Search PubMed⌕ Search

Biomedical subjects

M Chiba

Publications and source records attributed to M Chiba.

At least 91 records · Page 5Linked to original sources

Oxidative damage to mitochondrial DNA and its relationship to diabetic complications.

Increased oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine (dG) to 8-hydroxydeoxyguanosine (8-OHdG) in DNA, which is linked to increased mitochondrial DNA (mtDNA) deletions. We investigated mtDNA deletions and 8-OHdG in the muscle DNA of non-insulin-dependent diabetes mellitus (NIDDM) patients. mtDNA deletion of 4977 bp (delta mtDNA4977) and the content of 8-OHdG in the muscle DNA of the NIDDM patients were much higher than those of the control subjects. There was a significant correlation between delta mtDNA4977 and the 8-OHdG content (P < 0.0001). Both delta mtDNA4977 and the 8-OHdG content were also correlated with the duration of diabetes. Delta mtDNA4977 and the 8-OHdG content in muscle DNA increased in proportion to the severity of diabetic nephropathy and retinopathy. This is the first report that an increase in delta mtDNA4977 and 8-OHdG is proportional to the severity of diabetic complications. Oxidative mtDNA damage is speculated to contribute to the pathogenesis of diabetic complications though a defect in mitochondrial oxidative phosphorylation or other mechanisms. 8-OHdG and delta mtDNA4977 are useful markers to evaluate oxidative mtDNA damage in the diabetic patients.

8-Hydroxy-2'-Deoxyguanosine↗

Effects of NTE-122, an acyl-CoA:cholesterol acyltransferase inhibitor, on cholesterol esterification and lipid secretion from CaCo-2 cells, and cholesterol absorption in rats.

The effect of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl)ureido]methyl]cyclohexane), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on cholesterol absorption was investigated. NTE-122 inhibited whole-cell ACAT activity in CaCo-2 cells, a human intestinal cell line, with an IC50 value of 4.7 nM. In CaCo-2 cells cultured on a membrane filter, NTE-122 pronouncedly inhibited the basolateral secretion of newly synthesized cholesteryl esters, and significantly reduced the basolateral secretion of newly synthesized triglycerides without influencing the cellular triglyceride synthesis. Furthermore, NTE-122 (1 mg/kg, p.o.) inhibited [14C]cholesterol absorption in rats. These results suggest that NTE-122 is capable of exhibiting anti-hyperlipidemic effects by reducing the absorption of dietary cholesterol.

Aniline Compounds↗

[Sodium azide: a review of biological effects and case reports].

This report reviews the biological effects and case reports of suicidal or accidental ingestion of, and occupational exposure to sodium azide. Ingested doses of sodium azide were estimated for the 6 survival and 4 fatal cases studied. The lowest dose among survival cases was 5-10 mg. The patient reported headache, sweating, and faintness within approximately 5 minutes of ingestion. Four victims ingested 20 to 40 mg and recovered within 2 hours. However, a man who took 80 mg reported chest pain for 6 months after ingestion. The smallest doses among fatal cases were 0.7-0.8 g for women and 1.2-2 g for men. All victims suffered from hypotension, tachycardia, hyperventilation, diaphoresis, vomiting, nausea, and diarrhea. There is no antidote for sodium azide. Detoxicants for cyanide such as sodium nitrite or thiosulfate were tried, but were unfortunately, ineffective. Sodium nitrite may worsen the hypotension caused by sodium azide, and is not recommended. Occupational exposure to sodium azide is thought to be common, however, fatal exposure is rare. NIOSH "Recommended Exposure Limits" for sodium azide is 0.3 mg/m3.

Adolescent↗

Posterior lumbar interbody fusion: a retrospective study of complications after facet joint excision and pedicle screw fixation in 148 cases.

