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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 703 records · Page 39Linked to original sources

Can concordant criss-cross heart be ameliorated by hemodynamic changes?

A 2-year-old female child with "ameliorated" concordant criss-cross heart, complicated superior-inferior ventricles, complete transposition of great arteries, hypoplastic right ventricle, ventricular septal defect, and aortic coarctation is described. The patient underwent subclavian flap, pulmonary artery banding, and balloon atrioseptostomy at age 1 month. The ameliorated concordant criss-cross anatomy was obtained after 2 years of follow-up. This dynamic morphologic change allowed us to perform a subsequent anatomic correction.

Aortic Coarctation↗

Nicotine stimulates pepsinogen secretion from guinea pig gastric chief cells in monolayer culture.

We evaluated the effects of nicotine on pepsinogen secretion in vitro, using a monolayer culture system of guinea pig gastric chief cells. Pepsinogen secretion was increased by above 5 mM nicotine in a dose-dependent manner, as was the elevation of intracellular free calcium concentration ([Ca2+]i). The pepsinogen secretion stimulated by 10 mM nicotine was inhibited by above 1 mM d-tubocurarine, a nicotinic receptor antagonist, but not by same concentrations of scopolamine hydrobromide monohydrate or pirenzepine, a muscarinic receptor antagonist. The elevation of [Ca2+]i induced by 5 mM nicotine was also reduced by 10 mM d-tubocurarine, but not by 10 mM pirenzepine. A calmodulin inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), at the concentration of 10(-6) M and a myosin light-chain kinase inhibitor, 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), at concentrations above 10(-7) M also significantly blocked 10 mM nicotine-induced pepsinogen secretion. These finding indicate that nicotine directly stimulates pepsinogen secretion probably via nicotinic receptors on the gastric chief cells, and that the Ca(2+)-mediated messenger system, including calmodulin and myosin light-chain kinase, is involved in this event.

Animals↗

Low molecular weight immunomodulators produced by microorganisms.

In order to develop a new class of low molecular weight immunomodulators for the treatment of incurable diseases involving cancer, hematologic diseases and inflammation, we have sought cytokine inducers and inhibitors of cell adhesion to the extracellular matrix among the low molecular compounds produced by microorganisms. Cytogenin, cytoblastin (a monokine inducer), conagenin (a lymphokine inducer) and delaminomycins and IC-101 (inhibitors of cell adhesion to extracellular matrices) have been recently found in our institute. In this report, we describe the principles of screening and structures, and discuss their biological activities.

Actinobacteria↗

Production of bioactive enkephalin from the nonendocrine cell lines COS-7, NIH3T3, Ltk-, and C2C12.

Enkephalin is synthesized from proenkephalin in neuroendocrine cells. For the attempt to induce nonneuroendocrine origin cells to produce enkephalin, we used a mammalian expression vector for fusion peptides, pMEproCT beta, in which a fused peptide is designed to be cleaved by a yeast Kex2-like endoprotease furin. Met-Enkephalin was expressed in four nonneuroendocrine cell lines: COS-7, C2C12, Ltk-, and NIH3T3. The four cell lines produced a marked amount of Met-enkephalin, which appeared as a single peak on reverse-phase HPLC. Because transplantation of adrenal medullary cells to the subarachnoid space has been used to alleviate terminal cancer pain, and enkephalin appears to play a central role in relieving pain, this enkephalin expression vector may be useful for direct enkephalin expression in pericancerous tissues.

3T3 Cells↗

Patellofemoral contact pressures exceed the compressive yield strength of UHMWPE in total knee arthroplasties.

To address mechanisms involved in wear and permanent deformation of patellofemoral components in total knee arthroplasties, a previously reported knee joint loading model and pressure-sensitive film were used to measure patellofemoral contact areas and pressures in human cadaver knee joints after implantation with six different total knee joint designs. The joints were tested at three different Q angles (physiologic, -10 degrees, and +10 degrees) and four different flexion angles (30 degrees, 60 degrees, 90 degrees, and 120 degrees). Patellofemoral contact areas at normal Q angles ranged from 0.13 to 0.68 cm2 and increased with flexion angle up to 90 degrees. These contact areas differed significantly with flexion angle but not with Q angle. Variations in contact area with type of knee system were only marginally significant (P < .04), and post hoc tests showed no significant differences between individual knee designs. Contact pressures at normal Q angle also increased with flexion angle and ranged from 10 MPa to more than 49 MPa. Contact pressures at flexion angles greater than 60 degrees were, for all systems, well in excess of the compressive yield strength of ultrahigh-molecular-weight polyethylene and at least three to four times greater than the recommended maximum compressive stress level of 10 MPa.

