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Biomedical subjects

M Mizutani

Publications and source records attributed to M Mizutani.

At least 127 records · Page 7Linked to original sources

Clinical value of argyrophilic organizer region in bladder transitional cell carcinoma.

For the purpose of elucidating whether or not argyrophilic organizer regions (AgNORs) predict the biological behaviors of bladder tumors, the AgNOR was analyzed in 80 primary bladder transitional cell carcinomas (TCCs), using the computer-assisted image analyzer. The AgNOR parameters used were the mean AgNOR count (C-AgNOR) and the percentage of cells exhibiting more than 3 AgNOR dots or 4 AgNOR dots within nuclei (3P-AgNOR and 4P-AgNOR, respectively). The correlation of C-AgNOR with 3P-AgNOR and 4P-AgNOR reached a high statistical significance (p < 0.0001, respectively). All of these three AgNOR parameters correlated with histological grade, whereas the difference between grade I and II proved to be higher in 3P-AgNOR and in 4P-AgNOR (p < 0.01, respectively) as compared with that in C-AgNOR (p < 0.05). Similarly, these three parameters correlated with histological stage, whereas the statistical significance of the correlation was less prominent in C-AgNOR. Moreover, the prognostic relevance was noted in C-AgNOR (p = 0.041), whereas it was indicative in 3P-AgNOR as well as in 4P-AgNOR (p = 0.090 and p = 0.061, respectively). These results suggest that 3P-AgNOR and 4P-AgNOR reflect the difference in the proliferative activity of individual TCCs more precisely than C-AgNOR. Since the biological behaviors of individual TCCs cannot be predicted by the proliferative activity alone, the AgNOR in TCCs has a rather limited value regarding the prediction of survival.

Adult↗

Efficacy of Ibudilast on lower limb circulation of diabetic patients with minimally impaired baseline flow: a study using color Doppler ultrasonography and laser Doppler flowmetry.

Ibudilast is a prostacyclin-mediated vasodilator and antiplatelet agent. The hemodynamic effects of ibudilast were evaluated in 41 patients with non-insulin-dependent diabetes mellitus by means of two-dimensional Doppler ultrasonography and laser Doppler blood flowmetry. Before and one hour after oral administration of ibudilast (10 mg), or elastase (1800 U) as a control, the cross-sectional area (CSA) of the dorsal pedis artery, its blood flow index (BFI), and dermal microcirculatory blood volume (MBV) were measured. In the ibudilast group, all of the parameters (CSA, BFI, and MBV) significantly increased as compared with the elastase group. These data suggest that ibudilast is effective in ameliorating diabetic macroangiopathy and microangiopathy of the lower limbs.

Administration, Oral↗

A new inherited muscular disorder in Japanese quails (Coturnix coturnix japonica).

Thirteen adult mutant (LWC strain) Japanese quails (Coturnix coturnix japonica), between the ages of 8 and 60 weeks were examined for a progressive muscular disorder. The disorder, inherited as an autosomal dominant trait, was clinically apparent as early as 28 days of age; it was characterized by generalized myotonia, muscle stiffness, and muscle weakness. Affected birds were identified by their inability to lift their wings vertically upward and by their inability to right themselves when placed on their dorsum. Electromyographic studies in two mutant quails showed high-frequency repetitive discharges comparable to those of myotonic runs. These discharges persisted after nerve resection. The distinctive histopathologic changes in the various muscles examined were ring fibers, sarcoplasmic masses, and internal migration of sarcolemmal nuclei. A slight decrease in the size of type IIB muscle fibers and a slight increase in the size of type IIA fibers were observed in the M. pectoralis thoracicus of affected quails. In older affected birds, inter- and intrafascicular fatty infiltration with replacement of type IIB fibers by fat cells was seen in the pectoral muscles. Single fiber necrosis, nonspecific lymphorrages, and variations in the muscle fiber size and shape were also noted. The typical muscle lesions and multisystem involvement, which was manifested by testicular degeneration and atrophy in the male LWC specimens and bilateral lenticular cataracts in 6 of 13 affected mutant quails, suggest resemblance of this new inherited muscular disorder to myotonic dystrophy in man.

