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Biomedical subjects

M Goto

Publications and source records attributed to M Goto.

At least 181 records · Page 10Linked to original sources

Intramyocardial influences on blood flow distributions in the myocardial wall.

Flow velocity wave forms of coronary arterial inflow and venous outflow of myocardium are influenced by cardiac contraction and relaxation: arterial flow is exclusively diastolic; venous outflow is systolic. We first discuss the intramyocardial microvascular flow dynamics, then present some results of visualization of transmural microvessels by our needle-probe charge coupled device (CCD) microscope, along with an interpretation of the arteriolar and venular hemodynamics through a cardiac cycle. After describing a hierarchical system of coronary microvessels (small artery, arteriole, and capillary), we emphasize the importance of spatial heterogeneity of blood supply to myocardium with reference to a minimal vascular control unit (approximately 400 microm). An understanding of mechanoenergetic interaction is fundamentally important to an understanding of intramyocardial coronary circulation, and the Physiome Project will provide powerful tools for understanding the integrated role of the intramyocardial microcirculation system.

Blood Flow Velocity↗

Convenient test for screening metallo-beta-lactamase-producing gram-negative bacteria by using thiol compounds.

A simple disk diffusion test was constructed for detection of IMP-1-type metallo-beta-lactamase-producing gram-negative bacteria. Two Kirby-Bauer disks containing ceftazidime (CAZ) and a filter disk containing a metallo-beta-lactamase inhibitor were used in this test. Several IMP-1 inhibitors such as thiol compounds including 2-mercaptopropionic acid, heavy metal salts, and EDTA were evaluated for this test. Two CAZ disks were placed on a Mueller-Hinton agar plate on which a bacterial suspension was spread according to the method recommended by the National Committee for Clinical Laboratory Standards. The distance between the disks was kept to about 4 to 5 cm, and a filter disk containing a metallo-beta-lactamase inhibitor was placed near one of the CAZ disks within a center-to-center distance of 1.0 to 2.5 cm. For IMP-1-producing strains, the growth-inhibitory zone between the two disks expanded, while no evident change in the shape of the growth-inhibitory zone was observed for CAZ-resistant strains producing serine beta-lactamases such as AmpC or SHV-12. As a result, 2 to 3 microliter of undiluted 2-mercaptopropionic acid or mercaptoacetic acid able to block IMP-1 activity gave the most reproducible and clearest results, and CAZ-resistant strains producing AmpC or extended-spectrum beta-lactamases were distinguishable from IMP-1 producers by this test. A similar observation was made with IMP-1-producing clinical isolates such as Serratia marcescens, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas putida, Acinetobacter spp., and Alcaligenes xylosoxidans. The specificity and sensitivity of this test were comparable to those of PCR analysis using bla(IMP)-specific primers. Therefore, this convenient test would be valuable for daily use in clinical laboratories.

Bacterial Proteins↗

Polymorphism in the interleukin-4 promoter affects acquisition of human immunodeficiency virus type 1 syncytium-inducing phenotype.

The emergence of syncytium-inducing (SI) variants of human immunodeficiency virus type 1 (HIV-1) in infected individuals is an indicator of poor prognosis and is often correlated with faster CD4(+) cell depletion and rapid disease progression. Interleukin-4 (IL-4) is a pleiotropic cytokine with various immune-modulating functions including induction of immunoglobulin E (IgE) production in B cells, down-regulation of CCR5 (a coreceptor for HIV-1 non-SI [NSI] strains), and up-regulation of CXCR4 (a coreceptor for HIV-1 SI variants). Here we show that homozygosity of a polymorphism in the IL-4 promoter region, IL-4 -589T, is correlated with increased rates of SI variant acquisition in HIV-1-infected individuals in Japan. This mutation was also shown to be associated with elevated serum IgE levels in HIV-1-infected individuals, especially in those at advanced stages of disease. In contrast, neither a triallele polymorphism in IL-10, another Th2 cytokine, nor a biallele polymorphism in the RANTES promoter affected acquisition of the SI phenotype. This finding suggested that IL-4-589T increases IL-4 production in the human body and thus accelerates the phenotypic switch of HIV-1 from NSI to SI and possibly disease progression of AIDS.

