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Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 1,099 records · Page 61Linked to original sources
PubMed1996

Reduced vasodilator response of the right coronary artery to myocardial ischemia in the hypertrophied right ventricle.

The reduced reactive hyperemic response of the right coronary artery (RCA) to brief coronary occlusion was assessed in dogs with pressure-induced right ventricular hypertrophy (RVH). Right coronary reactive hyperemia was observed in normal dogs and in dogs with pressure-induced RVH. RVH was induced by chronic pulmonary artery banding in eight 3- to 6-month-old dogs, and reactive hyperemia responses to coronary occlusion lasting for 5, 10, 15, 20, 30, 45, and 60 sec were compared to those in normal dogs. In dogs with RVH, the peak reactive flow rate and excess blood flow debt repayment after the release of 5- to 60 sec RCA occlusion were markedly attenuated. The calculated minimum coronary resistance was higher in RVH dogs than in normal dogs (p < 0.02). The occlusion time that produced one-half of the maximum %PRHc, T1/2, was significantly (p < 0.01) shorter in RVH dogs than in normal dogs, where %PRHc = (peak reactive flow rate baseline flow rate)/(baseline flow rate). T1/2 in RVH dogs varied inversely with right ventricular systolic pressure. Therefore, blood flow in the RCA in RVH is characterized by an attenuated flow response to acute myocardial ischemia, suggesting inadequate development of the coronary vasculature supplying the hypertrophied ventricle.

Animals↗
PubMed1996

Histochemical study of follicles in the senescent porcine pituitary gland.

Follicles displaying a positive periodic acid-Schiff reaction to a colloid substance in the anterior pituitary gland have been observed in many vertebrates, including humans. It is also known that these follicles greatly increase in number and size with age. We therefore performed histochemical analysis of these colloid follicles in the senescent porcine pituitary gland in order to clarify their nature and biological significance. Results from various histological stains suggest that the colloid contains some polysaccharides or glycoproteins. In addition to the histological stains, lectin histochemistry revealed that the colloid contains sialic acid, N-acetyl galactosamine and galactose. Also, lectin staining indicated that some glycoproteins, most likely Asn-linked sialoglycoproteins, are localized in the colloid. The cells (FS cells) surrounding the colloid were densely stained with an antibody to S-100 protein but were not stained with antibodies to any other anterior pituitary hormones. Frequently mammotrophs (PRL cells), and occasionally gonadotrophs (LH cells) were found closely associated with folliculo-stellate cells (FS cells which lay next to the large colloid containing follicles. This suggests that not only are the FS cells important in the production of the colloids, but the adjacent LH and PRL cells in some way also contribute to their formation.

Aging↗
PubMed1996

Expression sites of two byssal protein genes of Mytilus galloprovincialis.

Mussels form byssal threads that can attach tenaciously to wet and irregular surfaces. The byssus consists of a fibrous collagenous core, and at least two types of polyphenolic proteins surround it. One of these proteins, designated Mgfp-1, coats the collagenous core; the other, designated Mgfp-2, is the major component of the terminal adhesive plaque of byssal threads. Both proteins contain 3,4-dihydroxyphenylalanine (DOPA) in their primary sequences. In this study, the sites of expression of the genes encoding the polyphenolic proteins were investigated in Mytilus galloprovincialis. By northern blot analysis, we found that the expression of both genes is foot-specific. Northern blot analysis of RNA isolated from the distal end and the remaining proximal portion of the foot indicated that the Mgfp-2 gene is expressed primarily in the distal part, whereas Mgfp-1 expression occurs in both parts. In situ hybridization indicated that the Mgfp-1 gene transcript is localized in the accessory gland along the ventral groove of the foot, and the Mgfp-2 gene transcript is localized in the phenol gland near the foot apex. Thus, it was shown that tissues expressing Mgfp-1 and Mgfp-2 are located around the ventral groove in an arrangement appropriate for byssus formation.

Amino Acid Sequence↗
PubMed1996

Effects of roxithromycin, erythromycin and troleandomycin on their N-demethylation by rat and human cytochrome P450 enzymes.

1. The effects of treatment of rat with roxithromycin, erythromycin and troleandomycin as well as other chemicals including typical cytochrome P450 inducers were examined in rat and human liver microsomes. 2. Erythromycin and troleandomycin but not roxithromycin caused slight increases in CYP3A1 levels and the N-demethylation of roxithromycin, erythromycin and troleandomycin and oxidation of nifedipine in rat, but none of these chemicals induced significantly CYP2B1 levels or benzphetamine N-demethylation activities. 3. Dexamethasone and pregnenolone 16 alpha-carbonitrile induced CYP3A1 levels and N-demethylation of roxithromycin, erythromycin and troleandomycin but not of benzphetamine, in rat liver microsomes. Treatment of rat with phenobarbital caused increases in both CYP2B1 and 3A1 levels and all of the N-demethylation activities examined. Phenytoin and metyrapone produced increases in contents of 2B1 and activities of benzphetamine N-demethylation as well as of roxithromycin, erythromycin and troleandomycin, although these two inducers did not induce 3A1 protein significantly. 4. In man, a liver sample that was high in CYP3A4 and nifedipine oxidation activity was found to be the most active in N-demethylation activities towards these substrates examined. In addition, recombinant 3A4 catalysed very efficiently the N-demethylation of roxithromycin, erythromycin and troleandomycin in reconstituted monooxygenase systems. 5. These data suggest that erythromycin and troleandomycin, but not roxithromycin, were able to induce CYP3A1 in rat liver microsomes, and that N-demethylation of roxithromycin, erythromycin and troleandomycin were catalysed mainly by 3A1 (and partly by 2B1) in rat and by 3A4 in man.