Animals↗

Indomethacin-induced lesion modifies contractile activity in rat small intestines.

BACKGROUND: Indomethacin induces intestinal lesions. The change in contractility of segments with lesions was studied. METHODS: Motility was recorded in segments with lesions isolated from the rat small intestine 24 h after a subcutaneous injection of indomethacin (20 mg/kg). RESULTS: Concentration-contraction curves for acetylcholine shifted leftward independently of the degree of severity of lesions, but the curves for carbachol and 5-hydroxytryptamine did not. Contractions produced by intramural nerve stimulation were enhanced in segments with no visible damage but decreased with progression of lesions. Neostigmine augmented them in normal rats but not in indomethacin-treated rats. The peristaltic activity was enhanced in segments with no visible lesions. CONCLUSIONS: The results suggest that treatment of the rat with indomethacin enhances contractility of the small intestine owing to diminution of acetylcholinesterase activity independently of the degree of lesions and reduces it owing to decreased responsiveness of enteric neurons with the progression of lesions.

Acetylcholine↗

[P-glycoprotein expression in hematological malignancies].

To clarify the common characteristics among P-glycoprotein (P-gp)-expressing hematological malignancies and whether chemotherapies could or could not induce P-gp expression, we analyzed P-gp/MDR1 expression in tumor cells from 200 Japanese patients (104 with acute myeloblastic leukemia (AML); 30 with acute lymphoblastic leukemia (ALL); 66 with mature lymphoid malignancies). Functional P-gp expression was examined by Rhodamine-123 efflux test, and estimated with the data by RT-PCR method. In mature lymphoid malignancies, the cells of T or natural killer (NK) cell malignancies frequently expressed P-gp/MDR1. In AML, frequent P-gp/MDR1 expression was associated with the expression of CD7 or c-kit and with 8; 21 chromosomal translocation (p < 0.01), which were thought to be the characteristics of the hematopoietic stem cell. Though the expression of P-gp/MDR1 was more frequent at onset than at relapse phase, the increase is thought to result from the expansion of blastic fraction expressing P-gp/MDR1. In ALL, P-gp/MDR1 expression was not frequent in B-cell precursor lineage (three of eighteen patients), but the incidence was high in CD7(+) surface CD3(-) cases (seven of the cases). These results indicate P-gp/MDR1 expression is more frequently in the tumor of T, NK cell and stem cell, reflecting the characteristics of its normal counterpart.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Eicosapentaenoic acid enhances intracellular free calcium in cultured human endothelial cells.

Eicosapentaenoic acid (EPA) caused elevations of intracellular free Ca2+ concentration ([Ca2+]i) measured by fura-2 fluorescence in cultured human endothelial cells. The EPA-induced increase in [Ca2+]i could still be observed when either cyclooxygenase or lipoxygenase inhibitors were added. These results suggest that EPA itself rather than its metabolites has direct effects on intracellular Ca2+ mobilization, causing the elevation of [Ca2+]i.

Calcium↗

A complete culture system for avian transgenesis, supporting quail embryos from the single-cell stage to hatching.

