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Biomedical subjects

K Mizuno

Publications and source records attributed to K Mizuno.

At least 253 records · Page 14Linked to original sources

Group additive contributions to the alcohol-induced alpha-helix formation of melittin: implication for the mechanism of the alcohol effects on proteins.

Detailed analysis of the effects of alcohols on proteins and peptides is important because of its wide range of applications in many fields. Whereas melittin, a major component of honeybee venom, is unfolded in an aqueous environment, the addition of alcohols induces an alpha-helical structure. We used circular dichroism (CD) to compare the effects of various alcohols on melittin. Whereas the alpha-helical state was basically independent of alcohol species, the effectiveness of alcohols varied significantly. Among alkanols, the effectiveness was proportional to the bulkiness of hydrocarbon groups, indicating that the hydrocarbon group contributes positively to the alcohol effects. Comparison of alcohols with the same hydrocarbon group but a different number of hydroxyl groups showed that the hydroxyl groups contribute negatively to the alcohol effects. Comparison of several halogenols indicated that halogen increases the effectiveness in the order of F < Cl < Br. These results suggested that the effects of alcohol can be interpreted by the additive contributions of each of the constituent groups of the alcohol, which are proportional to the solvent-accessible surface area. However, for markedly effective alcohols such as 1,1,1,3,3,3-hexafluoro-2-propanol, the aggregation of alcohols was suggested to further enhance these effects. We have constructed equations for estimating the effectiveness of alcohols in inducing alpha-helical structure, which should also be useful for predicting the other effects of alcohols on proteins.

Alcohols↗

Structural organization and chromosomal localization of the mouse tesk1 (testis-specific protein kinase 1) gene.

TESK1 (testis-specific protein kinase 1) is a protein serine-threonine kinase, containing characteristic structural features composed of an N-terminal kinase domain and a C-terminal proline-rich domain. Tesk1 mRNA is predominantly expressed in testicular germ cells, and developmental changes of expression in mouse testis suggest a role for this kinase in spermatogenesis. In the present study, we isolated and determined the overall sequence of the mouse Tesk1 gene, which spans 6.1 kilobases (kb) and contains 10 exons and 9 introns. The protein kinase domain is located in exons 1-9, while the proline-rich domain is in exons 9 and 10. The deduced 627 amino acid sequence of mouse TESK1 shows 97% and 94% identity with the rat and human TESK1, respectively. Sequence of the 5'-flanking and -untranslated region is devoid of a TATA box, but does contain several potential binding sites for transcription factors, including Sp1, AP-1, c-Myc, SRY and CREM (cyclic AMP-responsive element modulator). As CREM is implicated in the activation of several male germ cell-specific genes, it is suggested that the expression of the Tesk1 gene is under the control of CREM transcription activity. The Tesk1 gene was mapped to mouse chromosome 4A5-C1 by fluorescence in situ hybridization.

Amino Acid Sequence↗

Chronic inflammatory demyelinating polyradiculoneuropathy with diffuse and massive peripheral nerve hypertrophy: distinctive clinical and magnetic resonance imaging features.

We present 3 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with extensive and diffuse hypertrophy of the nerve roots and peripheral nerves. They exhibited slowly progressive sensory impairment and distally predominant limb weakness and muscular atrophy, and markedly enlarged palpable nerve trunks. They responded beneficially to corticosteroid. Magnetic resonance imaging demonstrated diffuse and extensive hypertrophy of the peripheral nerves in the four limbs and the spinal nerve roots, with gadolinium enhancement in the nerve roots but not in the peripheral nerves. These patients were considered to have a hypertrophic variant of CIDP.

Aged↗

Evaluation of functional deficits determined by four different hop tests in patients with anterior cruciate ligament deficiency.

