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Biomedical subjects

T Kanno

Publications and source records attributed to T Kanno.

At least 127 records · Page 7Linked to original sources
PubMed1999

Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP2alphaB gene associated with myeloblastic leukemias.

The AML1 gene encoding the DNA-binding alpha-subunit in the Runt domain family of heterodimeric transcription factors has been noted for its frequent involvement in chromosomal translocations associated with leukemia. Using reverse transcriptase-polymerase chain reaction (RT-PCR) combined with nonisotopic RNase cleavage assay (NIRCA), we found point mutations of the AML1 gene in 8 of 160 leukemia patients: silent mutations, heterozygous missense mutations, and biallelic nonsense or frameshift mutations in 2, 4, and 2 cases, respectively. The mutations were all clustered within the Runt domain. Missense mutations identified in 3 patients showed neither DNA binding nor transactivation, although being active in heterodimerization. These defective missense mutants may be relevant to the predisposition or progression of leukemia. On the other hand, the biallelic nonsense mutants encoding truncated AML1 proteins lost almost all functions examined and may play a role in leukemogenesis leading to acute myeloblastic leukemia.

Adult↗
PubMed1999

Increased heavy metal sensitivity of Escherichia coli producing the expression product of priA gene derived from the basidiomycete Lentinus edodes.

We have previously isolated a developmentally regulated novel gene, priA, from the basidiomycete Lentinus edodes. The deduced PRIA protein contains the two set of motifs similar to a 'zinc finger' typified by transcription factor TFIIIA and the motif of a 'zinc cluster' observed in metallothioneins. It also contains a hydrophobic N-terminal sequence. Here Escherichia coli cells producing PRIA were found to show a remarkable sensitivity to zinc ion and other heavy metal ions such as nickel and cadmium. Deletion analysis of PRIA revealed that the zinc-binding motifs and the hydrophobic N-terminal sequence are responsible for conferring the heavy metal sensitivity on the host cells.

Cloning, Molecular↗
PubMed1999

Alcohol-induced biphasic inhibition of myosin subfragment 1 K-EDTA-ATPase.

Butanol-induced inhibition of K-EDTA-ATPase of myosin subfragment 1 proceeded by biphasic kinetics, consisting of rapid and slow inactivations. The extent of the rapid inactivation, which was estimated by extrapolating the process of slow inactivation to zero time of the incubation period, was saturated with butanol concentration. Recovery of activity by dilution in the rapid phase indicates that the rapid process is reversible. The slow inactivation was concomitant with a partial denaturation of the 50 kDa domain of S1, which was detected by limited tryptic digestion. Other alcohols (methanol, ethanol, propanol and hexanol) also inhibited the K-EDTA-ATPase in the rapid phase. The Ki decreased with an increase in the number of methylene groups of alcohol. When K-EDTA-ATPase activity in the rapid phase was plotted against viscosity, surface tension or dielectric constant, the curves were different for each of the various alcohol solutions. The rapid inactivation appears to be caused by a binding of the alkyl group to S1, rather than by solvent effects. The kinetics of rapid butanol inhibitions indicate that butanol reduces the maximum activity of ATPase but enhances an apparent affinity of S1 with ATP. These indications suggest that alcohol stabilizes S1.KATP intermediate. The rapid K-EDTA-ATPase inhibition was observed at the same alcohol concentration where S1 Mg-ATPase was activated.

1-Butanol↗
PubMed1999

Positive and negative regulation of chondrogenesis by splice variants of PEBP2alphaA/CBFalpha1 in clonal mouse EC cells, ATDC5.

