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Biomedical subjects

N Suzuki

Publications and source records attributed to N Suzuki.

At least 595 records · Page 33Linked to original sources
PubMed1997

Prevalence of equine piroplasmosis in Central Mongolia.

Antigen for the indirect fluorescent antibody test (IFAT) was routinely prepared from infected erythrocytes from horses experimentally infected with Babesia equi and Babesia caballi. With the successful establishment of in vitro cultures of B. equi and B. caballi, it is now possible to employ culture-derived antigens in this test. In this study, in vitro-propagated B. equi- and B. caballi-infected erythrocytes were used as antigen in the IFAT. Various modifications to an established protocol had to be implemented to allow repeatable results. Cultures with 3-4% parasitized erythrocytes were found to be most suitable. As cross-reactions of control sera on heterologous antigen were observed at serum dilutions of up to 1/40, a reciprocal titre of 80 was considered to be positive. In positive samples, specific fluorescence of Babesia parasites and/or erythrocyte membranes was observed. Fifteen sera from Babesia-free horses from Japan all tested negative in the IFAT. One hundred and ten field-horse sera from Central Mongolia were investigated in this study. The results indicate that both B. equi and B. caballi are endemic in horses in Central Mongolia, with 88.2% and 84.5% of horses being seropositive to B. equi and B. caballi, respectively.

Animals↗
PubMed1997

Mechanisms of KE298, 2-acetylthiomethyl-3-(4-methylbenzoyl) propionic acid, to suppress abnormal synovial cell functions in patients with rheumatoid arthritis.

OBJECTIVE: 2-Acetylthiomethyl-3-(4-methylbenzoyl) propionic acid, KE298, a derivative or propionic acid developed in Japan has been shown to be effective for suppressing disease activity of rheumatoid arthritis (RA) in clinical trials in Japan. It is thus a candidate as a new disease modifying antirheumatic drug (DMARD). We analyzed effects of KE298 on synovial fibroblast-like cells in patients with RA to obtain insight into the clinical application of this medication. METHODS: RA synovial fibroblast-like cells were co-cultured with KE298 at 10(-4)-10(-5) M in the presence or absence of tumor necrosis factor-alpha 2 ng/ml, and their subsequent proliferative responses and proinflammatory cytokine and matrix metalloproteinase (MMP) production at the mRNA and protein levels were measured. Effects of KE298 on MMP-1 gene transcription and AP-1 transcription factor expression of RA synovial cells were studied by chloramphenicol acetyltransferase assay and gel shift assay, respectively. RESULTS: KE298 inhibited proliferation of RA synovial cells, proinflammatory cytokine production, and MMP-1 production mainly by reducing their transcription via downmodulation of AP-1 transcription factor. CONCLUSION: KE298 inhibits aberrant synovial cell functions of patients with RA by downregulating gene transcription, suggesting clinical application and usefulness of this new DMARD.

Antirheumatic Agents↗
PubMed1997

[Clinical study on air in epidural hematomas].

Air in epidural hematoma has previously been reported by some authors. With the advent of CT scan, the presence of air in epidural hematomas is not uncommon findings. In our series, 27 of 78 (34.6%) cases with acute epidural hematoma had air bubbles in epidural hematoma on CT scan. Acute epidural hematoma was located in the temporal in 18, frontal in 3, occipital in 2, parietal in one and posterior fossa in 3 cases. The air entrance was thought to be mastoid air cells in 13, open fracture in 5, frontal sinus in 3, sphenoid sinus in 3, and unknown in 3 cases. No patients in our series developed meningeal infection or tension pneumocephalus. There was no statistical difference of overall outcome or risk of increase in size of hematoma between acute epidural hematoma with and without air.

Acute Disease↗
PubMed1997

Location and action of angiotensin II type 1 receptor in the renal microcirculation.

