Search PubMed⌕ Search

Biomedical subjects

M Chiba

Publications and source records attributed to M Chiba.

At least 181 records · Page 10Linked to original sources

[A case of acute occlusion of left middle cerebral artery due to an embolus treated successfully with percutaneous transluminal angioplasty].

The acute occlusion of cerebral artery by embolism causes severe cerebral infarction. In cases with poor colateral circulation, cerebral infarction develops more severely. In these cases, quick recanalization of the occluded cerebral artery is necessary to prevent severe hemorrhagic infarction and brain edema. We report a case where interventional techniques were used to bring about quick recanalization of occluded cerebral artery. We encountered a case of a sixty-year-old male who experienced complete occlusion of the left middle cerebral artery due to an embolus. It was very hard to pass a guide wire through the embolic lesion. At first, we tried mild local fibrinolysis therapy using tissue plasminogen activator, but we could not get any recanalization. However, after mild local fibrinolysis therapy, the guide wire could be passed through the occlusion point. Secondly, we tried percutaneous transluminal angioplasty (PTA) with 2.0mm diameter angioplastic balloon using up to five atomic pressures, after which we obtained partial recanalization. Finally we achieved total recanalization of the middle cerebral artery by PTA with a 2.5mm diameter angioplastic balloon. We crushed this embolus using the angioplastic balloon with up to six atomic pressures. The point of the techniques is to press the embolus against the arterial wall. After this angioplasty, there was an occlusion of the common trunk of the posterior parietal artery and the angular artery. However there was neither massive hemorrhagic infarction nor massive brain edema on follow up CT. In the treatment of acute occlusion of the cerebral artery due to embolism, we found PTA is very effective against the embolus. In the future, we need to develop a retrieving device and a balloon that will prevent the production of small emboli during the crush process involved when bringing about recanalization using PTA.

Acute Disease↗

Sex-dependent pharmacokinetics of indinavir: in vivo and in vitro evidence.

Indinavir, a potent and specific inhibitor of human immunodeficiency virus protease, is used for the treatment of AIDS. This study was designed to investigate the sex-related differences in kinetics and metabolism of indinavir in rats, dogs, and monkeys to support the toxicity studies. When given intravenously, indinavir was cleared rapidly in a polyphasic manner in all species. Indinavir exhibited significant differences in elimination kinetics among species. The rat had the highest plasma clearance (CLp; 41-89 ml/min/kg), and the dog had the lowest CLp (15-26 ml/min/kg), with the monkey exhibiting an intermediate value (36-39 ml/min/kg). Furthermore, marked sex-related differences in CLp were observed in rats and dogs, but not in monkeys. The CLp was 89 ml/min/kg for male rats and 41 ml/min/kg for female rats. In contrast to rats, female dogs cleared indinavir more rapidly than male dogs; the CLp was 26 ml/min/kg for female dogs and 15 ml/min/kg for male dogs. Consistent with the in vivo observations, hepatic microsomes from male rats had a substantially higher metabolizing activity toward indinavir than that from females, whereas liver microsomes from female dogs catalyzed the drug at a higher rate than that from male dogs. Qualitatively, in vitro metabolic profiles of indinavir were similar among species and between male and female animals. Studies with an anti-rat cytochrome P450 (CYP) 3A1 antibody pointed to the probable involvement of isoforms in the CYP3A subfamily in the oxidative metabolism of indinavir in both males and females of all species. The functional activity of CYP3A measured by the formation of testosterone 6beta-hydroxylation and immunoblot analysis of the level of CYP3A proteins strongly suggested that gender differences in the levels of CYP3A isoforms may contribute to the observed sex-related differences in indinavir metabolism in rats and dogs.

Animals↗

[A case of acute occlusion of the cervical portion of the right internal carotid artery with successful stepwise vascular dilatation by rescue PTA and deferred PTA].