We report here a method to produce quail hatchlings by culture in vitro from the single-cell stage. The culture is composed of three steps. In the first step, the fertilized ovum surrounded by thick albumen obtained from the magnum is cultured for 24 hr at 41.5 degrees C in a tightly sealed 20-ml plastic cup with chicken thin albumen added to the equator level of the ovum (System Q1). In the second step, a quail egg shell, cut horizontally and emptied, is used as a bed shell. After the thick albumen is removed, the embryo with egg yolk is transferred to the bed shell and thin albumen from chicken eggs is added to fill the shell. Then, the embryo is cultured for an additional 52 hr at 37.5 degrees C while being rocked at an angle of 90 degrees at 30-min intervals (System Q2). The embryo is transferred again to a chicken bed shell and cultured at 37.5 degrees C with rocking at a 30-degree angle (System Q3). Just before hatching, the rocking of embryos is stopped. The procedure yielded a hatchability of 25%. For transgenesis, a plasmid construct containing a beta-actin-lacZ hybrid gene (pMiwZ) is microinjected into the ovum at the single-cell stage, which is cultured in vitro for 85-90 hr using Systems Q1 and Q2 consecutively. Seven out of 17 surviving embryos exhibited lacZ gene expression in embryonic tissues as detected by histochemistry. The procedure described here should be highly applicable for the production of transgenic birds.

Actins↗

Greater number of microtubules per axon of unmyelinated fibers of mutant quails deficient in neurofilaments: possible compensation for the absence of neurofilaments.

Morphometric evaluations were performed on the peroneal nerve from mutant quails deficient in neurofilaments (NF) to elucidate the effect of an absence of NF on unmyelinated axons. The diameter frequency distribution of unmyelinated axons was similar between controls and mutants. The mean transverse axonal area, axonal circumference and circularity index of the unmyelinated axons were also similar in controls and mutants. However, the number of microtubules (MT) per axon was greater (P < 0.01) in the mutants than in the controls. The regression analysis relating the number of MT per axon to the diameter of unmyelinated axons indicated a greater number of MT in the mutants than in the controls (P < 0.05-0.01). A significantly greater number of MT per axon in the mutants may suggest a compensatory increase of MT in the absence of NF. This may conserve the size and transverse circular profile of the unmyelinated axons which are probably maintained by both MT and NF in the controls. The number of MT may be increased at the expense of the soluble fraction of tubulin.

Animals↗

Eicosapentaenoic acid enhances myo-inositol uptake in cultured human aortic smooth muscle cells.

The effects of elevated glucose and Eicosapentaenoic acid (EPA, 20:5) on myoinositol uptake in human aortic smooth muscle cells (HASMC) were evaluated. Myo-inositol incorporation into HASMC was dependent on an active transport system via Na(+)-K+ ATPase activity based on the results with Na+ deprivation and Ouabain (5 mM). Although glucose (27.5, 55 mM) inhibited 2-[3H] myo-inositol uptake, the addition of EPA (3 x 10(-4) M) prevented glucose-mediated inhibition. In addition, EPA potentiated Na(+)-K+ ATPase activity of HASMC. Since EPA decrease glucose-mediated inhibition of myo-inositol uptake, this agent might ameliorate aortic smooth muscle cell function associated with diabetes.

Adult↗

Acrylamide-induced neurotoxicity in the central nervous system of Japanese quails. Comparative studies of normal and neurofilament-deficient quails.

Acrylamide (AC) neurotoxicity in the central nervous system (CNS) in normal and neurofilament (NF)-deficient mutant (Quv) Japanese quails was investigated. Acrylamide (100 mg/kg) was injected intraperitoneally every other day. After the birds manifested neurological signs, they were necropsied (after 10-30 AC injections) and examined morphologically. All of the AC-intoxicated normal quails showed distal, retrograde nerve fiber degeneration associated with neurofilamentous axonal swellings in the spinal nerve tracts. There were axonal swellings without degenerative changes in other parts of the CNS. In Quv quails, distal nerve fiber degeneration was not observed in the spinal nerve tracts, although AC-induced membranous organelle accumulations were found in preterminal and terminal nerve fibers. Cytological remodeling similar to the axon reaction was seen mainly in dorsal root ganglia of AC-intoxicated normal and Quv quails. In addition, perikaryal response indicating impaired metabolic activity was observed in Quv quails. The present study showed that Quv quails are sensitive to neurotoxic effects of AC. It is suggested that AC-induced neurotoxicity is not initiated exclusively through its action on NF.

