Endovascular stent-graft placement for thoracic aortic injury: case report.
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Accidents, Traffic↗
Biomedical subjects
M Shindo
Publications and source records attributed to M Shindo.
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↗
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↗
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↗
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↗
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↗
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↗
Stereoelectronic effect on stereoselective olefination of ketones providing tetrasubstituted olefins via ynolates
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Journal Article↗
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↗
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↗
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↗
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↗
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↗
Genomic variations in precore and cytotoxic T lymphocyte regions in chronic hepatitis B in relationship to interferon responsiveness.
AIMS: Treatment of chronic hepatitis B patients with interferon (IFN) alpha results in a sustained loss of viral replication in as many as 20-40% of cases. The resistance to antiviral treatment by some viruses is due to positive selection of variants harboring mutations that confer resistance. An HBV variant with a stop codon in the precore region (A1896 HBV) has been reported to be associated with the response to IFN therapy. Recently variations in amino acid residues 21 and 27 of the core protein that serve as either partial agonists or antagonists to cytotoxic T-lymphocyte (CTL) function have been demonstrated to affect response to IFN therapy. In this study, we investigated whether these genomic variations in precore and CTL regions can affect response to IFN therapy. PATIENTS: Twenty-three patients with chronic hepatitis B were treated with IFN alpha. Of these 23 patients, 6 were responders (defined as showing seroconversion to anti-HBe, loss of serum HBV DNA and normalization of serum aminotransferase levels), and the remaining 17 were non-responders. METHOD: A total of 75 serum samples (3 serial samples per patient collected before, at the end of therapy, and 6 months after therapy) were tested for core promoter and precore wildtype and mutant viral levels and for sequence in the CTL region. RESULTS: There were no significant differences in precore wildtype and mutant viral levels before therapy between responders and non-responders, and both viral levels significantly decreased equally when measured at the end of therapy. Approximately 90% of non-responders with HLA-A2 had no amino acid substitutions in the CTL region before therapy. IFN therapy did not induce any specific mutations in this region. CONCLUSION: These findings suggest that the precore wildtype and mutant had similar sensitivity to IFN, and that genomic variation in the CTL region does not appear to be associated with response to IFN therapy.
Adult↗
Suppression of adjuvant arthritis of rats by a novel matrix metalloproteinase-inhibitor.
BAY 12-9566 (4-[4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) is a newly developed, synthetic matrix metalloproteinase (MMP) inhibitor (MMPI) that selectively inhibits MMP-2, MMP-3 and MMP-9 isozymes. We study the effect of BAY 12-9566 on inflammation and cartilage destruction in adjuvant-induced arthritis (AA) in rats. Rats were injected with adjuvant and treated for 21 days with vehicle, Indomethacin or BAY 12-9566. AA was assessed: by measuring arthritic index, paw volume, urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr); by examining joint inflammation; and by microscopic morphometry of articular cartilages. Oral treatment of rats for 22 days with 50 mg kg(-1) body weight/d BAY 12-9566 showed decreased AA as determined by improvement in body weight gain (P<0.01), arthritic index (P<0.05) and swelling of paws contralateral to the adjuvant injection site (P<0.05). Neutrophil infiltration and collagen degradation were also significantly lower (P<0.01) in this treatment group. Cartilage destruction was successfully suppressed (P<0.01) in rats treated with either 50 mg kg(-1) body weight/d BAY 12-9566 or 1 mg kg(-1) body weight/d Indomethacin. These results indicate that BAY 12-9566 successfully suppressed inflammation and cartilage destruction in rats with AA. Moreover, these results also suggested that MMP-2, MMP-3 and MMP-9 are involved in arthritic diseases such as rheumatoid arthritis.
Amino Acids↗
Fas-mediated apoptosis of peripheral blood mononuclear cells in patients with hepatitis C.
In the present study, we demonstrated that a close relationship exists between hepatitis C virus (HCV) infection of peripheral blood mononuclear cells (PBMCs) and cell-surface Fas expression in patients with hepatitis C, and showed the possibility of PBMCs apoptosis via a Fas-mediated system. The expression of Fas on PBMCs was found by flowcytometric analysis to be significantly increased in these patients. In addition, the treatment of patients' PBMCs with anti-Fas antibody induced cell death, with nuclear condensation and fragmentation and cellular DNA fragmentation. These data indicate that the patients' PBMCs expressed a large amount of functional Fas on the cell surface and were susceptible to stimulation against Fas, causing apoptotic cell death. We then quantified the serum-soluble Fas ligand (sFasL), which was known to bind to Fas and induce the apoptotic signals into the sensitized cells. The patients' serum sFasL levels were significantly higher than those of normal subjects and showed a good negative correlation with their PBMC number. To demonstrate the correlation between Fas expression and HCV infection, nested reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect HCV RNA. Interestingly, HCV RNA was preferentially detected from Fas-positive cells but not from Fas-negative cells, which had been isolated from PBMCs by magnetic beads. These results suggest that HCV infection of PBMCs might induce Fas expression and additional stimulation such as sFasL might induce apoptosis in these Fas-expressing cells. These mechanisms, in addition to hypersplenism, may explain the decrease in the number of PBMCs observed in patients with chronic hepatitis C.
Adult↗
Facial reanimation with microneurovascular free flaps.
Numerous options are available for rehabilitation of chronic facial nerve paralysis, ranging from simple slings to complex procedures such as microneurovascular tissue transfer. Microneurovascular muscle transfer is generally indicated: 1) if the patient desires dynamic facial reanimation, particularly restoration of involuntary emotional facial expressions; 2) in the absence of distal facial nerve fibers or motor endplate function; 3) with an associated large soft tissue defect in the cheek; and 4) when other dynamic reanimation procedures have not been successful. The most commonly used free flaps for facial reanimation are gracilis, latissimus dorsi and inferior rectus abdominus muscle. When successfully performed free flaps yield excellent functional and aesthetic results in facial reanimation.
Anastomosis, Surgical↗
Neuropathology of auditory agnosia following bilateral temporal lobe lesions: a case study.
Our patient was first diagnosed with auditory agnosia following his second cerebral vascular accident (CVA) in 1975 when he was 37 years old. Comprehensive follow-up examinations of auditory function were periodically conducted until his sudden death 15 years later. His brain was studied postmortem for neuropathology. Initial pure-tone audiometry revealed moderate sensorineural hearing loss in the right ear and mild sensorineural hearing loss in the left ear. However, repeated pure-tone audiometry revealed that thresholds became progressively poorer over time, bilaterally. Speech audiometry of both ears consistently revealed that the patient was unable to discriminate any monosyllabic words (i.e. speech intelligibility scores were 0%, bilaterally). In general, speech and hearing tests demonstrated that he could not comprehend spoken words, but could comprehend written commands and gestures. Postmortem neuropathological study of the left hemisphere revealed total defect and neuronal loss of the superior temporal gyrus, including Heschl's gyrus, and total gliosis of the medial geniculate body. In the right hemisphere, examination revealed subcortical necrosis, gliosis in the centre of the superior temporal gyrus and partial gliosis of the medial geniculate body. The pathological examination supports clinical results in which the patient's imperception of speech sounds, music and environmental sounds could be caused by progressive degeneration of bilateral medial geniculate bodies.
Adult↗