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Biomedical subjects

I Saito

Publications and source records attributed to I Saito.

At least 37 records · Page 2Linked to original sources
PubMed2003

Miniature vibrating flow blood pump using a cross-slider mechanism for external shunt catheter.

The prototype of the miniature vibrating flow pump (VFP) is developed for the external shunt catheter. The cross-slider mechanism is applied to vibrate the tube, which causes the pumping effect. This mechanism results in successful development of the miniature and lightweight VFP. By the use of the prototype VFP, the experiment of the basic pump performance is made in detail based on the authorized procedure in the research field of fluids engineering. The typical H-Q curve of VFP, which is the relationship between the pump head and the flow rate, can be obtained. This result suggests that the miniature VFP developed here can be expected to be used as the booster pump for the external shunt catheter in clinical applications.

Arteriovenous Shunt, Surgical↗
PubMed2003

Microvessels of bulbar conjunctiva in UPTAH goats.

Aiming to observe directly the microcirculation after total artificial heart (TAH) implantation, we performed a long-term follow-up in 2 goats using conjunctival angioscopy. A short segment of parallel arteriole and venule was photographed and analyzed on computer picture program (magnification 40x). Three main parameters were measured: arteriole diameter, venule diameter, and arteriovenous ratio (A/V ratio). The intrathoracically implanted TAH was the undulation pump total artificial heart (UPTAH) with cardiac output of 100 ml/kg/min. To stabilize the peripheral hemodynamics a 1/R biofeedback control system was used. Our results provided only elementary data about morphology of bulbar microvessels. The main finding was the tendency to general vasoconstriction, more intensive on the venous side (*P < 0.05 in one goat). We did not observe any pathological shapes (e.g., tortuosities, varicosities, or sludge); this result could be attributed to the high effectivity of 1/R control method. These preliminary results should be considered only as an attempt to apply the widely used clinical method of conjunctival angioscopy to the conditions of TAH.

Animals↗
PubMed2003

Development of an implantable high-energy and compact battery system for artificial heart.

The purpose of this study was to demonstrate the feasibility of the use of an implantable, high-energy, and compact battery system for an undulation pump total artificial heart (UPTAH). The implantable battery system tested consists of six lithium-ion batteries in series, a charge unit, and a charge/discharge control unit. A lithium-ion battery is currently the best energy-storage device because it has more energy density, a better life cycle, and a smaller temperature rise than those of other secondary batteries. The performance of the implantable battery system was evaluated in an in vitro experiment using an electric load that simulated the UPTAH. Also, sufficiently reliable operation of a system for supplying energy to a UPTAH consisting of a transcutaneous energy transmission system (TETS) and an implantable battery system was confirmed in three experiments using goats. The results of the in vitro and in vivo experiments showed that the implantable battery system supplied sufficient current to the UPTAH for maintenance of physiological conditions in the goat with maximum rise in temperature to less than 43 degrees C.

Animals↗
PubMed2003

Estimated daily intake of plasticizers in 1-week duplicate diet samples following regulation of DEHP-containing PVC gloves in Japan.

Duplicate hospital diet samples obtained over 1 week in 2001 were analysed to estimate the daily intake of plasticizers and the results were compared with those obtained in 1999. The plasticizers quantified in this study were: dibutyl phthalate, butylbenzyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), di(2-ethylhexyl) adipate (DEHA), diisononyl adipate (DINA) and O-acetyl tributyl citrate (ATBC). Dipropyl, dipentyl, dihexyl and dicyclohexyl phthalate were also analysed but not detected. The analytical procedure for this follow-up study was essentially the same as in the previous one. Detection limits were 0.1-15.6 ng g(-1) for each plasticizer. One-week duplicate diet samples provided by three hospitals in three remote prefectures of Japan were analysed as individual meals. DEHP was detected at 6-675 ng g(-1) in 62 of 63 meals, significantly lower levels compared with those detected in 1999. Levels of DEHA and DINP also decreased. The mean intake of plasticizers estimated from all samples was 160 microg DEHP day(-1), 12.5 microg DEHA day(-1), 4.7 microg DINP day(-1) and 3.4 microg BBP day(-1). Levels of DINA were relatively high in meals from one hospital: in those meals, the average daily intake was 1338 microg day(-1). Those of ATBC were also higher in meals from another hospital: the average daily intake was 1228 microg day(-1). The sources of DINA and ATBC can be cling-film or sausage packaging.