Adult↗

Antitumoral efficacy and pharmacokinetic properties of pirarubicin upon hepatic intra-arterial injection in the rabbit V x 2 tumour model.

To improve the efficiency of hepatic intra-arterial (h.i.a.) chemotherapy, we selected pirarubicin (THP) because it shows good properties for h.i.a. chemotherapy, such as fast and efficient cellular uptake, and used it for h.i.a. chemotherapy in rabbits with V x 2 tumour implanted in the liver. The anti-tumour effect of THP upon h.i.a. administration was compared with that upon intravenous (i.v.) injection and also with the anti-tumour activity of epirubicin (EPI) upon h.i.a. injection using optimal and maximal tolerated doses of each drug. When tumour growth rates and morphometric examinations were evaluated, it was found that THP and EPI were effective against V x 2 tumour when injected via the h.i.a. route. The activity of THP was stronger than that of EPI. As regards h.i.a. injection-related complication, plasma transaminase levels were temporarily elevated. To demonstrate higher anti-tumour activity and other advantages of h.i.a. injection of THP, plasma and tumour drug concentrations were determined by high-performance liquid chromatography after THP or EPI was administered at an equal dose to the rabbit V x 2 model. Hepatic intra-arterial injection of THP accomplished a selective and higher uptake into the tumour and lower effusion into the plasma than i.v. injection of THP or h.i.a. injection of EPL. Our findings indicate that THP is the better candidate of the two drugs tested for the h.i.a. chemotherapy because of its greater anti-tumour activity and the lower systemic drug exposure achieved upon h.i.a. injection.

Animals↗

[Interferon-associated retinopathy].

BACKGROUND: Recently interferons have been utilized for hepatitis C or some other tumorous conditions. However, a new interferon-associated retinopathy has been reported. There are to our knowledge, no publications in German-speaking countries. PATIENTS: Four patients developed after interferon therapy cotton-wool spots combined with splinter hemorrhage. RESULTS: The retinopathy occurred 5-30 days after the beginning of the therapy. In one case the retinopathy aggravated following dose elevation, whereas in two other cases the cotton-wool spots and hemorrhages disappeared irrespective of continued interferon therapy. CONCLUSIONS: Interferons cannot be primarily responsible for the development of retinopathy.

Aged↗

Characterization of a 50 kDa surface membrane protein on thymic stromal cells as an important factor for early T cell development.

We previously reported that the nude mouse-derived splenic T cell clone, N-9F, exhibits a proliferative response to the SL10.3 thymic epithelial cell clone. In the present study we generated an Armenian hamster mAb, HS9, specific for SL10.3, which inhibited the N-9F's proliferative response to SL10.3. We performed thymocyte repopulation experiments using fetal liver cells and 2'-deoxyguanosine-treated thymic rudiments. After 14 days of culture, donor fetal liver cells proliferated and differentiated to CD4+CD8+ and CD4-CD8+ with some CD4+CD8- cells in the host thymic rudiments. However, most of the thymocytes remained at a CD4-CD8- immature stage in the presence of HS9 and the cell recovery was reduced to 30% of the control. Immunohistostaining and flow cytometry studies revealed that HS9 reacted with stromal cells of fetal thymus at the earliest from day 14 gestation. Neither thymocytes nor lymph node T cells were stained with HS9. HS9 antigen was distributed not only on thymic subcapsular and cortical stromal cells, but also on peripheral B cells in adult mice. The antigen that HS9 detected was found to be a 50 kDa surface membrane protein on thymic stromal cells. On the other hand, the 50 kDa molecule is associated with two other molecules of 80 and 100 kDa on the B cells. These data indicate that the HS9 antigen may have an important role for early T cell development, especially at a stage from CD4-CD8- to CD4+CD8+, and may have some unknown function on B cells.

Animals↗

Effect of a novel cholecystokinin receptor antagonist, FK480, administered intraduodenally, on pancreatic secretion in rats.