Alleles↗

Prophylactic treatment of endotoxic shock with monophosphoryl lipid A in newborn rats.

Mortality due to gram-negative septic shock remains high despite advances in medical care. Induction of endotoxin tolerance might be a new treatment strategy to prevent septic shock in the newborn. The present study was performed to show that an injection in pregnant rats of monophosphoryl lipid A (MPL), a nontoxic derivative of lipopolysaccharide (LPS), induces tolerance to Salmonella enteritidis LPS and tumor necrosis factor alpha (TNF-alpha) in their offspring. MPL at a dose of 2 mg/kg was injected into pregnant rats on the 19th day of gestation. Their 0-day-old offspring later received an intraperitoneal injection of S. enteritidis LPS or TNF-alpha. Newborn rats of MPL-treated dams exhibited a higher survival rate, absence of lactacidemia and lower plasma TNF-alpha concentration in response to S. enteritidis LPS when compared to the newborn rats of saline-treated dams. Newborn rats of MPL-treated dams were more tolerant to TNF-alpha than those of saline-treated dams. MPL injection into pregnant rats did not increase plasma endotoxin concentration in the fetuses, suggesting no placental passage took place, but it did increase plasma TNF-alpha concentration. We concluded that an injection of MPL into pregnant rats induced tolerance to LPS in their offspring, which might be due to TNF-alpha-induced TNF-alpha tolerance.

Adjuvants, Immunologic↗

Effect of polyclonal anti-TNFalpha antibody on endotoxic shock in suckling rats.

The aim of this study was to evaluate the effect of anti-tumor necrosis factor alpha (TNFalpha) antibodies on the TNFalpha gene expression in a neonatal septic shock model. Ten-day-old Sprague-Dawley rats were divided into four groups and given intraperitoneal (ip) injection as follows: group 1: 0.1 ml saline; group 2: 0.1 mg/kg Salmonella enteritidis lipopolysaccharide (LPS); group 3: 1 mg/kg of anti-TNFalpha antibodies (Ab); group 4: 0.1 mg/kg of LPS and 1 mg/kg of Ab. We found that in group 2, LPS induced shock, demonstrating hypoglycemia and lactacidemia (p < 0. 05) and death (81.8%). Ab decreased the mortality significantly (35%) and attenuated the hypoglycemia (35 +/- 8 mg/dl in group 2 vs. 53 +/- 3 mg/dl in group 4) and lactacidemia (5.40 +/- 0.63 vs. 2.35 +/- 0.45 mmol) at 8 h in group 4 when compared to group 2. Northern blot demonstrated a significant decrease in TNFalpha mRNA expression in group 4 as compared to group 2, at 2 h after LPS injection. We conclude that the beneficial effects of anti-TNFalpha antibodies on LPS-induced shock may be due to decreased TNFalpha gene expression.

Animals↗

Dietary nucleotides can up-regulate antigen-specific Th1 immune responses and suppress antigen-specific IgE responses in mice.

BACKGROUND: It has been reported that dietary nucleotides enhance T helper cell activities. In this study, we have determined the effects of dietary nucleotides on antigen-specific Th1 and Th2 responses and IgE responses. METHODS: Ovalbumin (OVA)-specific T cell receptor (TCR) transgenic (OVA-TCR Tg) mice, 3 weeks old, were fed a nucleotide-free diet (NT(-) diet) or the NT(-) diet supplemented with dietary nucleotides (NT(+) diet) for 4 weeks. Cytokine production by spleen cells and macrophages obtained from these mice was measured in vitro. BALB/c mice, 3 weeks old, immunized intraperitoneally with OVA adsorbed onto alum, were fed the NT(-) diet or the NT(+) diet for 4 weeks. Serum levels of antigen-specific antibodies in the BALB/c mice were determined by ELISA. RESULTS: The level of production of antigen-specific interferon-gamma by spleen cells was significantly higher in the OVA-TCR Tg mice fed the NT(+) diet than in the control mice. The levels of secretion of bioactive IL-12 by spleen cells and peritoneal macrophages were also significantly increased in the NT(+) diet group. The serum OVA-specific IgE level was significantly decreased in BALB/c mice fed the NT(+) diet compared with those fed the NT(-) diet. CONCLUSION: These results show that dietary nucleotides up-regulate the antigen-specific Th1 immune response through the enhancement of IL-12 production and suppress the antigen-specific IgE response.

