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Biomedical subjects

Y Goto

Publications and source records attributed to Y Goto.

At least 289 records · Page 16Linked to original sources

Properties of rat cone-mediated electroretinograms during light adaptation.

PURPOSE: Our aim was to better understand how to isolate the cone-mediated response in rats. Therefore, we studied the difference of ERGs in the course of light adaptation between 2 and 20 Hz stimulus frequencies. METHODS: A total of 90 rats divided into 18 different groups were used following overnight dark adaptation. ERGs were recorded against 3 different adapting field luminances (1.15, 1. 50 or 1.75 log cd/m(2)) with a combination of 3 stimulus flash intensities (0.86, 1.30 or 2.03 log cd sec/m( 2)). The responses were obtained at 2 minute intervals for 25 minutes of light adaptation. RESULTS: The response of the rat cone ERG was large despite the small number of cones. The mean amplitude increased systematically from the dark-adapted value requiring more than 15 minutes to reach an asymptote at 2 Hz stimulation, but only 10 minutes at 20 Hz stimulation. The 2 Hz adaptation curves had biphasic pattern compared to the monophasic 20 Hz curve. This second increase in the amplitude at 2 Hz appeared at around 7-8 minutes as a function of adaptation time. This tendency was most evident when using a low adapting field luminance with a high flash intensity. CONCLUSIONS: Our results suggest that the rods intrude much more during light adaptation at 2 Hz stimulation in rodents than in humans. Therefore, 20 Hz flicker stimulation can better isolate more the cone-mediated function than 2 Hz stimulation during the course of light adaptation in rats. Furthermore, the functional characteristics of the cone in rats may be different from that in humans.

Adaptation, Ocular↗

Localization of a gene for benign adult familial myoclonic epilepsy to chromosome 8q23.3-q24.1.

Benign adult familial myoclonic epilepsy is an autosomal dominant idiopathic epileptic syndrome characterized by adult-onset tremulous finger movement, myoclonus, epileptic seizures, and nonprogressive course. It was recently recognized in Japanese families. In this study, we report that the gene locus is assigned to the distal long arm of chromosome 8, by linkage analysis in a large Japanese kindred with a maximum two-point LOD score of 4.31 for D8S555 at recombination fraction of 0 (maximum multipoint LOD score of 5.42 for the interval between D8S555 and D8S1779). Analyses of recombinations place the locus within an 8-cM interval, between D8S1784 and D8S1694, in which three markers, D8S1830, D8S555, and D8S1779, show no recombination with the phenotypes. Although three other epilepsy-related loci on chromosome 8q have been recognized-one on chromosome 8q13-21 (familial febrile convulsion) and two others on chromosome 8q24 (KCNQ3 and childhood absence epilepsy)-the locus assigned here is distinct from these three epilepsy-related loci. This study establishes the presence of a new epilepsy-related locus on 8q23.3-q24.11.

Adolescent↗

Oxidation-dependent changes in the stability and permeability of lipid bilayers.

Peroxidation-dependent change in the permeability of lipid bilayers was mesaured by using artificial membrane systems, that is, planar lipid bilayers and liposomes. The unsaturated fatty acyl chains of phospholipids in small unilamellar vesicles were peroxidized time-dependently by the hydroxyl radical chemically generated by the reaction of H2O2 and Cu(en)2. In contrast, at the same hydroxyl radical concentration and time ranges, no ionic current through the planar lipid bilayers and no release of K+ from the liposomes were observed. These findings indicate that accumulation of lipid peroxide within lipid bilayers is not responsible for the permeability increase that is often observed in biomembranes exposed to oxidative stresses. Higher concentration of the hydroxyl radical caused break-down of the planar lipid bilayers composed of the mixture (7:3) of phosphatidylethanolamine (PE) and phosphatidylcholine (PC). The bilayer containing 100% PE at least at one leaflet of the bilayer (facing the hydroxyl radical-generating solution) was not broken-down by the application of the hydroxyl radical, suggesting that PE stabilizes the planar lipid bilayer against the attack of the hydroxyl radical.