The effect of a new cholecystokinin (CCK)-A receptor antagonist, FK480, developed in Japan, on pancreatic exocrine secretion stimulated by exogenous CCK and intraduodenal casein was investigated in vivo when administered to anesthetized rats intraduodenally, and its CCK antagonistic activity was compared with that of CR 1505. Intraduodenal administration of FK480 at graded doses of 0.0016-1.0 mg/kg-h produced dose-dependent inhibition of pancreatic juice volume and amylase output stimulated by intravenous infusion of CCK-8 at a dose of 0.06 micrograms/kg-h. The half-maximal inhibitory dose (ID50) of FK480 for CCK-8-stimulated amylase secretion was 0.025 mg/kg-h, whereas the ID50 of CR 1505 was 5.2 mg/kg-h, indicating that FK480 is 208 times more potent than CR 1505. Moreover, intraduodenal FK480 (0.2 mg/kg-h) significantly suppressed pancreatic juice volume and amylase output augmented by intraduodenal infusion of casein (400 mg/h). It is concluded that FK480 administered intraduodenally has a significant, potent inhibitory action on the exocrine pancreas stimulated by exogenous CCK and intraduodenal casein.

Amylases↗

Measurement of IL-4 in tears of patients with seasonal allergic conjunctivitis and vernal keratoconjunctivitis.

To elucidate the mechanism of ocular surface allergic disease, we focused on IL-4, which is one of the key factors in regulating IgE production, and thus determined the concentration of IL-4 in tears. IL-4 concentration was determined in the tears of 15 patients with seasonal allergic conjunctivitis, 15 vernal keratoconjunctivitis (VKC), 10 giant papillary conjunctivitis (GPC), 10 patients with non-allergic conjunctivitis and post-cataract surgical conjunctivitis as intermediate conjunctivitis, and 10 normal subjects using a highly sensitive sandwich ELISA. The mean level of IL-4 in normal controls was low, and seasonal allergic conjunctivitis, VKC and GPC showed a significant elevation (P < 0.05), respectively. IL-4 of VKC and GPC were also significantly higher than allergic conjunctivitis, and non-allergic conjunctivitis and post-cataract surgical conjunctivitis were not higher than normal. These results raise the possibility that the increased level of IL-4 in tears could play a role in allergic disease and its severity in patients.

Adolescent↗

Perinatal medical support in the area surrounding the Hanshin-Awaji earthquake.

After natural disaster, perinatal medical care must usually be provided from outside the disaster area, because most of the medical efforts inside the area focus on patients without special needs. This study reviews the emergency perinatal medical response after the great Hanshin-Awaji earthquake. In the present study, we summarize records of telephone calls and reports from the Neonatal Mutual Cooperative System (NMCS). The day of the earthquake, very little information was available to or from the disaster area. The day after the earthquake, Osaka City General Hospital (OCGH) and Osaka Medical Center and Research Institute for Maternal and Child Health were established as key facilities, and OCGH served as a center through which information passed to and from the disaster area. Most telephone calls to OCGH were placed on the second day after the earthquake by pregnant women concerned about their deliveries. Many high-risk pregnancies and newborn infants were transferred out of the disaster area over the next month. This analysis shows that although the emergency response was very rapid in this instance, the operation may be significantly improved in disasters of this magnitude: (i) if a communication mechanism able to serve a large volume is established; (ii) if helicopter transport was easily available; and (iii) if key facilities to handle communications were previously established so as to be available immediately.

Child Health Services↗

[A case of myelodysplastic syndrome who died of septic pulmonary embolism].

A case of myelodysplastic syndrome (MDS) complicated by septic pulmonary embolism is reported. A 61-year-old female who had been followed for refractory anemia with excess of blasts suddenly died of acute respiratory failure. An autopsy revealed massive pulmonary emboli with gram-positive cocci gathered in the emboli and alveolar spaces. Staphylococcus aureus was also detected through a blood culture from the right atrium. We speculate that pulmonary embolism was the result of septicemia induced by the immunosuppressive condition associated with MDS.

Fatal Outcome↗

Successful treatment of Pneumocystis carinii Pneumonia in mice with benanomicin A (ME1451).

