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Biomedical subjects

T Ishida

Publications and source records attributed to T Ishida.

At least 505 records · Page 28Linked to original sources

Three-dimensional structure of myeloid bodies in the retinal pigment epithelium of the frog, Rana pipiens.

The three-dimensional structures of myeloid bodies (MBs) in the retinal pigment epithelium (RPE) of the frog (Rana pipiens) were studied by transmission and scanning electron microscopy. MBs were observed to be an assemblies of numerous membranous lamellae that were formed by a flattened saccule of the paired membranes in the RPE. On thin-section, they appeared as lenticular, crescentic, circular and spherical forms and were associated with adjacent smooth endoplasmic reticulum (SER) and nuclear membranes. The lenticular MBs were observed to be in connection with the crescentic, circular and spherical forms. Under scanning electron microscopy, the lenticular and crescentic MBs showed a pile of disc-liked lamellae, while the circular and spherical MBs displayed an onion-liked appearance. It was noted that some tubular SER remained in the center of the circular MBs, while the lamellae were compactly arranged and filled the central region in the spherical MBs. All crescentic and spherical MBs were continuous with the lenticular and crescentic MBs. These results suggest that the lenticular MBs may be a precursor form of another variety of MBs which may be transformed into the crescentic, circular and spherical forms by the curving and fusion of the lamellar membranes at the MB's free ends.

Animals↗

Mitochondrial DNA mutation at nucleotide 1555 in a patient with bilateral sensorineural hearing loss of unknown etiology.

A mitochondrial DNA mutation at nucleotide 1555 in the ribosomal RNA gene was recently reported as a cause of maternally inherited non-syndromic sensorineural deafness. We assumed that the 1555 mutation is also associated with sporadic non-syndromic deafness and screened for the mutation in seven randomly selected sporadic cases with bilateral sensorineural hearing loss of unknown etiology. The mutation was found in one patient, who first noticed hearing loss when she was in her early teens with subsequent gradual progression. The results suggest that the 1555 mutation may contribute to the etiology of idiopathic bilateral sensorineural hearing loss in some cases.

Adult↗

Diffuse interstitial pulmonary amyloidosis in rheumatoid arthritis.

We describe a woman with seronegative rheumatoid arthritis (RA) who presented with diffuse septal pulmonary amyloidosis mimicking interstitial rheumatoid lung disease. Her systemic amyloidosis was diagnosed by biopsy of the kidney, stomach mucosa, and salivary glands 28 years after the onset of RA. Diffuse interstitial pulmonary infiltrates had been noted since that diagnosis, but infiltrates had been considered due to rheumatoid lung. Results of pulmonary function tests, which revealed restrictive changes and decreased diffusion capacity, were also compatible with rheumatoid lung disease. Pulmonary amyloidosis was diagnosed at autopsy. Pulmonary amyloidosis should be considered a cause of pulmonary infiltrates in patients with longstanding RA.

Amyloid↗

HLA serological and class II genotyping in sarcoidosis patients in Japan.

To investigate the HLA alleles that contribute to the genetic susceptibility to sarcoidosis, HLA serological typing was performed in 75 patients with sarcoidosis and 150 controls using the standard complement-dependent microcytotoxicity method. The genomic DNAs of the 75 patients and 130 of the 150 controls were used to analyze HLA-DRB1, -DQA1, -DQB1 and -DPB1 alleles, utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Serological typing showed that the frequencies of HLA-DR52, -DR5, -DR6 and -DR8 were significantly increased in the patients compared to the controls. In PCR-RFLP genotyping, the frequencies of the DR52-associated DRB1 alleles (DRB1*11, DRB1*14), DRB1*08, DQA1*0501 and DQB1*0301 were significantly increased in the patients compared to the controls. The frequencies of the DRB1*12 alleles were also increased among the patients, but this increase was not significant. The frequencies of DRB1*0101, DQB1*0501, and DPB*0402 were significantly lower in the patients than in the controls. The significant increases in the frequencies of DQA1*0501 and DQB1*0301 could be due to the linkage disequilibrium between the DR52-associated DRB1 alleles and DQA1*0501 and DQB1*0301 alleles among the Japanese. The significantly increased frequency of the DR8 (DRB1*08) haplotype, which lacks the DRB3 gene encoding DR52 antigen, suggested that the DR5 (DRB1*11), DR6 (DRB1*14) and DR8 (DRB1*08) of the DRB1 alleles may determine the susceptibility to sarcoidosis among the Japanese.