Copper↗

Solution structure and dynamics of bovine beta-lactoglobulin A.

Using heteronuclear NMR spectroscopy, we studied the solution structure and dynamics of bovine beta-lactoglobulin A at pH 2.0 and 45 degrees C, where the protein exists as a monomeric native state. The monomeric NMR structure, comprising an eight-stranded continuous antiparallel beta-barrel and one major alpha-helix, is similar to the X-ray dimeric structure obtained at pH 6.2, including betaI-strand that forms the dimer interface and loop EF that serves as a lid of the interior hydrophobic hole. [1H]-15N NOE revealed that betaF, betaG, and betaH strands buried under the major alpha-helix are rigid on a pico- to nanosecond time scale and also emphasized rapid fluctuations of loops and the N- and C-terminal regions.

Amino Acid Sequence↗

Significance of heterogeneous nuclear ribonucleoprotein B1 as a new early detection marker for oral squamous cell carcinoma.

The development of an early tumor detection marker for oral cancer is an obvious need due to the high recurrence rate and poor survival rate. Based on our previous report that overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) B1 protein was found in 100% of squamous cell carcinomas of human lung, we applied the same immunohistochemical method, using anti-hnRNP B1 antibody, to human oral squamous cell carcinoma (OSCC). Seven human tissue sections of OSCC showed strong staining with anti-hnRNP B1 antibody, and hnRNP B1 protein of 37 kDa was identified in protein fractions isolated from six of the cancerous tissue sections, while it was not found in adjacent noncancerous tissue. Moreover, three non-homogeneous (nodular) leukoplakia sections showed significant anti-hnRNP B1 staining. The results suggest that this antibody detects precancerous lesions as well as advanced lesions (stages I to IV) of OSCC. We also present positive results of cytodiagnosis for two smear specimens. All of the above results indicate that hnRNP B1 is a new and useful marker for early detection of OSCC.

Adult↗

Grouping of 20 reference strains of Legionella species by the growth ability within mouse and guinea pig macrophages.

20 Reference strains of Legionella species, isolated from human, were classified according to their ability to grow within thioglycolate-induced peritoneal macrophages of mice and guinea pigs. Inbred and congenic mice were used to study the effect of the natural resistance genes Lgn1 and Bcg that are expressed phenotypically in the mouse macrophages. The Lgn1 gene controlled the intracellular growth of Legionella pneumophila Philadelphia-1 and Legionella jordanis GIFU 12657, but the Bcg gene did not affect the intracellular growth of any organism examined. Based on these results and the growth ability in guinea pig macrophages, the 20 reference strains were divided into four groups. This grouping will help us to understand a variety of modes of interaction between Legionella species and macrophages.

Animals↗

Interspecies transmission of feline immunodeficiency virus from the domestic cat to the Tsushima cat (Felis bengalensis euptilura) in the wild.

Feline immunodeficiency virus (FIV) was isolated from a wild-caught Tsushima cat (Felis bengalensis euptilura), an endangered Japanese nondomestic subspecies of leopard cat (F. bengalensis). Phylogenetic analysis of the env gene sequences indicated that the FIV from the Tsushima cat belonged to a cluster of subtype D FIVs from domestic cats. FIVs from both the Tsushima cat and the domestic cat showed similar levels of replication and cytopathicity in lymphoid cell lines derived from these two species. The results indicated the occurrence of interspecies transmission of FIV from the domestic cat to the Tsushima cat in the wild.

Amino Acid Sequence↗

Plasma adrenomedullin as an indicator of prognosis after acute myocardial infarction.

