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Biomedical subjects

M Shindo

Publications and source records attributed to M Shindo.

At least 37 records · Page 2Linked to original sources
PubMed2001

Enhanced associated movements in the contralateral limbs elicited by brisk voluntary contraction in choreic disorders.

OBJECTIVES: To study the deficit of inhibition of excessive motor drive generated in the central nervous system in chorea. METHODS: Identical associated movements in the contralateral limb elicited by rapid hand squeezing were measured in 6 patients with Huntington's disease, 7 patients with peak-dose dyskinesia, 10 patients with Parkinson's disease, 8 patients with spinocerebellar degeneration and in 8 normal subjects. The intensity of associated movements was assessed by the EMG amplitude ratio of associated contractions to active contractions. RESULTS: The associated movement ratios were larger in Huntington's disease and peak-dose dyskinesia as compared to other groups. The ratios in akinetic "off" phase were smaller than those in dyskinetic "on" phase in all peak-dose dyskinesia patients. CONCLUSIONS: Enhanced associated movements support a possible common mechanism that chorea may result from failure in inhibition of phasic neural activity pathologically generated in the brain.

Aged↗
PubMed2001

Long-term follow-up study of sustained biochemical responders with interferon therapy.

A proportion of chronic hepatitis C patients who were treated with interferon have a sustained normalization of transaminase levels after interferon therapy without hepatitis C virus (HCV)-RNA clearance. We determined their clinical characteristics and long-term outcome in relation to progression to liver cirrhosis (LC) and the development of hepatocellular carcinoma (HCC). A total of 250 patients with chronic hepatitis C who were treated with interferon were studied for 8 to 11 years' posttherapy. Sixty-seven patients (27%) were complete responders with clearance of HCV RNA. Twenty-six (10%) were biochemical responders who had sustained normal alanine transaminase (ALT) levels without viral clearance. The remaining patients were short-term responders (n = 70) and nonresponders (n = 87). Biochemical responders were older, had higher levels of pretreatment HCV RNA in serum than complete responders, and had less advanced liver histology than nonresponders. Histologic grading scores decreased significantly at the end of therapy, while the staging scores did not change significantly. The annual incidence of cirrhosis was 0% in biochemical and complete responders, which was significantly lower than nonresponders and the controls (P = .0001). The annual incidence of HCC was 0.37% in complete responders and 0.50% in biochemical responders, which was significantly lower than nonresponders (P = .0001 for both). Our findings suggest that biochemical responders had high pretreatment viral levels with less advanced liver histology, and their long-term outcome appeared to be good irrespective of the persistence of the virus.

Adult↗
PubMed2001

Analysis of optokinetic nystagmus in patients with lesions on the left unilateral parietal lobe or the entire left hemisphere.

Optokinetic nystagmus (OKN) was studied by computer analysis in nine patients with lesions on the left unilateral parietal lobe (group A) and in five patients with lesions on the entire left hemisphere (group B), as confirmed by CAT or MRI scans. OKN stimulation and recordings were evaluated based on the optokinetic pattern (OKP). In group A, there was no directional preponderance. However, in group B, the Electronystagmography recordings showed typical asymmetry of OKP. This asymmetry was revealed by a low amplitude and a significantly impaired slow-phase eye velocity of the right OKP. Asymmetry of OKP resulted from the impaired slow-phase eye velocity of the contralateral OKN to the damaged hemisphere because of a slight change in fast-phase eye velocity.

Adolescent↗
PubMed2001

Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes.

