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Biomedical subjects

Y Ohta

Publications and source records attributed to Y Ohta.

At least 73 records · Page 4Linked to original sources

Atrial fibrillation impairs endothelial function of forearm vessels in humans.

BACKGROUND: Although there have been many studies on the effects of atrial fibrillation (AF) on cardiac function, few studies have been done on its effects on endothelial function. The present study was designed to examine the effects of AF on endothelial function in human subjects. METHODS AND RESULTS: Changes in forearm blood flow (FBF) induced by acetylcholine and nitroglycerin were measured by using plethysmography in 14 patients with lone AF, 13 patients with AF and underlying heart disease, and 12 normal control subjects. In the patients, these measurements were repeated after cardioversion. Although baseline FBF was the same in the 3 groups, acetylcholine-induced increases in FBF were significantly smaller in both patient groups than in the control group, and FBF increases were particularly depressed in AF patients with underlying heart disease. After restoration of sinus rhythm by cardioversion, FBF response to the highest dose of acetylcholine increased by 46% in patients with lone AF (n = 10) and by 90% in AF patients with underlying heart disease (n = 11). Nitroglycerin-induced vasodilatation was the same in all 3 groups and was not affected by cardioversion. CONCLUSIONS: These findings suggest that endothelium-dependent vasodilatation is impaired by AF and improves after sinus rhythm is restored.

Acetylcholine↗

Can tumor size be a guide for limited surgical intervention in patients with peripheral non-small cell lung cancer? Assessment from the point of view of nodal micrometastasis.

OBJECTIVE: We sought to determine the critical diameter of a peripheral non-small cell lung cancer tumor less than which no evidence of nodal micrometastasis is present. METHODS: Samples of 3081 lymph nodes from 181 patients with stage I peripheral lung cancer (155 with adenocarcinoma and 26 with squamous cell carcinoma) who had undergone complete resection with systematic lymphadenectomy were used in the study. In the samples immunohistochemical staining for cytokeratin was performed. The expression of vascular endothelial growth factor (VEGF) at primary sites was also immunohistochemically assessed. RESULTS: Nodal micrometastasis was detected in 44 patients. The mean tumor sizes were 2.2 +/- 1.3 cm (range, 1.0-7.0 cm) in nodal micrometastasis-positive adenocarcinoma, 2.1 +/- 0.9 cm (range, 0.5-6.0 cm) in nodal micrometastasis-negative adenocarcinoma, 4.8 +/- 2.3 cm (range, 2.2-10.0 cm) in nodal micrometastasis-positive squamous cell carcinoma, and 3.2 +/- 2.1 cm (range, 0-9.0 cm) in nodal micrometastasis-negative squamous cell carcinoma. The tumor size in the nodal micrometastasis-positive group tended to be greater than that in the nodal micrometastasis-negative group in squamous cell carcinomas, but there was no significant difference in adenocarcinomas. Nodal micrometastasis was not found in patients with squamous cell carcinoma of 2.0 cm or less in diameter. However, nodal micrometastasis was found in 20% (19/95) of the patients with adenocarcinoma of 1.1 to 2.0 cm in diameter and even in 4 of 11 patients with adenocarcinoma of 1.0 cm or less. Among the patients with nodal micrometastasis, survival of patients with vascular endothelial growth factor overexpression was worse than that of patients without it. The survival of patients with nodal micrometastasis without vascular endothelial growth factor overexpression was comparable with that of patients without nodal micrometastasis. CONCLUSION: A limited surgical intervention without lymphadenectomy is validated for squamous cell carcinoma of 2.0 cm or less without pleural involvement. In adenocarcinoma the tumor size itself is not a reliable guide for nodal micrometastasis status. In patients with nodal micrometastasis with vascular endothelial growth factor overexpression, the risk of systemic disease should be considered.

Adenocarcinoma↗

Focal cerebral hyperemia in postconcussive amnesia.