We retrospectively evaluated neurological and other complications related to posterior lumbar interbody fusion (PLIF) performed by facet joint excision and pedicle screw fixation, in 148 consecutive patients with degenerative disorders. Their mean age at surgery was 59 (19-80) years. The mean follow-up period was 3 (2-6.5) years. Overall, 91 complications in 75 cases were observed. Although no permanent neural damage was detected, transient neural palsy occurred in 8% of the cases. Dural tear, partial misplacement, loosening, breakage of the pedicle screw and loss of correction were seen in 6, 6, 4, 1 and 1 of the cases, respectively. Deep infection of the fused segment developed in 2 cases. We conclude that PLIF, performed by facet joint excision and pedicle screw fixation, demonstrated a very low incidence of osteosynthesis failure, such as screw loosening, breakage and loss of correction. However, the high incidence of other complications, particularly neurological impairment, is still a disadvantage of this technically-demanding procedure.

Adult↗

[Surgical indication and problems of patients aged over 70 years with unruptured aneurysms].

Surgical indication and problems of patients aged over 70 years with unruptured aneurysms were investigated. Clinical features of eighteen cases of unruptured cerebral aneurysms were analyzed. The location of the cerebral aneurysms were in the internal carotid artery in five cases, in the middle cerebral artery in ten cases, in the anterior cerebral artery in 2 cases and in the basilar artery in 1 case. The size of the aneurysms was less than 10 mm in diameter in 17 cases and giant in one case. Treatment of these aneurysms was classified into two groups as follows; the conservative treatment group (four cases) and the surgical treatment group (14 cases). The therapeutic results of the conservative group were good recovery in 2 cases, and death in 2 cases. On the other hand, the results of surgical group were good recovery in 12 cases and fair in 2 cases. Operative complications were recognized in two cases. Consciousness disturbance and left hemiparesis was recognized in one case. Right hemiparesis was recognized in the another case. Postoperative MR imagings or CT scan presented small cerebral infarctions in the corona radiata in both cases. The cause of infarction was thought to be the occlusion of lenticulostriate arteries. From these data, in patients aged over 70 years with unruptured cerebral aneurysms, surgery should be considered not only from the aspect of aneurysmal size and its site, but also from the aspect of cerebral blood flow of the patient.

Age Factors↗

[Prevention of MRSA spread in the neurological field: intranasal application of mupirocin calcium ointment].

From September 1997 to March 1998, forty patients with cerebral disorders were investigated. They were divided into two groups: one treated and the other untreated. Mupirocin calcium ointment (MCO) was applied three times a day for three days into the nasal cavities of the patients in the treated group. In order to check the growth of MRSA (methicillin-resistant Staphylococcus aureus), bacterial isolation culture from the nasal cavity was carried out on admission, one week after admission and one month after admission. MRSA was nor detected in isolation culture of any of the cases on admission. One week later MRSA was detected in isolation culture of one case of the 20 MCO treated patients and in three of the 20 untreated patients. There was no significant difference between treated and untreated groups. In isolation culture after one month, MRSA was recognized in four cases of 16 in the MCO treated group (three patients were discharged and one expired). On the other hand, it was recognized in eight cases of thirteen in the untreated group (seven cases were discharged). MRSA infection of the nasal cavity decreased significantly due to MCO treatment (p < 0.05). It is suggested that the nasal carriage of MRSA was prevented by intranasal application of MCO on admission.

Administration, Intranasal↗

Modulation of rat cytochrome P-450 by an investigational HIV protease inhibitor.