Benanomicin A (BNM-A) has antimycotic activities via binding to mannan in the cell walls of fungi. Anti-Pneumocystis carinii activity of the agent was examined in the P. carinii-infected BALB/c nu/nu female mouse model because P. carinii also possesses mannan in the membranes. The infected mice were treated with intraperitoneal injections of six doses of BNM-A (1, 2.5, 5, 10, 30, and 100 mg/kg of body weight), 4 mg of pentamidine isethionate per kg, 100 mg of sulfamethoxazole per kg combined with 20 mg of trimethoprim per kg (co-trimoxazole), or saline for 21 days. Each dosage group consisted of 10 mice. During treatment, five mice in the control group (saline) died, whereas 8 to 10 mice in all treatment groups survived. Almost the same efficacies were obtained for the groups treated with 5 mg or more and 10 mg or more of BNM-A per kg regarding the weight and number, respectively, of cysts found in the lungs as were obtained for the groups treated with pentamidine isethionate and co-trimoxazole. Overall, a dose of 10 mg of BNM-A per kg was effective against P. carinii pneumonia infection in the mice. Thus, BNM-A is a good candidate for a novel treatment for P. carinii pneumonia as a compound with a new mechanism of action against P. carinii.

Animals↗

Evaluation of influential factors of cognitive impairments in idiopathic Parkinson's disease.

Using multivariate analysis, we investigated the influence on cognitive functions of aging, brain atrophy, incidental cerebral hyperintensities (CHs), medication, and severity, duration and the initial symptoms of the disease in 53 patients with idiopathic Parkinson's disease (PD). We semiquantitatively assessed the degree of brain atrophy and CHs based on previously established methods. Cognitive functions were significantly and diffusely impaired in PD when compared with controls who were matched for age as well as for the degree and location of CHs. Patients with PD, however, had larger ventricles. Prefrontal dysfunctions were associated with a variety of predictors such as CHs, brain atrophy, severity of PD and medication whereas dorsolateral frontal functions were related simply to age and CHs in the periventricular region. Posterior brain functions had association with severity of illness, ventricular dilatation and total CH score. Clinically observed cognitive impairments in PD may consist of cognitive defects intrinsic to the disease which are variously modified by these factors. It is essential to consider all these predictors simultaneously in any discussion of cognitive functions in PD.

Aged↗

Assignment of CD38, the gene encoding human leukocyte antigen CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase), to chromosome 4p15.

CD38 has been used as a phenotype marker of lymphocyte differentiation. Recently, we have demonstrated that cyclic ADP-ribose can be synthesized and hydrolyzed by CD38 and acts as a second messenger in insulin secretion from pancreatic beta-cells. We have mapped the CD38 gene to human chromosome 4p15 by fluorescence in situ hybridization.

ADP-ribosyl Cyclase↗

A highly suspected case of chronic Chagas' heart disease diagnosed in Japan.

A 50-year-old South American Indian woman, a native of Brazil and now a resident of Shiga Prefecture, was admitted to our hospital because of dyspnea on exertion. We initially suspected dilated cardiomyopathy due to an enlarged and diffusely hypokinetic left ventricle (LV) on echocardiogram. Coronary arteriograms were normal, and histological examination of right ventricular endomyocardial biopsy specimens showed findings compatible with chronic myocarditis. Magnetic resonance imaging revealed localized thinning and a small apical aneurysm at the LV. Since she had previously lived in a high-risk region for Chagas' disease, two immunological examinations for Trypanosoma cruzi were performed. The results of both tests were compatible with the disease. Recently, an increasing number of patients with Chagas' disease have been found in the United States among immigrants from South American countries, and the risk of transmission of the disease through contaminated blood transfusion is becoming a national problem. We report this case with reference to the present state of the problem in the United States and the potential problems it presents in Japan because of the marked increase in the number of immigrants from the affected area.

Animals↗

Purification and characterization of extracellular alginate lyase from Enterobacter cloacae M-1.

An alginate lyase from the culture supernatant of Enterobacter cloacae M-1 was purified by ammonium sulfate precipitation, cation-exchange chromatography (SP-Toyopearl), and gel filtration (Ultrogel AcA44). The final preparation thus obtained showed a single band on SDS-PAGE. The purified enzyme had the molecular weight of 38,000 and 32,000 by SDS-PAGE and gel filtration, respectively. The pI of the enzyme was 8.9. The optimum pH and temperature for the enzyme reaction were around 7.8 and 30 degrees C, respectively. The enzyme was unstable on heating. EDTA completely inhibited the enzyme activity, but the activity was completely restored by the treatment with CaCl2. The enzyme was specific for poly-guluronate and produced several kinds of unsaturated oligomers from the gluluronate. This suggested that the enzyme could be classified as an endo poly-guluronate lyase.

Amino Acid Sequence↗