The alphaA type of the alpha subunit of the polyomavirus enhancer binding protein 2 (PEBP2alphaA), also called the core binding factor alpha1 (CBFalpha1) or til-1, plays crucial roles in osteogenesis. Little is known, however, about the function of PEBP2alphaA in chondrogenesis. Here, we examined the role of PEBP2alphaA in chondrogenesis of clonal mouse embryonal carcinoma cells, ATDC5, which are committed as chondroprogenitors. We found that as ATDC5 cells condensed and formed cartilaginous nodules, PEBP2alphaA increased, and the level was maintained throughout the process of chondrocytic maturation. When an established dominant negative form of PEBP2alphaA was introduced in undifferentiated ATDC5 cells, the cellular condensation and the subsequent processes were inhibited. This inhibition was overcome with BMP-4 treatment, which increased the endogenous expression of PEBP2alphaA. Thus, the process of chondrogenesis is regulated by the level of PEBP2alphaA activity. Along with the wild-type PEBP2alphaA, a splice variant form, til-1 G2, is naturally expressed in ATDC5 cells. In luciferase reporter assays, til-1 G2 not only exhibited a limited ability to transactivate the osteocalcin promoter but also inhibited the activity achieved by the wild-type PEBP2alphaA. When til-1 G2 was overexpressed by stable transfection in undifferentiated ATDC5 cells, it inhibited the progression of chondrogenesis. Therefore, we conclude that PEBP2alphaA acts as a positive regulator of chondrogenesis, and that this positive effect may be finely tuned by the opposing effect of the til-1 G2 isoform.

Alternative Splicing↗
PubMed1999

Presynaptic and postsynaptic dopaminergic binding densities in the nigrostriatal and mesocortical systems in early Parkinson's disease: a double-tracer positron emission tomography study.

To investigate changes in the relation between presynaptic and postsynaptic dopaminergic functions in vivo in both nigrostriatal and mesocortical systems in Parkinson's disease (PD), 10 drug-naive early PD patients were studied twice using positron emission tomography with [11C]CFT (dopamine transporter probe) followed by [11C]SCH 23390 (D1 receptor probe). Regional binding potentials (k3/k4) of [11C]CFT and [11C]SCH 23390 in the striatum (nigrostriatal system) and the orbitofrontal cortex (mesocortical system) were estimated by compartment analyses. Levels of [11C]CFT k3/k4 in the two projection areas were shown to be significantly lower in PD, whereas [11C]SCH 23390 levels remained unchanged. Regression analysis showed that estimates of CFT k3/k4 were positively correlated with those of SCH 23390 k3/k4 in the striatum in normal control, whereas the two binding estimates were less positively correlated in the caudate and inversely correlated in the putamen in PD. No significant correlation was observed in the orbitofrontal cortex in both groups. These results indicated that dopamine transporters and D1 receptors change in parallel in the normal striatal synapses, but the association becomes asymmetrical because of reduction in presynaptic and relative elevation in postsynaptic markers in PD. Alterations in synaptic parallel regulation in the nigrostriatal system might reflect early pathophysiology in the parkinsonian brain.

Aged↗
PubMed1999

Application of three-dimensional CT angiography (3D-CTA) to cerebral aneurysms.

BACKGROUND: 3D CT angiography (3D-CTA) is a noninvasive imaging modality for cerebral aneurysms. 3D-CTA is helpful in the evaluation of the configuration of the aneurysm, the surrounding vessels, and the inside of the aneurysm dome. Clinical application of this technique in complicated large cerebral aneurysms showed that with 3D-CT endoscopic imaging, anatomical details of cerebral aneurysms such as the orifice of the aneurysm, intraluminal thrombus, and calcification of the wall could be clearly demonstrated. Using the 3D-imaging method with helical CT, virtual views of various surgical approaches can be compared preoperatively. This information was found to be very useful for determining difficult aneurysms for coil embolization or direct surgery including complicated and broad-based aneurysms. METHODS: Helical CT scanners (TOSHIBA X-vigor) are used for intracranial vascular lesions. At present, nearly stereoscopic images at a pixel size of 0.35 x 0.35 x 0.4 mm are obtained by reconstruction under the following conditions: slice thickness, 0.8 mm; couch top speed, 1.0 mm/ sec.; 130 kV; 220 mA; visual field, 18 cm in diameter (11 cm after extension); pitch, 0.4 mm; and opposed beam interpolation. RESULTS AND CLINICAL APPLICATION: By virtual vascular 3D-CT endoscopy, the lumen of the cerebral aneurysm is displayed by the surface rendering method. Its clinical applications include 1) Demonstration of three-dimensional aneurysm morphology, including the dome and the neck region; 2) Preoperative simulation; 3) Confirmation of parent blood vessels flowing into and out of aneurysms and visualization of aneurysmal lumen calcification. Coronal and sagittal sections can demonstrate whether the branches arise from the aneurysm or aneurysmal neck. The limitation of 3D-CTA is in delineating perforating arteries that are less than 1.2 mm in diameter. The problem with virtual vascular 3D-CT endoscopic images is that endoscopic findings in the vascular wall are incomplete because of the partial volume effect and pulsation of the aneurysm and vascular wall. CONCLUSIONS: Helical Scanning-CT (HES-CT) is an excellent noninvasive diagnostic modality for cerebral aneurysm detection. 3D-CT angiography has distinct advantages in evaluating aneurysms and selecting the most appropriate therapeutic modality.