A case is reported of acute occlusion of the cervical portion of the internal carotid artery, which was recanalized and dilated by steps through rescue percutaneous transluminal angioplasty (PTA) and deferred PTA. A 53-year-old man, complaining of progressive disturbance of consciousness and hemiplegia, was admitted to our department at about 7 hours after onset. CT demonstrated no abnormality. Digital subtraction angiography revealed an occlusion of the right cervical internal carotid artery. After intra-arterial injection of t-PA, a guide wire was able to be passed through the artery. Recanalization of internal carotid artery was performed by rescue PTA with Stealth FS angioplastic balloons of small diameter. Residual stenosis ratio was about 80%. After rescue PTA, his symptoms improved. On the following day, deferred PTA with Stealth FS angioplastic balloons of larger diameter was performed. Stenosis ratio was 30%. After the procedure, his palsy was relieved. DSA in the 3rd week after the PTA revealed that the stenosis ratio had changed from 30% to 13%. Rescue PTA is very effective for prompt recanalization. Stepwise vascular dilatation by rescue PTA with small balloons followed by deferred PTA can improve symptoms and prevent fatal hemorrhagic infarction. This method is especially useful for high risk patients of cervical internal carotid artery occlusion.

Acute Disease↗

Direct measurement for elasticity of myosin head.

During muscle contraction, chemical energy from ATP hydrolysis is converted to the relative sliding movement of actin and myosin filaments. In order to elucidate the molecular mechanism of sliding-force generation, it is a crucial clue to know an elastic modulus of myosin. Here, we report direct measurements of Young's modulus of myosin head (myosin subfragment-1) isolated from rabbit skeletal muscle, using a surface forces apparatus. Our results show that the elasticity of myosin subfragment-1 has direction and is about 0.3 GPa along the long axis during ATP hydrolysis. When the bow-shaped subfragment-1 is modelled as an elastic rod, the stiffness and the bending fluctuations of subfragment-1 are calculated to be 3-7 pN/nm and about 1 nm, respectively. These results strongly support a model of multiple power strokes rather than the conventional tilting-crossbridge model.

Adenosine Triphosphate↗

Novel modification of ceramide: rat glioma ganglioside GM3 having 3-O-acetylated sphingenine.

A novel O-acetylated GM3 containing 3-O-acetyl 4-sphingenine was isolated with one having a non-acetylated base from transplanted rat glioma tissue. The presence and position of the acetyl group were estimated by one- and two-dimensional proton nuclear magnetic resonance, and fast atom bombardment-mass spectrometries. In addition, the O-acetyl GM3 showed higher immunological activity toward anti-melanoma antibody in the presence of non-acetylated GM3 in complement-dependent liposome lysis than did non-acetylated or acetylated GM3 alone in the liposome, suggesting enhancement of immunological reactivity of the intact tumor cells by a small amount of O-acetyl GM3.

Animals↗

Germ line mutations of hMSH2 and hMLH1 genes in Japanese families with hereditary nonpolyposis colorectal cancer (HNPCC): usefulness of DNA analysis for screening and diagnosis of HNPCC patients.

Mutations in hMSH2 and hMLH1 genes were analyzed in patients from 11 Japanese families that had been diagnosed as carrying hereditary nonpolyposis colorectal cancer (HNPCC) by clinical examination. Germ line mutations of hMSH2 gene were identified in 5 independent families in which colorectal (87% of patients), endometrial (30%), ovarian (17%), gastric (14%), and other cancers existed. Five mutations detected between codons 136 and 811 included single-base substitutions (C-->T and T-->G), a T deletion, and an A insertion, all of which produced stop codons resulting in truncated proteins, and an A-->T substitution at splice donor site of exon 5 which resulted in deletion of this exon. Moreover, one HNPCC family was presumed to have germ line mutation of hMSH2 gene because a somatic mutation of hMSH2 gene was detected in a cancer from a patient in this family. In addition to these 11 families already diagnosed with HNPCC, 3 new families with germ line mutations of hMSH2 gene and hMLH1 gene were found through analysis of DNA from patients who had multiple cancers with alteration in microsatellite DNA. These mutations included an AG deletion at codons 877-878 of hMSH2 gene, an AAG deletion at codons 616-618 of hMLH1 gene, and a C-->T single-base substitution at codon 217 of hMLH1 gene. Seven of eight germ line mutations found in this study are new mutations that have not been reported previously. In families in which germ line mutations were identified presymptomatic examination was then carried out using polymerase chain reaction single-strand conformation polymorphism analysis of DNA from peripheral blood, and the result was the detection of family members predisposed to HNPCC who did not yet show signs of cancer. These results indicate the value of DNA analysis in the screening and diagnosis of HNPCC patients and families.