Transient amnesia caused by minor head injury is commonly encountered in daily neurosurgical practice, but the mechanism of such amnesia has not been extensively studied. We measured the regional cerebral blood flow (rCBF) of patients with postconcussive amnesia with Xe/CT CBF to examine whether a focal disturbance of CBF exists. The Xe/CT CBF study was performed in eight patients with closed head injury without organic cerebral lesion while they were suffering from posttraumatic amnesia (concussion group). The time interval between accident and CBF measurement was less than 2 h in three patients, 5-6 h in two, 8-9 h in two, and 18 in one. The results were compared with those of nine normal volunteers and eight other age-matched patients who recovered without any neurological deficit despite the presence of hemorrhagic regions (mild hemorrhage group). The rCBF of the concussion group was significantly elevated in the bilateral mesial temporal cortex in comparison to the normal group. The rCBF in the mild hemorrhage group was lower than that of normal controls in all regions. The analysis of right-left difference in CBF indicated that there was significant asymmetry (right > left) in the frontal and temporal cortex in the concussion group, but not in the normal and mild hemorrhage group. This Xe/CT CBF study in acute stages of cerebral concussion, in which patients were amnestic, detected focal cerebral hyperemia. Such hyperemia in regions closely related to human memory function may be the result of vasoparalysis or the compensatory activation of memory circuits after denervation injury.

Adolescent↗

Optimum site for in ovo amino acid injection in broiler breeder eggs.

Three experiments were conducted to evaluate the effect of differences in in ovo amino acid (AA) injection sites in broiler breeder eggs on subsequent hatchability and BW of chicks. In Experiment 1, an AA solution was injected into eggs with 13-mm or 19-mm, 27-ga needles. Uninjected eggs served as controls. Hatchability was decreased (P < 0.05) in eggs receiving AA injections with the 19-mm needle in comparison to the control and 13-mm-injected groups. However, BW of chicks increased (P < 0.05) relative to pre-incubational egg weight by AA injection with the 13-mm needle. In order to evaluate the in ovo location of AA injections from Experiment 1, India ink was injected into eggs in Experiment 2 with a 13-or 19-mm needle. Immediately after injection, the air cell end of the egg was windowed in order to observe effects of injection site. Windowing of eggs was accomplished by removing a piece of the eggshell over the air cell and the underlying membrane at Day 7 of incubation. The amount of injected India ink was higher in the extra-embryonic coelom in eggs treated by both needles. However, the occurrence of India ink in the extra embryonic coelom was higher (P < 0.05) in the group injected with AA solution using a 13-mm needle as compared to that after injection using a 19-mm needle. The observation of India ink in the amniotic cavity was higher (P < 0.05) in the group injected with AA solution using a 19-mm needle rather than that using a 13-mm needle. In Experiment 3, treatments consisted of control (uninjected eggs) or windowed eggs. Windowed eggs received AA to the chorioallantoic membrane, the yolk, extra-embryonic coelom, or amniotic cavity at Day 7 of incubation. Hatchability was reduced, but chicks hatched when eggs were windowed and when AA were injected into the yolk sac or extra-embryonic coelom. However, chicks did not hatch when AA were administered to the chorioallantoic membrane or into the amniotic cavity. These results suggest that the best AA injection sites in ovo may be the yolk and extra-embryonic coelom.

Amino Acids↗

Embryo growth and amino acid concentration profiles of broiler breeder eggs, embryos, and chicks after in ovo administration of amino acids.

