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Biomedical subjects

A Hashimoto

Publications and source records attributed to A Hashimoto.

At least 199 records · Page 11Linked to original sources
PubMed1993

Free D-serine, D-aspartate and D-alanine in central nervous system and serum in mutant mice lacking D-amino acid oxidase.

We have examined whether D-amino acid oxidase (DAO) regulates free D-serine content using mutant ddY/DAO- mice lacking DAO activity. We find that the content of D-serine in the serum and cerebellum of mutant mice is much higher than that of normal mice, whereas a slight but significant difference in the cerebral D-serine level is observed between the two strains. These results suggest that, although DAO may participate in the catabolism of D-serine in the cerebellum and periphery, there appears to be other mechanisms for catabolism of endogenous D-serine in the brain.

Alanine↗
PubMed1993

Studies on percutaneous transvenous mitral commissurotomy using a modified transseptal approach.

A modified version of Brockenbrough's trans-septal catheterization technique was carried out in 11 patients indicated for percutaneous transvenous mitral commissurotomy (PTMC). In 8/11 (72.7%), a coiled guide-wire was successfully inserted through the foramen ovale without atrial septal puncture. The Brockenbrough needle was used merely to maintain stiffness and the orientation of the dilator. PTMC was performed with an Inoue single balloon without incident. Patent foramen ovale was found by transesophageal echocardiography prior to the operation in only 1/11 patients (9.0%); nonetheless, it proved not to be a critical factor for the success of the procedure. This procedure seems to have much potential to enable the treatment of mitral stenosis with a lowered risk to the patient, as long as it is performed with precision and caution.

Adult↗
PubMed1993

Synthesis and evaluation of 1-(1-[5-(2'-[18F]fluoroethyl)-2-thienyl]-cyclohexyl)piperidine as a potential in vivo radioligand for the NMDA receptor-channel complex.

1-(1-[5-(2'-[18F]Fluoroethyl)-2-thienyl]cyclohexyl)piperidine (18FE-TCP) was prepared as a fluorine-substituted analogue of the potent NMDA receptor channel blocker, 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), by the mesylate displacement with [18F]fluoride ion with isolated radiochemical yields of 6-12%, and the synthesis time including a two step HPLC purification was 120 min. The regional distribution in rat brain after i.v. injection of 18FE-TCP was heterogeneous and similar to the known distribution of phencyclidine recognition sites, with hippocampus-cerebellum, striatum-cerebellum and cerebral cortex-cerebellum concentration ratios of 2.08, 1.7 and 1.54, respectively, 15 min post-injection. Furthermore, this localized regional cerebral distribution was blocked by co-injection with the unlabelled FE-TCP or pretreatment with cis-2-hydroxymethyl-r-1-(N-piperidyl)-1-(2-thienyl)cyclohexane, with the greatest reductions seen in the hippocampus followed by the striatum and cerebral cortex. However, relatively low receptor binding affinity and high non-specific binding due to its high lipophilicity suggest that 18FE-TCP may not be a suitable radioligand for in vivo PET investigations of the NMDA receptor-channel complex.

Animals↗
PubMed1993

Vaccination with hatched but non-activated, non-viable oncospheres of Taenia taeniaeformis in rats.

The usefulness of hatched but non-activated oncospheres as a candidate vaccine was evaluated using a Taenia taeniaeformis/rat system, since preparation of these oncospheres in vitro is known to be very simple. The findings were: (1) rats vaccinated with non-viable oncospheres became completely resistant to challenge infection; (2) intra-venous injection was the most effective to induce complete resistance; (3) a single oncosphere was sufficient to induce complete resistance in infected rats, whereas approximately 50 and 500 non-viable oncospheres were required to evoke strong and complete resistance, respectively, in vaccinated rats. The usefulness of non-viable oncospheres without adjuvant is discussed.

Animals↗
PubMed1993

Endogenous D-serine in rat brain: N-methyl-D-aspartate receptor-related distribution and aging.