Acrylamide↗

Benign prostatic hyperplasia: value of MR imaging for determining histologic type.

PURPOSE: To assess the value of magnetic resonance (MR) imaging for determining the histologic type of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Unenhanced T1- and T2-weighted images and gadolinium-enhanced T1-weighted images were obtained in the transverse plane at 1.5 T in 33 patients with BPH. Hyperphasia was classified as stromal or nonstromal. Nonstromal hyperplasia was diagnosed if (a) the nodules in the inner gland had heterogeneous high signal intensity on T2-weighted images and peripheral enhancement on gadolinium-enhanced images, (b) a surgical capsule was present, or (c) the inner gland volume to total volume ratio was greater than 0.75. RESULTS: A correct diagnosis was made with MR imaging in 23 of 24 patients with nonstromal hyperplasia and eight of nine with stromal hyperplasia (94% accuracy). In nonstromal hyperplasia, nodular lesions were seen in 20 patients and a surgical capsule was seen in 19. Eighteen patients had a transition zone ratio greater than 0.75. CONCLUSION: MR imaging appears to be useful for choosing the type of pharmacotherapy performed because accurate histologic assessment is possible.

Aged↗

The effect of exercise on plasma biopterin levels.

The plasma total biopterin and tetrahydrobiopterin levels of 29 normal volunteers were measured before and after exercise by ergometer, and those of 10 were also measured until 24 h after exercise. An increase of plasma total biopterin and tetrahydrobiopterin was observed only after strong exercise, which exhausted the subjects, the ratio of tetrahydrobiopterin to total biopterin not differing before and after exercise. The increase of plasma biopterins disappeared 2 h after exercise. The mechanism of the increase of plasma biopterins was thought to be different from that of patients with affective disorders.

Adult↗

Changes in plasma tetrahydrobiopterin levels of depressives in depressive and remission phases: reconfirmed by measurement with an internal standard.

Plasma total biopterin and tetrahydrobiopterin levels of 10 normal controls and 10 patients with monopolar depression were measured with and without internal standard. The levels did not differ between the two methods. A significant increase of total biopterin levels and the lower ratio of tetrahydrobiopterin to total biopterin in the depressive phase were observed in the plasma of patients with depression compared to normal controls, and these changes in plasma biopterin tended to normalize in the remission phase.

Adult↗

Opioid peptides selective for receptor types modulate cocaine-induced behavioral responses in mice.

The effects of intracerebroventricular injection of mu-, kappa- and delta-selective opioid agonists on cocaine-induced behavior were investigated in mice using multidimensional behavioral analysis. Cocaine (3.0 mg/kg) produced a marked increase in linear locomotion, circling, rearing and/or grooming, although the mu-opioid agonist [D-Ala2, NMePhe4, Gly-ol] enkephalin (DAMGO) (0.003 and 0.01 microgram), the kappa-opioid agonist dynorphin A- (1-13) (3.0 and 12.5 micrograms) or the delta-opioid agonist [D-Pen2, L-Pen5]enkephalin (DPLPE) (0.3 and 1.0 micrograms) did not significantly affect behavioral responses. DAMGO (0.003 and 0.01 microgram) and dynorphin A- (1-13) (12.5 micrograms) inhibited the cocaine (3.0 mg/kg)-induced increase in linear locomotion, circling and/or rearing. In contrast, DPLPE (1.0 micrograms) enhanced the cocaine (3.0 mg/kg)-induced increase in circling. The effects of DAMGO (0.003 microgram), dynorphin A- (1-13) (12.5 micrograms) and DPLPE (1.0 micrograms) were fully reversed by receptor-selective opioid antagonists, such as beta-funaltrexamine (5.0 micrograms), Mr2266 (5.6 mg/kg) and naltrindole (10.0 mg/kg), respectively. These results suggest that the activation of mu- and kappa-opioid receptors inhibits cocaine-induced behavior, while that of delta-opioid receptors enhances the behavior.

