sizes.

We measured des-gamma-carboxyprothrombin (DCP) (prothrombin induced by vitamin K absence or antagonist-II, abbreviated as PIVKA-II) by a newly developed enzyme immunoassay using an anti-DCP monoclonal antibody in 665 human subjects, of which 112 were patients with hepatocellular carcinoma (HCC). PIVKA-II was elevated to more than 0.1 AU/ml in 54 of the 112 patients (48.2%) with HCC, while it was positive only in 7.1% of those with liver cirrhosis and 3.1% of those with chronic hepatitis. Three patients with elevated PIVKA-II greater than 0.1 AU/ml who had been diagnosed as having liver cirrhosis by ultrasonography and computed tomography at the start of this study developed a diffuse type of HCC three or six months later, which was detected by angiography. No obvious correlation was observed between plasma PIVKA-II concentration and serum alpha-fetoprotein (AFP) level in HCC patients. Of the 112 HCC patients, 40.2% showed an increase in AFP to above 200 ng/ml. In the remaining patients, 32.8% had a PIVKA-II concentration greater than 0.1 AU/ml. In these patients with a negative or low serum AFP concentration, PIVKA-II proved to be a valuable tumor marker for laboratory diagnosis of HCC. Among them, 59.8% tested positive for PIVKA-II and/or AFP. Thus, combination assay with PIVKA-II and AFP seems useful for increasing the accuracy of laboratory diagnosis of HCC. None of patients with a solitary tumor smaller than 2 cm had elevated PIVKA-II. In patients with larger-sized and multiple HCC, positive results of elevated PIVKA-II were more frequent than those of increased AFP.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗

Longer transplanted heart allograft survival in rats without immunosuppressants after intrathymic myocardial cell inoculation in the neonatal period.

In order to induce immunological tolerance, intrathymic inoculation of incompatible donor myocardial cells in rats was performed in the neonatal period. Isolated myocardial cells harvested from donor rat hearts were inoculated into the thymus of incompatible neonatal recipient rats without administration of immunosuppressive agents. Ten weeks later, the hearts from the donors were transplanted heterotopically to these pretreated rats. The animals were sacrificed on the 7th day of heterotopic transplantation and were examined histopathologically. The results showed no early rejection in the group in which intrathymic myocardial cell inoculation had been performed in the neonatal period. Immunohistochemical staining for myoglobin of the thymus from the inoculated recipient revealed that the donor myocardial cells continued to survive. The longest proven graft survival in this series, thus far, was 60 days, while it was only 7 days in the control group.

Animals↗