Two experiments were conducted to evaluate the effect of in ovo amino acid (AA) injections in broiler breeder eggs on AA utilization of embryos. All AA used in these experiments were pure crystalline AA in free-base form. Treatments in Experiment 1 comprised 1) control eggs (no injection), 2) 0.5 mL sterile-distilled water injected eggs, and 3) eggs injected with an AA solution suspended in 0.5 mL sterile-distilled water. Injections were administered into the yolk at Day 7 of incubation. At hatch, chicks were killed and bled, and plasma AA concentration was determined. Plasma AA concentration of hatched chicks decreased (P < 0.05) when water was injected. In addition, all AA from eggs injected with AA, except Glu and Lys, were decreased (P < 0.05) at hatch as compared to control eggs. However, AA pattern was not affected by in ovo water injection, but the AA ratio to Lys was reduced by in ovo AA injection. Experiment 2 was conducted to evaluate whole internal egg AA concentrations over incubation time in the presence or absence of in ovo AA administration. Treatments in Experiment 2 comprised 1) control eggs (no injection), and 2) eggs injected with a AA solution at Day 7 of incubation. The AA contents of embryo, yolk, albumen, and allantoic and amnion fluids were analyzed over time during incubation (Days 0, 7, 14, and 19 of incubation). On Day 14 of incubation, there were no differences in AA contents of all tissues between the control group and the group injected with AA on Day 7 of incubation. On Day 19 of incubation, AA contents of embryo, yolk, albumen, and allantoic and amnion fluids were increased (P < 0.05) as mediated by in ovo administration of AA at Day 7 of incubation. These results suggest that in ovo administration of AA may increase AA concentrations in chicken embryos and other egg contents.

Amino Acids↗

Inhibition of progression of heart failure and expression of TGF-beta 1 mRNA in rats with heart failure by the ACE inhibitor quinapril.

The cardioprotective effects of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of heart failure. Twenty-six rats were divided into two groups: one given 20 mg/kg/day quinapril (n = 11), and controls given 0.5% methylcellulose (n = 15). After oral administration for 1 month, quinapril reduced heart weight (from 1.28+/-0.05 to 0.87+/-0.02 g; p < 0.05) without changing body weight. Quinapril lowered left ventricular end-diastolic pressure (from 14.1+/-2.0 to 6.6+/-1.5 mmHg; p < 0.05) and central venous pressure (from 2.7+/-0.9 to 0.7+/-0.4 mmHg), and increased +/- dP/dt (from +2409+/-50 to +3569+/-169 mmHg/s, and from -2318+/-235 to -3960+/-203 mmHg/s; both p < 0.01). The area of myocardial fibrosis was markedly reduced by quinapril (6+/-3%) as compared with controls (29+/-6%; p < 0.01). Expression of transforming growth factor (TGF)-beta1 mRNA was markedly increased in controls as compared with age-matched normal rats. The increase in level of TGF-beta1 mRNA was significantly suppressed by quinapril (from 17.1+/-6.2 to 9.00+/-2.40; p < 0.05). These observations indicated that quinapril has cardioprotective effects on heart failure, and that the beneficial effects may be partly explained by attenuation of fibrotic response through suppression of TGF-beta1 mRNA expression.

Administration, Oral↗

Bisoprolol improves survival in rats with heart failure.

The cardioprotective effects of bisoprolol were studied in a rat model of severe heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization, Lewis rats were divided into four groups: 0.1 mg/kg/day bisoprolol (Group 0.1), 1.0 mg/kg/day bisoprolol (Group 1) and 10 mg/kg/day bisoprolol (Group 10), and vehicle (0.5% methylcellulose; Group V) (all groups, n = 13). After oral administration for 1 month, heart weight, mean blood pressure, heart rate, central venous pressure, peak left ventricular pressure, left ventricular end-diastolic pressure, +/- dP/dt, and area of fibrosis were measured. Although bisoprolol reduced heart rate (399+/-11/min in Group V, 382+/-10/min in Group 0.1, 348+/-8/min in Group 1 and 302+/-9/min in Group 10) and increased survival (62% in Group V, 69% in Group 0.1, and 100% in Group 1 and Group 10) in a dose-dependent manner, this drug did not change heart weight, the area of myocardial fibrosis or hemodynamic parameters. These observations suggested that bisoprolol may improve survival independently of its effect on left ventricular function by reducing sudden death in patients with severe heart failure.