Previous studies in vitro have revealed that L-754,394, an HIV protease inhibitor, is a potent suicide inhibitor of cytochrome P-450 enzymes. The present report examines the effect of chronic treatment of L-754,394 on hepatic cytochrome P-450s in adult male rats. L-754,394 was administered orally once a day for 7 days and resulted in significant changes in marker activities. An unusual parabolic (ascending, then descending) profile was observed for testosterone 2beta-/6beta-(CYP 3A1/2-catalyzed) hydroxylase activities during the 7-day treatment with 20 mg/kg L-754,394. These activities, which were elevated 2-fold on day 2, returned to basal levels by day 8. In contrast, testosterone 2alpha-/16alpha-(CYP2C11-catalyzed) hydroxylase activities showed an opposite parabolic (descending, then ascending) profile during the same period, reducing to 40% of control activities on day 4, followed by a rebounding trend. Immunoquantitation of CYP 3A1/2 and 2C11 showed that the expressed protein levels were in parallel with the associated activities. Furthermore, mRNA levels of CYP 3A2 and CYP2C11 showed the same trends as the protein expression of the respective isoforms. These observations show that L-754,394 perturbs the relative abundance of P-450 isoforms in rat liver by affecting the regulation at a pretranslational step. This may further involve a disturbance of hormonal homeostasis. Although serum levels of testosterone did not show a marked change during treatment, thyroxine and triiodothyronine markedly decreased on days 2 and 4, and subsequently increased to basal levels.

Animals↗

Evaluation of immune responses to inactivated influenza vaccines prepared in embryonated chicken eggs and MDCK cells in a mouse model.

This study was initiated with the isolation of influenza A and B viruses from clinical throat swabs in both fertile chicken eggs (egg) and MDCK cells, which were used in subsequent vaccine production in the above two hosts. On the basis of haemagglutination-inhibiting (HI) tests, immune mouse sera from mice vaccinated with MDCK cell-derived vaccines revealed antigenic similarities among H3N2 or B viruses isolated in MDCK cells or eggs. Similarly, antiserum prepared by immunization with egg-derived H3N2 vaccine showed equivalent antigenicity between homologous and heterologous (MDCK cell-derived) viruses. In contrast, antigenicity of egg-derived B vaccines was differed somewhat from that of MDCK cell-derived vaccines, suggesting the occurrence of antigenic change due to passaging in eggs. The time-course of immune responses based on HI titres indicated that MDCK cell-derived vaccines elicited extremely high antibody levels. Also, it was evident that antibody production by MDCK cell-grown H3N2 vaccine was very similar to that of vaccine prepared from egg-grown viruses. These results were comparable to those of plaque neutralization tests, although antigenic differences between egg- and MDCK cell-derived challenge viruses were confirmed in the test with antiserum to MDCK cell-derived vaccine. Consistent with HI-antibody production, the immunogenicity of MDCK cell-derived B vaccine appeared to be low by plaque neutralization test, while immune responses in mice which received egg-derived vaccines were significantly higher than that of the former. Furthermore, immune responses confirmed in mice immunized with B virus vaccines prepared in eggs revealed slight antigenic differences between two viruses derived from their respective hosts. Nevertheless, through evaluation of immune responses, MDCK cell-derived influenza vaccines may be useful when weak immunogenicity of B virus vaccine is improved.

Animals↗

Effect of dexamethasone on the intestinal first-pass metabolism of indinavir in rats: evidence of cytochrome P-450 3A [correction of P-450 A] and p-glycoprotein induction .

Indinavir, a potent and specific inhibitor of HIV protease, is a known substrate of cytochrome P-450 (CYP) 3A and p-glycoprotein. The purpose of this study is to investigate and compare the inducing effect of dexamethasone (DEX) on CYP3A and p-glycoprotein in the hepatic and intestinal first-pass metabolism of indinavir in rats. Pretreatment of rats with DEX had little effect on the pharmacokinetics (Cl and T(1/2)) after i.v. administration of indinavir, whereas DEX markedly altered the peak concentration (C(max)) and bioavailability of indinavir after oral dosing. The C(max) decreased from 2.8 microM in control rats to 0.28 microM in DEX-treated rats, and bioavailability decreased from 28 to 12.4%. The decreased bioavailability after DEX pretreatment was due mainly to an increase in first-pass metabolism. Intestinal first-pass metabolism (E(G)) increased from 6% in control rats to 34% in DEX-treated rats, and hepatic first-pass metabolism (E(H)) increased from 65 to 82%. Analysis of in vitro kinetic data revealed that the increased intestinal and hepatic metabolism by DEX was attributed to an increase in the V(max), as a result of CYP3A induction, without a significant change in the K(m) values. DEX pretreatment also induced p-glycoprotein in the intestine and liver of rats. p-Glycoprotein appeared to increase the intestinal metabolism of indinavir whereas it had little effect on the hepatic metabolism of indinavir. Although it has been suggested that the role of intestinal metabolism for some drugs is quantitatively greater than that of hepatic metabolism in the overall first-pass metabolism, the contribution of intestinal metabolism to the overall first-pass metabolism of indinavir in rats is not quantitatively as important as the hepatic metabolism, regardless of DEX induction.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Modified expansive open-door laminoplasty in cervical myelopathy.