The purpose of this study was to analyze the validity of the newly designed functional ability test (FAT) for the normal population and patients with deficiency of the anterior cruciate ligament (ACL). The FAT consists of four tests: the figure-of-eight hop, the up-down hop, the side hop, and the single hop. Sixty control subjects and 50 patients with unilateral ACL deficiency were tested. In the control group, the values measured were significantly different between males and females in all of the tests. On the other hand, when left/right difference values were compared, no significant difference was found between males and females in any of the tests. More than 95% of control group exhibited symmetrical function in each part of the FAT, whereas in the ACL-deficient group, the percentage of patients who showed abnormal symmetry was 68% in the figure-of-eight hop, 58% in the up-down hop, 44% in the side hop, and 42% in the single hop. The percentage of ACL-deficient patients with functional asymmetry in at least one of the four tests was 82%. The FAT was found to be useful in evaluating lower limb function in ACL-deficient patients.

Adolescent↗

The rotational angle in osteoarthritic knees.

The angle of rotation of the knee joint during weight-bearing in osteoarthritic knees has not been fully determined. The authors aimed to examine the nature and extent of rotation during weight-bearing by means of ultrasonic investigation. There was a highly significant correlation between the rotational angle measured by ultrasound and that determined by CT. The dynamic rotatory movement during weight-bearing was measured in 107 osteoarthritic and 40 control knees. At 20 degrees of flexion the internal rotation of the early grade I osteoarthritic knees (-1.6 degrees) was significantly less than that of the control knees (-4.8 degrees, P = 0.004). This abnormality was the initial pathological rotational change in osteoarthritis of the knee joint. The external rotation at maximal extension and the rotation of the screw-home movement proportionately decreased with progression of medial compartment osteoarthritis. By virtue of these observations we have clarified the dynamic rotatory movement in osteoarthritic knees during weight-bearing.

Adult↗

Comparisons of serum testosterone and corticosterone between exercise training during normoxia and hypobaric hypoxia in rats.

The purpose of this study was to compare the effects of continuous and intermittent exercise training on serum testosterone [T] and corticosterone concentrations [Cort] during normoxia and hypobaric hypoxia. Male rats swam with loads of 3% (normoxia) or 2.25% (462 mmHg) body mass for 60 min in the continuous training groups, and 15 min separated by a 7-min rest x 4, with 60-min total exercise duration in the intermittent training groups, 5 days week(-1) for 6 weeks. Serum [T] were measured at rest and following exercise after 6 weeks of training. Serum [Cort] were measured immediately after an acute period of exercise or after 6 weeks of training at rest and following exercise. Continuous exercise induced decreases in [T] under both conditions. Intermittent exercise showed a tendency to increase [T] during normoxia, but caused a suppression during hypobaric hypoxia. The [Cort] was elevated by a similar margin after an acute period of exercise during both conditions. After 6 weeks of training, however, [Cort] increased slightly after exercise during normoxia. A lower resting [Cort], which was increased after exercise, was found in the training groups during hypoxia. No relevant relationship was found between the behaviours of [T] and [Cort] after exercise during either conditions.

Animals↗

Founder-haplotype analysis in Fukuyama-type congenital muscular dystrophy (FCMD).

Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive, severe muscular dystrophy associated with brain anomalies. After our initial mapping of the FCMD locus to 9q31-33, we performed linkage disequilibrium analysis, which led us to suspect that the FCMD gene lay within a region of less than 100 kb containing D9S2107. In the present study, we developed two new microsatellites (D9S2170 and D9S2171) in close vicinity to D9S2107 and examined haplotypes of FCMD chromosomes by using four markers (cen-D9S2105-D9S2170-D9S2171-D9S2107-tel). As 82% of the FCMD chromosomes that we examined shared the founder haplotype (138-192-147-183) and 94% of the FCMD patients in our panel carried founder haplotypes on one or both chromosomes, the data supported the hypothesis of a single founder of this disease in the Japanese population. Eight haplotypes different from the founder's were observed in FCMD chromosomes, indicating that eight different FCMD mutations in addition to the founder's have occurred in Japan. Moreover, we have detected several historical recombinations that have disrupted the founder haplotype at D9S2105 or D9S2170 and conclude that the FCMD gene is probably located just centromeric to D9S2170.

Chromosomes, Human, Pair 9↗

Which vertebrae should be assessed in diagnosing osteoporosis by plain radiography? Comparative study of radiographic findings and bone mineral density measured by dual energy X-ray absorptiometry.