Adrenergic beta-Antagonists↗

Reduction of cardiac norepinephrine improves postischemic heart function in stroke-prone spontaneously hypertensive rats.

Although mammalian ventricle is richly supplied with adrenergic nerves, endogenous norepinephrine is not essential to the intrinsic contractility of the normal heart. However, it is not clear whether acute changes in cardiac norepinephrine could alter heart function in genetically hypertensive rats. The purpose of this study was to examine the effect of cardiac norepinephrine reduction on basal and postischemic heart function in stroke-prone spontaneously hypertensive rats (SHRSPs) using an isolated working heart preparation. Hypertrophied hearts of SHRSPs showed higher cardiac norepinephrine content and impaired heart function at 4 months of age as compared with normal Wistar-Kyoto rats. Poor postischemic recovery of heart function observed in SHRSPs was accompanied by large amounts of coronary norepinephrine overflow. Cardiac norepinephrine reduction or depletion did not affect basal heart function in SHRSPs. Considerable reduction in cardiac norepinephrine with acute reserpine injection (5 mg/kg) in SHRSPs significantly improved postischemic recovery of cardiac output, coronary flow, and rate-pressure product. However, complete norepinephrine depletion with reserpine (10 mg/kg) was detrimental to myocardial automaticity and limited the postischemic recovery of systolic function in the hypertrophied hearts. These results suggest that acute reduction in cardiac norepinephrine may be of potential therapeutic importance to postischemic dysfunction in the hypertrophied hearts.

Animals↗

Pseudomonas putida CE2010 can degrade biphenyl by a mosaic pathway encoded by the tod operon and cmtE, which are identical to those of P. putida F1 except for a single base difference in the operator-promoter region of the cmt operon.

Psudomonas putida CE2010 can assimilate biphenyl despite its high similarity to P. putida F1. Biphenyl degradation in strain CE2010 was achieved using a mosaic of pathways consisting of the cmt and tod operons. CmtE hydrolysed 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid, the meta-cleavage product of 2,3-dihydroxybiphenyl. This enzyme was expressed differently in strains CE2010 and F1. A cmtE disruption mutant, a tod operon disruption mutant and a cmt operon disruption mutant were unable to utilize biphenyl. The introduction of the cmtE gene enabled the cmt operon disruption mutant to grow on biphenyl. A single base difference was found in the cmt promoter-operator region in strain CE2010, compared with that of strain F1. CymR protein was purified from Escherichia coli and binding assays were performed, the results of which suggested that the protein bound less strongly to the CE2010 operator sequence than to the F1 operator sequence. Exchanging the F1 promoter-operator fragment into strain CE2010 resulted in a loss of biphenyl degradation capacity. These results indicate that cmtE is not effectively repressed by CymR in strain CE2010, leading to low constitutive expression and, therefore, low growth on biphenyl.

Bacterial Proteins↗

The predictive value of vascular endothelial growth factor and nm23 for the diagnosis of occult metastasis in non-small cell lung cancer.

We assessed the association of vascular endothelial growth factor (VEGF) and nm23 expression with occult micrometastasis in lung cancer. As destination sites for micrometastasis, we scrutinized lymph node (LN) and bone marrow (BM) specimens. For LN, 122 stage I patients who had received curative operations were studied. As regards BM, 203 patients in stage I - IV who underwent operations were registered. Immunohistochemical anti-cytokeratin staining was used to detect microdissemination of cancer cells. The VEGF and the nm23 expression at the primary sites were immunohistochemically studied in 285 cases in total. The percentages of the patients with microdissemination were 28.7% for LN and 42.4% for BM. The outcome for the patients with LN or BM microdissemination was significantly worse than that for patients without it. The increased VEGF and the decreased nm23 expression within primary tumors were significantly associated with LN and BM microdissemination. The results indicate possible value of using these biological markers to predict the risk of systemic micrometastasis in non-small cell lung cancer.

Adenocarcinoma↗

Discordance between cerebral oxygen and glucose metabolism, and hemodynamics in a mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode patient.