Adipates↗
PubMed2003

Juxtaoral organ of Chievitz presenting clinically as a tumour.

An extremely rare hamartomatous lesion of the juxtaoral organ of Chievitz (JOOC) in a 63 year old man is reported. The tumour appeared as a large mass in the infratemporal fossa with associated mandibular bone resorption; histologically, it was well encapsulated and composed of numerous tangled masses of benign squamous epithelial nests and mature fibrofatty tissue. There were no histological features suggestive of neoplastic transformation. A literature survey confirmed that this is the first adult case of JOOC presenting clinically as an extraoral tumour.

Biomarkers↗
PubMed2002

Characteristics of immunity induced by viral antigen or conferred by antibody via different administration routes.

The characteristics of the immunity induced by viral antigens or conferred by antiviral antibody via different routes of administration were evaluated comparatively. C57BL/6 mice were immunized via intranasal, intradermal or enteric routes with a live recombinant vaccinia virus expressing the respiratory syncytial virus (RSV) F glycoprotein (F.rVV) or RSV, and then challenged intranasally with RSV. Inhibition of RSV replication was observed in the lungs of all the mice; however, only intranasal immunization hindered virus replication in the nose. Lung inflammation, characterized by infiltration of neutrophils and of mononuclear cells was strongest in the intradermally immunized mice, but was observed in all F.rVV immunized mice to various degrees. Intranasal administration of a potently neutralizing human anti-RSV antibody Fab fragment to infected mice inhibited RSV replication in the nose and, when combined with intraperitoneal administration, protected both the lung and the nose in the absence of deleterious lung pathology. These data suggest that intranasal immunization with F.rVV reduces RSV replication in the respiratory tract, but still induces pathological lung inflammation, even though this is milder than that observed following intradermal immunization. Local neutralizing antibody is indispensable for protection in the nose.

Administration, Cutaneous↗
PubMed2002

Increased cellular infiltrate in inflammatory synovia of osteoarthritic knees.

OBJECTIVE: To determine the nature and origin of synovial inflammation in knees with osteoarthritis (OA). METHOD: Synovial samples were obtained from 21 medial compartmental knee OAs from 19 patients. First, using 11 medial knee synovial samples from 9 patients, a quantitative estimation of synovitis was made with both ordinary and immunohistochemical staining. Second, from the other 10 knees, tissue samples were taken from both the medial and the lateral compartments to quantify cells that infiltrated into the synovium. Medial synovium was immunostained using antibodies to anti-type II collagen, CD68, CD2, CD4, CD8, CD15, CD19, CD25, HLA-DR, CD1a and LN5. The lateral synovium was immunostained with anti-type II collagen, CD68, HLA-DR and CD4 antibody as a control. RESULT: Denatured cartilaginous detritus was found captured by synovial lining cells with a strong immunoreactivity to CD68 antibody, and whose phagocytic potential was activated. The number of anti-type II collagen-positive fragments in the medial compartment of the knee was larger than that found in the lateral compartment. Moreover, the population of CD68-positive cells in synovial tissue and HLA-DR-positive cells in the lining layer was larger in the medial compartment than in the lateral compartment. The number of CD4-positive cells (defined as helper/inducer T lymphocytes) was greater in medial synovium than in lateral synovium. CONCLUSION: Overall, this study strongly supports the concept that the synovitis observed in patients with knee OA might be induced by an immunological mechanism involving, to some extent, a macrophage/helper T cell interaction.

