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Biomedical subjects

M Usui

Publications and source records attributed to M Usui.

At least 199 records · Page 11Linked to original sources

Slow abnormal conduction in the low right atrium: its anatomic basis and relevance to atrial reentry.

To characterize slow abnormal conduction in the low right atrium, which is known to be responsible for atrial flutter, electrophysiologic findings were correlated with anatomic features in a canine model of atrial flutter with ligation of the crista terminalis in the midright atrium. Activation in the low right atrium was mapped with a patch electrode containing 52 bipolar electrodes and a multiplexing system. A particular region in the low right atrium showed atrioventricular node-like electrophysiologic properties, a rate-dependent conduction delay, and Wenckebach periodicity. This area coincided with an area responsible for slow conduction during atrial flutter and unidirectional block at its initiation. Both pilsicainide and E-4031 preferentially blocked conduction in the specific area, leading to the termination of atrial flutter. Although refractoriness could not explain the abnormal conduction, anatomic studies consistently found the specific region to be in or around a thick muscle bundle, that is, the crista terminalis, or a thick pectinate muscle branching from the crista, located perpendicular to the wavefront of the pacing impulse and atrial flutter. These electrophysiologic and anatomic findings suggest that slow abnormal and atrioventricular node-like conduction over a thick muscle bundle, which is a normal anatomic feature of the low right atrium, plays a role in the initiation, maintenance, and termination of atrial reentry.

Animals↗

Digital lengthening in congenital hand deformities.

12 hands with congenital short finger in 11 patients were treated with various types of metacarpal bone lengthening. These included three patients with brachydactyly, seven with transverse deficiency, and one with constriction ring syndrome. All cases involved metacarpal lengthening and surgery was performed 16 times in 15 digits. Single-stage lengthening was performed in seven cases, on-top plasty in three cases, and distraction lengthening in six cases. The length gained ranged from 2 to 10 mm in single-stage lengthening, 3 to 17 mm in on-top plasty, and 12 to 30 mm in distraction lengthening. Delayed union and malunion occurred in single-stage lengthening or on-top plasty. After metacarpal lengthening, pinch function was improved in seven out of eight patients with either transverse deficiency or constriction band syndrome, and aesthetic improvement was achieved in three patients with brachydactyly.

Adolescent↗

Dorsal and circumferential sheath reconstructions for flexor sheath defect with concomitant bony injury.

Dorsal and circumferential flexor sheaths were reconstructed by autogenous sheath graft in flexor tendon repair in 28 white leghorn chickens. The effect of the sheath reconstructions was evaluated by use of an experimental model of tendon transection associated with bony injury, superficial tendon excision, and 3 weeks of immobilization. Six weeks after reconstruction, the gliding excursion was assessed and adhesion formation, tendon healing, and survival of the grafted sheath were evaluated both macroscopically and histologically. Dorsal and circumferential sheath grafts resulted in tendon gliding that was significantly better than the group with sheath defect not reconstructed. The adhesion formation was apparently less severe, and tendon healing was better in the groups with sheath reconstruction than in the group without reconstruction. The group with dorsal sheath reconstruction did not differ significantly from that with circumferential reconstruction in gliding excursion and adhesion formation. This study demonstrates that separation of the injured tendons from the bony surface by autogenous sheath grafts may be beneficial to tendon gliding and for reducing adhesion formation.

Animals↗

Flexor sheath closure during delayed primary tendon repair.

We studied the effect of flexor tendon sheath closure on flexor tendon function after delayed primary flexor tendon suture in white leghorn chickens. The tendon suture was carried out after a tendon laceration. In the left foot the tendon sheath was closed after tendon suture, and in the right the sheath was excised over the tendon suture. Tendon gliding, joint motion, the fate of the closed sheath, peritendinous adhesions, and tendon healing were studied. The sutured sheath disappeared after suturing and was associated with poor tendon healing. Sheath closure did not improve flexor tendon function in a delayed primary repair.

Animals↗

Shock-induced refractory period extension and pharmacologic modulation of defibrillation threshold.