Cerebral Angiography↗
PubMed1999

Thyroxine enhancement and the role of reactive oxygen species in tadpole tail apoptosis.

Our objective is to clarify the role of reactive oxygen species (ROS) in the atrophying tail of anuran tadpoles (tail apoptosis). Changes in catalase, superoxide dismutase (SOD) and caspase activity, genomic DNA, and nitric oxide (NO) generation were investigated biochemically using Rana japonica tadpole tails undergoing regression during thyroid hormone enhancement. DNA fragmentation and ladder formation with concomitant shortening of tadpole tail were induced by DL-thyroxine (T4) in culture medium. Catalase activity was also decreased by T4 treatment. T4 was also found to increase NO synthase (NOS) activity in cultured tadpole tail with concomitant increase in the concentration of NO2- plus NO3- (NOx) in the culture medium. Additional treatment with N-monomethyl-L-arginine (NMMA), a potent inhibitor of NOS, suppressed the enhancing effects of T4 on tail shortening and catalase activity reduction. It was also found that treatment with isosorbide dinitrate (ISDN), a NO generating drug, alone also had an enhancing effect on tail shortening and catalase activity reduction similar to that seen with T4. Both NO and an NO donor (ISDN) strongly suppressed catalase activity. Kinetic analysis revealed that catalase activity decreased and caspase-3-like activity increased during normal tadpole tail atrophy (apoptosis). These results suggested that T4 enhances NO generation, thereby strongly inhibiting catalase activity, resulting in an increase in hydrogen peroxide, and that the oxidative stress elicited by excess hydrogen peroxide might activate cysteine-dependent aspartate-directed protease-3 (caspase-3-like protease), which is thought to cause DNA fragmentation, leading to apoptosis.

Animals↗
PubMed1999

New vinegar production from onions.

The possibility of producing a new type of vinegar from worthless onions, which fail to meet the quality standards required for marketing, was investigated. Several kinds of onion were initially tested as raw material for vinegar production, and vinegar was successfully produced from the juice of a red onion, the cultivar Kurenai, by batch culture using yeast and Acetobacter aceti. Nutritional analysis revealed that the potassium content of onion vinegar was extremely high, while the amount of sodium was lower than that in conventional vinegars. It was also shown that the total amino acid and total organic acid contents of the onion vinegar were respectively 1.6-6.9 times and 3.5-11.5 times those in other kinds of vinegars.

Journal Article↗
PubMed1999

Activation of Ca(2+)-dependent K(+) channels contributes to rhythmic firing of action potentials in mouse pancreatic beta cells.

We have applied the perforated patch whole-cell technique to beta cells within intact pancreatic islets to identify the current underlying the glucose-induced rhythmic firing of action potentials. Trains of depolarizations (to simulate glucose-induced electrical activity) resulted in the gradual (time constant: 2.3 s) development of a small (<0.8 nS) K(+) conductance. The current was dependent on Ca(2+) influx but unaffected by apamin and charybdotoxin, two blockers of Ca(2+)-activated K(+) channels, and was insensitive to tolbutamide (a blocker of ATP-regulated K(+) channels) but partially (>60%) blocked by high (10-20 mM) concentrations of tetraethylammonium. Upon cessation of electrical stimulation, the current deactivated exponentially with a time constant of 6.5 s. This is similar to the interval between two successive bursts of action potentials. We propose that this Ca(2+)-activated K(+) current plays an important role in the generation of oscillatory electrical activity in the beta cell.

ATP-Binding Cassette Transporters↗
PubMed1999

Beneficial effects of MET-88 on left ventricular dysfunction and hypertrophy with volume overload in rats.