Adjuvants, Immunologic↗

Enhanced effect of sulfonylurea (SU) in copolymer comprising a sugar moiety and SU derivative as double ligands on insulin secretion from MIN6 cells.

Copolymers composed of sulfonylurea (SU) as an antagonist of ATP-sensitive K+ channel and sugar moieties as double ligands were synthesized. Insulin secretion from MIN6 cells (insulinoma cell line) in contact with the copolymers was evaluated. MIN6 cells attached to the poly(N-p-vinylbenzyl-D-maltonamide-co-SU) [P(VMA-co-SU)]-coated dishes were in the more aggregated form as compared to other polymer-coated surfaces. By introducing SU into the sugar bearing homopolymer, an enhanced effect on insulin secretion from MIN6 cells was observed due to the specific interaction between SU ligands and SU receptors on the beta-cell membrane. P(VMA-co-SU) composed of SU and non-reducing glucose moieties demonstrated enhanced insulin secretion from MIN6 cells and faster proliferation of MIN6 cells as compared to poly(N-p-vinylbenzyl-D-lactonamide-co-SU) [P(VLA-co-SU)] probably owing to the glucose transporters presence on the MIN6 cell membrane. Insulin secretion from MIN6 cells pretreated with diazoxide as an agonist of ATP-sensitive K+ channel was suppressed.

Adenosine Triphosphate↗

Rate enhancement with high ratio of the monoalkylated product to the dialkylated product in the alkylation of the lithium enolate of 1-tetralone with reactive alkyl halides.

The reactions of the lithium enolate of 1-tetralone with reactive alkyl halides were examined in the absence and in the presence of 3 eq of various ligands for the lithium. It is shown that the rates of the reactions are enhanced greatly in the presence a tetradentate amine (1,1,4,7,10,10-hexamethyltriethylenetetramine), and the ratio of the monoalkylated product to the dialkylated product is increased under shorter reaction times.

Alkylation↗

Structural and spectral characteristics of the electrogenerated tetracyanoethylene dianion.

Structural and spectral characteristics of the electrogenerated tetracyanoethylene dianion (TCNE2-) were experimentally and theoretically examined. Spectroelectrochemistry of TCNE gives the spectra of TCNE2- in CH3CN at 220 nm, and in CH2Cl2 at 300 nm. These spectral characteristics are well explained by CIS/6-31G(d) and semiempirical CNDO/S-CI calculations. The bands in CH3CN and in CH2Cl2 are assigned to the degenerate 1E<--1A1 transition at the D2d structure and the 1B2u<--1Ag transition at the D2h structure, respectively. The rotation barrier of the C=C bond in TCNE2- is estimated by Hartree-Fock (HF), second-order Møller-Plesset perturbation (MP2) and fourth-order MP (MP4) calculations with 6-31G(d), 6-31+G(d) and 6-311+G(d) basis sets as 42-51 kJ mol(-1). The D2d structure is most stable, and the D2h structure represents the transition state of the internal rotation. The calculations reveal that the two-electron addition to the antibonding LUMO of TCNE causes an easy rotation around the C=C bond of TCNE2- characterized by the formal single bond. These results show that TCNE2- preferentially adopts D2d and D2h structures in solvents depending upon the solvent nature by virtue of the easy rotation around the C=C bond.

Anions↗

A peculiar form of focal atrial tachycardia mimicking atypical atrial flutter.

A 55-year-old man was referred because of congestive heart failure and atrial flutter. A 12-lead electrocardiogram (ECG) showed positive P waves in leads II, III, and aVF with a continuously undulating pattern that lacked an isoelectric baseline. Tachycardia was diagnosed as atypical atrial flutter based on classical criteria. An electrophysiological study and catheter ablation using an electroanatomical system revealed the mechanism of the tachycardia to be focal atrial tachycardia originating from the left atrial roof. This case indicates that focal atrial tachycardia may present as atypical atrial flutter on the surface ECG.

Atrial Flutter↗

[Model and inference for quantal response pharmacological assay].