OBJECTIVE: To elucidate whether prognosis after acute myocardial infarction can be predicted by measuring plasma adrenomedullin, a novel vasorelaxant peptide. PATIENTS AND DESIGN: Plasma adrenomedullin concentrations on day 2 after myocardial infarction were measured in 113 patients with myocardial infarction with other clinical and haemodynamic variables related to mortality. RESULTS: During a mean follow up period of 25 months, 16 patients died of cardiac causes. Plasma adrenomedullin concentrations on day 2 increased significantly in patients with myocardial infarction compared with controls (mean (SD), 12.3 (8.8) v 4.9 (1.0) pmol/l, p < 0.001). Plasma adrenomedullin correlated negatively with left ventricular ejection fraction on admission (r = -0.47, p < 0.001), although it did not significantly correlate with any other haemodynamic variable. By univariate Cox proportional hazards analysis, plasma adrenomedullin, age, coronary reperfusion, maximum creatine kinase concentrations, pulmonary congestion, pulmonary capillary wedge pressure, cardiac index, and left ventricular ejection fraction were all significantly related to mortality. Among the non-invasive variables, only plasma adrenomedullin was an independent predictor of mortality after myocardial infarction (p < 0.05). The Kaplan-Meier survival curves based on the median plasma adrenomedullin concentration (10.3 pmol/l) showed that patients with high plasma adrenomedullin had a higher mortality than those with low plasma adrenomedullin (p < 0.01). CONCLUSIONS: Plasma adrenomedullin on day 2 after myocardial infarction is strongly associated with long term mortality, and thus may complement standard prognostic indicators.

Adrenomedullin↗

Angiotensin-converting enzyme inhibition restores hepatocyte growth factor production in patients with congestive heart failure.

Endothelium-dependent vasodilation is impaired in patients with congestive heart failure. For vascular endothelium, hepatocyte growth factor (HGF) is one of the most potent and specific growth factors, which acts protectively against endothelial dysfunction. HGF production is downregulated by angiotensin II (Ang II) in vitro. We hypothesized that HGF production is impaired as the result of increased Ang II in patients with congestive heart failure, and that if so, the impaired production should be restored with angiotensin-converting enzyme inhibitors (ACE-I). We studied 16 patients with congestive heart failure caused by previous anterior myocardial infarction in whom left ventricular ejection fraction was 35+/-8% (mean+/-SD). Before and approximately 4 weeks after the treatment with ACE-I, blood samples were collected to measure the levels of HGF, Ang II, and brain natriuretic peptide as a biochemical marker for severity of heart failure. We also studied 5 control subjects, in whom heparin increased HGF production to 48+/-5-fold. However, in patients with heart failure, HGF response to heparin was significantly attenuated (24+/-5-fold, P<0.05 vs control). Therapy with ACE-I decreased the levels of Ang II and brain natriuretic peptide and restored HGF production in response to heparin by 43+/-7-fold, comparable to the control response. In conclusion, impaired HGF production was restored after the treatment with ACE-I probably by the mechanism of Ang II suppression. This novel effect of ACE-I may contribute to the clinical improvement in patients with heart failure and thereby may have an important therapeutic implication.

Aged↗

In vitro reconstitution of the tracheal epithelium.

We have developed a unique in vitro reconstitution system for tracheal epithelia of guinea pigs. In the system, a human amnion membrane was used as a basement membrane and the tracheal epithelial cells were cultured on the epithelial side of the membrane. Three weeks later, the tracheal fibroblasts were co-cultured on the serosal side of the amnion membrane and the culturing was continued for an additional 10 d. The morphology of the cultured epithelial cells consisted of a pseudostratified columnar ciliated epithelium from cuboidal ciliated epithelium during the last 10 d of the culture period. Epithelial cells included both goblet-like and basal cells. In addition, the frequency of each type of differentiated cells was almost identical to that of in vivo tracheas. Interestingly, the same results were obtained when the conditioned medium of the tracheal fibroblasts was used instead of the fibroblasts themselves. These results suggest that epithelial-mesenchymal interaction is likely involved in growth and differentiation of epithelial cells in vivo in a soluble factor(s)-mediated manner. As well as the epithelial cells, the fibroblasts also formed a multilayer during the last 10 d of co-culturing. This indicates that in vitro reconstitution of tracheal epithelia is achieved without addition of any exogenous growth or differentiation factors. The reconstitution system is shown to be useful for investigating the cellular and molecular interaction of epithelial and mesenchymal cells. Possible applications of the culture system and possible factors involved in growth and differentiation of epithelial cells are discussed.