We examined the effects of MET-88 on haemodynamics and cardiac hypertrophy in rats with an aortocaval shunt (A-V shunt). On the day of surgery, an A-V shunt was produced by using an 18-gauge needle in Wistar rats as described by Garcia and Diebold. MET-88 and captopril were orally administered to rats 1 week after surgery, and the administration was continued for 3 weeks. Four weeks after the surgery, A-V shunt-operated rats had biventricular hypertrophy and higher right atrial pressure (RAP) and left ventricular end-diastolic pressure (LVEDP) than sham-operated rats. Compared with untreated A-V shunt rats, those treated with MET-88 showed significant attenuation of the development of left ventricular (LV) hypertrophy and of the increased LVEDP. Captopril-treated A-V shunt rats also failed to show increases in LV weight and LVEDP. In in vitro studies, MET-88 had no effect on renin and angiotensin-converting enzyme (ACE) activities in the plasma of normal rats. These results suggest that MET-88 improved LV hypertrophy and LV dysfunction in rats with an A-V shunt. Furthermore, the data indicate that the beneficial effects of MET-88 may be attributed to some pathway, not involving the renin-angiotensin system, such as myocardial energy metabolism, venous return, etc. We conclude that MET-88 may be a novel agent for the therapy of chronic heart failure.

Animals↗
PubMed1999

Mapping the genetic determinants of pathogenicity and plaque phenotype in swine vesicular disease virus.

A series of recombinant viruses were constructed using infectious cDNA clones of the virulent J1'73 (large plaque phenotype) and the avirulent H/3'76 (small plaque phenotype) strains of swine vesicular disease virus to identify the genetic determinants of pathogenicity and plaque phenotype. Both traits could be mapped to the region between nucleotides (nt) 2233 and 3368 corresponding to the C terminus of VP3, the whole of VP1, and the N terminus of 2A. In this region, there are eight nucleotide differences leading to amino acid changes between the J1'73 and the H/3'76 strains. Site-directed mutagenesis of individual nucleotides from the virulent to the avirulent genotype and vice versa indicated that A at nt 2832, encoding glycine at VP1-132, and G at nt 3355, encoding arginine at 2APRO-20, correlated with a large-plaque phenotype and virulence in pigs, irrespective of the origin of the remainder of the genome. Of these two sites, 2APRO-20 appeared to be the dominant determinant for the large-plaque phenotype but further studies are required to elucidate their relative importance for virulence in pigs.

Animals↗
PubMed1999

Effects of milk and colostrum on superoxide generation of oral polymorphonuclear neutrophils and the changes that occur during storage at low temperature.

Human oral polymorphonuclear neutrophils (OPMN) generate reactive oxygen species even in the absence of stimulants. Because OPMN from newborn babies are exposed to colostrum and mature milk, the biological properties of these cells including the generation of reactive oxygen species might possibly be affected by the constituents of colostrum and milk. The present work reports the effects of colostrum and mature milk, including the effects of storage at low temperature, on superoxide generation by OPMN. Fresh colostrum and mature milk did not affect either endogenous or formyl-methionyl-leucyl-phenylalanine-induced generation of superoxide by OPMN. However, superoxide generation stimulated by phorbol myristate acetate or arachidonic acid was inhibited by colostrum and mature milk presumably due to binding of the ligands to milk proteins. During the storage of milk at 4 degrees C, free forms of unsaturated long-chain fatty acids increased, and there was concomitant increase in the ability of milk to generate superoxide radicals in OPMN. Kinetic analysis suggested that colostrum and mature milk regulate superoxide generation by OPMN, thereby modulating the bactericidal activity of these cells in the oral cavity.

Animals↗
PubMed1999

Impact of congenital narrowing of the bulbar urethra (Cobb's collar) and its transurethral incision in children.