Animals↗
PubMed1996

The expression of IL-6 and its related genes in acute leukemia.

Acute myeloid leukemia (AML) blast cells frequently produce interleukin-6 (IL-6) and other cytokines such as colony-stimulating factors (CSF: G-CSF, M-CSF, and GM-CSF), tumor necrosis factor (TNF)-alpha, and IL-1. The AML blast cells that produced IL-6 alone could not form autonomous in vitro colonies, whereas the blast cells that coexpressed CSF in addition to IL-6 were able to form such colonies. This suggests that IL-6 acts as a costimulator to enhance CSF-induced clonogenicity of AML blast cells. TNF-alpha and IL-1 that are produced from the blast cells may stimulate the growth of the AML blast cells by inducing production of CSF in bone marrow stromal cells or in the blast cell population itself. Improvement of clinical manifestations by the administration of an anti-IL-6 murine monoclonal antibody in a patient with AML-M5B confirmed an important role of IL-6 in in-vivo growth of the blast cells. The mRNA expression of IL-6 and its related genes in AML and acute lymphoid leukemia (ALL) blast cells was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). IL-6 mRNA expression was common in AML, but rare in ALL, whereas the IL-6 receptor (IL-6R) mRNA was expressed in almost all cases of AML and in more than half of the cases of ALL. In contrast, gp130 was ubiquitously expressed in both AML and ALL. A significant correlation between the levels of IL-6R expression and the responsiveness of the blast cells to exogenous IL-6 was observed. This suggests the possibility of the rapid prediction of the responsiveness of leukemic cells to exogenous IL-6 (IL-6 administration for therapy) by rapid measurement of IL-6R mRNA by RT-PCR.

Acute Disease↗
PubMed1996

Age-related changes of alpha-tocopherol transfer protein expression in rat liver.

Developmental changes in expression of alpha-tocopherol transfer protein (alpha-TTP) after birth were investigated using rats with respect to plasma changes of tocopherols. The expression of alpha-TTP in the neonatal rat liver, which was very low immediately after birth, increased steadily during the two weeks of life before weanling and reached the adult level at four weeks. During the suckling period, the plasma ratio of alpha-tocopherol to gamma-tocopherol linearly increased, because plasma alpha-tocopherol which was low immediately after birth, increased rapidly during the period, while gamma-tocopherol remained unchanged. The increase in the ratio seemed to correlate with the developmental expression of alpha-TTP in the liver during this period. The ratio also reached the adult level after four weeks. The expression of alpha-TTP was investigated using primary cultured rat hepatocytes. The expression of alpha-TTP was found to be extremely low after 20h of culture. The decrease in alpha-TTP expression was exacerbated by adding epidermal growth factor to the culture medium and was inhibited by adding dexamethasone. These observations suggest that expression of alpha-TTP may be affected by the state of hepatic differentiation.

Aging↗
PubMed1996

[The efficacy of ATP sensitivity assay on intravesical prophylactic instillation for superficial bladder cancer].

BACKGROUND: The object of this study is to evaluate the usefulness of the ATP sensitivity assay for appropriate selection of anticancer drugs for prophylactic bladder instillation therapy in patients with superficial bladder cancer. METHODS: The ATP assay was performed using the method reported previously. The anticancer drugs examined were ADM, MMC, THP-ADM and EPI. The 5-year rate of non-recurrence in group A (32 cases) which had been treated using the results of ATP assay, was compared with that of group B (37 cases), for which the ATP assay was not performed. RESULTS: The most sensitive anticancer drug was THP-ADM. The 5-year rate of non-recurrence in group A (80.9%) was significantly higher than that in group B (39.4%) (p < 0.001). Tumor recurrences in group A was observed within 2 years post-operatively in all cases. When the ATP assay was re-performed in 3 cases with recurrent disease, altered antitumor sensitivity was observed. CONCLUSION: These findings suggested that ATP assay was useful for choosing effective anti-cancer drugs for prophylactic instillation, especially for patients with primary or solitary tumor, grade 2 disease or tumor of a certain size (> or = 1 cm). It also appeared that the ATP assay should be performed for patients with primary superficial bladder cancer as a screening test for the selection of drugs for prophylactic instillation therapy.

Administration, Intravesical↗
PubMed1996

[Usefulness of bladder auto-augmentation in neurogenic bladder: a case report].

