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Biomedical subjects

Y Ina

Publications and source records attributed to Y Ina.

At least 19 recordsLinked to original sources

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

[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

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

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

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

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

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

[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

[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

[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

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

Six-year longitudinal analysis of adenovirus type 3 genome types isolated in Yamagata, Japan.

Five hundred eighty-seven adenovirus type 3 (Ad3) isolates were established from children with acute respiratory infections (ARI) from 1986 to 1991, in Yamagata, Japan. Ad3 could be found in almost all the months during the 6 years when two epidemics occurred, in 1987 and 1989. A molecular epidemiological study was done on 346 of the 587 isolates, using restriction endonucleases; BamHI, HindIII, SmaI, and BgIII were used. The Ad3 isolates were classified into seven genome types. The genetic differences among the seven genome types were < 0.9%, and their phylogenetic tree, estimated by the neighbor-joining method, correlated highly with their monthly distribution. One genome type predominated for 56 months, while the other six related genome types cocirculated for a short period. These results suggested that the predominant genome type of Ad3 might have been endemically perpetuated in the Yamagata area with minor genomic variations. Furthermore, the outbreaks of Ad3 may have been due not to the appearance of a new genome type but rather to the endemic genome type.

Adenovirus Infections, Human

Reduction of synonymous substitutions in the core protein gene of hepatitis C virus.

Molecular evolutionary analyses were carried out to elucidate the phylogenetic relationships, the evolutionary rate, and the divergence times of hepatitis C viruses. Using the nucleotide sequences of the viruses isolated from various locations in the world, we constructed phylogenetic trees. The trees showed that strains isolated from a single location were not necessarily clustered as a group. This suggests that the viruses may be transferred with blood on a worldwide scale. We estimated the evolutionary rates at synonymous and nonsynonymous sites for all genes in the viral genome. We then found that the rate (1.35 x 10(-3) per site per year) at synonymous sites for the C gene was much smaller than those for the other genes (e.g., 6.29 x 10(-3) per site per year for the E gene). This indicates that a special type of functional constraint on synonymous substitutions may exist in the C gene. Because we found an open reading frame (ORF) with the C gene region, the possibility exists that synonymous substitutions for the C gene are constrained by the overlapping ORF whose reading frame is different from that of the C gene. Applying the evolutionary rates to the trees, we also suggest that major groups of hepatitis C viruses diverged from their common ancestor several hundred years ago.

Biological Evolution

[Effects of voluntary wheel running on health indexes in rats with SRBC-induced inflammation].

The effects of voluntary running exercise on health indexes in rats were studied before and after Sheep Red Blood Cell (SRBC)-induced inflammation. Male Fischer rats (SPF) 8 weeks of age were housed in individual sedentary cages (sedentary group) or in individual wheel-running cages (exercise group) for 4 months. Then all rats were injected with 20% SRBC (0.5 ml/100g body weight) i.p. Voluntary running activity averaged 1408m/day, reached a peak (2913m/day) at the 25th day and waned over time, reaching a plateau at the 60th day (about 1000m/day). In spite of a significant increase in food intake (117%), exercising rats gained significantly less weight (93%) than sedentary rats at all times in experimental period. The exercise group also showed a significant decrease in the value of serum triglyceride (TG) and total cholesterol (T. CHO) (TG p < 0.0002, T. CHO p < 0.03). The hematocrit (Ht) and hemoglobin concentration (Hb) were higher in the exercised rats, and at 4 days after i.p. SRBC, the difference became statistically significant (Ht p < 0.0002, Hb p < 0.003). Thus, protective effects against the decrease of Ht and Hb were demonstrated in the exercised group. Perhaps this inflammation did not impair liver function severely; sedentary rats had normal or slightly higher levels of GOT and GPT. On the other hand, exercised rats had lower GOT and GPT. Significant differences were found between the groups (GOT, GPT p < 0.0001).

Animals

[Effects of crowding on immune functions in mice].