OBJECTIVES: We described the clinical manifestation and outcome after transurethral incision (TUI) of a congenital narrowing of the bulbar urethra (Cobb's collar). MATERIALS AND METHODS: Over a period of 11 years a total of 74 boys, from 3 months to 16 years old with a mean age of 5 years, were subjected to TUI. A febrile urinary tract infection (UTI) was the most common symptom in 40 cases, enuresis in 15, urinary incontinence in 11, hematuria in 9, antenatally diagnosed dilated urinary tract in 4 and others in 9. Concurrent bladder instability was detected by cystometry in 27/31 boys older than 3 years with suspicious bladder urgency. When the bulbar narrowing was detected by cystourethroscopy under 8 Fr, the lesion was simultaneously incised by using an infantile resectoscope (Olympus 10 Fr with a knife electrode or Storz 10 F with a cold knife). RESULTS: Vesicoureteral refluxes (VURs) occurred in 39 cases (53%) and it was diminished in 11 and improved in 25 after TUI. Of the 40 cases, 38 (95%) were free from UTI after TUI. For enuresis and urinary incontinence, 14/15 and all 11, respectively, thrived after TUI and the anticholinergic supplement. Although 61 cases were primarily cured with no complications, insufficient cutting and recurrence of the stricture required an additional TUI in 13 cases for whom the knife electrode was mostly used. Overall clinical improvement was obtained in 71/74 (93%) cases after TUI. CONCLUSION: Meticulous cystourethroscopy is indispensable for detecting a clinically significant bulbar narrowing. TUI of the lesion is useful as a primary treatment in the majority of cases even with concurrent VUR and unstable bladder. A cold knife is preferable to electrocautery in incising this fine anterior urethral lesion.

Adolescent↗
PubMed1999

Effect of pretreatment with FTY720 and cyclosporin on ischaemia-reperfusion injury of the liver in rats.

The effect of pretreatment with FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochloride) or cyclosporin, or both, on neutrophil-mediated injury has been examined by use of a rat model of transient clamping of hepatic flow. Pretreatment with FTY720 alone or with cyclosporin induced a marked reduction of circulatory lymphocytes, whereas the use of these drugs in combination was very effective at suppressing the elevation of the number of peripheral polymorphonuclear neutrophils (PMN) after reperfusion. Pretreatment with cyclosporin, with or without FTY720, significantly reduced hepatic damage, whereas FTY720 alone tended to prolong hepatic damage. Pretreatment of cyclosporin alone, but not in combination with FTY720, significantly reduced the accumulation of PMN and led to lower myeloperoxidase levels in the damaged liver. In conclusion, pretreatment with cyclosporin, with or without FTY720, reduced hepatic damage after warm ischaemia-reperfusion, whereas pretreatment with FTY720 alone tended to prolong this damage.

Animals↗
PubMed1999

Geranylgeranylacetone induces apoptosis in HL-60 cells.

Geranylgeranylacetone (GGA) induces apoptosis in human leukemia HL-60 cells in a dose- and time-dependent manner. This effect was completely prevented by the pan-caspase inhibitor z-Val-Ala-Asp(OMe) fluoromethylketone, thereby implicating the caspase cascade in the process. Prior to DNA fragmentation, GGA treatment markedly activated caspase-3(-like) proteases, which might be responsible for the observed apoptosis. In addition, GGA treatment interfered with the processing and membrane localization of Rap1 and Ras, and these changes may be a result of apoptosis. Moreover, nitric oxide donors significantly accentuated the GGA-induced apoptosis, suggesting that the apoptotic pathway induced by GGA might be regulated by a redox-sensitive mechanism. Taken together, these data suggest that the isoprenoid, GGA, is an effective inducer of apoptotic cell death in HL-60 cells.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Participation of a cathepsin L-type protease in the activation of caspase-3.

A previous paper from this laboratory reported the activation of a caspase-3-like protease by a digitonin-treated lysosomal fraction [FEBS Lett. 435, 233-236, 1998]. In this study, we examined the effects of specific inhibitors of lysosomal cysteine proteases, such as cathepsins B, S, and L, on the activation of caspase-3 to find out which cathepsin is responsible for the activation. Pro-caspase-3 in the cytosol was cleaved by a lysosomal protease(s) contained in the supernatant of a digitonin-treated crude mitochondrial fraction containing lysosomes (ML) and the cleaved product was detected by Western blotting using anti-caspase-3 antibody. The activation of caspase-3 by the lysosomal protease(s) was pH dependent and the optimum pH for activation was pH 6.6-6.8. This activation was not inhibited by CA-074, a specific inhibitor of cathepsin B, but was strongly inhibited by CLIK-066 and CLIK-181, specific inhibitors of cathepsin L. The inhibitory effect of CLIK-060, a specific inhibitor of cathepsin S, was very weak. Furthermore, the activation of caspase-3 was enhanced by addition of purified cathepsin L only in the presence of the supernatant of the digitonin-treated ML. These results suggested that a cathepsin L-type protease activity might participate in the activation mechanism of caspase-3 in the presence of the supernatnat from the ML.

Adenosine Triphosphate↗