Biomedical subjects

T Hirata

Publications and source records attributed to T Hirata.

At least 289 records · Page 16Linked to original sources

PubMed1993

PKC gamma gene expression is delayed in postnatal central nervous system of mi/mi mice.

In the central nervous system (CNS), the expression of protein kinase C (PKC) genes is strictly controlled by the developmental stage. We have examined the expression of PKC genes (cPKC alpha, beta, gamma, and nPKC delta, epsilon) in the process of the postnatal development in normal (+/+) C57BL/6 and microphthalmic (mi/mi) C57BL/6 mouse brains by Northern blotting and in situ hybridization. By Northern blotting, the expression level of cPKC gamma mRNA in mi/mi mice was significantly lower than that in +/+ littermates at d 9, 13, and 17. By in situ hybridization analysis, cPKC gamma mRNA-positive cells were detected in hippocampal and Purkinje cells in +/+ and mi/mi mice, but the magnitude of the signals in mi/mi mice was lower than that of +/+ mice, and the number of positive cells was smaller, whereas other isozymes (cPKC alpha, beta, and nPKC delta, epsilon) showed no significant difference between normal and mi/mi mice. The neuronal morphometric analysis by anti-P400 antibody revealed the same number and expression level of P400 protein in cerebellar Purkinje cells compared with +/+ mice. These results indicate that the deficiency of mi gene product causes the delayed expression of the cPKC gamma gene.

Animals↗

PubMed1993

The membrane protein A5, a putative neuronal recognition molecule, promotes neurite outgrowth.

The A5 is an unique membrane protein that is expressed in the neurons of the visual system and general somatic sensory system of Xenopus laevis. We cultured retinal explants or trigeminal ganglion neurons on the monolayers of A5-expressing line cells obtained by transfection with the cDNA, and found that the A5-expressing transfectants promote neurite outgrowth for these A5-expressing neurons. The neurite outgrowth-promoting effect was inhibited by anti-A5 antibodies. While, the neurite outgrowth-promotion by the A5 transfectants was not observed for the vestibulocochlear ganglion neurons which lack the A5. These results indicate that the membrane protein A5 is a potent substrate for neurite extension of the A5-expressing neurons but not for the A5-negative ones, suggesting its involvement in specific neuronal interaction.

Animals↗

PubMed1993

Effects of trehalose in preservation of canine lung for transplants.

The effect of trehalose, a non-reducing disaccharide which stabilizes and protects membranes, in the preservation of canine lungs was examined when Euro-Collins solution was basically used as a preservant. In group I, five lungs were perfused and preserved in an Euro-Collins solution modified by replacing the glucose with 35.0 g/L of trehalose. Five control lungs (group II) were perfused and preserved with Euro-Collins solution containing 35.0 g/L glucose. In both groups, no vasodilators were used. After preservation for 12 hours, left lung allotransplantation was performed. At 10, 40, 70, and 130 minutes after reperfusion, the right pulmonary artery was clamped for 10 minutes and four parameters were measured: arterial oxygen tension, mean pulmonary arterial pressure, peak inspiratory pressure, and wet/dry weight ratios. The transplanted lung was also examined histologically. At 10, 40, 70, and 130 minutes after reperfusion, oxygen-tension levels from group I were 263.2 +/- 19.2, 283.4 +/- 14.0, 277.5 +/- 19.9 and 264.9 +/- 26.2 mmHg, respectively. In group II, the corresponding values were 191.2 +/- 33.9, 188.0 +/- 40.3, 153.4 +/- 40.0 and 134.7 +/- 49.4 mmHg, respectively. At 70 and 130 minutes the difference were significant (p < 0.05). All transplanted lungs from group I showed normal histology, whereas four dogs in group II developed severe pulmonary edema and one had a partially edematous lung. These findings suggest that simple substitution of trehalose for glucose has a beneficial effect on preservation of canine lung for 12 hours.

Anesthesia↗

PubMed1993

Preparation of in-vivo rat lung model for ischemia-reperfusion injury.

