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Biomedical subjects

Y Ina

Publications and source records attributed to Y Ina.

At least 55 records · Page 3Linked to original sources

Evolutionary origin of human and simian immunodeficiency viruses.

From what viruses the human immunodeficiency viruses (HIVs) originated is an extremely controversial question. To address this question, we have analyzed nucleotide sequences of simian immunodeficiency viruses (SIVs) and HIVs by using the techniques for understanding molecular evolution. In particular, we compared the nucleotide sequences of whole genomes, gene region by gene region, between a given pair of viruses, including four types of SIVs--isolated from mandrills (Papio sphinx), African green monkeys (Cercopithecus aethiops), sooty mangabeys (Cercocebus atys), and rhesus macaques (Macaca mulatta)--as well as HIVs. Phylogenetic trees for all gene regions examined showed that the present HIVs may have emerged as different variants of SIVs of Old World monkeys, possibly from recombination between viruses related to SIVs.

Biological Evolution

Antigen-presenting capacity in patients with sarcoidosis.

Antigen-presenting capacity by monocytes and AMs was determined in 13 patients with sarcoidosis and nine healthy control subjects, using PPD as the antigen. The patients and healthy control subjects all had positive PPD skin tests. Monocytes from both the control subjects and the patients with sarcoidosis exhibited antigen-presenting capacity to autologous peripheral T-lymphocytes, without any significant difference between the two groups. The AMs from patients, but not control subjects, demonstrated antigen-presenting capacity to autologous peripheral T-lymphocytes. Antigen-presenting capacity by monocytes and AMs to lung T-lymphocytes was lower than to peripheral T-lymphocytes, but not significantly. Antigen-presenting capacity was not significantly different between patients with sarcoidosis who had positive and negative PPD skin tests. The mechanism of enhanced antigen-presenting capacity by AMs in sarcoidosis is uncertain at present, but no significant difference was observed in DR antigen expression on AMs between controls and patients with sarcoidosis, and the addition of exogenous IL-1 or IFN-gamma did not induce antigen-presenting capacity by AMs in controls, suggesting that neither increased DR antigen expression on AMs nor increased release of IL-1 or IFN-gamma from AMs is responsible. Thus, these results suggest that T-lymphocyte activation in sarcoidosis may in part be attributable to an enhanced antigen-presenting capacity by AMs.

Antigen-Presenting Cells

[Bronchiolitis obliterans organizing pneumonia (BOOP) in Japan].

Twenty-nine patients with bronchiolitis obliterans organizing pneumonia (BOOP) in Japan diagnosed by an open lung biopsy were reviewed. A total of 70% of the patients were idiopathic and 2/3 of the remaining were associated with connective tissue disease. All 29 cases of BOOP showed bilateral pulmonary infiltration on chest X-rays. BOOP can be classified based on the chest X-ray findings into three major types, Type I, Type II and unclasSified type. In Type I shadows appear in the lung fields. In Type II abnormal shadows are seen in the bi-basilar peripheral field with the reduction of the lung volume. Cases of Type I showed inflammatory findings more frequently than cases of Type II. Among 29 BOOP patients, two idiopathic cases died.

Adult

[Long-term therapeutic effects of erythromycin and newquinolone antibacterial agents on diffuse panbronchiolitis].

The present study reviewed and summarized the long-term therapeutic effects of erythromycin or newquinolone antibacterial agents on diffuse panbronchiolitis. Various parameters before and after the treatment were analyzed in 101 patients selected from 227 diffuse panbronchiolitis patients gathered from 26 institutes in Japan. Patients had been treated with either erythromycin or newquinolone antibacterial agent for more than 3 months. Patients treated with erythromycin showed significant improvement of dyspnea on exertion, findings of chest X-ray, data on blood gas analysis, rate of ESR, titer of cold coagulation and amount of sputum, compared with patients treated with the newquinolone antibacterial agent. Among the patients treated with erythromycin, those patients with the initial high cold coagulation titer showed better improvement following treatment. However, there was no significant difference in improvement, depending upon either the duration between the time of onset of the disease, the initiation of treatment, and the initial severity of the disease.

4-Quinolones

[A case of miliary tuberculosis with prolonged high fever for more than 2 months under antituberculous therapy].

A 28 year-old male was admitted to our hospital with persistent cough and high fever. He was diagnosed to have miliary tuberculosis by the transbronchial lung biopsy specimen and tuberculous choroidal lesions in the ocular fundus. Antituberculosis therapy was immediately started. In spite of the fact that the bacilli were sensitive to the antituberculosis drugs used and he had no other complications, high fever persisted and lasted for more than 2 months. When tuberculosis is suspected, and antituberculosis treatment is tried to observe its clinical response, the presence of similar cases mentioned above should be taken into consideration.