Adult↗

Topographic study of Helicobacter pylori and HLA-DR antigen expression on gastric epithelium.

Helicobacter pylori and HLA-DR antigen expression on gastric epithelium, identified by an indirect immunoperoxidase staining method using monoclonal antibodies against H. pylori and HLA-DR antigens, were studied topographically. Fifty-nine biopsy specimens from 41 patients who had neither gastric cancer nor peptic ulcers were examined. H. pylori was observed predominantly over or on the surface epithelium, while HLA-DR antigens were frequently expressed on the epithelium of the isthmus region. These observations led to the conclusion that there was no direct topographic association between H. pylori and epithelial HLA-DR expression. However, the frequency of HLA-DR expression in H. pylori-positive (28/29) specimens was significantly higher than that in H. pylori-negative (18/30) specimens (P < 0.01). Furthermore, a greater number of H. pylori was associated with a stronger expression of HLA-DR antigens (P < 0.001). We conclude that H. pylori is indirectly related to HLA-DR expression on gastric epithelium. H. pylori is the first microbial agent that has been suggested to be associated with epithelial HLA-DR expression in the human gastrointestinal tract.

Adolescent↗

Axial movements of rat mandibular incisors measured under artificial respiration with halothane anaesthesia.

The axial movements of rat incisors were recorded continuously for over 20 h. The rats were anaesthetized with halothane delivered by intratracheal intubation using an artificial respirator. A haemostatic clamp was used to immobilize the jaw and the displacement detector exhibited high resolution, good linearity and low drift. The previously impeded and unimpeded eruption rates (the average extrusive movements) were 406 and 548 microns/24 h, respectively. The previously unimpeded rate was lower than the normal unimpeded rates obtained by other investigators. It appears that the eruptive movement of the previously unimpeded incisor was inhibited by halothane anaesthesia. Circadian rhythm was not observed in the eruption rates of previously impeded or unimpeded incisors. Following the i.p. injection of a lethal dose of pentobarbital sodium, the incisors retracted. The average intrusive movement was significantly greater in the previously impeded group (29 microns) than in the previously unimpeded group (12 microns) at 30 min after the lethal injection. It is assumed that the elimination of the pushing force at death may cause the stretched periodontal fibres to recoil, thereby pulling the tooth in an intrusive direction. It is also likely that the mechanical strength of the ligament is reduced in the previously unimpeded group by repeated shortening of the incisors; therefore the force needed to retract previously unimpeded incisors may be less than that needed to retract previously impeded incisors.

Animals↗

Ventral pancreatitis in a patient with pancreas divisum.

Pancreas divisum results in drainage of most pancreatic secretions through the minor papilla via the dorsal duct, and the association of minor papilla stenosis has been implicated as a cause of pancreatitis. Most of the reported cases represent pancreatitis confined to the dorsal part. The authors treated a 10-year-old boy with recurrent pancreatitis that was substantially more severe in the ventral part. The patient was referred with a brief history of abdominal pain and had undergone a laparotomy when segmental ventral pancreatitis had been observed. Severe pancreatitis and acute renal failure developed, which required drainage of the lesser sac and hemodialysis, respectively. After 5 months, he had another episode that subsequently led to a pseudocyst in the ventral part. Endoscopic retrograde cholangiopancreatography via minor papilla showed a normal-caliber dorsal duct communicating with a part of the fine ventral ducts. A normal biliary tree was shown, but no ventral duct was visualized by cannulation to the major papilla of Vater. Dual sphincteroplasties and a cholecystectomy were performed. The minor papilla was stenotic and admitted only the finest lacrimal duct probe. The orifice of the ventral duct could not be observed. Thus it was clarified that the dorsal duct with its stenotic orifice had drained both the dorsal and ventral pancreas. The patient has remained asymptomatic over 36 months postoperatively. Despite their limited experience, the authors believe that (1) this anatomic variant led to ventral pancreatitis, and (2) the sphincteroplasty of the minor papilla was successful.