To localize angiotensin II type 1a (AT-1a) receptor and to reveal the physiological roles of angiotensin II in the renal microcirculation, we investigated the AT-1a gene deficient mice, generated by a targeted replacement of the AT-1a receptor loci by the lacZ gene (Sugaya et al, J Biol Chem 270: 18719, 1995). Immunohistochemical localization of beta-galactosidase was performed in the heterozygous mutant mice to reveal the expression sites of AT-1a. The AT-1a receptor (that is, beta-galactosidase) was expressed both in the afferent and efferent arteriolar smooth muscles and also in the mesangial cells. The effect of angiotensin II on glomerular arterioles was directly observed using the hydronephrotic mice. Angiotensin II similarly constricted both the afferent and efferent arterioles in the wild-type and heterozygous mutant mice in a dose-dependent manner. This constriction was completely abolished by an AT-1 antagonist, CV-11974. In the homozygous null mutant mice, however, angiotensin II did not affect the arterioles at all. Electron microscopic studies revealed that the mesangial cells made contact with the glomerular basement membrane (GBM) at the capillary neck and also with each other in the wild-type mice. However, in the homozygous null mutant mice, the mesangial cells lost the contact either with GBM or with each other and thus the capillary neck became remarkably wider. The mesangial matrix area appeared loose and enlarged, suggesting impaired mesangial matrix formation. In conclusion, via the AT-1a receptor, angiotensin II equally constricts both the afferent and efferent arterioles and plays an essential role in maintaining the normal glomerular function and structure.

Angiotensin II↗
PubMed1997

[Perinatal surgery and perinatal treatment].

Recent results of neonatal surgery in Japan are presented. Nowadays, babies born with esophageal atresia, diaphragmatic and abdominal wall defects (gastroschisis and amphalocele) require special intensive surgical care after delivery, while those with imperforate anus, hirschoprung's disease and intestinal atresia will follow a relatively smooth postoperative course. Prenatal surgery or treatment may be necessary for some fetuses with congenital diaphragmatic hernia and congenital cystic adenomatoid malformation of the lung. Experiences at the authors institutions were reported, and recent results at institutions in the united states are introduced.

Congenital Abnormalities↗
PubMed1996

Analysis of the pancreatic beta cell in the mouse with targeted disruption of the pancreatic beta cell-specific glucokinase gene.

This is the first systematic study on the pancreatic beta cell function in the heterozygous mouse with targeted disruption of the beta cell glucokinase gene. The heterozygotes' beta cell displayed the following characteristics: (1) impaired glucose sensitivity with normal glucose responsiveness, (2) poor discrimination of alpha and beta glucose anomers, and (3) normal response to glucose in the presence of 25 mM K+ and 150 microM diazoxide. Both the first and the second phases of glucose-stimulated insulin release were depressed. Although the heterozygotes were mildly hyperglycemic, insulin treatment further suppressed beta cell function, implying the beta cell glucose toxicity is not the cause of impaired glucose sensitivity. The data are compatible with the glucokinase glucose sensor concept inasmuch as glucose sensitivity is reduced in the heterozygotes' beta cell. The anomeric malaise and preservation of the ATP-sensitive K+ channel-independent glucose action were considered due to chronic hyperglycemia.

Animals↗
PubMed1996

Miscoding properties of 3,N4-etheno-2'-deoxycytidine in reactions catalyzed by mammalian DNA polymerases.

We have investigated the miscoding properties of the exocyclic DNA adduct, 3,N4-etheno-2'-deoxycytidine (epsilon dC), using an experimental system designed to detect and quantify base substitutions and deletions generated by primer extension in reactions catalyzed by DNA polymerases alpha, beta, and delta. Oligodeoxynucleotides modified site-specifically with epsilon dC were used as DNA templates for this study. Pol alpha catalyzed incorporation of dTMP and dAMP opposite epsilon dC, accompanied by lesser amounts of dCMP and dGMP and some two-base deletions. Pol beta promoted incorporation of dCMP and dAMP, along with small amounts of one-base and two-base deletions. Pol delta catalyzed incorporation of dTMP and lesser amounts of dAMP and dGMP. The frequency of nucleotide insertion opposite epsilon dC and of chain extension from the 3'-primer terminus in reactions catalyzed by pol alpha and pol beta was established by steady-state kinetic analysis. Results of this study were consistent with those obtained in primer extension experiments. The miscoding properties of epsilon dC determined in vitro are consistent with observations of epsilon dC-->A transversions and epsilon dC-->T transitions in site-specific mutagenesis experiments in mammalian cells (Moriya et al. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 11899). We conclude from this study that DNA polymerases may differ significantly in their miscoding potential and that in vitro analysis can be used to predict mutagenic specificity of exocyclic DNA adducts in mammalian cells.