Shock-induced refractory period extension (RPE) has been suggested as a mechanism of electrical defibrillation. We measured RPE caused by localized field stimulation measured before and during infusion of disopyramide (n = 5), flecainide (n = 5), or E-4031 (n = 5) in anesthetized dogs and determined the effect of the drugs on the internal defibrillation threshold (DFT). In the baseline state (n = 15), 16 V/cm S2 field stimulation prolonged the effective RP by 36 +/- 15 ms (22 +/- 12% of RP without S2), whereas 4 and 8 V/cm S2 stimuli did not cause marked RPE. The RPE normalized by the RP without S2 was not significantly influenced by any drug (16 V/cm: disopyramide 30 +/- 11 vs. 27 +/- 11, flecainide 25 +/- 5 vs. 19 +/- 12, and E-4031 18 +/- 13 vs. 22 +/- 14%). Disopyramide did not alter the defibrillation threshold (4.2 +/- 0.6-4.4 +/- 0.6 J). In 2 dogs given flecainide, ventricular fibrillation became refractory to defibrillation. In contrast, E-4031 lowered the threshold from 4.5 +/- 2.4 to 2.2 +/- 1.2 J (p < 0.01). The results suggest that flecainide and E-4031 do not modulate defibrillation efficiency through their effects on RPE.

Animals↗

Attenuation of antifibrillatory effects of lidocaine by its metabolite, glycylxylidide: application of modulated receptor hypothesis.

Lidocaine, one of the drugs effective in treating ventricular arrhythmias in acute myocardial infarction (AMI), sometimes loses its efficacy after prolonged administration, possibly owing to the counteraction of glycylxylidide, one of the metabolites of lidocaine, through modulation of binding of lidocaine to sodium channels. To determine whether glycylxylidide interferes with the antiarrhythmic action of lidocaine, we compared the antifibrillatory effects of lidocaine, glycylxylidide, and their combination in 14 anesthetized open-chest dogs. Although glycylxylidide alone prolonged intraventricular conduction time (CT) and did not affect ventricular effective refractory period (VERP), it had different effects when added to lidocaine; i.e., it had no effect on intraventricular conduction time but shortened VERP. Although glycylxylidide alone did not change ventricular fibrillation threshold (VFT), the increase in VFT induced by lidocaine was decreased by addition of glycylxylidide, possibly as a result of competition for the same cardiac sodium channels between lidocaine and glycylxylidide with similar onset but different offset kinetics, which may explain, at least in part, the drug-resistance phenomena that ensue from prolonged lidocaine administration.

Animals↗

Analysis of the uveitogenic determinant in repeat structure of retinal interphotoreceptor retinoid-binding protein (IRBP).

IRBP is a glycolipoprotein with a four-fold partially homologous repeat structure approximately 300 residues in length, and is one of the retinal antigens capable of inducing experimental autoimmune uveoretinitis (EAU) in susceptible animals by their active immunization. The most immunopathogenic peptide of bovine IRBP for EAU in Lewis rats is reported to be the sequence 1169-1191 (PTARSVGAADGSSWEGVGVVPDV) with two immunogenic motifs common to T cell epitopes (underlined). The uveitogenic site of peptide 1169-1191 was localized at the carboxyl terminus (peptide 1182-1191) and not at the amino acid terminus (peptide 1169-1182). Repeat peptides of sequence 1179-1191 containing the four homologous residues (1182W, 1186G, 1187V and 1189P), that is the peptides 271-283, 579-591 and 880-892, all elicited EAU. Peptide 579-591 could not stimulate proliferation of lymphocytes from rats immunized with IRBP, but had the capacity to adoptively transfer EAU. The role of the homologous residues was examined using analogues of the uveitogenic peptide 1182-1194, in which each homologous residue was substituted by glycine (G) or leucine (L) (1182W-->G, 1186G-->L, 1187V-->G, and 1189P-->G). One analogue (1186G-->L) strongly diminished the ability to induce EAU, while the other three analogues completely abolished the ability, indicating that these homologous residues were essential for the induction of EAU. In addition, the uveitogenic peptides tested in this study were found not to contain the major epitope for antibody production.

Amino Acid Sequence↗

Primary structures of the wild-type and mutant alleles encoding the phosphatidylglycerophosphate synthase of Escherichia coli.