Acute Disease↗

Impaired cholinergic peripheral vasodilation and its relationship to hyperemic calf blood flow response and exercise intolerance in patients with chronic heart failure.

This study examined the peripheral endothelium-dependent vasodilatory response to acetylcholine and the endothelium-independent vasodilatory response to nitroprusside in 19 patients with chronic heart failure and eight controls. These peripheral blood flow responses were compared with hyperemic calf blood flow changes after maximum leg exercise and 5-min femoral occlusion. The peripheral blood flow response to forearm intra-arterial infusion of acetylcholine and sodium nitroprusside, and reactive hyperemic calf blood flow changes were measured by plethysmography. All peripheral blood flow responses were significantly reduced in patients with chronic heart failure (P < 0.05). Reduction of acetylcholine-mediated changes in peripheral blood flow was correlated with exercise-induced calf blood flow response (r = 0.51, P < 0.05), but not with occlusion-induced calf blood flow response (r = 0.02, NS). Sodium nitroprusside-mediated changes were not correlated with any reactive hyperemic blood flow responses (exercise: r = 0.27, NS; occlusion: r = 0.11, NS). When the patients were divided into two subgroups based on the median exercise-induced calf blood flow change, the subgroup with the lower calf blood flow response showed a reduction in exercise capacity (anaerobic threshold: 11.8 +/- 0.6 vs. 14.6 +/- 1.0 ml/kg/min; P < 0.05). These findings suggest that endothelial dysfunction is related to a decrease in exercise-induced skeletal muscle blood flow and exercise capacity in patients with chronic heart failure.

Acetylcholine↗

Further studies of HLA-DR antigens on colonic epithelium in ulcerative colitis.

The aim of this study was to determine whether HLA-DR antigens are expressed on colonic epithelium in macroscopically involved areas in all cases of ulcerative colitis and whether the expression precedes inflammation (colitis). Thirty-four cases of active ulcerative colitis were studied including two cases in which island-like lesions were observed proximally apart from the main lesion, and three cases in which distal colitis became entire colitis in 8 months or less. Detection of HLA-DR antigens on colonic epithelium was performed with the immunoperoxidase method using anti-HLA-DR monoclonal antibodies. HLA-DR antigens were expressed on colonic epithelium in macroscopically involved areas in all 34 cases. In the macroscopically normal areas, the antigens were modestly expressed in six of 16 specimens (cases) in the presence of microscopic inflammation. The antigens were expressed on colonic epithelium in island-like lesions, but not in the intervening mucosa between the proximal island-like lesions and the distal main lesion. HLA-DR antigens were not expressed on colonic epithelium in the proximal non-inflamed mucosa where colitis later developed. These results lead to the conclusion that HLA-DR antigen expression does not precede, but is associated with the inflammation.

Adolescent↗

Toxicity study of europium chloride in rats.

EuCl3.6H2O was administered by gavage for 28 consecutive days to groups of 10 male and 10 female rats (Slc:Wistar strain) at doses of 0, 40, 200, or 1000 mg/kg/day. Additional groups of male and female rats receiving the 0 and 1000 mg/kg doses were used to assess recovery after 14 days subsequent to cessation of compound administration. Body weights and food consumption were measured, and hematological, clinical biochemistry, and histopathological examination were performed. The concentrations of europium (Eu) and of essential elements in organs were determined by ICP-MS or ICP-AES. In the rats of each sex dosed at 200 and 1000 mg/kg, the body weight gain significantly decreased because of reduction in food consumption. Hyperkeratosis of the forestomach and eosinocyte infiltration of the stomach submucosa were found in both sexes receiving the 1000 mg/kg dose group, suggesting an irritation effect by EuCl3.6H2O. The Eu levels increased dose dependently in the liver, kidneys, spleen, and femurs, and the accumulated volume of Eu in these organs was estimated to be about 1/100,000 of the total dosed amount. The administration of EuCl3.6H2O increased the serum iron concentration in males and the serum total iron binding capacity in each sex and decreased cholinesterase activity in females in the 1000 mg/kg dosed group. Iron concentrations in the spleen and strontium concentrations in the femurs of rats of both sexes dosed at 1000 mg/kg were significantly decreased. We concluded that the no-observed-effect level is 200 mg/kg/day. Our investigation demonstrated that elemental analyses of organs is a useful approach to toxicological study.

