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Biomedical subjects

M Terada

Publications and source records attributed to M Terada.

At least 73 records · Page 4Linked to original sources

Autologous tissue-fragmented extracardiac conduit with rapid, stable endothelialization due to angiogenesis.

OBJECTIVES: Autologous angiogenic cytokines are known to activated by mincing stimulation, and well regulated in vivo. We applied this tissue fragmentation technique to a low-pressure pulmonary extracardiac conduit to obtain rapid endothelialization and stable neointima formation due to angiogenesis. METHODS: Subcutaneous adipose tissue was obtained, minced, suspended, and sieved through highly porous fabric vascular prosthesis by pressurized injection. The adipose tissue fragmented graft with an autologous fresh pericardial monocusp valve was implanted between the right ventricle and the pulmonary artery in 13 dogs. The same grafts without fragments were implanted in 8 dogs as controls. No anticoagulation therapy was given. RESULTS: Grafts were removed 6 to 1,128 days after implantation. In the developed grafts, angiogenesis occurred throughout the interstices of the graft wall from the adventitial side, and host cells proliferated and migrated. Endothelialization was completed throughout developed grafts at 2 weeks. The intima was still thin up to 1,128 days and free of degenerative changes. In control grafts, however, capillary infiltration was limited to perigraft tissue at 2 weeks and endothelialization was not completed by 3 months. Under the endothelial cell layer, laminal elastic fibers were formed through the developed graft wall by 4 months and still maintained at 1,128 days. CONCLUSIONS: The results demonstrated that adipose tissue fragmented extracardiac conduits induce rapid endothelialization and maintained thin intima with laminal elastic fibers. Long-term durability is expected based on results from using this technique in a low-pressure pulmonary system in dogs.

Adipose Tissue↗

Definite improvement in left ventricular function at six years after the Takeuchi procedure.

We report a case of a six-year-old girl who underwent the Takeuchi procedure for anomalous origin of the left coronary artery from the pulmonary artery at the age of 4 months. The left ventricular function was severely deteriorated before the initial operation and at 6 years after the procedure showed a remarkable improvement. Mitral regurgitation disappeared during the 6 years. The intrapulmonary tunnel was sufficiently patent to provide adequate blood flow for the anomalous coronary artery. This patient showed supravalvular stenosis due to shrinkage and thickening in the equine pericardium used for reconstruction of the pulmonary artery, and this stenosis was successfully released by autologous pericardial patch angioplasty.

Cardiac Surgical Procedures↗

Anatomic biventricular correction by taking down bicaval Glenn shunt.

A 7-year-old boy underwent ventricular and atrial septal defect patch closures, pulmonary valvulotomy, left pulmonary artery dilatation, and bicaval Glenn shunt, which maintained good patency between the superior vena cava and right atrium, because of a reduced right ventricular end-diastolic volume (RVEDV). The RVEDV had increased at 15 years of age; therefore, we performed an anatomic biventricular correction by removing the bicaval Glenn shunt. We found that anatomic biventricular correction becomes possible if RVEDV increases postoperatively.

Adolescent↗

Effect of hemofiltrated whole blood pump priming on hemodynamics and respiratory function after the arterial switch operation in neonates.

BACKGROUND: Primed blood might have some deleterious effects on neonates during cardiopulmonary bypass (CPB) due to unbalanced electrolytes and inflammatory mediators. We hemofiltrated pump-primed blood before CPB to reduce inflammatory mediators and to adjust pH and the concentrations of electrolytes. The current study investigated the effects of hemofiltrated whole blood priming on hemodynamics and respiratory function after CPB in neonates. METHODS: Patients who underwent the arterial switch operation in the neonatal period for transposition of the great arteries with intact ventricular septum were chosen for this study. Seventeen patients underwent CPB with hemofiltrated blood priming (group HF) and 23 patients underwent CPB with nonhemofiltrated blood priming (group N). The concentrations of electrolytes and bradykinin and high molecular weight kininogen of the primed blood before and after hemofiltration were measured. At 4 hours after completion of CPB, the left ventricular percent fractional shortening, and the relation between the mean velocity of shortening and the end-systolic wall stress (stress velocity index), were measured by echocardiogram in 7 patients in group HF and 6 patients in group N. Alveolar--arterial oxygen tension difference (AaDO2) and respiratory index (AaDO2 divided by arterial oxygen tension) were measured at several points for 48 hours after CPB in all patients. RESULTS: Hemofiltration of the primed blood maintained electrolytes within a physiologic level and significantly reduced the concentrations of bradykinin (5,649 +/- 1,353 pg/mL versus 510 +/- 35 pg/mL, p < 0.05) and high molecular weight kininogen (52.7% +/- 3.2% versus 40.1% +/- 3.0% of normal plasma value, p < 0.05). The percent of fractional shortening at 4 hours after completion of CPB was significantly higher in group HF (n = 7) than in group N (n = 6) (22.0% +/- 0.7% versus 16.0% +/- 0.4%, p < 0.01). There was also a trend toward better stress velocity index in group HF than in group N (0.81 +/- 0.81 versus -2.17 +/- 0.45, p = 0.09). AaDO2 and respiratory index were significantly lower in group HF than in group N for 48 hours after CPB, respectively (p < 0.05). CONCLUSIONS: Hemofiltrated fresh whole blood used for CPB priming attenuated cardiac impairment at early reperfusion periods and reduced pulmonary dysfunction in neonates with transposition of the great arteries with intact ventricular septum. This therapeutic strategy may have an advantage in preventing lung and heart dysfunction in pediatric patients who need CPB priming with blood.