1. Oxidation of 1,4-cineole, a monoterpene cyclic ether, was studied in rat and human liver microsomes and recombinant cytochrome P450 (P450 or CYP) enzymes expressed in insect cells in which human P450 and NADPH-P450 reductase cDNAs have been introduced. On analysis with gas chromatography/mass spectrometry, 2-exo-hydroxy-1,4-cineole was identified as a principal oxidation product of 1,4-cineole catalysed by rat and human P450 enzymes. 2. CYP3A4 was a major enzyme involved in the 2-hydroxylation of 1,4-cineole by human liver microsomes, based on the following lines of evidence. First, 1,4-cineole 2-hydroxylation activities catalysed by human liver microsomes were inhibited by ketoconazole, a potent inhibitor of CYP3A activities, and an anti-CYP3A4 antibody. Second, there was a good correlation beteeen CYP3A4 contents and 1,4-cineole 2-hydroxylation activities in liver microsomes of eighteen human samples examined. Finally, of 10 recombinant human P450 enzymes examined, CYP3A4 had the highest activity for 1,4-cineole 2-hydroxylation. 3. Liver microsomal 1,4-cineole 2-hydroxylation activities were induced in rat by pregnenolone 16alpha-carbonitrile and dexamethasone and extensively inhibited by ketoconazole, indicative of the possible roles of CYP3A enzymes in this reaction. 4. Kinetic analysis showed that Vmax/Km for 1,4-cineole 2-hydroxylation catalysed by liver microsomes was higher in a human sample HL-104 (4.6 microM(-1) min(-1)) than those of rat treated with pregnenolone 16alpha-carbonitrile (0.49 microM(-1) min(-1)) and dexamethasone (0.36 microM(-1) min(-1)). 5. 1,8-Cineole, a structurally related monoterpene previously shown to be catalysed by CYP3A enzymes, inhibited 1,4-cineole 2-hydroxylation catalysed by human liver microsomes, whereas 1,4-cineole did not inhibit 1,8-cineole 2-hydroxylation activities. Both compounds caused inhibition of testosterone 6beta-hydroxylation by human liver microsomes, the former compound being more inhibitory than the latter. 6. These results suggest that 1,4-cineole and 1,8-cineole, two plant essential oils present in Citrus medica L. var. acida and Eucalyptus polybractea, respectively, are converted to 2-hydroxylated products by CYP3A enzymes in rat and human liver microsomes. It is unknown at present whether the 2-hydroxylation products of these compounds are more active biologically than the parent compound.

Adult↗
PubMed2001

Biotransformation of 1,8-cineole by human liver microsomes.

The biotransformation of 1,8-cineole has been investigated by using human liver microsomes. A single oxidized metabolite, 2-exo-hydroxy-1,8-cineole, was isolated. Its formation was investigated under various conditions by changing incubation time, P450 level in liver microsomes, and substrate concentration.

Biotransformation↗
PubMed2001

Propofol versus midazolam regarding their antioxidant activities.

Propofol and midazolam are commonly used as sedatives for critically ill patients. These patients usually suffer from the pathologic effects of oxidative stress, predominantly caused by an imbalance between the generation of reactive oxygen species and the antioxidant defense system. Therefore, the antioxidant activities of propofol and midazolam may be of clinical importance. We investigated the activities of these two sedatives against hydrophilic or lipophilic peroxyl radicals in a homogeneous solution and in the presence of erythrocyte membranes. A chemical analysis of the homogeneous solution revealed that propofol efficiently scavenged hydrophilic peroxyl radicals (50% inhibitory concentration [IC50] = 1.3 x 10(-4) M), whereas midazolam efficiently scavenged lipophilic radicals (IC50 = 1.5 x 10(-5) M). Further, in membrane systems, propofol inhibited the oxidative damage induced by either hydrophilic or lipophilic radicals (IC50 = 1.5 x 10(-5) M for hydrophilic radicals and IC50 = 3.0 x 10(-4) M for lipophilic radicals), whereas midazolam did very little. In previous studies, we demonstrated that antioxidant activity is highly affected by the location and properties of the reaction site. The discrepancy in antioxidant activity between a homogeneous condition and in the presence of membranes can be well explained by this concept, and again emphasizes the importance of membranes in determining antioxidant activity. To further understand the biologic significance of these antioxidant properties, the effect of the two agents on endothelium-dependent relaxation was studied. Application of oxidative stress to aortic rings by treating them with peroxyl radicals led to a significant blockade of acetylcholine-induced relaxation after submaximal contraction with phenylephrine. Propofol pretreatment greatly attenuated the impairment in comparison with midazolam, which agrees with the concept of antioxidant activity in the presence of membranes. The results of the present study suggest that propofol has a greater potential to reduce oxidative stress than midazolam.

Antioxidants↗
PubMed2001

Passage of dextran magnetite nanoparticles through the subcupular space of the pigeon.

We examined the permeability of the subcupular space for endolymph flow in the pigeon. A new technique was developed in which nanoparticles consisting of dextran magnetite were attracted by use of a magnet, instead of injecting a dye solution. The method was revealed to prevent an excess pressure application by the injection of dye solution. The Berlin blue color resulting from the dextran magnetite nanoparticles was found mainly within the subcupular space contacting with the sensory hairs. Further formation of the Berlin blue was found within the sensory cells. The result supports the idea that the fluid passes through the subcupular space.

Animals↗
PubMed2001

Cupular response and functional anatomy to pressure application in the pigeon.