In 1990, the Ministry of Health and Welfare of Japan advocated a criterion for the diagnosis radiographic bone atrophy in lumbar vertebrae. We carried out a comparative study of this criterion (i.e. , radiographic bone atrophy grading) and bone mineral density measured by posteroanterior and lateral dual energy X-ray absorptiometry. We investigated the second to fourth lumbar vertebrae of 47 postmenopausal women (mean age, 67.2 years; range, 57-82 years), to determine which vertebra would most accurately indicate osteoporosis. A significant difference in bone mineral density (P < 0.01) was found between each grade of radiographic bone atrophy in all of the second, third, and fourth vertebrae examined. The highest correlation (r = 0.714) was found between the radiographic grades and the bone mineral density on lateral dual energy X-ray absorptiometry of the third lumbar vertebrae. Our visual determinations were dependable, radiographic and a examination of the third lumbar vertebra rather than that of other lumbar vertebrae was more helpful for the detection of radiographic bone atrophy. Plain radiographic film can provide a rough estimation of bone atrophy.

Absorptiometry, Photon↗

Change in nitric oxide in humans due to application of a pneumatic tourniquet.

The nitric oxide profile produced by application of a pneumatic tourniquet was investigated in the plasma of 15 patients. Nitrite (NO2-) and nitrate (NO3-) plasma concentrations were measured simultaneously by high-performance liquid chromatography (HPLC). UV detection using the Griess reaction was done after the reduction of nitrate to nitrite. The plasma nitrate concentration 5 min after reperfusion was significantly higher than the concentrations before ischemia, immediately before reperfusion, and the next day. In contrast, there was no significant difference in the plasma nitrite concentrations before ischemia, immediately before reperfusion, 5 min after reperfusion, and the next day. These findings suggest that the generation of NO is important in ischemic reperfusion injury.

Adolescent↗

Characterization of mastoparan-induced histamine release from RBL-2H3 cells.

Mastoparan (5-30 microM), a tetradecapeptide isolated from wasp venom, caused histamine release from RBL-2H3 cells in a concentration- and time-dependent manner. Mastoparan-induced histamine release remained after removing the extracellular Ca2+, whereas the antigen-induced one disappeared. Pertussis toxin did not inhibit mastoparan-induced histamine release from the cells, and mastoparan did not stimulate phosphoinositide hydrolysis. In agreement with the results, RBL-2H3 cells had a small amount of ADP-ribosylation substrates for pertussis toxin. Neomycin (1-5 mM) suppressed mastoparan-induced histamine release and phospholipase D activation. However, butanol slightly inhibited mastoparan-induced histamine release. Moreover, 2,3-diphosphoglycerate inhibited mastoparan-induced phospholipase D activation, but not it's histamine release. On the other hand, mastoparan caused the leakage of lactate dehydrogenase from the cells in a similar concentration range to the histamine release. This leakage was also suppressed by neomycin. These results suggest that mastoparan enhances the membrane permeability, resulting in histamine release in a pertussis toxin-insensitive manner, and that mastoparan-induced phospholipase D activation may not relate to histamine release.

1-Butanol↗

Effects of carbamazepine on hippocampal serotonergic system.