The effects of several types of crowding on immune functions were studied in mice. This study consisted of two experiments. Experiment one: Male BALB/c mice were initially housed in groups of four mice per cage. After fourteen days of acclimation, the mice were randomly divided into three groups, Control (four mice per cage, control group), Crowd-I (four mice per small space) and Crowd-II (sixteen mice per cage). These conditions were maintained for seven days. The results of experiment one were as follows: (1) The percentage of lymphocytes in the blood of Crowd-II was significantly lower than that of Control (p < 0.05). (2) The percentage of neutrophils and the absolute number of neutrophils in blood of Crowd-II were significantly higher than in Control (p < 0.05). (3) Superoxide production activity (NBT reduction activity) of blood neutrophils in Crowd-II tended to be depressed, and phagocytic activity of neutrophils was significantly depressed in Crowd-II as compared with Control (p < 0.01). These results suggest that the complexity of interrelationships among mice caused by an increase in the number of animals per cage is a very important stress factor. Experiment two: Male BALB/c mice were initially housed in groups of five mice per cage. After fourteen days of acclimation, the mice were divided into three groups, Control (five mice per cage, control group), Crowd-(1) (five mice per cmall space) and Crowd-(2) (twenty mice per cage). In Control and Crowd-(1), the same mice were used as in the acclimation period. These conditions were maintained for seven days. In this period, on the second day, all the mice were injected intraperitoneally with sheep red blood cells (SRBC). The results of experiment two were as follows: (1) The specific humoral immune response to SRBC was investigated in terms of the number of PFC in the spleens and hemagglutination in sera, but significant differences were not found among the groups. (2) Plasma IgG levels in the Crowd-(1) were significantly higher than those in Control (p < 0.05). (3) Both superoxide production activity and phagocytic activity of neutrophils were significantly depressed in Crowd-(2) as compared with Control (p < 0.01, respectively), whereas each neutrophil function of Crowd-(1) tended to be enhanced as compared with Control.

Animals

Antiphospholipid antibodies. A prognostic factor in sarcoidosis?

Serum antibodies against five types of phospholipids, antiphospholipid antibodies (aPL), were determined by an enzyme-linked immunosorbent assay in 55 patients with sarcoidosis. Either IgG or IgM aPL were detected in 21 patients (38 percent). This positive rate was significantly higher than that (7 percent) of healthy control subjects (p < 0.001). In terms of immunoglobulin classes, 5 cases had IgG aPL only, 11 cases had IgM aPL only, and 5 cases had both classes of aPL. No correlation was observed between the occurrence of aPL and disease activity of sarcoidosis. A significant correlation was noted between the occurrence of aPL and many extrathoracic organ lesions or the persistence of abnormal chest x-ray film findings for periods of 2 and 5 years. Taken together, the presence of aPL in sarcoidosis is a useful index to judge the prolongation of the disease.

Adult

Significance of interleukin 6 in patients with sarcoidosis.

Interleukin 6 (IL-6) levels in various materials from patients with sarcoidosis were determined. The subjects of the study were 38 patients with sarcoidosis and 28 healthy controls. For detection of IL-6, an enzyme-linked immunosorbent assay method was used. Interleukin 6 activity in serum was detected in 4 of 30 patients, but not in 19 controls. In bronchoalveolar lavage (BAL) fluid, following 20-fold concentration, IL-6 activity was detected in four of ten patients (nonsmokers) and three of seven controls (two of two smokers and one of five nonsmokers). Interleukin 6 levels in the supernatants of cultured monocytes and alveolar macrophages (AMs) were significantly higher (p < 0.01 and p < 0.01, respectively) in patients with sarcoidosis than in controls. Interleukin 6 production from monocytes tended to correlate with that from AMs. A significant correlation (r = 0.70, p < 0.05) was found between IL-6 production from AMs and the ratio of CD4+/CD8+ in BAL fluid, although no correlation was observed between that from monocytes and CD4+/CD8+ ratio in BAL fluid. Taken together, IL-6 may be involved in the initiation and maintenance of alveolitis by activating and causing the proliferation of T cells.

Adult