Biomedical subjects

Y Ina

Publications and source records attributed to Y Ina.

At least 19 recordsLinked to original sources

PubMed2000

Benidipine inhibits apoptosis during ischaemic acute renal failure in rats.

We have investigated the effects of benidipine (hydrochloride), a calcium antagonist, against ischaemic acute renal failure in rats. Using histological examination, we studied whether the inhibition of apoptosis was associated with the protective effects of benidipine on the ischaemic renal injury. Acute renal failure was induced by the unilateral clamping of the left renal artery for 60 min, followed by reperfusion and contralateral nephrectomy. Drugs were given intravenously 5 min before the unilateral clamping. Prophylactic administrations of benidipine (10 microg kg(-1), i.v.) significantly ameliorated the development of renal failure as estimated by the measurements of serum creatinine and blood urea nitrogen 24 h after the reperfusion. Amlodipine (besilate, 100 and 300 microg kg(-1), i.v.) tended to attenuate renal dysfunction. Lisinopril (300 and 1000 microg kg(-1), i.v.), an angiotensin converting enzyme inhibitor, was ineffective in this acute renal failure model. Histological examination using the terminal transferase-mediated dUTP-biotin nick end-labelling (TUNEL) method to detect apoptotic cells revealed that the TUNEL-positive tubular epithelium was prominent in the renal cortex 24 h after the reperfusion. The TUNEL-positive cells were significantly reduced by pretreatment with benidipine. The results demonstrate that benidipine can ameliorate the ischaemic acute renal failure in rats and suggest that the renoprotective effect of benidipine was at least partly attributable to the reduction of apoptosis in tubular epithelial cells.

Acute Kidney Injury↗

PubMed2000

Antioxidant effects of calcium antagonists in rat brain homogenates.

We studied the antioxidant activities of calcium antagonists against autoxidation in rat brain homogenates. The homogenates were incubated for 30 min at 37 degrees C with or without a calcium antagonist and subsequently assayed for lipid peroxide content. Percent inhibition of the lipid peroxidation was used as an index of the antioxidant effect. Dihydropyridine calcium antagonists exhibited concentration-dependent (3-300 micromol/l) inhibitory effects against lipid peroxidation. The relative order of antioxidant potency and associated IC50 values (micromol/l) of the calcium antagonists for inhibition of the lipid peroxidation were as follows: nifedipine (51.5)>barnidipine (58.6)>benidipine (71.2)>nicardipine (129.3)>amlodipine (135.5)>nilvadipine (167.3)>nitrendipine (252.1)>> diltiazem (>300)=verapamil (>300). These results suggest that some dihydropyridine calcium antagonists show antioxidant properties. The antioxidant effects of the calcium antagonists may contribute to their pharmacological actions.

Animals↗

PubMed2000

New approach for measurement of sympathetic nervous abnormality in conscious, spontaneously hypertensive rats.

We previously reported a highly sensitive chemiluminescence high-performance liquid chromatographic method to determine catecholamines in plasma. In this study, we employed this method to measure the cardiac function and plasma norepinephrine (NE) concentration in conscious rats. Benidipine, 1,4-dihydropyridine calcium antagonist (4 mg/kg), and beta-blocker (propranolol, 30 mg/kg) were administered orally to conscious spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats, and blood pressure, heart rate and plasma NE levels were measured. Plasma NE concentration was used as an index of sympathetic nervous system activity in conscious rats. The basal plasma NE levels were significantly higher in SHRs than in WKY rats (P<0.05), indicating the activity of the basal sympathetic nervous system in SHRs was elevated. The sensitivity of the baroreflex-mediated sympathetic nervous response was reduced in SHRs as compared to that in WKY rats. The concomitant administration of benidipine and a beta-blocker decreased heart rate without affecting the baroreflex-mediated sympathetic nervous response, indicating that propranolol might suppress mainly the cardiac beta-adrenoceptor. The present study suggested the high activity of the basal sympathetic nervous system and the reduced response of the baroreflex-mediated sympathetic nervous system in SHRs compared to WKY rats in the conscious condition.

Animals↗

PubMed2000

Effect of the selective adenosine A1-receptor antagonist KW-3902 on lipopolysaccharide-induced reductions in urine volume and renal blood flow in anesthetized dogs.