Adolescent↗

[Diffuse alveolar hemorrhage after allogeneic bone marrow transplantation].

A 44-year-old woman with malignant T-cell lymphoma and secondary leukemia received an allogeneic bone marrow transplant (BMT). She had received BMT conditioning treatment with total body irradiation and chemotherapy. Hemoptysis and progressive dyspnea developed 11 days after the transplant. A chest roentgenogram showed bilateral diffuse infiltrates. Bronchoalveolar lavage fluid was bloody, and diffuse alveolar hemorrhage (DAH) was diagnosed. Respiratory failure progressed despite mechanical ventilation and administration of corticosteroids. The patient died 58 days after the transplant DAH after BMT has been recognized in western countries as a syndrome with high mortality. We draw attention to the fact that DAH is a serious early pulmonary complication of BMT also in Japan.

Adult↗

[Prospective study of the etiology of community-acquired pneumonia among patients in a general hospital].

We prospectively studied the etiology of community-acquired pneumonia among all patients who were admitted to our hospital from July 1994 to June 1995. Tests for microbial pathogens including Chlamydia spp. and Legionella spp. were performed and diagnoses were made with strict criteria. A total 110 patients with 111 episodes of pneumonia were evaluated, and a pathogen was identified in 61 episodes (55%). The most common pathogen was Streptococcus pneumoniae (18%), followed by Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Mycoplasma pneumoniae, and Chlamydia spp. Infection with Legionella pneumophila was not found. Dual pathogens were identified in five episodes. Few prospective studies of the etiology of community-acquired pneumonia have been done in Japan. To prepare guidelines for the management of community-acquired pneumonia in Japan, a national study of the etiology of pneumonia is necessary.

Adult↗

[A new embolic material: super absorbent polymer (SAP) microsphere and its embolic effects].

SAP-Microsphere (sodium acrylic acid-vinyl alcohol copolymer) has the ability to absorb fluids within a few minutes and increase its diameter. Its diameter can also be calibrated. The diameters in ionic contrast material and human serum are 2.1 and 3.5 times larger, respectively, than the original size. It can pass through a microcatheter with an ionic contrast material, and swells at the occluding point into the desired size. It can be recognized under fluoroscopy due to its absorption of contrast material. A total of 10 rabbit kidney embolizations were done followed by resection in 1-14 weeks. Recanalization was absent in all cases. No adhesion to the perirenal tissue was found. Limited reactive change in endothelial cells was found at one week. No changes in the smooth muscle layer were found at any time during the study. Limited infiltration of neutrophil cells was found in perivascular tissue within a period of one week. SAP-Microspheres maintained their spherical shape during a 14-week period. Extensive fibrosis and calcification were found after 4 weeks. SAP-Microspheres are promising as an embolic agent to obtain satisfactory results of embolization therapy.

Absorption↗

Results of surgery for paralytic esotropia due to abducens palsy.

The surgical effects of three methods, transposition of the vertical rectus muscles, Jensen's procedure, and resection (advancement) of the lateral rectus muscle, were compared among 109 cases of paralytic esotropia due to abducens palsy. These procedures were combined with recession of the medial rectus muscle in about half the cases. Of the 109 cases, 22 were followed up for 4 years or longer. Results were similar, provided that the following protocols for surgery were adhered to: in cases of complete paralysis, transposition of the vertical rectus muscles was done, and in cases of incomplete paralysis, resection (advancement) of the lateral rectus muscle was performed. With both procedures, results were improved if recession of the medial rectus muscle was carried out at the same time.

Abducens Nerve↗

Long-term results of surgery for superior oblique palsy.