An in-vivo rat lung model for ischemia-reperfusion injury was prepared. The left lung was collapsed after hilar stripping, and the left main pulmonary artery and bronchus were clamped. After the determined period of clamping the left main pulmonary artery and bronchus were declamped and the right main pulmonary artery was clamped. Arterial gas analyses were performed, 1, 10, and 20 minutes after reperfusion. The wet/dry lung eight ratio was calculated and lungs were histologically examined. Before clamping, PaO2 was 102-155 mmHg in all animals. The experimental animals were divided into 4 groups; Group I: temperature 19 degrees C, humidity 55% and duration of clamping 120 minutes (n = 2); Group II: 23 degrees C, 55% and 120 minutes (n = 4); Group III: 23 degrees C, 55% and 90 minutes (n = 5); Group IV: 23 degrees C, 65% and 75 minutes (n = 9). In Group IV, PaO2 decreased significantly in all 9 animals immediately after reperfusion, and at 1, 10, and 20 minutes it was 53.2 +/- 6.1 mmHg, 53.4 +/- 10.2 mmHg, and 67.0 +/- 10.2 mmHg, respectively. Pulmonary edema was observed histologically in 7 of the 9 animals. In-vivo rat lung models for ischemia-reperfusion injury are affected by the surrounding conditions. We established a stable model by setting ischemic time, temperature, and humidity at 75 minutes, 23 degrees C, and 65%, respectively.

Animals↗

PubMed1993

Reduced bone marrow toxicity of KW-2149, a mitomycin C derivative, in mice.

The bone marrow toxicity of KW-2149, a newly synthesized mitomycin C (MMC) derivative, was compared with MMC in different aged ddY mice. Both MMC and KW-2149 exhibited a similar type of leukopenia in young adult mice. However, in mature adult mice, the recovery from leukopenia was rapid in KW-2149-treated mice, whereas in the MMC-treated mice, it was delayed. The difference between KW-2149 and MMC was more significant in thrombocytopenia in mature mice, and that induced by KW-2149 was mild, whereas that by MMC was severe and delayed. This reduced bone marrow toxicity of KW-2149 in mature mice was confirmed by the assay of colony-forming units in culture, progenitors of granulocytes or macrophages, and megakaryocytic colony-forming units, progenitors of platelets, in the bone marrow cells. The bone marrow toxicity and lethal toxicity of MMC was augmented by weekly intermittent treatment; in contrast, that of KW-2149 was not, suggesting that bone marrow toxicity may have a critical role in the lethal toxicity of MMC. The non-cumulative bone marrow toxicity of KW-2149 enabled the weekly intermittent treatment of human lung adenocarcinoma L-27 inoculated into nude mice. Thus its antitumor activity was greater than with single treatment.

Adenocarcinoma↗

PubMed1993

Combination effect of navelbine (vinorelbine ditartrate) with cisplatin against murine P388 leukemia and human lung carcinoma xenografts in mice.

The in vivo combination effect of navelbine (NVB, KW-2307) plus cisplatin was compared with that of vindesine (VDS) plus cisplatin in terms of antitumor activity and side effects. The antitumor activity of NVB or cisplatin against i.p. inoculated P388 leukemia was augmented by their combination on various schedules when the interval of administrations was within 24 h. Against i.v. inoculated P388 leukemia, the most significant combination effect was observed when cisplatin was administered 4 h after NVB injection (ILS(%) > 451) and three long-term survivors were observed. On this schedule, the combination of LD10 of each drug was achieved, indicating the lack of addition of toxicity. This was further proved by examination of body weight change, white blood cell count and platelet count. Interestingly, significant elevation of blood urea nitrogen concentration by cisplatin was prevented by the combination with NVB. The combination of maximum tolerated dose of NVB and cisplatin was also tolerable in nude mice, and their combination effect was observed against human lung large cell carcinoma Lu-65 and adenocarcinoma PC-12. The number of toxic death mice was more in VDS plus cisplatin-treated groups than in NVB plus cisplatin-treated groups, indicating that the combination chemotherapy of NVB plus cisplatin is a better regimen than that of VDS plus cisplatin in experimental tumor systems.

Animals↗

PubMed1993

Electrophysiologic effects of a new class III antiarrhythmic agent, E-4031, on atrial flutter, atrial refractoriness, and conduction delay in a canine sterile pericarditis model.