Aged↗
PubMed2002

Notch3 gene polymorphism and ischaemic cerebrovascular disease.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a type of hereditary stroke and dementia. More than 90% of patients with CADASIL have mutations in the Notch3 gene. All mutations either create or destroy a cysteine residue in the epidermal growth factor-like repeats. In addition, five polymorphisms, which lead to amino acid substitutions, have been identified within the Notch3 coding sequence. However, whether these polymorphisms affect Notch signalling or are involved in cerebrovascular diseases is unknown. In the present study, we investigated a possible association between a T6746C polymorphism in the Notch3 coding region and the occurrence of symptomatic ischaemic cerebrovascular disease (CVD) was investigated. Two hundred and thirty five patients with CVD, as confirmed by brain CT or MRI, and 315 age and sex matched control subjects were analyzed for genotype frequencies of the T6746C polymorphism in Notch3. The genotype distributions were: patients with CVD, C/C 14.0%, C/T 45.5%, and T/T 40.4%; controls, C/C, 14.3%; C/T, 47.9%; T/T, 37.8%. The Japanese population has a higher C allele frequency of the T6746C polymorphism than European populations. There was no significant difference between the T6746C polymorphism in patients with CVD and controls (chi(2)=0.414, p=0.813). This was confirmed by the results of multiple logistic regression analysis including established risk factors (chi(2) =4.65, p=0.311). In conclusion, the results indicate that T6746C polymorphism in the intracellular domain of the Notch3 gene is not associated with an increased risk for CVD.

Aged↗
PubMed2001

Recognition of guanine-guanine mismatches by the dimeric form of 2-amino-1,8-naphthyridine.

Dimeric 2-amino-1,8-naphthyridine selectively binds to a G-G mismatch with high affinity (K(d) = 53 nM). We have investigated a binding mechanism of naphthyridine dimer 2 to a G-G mismatch by spectroscopic studies, thermodynamic analysis, and structure-activity studies for the thermal stabilization of the mismatch. 1H NMR spectra of a complex of 2 with 9-mer duplex d(CATCGGATG)2 containing a G-G mismatch showed that all hydrogens in two naphthyridine rings of 2 were observed upfield compared to those of 2 in a free state. The 2D-NOESY experiments showed that each naphthyridine of 2 binds to a guanine in the G-G mismatch within the pi-stack. In CD spectra, a large conformational change of the G-G mismatch-containing duplex was observed upon complex formation with 2. Isothermal calorimetry titration of 2 binding to the G-G mismatch showed that the stoichiometry for the binding is about 1:1 and that the binding is enthalpy-controlled. It is clarified by structure-activity studies that show (i) the linker connecting two naphthyridine rings was essential for the stabilization of the G-G mismatch, (ii) the binding efficiency was very sensitive to the linker structure, and (iii) the binding of two naphthyridines to each one of two Gs in the G-G mismatch is essential for a strong stabilization. These results strongly supported the intercalation of both naphthyridine rings of 2 into DNA base pairs and the formation of a hydrogen bonded complex with the G-G mismatch.

Base Pair Mismatch↗
PubMed2001

Possible role of organ-specific autoantigen for Fas ligand-mediated activation-induced cell death in murine Sjögren's syndrome.