Adult

[The treatment, course and prognosis of sarcoidosis cases].

Sarcoidosis is a disorder with a highly variable prognosis. Although spontaneous cure is common, a small number of patients become progressively worse. In this study, we analysed 433 patients with sarcoidosis who presented to our institute. Twenty-seven patients (6.2%) of them developed serious morbidity. We studied the clinical course, prognosis and use of steroid therapy in those 27 patients. Eight (29.6%) of the 27 patients developed severe disability during their clinical course, in spite of their mild clinical symptoms and findings at first presentation. Therefore, clinical symptoms and findings, such as ocular disorders, ECG abnormalities, negative reaction to PPD, serum ACE values and lymphocyte count are not always useful markers for the prognosis of sarcoidosis. The relationship between maximum serum ACE values during the course and the duration of the active phase was investigated in 93 patients who were followed throughout their course of the disease. Improvement occurred more often within 5 years in the patients with DR5(+) HLA class II or DRw53(-) compared to patients with DR5(-) or DRw53(+). Using various combinations of specific antigens, the following 5 groups revealed good prognoses, frequently improving within 5 years, 1) DR5(+) and DR4(-), 2) DR5(+) and DRw53(-), 3) DR5(+), DR4(-) and DR8(-), 4) DR5(+), DR4(-) and DR9(-), 5) DR5(+), DR4(-), DR8(-) and DR9(-). HLA class II antigens may also play an important role in the prognosis of sarcoidosis. Since relapses almost always occurred after cessation of steroid therapy, the duration of treatment should be as long as possible and the dosage should also be tapered carefully.

Adolescent

[A case of pigeon breeder's disease].

A 73-year-old woman developed dry cough and exertional dyspnea. She had been breeding pigeons for thirty years. Her serum showed positive precipitin reaction against pigeon serum. Furthermore the lymphocyte stimulation test against pigeon serum was positive. An X-ray film of the chest showed diffuse ground glass infiltrate, fine nodular shadows and reticular shadows. Histopathology revealed diffuse interstitial infiltration with mononuclear cells and occasional giant cell formation as well as granuloma formation in the bronchiole. The symptoms subsided after admission. From these results, this case was diagnosed as pigeon breeder's disease. She had the subacute form probably because of her old age and smoking. It could be that exacerbation of pneumonitis was caused by cessation of smoking in an attempt to alleviate the symptoms. This is the fifth case reported in Japan.

Aged

Host-independent evolution and a genetic classification of the hepadnavirus family based on nucleotide sequences.

An analysis of molecular phylogeny was undertaken to examine whether the evolution of the hepadnavirus family is host-dependent. Using the nucleotide sequences of 18 strains, we constructed phylogenetic trees. The trees obtained show that all 12 strains of hepatitis B virus can be classified into four subgroups that are not compatible with conventional subtypes. We estimated the rate of synonymous (silent) substitution for hepatitis B virus to be 4.57 x 10(-5) per site per year. Applying this rate to the phylogenetic tree, we estimated that duck hepatitis B virus diverged from a common ancestor about 30,000 years ago at the earliest, that woodchuck hepatitis virus and ground squirrel hepatitis virus diverged about 10,000 years ago, and that hepatitis B virus diverged within the last 3000 years. Because these divergence times of the viruses are much more recent than those of the host species, it suggests that the hepadnavirus family evolved independently of host-species divergence.

Animals

HLA and sarcoidosis in the Japanese.

One hundred fourteen patients with sarcoidosis, who were diagnosed as having sarcoidosis histologically, have been typed for HLA class 1 (A, B, and C) and class 2 (DR and DQ) antigens. Controls consisted of 478 healthy Japanese subjects. The frequencies of HLA-A1, HLA-Bw46, HLA-Cx46, HLA-DRw8, HLA-DRw9, and HLA-DRw52 were significantly increased in sarcoidosis compared to control subjects, but only four patients were positive for HLA-A1. Increased frequencies of HLA-Bw46 and HLA-Cx46 were thought to be attributable to linkage disequilibrium with HLA-DRw8. Patients with HLA-DRw52 were the most frequent (84 cases of 113). No significant differences were observed between HLA-DRw52-positive and HLA-DRw52-negative patients in their clinical features, but all of the patients with muscular involvement (six cases) were positive for HLA-DRw52. Among patients positive for HLA-DRw52, those with HLA-DR5 showed a significantly better clinical course and earlier onset of the disease than those with HLA-DRw8. These results suggest that HLA antigens may play an important role in the pathogenesis of sarcoidosis.

Adult

[Antigen presentation in pulmonary tuberculosis].