Recently, a substantial amount of free D-serine has been demonstrated in rat brain, although it has long been presumed that D-amino acids are uncommon in mammals. The anatomical distribution and age-related changes in endogenous D-serine have been examined here to obtain insight into its physiological functions. Free D-serine exclusively occurs in brains, with a persistent high content from birth to at least 86 postnatal weeks. The patterns of the regional variations and the postnatal changes in brain D-serine are closely correlated with those of the N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. Because D-serine potentiates NMDA receptor-mediated transmission by selective stimulation of the strychnine-insensitive glycine site of the NMDA receptor, it is proposed that D-serine is a novel candidate as an intrinsic ligand for the glycine site in mammalian brain.

Aging↗
PubMed1993

Embryonic development and postnatal changes in free D-aspartate and D-serine in the human prefrontal cortex.

We have analyzed free chiral amino acids (aspartate and serine) in the human frontal cortex at different ontogenic stages (from 14 weeks of gestation to 101 years of age) by HPLC with fluorometric detection after derivatization with N-tert-butyl-oxycarbonyl-L-cysteine and o-phthaldialdehyde. Exceptionally high levels of free D-aspartate and D-serine were demonstrated in the fetal cortex at gestational week 14. The ratios of D-aspartate and of D-serine to the total corresponding amino acids were also high, at 0.63 and 0.27, respectively. The concentration of D-aspartate dramatically decreased to a trace level by gestational week 41 and then remained very low during all postnatal stages. In contrast, the frontal tip contained persistently high levels of D-serine throughout embryonic and postnatal life, whereas the D-amino acid content in adolescents and aged individuals was about half of that in the fetuses. Because D-aspartate and D-serine are known to have selective actions at the NMDA-type excitatory amino acid receptor, the present data suggest that these D-amino acids might play a pivotal role in cerebral development and functions that are related to the NMDA receptor.

Adolescent↗
PubMed1993

Mechanical circulatory support for postcardiotomy ventricular failure: the Heart Institute of Japan experience 1984-1992.

In the last 9 years, 30 patients received assisted circulation or a ventricular assist device after open-heart operations at the Heart Institute of Japan. After cardiovascular surgery, 9 of those patients underwent venoarterial bypass, 10 had biventricular bypass, 7 had left ventricular bypass, and the remaining 4 received a left ventricular assist device. Of the first 15 patients, only 3 (20%) were discharged from the hospital. In contrast, 7 (46.7%) of the last 15 patients were discharged without major complications. With respect to complications, bleeding and ventricular arrhythmia (immature weaning) decreased with low-heparinized isolated left ventricular supports. However, profound biventricular failure, infection, and multiple organ failure remain as possible complications with any type of assisted circulation. These results suggest that early application of circulatory support and appropriate selection of the mode of support and devices used are important for successful circulatory support.

Adult↗
PubMed1993

Percutaneous cardiopulmonary support as the second generation of venoarterial bypass: current status and future direction.

We have developed a new percutaneous cardiopulmonary support (PCPS) system in cooperation with Terumo Corporation, called the Emergency Bypass System (EBS). This preassembled system is unique in terms of its small priming volume (470 cc), fully automatic priming function, originally developed membrane oxygenator, and Capiox straight path centrifugal pump. The priming process takes only 5 min. We have used this system in 4 patients (all were male; mean age 56 years, range 35-73 years). The duration of assist ranged from 15 min to 210 h. Maximum bypass flow ranged from 2.2 to 3.6 L/min, systemic circulation was very well maintained, and urinary output was acceptable. Although the centrifugal pump was in good working condition, we had to change the oxygenator because of serum leakage 36 to 48 h after initiation of the assist. One patient was weaned from the PCPS, but died of brain death. The other patients could not be weaned from the PCPS. The cause of death in these patients was irreversible myocardial damage. Disseminated intravascular coagulopathy triggered by surgical trauma related to various procedures developed in 2 patients during assist and was the cause of cessation of the assist. Problems to be ratified and future directions in the EBS and PCPS were earlier introduction through the establishment of clear indications and endpoint, heparin coating, improvement in durability of the oxygenator, and cost.

Adult↗
PubMed1993

Clinical experience of assisted circulation with a centrifugal pump at Tokyo Women's Medical College.