To establish the mechanism of action of the antiepileptic and psychotropic effects of carbamazepine (CBZ), its effects on serotonin (5-HT) transmission, metabolism and re-uptake activity in the rat hippocampus were studied. After acute and chronic administrations of 25 mg/kg CBZ, the plasma concentration of CBZ was found to be within the therapeutic range, whereas both acute and chronic administrations of 50 and 100 mg/kg CBZ resulted in a supratherapeutic plasma concentration. Acute administration of the therapeutic dose of CBZ resulted in an increase in the hippocampal extracellular and total level of 5-HT, its metabolite, 5-hydroxydoleacetic acid (5-HIAA) and its precursor, 5-hydroxytryptophan (5-HTP). The acute administration of 50 mg/kg CBZ resulted in an increase in the hippocampal levels of extracellular 5-HT and 5-HIAA as well as in the total levels of 5-HTP, whereas hippocampal levels of extracellular 5-HTP, total 5-HT and 5-HIAA remained unaffected. CBZ at a dose of 100 mg/kg decreased the levels of all of these substances. After chronic administration, 25 mg/kg/day CBZ increased hippocampal total levels of 5-HT, 5-HTP and 5-HIAA, whereas 100 mg/kg/day CBZ decreased all of these total levels. CBZ at a dose of 50 mg/kg/day decreased total levels of 5-HT, however neither total levels of 5-HIAA nor 5-HTP were affected. Both therapeutic and supratherapeutic plasma concentrations of CBZ inhibited 5-HTP accumulation, and did not affect 5-HT re-uptake activity in vitro. These results suggest that a therapeutic concentration of CBZ enhances 5-HT turnover and transmission, whereas a supratherapeutic concentration of CBZ inhibits 5-HT turnover and transmission without affecting 5-HT re-uptake activity. These effects of CBZ on serotonergic systems may be, at least partially, involved in the mechanisms of action of CBZ.

5-Hydroxytryptophan↗

Effects of Ca2+ channel antagonists on striatal dopamine and DOPA release, studied by in vivo microdialysis.

1. To elucidate the mechanisms regulating the release of striatal dopamine and its precursor, 3,4-dihydroxyphenylalanine (DOPA), we determined the effects of various Ca2+ channel antagonists, an N-type Ca2+ channel antagonist, omega-conotoxin GVIA, a P-type Ca2+ channel antagonist, omega-agatoxin IVA, and a Q-type Ca2+ channel antagonist, omega-conotoxin MVIIC, on the basal and Ca2+- and K+-evoked release of striatal dopamine and DOPA, by use of in vivo microdialysis. 2. Omega-conotoxin GVIA strongly inhibited striatal basal dopamine release (IC50 = 0.48 nM), whereas this toxin only weakly modulated basal striatal DOPA release (IC50 = 9.55 nM). Neither omega-agatoxin IVA nor omega-conotoxin MVIIC affected the basal striatal release of dopamine and DOPA. 3. Omega-conotoxin GVIA strongly inhibited Ca2+-evoked striatal dopamine release (IC50 = 0.40 nM), whereas Ca2+-evoked striatal DOPA release only was weakly modulated (IC50 = 10.51 nM). Neither omega-agatoxin IVA nor omega-conotoxin MVIIC affected the Ca2+-evoked release of striatal dopamine and DOPA. 4. Both omega-agatoxin IVA and omega-conotoxin MVIIC inhibited the K+-evoked release of striatal dopamine (IC50 of omega-agatoxin IVA = 2.65 nM; IC50 of omega-conotoxin MVIIC = 12.54 nM) and DOPA (IC50 of omega-agatoxin IVA = 0.15 nM; IC50 of omega-conotoxin MVIIC = 3.05 nM), whereas omega-conotoxin GVIA had no effect on the K+-evoked release of striatal dopamine and DOPA. 5. An increase in the extracellular Ca2+ and K+ concentrations (Ca2+- and K+-evoked stimulation) did not affect tyrosine hydroxylase activity in vivo. 6. These findings suggest that striatal DOPA release is neurotransmitter-like and that, unlike the mechanisms of striatal dopaminergic transmission, this striatal DOPA transmission is at least partly regulated by voltage-sensitive Ca2+ channels.

Animals↗

Interaction between Ca2+, K+, carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode.