A patient with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode (MELAS) syndrome underwent serial measurement of cerebral blood flow with xenon computed tomography (Xe-CBF) while presenting with strokelike episodes accompanied by a cerebral lesion. He underwent positron emission tomography (PET) measurement of the regional cerebral blood flow (PET-CBF), metabolic rate of oxygen (CMRO2), and glucose (CMRGlu) after his symptoms and lesion disappeared. During the symptomatic period, Xe-CBF and the Xe-CBF response to acetazolamide loading were well preserved both in and outside the low-density lesion. In the PET study, decreased CMRO2 and increased PET-CBF and CMRGlu were noted in the entire brain. The strokelike episodes of patients with MELAS are more likely attributed to the failure of oxygen metabolism than to a vascular accident.

Acetazolamide↗

Rapid detection of Brevibacillus formosus BN53-1 in chicken feces.

Here we describe a rapid method for detecting the hydrogen sulfide-decomposing bacterium Brevibacillus formosus BN53-1 in chicken feces. The method, which can be adapted to the specific detection of a variety of useful eubacteria, is based on blot hybridization and polymerase chain reaction (PCR), and makes use of the genus or species hypervariable region of eubacterial 16S rDNA. The approximate limit of detection under the conditions we tested was 1.0 x 10(3) cells in 10 mg of chicken feces.

Animals↗

Binding activity of natto (a fermented food) and Bacillus natto isolates to mutagenic-carcinogenic heterocyclic amines.

The fermented food, whole meal Natto, viscous polymeric material from Natto, Natto bean, cooked soya bean, and 28 bacterial isolates from Natto were studied for their binding capacity to foodborne mutagenic-carcinogenic heterocyclic amines. The mutagenic heterocyclic amines used were Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole); Trp-P-2 (3-amino-1-methyl-5H-pyrido(4,3-b)indole); Glu-P-1 (2-amino-6-methyldipyrido(1,2-a:3'2'-d)imidazole); PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine); IQ (2-amino-3-methylimidazo(4,5-f)quinoline); MeIQ (2-amino-3,4-dimethylimidazo(4,5-f)quinoxaline); MeIQx (2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline); and MeAalphaC (2-amino-3-methyl-9H-pyrido(2,3)indole). The lyophilized Natto and other fractions of Natto exhibited high binding activity towards Trp-P-1, Trp-P-2, PhIP, and MeAalphaC, while Glu-P-1, IQ, and MeIQ were not effectively bound. The binding capacity of bacterial isolates (Bacillus natto) were isolate-mutagen dependent. Heat treated lyophilized cells, cell wall, and cytoplasmic contents of the bacterial isolate with the highest binding capacity were analyzed for their ability to bind different heterocyclic amines. The results indicate the importance of the cell wall in binding to heterocyclic amines, whereas the cytoplasmic contents were less effective. Heat-treated cells were not much different from that of viable cells in their binding. The impact of different factors, such as pH, incubation time, metal ions, different concentrations of sodium chloride and alcohol, various enzymes, and acetylation of mutagens on binding of Trp-P-1 and IQ, were discussed. The significance of the present results is also discussed from the viewpoint that Natto, a fermented food, is able to scavenge dietary mutagenic heterocyclic amines through binding.

Amines↗

Genetic polymorphism of the MxA gene promoter and interferon responsiveness of hepatitis C patients: revisited by analyzing two SNP sites (-123 and -88) in vivo and in vitro.

We have previously reported a single nucleotide polymorphism (SNP) at nucleotide (nt) position -88 (G or T) within an interferon-stimulated response element-like sequence in the promoter region of the MxA gene, which correlated with responsiveness of hepatitis C patients to interferon. Upstream of it, we then identified another SNP (C or A at nt -123) and investigated whether this SNP also correlates with interferon responsiveness. The two SNPs showed a high linkage to each other: all the individuals having G at -88 had C at -123, and 73% of those having T at -88 had A at -123. As was expected from this observation, the SNP at -123 also exhibited a correlation with interferon responsiveness (C/C homozygotes were more frequent among nonresponders than among responders: 65% of 107 vs. 40% of 52, p = 0.0028). These in vivo data from patients were further supported by results from in vitro experiments. The MxA promoter sequence with A at -123 and T at -88 showed about 4-fold higher activity of upregulating the downstream reporter gene than that with C at -123 and G at -88, in a luciferase reporter assay.