Amnion↗

Does coronary artery morphology predict favorable results of intracoronary thrombolysis in patients with unstable angina pectoris?

The efficacy of intracoronary thrombolysis (ICT) for unstable angina pectoris (UAP) has been limited, despite the similar pathogenesis between UAP and acute myocardial infarction. To ascertain the subset of UAP suitable for ICT, the clinical responses to ICT were assessed in patients with UAP. Eighty-2 patients with medically refractory angina were divided into 2 groups according to the coronary artery morphology of the culprit lesion before ICT: (1) lesions with acute cut off and/or filling defects (AC) and (2) lesions with a tapered shape (TA). The TIMI flow grade was determined from coronary angiograms before and immediately after ICT. The diameter stenosis (%DS) and minimal lumen diameter (MLD) of the culprit lesion were determined using quantitative coronary angiographic analysis before and immediately after ICT. In addition, inhospital cardiac event rates including urgent/emergency coronary angioplasty or bypass surgery, nonfatal myocardial infarction or cardiac death were compared between the 2 groups. Multivariate logistic regression analysis was performed using 13 clinical factors contributing to successful ICT. The results showed that all 3 coronary angiographic parameters (TIMI flow, %DS, and MLD) significantly improved in the AC group (p<0.01, p<0.01 and p<0.05, respectively), whereas none of these parameters improved in the TA group. The inhospital cardiac event rate after ICT was significantly higher in the TA group (76%) than in the AC group (48%; p=0.016). Odds ratio predicting successful ICT was 7.09 (p<0.01) for the AC lesion, and 2.54 (p<0.01) for new angina. In conclusion the AC lesions are more commonly associated with coronary thrombosis that responds to ICT than are the TA lesions. Thus, the coronary angiographic morphology may be an important predictor for a successful ICT in patients with medically refractory UAP.

Aged↗

Role of cytokines and adhesion molecules in ischemia and reperfusion in patients with acute myocardial infarction.

Although acute myocardial infarction (AMI) may involve both plaque rupture and ischemia-reperfusion injury, the pathogenesis of these phenomena is unclear. To elucidate the pathogenesis of AMI, serial measurements of platelet activating factor (PAF), interleukin-6 and cell adhesion molecules were made in patients with AMI. The PAF levels were measured upon hospital admission and at 24 and 72h in 8 patients with AMI. Serum levels of interleukin-6, soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule- 1 (sVCAM- 1) were measured upon admission and at 24 h and 4 weeks in 30 patients with AMI and 15 patients with stable effort angina. PAF levels were higher in patients with AMI than in normal volunteers; the increased levels lasting at least 72h. In contrast, interleukin-6 increased at 24h. sE-selectin was elevated at admission and sVCAM-1 increased later. sE-selectin levels upon admission in patients with additional ST-segment elevation after reperfusion were significantly higher than those in patients without ST-elevation. In patients with AMI, the time-course of changes in blood levels of cytokines varied according to the individual substances. Although it is unclear what is the precise role of each of the cytokines in the pathophysiology of AMI, sE-selectin may be possibly related to the reperfusion injury in the infarcted myocardium.

Acute Disease↗

Sequence analysis and expression of Nramp-1 gene in Bcgr and Bcgs mice.

Nucleic acid sequence of complemental DNA open reading frame for Nramp-1 gene was compared among DBA/2 (Bcgr), C57BL/6 (Bcgs) and C57BL/6-Bcgr mice which was previously developed as M. avium-resistant mouse strain (Xu, et al. Veterinary Microbiology 50:73-79 (1996). Total RNA was isolated from various organs of DBA/2, C57BL/6 and C57BL/6-Bcgr. Nramp-1 cDNA was constructed from their mRNAs by gene amplification (PCR) technique and their open reading frame sequences were compared. The results clearly showed that our C57BL/6-Bcgr was almost identical with the DNA sequence of the DBA/2 mice. In contrast, C57BL/6-Bcgs mice differed only on the substitution of adenine for guanine of the nucleic acid at position 596. This corresponded to the site of amino acid substitution (glycine to asparate) at position 169 in predicted NRAMP which had been reported. The expression of Nramp-1 mRNA was more prominent in spleens and livers and there appeared to be no significant difference among the strains of mice.