We investigated the effects of KW-3902 (8-noradamantan-3-yl-1,3-dipropylxanthine), a potent and selective adenosine A1-receptor antagonist, on lipopolysaccharide (LPS)-induced reduction of urine volume (UV) in anesthetized dogs, in comparison with those of furosemide. LPS was intravenously administered at a dose of 0.5 mg/kg; and the heart rate (HR), systemic blood pressure (BP), renal blood flow (RBF) and UV were measured every 15 min for 4 h. Administration of LPS continuously decreased HR, BP, RBF and UV. KW-3902, furosemide or their corresponding vehicle was given as a bolus injection 5 min after the LPS injection. Treatment with KW-3902 (1 mg/kg, i.v.) ameliorated the LPS-induced decline of UV and RBF. Furosemide (3.2 mg/kg, i.v.) tended to ameliorate the LPS-induced decline of UV but not RBF, the duration of the effect being shorter than that of KW-3902. These results suggest that KW-3902 can ameliorate the oliguria and the decrease in RBF during the early phase of LPS-induced shock. Endogenous adenosine may be involved in the endotoxin-induced oliguria via the adenosine A1-receptor.

Animals↗

PubMed2000

Immune effects of low-dose radiation: short-term induction of thymocyte apoptosis and long-term augmentation of T-cell-dependent immune responses.

We and others have shown that low-dose X or gamma irradiation of mice leads to an increase in their survival after a subsequent lethal high-dose irradiation. The greatest increase in radioresistance appears at a fixed window of dose and time, e.g. 8 weeks after 5-10 cGy or 2 weeks after 50 cGy preirradiation. We show that low-dose irradiation induces thymocyte apoptosis with a maximal level at 6 h postirradiation that returns to background levels after 24 h. At the same time, we observed no morphological alteration of splenocytes and no early modification of the intensity of T-cell-dependent immune responses as measured by plaque-forming cell (PFC) counts. Nevertheless, we found that PFCs were increased 2 weeks after 50 cGy irradiation, which is the same time at which mice expressed the optimal increase in survival after a second lethal irradiation. We also examined thymocyte apoptosis and spleen PFCs in mice subjected to other stress-inducing pretreatments. Our results emphasize the existence of a lag time between the time of low-dose irradiation in vivo and the appearance of radioresistance. A mechanism that interconnects an environmental stimulus with the response of the animal is proposed based on the evidence presented here and reported in the literature.

Animals↗

PubMed1999

Reproductive and genetic evidence for a reticulate evolutionary history of mass-spawning corals.

Reef-building corals, which reproduce through simultaneous multispecies spawning, are thought to hybridize frequently, and it is hypothesized that they have evolved in repeated rounds of species separation and fusion. We conducted cross-fertilization experiments and molecular analyses with a number of mass-spawning coral species in the genus Acropora. A high rate of interspecific fertilization occurred between some species despite very different morphologies. The hybrid larvae developed normally and contained an allelic sequence transmitted from each parent, suggesting common diploid hybridization. Molecular phylogenetic analyses provided strong evidence for a gene pool shared between the hybridizing species. These reproductive and genetic characteristics are consistent with a species complex formed under the separation/fusion processes predicted for a reticulate evolutionary history.

Animals↗

PubMed1998

Estimation of the transition/transversion ratio.

A simple method for estimating the transition/transversion ratio was developed. This method can be applied to not only two sequences but also more than two sequences. The statistical properties of the method and some other methods were examined by numerical computation and computer simulation. The results obtained showed that, in terms of bias and variance, the new method gives a better estimate of the transition/transversion ratio than do the other examined methods. The new method was applied to human and chimpanzee mitochondrial control region sequences.

Animals↗

PubMed1997

Polymorphism in the angiotensin-converting enzyme (ACE) gene and sarcoidosis.