The authors modified the technique of open-door cervical laminoplasty with a patency maintenance method that relies only on soft tissue reconstruction. Thirty-five patients who underwent this procedure were evaluated at more than 2 years' follow-up. The expanded open-door lamina and excellent alignment on the lateral view of the cervical spine were well maintained after surgery. Atrophy of the posterior cervical muscles was not seen. Clinical outcomes were rated satisfactory. Nuchal pain seen in the series of patients who underwent the original expansive open-door laminoplasty or a suspension laminotomy from 1983 to 1993 was decreased in the patients with the modified expansive open-door laminoplasty.

Adult↗

How to stabilize a single level lesion of degenerative lumbar spondylolisthesis.

The purpose of this study was to compare the success rate of bony fusion and the clinical results of rigid instrumentation, nonrigid instrumentation, and no instrumentation for a single level lesion for degenerative lumbar spondylolisthesis. Thirty-three patients with degenerative spondylolisthesis of L4 who had undergone posterior decompression and posterolateral fusion with autogenous bone graft that included the facet joints had a single level stabilization with a newly designed syndesmoplasty using Leeds-Keio artificial ligaments (Group Leeds-Keio-nonrigid). Thirty-four patients with degenerative spondylolisthesis of L4 who had the same procedure were stabilized with the Steffee system (Group Steffee-rigid). Thirty-five patients who had the same decompression and bony fusion without instrumentation (Group Noninstrumented) were compared with the former two groups. Clinical results were correlated with the stage of bony fusion. The Steffee system was reliable for stabilizing intervertebral angular instability such as a preoperative intervertebral angle difference of more than 11 degrees in flexion and extension. In the patients who preoperatively had an angle difference of less than 10 degrees, no significant difference was seen between Group Leeds-Keio and Group Steffee. The authors concluded that nonrigid instrumentation can be used to achieve successful bony fusion in patients with degenerative spondylolisthesis, who have a preoperative angle difference less than 10 degrees, with excellent clinical results.

Adult↗

What are the predictors of restoration of sinus rhythm after combined treatment with surgical repair for organic heart disease and the Maze procedure for atrial fibrillation?

BACKGROUND: Recently, combined treatment using the Maze procedure for organic heart disease and atrial fibrillation has been reported, but there have been few studies of cardiac rhythm after combined treatment. Predictors of cardiac rhythm after combined surgical treatment have been unknown. METHODS: Thirty patients who underwent cardiac surgery with the Maze procedure were retrospectively enrolled in this study. Two groups consisted of the patients with restoration of sinus rhythm after surgery (SR: n=15, 6 males and 9 females, mean age of 64 years), and the patients with maintenance of atrial fibrillation (AF; n=15, 5 males and 10 females, mean age of 61 years). Before cardiac surgery, all patients underwent exercise testing with measurement of atrial natriuretic peptide (ANP) before and after exercise testing, two-dimensional echocardiography, and right and left heart catheterization. RESULTS: The mean maximal heart rate and the ANP level after exercise testing in SR were significantly higher than those in AF. The left atrial dimension and right atrial and pulmonary capillary wedge pressures were significantly higher in AF than in SR. These findings indicate that subjects in SR exhibited less impaired atrial function which were evaluated by exercise testing with measurement of ANP, echocardiography, and cardiac catheterization. CONCLUSIONS: The atrial function of patients with sinus rhythm after the Maze procedure may be less impaired than that of patients remaining in atrial fibrillation.