The results one month after surgery in 159 cases of superior oblique palsy were compared according to the method of surgery with the results 4 years or longer after surgery. There were 141 cases of congenital palsy and 18 cases of acquired palsy, for a total of 159 cases. Our study showed that surgery on the oblique muscle provided long-lasting effects, while recession of the superior rectus muscle or recession of the contralateral inferior rectus muscle could cause late overcorrection. When performing surgery on the rectus muscle, careful attention must be paid to suturing the muscle.

Humans↗

Antihypertensive effects of a new transdermal delivery system for clonidine in genetic and experimental hypertensive rats.

The antihypertensive effects of a new transdermal delivery system for clonidine (CAS 4205-90-7, clonidine tape, M-5041T) were investigated in spontaneously hypertensive rats (SHR), 2-kidney, 1-clip renal hypertensive rats (RHR) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. M-5041T (0.5-4.5 mg/kg) elicited a long-lasting hypotensive effect that was accompanied by bradycardia in a dose-dependent manner during 24-h patching on the backs of rats in all three hypertensive rat models. The hypotensive effect of M-5041T was more persistent than that of oral administration of clonidine (50 and 100 micrograms/kg) in both SHR and RHR. The most pronounced hypotensive effect of M-5041T was observed in DOCA-salt hypertensive rats. Plasma clonidine concentrations following transdermal application of M-5041T (1.5 mg/kg) were approximately 2-3 fold higher in DOCA-salt hypertensive rats compared with SHR. Electrical conductance of the skin surface, an index of the water content of the stratum corneum, was greater in DOCA-salt hypertensive rats than in SHR, suggesting that the delivery of clonidine may have been enhanced as a result of an increase in skin permeability due to the increase in water content of the stratum corneum in DOCA-salt hypertensive rats. Co-administration of M-5041T (0.5 mg/kg) with either trichloromethiazide (1 mg/kg, orally) or nifedipine (3 mg/kg, orally) at each sub-dose which affected both systolic blood pressure and heart rate produced significant hypotensive and bradycardic effects in SHR. Following repeated daily applications of M-5041T (1.5 mg/kg) for 7 consecutive days in SHR, significant hypotensive and bradycardic effects were produced at 6 h post-patching and then disappeared at 24 h post-patching in each trial. The plasma clonidine concentrations at 6 and 24 h post-patching were similar from the first to the seventh trial. No significant changes in blood pressure and heart rate were observed after termination of the regimen. These findings suggest that M-5041T could serve as an efficient and useful antihypertensive transdermal delivery system in humans without producing tolerance to the hypotensive effect and withdrawal syndrome after abrupt cessation of the treatment when used alone or with either a diuretic or a calcium channel blocker.

Administration, Cutaneous↗

HLA class II genotyping of sarcoidosis patients in Hokkaido by PCR-RFLP.

To confirm the significant association of sarcoidosis with HLA-DR5, -DR6, and -DR8 associated DRB1 alleles, in sarcoidosis patients from the eastern Japan (Kanto) area found in our previous study, we used HLA class II genotyping of patients in another region-Hokkaido, in northern Japan. The annual incidence of sarcoidosis in Hokkaido is about three times that of eastern Japan, and Hokkaido has one of the world's highest incidences of this disease. For the HLA class II (HLA-DRB1, -DRB3, -DQA1, -DQB1) genotyping, we used the polymerase chain reaction restriction fragment polymorphism (PCR-RFLP) method with 150 subjects: 40 sarcoidosis patients and 110 healthy controls. The frequencies of DRB1*12, DRB1*14, DRB1*08, DQA1*0501, and DQB1*0301 were significantly increased in the patients, compared with the controls. Our finding of a high frequency of DRB1*08 (which lacks the DRB3 gene encoding the DR52 antigen) in patients living in both eastern Japan and in Hokkaido, confirms that it is the HLA-DRB1 locus, rather than that of the HLA-DRB3, -DQA1, or -DQB1, which determines the susceptibility to sarcoidosis.

Adolescent↗

Prognostic value and clinicopathological correlation of thrombomodulin in squamous cell carcinoma of the human lung.