Animals↗
PubMed1996

Involvement of antipain-sensitive protease activity in the interferon-beta-induced UV-refractoriness of Cockayne syndrome fibroblasts.

Fibroblast cells obtained from two siblings and a female patient with Cockayne syndrome (CS), when pretreated with human interferon (HuIFN)-beta prior to irradiation with UV light (254 nm wavelength), exhibited transiently induced fibrinolytic protease activity immediately after the irradiation in association with increased refractoriness to UV cell-killing. A protease inhibitor, antipain, inhibited the induction of protease activity in lysates of the CS fibroblasts from these 3 cases after the combination of HuIFN-beta pretreatment and UV irradiation, whereas elastatinal and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) inhibited the activity less than antipain did. Antipain also suppressed the increase in UV-refractoriness of HuIFN-beta-pretreated CS fibroblasts, as revealed by culturing cells for 24 h in medium containing the inhibitor immediately after UV exposure and thereafter evaluating the ability of colony formation by the cells. Thus, an antipain-sensitive protease may be involved in the UV-refractoriness induced by HuIFN-beta in CS fibroblast strains.

Antipain↗
PubMed1996

Toxoplasma gondii: experimental infection in cats vaccinated with 60Co-irradiated tachyzoites.

The effects of 60Co-irradiation on the viability and immunogenicity of RH and Beverley strains of Toxoplasma gondii was examined. While 60Co-irradiated tachyzoites retained invasive activity in mouse embryonal cells and sustained antigenicity in mouse peritoneal macrophages, the parasites did not develop in host cells. Vaccination of mice with 60Co-irradiated tachyzoites of either RH or Beverley strains induced resistance to challenge with a highly virulent strain (RH strain). Vaccination of kittens with 60Co-irradiated tachyzoites of the Beverley strain partially prevented oocyst shedding when challenged with cysts (bradyzoites) from the Beverley strain. But kittens vaccinated with 60Co-irradiated or fixed tachyzoites of the RH strain shed oocysts when challenged with cysts (bradyzoites) from the Beverley strain. These results suggest that the development of protective immunity in feline toxoplasmosis seems to be strain and/or stage-specific.

Animals↗
PubMed1996

Characterization of a germline Vk gene encoding cationic anti-DNA antibody and role of receptor editing for development of the autoantibody in patients with systemic lupus erythematosus.

We found previously that cationic anti-DNA autoantibodies (autoAbs) have nephritogenic potential and usage of a specific germline Vk gene, A30, has major influences on cationic charge of the autoAb in human lupus nephritis. In the present study, we have characterized A30 germline Vk gene using cosmid cloning technique in patients with SLE. A30 gene locus locates in less than 250 kb from the Ck region, and the cationic anti-DNA mRNA used the upstream Jk2 gene, indicating that cationic anti-DNA mRNA is a product of primary gene rearrangement. By using PCR technique, we found that A30 gene locus in the genome was defective in eight out of nine SLE patients without nephritis. In contrast, all nine patients with lupus nephritis had intact A30 gene. The presence and absence of A30 gene was associated with the development of lupus nephritis or not (P < 0.01, by Fisher's exact test, two-sided). It was thus suggested that absence of functional A30 gene may rescue from developing lupus nephritis in the patients. A30 is reported to be a potentially functional but rarely expressed Vk gene in humans. It is possible that normal B cells edit primarily rearranged A30 gene with autoreactive potentials by receptor editing mechanism for changing the affinity of the B cell Ag receptor to avoid self-reactivity, whereas SLE B cells may have a defect in this mechanism. Indeed, we found that normal B cells edit A30-Jk2 gene in their genome possibly by inversion mechanism, whereas SLE B cells contain rearranged A30-Jk2-Ck gene in the genome and express A30-associated mRNA, suggesting that receptor editing mechanism is also defective in patients with SLE. Our study suggests that polymorphism of Ig Vk locus, and failure of receptor editing may contribute to the development of pathogenic anti-DNA responses in humans.