In postpericardiotomy patients, the use of pulsatile pumps is limited in a semielective fashion to patients whose postoperative marginal hemodynamics are expected preoperatively. Since 1989, 25 patients have undergone assisted circulation with a centrifugal pump: 15 (60%) were weaned from the pump, and 7 (28%) survived. In 1988, we heparin-coated the Bio-Pump using the Carmeda technique and developed a totally heparin-coated left heart bypass system together with heparin-coated cannulas and tubing. Four postpericardiotomy patients underwent left heart bypass with this system without heparin for 2 to 9 days. No thrombus was detected in the system. Left heart bypass with a centrifugal pump has been used as a supportive method in surgical repair of thoracic or thoracoabdominal aortic aneurysm. To overcome intraoperative hypothermia and hypoxia, we used a small membrane oxygenator with a heat exchanger in 11 patients, and postoperative recovery dramatically improved. We also developed a preassembled percutaneous cardiopulmonary support (PCPS) system with an automatic priming function using Terumo's straight path centrifugal pump and small membrane oxygenator in cooperation with the Terumo Corporation. This system was used in a patient with cardiogenic shock after acute myocardial infarction. The setup and priming took only 5 min, and 2.5-3.5 L/min of flow was obtained.

Adult↗
PubMed1993

[Treatment of experimental invasive pulmonary aspergillosis in rats with liposomal amphotericin B].

Liposomal amphotericin B was evaluated for toxicity, pharmacokinetic properties and therapeutic efficacy in invasive pulmonary aspergillosis in Sprague-Dawley rats. The protective effect of liposomes against the toxicity induced by repeated amphotericin B infusions was observed in a survival study of rats, thereby allowing higher dosages to be administered. Pharmacokinetic studies showed that liposomes led to high levels of amphotericin B in the spleen and liver. Drug levels in the lung were higher at ten minutes after intravenous injection of liposomal amphotericin B at 20 mg/kg than of free amphotericin B at 1.5 mg/kg. Efficacy was assessed in rats treated with cortisone acetate, fed a low-protein diet and infected transtracheally with 8 x 10(4) Aspergillus fumigatus spores to cause fetal pneumonia and pulmonary bleeding. Dosages of 20 or 4 mg/kg of liposomal amphotericin B, or 1.5 mg/kg of free amphotericin B were administered intravenously to rats once daily for 8 days. Control rats received saline. Twenty mg/kg of liposomal amphotericin B was as effective on survival rate as 1.5 mg/kg of free amphotericin B. However, 4 mg/kg of liposomal amphotericin B was less effective than 1.5 mg/kg of free amphotericin B, prolonging the mean survival time of rats treated with saline, which showed elevation of galactomannan antigen titers of Aspergillus fumigatus in sera and invasive proliferation or mycelia with bleeding in histopathological sections of the lung. We conclude that liposomal amphotericin B reduces toxicity of the drug, thereby increasing the concentration of the drug in the lung by high-dose administration, but decreases the efficacy of the drug in experimental pulmonary aspergillosis.

Amphotericin B↗
PubMed1993

Immunological cross-reactivity of the C-terminal 42-kilodalton fragment of Plasmodium falciparum merozoite surface protein 1 expressed in baculovirus.

The roles of allelic and conserved epitopes in vaccine-induced immunity to the C-terminal 42-kDa fragment of the Plasmodium falciparum merozoite surface protein 1 (MSP1) were investigated. The C-terminal fragment of MSP1 was expressed as a baculovirus recombinant protein, BVp42. Rabbits were immunized with BVp42, and antibodies were tested for reactivity to MSP1s of the homologous and heterologous allelic forms, represented by the FUP, FVO, FC27, and Honduras parasite isolates, by enzyme-linked immunosorbent assay and indirect immunofluorescence antibody assay. Despite the fact that allelic sequences accounted for approximately 50% of the BVp42 molecule, anti-BVp42 antibodies cross-reacted extensively with parasites carrying heterologous MSP1 alleles. Enzyme-linked immunosorbent inhibition assays confirmed that an overwhelming majority of the anti-BVp42 antibodies were cross-reactive, suggesting that determinants within conserved block 17 are dominant B-cell epitopes in the anti-BVp42 response. Moreover, the BVp42 polypeptide could inhibit (> 90%) the cross-reactivity of anti-MSP1 antibodies in animals immunized with the complete native MSP1 protein. Anti-BVp42 antibodies were equally effective in inhibiting the in vitro growth of parasites carrying homologous or heterologous MSP1 alleles. Serotyping by monoclonal antibodies indicated that the immunological and biological cross-reactivities were not caused by identical variant-specific amino acid substitutions within conserved block 17. These results should provide the impetus to develop a vaccine based on the C-terminal conserved region(s) of MSP1 against parasites of diverse genetic makeup.