Aggregation of host platelets by circulating tumor cells is believed to play an important role in the metastatic process. Because thrombomodulin (TM) is one of the major mediators of the activation of the anticoagulant protein C by thrombin, we examined 136 primary tumor tissues and 45 metastatic lymph node tissues of lung squamous cell carcinomas for TM expression using immunohistochemical methods. The number of tumors with positive TM staining was less in metastatic tumors (44%) than in primary tumors (74%) (P < 0.01). Of various clinicopathological factors, better differentiation and lower N stage were significantly associated with TM expression. A loss of TM expression was associated with a shortened survival in 113 patients who underwent complete resection of the lung tumor (P < 0.01). In this group, TM expression and tumor-node-metastasis staging were independent significant determinants for survival, determined using Cox's multivariate survival analysis. Since TM is apparently associated with tumor progression and differentiation, this correlation may serve as a prognostic indicator in squamous cell carcinoma of the lung.

Aged↗

Phorbol ester and okadaic acid-resistant cells: the crossroads of signal transduction and drug resistance.

Many factors are involved in the development of drug resistance for anticancer drugs. The drugs should pharmacokinetically attain the appropriate concentration. They should be metabolized to the active forms. Tumor cells should have sensitivity to them. Several molecular and biochemical mechanisms that may explain cellular drug resistance have been identified. The contribution of protein phosphorylation and dephosphorylation for drug resistance is demonstrated in phorbol ester and okadaic-acid-resistant cells. The modulation of drug resistance by substances that affect the signal transduction pathway is an important issue in the development of an effective method for overcoming drug resistance.

Antineoplastic Agents↗

CD40 signaling-mediated induction of Bcl-XL, Cdk4, and Cdk6. Implication of their cooperation in selective B cell growth.

Signals sent through CD40 play crucial roles in B cell differentiation, including blocking apoptosis of germinal center B cells. In this study, using a murine B cell WEHI-231 line that undergoes apoptosis by the cross-linking of surface Ag receptors (sIgM), we have demonstrated that CD40 signalings are linked to induction of the Bcl-xL, Cdk4, and Cdk6 proteins whose expression was significantly suppressed by the apoptotic signal through sIgM. Mutational analyses of CD40 revealed that the domain of human CD40 required for blocking apoptosis of WEHI-231 cells coincides with that required for Bcl-xL induction. Signals through sIgM arrest cells in the G1 phase of the cell cycle, which is followed by apoptosis. However, while constitutive expression of Bcl-XL leads to the inhibition of apoptosis. Nevertheless, Bcl-xL fails to induce S phase entry. By CD40 signalings, both Cdk4 and Cdk6 resume their normal expression levels, which are sufficient for passing the restriction point in G1 even in the presence of the apoptotic signals mediated by sIgM. These results suggest that cooperation of Bcl-xL, Cdk4, and Cdk6 induced by CD40 signaling plays a key role in CD40-mediated selective growth of B cells.

Amino Acid Sequence↗

Enhanced interaction between tubulin and microtubule-associated protein 2 via inhibition of MAP kinase and CDC2 kinase by paclitaxel.