Adolescent↗
PubMed1996

A unique human gene that spans over 230 kb in the human chromosome 8p11-12 and codes multiple family proteins sharing RNA-binding motifs.

A unique gene, RBP-MS, spanning over 230 kb in the human chromosome 8p11-12 near the Werner syndrome gene locus is described. The single-copy RBP-MS gene is alternatively spliced, resulting in a family of at least 12 transcripts (average length of 1.5 kb). Nine different types of cDNAs that encode an RNa-binding motif at the N terminus and helix-rich sequences at the C terminus have been identified thus far. Among the 16 exons identified, four 5'-proximal exons contained sequences homologous to the RNA-binding domain of Drosophila couch potato gene. Northern blot analysis showed that the RBP-MS gene was expressed strongly in the heart, prostate, intestine, and ovary, and poorly in the skeletal muscle, spleen, thymus, brain, and peripheral leukocytes. The possible role of this gene in RNA metabolism is discussed.

Alternative Splicing↗
PubMed1996

Inhibitory effect of neuropeptide Y on growth hormone secretion in rats is mediated by both Y1- and Y2-receptor subtypes and abolished after anterolateral deafferentation of the medial basal hypothalamus.

Neuropeptide Y (NPY) may play a physiological role in the regulation of growth hormone (GH) secretion by acting via somatostatin (SS) in the periventricular nucleus (PeV), as well as via the GH-releasing factor in the arcuate nucleus (ARC) of the medial basal hypothalamus (MBH). The objectives of the present study were to determine the neuron structures and receptor subtypes necessary for mediating the inhibitory effect of NPY on GH secretion in unanesthetized male rats. To eliminate the influence of hypophyseotropic SS, anterolateral deafferentation (ALC) of the hypothalamus was performed. Intracerebroventricular (i.c.v.) administration of 1.17 nmol of NPY decreased the blood level of GH for 3-4 h in sham-operated rats, while the procedure was without effect in ALC rats. The i.c.v. administration of 1.17 nmol of a Y1-receptor agonist ([Leu31, Pro34]-NPY) or a Y2-receptor agonist (NPY 13-36 and NPY 3-36) similarly suppressed the blood GH level. The data support the hypothesis that neuron structures anterolateral to the MBH are required for NPY-induced inhibition of GH secretion that is mediated via Y1- and Y2-receptor subtypes. Combined with data of other investigators, SS is likely the neurohumoral mediator of the effect of NPY on GH secretion.

Afferent Pathways↗
PubMed1996

Electrospray ionization mass spectrometric composition of the 400 kDa hemoglobin from the pogonophoran Oligobrachia mashikoi and the primary structures of three major globin chains.

Maximum entropy analysis of the electrospray ionization mass spectra of the native, carbamidomethylated, reduced and reduced and carbamidomethylated forms of the extracellular ca. 400 kDa hemoglobin of the pogonophoran Oligobrachia mashikoi has shown it to consist of eight globin chains: (a1-a5), 14861.1, 14937.1, 15040.7, 15070.6 and 15310.6 Da and b-dl, 15173.2, 15605.1 and 14775.4 Da, respectively. Although chains a1-a5 are monomeric, chains b + c form a disulfide-bonded dimer of 30776.8 Da and chains b + c + d1 form a disulfide-bonded trimer of 45551.9 Da. The major chains a5, b and c were separated by reverse-phase chromatography, and their cDNA's amplified by PCR using redundant oligomers based on their N-terminal amino-acid sequences. The complete amino-acid sequences of chains a5 (142 residues), b (140 residues) and c (147 residues) were derived from protein and cDNA sequencing and represent the first pogonophoran globin sequences. They have a high percent identity (35-52%) with the globin chains of the approximately 3500 kDa hexagonal bilayer hemoglobins from the annelids Lumbricus and Tylorrhynchus and the vestimentiferan Lamellibrachia, suggesting a very close relationship among the phyla Annelida, Pogonophora and Vestimentifera. Two free cysteine residues (Cys-73 and Cys-83), which we proposed to be the most probable candidates for the sulfide-binding sites in the Lamellibrachia chains (Suzuki, T., Takagi, T. and Ohta, S. (1990) Biochem. J. 266, 221-225), are also conserved in three chains (Cys-73 for chains b and c, and Cys-83 for chain a5) of Oligobrachia hemoglobin, in agreement with the probable role of the hemoglobin in the binding and transport of sulfide to the symbiotic bacteria which provide the metabolic fuel in the two phyla.