It has recently been shown that an insertion (I)/deletion (D) polymorphism exists in the angiotensin-converting enzyme (ACE) gene, and that this polymorphism affects the serum ACE level. There are three genotypes: DD, DI, and II, with the ACE level highest in DD, intermediate in DI, and lowest in II. In the present investigation of the possible significance of the polymorphism for sarcoidosis, a total of 207 patients and 314 normal control subjects were examined. There were no significant differences in the I/D ratio and the genotype distribution between the two groups, and no significant variation in organ involvement (i.e., eye, skin, and heart) was noted among the three genotypes. To determine any prognostic influence of the polymorphism, we examined the disappearance ratio of abnormal shadow on chest radiography over 3 and 5 yr. No significant difference among the three genotypes was observed. New normal ranges of serum ACE level were determined for each genotype, and found to be 22% more sensitive overall than the conventional normal range and 39% more so for II type, suggesting an advantage for diagnosis and assessment of the disease activity of sarcoidosis.

Case-Control Studies↗

PubMed1996

[Serum levels of solubule tumor necrosis factor (TNF) receptors in patients with pulmonary tuberculosis].

Tumor necrosis factor alpha (TNF-alpha) is released from cells of monocyte/macrophage lincage and mediates the development of a variety of clinical and pathomorphological features in various infectious diseases, autoimmune diseases and cancer. In the case of tuberculosis, it is suggested that the release of TNF-alpha in the affected regions and into the circulation could account for the pathological and clinical features such as the development of necrotic lesions and fever and weight loss in TB patients. In the present study, the levels of soluble TNF receptor type I (sTNFR type I) and type II (sTNFR type II) and TNF-alpha in the sera of patients with pulmonary TB were assayed, and we tried to know whether these levels have clinical significance in determining the disease activity in TB patients. The serum levels of both sTNFR types I and II were significantly higher in TB patients (n = 22) who were previously untreated than in the healthy control (n = 14): for sTNFR type I, 2.82 +/- 1.37 ng/ml vs. 1.40 +/- 0.33 ng/ml (p < 0.0001), and for sTNFR type II, 3.83 +/- 1.76 ng/ml vs. 1.62 +/- ng/ml (p < 0.0001). The serum levels of sTNFR types I and II in TB patients showed significant correlations with their serum levels of CRP. The serum levels of TNF-alpha in these TB patients was 2.21 +/- 1.72 pg/ml, whereas TNF-alpha was not detectable in the sera of 9 healthy control. The serum levels of sTNFR type I and II were significantly higher in cavitary TB (n = 17) than in non-cavitary TB (n = 5). When TB patients were treated with antituberculosis drugs and clinical improvements were achieved, the elevated levels of sTNFR type I and TNF-alpha in the sera of same 5 patients measured before starting treatment showed significant decline and the serum levels of sTNFR type II showed also declined, however, the decline was statistically not significant. From all the results obtained in this study, we conclude that the assay of the serum levels of sTNFR in TB patients is useful in the evaluation of the disease activity of TB.

Adult↗

PubMed1995

New methods for estimating the numbers of synonymous and nonsynonymous substitutions.

New methods for estimating the numbers of synonymous and nonsynonymous substitutions per site were developed. The methods are unweighted pathway methods based on Kimura's two-parameter model. Computer simulations were conducted to evaluate the accuracies of the new methods, Nei and Gojobori's (NG) method, Miyata and Yasunaga's (MY) method, Li, Wu, and Luo's (LWL) method, and Pamilo, Bianchi, and Li's (PBL) method. The following results were obtained: (1) The NG, MY, and LWL methods give overestimates of the number of synonymous substitutions and underestimates of the number of nonsynonymous substitutions. The major cause for the biased estimation is that these three methods underestimate the number of synonymous sites and overestimate the number of nonsynonymous sites. (2) The PBL method gives better estimates of the numbers of synonymous and nonsynonymous substitutions than those obtained by the NG, MY, and LWL methods. (3) The new methods also give better estimates of the numbers of synonymous and nonsynonymous substitutions than those obtained by the NG, MY, and LWL methods. In addition, estimates of the numbers of synonymous and nonsynonymous sites obtained by the new methods are reasonably accurate. (4) In some cases, the new methods and the PBL method give biased estimates of substitution numbers. However, from the number of nucleotide substitutions at the third position of codons, we can examine whether estimates obtained by the new methods are good or not, whereas we cannot make an examination of estimates obtained by the PBL method. (5) When there are strong transition/transversion and nucleotide-frequency biases like mitochondrial genes, all of the above methods give biased estimates of substitution numbers. In such cases, Kondo et al.'s method is recommended to be used for estimating the number of synonymous substitutions, although their method cannot estimate the number of nonsynonymous substitutions and is time-consuming. These results, particularly result (1), call for reexaminations of some genes. This is because evolutionary pictures of genes have often been discussed on the basis of results obtained by the NG, MY, and LWL methods, which are favorable for the neutral theory of molecular evolution.