The nucleotide sequence of the Escherichia coli pgsA gene, encoding phosphatidylglycerophosphate synthase, is revised to code for an enzyme of 182 amino acid residues, instead of the 216 of a previous work (A. S. Gopalakrishnan, Y.-C. Chen, M. Temkin, and W. Dowhan, J. Biol. Chem. 261:1329-1338, 1986). The revised structure now explains the properties of the enzyme. Three pgsA mutants of different phenotypes were also analyzed: pgsA3, pgsA36, and pgsA10 have single-base replacements in codons 60 (Thr-->Pro), 1 (ATG-->ATA), and 92 (Thr-->Ile), respectively.

Alleles↗

Vasospasm prevention with postoperative intrathecal thrombolytic therapy: a retrospective comparison of urokinase, tissue plasminogen activator, and cisternal drainage alone.

The authors report the results of a retrospective review, between January 1986 and December 1991, of the results of early surgery and intrathecal thrombolytic therapy in 111 patients with aneurysmal subarachnoid hemorrhage. Effects on clot lysis, angiographic and symptomatic vasospasm, cerebral infarction, and clinical outcome were compared in 60 patients treated with urokinase (UK) 60,000 IU/d for 7 days (UK group), 22 patients treated with 0.042 to 1 mg tissue plasminogen activator (tPA) every 6 to 8 hours for 5 days (tPA group), and 29 patients who did not receive treatment with either thrombolytic agent (no-treatment group). The no-treatment group consisted of all patients treated before July 1986 and of patients in whom thrombolytic therapy was attempted but failed to start or in whom the therapy was not used intentionally because of small subarachnoid clot. Treatment with UK was employed between July 1986 and March 1991, and tPA was employed during the remainder of the study for patients at a higher risk for vasospasm. The severity of angiographic vasospasm and the incidence of infarction in the UK and the tPA groups were less than those of the no-treatment group (P < 0.01), in spite of a larger amount of initial subarachnoid blood clot in both thrombolytic groups. This appears to be the result of the more rapid clearance of cisternal clot in the thrombolytic groups than the no-treatment group (P < 0.01). Only tPA therapy reduced the incidence of symptomatic vasospasm (P < 0.05). No serious complications were observed, although in the tPA group, asymptomatic intraventricular hemorrhage occurred in one patient, and transient confusion in another. Both received 4 mg tPA/d. Meningitis was suspected in 16 patients of the UK group. However, in this relatively small retrospective series, there were no differences among the three groups in overall outcome at 3 months. This study indicates that postoperative intrathecal thrombolytic therapies, especially with less than 4 mg/d of tPA, are effective in lysing subarachnoid clot and preventing vasospasm and infarction safely.

Adult↗

A phase II clinical trial of recombinant human tissue-type plasminogen activator against cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

The results of a Phase II clinical trial of intrathecal recombinant tissue-type plasminogen activator for the prevention of vasospasm were reported. The subjects were 53 patients with aneurysmal subarachnoid hemorrhage (SAH), Groups 2 to 4 in Fisher's preoperative computed tomography classification and Grades II to IV in the Hunt-Kosnik classification. Twenty-four hours after surgery, tissue-type plasminogen activator (TD-2061) was intracisternally administered via a catheter (0.1, 0.2, or 0.4 mg, three times daily for 5 days). The clot-dissolving effects assessed as "effective" and "markedly effective" were virtually the same in the 0.1- and 0.2-mg groups (66.7% and 64.3%, respectively) but slightly lower (53.3%) in the 0.4-mg group, suggesting an adequate effect in the 0.1- and 0.2-mg groups. Severe angiographic vasospasm was not observed in any of three groups. No intergroup differences were noted in the incidence of symptomatic vasospasm, low density on computed tomography 1 month after SAH, and functional prognosis. Bleeding complications were noted in 4 patients (7.5%), including 1 case of SAH in the low 0.1-mg group, 2 cases of SAH in the 0.2-mg group, and 1 case of epidural hematoma in the 0.4-mg group. In overall safety rating, 3 cases with increased SAH and 1 case of epidural hematoma were assessed as "safety doubtful." Other minor side effects such as headache and hepatic dysfunction attributed to the effect of other simultaneously used drugs were assessed as "almost safe," and the rate of "almost safe" and "better" for all dose groups was about 90%, suggesting a safe dose level for all groups. These results suggest that repeated intrathecal administration of tissue-type plasminogen activator is useful for preventing vasospasm even in the low dose of 0.1 mg.