Numerous studies have shown that E-4031 generally prolongs the atrial effective refractory period (AERP) without affecting cardiac conduction. The effects of E-4031 on AERP and cardiac conduction at short cycle lengths (CLs) close to the AERP were measured in 12 dogs with sterile pericarditis. Three pairs of electrodes were sutured at three sites in the atria 4 days after the model was created. We measured AERP and maximum conduction delay (MCD) after 8 beats train at CLs of 400, 300, 200 and 150 ms before and during continuous infusion of E-4031 (0.1 microgram/kg/min) that followed an initial dose of 10 micrograms/kg/min/5 min. E-4031 interrupted sustained atrial flutter (AF) (> or = 10 min) in 4 of 5 episodes and atrial fibrillation (> or = 10 min) in 4 of 4. The CL of AF defined as a rapid atrial rhythm (rate > or = 240 beats/min) in five episodes studied in the sterile pericarditis model was significantly (p < 0.005) prolonged from 120 +/- 8 to 160 +/- 17 ms. There were significant (p < 0.005) increases in AERP at each CL, and prolongation of AERP was 39 +/- 18, 31 +/- 14, 23 +/- 14, and 16 +/- 14 ms at CL 400, 300, 200, and 150 ms, respectively. E-4031 produced less prolongation of AERP at short pacing CLs and had no effect on conduction time during atrial rapid pacing at CLs > 150 ms. E-4031 did not prolong MCD at CL 400 ms, but did prolong MCD at CLs of 300, 200, and 150 ms, despite prolongation of AERP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Double-barrelled tubular duplication of the ileum.

A three year old boy with a 10 cm double-barrelled tubular duplication of the distal ileum is reported. He presented with a small bowel obstruction after a large meal of mandarin oranges. At laparotomy an obstruction of both lumens was found which communicated at both ends with the normal ileal lumen. Although cystic duplications of the small intestine are common, tubular duplications are relatively rare, especially an obstruction with impacted undigested foods.

Child, Preschool↗

PubMed1993

Relationship between atrial conduction defects and fractionated atrial endocardial electrograms in patients with sick sinus syndrome.

The relationship between abnormal atrial electrograms (AAE) recorded during sinus rhythm by endocardial catheter mapping of the right atrium and the atrial conduction defects of sinus impulses or single atrial extrastimuli was investigated in 44 patients with sick sinus syndrome. The patients were divided into two groups on the basis of the presence (n = 29) or absence (n = 15) of AAE recorded during sinus rhythm. The P wave duration in the AAE (+) Group patients was 137 +/- 14 msec, and 125 +/- 15 msec in the AAE (-) Group; P < 0.02. The intraatrial conduction time of sinus impulses in the AAE (+) Group was 54 +/- 12 msec, and 39 +/- 9 msec in the AAE (-) Group; P < 0.001. The interatrial conduction time in the AAE (+) Group was 101 +/- 14 msec, and 78 +/- 16 msec in the AAE (-) Group; P < 0.001. In the AAE (+) Group, 11 (38%) patients had a sinus node recovery time > 4 seconds, whereas in the AAE (-) Group there was only one (6%) patient; P < 0.03. AAE showed a specificity of 93% and a positive predictive accuracy of 91% in predicting inducibility of atrial fibrillation. The sensitivity was 35% and the negative predictive accuracy was 42%. Sustained atrial fibrillation was induced in ten (35%) patients of the AAE (+) Group, and in one (7%) patient of the AAE (-) Group; P < 0.05. These data suggest that in patients with sick sinus syndrome who possess abnormal endocardial electrograms in sinus rhythm within the right atrium have: (1) a significantly longer P wave duration; (2) a significantly longer intraatrial and interatrial conduction time of sinus impulses; and (3) a significantly greater sinus node dysfunction and higher incidence of induction of sustained atrial fibrillation. It is concluded that there are significantly greater atrial conduction defects in patients with sick sinus syndrome who possess AAE within the right atrium during sinus rhythm.

Adult↗

PubMed1993

Biological characterization of cyclothialidine, a new DNA gyrase inhibitor.

Cyclothialidine is a new DNA gyrase inhibitor isolated from Streptomyces filipinensis NR0484. Structurally, it belongs to a new class of natural products containing a unique 12-membered lactone ring that is partly integrated into a pentapeptide chain. Cyclothialidine was found to be one of the most active of all the DNA gyrase inhibitors tested in the DNA supercoiling reaction of Escherichia coli DNA gyrase; 50% inhibitory concentrations (in micrograms per milliliter) of 0.03 (cyclothialidine), 0.06 (novobiocin), 0.06 (coumermycin A1), 0.66 (norfloxacin), 0.88 (ciprofloxacin), and 26 (nalidixic acid) were found. In addition, DNA gyrases from gram-positive species were inhibited equally as well as DNA gyrase from E. coli. Cyclothialidine also inhibited the in vitro DNA replication directed from oriC of E. coli. Among the bacterial species tested, only Eubacterium spp. were inhibited by cyclothialidine, suggesting that it can enter the cells of Eubacterium and exert antibacterial activity through interference with the DNA gyrase within the cells, although its penetration into most bacterial cells appears to be poor. These results provide a basis for cyclothialidine to be a lead structure for novel antibacterial agents with DNA gyrase inhibitory activities.