Cardiopulmonary Bypass↗

Fatty liver and hyperlipidemia in IDDM (insulin-dependent diabetes mellitus) of streptozotocin-treated shrews.

Severe IDDM (insulin-dependent diabetes mellitus) was produced in the musk shrew (Suncus murimus, Insectivora) by a high dose (a single intraperitoneal injection of 100 mg/kg Body Weight) of streptozotocin (STZ) injection. All shrews that were administered a high dose of STZ exhibited hyperglycemia (449 +/- 16 mg/dl vs 73 +/- 4 mg/dl in controls) and hypoinsulinemia(0.25 +/- 0.07 ng/ml vs 10.96 +/- 1.97 ng/ml in controls) with ketosuria 10 days after injection. Their livers were enlarged and exhibited ayellowish-brown color with marked triglyceride (TG) accumulation (63.25 +/- 7.10 mg/g Liver vs 2.11 +/- 0.19 mg/g Liver in controls). It is probable that the increased influx of fatty acids into the liver induced by hypoinsulinemia and the low capacity of excretion of lipoprotein secretion from liver in the musk shrew resulting from a deficiency of apolipoprotein B synthesis play important roles in fatty liver formation. Hyperlipidemia was another feature in shrews with severe IDDM. The blood TG level was especially high in these shrews (899 +/- 178 mg/dl vs 23 +/- 5 mg/dl in controls). These results indicate that the IDDM shrew, induced by high doses of STZ, is a unique model characterized by fatty liver and hyperlipidemia and may be useful for studying lipid metabolism of IDDM.

Animals↗

Antiviral activity of NMSO3 against respiratory syncytial virus infection in vitro and in vivo.

NMSO3, a sulfated sialyl lipid was evaluated for its efficacy against respiratory syncytial virus (RSV) and other myxovirus infections in cell culture. The median effective concentration (50% effective concentration, EC(50)) of NMSO3 against replication of the Long strain of RSV in HEp-2 cells was 0.2 and 0.32 microM by optical ELISA and the plaque reduction method, respectively. On the other hand, the corresponding values for ribavirin were 10.5 and 11.2 microM, respectively. NMSO3 showed potent activity against other laboratory strains as well as fresh clinical isolates of RSV, and the average EC(50) was similar to that for Long strain. NMSO3 exhibited minimal cytotoxicity against HEp-2, MDCK, HMV-2 and Vero cells for which the median cytotoxic concentration (CC(50)) was more than 685 microM. The selectivity index [SI=(CC(50) for HEp-2/EC(50))] of NMSO3 for RSV exceeded 2978 and that of ribavirin was 6. The EC(50) of NMSO3 against influenza virus (FluV) A (H3N2) was 23.8 by the MTT method using HMV-2 cells, and 17.8 microM by the TCID(50) method using MDCK cells. NMSO3 did not inhibit replication of influenza B virus, parainfluenza virus type 2 and canine distemper virus at 103 microM. NMSO3 inhibited RSV infection of HEp-2 cells when it was added between 0 and 1.5 h after virus infection. By a temperature shift experiment during the period of contact between the virus and cells, NMSO3 inhibited both the binding of RSV to the cells and its penetration into the cells. Prophylactic and therapeutic efficacy of NMSO3 against RSV infection in cotton rats was examined. Intraperitoneal administration of 100 mg/kg per day of NMSO3 to cotton rats from 1 day before or 1 h after to 3 days after the RSV infection, once a day every day, decreased the RSV titer in lungs to 10(-1.26) to 10(-1.63) compared to the control rats which were infected with RSV and left untreated.