Adult↗

Retinoic acid transport to lens epithelium in human aqueous humor.

Retinoids, in particular retinoic acid, are required for the normal growth and maintenance of many types of cells, including epithelial cells. The metabolism of lens epithelial cells, which are exposed to aqueous humor in the anterior chamber, is thought to be dependent upon aqueous humor dynamics. In human eyes undergoing cataract surgery, we measured retinoic acid levels using reverse-phase high performance liquid chromatography to investigate the possible role of aqueous humor in the transport of retinoic acid to lens epithelial cells. The retinoic acid level in the aqueous humor and the lens epithelial cells was 23.3 +/- 2.3 pmol/ml and 1.8 +/- 0.8 pmol/micrograms protein, respectively. Fluorescence spectra study suggested the presence of endogenous retinoid-protein complexes in the aqueous humor. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the major protein in aqueous humor was albumin, a natural carrier protein of retinoic acid in the blood. From these results, we conclude that the aqueous humor may supply retinoic acid to the lens epithelial cells in human eyes.

Aged↗

[201Tl scintigraphic evaluation of tumor mass and viability of bone and soft-tissue tumors].

To characterize 201Tl uptake in patients with bone and soft-tissue tumor, we studied 49 patients with surgically proven tumors and one patient with a tumor diagnosed arteriographically. In 37 of our 50 patients, the tumor was evaluated with 201Tl and arteriography. Moreover, in 14 of patients with pre-operative chemotherapy, pathologic changes were graded on the basis of percent tumor necrosis as defined histologically. The percent tumor necrosis histologically was compared with changes in the scintigraphic and conventional angiographic studies. Radiologic comparisons demonstrated a high degree of correlation with images of 201Tl and both arterial and blood pool phase of 99mTc-HMDP. Ninety-six percent of 28 malignant tumors had positive 201Tl uptake. None of the patients showed any thallium accumulation in the soft tissues or skeleton adjacent to the lesion. Activity of 201Tl was mainly dependent upon a tumor blood flow and a vascular density. In of 14 cases with the preoperative chemotherapeutic treatment, 201Tl scintigraphic changes showed concordance with % tumor necrosis. Thallium-201 was superior to 99mTc-HMDP in predicting tumor response to chemotherapy. Interestingly, delayed images of 99mTc-HMDP of 5 responders with > 90% tumor necrosis showed decreased uptake in the adjacent bone to the tumor mass lesions. It seems to be quite all right to consider that a major determinant of 201Tl uptake is intratumoral angiogenecity, which is closely connected with tumor viability. Therefore, 201Tl is a sensitive radiopharmaceutical for detection of vascular rich bone and soft-tissue tumors, and appears to be a simple and an accurate test for evaluating the response to specific therapeutic regimens of malignant bone and soft-tissue tumors.

Adolescent↗

[An investigation of factors in the pathogenesis of experimental autoimmune uveoretinitis (EAU) in congenic mice].

S-antigen or interphotoreceptor retinoid-binding protein (IRBP), when injected with Freund's complete adjuvant into mice, does not easily cause experimental autoimmune uveoretinitis (EAU). In this report, we describe the results of injecting IRBP with Freund's complete adjuvant, together with the intraperitoneal administration of Bordetella pertussis, into several types of congenic mice (B10, B10A, B10BR, B10D2). These congenic mice, of C57BL/10 (B10) origin, differ at the H-2 locus on chromosome 17. We were able to produce EAU in 38.5% of B10A mice, and 12.5% of B10BR mice, confirming that EAU can develop in these mice that carry the k genotype at the K, I-A, and I-E regions of the major histocompatibility complex (MHC) H-2 locus. We believe that the k genotype of the K, I-A, and I-E regions is important as a factor in the pathogenesis of EAU in congenic B10 mice.

Animals↗

[Superoxide generated by polymorphonuclear leukocytes and retinal lipid peroxidation in uveoretinitis].