Alleles↗
PubMed1993

Experimental chemonucleolysis with chymopapain in canine intervertebral disks.

The present study describes the radiological and histological changes in the canine intervertebral disk after the experimental injection of chymopapain as the chemical reagent, and determines the appropriate dose of the enzyme for treatment of herniated disks. By radiography, narrowing of the disk space was observed within 2 weeks after the injection of chymopapain, and recovered to 74.1% in the 0.1 mg group, 61.1% in the 1.0 mg group and 71.7% in the 10.0 mg group at 12 weeks. The disk space recovery showed a tendency to delay with aging. Microscopically, proteoglycan positive matrix appeared and the nuclear space was reduced in each disk at 2 weeks after chymopapain injection. The nucleus pulposus contained an irregularly-defined mass consisting of clusters of degenerated notochordal cells surrounded by proliferated chondrocytes and collagen matrix. In each disk at 12 weeks after chymopapain injection, the center of the nucleus pulposus was replaced by fibrocartilage tissue. In the disk into which 10.0 mg chymopapain was injected, the nuclear space filled with dense fibrocartilage tissue without a regenerated matrix component and narrowing of the disk were maintained. It is suggested that canine chemonucleolysis with 10.0 mg of chymopapain reduces the interdiskal pressure. This treatment may therefore relieve the signs and symptoms of herniation of the nucleus pulposus, and may effect chemical disk decompression.

Animals↗
PubMed1993

Cerebral death-like conditions after aortic aneurysm surgery using retrograde cerebral perfusion.

A patient with Stanford type A acute aortic dissection who developed severe cerebral dysfunction after surgery using retrograde cerebral perfusion through the superior vena cava was examined. The patient was able to regain normal brain function with no neurological deficit. Postoperative venography taken through the superior vena cava showed the presence of competent venous valves at the venous angles. This suggests that the valves interrupted cerebral perfusion, decreasing blood flow to less than that required. After consideration of the possible causes of brain damage incurred during surgery for aortic aneurysm using retrograde cerebral perfusion, it was concluded that this patient was able to recover normal brain function because the surgery was performed under profound hypothermia.

Adult↗
PubMed1993

[International normalized ratio (INR) for optimal anticoagulant therapy].

Optimal therapeutic ranges for an oral anticoagulant therapy has been discussed for many years. Prothrombin time, prothrombin time ratios (PTR) and thrombotest have been employed so far, but, recently, International Normalized Ratio of prothrombin time (PT-INR or INR) has been introduced. We investigated paying special interest to INR, the effectiveness of oral anticoagulant therapy in 170 prosthetic valve patients and in 157 patients with various cardiovascular diseases who received warfarin at two different centers. The thrombotest, prothrombin time and INR were measured at follow-up visits every month. Regarding the 170 patients with prosthetic valves with a mean follow-up period of 2.44 years, 9 thromboembolisms (TE) were reported. The average TT and INR values in TE-free patients among 101 in whom coagulability could be measured, were 21.1% and 1.73 respectively. The average TT and INR values in 5 patients with TE were 26.4% and 1.53 respectively and this was significantly (p < 0.01) higher (smaller) than in TE-free patients. 157 patients (mean age 55 +/- 12 y.o.) with various cardiovascular diseases (Table 2) were followed up for a mean of 4.9 +/- 3.2 years. As is seen in figure 4, mean INR values in TE patients were 1.28, in patients with bleeding complications 4.1, and in event free patients 2.07 respectively. In conclusion, with INR greater than 2.75, no thromboembolic complication occurred, but several hemorrhagic complications occurred at INR greater than 3. Therefore INR therapeutic ranges between 2.0-3.0 are recommendable both for the prevention of TE and bleeding complications.