Animals↗

Dominant distribution of mitochondrial DNA from recipient oocytes in bovine embryos and offspring after nuclear transfer.

In the process of nuclear transfer, heteroplasmic sources of mitochondrial DNA from a donor cell and a recipient oocyte are mixed in the cytoplasm of the reconstituted embryo. The distribution of mitochondrial DNA heteroplasmy in nuclear transfer bovine embryos and resultant offspring was investigated by measuring polymorphism in the displacement loop region of mitochondrial DNA using PCR-mediated single-strand conformation polymorphism. Most offspring (20 of 21 calves) from recipient oocytes of undefined mitochondrial DNA genotypes showed different genotypes from the mitochondrial DNA of donor cells. The single calf that was an exception showed heteroplasmy, including the donor mitochondrial DNA genotype. Six cloned calves were produced from oocytes of a defined mitochondrial DNA genotype. All of these clonal members and various tissues showed only the mitochondrial DNA genotype derived from the oocyte. The mitochondrial DNA from donor cells appeared to be eliminated during early embryonic development; it gradually decreased at the early cleavage stages and was hardly detectable by the blastocyst stage. These results indicate that the genotype of mitochondrial DNA from recipient oocytes may become the dominant category of mitochondrial DNA in calves resulting from nuclear transfer.

Animals↗

Influence of calcium antagonists on long-term survival of patients treated with coronary angioplasty.

A meta-analysis reported that nifedipine increased mortality dose-dependently in patients with coronary artery disease. However, there have been few studies (specifically in Asians) on the long-term prognosis of patients treated with calcium antagonists after successful coronary angioplasty (PTCA). The subjects consisted of 583 consecutive patients (461 males, aged 59 +/- 10), who underwent successful elective PTCA between 1985 and 1990. First, they were divided into two groups; the calcium antagonist (+) group (n = 560) and the calcium antagonist (-) group (n = 23), and were evaluated in terms of total survival and cardiac events. Second, the calcium antagonist (+) group was further divided into 4 groups according to calcium antagonist type, i.e., short-acting nifedipine group (n = 156), long-acting nifedipine group (n = 203), diltiazem group (n = 184) and the other group (n = 17), and these groups were evaluated in the same way. The primary end-point was set as death from any cause. Secondary end-points were any cardiac events, including non-fatal acute myocardial infarction, coronary artery bypass surgery and repeat PTCA. The mean follow-up period was 4.5 +/- 1.8 years. A multivariate analysis was performed with the Cox proportional-hazard model. The Kaplan-Meier analysis showed that the calcium antagonist (-) group had significantly worse prognoses than the calcium antagonist (+) group (p < 0.05), and that there was no significant difference among the prognoses of the four calcium antagonists groups. The multivariate analysis revealed that the use of a calcium antagonist was one of the independent factors positively contributing to the prognosis. The use of any type of calcium antagonist did not increase mortality in patients who underwent successful elective PTCA, rather, it contributed to a favorable outcome.

Aged↗

Relation with preoperative fructosamine and autonomic nerve function and blood pressure during anesthesia in diabetics: a retrospective study.