In this study, horizontal semicircular canal of the pigeon was inserted with a microfill, 164 micrometers in outer diameter, to gauge the pressure change in the canal and to clarify two things. One is whether the endolymph passes through the crista ampullaris or not. The other is as to the space where the endolymph passes through in the crista ampullaris if the endolymph goes through the crista. The pressure applications were performed by using Evans blue solution and as a result three pressure groups, i.e., 1) high, 2) moderate and 3) low were discriminated. Our results suggest that the endolymphatic fluid passes through the subcupular space or the top of the crista ampullaris when the pressure is enough small like the head rotates in daily life. Accordingly we present a new hypothesis as to the functional anatomy of the cupula in contrast to current hypotheses e.g. drum membrane or revolving door.

Animals↗
PubMed2001

Effect of mild exercise training on glucose effectiveness in healthy men.

OBJECTIVE: To detect whether mild exercise training improves glucose effectiveness (S(G)), which is the ability of hyperglycemia to promote glucose disposal at basal insulin, in healthy men. RESEARCH DESIGN AND METHODS: Eight healthy men (18-25 years of age) underwent ergometer training at lactate threshold (LT) intensity for 60 min/day for 5 days/week for 6 weeks. An insulin-modified intravenous glucose tolerance test was performed before as well as at 16 h and 1 week after the last training session. S(G) and insulin sensitivity (S(I)) were estimated using a minimal-model approach. RESULTS: After the exercise training, VO(2max) and VO(2) at LT increased by 5 and 34%, respectively (P < 0.05). The mild exercise training improves S(G) measured 16 h after the last training session, from 0.018 +/- 0.002 to 0.024 +/- 0.001 min(-1) (P < 0.05). The elevated S(G) after exercise training tends to be maintained regardless of detraining for 1 week (0.023 +/- 0.002 min(-1), P = 0.09). S(I) measured at 16 h after the last training session significantly increased (pre-exercise training, 13.9 +/- 2.2; 16 h, 18.3 +/- 2.4, x10(-5). min(-1). pmol/l(-1), P < 0.05) and still remained elevated 1 week after stopping the training regimen (18.6 +/- 2.2, x10(-5). min(-1). pmol/l(-1), P < 0.05). CONCLUSIONS: Mild exercise training at LT improves S(G) in healthy men with no change in the body composition. Improving not only S(I) but also S(G) through mild exercise training is thus considered to be an effective method for preventing glucose intolerance.

Adult↗
PubMed2001

Oxidation of 1,8-cineole, the monoterpene cyclic ether originated from eucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes.

1,8-Cineole, the monoterpene cyclic ether known as eucalyptol, is one of the components in essential oils from Eucalyptus polybractea. We investigated the metabolism of 1,8-cineole by liver microsomes of rats and humans and by recombinant cytochrome P450 (P450 or CYP) enzymes in insect cells in which human P450 and NADPH-P450 reductase cDNAs had been introduced. 1,8-Cineole was found to be oxidized at high rates to 2-exo-hydroxy-1,8-cineole by rat and human liver microsomal P450 enzymes. In rats, pregenolone-16alpha-carbonitrile (PCN) and phenobarbital induced the 1,8-cineole 2-hydroxylation activities by liver microsomes. Several lines of evidence suggested that CYP3A4 is a major enzyme involved in the oxidation of 1,8-cineole by human liver microsomes: (1), 1,8-cineole 2-hydroxylation activities by liver microsomes were inhibited very significantly by ketoconazole, a CYP3A inhibitor, and anti-CYP3A4 immunoglobulin G; (2), there was a good correlation between CYP3A4 contents and 1,8-cineole 2-hydroxylation activities in liver microsomes of eighteen human samples; and (3), of various recombinant human P450 enzymes examined, CYP3A4 had the highest activities for 1,8-cineole 2-hydroxylation; the rate catalyzed by CYP3A5 was about one-fourth of that catalyzed by CYP3A4. Kinetic analysis showed that K(m) and V(max) values for the oxidation of 1,8-cineole by liver microsomes of human sample HL-104 and rats treated with PCN were 50 microM and 91 nmol/min/nmol P450 and 20 microM and 12 nmol/min/nmol P450, respectively. The rates observed using human liver microsomes and recombinant CYP3A4 were very high among other CYP3A4 substrates reported so far. These results suggest that 1,8-cineole, a monoterpenoid present in nature, is one of the effective substrates for CYP3A enzymes in rat and human liver microsomes.