Animals↗

Glutathione depletion kinetics with acetaminophen. A simulation study.

A tubular-flow model with known published parameters on glutathione (GSH) synthesis, degradation, and transport was developed to examine the distributed-in-space bimolecular reaction of GSH conjugation with acceptor substrates. Simulations were performed to obtain the vascular and intracellular GSH concentrations in the absence and presence of acetaminophen. Zonal localization of GSH was found to be effectively modified upon varying the activities for GSH synthesis and degradation along the sinusoidal flow path. A periportal (zone 1) GSH distribution resulted when GSH synthetic activity was distributed anterior to the degradation activity (models A and D); a perivenous (zone 3) GSH enrichment existed when these activities were reversed (model B), whereas when the synthetic and degradation activities for GSH were homogeneously distributed (model C), GSH concentration was unchanged in all zones. Although the zonation of GSH was model-dependent (models A-D ), only minor differences were found to exist for the length-averaged tissue GSH concentration (5.8-6 mumol/g liver) and the outflow of the liver (approximately 15 microM). With acetaminophen, a substrate known to deplete GSH via its reactive intermediate, N-acetyl-p-quinoneimine (NAPQI), acinar GSH patterns were not greatly perturbed at concentrations < 1 mM. At 10 mM acetaminophen, however, differential patterns of GSH zonal depletion were observed among models, although there was virtually no difference in the length-averaged intracellular GSH concentration (3 mumol/g liver) nor in the formation of the acetaminophen GSH adduct, with the latter being rate-limited by the bioactivation of acetaminophen to NAPQI.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

Time- and dose-dependent pharmacokinetics of L-754,394, an HIV protease inhibitor, in rats, dogs and monkeys.

L-754,394 is a potent and specific inhibitor of the HIV-1 encoded protease that is essential for the maturation of the infectious virus. The drug exhibited dose-dependent kinetics in all species studied (rat, dog and monkey); the apparent clearance decreased when the dose was increased. However, the dose-dependency cannot be explained by Michaelis-Menten kinetics. L-754,394 in plasma declined log-linearly with time, but with an apparent half-life that increased with dose. The apparent terminal half-life of L-754,394 in rats increased from 20 min at 0.5 mg/kg i.v. to 118 min at 10 mg/kg i.v. Furthermore, L-754,394 exhibited time-dependent pharmacokinetics. After chronic i.v. doses for 7 days (1 mg/kg/dose/day), the apparent clearance of L-754,394 in rats decreased from 87 ml/min/kg after the first dose to 25 ml/min/kg after the last dose. Similar results were observed in dogs and monkeys. In vitro spectral studies indicated that approximately 40 to 60% of the content of cytochrome P-450 was inactivated when L-754,394 (10 microM) was incubated with rat, dog and monkey liver microsomes in the presence of NADPH. Little or no inactivation of cytochrome P-450 was observed when either NADPH or L-754,394 was omitted. In addition, L-754,394 selectively inhibited CYP 2C11-dependent testosterone 2 alpha- and 16 alpha-hydroxylase activity and CYP 3A1/2-dependent testosterone 6 beta-hydroxylase activity, but not CYP 2D1/2-dependent bufuralol 1'-hydroxylase activity nor CYP 1A2-dependent phenacetin O-deethylase activity in rat liver microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