Animals↗

PubMed1995

Variation in synonymous substitution rates among mammalian genes and the correlation between synonymous and nonsynonymous divergences.

Using mammalian gene sequences, the variances in the numbers of synonymous and nonsynonymous substitutions among genes were estimated together with the correlation coefficient between the two. The expected correlation coefficient can be obtained under the neutral theory using these estimated values of the variances. The expected coefficient is found to often be one-half to two-thirds of the observed value. Possible causes for the disagreement were discussed, such as correlated selective constraints on the two types of substitutions and excess doublet mutations. The variance of mutation rate and that of selective constraint were also estimated. The results show that the coefficient of variation of the former is 0.2-0.3, whereas that of the latter is 0.7-0.9.

Animals↗

PubMed1995

Classification of hepatitis C virus into major types and subtypes based on molecular evolutionary analysis.

Molecular evolutionary analysis was applied to determine the number of hepatitis C virus (HCV) types and subtypes based on all the HCV nucleotide sequences available from the DNA data banks (DDBJ, GenBank (NCBI), EMBL) and the literature. There was an excellent concordance among the types and subtypes assigned based on different HCV genomic regions. Only one HCV isolate was assigned to different HCV types based on the 5' non-coding (NC) and envelope 1 (E1) regions. The 5' NC region was well conserved and could be used to assign only types and not subtypes. From the sequence data available there were 13 subtypes based on the core region and 14 subtypes based on the E1 and non-structural protein 5 (NS5) regions.

Biological Evolution↗

PubMed1995

Relationships between serotypes and genotypes of hepatitis B virus: genetic classification of HBV by use of surface genes.

Hepatitis B virus (HBV) surface antigen (HBsAg), which is encoded by the HBV S gene, is conventionally classified into 4 serological subtypes, adw, adr, ayw and ayr. To determine the relationship between the HBsAg seroreactivity and the nucleotide sequence diversity of the HBV S gene, the nucleotide sequences of S genes for HBV isolates reported so far were aligned with each other. The numbers of nucleotide substitutions were then estimated by the 6-parameter method, and a phylogenetic tree was constructed by the unweighted paired grouping method with arithmetic mean (UPGMA) and the neighboring-joining (NJ) method. The phylogenetic trees constructed showed that all isolates were grouped into 4 genotypes (gyw, gdw-1, gdw-2, and gdr). More importantly, the genotypes did not necessarily correspond to the conventional serotypes. In particular, serotype 'adw' can be any of genotypes gdw-1, gdw-2, or gdr. Thus, genotyping by S genes gives more accurate information about genetic variation of HBV.

Amino Acid Sequence↗

PubMed1995

Excitation and inhibition via adenosine receptors of the twitch response to electrical stimulation in isolated guinea pig ileum.

The effects of adenosine and its related compounds on the cholinergic twitch response were examined in electrically stimulated guinea pig ileum. Adenosine (3 x 10(-7)-10(-5) M) and an adenosine A1-receptor agonist N6-cyclohexyladenosine (CHA, 10(-8)-10(-6) M) suppressed the twitch. Conversely, the A2a-receptor agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N- ethylcarboxamidoadenosine (CGS 21680, 10(-9)-10(-7) M) potentiated the twitch in half the preparations examined. The A1-antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), which per se did not affect the twitch, recovered the attenuated twitch caused by CHA (10(-7) M) or adenosine (10(-6) M) and converted it into a potentiated twitch. These results suggest the presence of adenosine A1- and A2a-receptors coupled negatively and positively, respectively, to acetylcholine release in the preparation.

Adenosine↗

PubMed1995

[Serum levels of soluble receptors for tumor necrosis factor in sarcoidosis].