A quantal response bioassay is defined as an experiment for estimating the potency of a drug, material or process by means of the reaction (quantal response) that follows its application to living matter. For example, the main object of bioassays in drug development is to measure the potency of some new compounds relative to some standard drug in terms of magnitudes of their effects on responses from living subjects. The quantitative estimates of their potency are summarized by comparing these dose-response curves. In this paper, we focus on analyses intended to compare two dose-response curves with quantal response and consider the model validation and the interpretation of fitting results from a statistical point of view.

Animals↗

Dietary nucleotides increase the proportion of a TCR gammadelta+ subset of intraepithelial lymphocytes (IEL) and IL-7 production by intestinal epithelial cells (IEC); implications for modification of cellular and molecular cross-talk between IEL and IEC by dietary nucleotides.

We have investigated the effects of dietary nucleotides on intraepithelial lymphocytes (IEL) and intestinal epithelial cells (IEC) in weanling mice. The proportion of T-cell receptor (TCR) gammadelta+ IEL in BALB/c mice fed a diet supplemented with nucleotides (NT(+) diet) was significantly higher than that in mice fed the nucleotide-free diet, while the proportion of TCR alphabeta+ IEL in NT(+) diet-fed mice was significantly decreased. The change of the TCR alphabeta+/TCR gammadelta+ ratio was mainly observed in a CD8 alphaalpha+ subset of IEL. IEC from NT(+) diet-fed mice produced a higher level of IL-7, which is important in the development of TCR gammadelta+ IEL, than those from control diet-fed mice. The expression levels of IL-7 and IL-2 receptors on IEL were not different between the two dietary groups. Our findings suggest that the increased population of a TCR gammadelta+ IEL subset by feeding nucleotides may be caused by the increased production of IL-7 by IEC.

Animals↗

Analysis of oxidation sensitivity of maleate cis-trans isomerase from Serratia marcescens.

The maleate cis-trans isomerase gene (maiA) from Serratia marcescens IFO3736 was cloned and sequenced. Serratia MaiA has 62.4% amino acid identity with Alcaligenes faecalis IFO13111 MaiA and 64.9% with Bacillus stearothermophilus MI-102 MaiA. All known ten amino acid sequences of MaiA had significant conserved regions containing cysteine residues, which were previously suggested to be involved in an active site of the enzyme. The maiA gene was expressed in Escherichia coli, and expressed products MaiA was purified and characterized. The purified enzyme of strain IFO3736 showed high activity at room temperature and high heat stability. It also showed higher activity in the presence of high concentration of aspartic acid than the enzyme of A. faecalis IFO13111, but it was also sensitive to chemical oxidation. By amino acid composition analysis, cysteine, methionine, and tyrosine residues were suggested to be oxidized to inactivate the enzyme by chemical oxidation. To investigate the mechanism of chemical oxidation of the enzyme, six methionine residues in the conserved regions of S. marcescens MaiA were replaced with cysteine residues by site-directed mutagenesis. The analysis of the constructed mutants suggested that the Met201 residue near the Cys198 residue is involved in the sensitivity of the enzyme to chemical oxidation.

Amino Acid Sequence↗

Molecular analysis of maleate cis-trans isomerase from thermophilic bacteria.

Several strains of thermophilic bacteria containing maleate cis-trans isomerase were isolated from soil samples and identified as Bacillus stearothermophilus, Bacillus circulans, Bacillus brevis, and Deleya halophila. The maleate cis-trans isomerase was purified and characterized from one of the isolated strains, B. stearothermophilus MI-102. The purified enzyme of strain MI-102 showed higher thermal stability than the enzyme of a mesophile, Alcaligenes faecalis IFO13111. The seven maleate cis-trans isomerase genes (maiA) of thermophile were cloned and sequenced. B. stearothemophilus MI-102 MaiA has 67% amino acid identity with A. faecalis MaiA. All eight amino acid sequences of maiA gene products had significant conserved regions containing cysteine residues, which were previously suggested to be involved in an active site of the enzyme. To probe the catalytic mechanism, three cysteine residues in the conserved regions of A. faecalis MaiA were replaced with serine by site-directed mutagenesis. The results suggest that Cys80 and Cys198 play important roles in the enzyme activity.