Animals↗

Catalytic asymmetric syntheses and biological activities of singly dehydroxylated 19-nor-1alpha,25-dihydroxyvitamin D(3) A-ring analogs in cancer cell differentiation and apoptosis.

BACKGROUND: 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) has been shown to modulate not only proliferation and differentiation, but also apoptosis in malignant cells, indicating that it could be useful for treating cancer. Little information is available concerning the structural motifs of the 1alpha, 25(OH)(2)D(3) molecule responsible for modulation of differentiation and apoptosis, however. We set out to synthesize singly dehydroxylated A-ring analogs of 19-nor-1alpha,25(OH)(2)D(3) in a catalytic asymmetric fashion, and to investigate their biological activities in leukemia HL-60 cells. RESULTS: A series of singly dehydroxylated 19-nor-1alpha,25-dihydroxyvitamin D(3) A-ring analogs were synthesized using a combinatiorial sequence of regioselective propiolate-ene reaction and catalytic asymmetric carbonyl-ene cyclization. Surprisingly, the analogs could be clearly divided into two categories; one group, bearing 1alpha-hydroxy or 3beta-hydroxy groups in the A-ring, were potent differentiators and the second group, bearing 1beta-hydroxy or 3alpha-hydroxy groups, were potent stimulators of apoptosis. CONCLUSIONS: We have clearly identified the structural motifs of 19-nor-1alpha,25(OH)(2)D(3) analogs responsible for differentiation and apoptosis in HL-60 cells. These findings will provide useful information not only for development of therapeutic agents for treatment of leukemia and other cancers, but also for structure-function studies of 1alpha,25(OH)(2)D(3).

Antineoplastic Agents↗

An autopsy case of salt poisoning from drinking a large quantity of shoyu (Japanese soy sauce).

We report herein a suicide case of salt poisoning from drinking a large quantity of shoyu (Japanese soy sauce). The deceased was a 60-year-old housewife who was found dead in her bedroom by her husband. An empty 1,000 ml bottle of shoyu, which had been purchased on the day before death, was discovered in the kitchen. Macroscopically, the alimentary tract contained a yellowish-brown liquid-like material with the strong smell of shoyu, and slight lung and brain edema were noted. The 1,000 ml bottle of shoyu contained approximately 160 g of salt. Therefore, the cause of death was determined to have been salt poisoning from drinking a large quantity of shoyu.

Journal Article↗

Genetic analysis of mortality in murine angiostrongyliasis costaricensis using SMXA recombinant inbred mouse strains.

The SMXA recombinant inbred mouse strain set was produced by systematic inbreeding from the F2 generation of a cross between two progenitor inbred strains, A/J and SM/J, which differed markedly with respect to the patterns of infection with Angiostrongylus costaricensis. We have applied this set to genetic analysis of mouse susceptibility to this nematode infection. The mortality was variable among substrains of the SMXA RI strains, indicating the involvement of multiple genes. Linkage analysis showed several chromosomal regions closely linked to mortality; chromosome 6 (D6Rik86, 87; P<==0.001), 10 (D10Rik66-D10Mit12; P=0.0058), 13 (D13Rik79, 80; P=0.0096) and 17 (D17Mit28-D17Rik76; P=0.0088).

Angiostrongylus↗

Enantiomer-selective activation of racemic catalysts.

Asymmetric catalysts can be evolved into highly activated catalysts by association with chiral activators. This asymmetric activation process is particularly useful in racemic catalysis through selective activation of one enantiomer of the racemic catalysts. Recently, a strategy whereby a racemic catalyst is selectively deactivated by a chiral additive has been reported to yield nonracemic products. However, we have reported a strategy that is an alternative to asymmetric catalysts but is conceptually opposite, in which a chiral activator selectively activates rather than deactivates one enantiomer of a racemic chiral catalyst. The advantage of this activation strategy over the deactivation counterpart is that the activated catalyst can produce a greater enantiomeric excess (x(act)% ee) in the products than the ee attained by the enantiomerically pure catalyst on its own. Therefore, 'asymmetric activation' could provide a general and powerful strategy for the use of not only atropisomeric and, hence, racemic ligands but also chirally flexible and 'pro-atropisomeric' ligands without enantiomeric resolution!

Catalysis↗

Cytochrome P450 2E1: its clinical and toxicological role.