Tumor necrosis factor alpha (TNF-alpha) has been shown to play an important role in granulomatous diseases, including sarcoidosis. TNF-alpha starts affecting cell function by binding to specific, high-affinity receptors on the cell surface, and two types of TNF-alpha receptors have been identified. Recently, soluble forms derived these cell surface receptors (sTNF-R type I and type II) have been shown to exist and have been investigated in several diseases. The levels of sTNF-R type I and type II in serum from patients with sarcoidosis were measured, and the clinical significance of sTNF-R was evaluated. The levels of both sTNF-R type I and type II were significantly higher in serum from patients with sarcoidosis (n = 36) than in serum from control subjects (n = 15): type I, 1.93 +/- 1.28 ng/ml vs 1.31 +/- 0.40 ng/ml, p < 0.01; type II, 3.48 +/- 2.60 ng/ml vs 1.56 +/- 0.35 ng/ml, p < 0.001. The levels of these receptors were significantly higher in patients with active sarcoidosis than in those with inactive sarcoidosis: type I, 2.43 +/- 1.83 ng/ml vs 1.57 +/- 0.45 ng/ml, p < 0.05; type 4.71 +/- 2.24 ng/ml vs 2.25 +/- 0.77 ng/ml, p < 0.01. The levels of sTNF-R type I and type II correlated significantly with the level of ACE, r = 0.70, p < 0.01; and r = 0.55, p < 0.05, respectively. We conclude that measurement of the levels of both types of sTNF-R may be useful in the evaluation of disease activity in sarcoidosis.

Adolescent↗

PubMed1995

[A case of acute eosinophilic pneumonia with acute onset of dyspnea].

A 16-year-Old boy was admitted with acute onset of fever, cough, and dyspnea. Chest radiography showed diffuse infiltrated shadow and right pleural effusion. BALF revealed a high level of eosinophils (56.8%), and TBLB specimen showed infiltration of inflammatory cells, chiefly eosinophils. Symptoms and radiographic findings resolved spontaneously within a few days after admission. Acute eosinophilic pneumonia was diagnosed as in the case reported by Allen et al. However, the present patient had a high IgE level and history of atopic allergic rhinitis. In more than one third of previously reported cases in Japan, there was a history of atopy, unlike in Allen's report.

Acute Disease↗

PubMed1995

[Severe cases of pulmonary tuberculosis required mechanical ventilation].

We report severe cases of pulmonary tuberculosis with respiratory failure who required mechanical ventilation. Of 99 patients with pulmonary tuberculosis admitted to Daido Hospital from November 1991 to November 1993, 6 patients had been mechanically ventilated. Four of these 6 patients were vagrants and had long delay from onset of the symptom to the admission. Chest X-rays of ventilated patients showed bilateral, extensive shadows consistent with those of typical pulmonary tuberculosis, and a large number of acid-fast bacilli were detected in their sputa. Though all ventilated patients except one HCV carrier had no underlying disease, they showed remarkable emaciation and malnutrition. They also showed weak PPD-skin reactions and reduced number of lymphocytes that suggested immunological disorders. Four cases have recovered, so we conclude that mechanical ventilation is necessary and useful for the treatment of severe cases of pulmonary tuberculosis.

Adult↗

PubMed1994

Statistical analysis of nucleotide sequences of the hemagglutinin gene of human influenza A viruses.

To examine whether positive selection operates on the hemagglutinin 1 (HA1) gene of human influenza A viruses (H1 subtype), 21 nucleotide sequences of the HA1 gene were statistically analyzed. The nucleotide sequences were divided into antigenic and nonantigenic sites. The nucleotide diversities for antigenic and nonantigenic sites of the HA1 gene were computed at synonymous and nonsynonymous sites separately. For nonantigenic sites, the nucleotide diversities were larger at synonymous sites than at nonsynonymous sites. This is consistent with the neutral theory of molecular evolution. For antigenic sites, however, the nucleotide diversities at nonsynonymous sites were larger than those at synonymous sites. These results suggest that positive selection operates on antigenic sites of the HA1 gene of human influenza A viruses (H1 subtype).

Antigens, Viral↗