Animals↗

PubMed1993

Trilineage response in severe aplastic anemia following long-term therapy with recombinant human granulocyte colony-stimulating factor.

We investigated the effects of long-term therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a 69-year-old man with severe aplastic anemia (SAA). The patient was too old to receive a bone marrow transplantation, and high-dose methylprednisolone and antilymphocyte globulin were ineffective. We administered rhG-CSF in combination with metenolone acetate. Trilineage blood cell components were recovered 6 months later. These findings suggest that long-term G-CSF therapy may be beneficial in patients with SAA who are not candidates for bone marrow transplantation.

Aged↗

PubMed1993

Recombinant human granulocyte colony-stimulating factor in combination with continuous infusion of cytosine arabinoside for the treatment of refractory acute myelogenous leukemia.

Because recombinant human granulocyte colony-stimulating factor (G-CSF) has been reported to increase the sensitivity of acute myelogenous leukemia (AML) blast cells to cytosine arabinoside (Ara-C) in vitro, we treated a patient with refractory AML with an Ara-C-based regimen in combination with G-CSF (G-CSF/Ara-C therapy). G-CSF (50 micrograms/m2/day, subcutaneous injection) was administered simultaneously with a continuous intravenous infusion of Ara-C (70 mg/m2/day). Complete remission was achieved, however, severe neutropenia, documented infection, stomatitis, and diarrhea were observed. In vitro studies using 3H-thymidine uptake and dual parameter flow-cytometric analysis of DNA and proliferating cell nuclear antigen showed that leukemic blast cells in S phase were increased after incubation with G-CSF. G-CSF also enhanced expression of the transferrin receptor (CD71) on blast cells in vitro. These observations suggest that G-CSF/Ara-C therapy may be useful in the treatment of high-risk AML.

Bone Marrow↗

PubMed1993

Stem cell factor induces outgrowth of c-kit-positive neurites and supports the survival of c-kit-positive neurons in dorsal root ganglia of mouse embryos.

The c-kit receptor tyrosine kinase is highly expressed by about 10% of the neurons in the dorsal root ganglia (DRGs) of mouse embryos. We investigated the in vitro effect of stem cell factor (SCF), the ligand for c-kit receptor, on DRGs. Recombinant murine SCF (rmSCF) induced the outgrowth of c-kit-positive neurites from DRGs of normal (+/+) embryos. The effect of SCF was dose dependent and completely abolished by anti-c-kit ACK2 monoclonal antibody (mAb). Some neurites whose outgrowth was induced by nerve growth factor (NGF) were c-kit-positive, but anti-NGF mAb did not inhibit the rmSCF-induced neurite outgrowth. rmSCF did not induce neurite outgrowth from DRGs of W/W embryos that did not express c-kit receptors on the cell surface and of W42/W42 mutant embryos that expressed c-kit receptors without tyrosine kinase activity. rmSCF also had a trophic effect on c-kit-positive neurons in the culture of dissociated DRG cells. Most c-kit-positive neurons appeared to respond to NGF as well, and the SCF-responsive subpopulation represented about 10% of NGF-responsive neurons. rmSCF did not support the survival of DRG neurons from embryos of W/W and W42/W42 genotypes. These results suggest that the stimulus through the c-kit receptor tyrosine kinase has an important role in development of the peripheral nervous system.

Animals↗

PubMed1993

Serum viral antibody titer in vestibular neuronitis.

Fifty-seven cases of vestibular neuronitis were evaluated for viral infection by means of serum antibody titer. The viruses tested were herpes simplex virus, varicella-zoster virus, cytomegalovirus, EB virus, adenovirus, influenza virus A, influenza virus B, parainfluenza virus 3, mumps virus, rubella virus and measles virus. Paired sera were examined in 49 cases among 57 cases, 26 cases showed significant change (four-fold or greater change) in viral antibody titer. Only one case (53-year old female) showed high HSV 1 IgM antibody level by ELISA method, so the vestibular neuronitis in this case was assumed to have a close relation to viral infection.

Adolescent↗

PubMed1993

Detection of HSV-I nucleic acids in rat vestibular ganglia.