Cytochrome (CYP) P450 2E1 is clinically and toxicologically important and it is constitutively expressed in the liver and many other tissues. In contrast to many other CYP isoenzymes, indisputable evidence for a functionally important polymorphism of CYP2E1 in the human population is lacking. CYP2E1 metabolizes a wide variety of chemicals with different structures, in particular small and hydrophobic compounds, including potential cytotoxic and carcinogenic agents. In addition, chlorzoxazone and trimethadione metabolism are good CYP2E1 probes for liver disease in vivo and in vitro. In the future, methods for fully analysing the function of CYP2E1 using knockout mice will be established. This article reviews recent advances in our understanding of the role of human CYP2E1 in drug metabolism.

Anesthetics↗

Virolysis and in vitro neutralization of HIV-1 by humanized monoclonal antibody hNM-01.

Antibody humanization by transplanting the complimentarity determining region (CDR) to a human framework aims to reduce the response of the human immune system against a foreign molecule during passive immunization. We transferred the CDR from the murine monoclonal antibody (MAb) NM-01 to a human IgG frame. The humanized NM-01 (hNM-01) recognizes the same epitope on Human Immunodeficiency Virus type 1 (HIV-1) envelope as its murine progenitor, but with greater efficiency, and shows enhanced neutralization of HIV-1. We have shown that this increase in reactivity may be attributed to residue 4 of the humanized kappa chain, where the presence of a methionine residue rather than the murine leucine appears to promote a more advantageous conformation of the antigen-binding site, perhaps via packing interactions with the V(kappa) CDR1. The capacity of humanized NM-01 to neutralize direct clinical isolates was also examined with the expectation that hNM-01 will prove suitable for development as a therapeutic agent. This reshaped antibody reacted with several clinical isolates of HIV-1 tested. Moreover, we proved the ability of this antibody of its activation of complement by flow cytometry and electron microscopy analysis. Although hNM-01 alone was capable of neutralizing HIV-1, the presence of complement enhanced neutralization. The enhancement of complement activation was also observed in hNM-01 than murine progenitor. This finding supports a potential role for antibody-dependent complement-mediated virolysis and more effective neutralization in HIV-1 therapy.

Amino Acid Sequence↗

Detection of thioredoxin in gastric cancer: association with histological type.

Thioredoxin (TRX) is a redox-active protein with multiple intra- and extracellular functions. This protein exists ubiquitously in all life forms, from primitive living cells, such as Escherichia coli and yeast, to higher mammals. Recently, augmentation of the expression and transcription level of TRX has been reported in tumors of various organs. In this study, we examined the expression of TRX in gastric cancer with respect to its histological type and depth of invasion. The association with cell proliferation was also studied. Results of histochemical analysis of surgical specimens as well as cytochemical analysis and Northern blot analysis of gastric cancer cell lines indicated that TRX is predominantly expressed in undifferentiated type gastric cancer rather than in the differentiated type. Neither the depth of tumor invasion nor cell proliferation significantly determined the staining intensity for TRX.

Adenocarcinoma↗

Transgenic rats carrying human c-Ha-ras proto-oncogenes are highly susceptible to N-methyl-N-nitrosourea mammary carcinogenesis.

A rat line carrying three copies of the human c-Ha-ras proto-oncogene, including its own promoter region, was established and designated Hras128. Expression of the transgene was detected in all organs examined from Hras128 rats by northern blot analysis. To examine its influence on susceptibility to N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis, female rats were treated with 50 mg/kg MNU i.v. at 50 days of age. All 22 Hras128 transgenic rats rapidly developed multiple and large mammary carcinomas within as little as 8 weeks after MNU treatment (14.1 tumors/rat, average diameter 16.4 mm). In contrast, 24 non-transgenic littermates developed no or only small tumors (0.46 tumors/rat, average diameter 7.4 mm) within this period. PCR-restriction fragment length polymorphism (RFLP) analysis and direct sequencing for the transduced human c-Ha-ras proto-oncogene indicated that 38 out of 44 tumors (86.4%) contained cells with mutations at codon 12 in exon 1. However, the signal densities of the mutated bands observed in the RFLP analyses revealed the presence of mixed populations of mutated and non-mutated cells in the tumors, the latter being in the majority. PCR-single strand conformation polymorphism analysis detected no mutations in codons 12 or 61 of the endogenous rat c-Ha-ras gene of Hras128 rat tumors. The results thus indicate that rats carrying the transduced human c-Ha-ras proto-oncogene are highly susceptible to MNU-induced mammary carcinogenesis and that this is not primarily due to mutations of the transgene or endogenous c-Ha-ras gene.

Animals↗