1. Multiple components of hippocampal glutamate release were examined by study of Ca2+- and K+-evoked hippocampal extracellular glutamate release using an in vivo microdialysis glutamate biosensor in urethane-anaesthetized rats. In addition, the effects of the antiepileptic drugs, carbamazepine (CBZ) and zonisamide (ZNS) perfused through the probe on glutamate release were assessed. 2. Basal glutamate levels were below detection limits (approximately 0.1 microM). An increase in extracellular KCl (from 2.7 to 50 and 100 mM) increased extracellular hippocampal glutamate levels to 9.2+/-1.4 and 20.0+/-2.6 microM, respectively, calculated from the area under curve (AUC) for 60 min. 3. This KCl-evoked glutamate release consisted of three components: an initial transient rise, a late gentle rise, and late multiple phasic transient rises. 4. An increase in or removal of extracellular CaCl2 levels respectively enhanced and reduced the 50 mM KCl-evoked hippocampal glutamate release (AUC for 60 min) from 9.2+/-1.4 to 12.4+/-2.1 and 5.8+/-0.9 microM. 5. Perfusion with 100 microM CBZ or 1 mM ZNS inhibited both the 50 mM KCl-evoked hippocampal glutamate release (AUC for 60 min) from 9.2+/-1.4 to 5.5+/-1.1 and to 5.8+/-1.3 microM, respectively, as well as the stimulatory effects of Ca2+ on KCl-evoked hippocampal glutamate release. 6. These results suggest that both CBZ and ZNS may reduce epileptiform events by inhibiting excitatory glutamatergic transmission.

Animals↗

Enhancement of apoptotic susceptibility in human endometrial epithelial cell line HHUA by transforming growth factor-beta 1.

Although reports have been published on the generation of transforming growth factor-beta 1 (TGF-beta 1) and expression of TGF-beta receptors in human endometrial tissues, the biological functions of endometrial TGF-beta 1 have remained unclear. In this study, the effects of TGF-beta 1 on endometrial apoptosis were examined by using an endometrial epithelial cell line HHUA which is susceptible to Fas-mediated apoptosis. TGF-beta 1 alone did not affect the cell growth of HHUA, but pretreatment of HHUA with TGF-beta 1 enhanced Fas-mediated growth suppression and DNA fragmentation of the cells. Flow cytometric analyses showed that TGF-beta 1 did not affect Fas expression on the cell surface. These findings lead to the conclusion that TGF-beta 1 enhances susceptibility to Fas-mediated apoptosis in the endometrial epithelial cell. Modulation of Fas-mediated endometrial apoptosis by TGF-beta 1 may thus be a tissue-specific effect which is distinct from other TGF-beta 1 effects on Fas-mediated apoptosis in activated T-cells and rheumatoid synovial cells. The biological functions of endometrial TGF-beta 1 and endometrial apoptosis are also discussed.

Apoptosis↗

Pulmonary mechanics of normal very-low-birth-weight infants at 40 weeks postconception: a comparison with normal term infants.

We evaluated pulmonary function status in healthy, nonventilated very-low-birth-weight (VLBW) infants at 40 weeks postconception because little is known about the pulmonary function status of these infants at the time of discharge. Seven normal VLBW infants were evaluated at 40 weeks postconception, and five normal term infants were examined as a control. The neonates were placed supine with their heads in the neutral position. Data were obtained while the infant was resting quietly and breathing spontaneously prior to feeding. Pulmonary mechanics and energetics were measured with a CP-100 pulmonary monitor (Bicore Co. Ltd.). Pulmonary mechanics and energetics were determined by the least mean square technique. Dynamic compliance (Cdyn), resistance (Rtot, Re), and work of breathing (WOB) were calculated for the total breath, and tidal volume, minute ventilation, ratio of inspiratory time to respiratory period (Ti/Ttot), and respiratory rate were measured. There were no significant differences between normal VLBW infants and term infants in regard to ventilation, mechanics, or energetics. Although the respiratory system of normal VLBW infants is immature at birth, its development caught up to term infants by the time of discharge.

Aging↗

Transgenic mouse expressing a full-length hepatitis C virus cDNA.

Hepatitis C virus (HCV), a major causative agent of post transfusion non-A, non-B hepatitis (NANBH), can only infect humans and chimpanzees. We produced nine transgenic mouse lines carrying a full-length HCV cDNA with the human serum amyloid P component (hSAP) promoter that can direct liver-specific expression. In one of these lines HCV mRNA and HCV core protein were detected in the liver of the transgenic mouse, although the levels of expression were very low. In addition, HCV-related antibody was detected in the serum.

Alanine Transaminase↗