Rats were infected with HSV-I through the middle ear. DNA and RNA were extracted from the vestibular ganglia, trigeminal ganglia, cerebrum, cerebellum and brainstem in the productive or latent state after inoculation. DNA and RNA were applied for polymerase chain reaction (PCR) to detect HSV-I genomes. In particular, in the RNA PCR, the latent-associated transcript (LAT) mRNA, which is said to be present in the cervical or trigeminal ganglia at much lower levels during the productive state, was detected. In the productive state, DNA was clearly detected in all samples whereas LAT was detected only in the trigeminal ganglion on the inoculated side, cerebrum and cerebellum. In the latent state, DNA was detected in the vestibular ganglion only on the inoculated side, bilateral trigeminal ganglia, cerebrum, cerebellum and brainstem; LAT was detected in the vestibular ganglion on the inoculated side, the bilateral trigeminal ganglia and brainstem. These data indicate that HSV-I can establish latent infection in the vestibular ganglia in a similar way as in the cervical or trigeminai ganglia.

Animals↗

PubMed1993

[Outpatient ESWL in 500 kidneys].

Between March 1989 and January 1992, 600 cases (636 kidneys) with upper urinary tract stones were treated with ESWL, using a Lithostar. Of these, 78.6% were carried out in our outpatient service, and in the last two years approximately 90% of cases have been treated as outpatient. We evaluated first 500 kidneys, treated with ESWL as outpatient. There were 481 cases involving 500 kidneys (19 bilateral cases). The ages of the 367 men and 114 women ranged from 16 to 77 years. There were 227 kidney stones and 273 ureter stones. Most of the stones were less than 20 mm. The average number of sessions and shock waves for each patient were 1.4 times and 6,988 waves, respectively. While 74% of the patients could be treated in only one session, 9% of them needed 3 sessions or more. Auxiliary measures were needed in 23 cases (D-J stent insertion in 5 cases and ureteral catheterization in 18 cases) and 474 cases (94.8%) were treated by in-situ procedures. At 3 months after treatment, 470 cases were evaluated and the stone-free rates of kidney stones and ureter stones were 70.3% and 84.5%, respectively with an overall stone-free rate of 78.1%. With regard to complications, the rate of the clinic visit because of pain after treatment was observed in 4.6% and higher than 38 degrees C in 2.5%. However, no serious perioperative complications occurred. From these results, outpatient ESWL was considered to be safe and efficient without serious complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Autoimmune thrombocytopenia following peripheral blood stem cell autografting.

A 22-year-old woman diagnosed as AML (M3) received myeloablative chemotherapy followed by autologous peripheral stem cell transplantation (PBSCT). Rapid hematopoietic reconstitution occurred. By day 10, the neutrophil count was > 0.5 x 10(9)/l and the platelet count > 50 x 10(9)/l. The platelet count was 145 x 10(9)/l on day 20. Purpura developed on the anterior chest and legs on day 50, at which time the platelet count fell to 17 x 10(9)/l. The BM was hypocellular with an increase in megakaryocytes. Platelet-associated IgG (PAIgG) was 88.1 ng/10(7) platelets (normal range 9-25 ng/10(7)); a diagnosis of idiopathic thrombocytopenic purpura (ITP) was made. Prednisolone administration led to an increase in the platelet count and a decrease in PAIgG. Analysis of lymphocyte subsets revealed an increased number of CD3+ gamma/delta T cells. It is postulated that the thrombocytopenia in this case was due to an autoimmune mechanism such as ITP.

Adult↗

PubMed1993

[Chemotherapy with high-dose carboplatin for inoperable non-small cell lung cancer].

The clinical efficacy and side effects of high-dose CBDCA therapy were studied in 35 cases of inoperable non-small cell lung cancer. A positive effect was obtained in about 30% of the subjects, all of who were squamous cell carcinoma patients. Incidence of clinical side effects was very low, thrombocytopenia being the major hematologic side effect. AUC, calculated from periodic measurements of free-Pt concentration in 19 subjects, was sensitive renal function, having a positive correlation with Cmax and a negative correlation with platelet nadir levels. This finding suggested the importance of establishing optimum dose levels with regard to pharmacokinetics. Patients in whom bone marrow suppression did not hamper continued therapy were treated as outpatients, many of whom retained sufficient QOL while undergoing outpatient therapy. Considering the present status of chemotherapy for NSCLC, characterized by the lack of long-term clinical efficacy and the presence of severe side effects, the present therapy is of great importance, since it can be continued with constant efficacy rates while maintaining good PS.

Adult↗