Paclitaxel, an anti-mitotic anti-cancer agent, is active against solid tumors. The inhibition of depolymerization and promotion of microtubular assembly are essential for the anti-tumor activity of paclitaxel. Microtubule-associated proteins (MAPs) co-polymerize with tubulin and play some roles in microtubular dynamics. We examined the effect of paclitaxel on the interaction between tubulin and MAPs. Human lung-cancer cells, PC-14, were synchronized to G1/S border by the thymidine-double-block technique. After release from exposure to thymidine, the cells were treated briefly with 2 nM paclitaxel and the levels of alpha and beta tubulins and MAPs were examined after various times. Immunoblot analysis of paclitaxel-treated cells showed no changes in the overall expression of alpha and beta tubulins, microtubule-associated protein 2 (MAP2) or MAPs in comparison with controls. The samples were immunoprecipitated with anti-alpha- and anti-beta-tubulin antibodies and reblotted with an anti-MAP2 antibody, which showed that the amount of co-immuno-precipitated MAP2 in the synchronized cells, were increased by the brief paclitaxel treatment. These results suggest that paclitaxel treatment enhances the interaction between alpha and beta tubulins and MAP2. Since the phosphorylation state of MAP2 regulates the affinity of MAP2 for tubulins, and mitogen-activated protein (MAP) kinase is considered to be one of the kinases responsible for MAP2 phosphorylation, the effect of paclitaxel treatment on the MAP-kinase activity of synchronized PC-14 cells was examined. Two bands with molecular masses of 42 and 44 kDa were detected by an "intra-gel" MAP-kinase assay using myelin basic protein as the substrate. Paclitaxel treatment inhibited the MAP-kinase activity of PC-14 cells and inhibition was maximal at the G2/M phase of the cell cycle. Similar, concentration-dependent inhibition by paclitaxel of cellular MAP kinase of human synchronized small-cell lung carcinoma, H69, was observed. No inhibition of the MAP kinase of the paclitaxel-resistant sub-line H69/Txl by paclitaxel was observed, suggesting that some change of the MAP-kinase cascade had occurred in these cells. No direct inhibition of MAP-kinase activity by paclitaxel was observed in the cell-free assay (in vitro), suggesting that paclitaxel did not inhibit MAP kinase directly. Since it has been speculated that p34cdc2 kinase is also a kinase that phosphorylates MAP2, the effect of paclitaxel treatment on the p34cdc2-kinase activity of synchronized PC-14 and PC-9 cells was examined. Paclitaxel inhibited p34cdc2-kinase activation at the G2/M phase. These results suggest that paclitaxel inhibited MAP kinase and p34cdc2 kinase in vivo indirectly. These actions of paclitaxel may be responsible for the increased affinity between MAP2 and tubulins that it induces.

Amino Acid Sequence↗

Gamma-glutamylcysteine synthetase gene overexpression results in increased activity of the ATP-dependent glutathione S-conjugate export pump and cisplatin resistance.

The ATP-dependent glutathione S-conjugate export pump (GS-X pump) has been suggested to play a role in the mechanism of cisplatin resistance. The purpose of this study was to determine the relationship between intracellular glutathione (GSH) levels and GS-X pump activity and whether GS-X pump overexpression results in cisplatin resistance. We transfected the human gamma-glutamylcysteine synthetase (gamma-GCS) gene into a human small-cell lung cancer cell line, SBC-3, producing SBC-3/GCS. The intracellular GSH content of SBC-3/GCS was twice that of the parental line, its GS-X pump activity was significantly enhanced and cellular cisplatin accumulation decreased. SBC-3/GCS showed higher resistance (relative resistance value of 7.4) to cisplatin than the parental line SBC-3. These data indicate that gamma-GCS gene overexpression induces cellular cisplatin resistance associated with increases in both the GSH content and GS-X pump activity, resulting in reduced cisplatin accumulation. In conclusion, GS-X pump expression is related to cellular GSH metabolism and involved in cisplatin resistance.

Adenosine Triphosphate↗

Unique binding of a novel synthetic inhibitor, N-[3-[4-[4-(amidinophenoxy)carbonyl]phenyl]-2-methyl-2-propenoyl]- N-allylglycine methanesulfonate, to bovine trypsin, revealed by the crystal structure of the complex.

Trypsin and N-[3-[4-[4-(amidinophenoxy)carbonyl]phenyl]-2-methyl-2-propenoyl]- N-allylglycine methanesulfonate (1), a newly designed and orally active synthetic trypsin inhibitor, were cocrystallized. The space group of the crystal is P2(1)2(1)2(1) with cell constants a = 63.74 A, b = 63.08 A, and c = 69.38 A, which is nearly identical to that of the orthorhombic crystal of guanidinobenzoyltrypsin. The structure was refined to a crystallographic residual R = 0.176. The refined model of the 1-trypsin complex provides the structural basis for the reaction mechanism of 1. On the basis of the present X-ray results, it is proposed that the potent inhibitory activity of 1 is mainly due to the formation of an acylated trypsin through an "inverse substrate mechanism" and its low rate of deacylation.

Allylglycine↗