The presence of superoxide generated by polymorphonuclear leukocytes (PMNs) was demonstrated in an experimental autoimmune uveoretinitis (EAU) model. Histopathological examination of the eyes, enucleated sequentially after the onset of EAU, and determination of retinal lipid peroxidation (LPO) revealed an increase in LPO products with progressive retinal tissue damage. In addition, histopathological changes, predominantly degeneration of the retinal outer segments, and increased retinal LPO were confirmed in vitro by culturing naive neural retina with activated PMNs. This increased LPO was inhibited by superoxide dismutase (SOD). These data suggest that lipid peroxidation reaction involving superoxide may play an important role in the pathogenesis of retinal tissue damage in ocular inflammatory disease characterized by the infiltration of PMNs.

Animals↗

[The effect of ocular and/or pineal body removal in mice with spontaneously developing uveoretinitis].

Autoimmune uveoretinitis and pinealitis have been shown to develop spontaneously in BALB/c nude mice after their T cell function has been reconstituted by embryonic F344 rat thymus grafting (TG nude mice). Because anti-IRBP antibodies were detected in these mice, it was concluded that IRBP was the target antigen. In this study, we removed the eyes and/or the pineal body from TG nude mice, and examined anti-IRBP antibodies in their sera. It appeared that IRBP originating from the eyes and the pineal body were the immunogenic antigens in the TG nude mice, but the IRBP from the eyes was found to be more immunogenic and pathogenic than that from the pineal body. We also found that the incidence of uveoretinitis increases with pinealectomy in TG nude mice, even though the immune system is not affected.

Animals↗

[Enzyme-linked immunosorbent assay for the quantification of Cry j I and Cry j II].

Enzyme-linked immunosorbent assays (ELISA) were developed to specifically quantify the two major allergens from Japanese cedar pollen, Cry j I and Cry j II. Polystyrene microplates coated with antibodies specific for Cry j I or Cry j II were incubated with an allergen and then with biotinylated anti-Cry j I or Cry j II antibody. The bound allergen-biotin Ab complexes were detected with HRPO-conjugated streptavidin and an enzyme substrate. The working ranges of Cry j I ELISA and Cry j II ELISA were 0.3-20 ng/ml and 0.6-20 ng/ml, respectively. Intra- and inter-assay coefficients of variation for reproducibility were 1.5-10.3% and 0.9-12.9%. These ELISA systems showed no cross-reactivity between Cry j I and Cry j II and showed little cross-reactivity with pollen allergens of plants botanically related to the Japanese cedar. Using the Cry j I ELISA and the Cry j II ELISA, it was possible to quantify Cry j I and Cry j II easily and accurately. These ELISA systems will be useful in various fields, especially for the analysis and standardization of the allergens necessary for diagnosis and treatment of Japanese cedar pollinosis.

Allergens↗

A clinical trial of FK506 in refractory uveitis.

We performed a clinical open trial to evaluate the efficacy and the adverse side effects of a single therapy with FK506 in refractory uveitis as a multicenter study in Japan. Fifty-three patients (41 patients with Bechçet's disease, five with Vogt-Koyanagi-Harada disease, four with idiopathic retinal vasculitis, and three with other forms of uveitis) were enrolled in the study. FK506 was given orally for 12 weeks. Treatment with FK506 exhibited therapeutic effects in a dosage-dependent manner: the effectiveness was 38% in patients treated with an initial dosage of 0.05 mg/kg of body weight per day, 60% with 0.10 mg/kg of body weight per day, 83% with 0.15 mg/kg of body weight per day, and 79% with 0.20 mg/kg of body weight per day. Overall efficacy with dosage adjustment when needed was 76.5% at the conclusion of the study at the end of the 12th week. The FK506 therapy induced a variety of adverse side effects, the incidence of which depended on the dosage. The major side effects were renal impairment (28.3%, 15 of 53 patients), neurologic symptoms (20.8%, 11 of 53 patients), gastrointestinal symptoms (18.9%, ten of 53 patients), and hyperglycemia (13.2%, seven of 53 patients). The trough level of FK506 in the whole blood correlated with both the efficacy of the therapy and with the incidence of adverse effects. It is recommended to maintain the trough level between 15 and 25 ng/ml. On the basis of these results, a daily dosage of 0.10 to 0.15 mg/kg of body weight per day was suggested as an appropriate therapeutic dosage for refractory uveitis.

Administration, Oral↗