Many diabetics may have a high risk involving the cardiovascular system. In an attempt to predict the intraoperative risks of diabetics during anesthesia, we evaluated retrospectively the relationship among the biochemical assay or autonomic nerve function obtained as parts of the preoperative examination, and the blood pressure changes relating to the stimulation of intubation and extubation for anesthesia. In 40 diabetic surgical patients examined the biochemical assay (HbA1c, fructosamine level and blood glucose level) beforehand, the autonomic nerve function was quantified preoperatively by analysis of ECG R-R variability recorded in supine and subsequent standing position using an HRV analyzer, and some parameters of autonomic nerve function especially responsive sympathetic nerve activities were obtained. We assessed the correlation with systolic blood pressure changes in these cases at intubation for general anesthesia comparing to similar conditioned 40 non-diabetics. A diabetics with low vagal activity became larger systolic blood pressure afterdrop at tracheal intubation for anesthesia (r=0.513, p<0.001). Otherwise the blood pressure afterdrop at extubation became larger in a non-diabetics with high sympathetic activity (r=0.502, p<0.001). The preoperative fructosamine concentration in diabetics correlated positively with the responsive sympathetic nerve irritability index; "mRR(sup)-RRmin(std)" (r=0.432, p<0.05) and the responsive sympathetic nerve excitability index; "mRR(sup-std)" (r=0.448, p<0.05). However HbA1c had no correlation with these parameters of autonomic nerve function and blood pressure rise at tracheal intubation. Because of above correlation with blood pressure rise at intubation for anesthesia induction, the preoperative fructosamine examination and the responsive sympathetic nerve function test must be useful preoperative examination for detection of the unexpected heart events of diabetic patients during operation.

Aged↗

Pharmacological effects of a novel recombinant hirudin, CX-397, in vivo and in vitro: comparison with recombinant hirudin variant-1, heparin, and argatroban.

The novel recombinant hirudin analog CX-397 was investigated with respect to its pharmacological activity and antithrombin profiles in vivo and in vitro. In three different types of thrombosis models in rats, including stasis and thrombin-induced venous, glass surface-activated arterio-venous shunt, and ferric chloride-induced arterial thrombosis models, CX-397 and rHV-1 elicited potent antithrombotic effects, where the minimum effective doses of rHV-1 tended to be higher than those of CX-397 in the arterio-venous shunt and arterial thrombosis models. The hemorrhagic risk of CX-397 in template bleeding in rats was not higher than that of rHV-1, indicating that CX-397 is superior to rHV-1 for treating the platelet-dominant type of thrombosis. However, no differences were detected between CX-397 and rHV-1 in their effects on in vitro coagulation times and thrombin-induced platelet aggregation, suggesting the possibility that some unknown mechanisms other than simple thrombin inhibition are also involved in their antithrombotic actions.

Amino Acid Sequence↗

[Estimation of left internal thoracic artery flow reserve after coronary artery bypass grafting using Doppler flow wire].

The usefulness of the left internal thoracic artery (LITA) for aortocoronary bypass grafting is now established. Reports of variation in LITA graft function are rare. Graft flow was measured using a Doppler flow wire to estimate graft function in 27 patients (24 males, 3 females) who underwent LITA grafting to the left anterior descending artery. Patients were classified into the following 3 groups: Group A consisted of 9 patients with normal left ventricular function and no native flow; Group B consisted of 11 patients with normal ventricular function and good native flow; Group C consisted of 7 patients with abnormal left ventricular function and no native flow. LITA graft function was also estimated 1 year after operation in 12 of these 27 patients (4 in each group). Diastolic/systolic velocity ratio (DSVR) and flow reserve were determined in the proximal, middle, and distal portions of the LITA graft and native left anterior descending artery before and after papaverine administration (8-10 mg). DSVR was significantly higher in the distal portion than in the proximal portion (p < 0.01), but this value did not change after papaverine administration. After 1 year, DSVR in the proximal portion was significantly higher in Group C than in Groups A or B (p < 0.05 for both). Four weeks after operation, the flow reserve of the distal portion was significantly higher in Group A than in Group C (p < 0.001). After 1 year, this value was significantly higher in Group A than in either Groups B or C (p < 0.01, p < 0.001, respectively). The rate of increase in flow reserve in the distal portion was significantly greater in Group A (23.4%) than in groups B (2.53%) or C (1.94%; p < 0.05 for both). The distal portion of the LITA was the best measurement site, since the flow pattern in the LITA graft varied throughout all portions. Diastolic flow velocity in the LITA graft was dominant in patients with myocardial damage. The results indicate that flow reserve of the LITA graft depends on antegrade native coronary flow and distal myocardial damage.

Coronary Artery Bypass↗