A 41-year-old male with myelomenigocele underwent a bladder auto-augmentation and endoscopic collagen injections. He has been performing self intermittent catheterization for 10 years but urinary incontinence remained unchanged. Furthermore, he suffered from recurrent pyelonephritis due to the left vesicoureteral reflux. A preoperative fluoroscopic urodynamic study showed a poorly compliant bladder with the maximal bladder capacity of 200 ml at 60 cmH2O. The left vesicoureteral reflux was observed at 10 cmH2O. The low compliant bladder was treated with the bladder autoaugmentation and the left vesicoureteral reflux was treated with the endoscopic subureteral injection of collagen 5 months after the previous operation. A fluoroscopic urodynamic study 6 months postoperatively showed the increase of the maximal bladder capacity of 300 ml at 18 cmH2O and the reflux disappeared completely. The endoscopic periurethral injections of collagen improved his persisting urinary incontinence. In patient with neurogenic bladder having a lot of clinical problems, bladder auto-augmentation is less invasive and offers many advantages over enterocystoplasy.

Adult↗
PubMed1996

Determination of absolute configuration and biological activity of new immunosuppressants, mycestericins D, E, F and G.

Mycestericins D, E, F and G were isolated from the culture broth of Mycelia sterilia ATCC 20349 as potent immunosuppressants. Mycestericins F and G were identical with dihydromycestericins D and E, respectively. Their absolute configurations were determined by use of the modified MOSHER'S method and by comparison of the CD spectra of their benzoate derivatives with those of synthetic analogs. Mycestericins D, E, F and G suppressed the proliferation of lymphocytes in the mouse allogeneic mixed lymphocyte reaction.

Animals↗
PubMed1996

Characterization of CYP2A6 involved in 3'-hydroxylation of cotinine in human liver microsomes.

Nicotine is primarily metabolized to cotinine, and cotinine is further metabolized to trans-3'-hydroxycotinine in human liver, which is a major metabolite of nicotine in humans. We studied the formation of trans-3'-hydroxycotinine from cotinine in human liver microsomes. trans-3'-Hydroxycotinine formation demonstrated single enzyme Michaelis-Menten kinetics (Km, 234.5 +/- 26.8 MicroM; Vmax, 37.2 +/- 2.4 pmol/min/mg protein). Significant correlation (r = .967, P < .001) between cotinine 3'-hydroxylase activities at low (50 microM) and high (1 microM) cotinine concentrations in 20 human liver microsomes suggested the contribution of a single enzyme to cotinine 3'-hydroxylation. The cotinine 3'-hydroxylase activity correlated significantly with immunoreactive cytochrome P450 (CYP)2A6 contents (r = .756, P < .01) and coumarin 7-hydroxylase activity (r = .887, P < .001). The cotinine 3'-hydroxylase activity was inhibited by coumarin, alpha-naphthoflavone, chlorzoxazone and anti-rat CYP2A1 antibodies. Microsomes of B-lymphoblastoid cells expressing human CYP2A6 exhibited cotinine 3'-hydroxylase activity. The Km value of the expressed CYP2A6 (264.7 microM) was almost identical to that of human liver microsomes. In conclusion, cotinine 3'-hydroxylation appears to be catalyzed solely by CYP2A6 in humans. Cotinine is a candidate for a new substrate for CYP2A6 in humans.

Aryl Hydrocarbon Hydroxylases↗
PubMed1996

(+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502) as a novel substrate for cytochrome P450 2A6 in human liver microsomes.

(+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) was oxidized by human liver microsomes to produce the S-oxide as a sole metabolite. Indirect evidence suggested that the S-oxidation was catalyzed by cytochrome P450 (CYP). Eadie-Hofstee plots showed biphasic pattern, suggesting that at least two enzymes were involved in the S-oxidation in human liver microsomes. Kinetic parameters of the S-oxidase with high-affinity showed Km and Vmax values of 20.9 +/- 4.4 microM and 0.111 +/- 0.051 nmol/min/mg microsomal protein, respectively. The S-oxidase activity was inhibited by coumarin and anti-CYP2A antibody. Among the contents of forms of CYP 20 samples of human liver microsomes, the content of CYP2A6 correlated with S-oxidase activity measured with 50 microM SM-12502 (r = .808, P < .0005). A close correlation (r = .908, P < .0001) was observed between activities of SM-12502 S-oxidase and coumarin 7-hydroxylase. Microsomes from genetically engineered human B-lymphoblastoid cells expressing CYP2A6 metabolized SM-12502 to the S-oxide efficiently. The results indicate that CYP2A6 isozyme is a major form of CYP responsible for the S-oxidation of SM-12502 in human liver microsomes. Thus, SM-12502 will be a useful tool in further research to analyze a human genetic polymorphism of CYP2A6.

Animals↗
PubMed1996

Alternating sciatica while jogging: an early symptom of cauda equina tumor.

Three athletic patients with cauda equina or lumbosacral cord tumor noticed, as an early symptom of the disease, alternating bilateral sciatica synchronized with each stride while jogging. Comparison with athletic patients who developed lumbar disc hernia suggested that this symptom was significant. The authors speculated that the mechanism producing this symptom is the inertial force induced while jogging, which acts on the tumor in its early stage, when it is still quite mobile in the intradural space. The diagnostic role of this symptom in cauda equina and lumbosacral cord tumor should be recognized.

Adolescent↗