Alcaligenes↗

Occlusion of transition metal ions by new adsorbents synthesized from plant polyphenols and animal fibrous proteins.

Removing and collecting heavy and rare metal ions from industrial effluents and waste aqueous solutions are important problems. Our previous studies showed that animal fibrous proteins (AFPs) such as hen eggshell membrane, chicken feather (CF), wool, and silk were stable and insoluble proteins and had an excellent ability to bind not only hard (Mn2+ and Fe3+) but also soft (Ag+, Au+, Pd2+, Pt2+, and Hg2+) acids from aqueous solutions. In this study, we synthesized some adsorbents for transition (Cr6+, Mn2+, Co2+, Ni2+, and Cu2+) and heavy (Cd2+) metal ions from AFPs (gelatin, CF, and wool) and plant polyphenols (lignin and tannin) by heating a mixture of AFPs and plant polyphenols under acidic conditions. In batch experiments, pH profile, time dependency, and isotherm analysis were performed to determine binding properties of adsorbents for transition and heavy metal ions. Column experiments were also performed to remove copper ion from aqueous solution. The results showed that the new adsorbents were effective for collecting and removing transition and heavy metal ions from aqueous solutions.

Animals↗

Sacrococcygeal teratoma with hydrops fetalis and bilateral hydronephrosis.

A 29-year-old Japanese primipara with fetal sacrococcygeal teratoma and hydronephrosis was referred to our department at 22 weeks of gestation. The preload index of the inferior vena cava (PLI) was 0.75 and fetal cardiac failure was suspected at 28 weeks of gestation. The sodium and chloride concentrations and osmolarity of the fetal urine were 96 mEq/L, 81 mEq/L and 204 mOsm/L, respectively, and we predicted a good renal function. Then, a vesico-amniotic shunting operation was performed at 28 weeks of gestation to keep the renal function and PLI decreased 0.41 after this operation. At 30 weeks of gestation, the fetus was delivered by a cesarean section owing to preterm PROM and a huge growing sacrococcygeal teratoma. The baby was female, weighing 2,020 g, and the 1 minute Apgar score was 1. She died almost 7 hours after birth due to respiratory insufficiency. An autopsy confirmed bilateral hydronephrosis, urethral stenosis, sacrococcygeal immature teratoma, and pulmonary hypoplasia. The size of this tumor revealed 80 x 70 x 45 mm in intrapelvic cavity and 130 x 90 x 50 mm out of body, and this tumor was classified as Type II according to the American Academy of Pediatrics Surgery Section classification.

Adult↗

[A case of common variable immunodeficiency with intractable diarrhea and the functional disorder of renal tubules].

We report a case of a 31-year-old woman with common variable immunodeficiency (CVID) complicated with intractable diarrhea and the functional disorder of renal tubules. The patient became hypogammaglobulinemic after she suffered from measles at 6 years of age. She also suffered from lupus-like syndrome at 7 years of age. The complete remission was obtained by glucocorticosteroid treatment. An intravenous immunoglobulin replacement therapy was introduced at 11 years of age, since then her general condition was stable for more than 20 years. When she was 29 years old, she suffered from generalized malaise, anorexia with body weight loss, and numbness of face. The intractable diarrhea as protein loosing syndrome, and the severe abnormality of electrolyte balance with metabolic acidosis as the functional disorder of renal tubules were found. Her condition was not improved by the electrolytes or alkali replacement therapy. She was admitted for further evaluation and treatment. The intractable diarrhea and the functional disorder of renal tubules were dramatically improved after absolute restriction of food intake under hyperalimentation. When she began to take food, the symptom and sign became worse again. The interstitial nephritis and nonspecific inflammation of intestine were found by the tissue biopsy. The most characteristic finding was the infiltration of lymphocytes (predominantly CD 8 + T lymphocytes) in both intestinal mucosa and renal interstitium. The introduction of glucocorticosteroids improved her general condition and biochemical findings. This CVID case is complicated with intractable diarrhea and the functional disorder of renal tubules which is associated with the infiltration of CD 8 + lymphocytes in intestine and kidney. We consider that such case is very rare and valuable to report.

Adult↗