Amino Acid Sequence↗
PubMed1996

Functional correlation of NMDA receptor epsilon subunits expression with the properties of single-channel and synaptic currents in the developing cerebellum.

NMDA receptor (NMDAR) subunits epsilon 1-epsilon 4 are expressed differentially with respect to brain region and ontogenic period, but their functional roles still are unclear. We have compared an epsilon 1 subunit-ablated mutant mouse with the wild-type to characterize the effect of epsilon subunit expression on NMDAR-mediated single-channel currents and synaptic currents of granule cells in cerebellar slices. Single-channel and Western blot analyses indicated that the epsilon 2 subunit disappeared gradually during the first postnatal month in both wild-type and mutant mice. Concomitantly, the voltage-dependent Mg2+ block of NMDAR-mediated EPSCs (NMDA-EPSCs) was decreased. Throughout the developmental period studied, postnatal day 7-24 (P7-P24), the decay time course of NMDA-EPSCs in epsilon 1 mutant (-/-) mice was slower than in wild-type mice. We suggest that the expression of the epsilon 3 subunit late in development is responsible for a reduction in the sensitivity of NMDA-EPSCs to block by extracellular Mg2+ and that receptors containing the epsilon 1 subunit determine the fast kinetics of the NMDA-EPSCs.

Age Distribution↗
PubMed1996

Cloning, sequencing and mapping of a manganese superoxide dismutase gene of the nematode Caenorhabditis elegans.

We have cloned, sequenced and mapped a gene (sod-2) encoding manganese superoxide dismutase [EC 1.15.1.1] from the nematode Caenorhabditis elegans. The sod-2 was mapped to chromosome I by hybridization with a YAC polytene filter. The protein-coding region spans 1129 base pairs including 4 introns and encodes a protein of 221 amino acids (aa) (M(r) = 24536) of which the first 24 aa are the presumed mitochondorial-targeting signal peptide. The gene sequence of sod-2 was slightly different from an isoform, sod-3.

Amino Acid Sequence↗
PubMed1996

Fractionation of amyloid beta-protein (A beta) in Alzheimer's disease and Down's syndrome brains. Presence of membrane-bound A beta.

To investigate the early stage of beta-amyloidogenesis in Alzheimer's disease (AD), we performed sucrose density gradient fractionation of amyloid beta-protein (A beta) deposited in cerebral cortices from AD and Down's syndrome patients and normal aged individuals. Each fraction was subjected to Western blotting with monoclonal antibodies BA27 and BC05, which specifically recognize A beta 40 and A beta 42, respectively. The samples from brains with a large number of diffuse plaques showed strong BC05 immunoreactivity at the 1.0/1.2 M (F1) and 1.2/1.5 M (F2) interfaces. In contrast, in brains with advanced AD pathology, most of the BC05 immunoreactivity was recovered at the 1.5/2.0 M (F3) interface. In all cases, the level of BA27 immunoreactivity was negligible. Although F1A beta was determined to be A beta 1-42, it was only weakly reactive with BAN50 (monoclonal antibody raised against A beta 1-16). Delipidation of F1A beta restored full BAN50 immunoreactivity, indicating that F1A beta is bound to membrane. The present results suggest that diffuse plaques are associated with this membrane-bound A beta and thus that this novel A beta species is an initially deposited one.

Alzheimer Disease↗