Antigen presenting capacity (APCC) by monocytes (Mono) and alveolar macrophages (AM), using PPD as the antigen, was determined in 15 patients with pulmonary tuberculosis and 9 healthy controls who all showed positive PPD skin tests. Results were as follows: 1) Mono from both healthy controls and tuberculosis showed APCC to autologous peripheral T lymphocytes, and no significant difference was observed between the two groups. 2) AM from tuberculosis showed APCC to autologous peripheral T lymphocytes, however AM from healthy controls did not. 3) APCC by autologous Mono or AM to lung T-lymphocytes was lower than that to peripheral T-lymphocytes, but the difference was not significant. 4) In tuberculosis, APCC, observed before chemotherapy, was remarkably weakened during the first two months of therapy, and almost recovered to the previous level thereafter. 5) The mechanism which enhances APCC by AM in tuberculosis is uncertain. But neither increased DR antigen expression on AM nor release of IL-1 from AM suggested to be be responsible for the enhanced APCC in tuberculosis.

Adult

Calcium influx and the Ca2+-calmodulin complex are involved in interferon-gamma-induced expression of HLA class II molecules on HL-60 cells.

Interferon gamma (IFN-gamma) induces HLA-DR and -DQ molecules and causes an accumulation of transcripts in HL-60 cells. Experiments were, therefore, designed to investigate the intracellular signaling molecules regulating the appearance of HLA class II molecules. The expression of HLA class II (DR and DQ) molecules induced by IFN-gamma was blocked by a calmodulin antagonist, W7, but not by a protein kinase C inhibitor, H7. Furthermore, a direct activator of protein kinase C, phorbol 12-myristate 13-acetate, was unable to induce HLA class II (DR) molecule expression. These results suggest that IFN-gamma induces HLA class II molecules on HL-60 cells by way of a calcium-calmodulin pathway and not by way of a protein kinase C pathway. Calmodulin is activated by a transient rise in the cytosolic free calcium. In fact, IFN-gamma evoked a calcium influx into HL-60 cells, whereas depletion of Ca2+ from culture medium resulted in a failure of IFN-gamma to induce DR expression. Furthermore, the calcium ionophore A23187 by itself induced DR molecule expression. These results suggest that IFN-gamma stimulates calcium influx by a so-called receptor-mediated calcium channel and activates the calmodulin branch of the calcium messenger system, resulting in the induction of DR molecules on the surface of HL-60 cells.

Calcimycin

Regulation of HLA class II antigen expression: intracellular signaling molecules responsible for the regulation by IFN-gamma and cross-linking of Fc receptors in HL-60 cells.

The cross-linking of Fc receptors (FcR) on HL-60 cells inhibited the ability of recombinant IFN-gamma to induce HLA class II antigens. This appeared to be correlated with intracellular mRNA level. HL-60 lacked detectable HLA class II mRNA. IFN-gamma led to appearance of these transcripts, which were canceled by the cross-linking of FcR. Therefore, experiments were designed to investigate the intracellular signaling molecules regulating the appearance of HLA class II molecules or transcripts. The expression of HLA class II antigen induced by IFN-gamma was blocked by a calmodulin antagonist, W-7, but not by a protein kinase C (PKC) inhibitor, H-7. Furthermore, a direct activator of PKC, phorbol myristate acetate, was not able to induce the HLA class II antigen expression. These results suggest that IFN-gamma induces HLA class II antigens on HL-60 cells via a calcium-calmodulin pathway and not via a PKC pathway. Calmodulin is activated by a transient rise in the cytosolic free calcium. In fact, the measurement of calcium influx into HL-60 cells showed that a remarkable and time-dependent calcium accumulation was caused by IFN-gamma, and that depletion of Ca2+ from culture medium resulted in failure of IFN-gamma to induce class II antigen expression. Furthermore, calcium ionophore, A23187, by itself induced HLA class II antigen expression. These results suggest that IFN-gamma stimulates calcium influx and activates the calmodulin branch of the calcium messenger system, resulting in the induction of class II antigen expression on HL-60 cells. On the other hand, cross-linking of FcR elicited the accumulation of intracellular cAMP, which appeared to suppress the IFN-gamma-induced calcium influx, resulting in annulling HLA class II antigen-inducing activity of IFN-gamma. These intracellular events of HL-60 regulate the expression of HLA class II transcripts and molecules.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

[Complement components, whole complement activity, and circulating immune complexes in neoplastic diseases].

Serum levels of complement components(cc), whole complement activity (CH 50), and circulating immune complexes (IC) were measured in 41 patients with neoplastic diseases. The level of cc was higher than in healthy controls; the levels of C1q, C1INA, C4, C3c, C3ACT, C5, and C9 were statistically higher. In patients with lung cancer, the levels of cc were correlated with the clinical stage as well as the performance status. Both the IC serum level and the incidence of high serum IC levels in lung cancer were higher in stage III and IV than in stage I and II. Serum CH 50 was higher than in healthy controls, but not correlated with the clinical stage.

Aged