Aged↗

The first report on human cases serologically diagnosed as Japanese encephalitis in Indonesia.

Although Japanese encephalitis (JE) virus was isolated from mosquitos in 1974, human JE cases have never been reported in Indonesia in spite of the prevalence of anti-JE antibodies among human and pig populations as well as abundant JE vector mosquitos. In this report, we describe serological diagnosis of JE cases in Bali. Indonesia. using IgM-capture ELISA both on serum and cerebrospinal fluid (CSF) of the patients. In the first series of our investigation (Series 1), we examined serum specimens from 12 patients with clinical diagnosis of viral encephalitis, meningitis or dengue hemorrhagic fever (DHF), and found 2 possible JE cases. In the next series (Series 2), we examined both serum and CSF from encephalitis patients and gave laboratory diagnosis of JE. One of them was suspected to have concomitant or recent infection with dengue virus, probably type 3. These results strongly indicated that JE has been prevalent in Bali, Indonesia.

Child, Preschool↗

Estimation of stature from somatometry of skull.

In order to investigate the possibility of estimating stature from somatometry of the skull, we carried out a study on 124 Japanese cadavers (comprising 77 males and 47 females) that had been autopsied at our laboratory between July 1986 and June 1991. Somatometry of the skull was performed on diameter (distance between glabella and external protuberance) and circumference (length around the skull through two points: the glabella and the external protuberance). The regression equations calculated were as follows: stature in males = (diameter + circumference) x 1.35 + 70.6 (standard error of estimate (S.E.) = 6.96 cm); stature in females = circumference x 1.28 + 87.8 (S.E. = 6.59 cm); stature in both sexes = (diameter + circumference) x 1.95 + 25.2 (S.E. = 7.95 cm). These S.E.s appear to be larger than those obtained for other parts of the body. However, in cases where identification is required by means of only the skull, this method could prove useful.

Adult↗

Metabolite-P450 complex formation by methylenedioxyphenyl HIV protease inhibitors in rat and human liver microsomes.

P450 complex formation and the unusual pharmacokinetics of methylenedioxyphenyl HIV protease inhibitors were examined by in vitro studies using human and rat liver microsomes and by in vivo oral dosing studies. In vitro spectral studies indicated that the formation of a P450 complex having absorbance maxima at 425 and 456 nm was time and concentration dependent; 27-60% of the total P450 was complexed in dexamethasone-induced rat liver microsomes after a 30-min incubation with 100 microM HIV protease inhibitors. Methoxy substitution on the phenyl ring of the methylenedioxyphenyl moiety increased formation of the P450 complex, whereas chlorine substitution markedly decreased the P450 complexation. Kinetic studies on the P450 complex formation indicated that both methoxy and chlorine substitution affected the maximum complex formation rate (Vmax), while it had little effect on Km values (approximately 10 microM). This complexation in human liver microsomes was inhibited markedly by an anti-CYP3A1 antibody. Furthermore, the P450 complex formation resulted in a time-dependent loss of CYP3A-catalyzed marker activities (testosterone 2beta/6beta-hydroxylase) in both rat and human liver microsomes. Collectively, these results point to the involvement of CYP3A isoforms in P450 complexation by methylenedioxyphenyl HIV protease inhibitors. Additionally, after oral administration to rats, one of these HIV protease inhibitors (Compound I), which complexed P450 to the greatest extent, showed no elimination over a period of 500 min after administration of the highest dose. It is suggested that formation of a quasi-irreversible metabolite-CYP3A complex with methylenedioxyphenyl HIV protease inhibitors was responsible for the CYP3A-selective time-dependent loss of catalytic function and the unusual dose-dependent pharmacokinetics after oral administration.

Animals↗