Administration, Oral↗
PubMed1993

[Effect of retrograde cerebral perfusion in preserving cerebral function during circulatory arrest].

The efficacy of retrograde cerebral perfusion (RCP) method was evaluated in 26 patients who underwent aortic arch reconstruction. Surgical procedures were; ascending-proxymal arch replacement involving Bentall type procedures (17 cases), total arch replacement (4 cases), and distal arch replacement (5 cases). The RCP were performed through selective cannulation on the superior vena cava at 18.4 degrees C of the average rectal temperature. The perfusion pressure was 28.3 (+/- 5.9) cmH2O and flow was 360 (+/- 15.4) ml/min. RCP time was 74.1 (+/- 26.2) min. Twenty-four patients survived among 26 patients and 2 patients died after operation. Postoperative consciousness was confirmed in 25 patients. Postoperative neurological complications were 1) delayed arousal 5 cases, 2) delirium 3 cases, 3) respiratory disorders 5 cases, 4) double vision 2 cases, 5) cerebral infarction (CI) 1 case. These complications except-CI were resolved in early postoperative period. And regarding effective time period of RCP, incidence of neurological complications were significantly higher in cases which received RCP over 80 min. Therefore we consider that 80 min is a safety time period. In conclusion, RCP is a useful step for preserving the brain during the operation of graft replacement of aorta involving aortic arch.

Aortic Dissection↗
PubMed1993

Repeated canine herpesvirus (CHV) reactivation in dogs by an immunosuppressive drug.

To examine the possibility of repeated reactivation of canine herpesvirus (CHV), 2 serial treatments with the corticosteroid drug prednisolone (PD) were given at different periods following oral-nasal infection of pups and adult dogs. CHV was not recovered from infected, untreated dogs or from uninfected, treated controls. Viral reactivation of CHV, without clinical signs, was induced twice in 2/3 adults and in 2/3 pups treated at intervals that ranged from 1 to 3 months following the initial infections. Highest viral titers were obtained from nasal swab samples, with lower titers found in the oral pharynx, penis or vagina. In some, but not all dogs, the infectivity titers of the nasal secretion samples were higher after the initial prednisolone treatments than after the second treatments. The duration of viral shedding after the second series of steroid treatments also was shorter than the shedding period following the initial reactivations. The results presented here suggest that latent CHV occurs in both pups and adults dogs following infection and that active infections, with viral shedding, may occur repeatedly for prolonged, but undetermined, periods.

Age Factors↗
PubMed1993

[Effectiveness of continuous retrograde cerebral perfusion for surgical treatment of aneurysms of the aortic arch--comparison with antegrade cerebral perfusion].

Several methods have been used for an adjunct to perform operation of aortic arch aneurysms. However, their results were often not so reasonable. Recently retrograde cerebral perfusion was reported as a new adjunctive method. In our institute, for the past 6 and a half years from May 1985 to April 1992, 50 patients underwent reconstruction of the transverse aortic arch by using two methods of artificial cerebral perfusion. One method is continuous antegrade cerebral perfusion (ACP, for 32 patients), and the other is continuous retrograde cerebral perfusion (RCP, for 18 patients), each technique was combined with deep hypothermia (18-20 degrees C) and low flow perfusion (10-30 ml/kg/min) to lower half body performed from femoral artery. In our RCP circuit, an additional pump was used for cerebral perfusion to superior vena cava, but the circuit was much simpler than the circuit in ACP. We compared the two methods (ACP versus RCP) as regards to the following items and the results were showed in parentheses; hospital death (8/32, 25%: 2/18, 11%), respiratory complication (8.27, 30%: 3/18, 17%), neurological complication (7/29, 24%: 1/18, 5.5%), duration of extracorporeal circulation (306.8 +/- 74.5 min: 260.4 +/- 60.0 min), periods of pre-ECC in the operation (160.3 +/- 69.2 min: 117.7 +/- 35.3 min), duration of cerebral perfusion (113.6 +/- 45.4 min: 74.1 30.5 min) and amount of bleeding (3424 +/- 2881 ml: 1802 +/- 1291 ml). RCP has superior advantages in all of those in comparison with ACP. These results suggest that RCP is a useful adjunctive method for reconstruction of aortic arch with a low operative risk.

Adult↗