Animals↗
PubMed2000

Novel expression of equivocal messages containing both regions of choline/ethanolamine kinase and muscle type carnitine palmitoyltransferase I.

For characterization of the detailed gene structure of human muscle type carnitine palmitoyltransferase I (M-CPTI), we analyzed the 5'-upstream region of the M-CPTI transcripts. As a result, we found a cDNA clone containing a nucleotide sequence unexpected from the reported M-CPTI gene structure in the upstream region of its 5' end. Comparison of this nucleotide sequence with that of genomic DNA showed that this sequence was derived from the 3'-untranslated region of the gene encoding choline/ethanolamine kinase-beta (CK/EK-beta) located upstream of the M-CPTI gene. Southern blot analysis showed that there was no other region homologous to the CK/EK-beta gene in the whole human genome. Thus, the overlapping transcript was concluded to be produced from the functional genes of CK/EK-beta and M-CPTI. Furthermore, cDNAs containing both exons of these genes were detected by the polymerase chain reaction using the cDNA of human heart M-CPTI obtained by specific reverse transcription from its 3'-untranslated region as a template. From these results, the production and organization of these overlapping transcripts are discussed.

3' Untranslated Regions↗
PubMed2000

The fibula osteocutaneous flap in head and neck reconstruction: a critical evaluation of donor site morbidity.

OBJECTIVES: To (1) compare the complications and functional outcome of primary closure vs split-thickness skin grafting of the fibula osteocutaneous flap donor site, (2) identify patient-mix or treatment factors related to donor site complications, and (3) address early detection and management of donor site complications. DESIGN: Retrospective review and questionnaire study. SETTING: Two university tertiary referral centers. PATIENTS: Fifty-three patients (31 men and 22 women, ages 20 to 80 years) who underwent fibula osteocutaneous free tissue transfer between February 1992 and January 1997. MAIN OUTCOME MEASURES: Minor complications; major complications; and postoperative function, including sensory and motor deficits, pain, swelling, temperature intolerance, and activities of daily living. RESULTS: Four patients developed major wound complications (group 1), 11 patients developed minor wound complications (group 2), and 38 patients had no wound complications (group 3). The donor site was closed primarily in 26 patients and with a split-thickness skin graft in the remaining 27 patients. Major wound complications developed in 3 patients (12%) who underwent primary closure and 1 patient (4%) who underwent split-thickness skin grafting. Minor wound complications developed in 7 (27%) of the patients who underwent primary closure and 4 patients (15%) who underwent split-thickness skin grafting. Three patients who had major complications had residual sensory or motor deficits that resulted in impaired gait or alteration in their daily activities. Comparing all patients with complications (groups 1 and 2) to patients with no complications (group 3) demonstrated an increased incidence of donor site complications in heavy smokers (P<.05) and a strong trend toward higher donor site complications in patients who underwent primary closure (P =.10). Although trends were identified, no significant differences were found in age, comorbid illnesses, alcohol use, preoperative laboratory values, operating time, tourniquet time, or skin paddle width. CONCLUSIONS: A variety of patient-mix and operative factors are likely related to the development of donor site wound complications. Width of the skin paddle alone is not a reliable criterion for determining the need to skin graft the donor site. Primary closure tended to result in a higher rate of both major and minor wound complications compared with split-thickness skin grafting. Primary closure of fibula donor site defects should be undertaken if this can be accomplished with no tension along the suture line. If tension at the suture line is present, a skin graft should be strongly considered to minimize the possibility of a wound complication. Arch Otolaryngol Head Neck Surg. 2000;126:1467-1472

Adult↗
PubMed2000

IL-4, but not vitamin D(3), induces monoblastic cell line UG3 to differentiate into multinucleated giant cells on osteoclast lineage.