Activation-induced cell death (AICD) is a well-known mechanism of peripheral T cell tolerance that depends upon an interaction between Fas and Fas ligand (FasL). In this study, we demonstrate that the administration of a soluble form of anti-FasL Ab, FLIM58, results in severe destructive autoimmune exocrinopathy in the murine model of human Sjögren's syndrome (SS), and we found that an organ-specific autoantigen may play an important role on down-modulation of AICD. A high titer of serum autoantibodies against 120-kDa alpha-fodrin autoantigen was detected in the FLIM58-treated mice, and splenic T cell culture supernatants contained high levels of IFN-gamma. In vitro T cell apoptosis assay indicated that FasL-mediated AICD is down-regulated by autoantigen stimulation in spleen cells from the murine SS model, but not from Fas-deficient MRL/lpr mice and FasL-deficient MRL/gld mice. FasL undergo metalloproteinase-mediated proteolytic processing in their extracellular domains, resulting in the release of soluble trimeric ligands (soluble FasL). We showed that the processing of soluble FasL occurs in autoantigen-specific CD4(+) T cells, and that a significant increase in expressions of metalloproteinase-9 mRNA was observed in spleen cells from SS model mice. These findings indicate that the increased generation of soluble FasL inhibits the normal AICD process, leading to the proliferation of effector CD4(+) T cells in the murine SS model.

Animals↗
PubMed2001

Selective intercalation of charge neutral intercalators into GG and CG steps: implication of HOMO-LUMO interaction for sequence-selective drug intercalation into DNA.

We have synthesized naphthopyranone epoxide 4 from D-isoascorbic acid together with its three diastereoisomers. DNA alkylation of ODNs containing 5'XGT3' and 5'TGY3' by 4 (11R, 13R), where X and Y are any nucleotide bases, occurred at all G residues except at G of the 5'TGC3' sequence. In contrast, the three other diastereoisomers of 4 showed only weak G alkylation activity. Differential (1)H NMR NOE of the 4-G adduct confirmed the G-N7 alkylation at the epoxide carbon of 4 with concomitant S(N)2 ring opening of the epoxide. Quantitative HPLC analysis of G alkylation efficiency for 4 showed the order of G alkylation susceptibility as TGGT approximately CGT >> TGA > AGT > TGT >> TGC. The order was fully consistent with those reported for aflatoxin B(1) oxide and kapurimycin A(3), suggesting that the sequence selectivity observed for these DNA alkylating agents is not structure dependent but most likely due to the intrinsic property of DNA sequences. We found that the order of G alkylation susceptibility obtained for 4 completely matched the calculated HOMO energy level of G-containing sequences. These results underscore that 4 is a unique molecular probe for ranking the HOMO level of G-containing sequences by well-known G alkylation chemistry and suggests that the intercalation of charge neutral intercalators is a HOMO-controlled process.

Base Sequence↗
PubMed2001

Successful gene therapy via intraarticular injection of adenovirus vector containing CTLA4IgG in a murine model of type II collagen-induced arthritis.

We previously constructed an adenovirus vector carrying a gene encoding a soluble form of fusion protein, consisting of the extracellular portion of cytotoxic lymphocyte antigen 4 (CTLA4) and the Fc portion of human immunoglobulin G1 (Adex1CACTLA4IgG). Murine type II collagen-induced arthritis (CIA) was treated with Adex1CACTLA4IgG. A single intraarticular injection of 1 x 10(5) PFU was able to support serum CTLA4IgG at more than 10 microg/ml for at least 12 weeks and was able to inhibit the CIA clinically and histologically. In contrast, intravenous, intramuscular, or subcutaneous injection of 1 x 10(5) PFU was unable to support a significant level of serum CTLA4IgG and thus was unable to inhibit the development of arthritis. Thus, we demonstrated that (1) a low-dose intraarticular injection of Adex1CACTLA4IgG was effective in delaying the onset of CIA and reducing the severity of arthritis; (2) an intraarticular (knee joint) injection of Adex1CACTLA4IgG effectively blocked the development of arthritis in distal paws; (3) the inhibitory effect of Adex1CACTLA4IgG lasted at least up to 20 weeks; (4) although serum CTLA4IgG at more than 10 microg/ml persisted for at least 12 weeks, mice treated by intraarticular injection of Adex1CACTLA4IgG were not anergic to adenovirus and were able to mount antibody responses against various antigens.

Abatacept↗