Animals↗

Differential modulation of behavioral responses by [D-Ala2, NMePhe4, Gly-ol]enkephalin, [D-Ala2] deltorphin II and [D-Pen2, L-Pen5]enkephalin in the mouse.

The effects of [D-Ala2, NMePhe4, Gly-ol]enkephalin (DAMGO), a mu-selective opioid receptor agonist, [D-Ala2]deltorphin II (DELT) and [D-Pen2, L-Pen5]enkephalin (DPLPE), delta-selective opioid receptor agonists, on different behavioral responses were investigated in mice by multidimensional behavioral analyses. DAMGO (0.1 and/or 0.3 microgram) produced a marked increase in circling, rearing and grooming within 15-30 min after the start of behavioral measurements. DELT (0.3, 1.0 and/or 3.0 micrograms) produced a significant increase in linear locomotion and circling within 15-30 min after the start of behavioral measurements, whereas DPLPE (10.0 micrograms) increased only circling. The behavioral effects of DAMGO, DELT or DPLPE were almost completely antagonized by beta-funaltrexamine (2.5 and 5.0 micrograms) or naltrindole (3.0 and 10.0 mg/kg). These results suggest that opioid peptides selective for receptor types elicit different behavioral responses in mice. Moreover, the different behavioral effects between DPLPE and DELT may be due to the delta opioid receptor subtypes such as delta-1 and delta-2.

Analysis of Variance↗

Molecular cloning of rat amidophosphoribosyltransferase.

The cDNA of rat amidophosphoribosyltransferase (EC 2.4.2.14, ATase), which is the supposed regulatory allosteric enzyme of de novo purine nucleotide biosynthesis, has been cloned by polymerase chain reaction. The predicted open reading frame encodes a protein of 517 amino acids with a deduced molecular weight of 57,436 including a supposed 11-amino acid propeptide. The 16 amino acid residues next to the propeptide were identical to the N-terminal amino acid microsequence of a purified rat liver ATase, which is consistent with the cleavage of the propeptide from the proenzyme in rat liver. The derived amino acid sequence is the first sequence reported for a mammalian ATase and it exhibits 81, 41, 36, and 31% identity with the sequences of chicken, Bacillus subtilis, Escherichia coli, and Saccharomyces cerevisiae ATases, respectively. The molecular weight (M(r)) of 57,436 suggests a tetrameric structure of native ATase with a M(r) of 240,000-248,000. Southern blot analysis suggested that the ATase gene exists as a single copy in the rat genome. Northern blot analysis revealed that ATase is expressed at a high level in brain, heart, liver, and stomach. The ATase mRNA in brain, heart, and stomach was 3.5 kilobases (kb) and in liver the 3.5-kb band was observed as well as an additional band of 4.2 kb. Reverse transcription-polymerase chain reaction analysis showed that ATase is ubiquitously expressed in all tissues examined. Comparison with chicken ATase showed that 2 cysteine residues for an iron-sulfur cluster were conserved. Three conserved and two non-conserved consensus phosphorylation sites for cAMP-dependent protein kinase were found.

Amidophosphoribosyltransferase↗

Molecular cloning and sequencing of a cDNA encoding mung bean cytochrome P450 (P450C4H) possessing cinnamate 4-hydroxylase activity.

With the aid of partial amino acid sequences determined for cinnamate 4-hydroxylase (P450C4H) purified from mung bean seedlings, two cDNA clones were isolated and their inserts were completely sequenced. The nucleotide sequences of the two clones were nearly identical and contained an open reading frame predicted to encode a polypeptide consisting of 505 amino acid residues. The partial sequences determined from the purified P450C4H closely corresponded to the primary structures deduced from the cDNA sequences. This is the first isolation of cDNA clones encoding a higher plant P450 possessing clear physiological activity. Comparison to known cytochromes P450 indicated that P450C4H belongs to a novel P450 gene family.

Amino Acid Sequence↗