GTP-Binding Proteins↗

Bronchial sleeve resection with complete preservation of the lung for carcinoma.

Conservative sleeve resection with complete preservation of the lung parenchyma is very rarely applicable for the treatment of bronchial carcinomas. We used this surgical procedure in four patients with bronchial carcinoma in various sites of the central airway, and we obtained successful results. The pathological types were two squamous cell carcinomas and two low-grade malignant tumors (mucoepidermoid carcinoma and adenoid cystic carcinoma). If patients are properly selected, this operative procedure appears to be a safe and radical therapeutic option for the treatment of bronchial neoplasms arising from major bronchi.

Adult↗

Globosal basal cells are identified as proliferating cells in mouse olfactory epithelium.

Although anti-bromodeoxyuridine (BrdU) antibodies are used for detecting proliferating cells, they may stain proliferating cells in phases following the S-phase, except for G1. Anti-Ki67 antibodies are widely used for detecting proliferating cells in all phases of the cell cycle (G1-, S-, G2-, and M-phase), but not in resting cells (G0-phase). Anti-cyclin D1 antibodies are used to detect proliferating cells in the G1-phase. The present study investigated the olfactory epithelium of mice by double immunostaining using antibodies to BrdU, Ki67. cyclin D1, and cytokeratin 14 (CK14). The cells positive to the anti-BrdU antibody, the anti-Ki67 antibody, and the anti-cyclin D1 antibody differed from the cells positive to the anti-CK14 antibody. Thus, we confirmed that the proliferating cells in all the phases of the cell cycle, including the G1-phase, were globosal basal cells, which were the precursors of the olfactory cells.

Animals↗

Neurosteroid synthesis by cytochrome p450-containing systems localized in the rat brain hippocampal neurons: N-methyl-D-aspartate and calcium-dependent synthesis.

Neurosteroidogenesis has not been well elucidated due to the very low level of steroidogenic proteins in the brain. Here we report the first demonstration of the neuronal localization of neurosteroidogenic systems as well as the regulation of neurosteroidogenic activity in the adult rat hippocampus. Significant localization of cytochrome P450scc was observed in pyramidal neurons and granule neurons by means of immunohistochemical staining of slices. We also observed the colocalization, in hippocampal neurons, of P450scc with redox partners, hydroxysteroid sulfotransferase and steroidogenic acute regulatory protein. The distributions of astroglial cells and oligodendroglial cells showed very different patterns from that of the P450scc-containing cells. The expression of P450scc, redox partners, the sulfotransferase, and steroidogenic acute regulatory protein was also confirmed by Western blot analysis. The process of active neurosteroidogenesis was stimulated by exposing neurons to N-methyl-D-aspartate. Upon stimulation with N-methyl-D-aspartate, Ca(2+) influx through the N-methyl-D-aspartate subtype of glutamate receptors occurred, and significant net production of pregnenolone and pregnenolone sulfate was observed in the hippocampus. This neurosteroid production was considerably suppressed by the addition of antagonists of N-methyl-D-aspartate receptors, by Ca(2+) depletion, or by the addition of an inhibitor of P450scc. Upon stimulation with N-methyl-D-aspartate, the processing of full-length steroidogenic acute regulatory protein (37-kDa) to the truncated 30-kDa steroidogenic acute regulatory protein was observed. Taken together, these observations imply that hippocampal neurons synthesize neurosteroids. This synthesis may be stimulated and regulated by glutamate-mediated synaptic communication.

Animals↗