The formation of multinucleated giant cells (MGCs) from monocytes/macrophages is controlled by various cytokines, the roles of which are not fully understood. Both interleukin (IL)-4 and 1alpha,25(OH)(2) vitamin D(3) (D(3)) are known to induce MGC formation from monocytes/macrophages. D(3) is also known as a stimulator of osteoclast formation in the presence of stroma cells, and IL-4 as an inhibitor. Previously, we showed that IL-4-induced MGCs from monocytes/macrophages expressed tartrate resistant acid phosphatase (TRAP) activity and hydroxyapatite-resorptive activity in the presence of M-CSF without stroma cells. In this study, we examined the effects of D(3) and/or IL-4 on MGC formation and the characteristics of these MGCs using a monoblastic cell line (UG3), to elucidate the involvement of these factors in osteoclast development without stroma cells. D(3)-induced MGCs showed none of the markers of osteoclasts, such as TRAP activity, calcitonin receptor (cal-R) expression, hydroxyapatite-resorptive activity, and bone-resorptive activity. A low concentration of D(3) synergistically stimulated IL-4-induced TRAP-positive MGC formation, whereas a high concentration of D(3) inhibited it. When IL-4 was added on day 7 of the 2-week culture with D(3), TRAP positivity reached maximum. On the other hand, delayed addition of D(3) on day 7 of culture did not increase the TRAP positivity. Although the fusion rate increased during the first week of the 2-week culture in the presence of D(3), it increased further in the second week following the addition of IL-4 on day 7. Furthermore, IL-4-induced, or IL-4- and D(3)-induced MGCs differentiated into functional osteoclasts with bone-resorptive activity following coculture with osteoblastic cells, whereas D(3)-induced MGCs did not acquire bone-resorptive activity even after coculture with osteoblastic cells in the presence of D(3). These findings suggest that IL-4 initiates osteoclast development of UG3 cells, although stroma cells were necessary for development of functional osteoclasts. On the other hand, D(3) had only a "supportive" effect on this differentiation. IL-4 and direct contact with stroma cells may regulate different stages in the multistep process of osteoclastogenesis of UG3 cells.

3T3 Cells↗
PubMed2000

Decrease in presynaptic inhibition on heteronymous monosynaptic Ia terminals in patients with Parkinson's disease.

PURPOSE: Heteronymous Ia facilitation from the quadriceps to the soleus was studied to clarify central motor control through presynaptic inhibition (PSI) on Ia terminals of spinal motoneurons in Parkinson's disease. METHODS: 17 patients with Parkinson's disease and 36 control subjects participated in the study. Because the early part of facilitation reflects the degree of PSI, the extent of facilitation was quantified as the slope, within 0.8 msec of onset. RESULTS: Heteronymous Ia facilitation in the patients was greater than in the age-matched control participants. PSI was negatively correlated with the walking speed of the patients. In the patients examined twice, lessening of bradykinesia was correlated to a decrease in PSI but not lessening of rigidity. CONCLUSION: These findings indicate that the degree of PSI is decreased and disturbance of the central control of PSI may relate to gait disturbance in Parkinson's disease.

Adult↗
PubMed2000

A novel type of ATP block on a Ca(2+)-activated K(+) channel from bullfrog erythrocytes.

Using the patch-clamp technique, we have identified an intermediate conductance Ca(2+)-activated K(+) channel from bullfrog (Rana catesbeiana) erythrocytes and have investigated the regulation of channel activity by cytosolic ATP. The channel was highly selective for K(+) over Na(+), gave a linear I-V relationship with symmetrical 117.5 mM K(+) solutions and had a single-channel conductance of 60 pS. Channel activity was dependent on Ca(2+) concentration (K(1/2) = 600 nM) but voltage-independent. These basic characteristics are similar to those of human and frog erythrocyte Ca(2+)-activated K(+) (Gardos) channels previously reported. However, cytoplasmic application of ATP reduced channel activity with block exhibiting a novel bell-shaped concentration dependence. The channel was inhibited most by approximately 10 microM ATP (P(0) reduced to 5% of control) but less blocked by lower and higher concentrations of ATP. Moreover, the novel type of ATP block did not require Mg(2+), was independent of PKA or PKC, and was mimicked by a nonhydrolyzable ATP analog, AMP-PNP. This suggests that ATP exerts its effect by direct binding to sites on the channel or associated regulatory proteins, but not by phosphorylation of either of these components.

Adenosine Diphosphate↗
PubMed2000

A polymorphism upstream from the human paraoxonase (PON1) gene and its association with PON1 expression.

Human serum paraoxonase (PON1) is an esterase that has been shown to decrease the susceptibility of lipoproteins to lipid peroxidation. We found a polymorphism of cytosine/thymidine (-108C/T, the number is from the ATG codon) in the upstream region of the PON1 gene. The luciferase activity was lower in the -108T allele than in the -108C allele. The serum PON1 concentrations in 132 normal subjects were as follows: -108CC>-108CT and>-108TT genotypes. The polymorphism upstream from the PON1 gene is associated with transcription of the PON1 gene and the serum PON1 concentration.

Alleles↗