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Biomedical subjects

J Yasuda

Publications and source records attributed to J Yasuda.

At least 37 records · Page 2Linked to original sources

Structure of the infected cell protein 0 gene of canine herpesvirus.

The canine herpesvirus infected cell protein 0 (CICP0) gene was sequenced. The CICP0 gene was transcribed as a 1.4 kb mRNA from the end of the unique long region nearby the internal repeat during early phase of productive infection of the virus. An open reading frame of the gene encodes a polypeptide of 333 amino acids. The RING finger domain and acidic transcriptional activation domain were found at the N-terminus and within the middle region in the deduced amino acid sequence, respectively, suggesting that the CICP0, like the ICP0 of herpes simplex virus 1, is a transactivating protein.

Amino Acid Sequence↗

Significance of the Grb2 and son of sevenless (Sos) proteins in human bladder cancer cell lines.

The epidermal growth factor (EGF) receptor has been suggested to have an important role in tumor initiation and progression of human bladder cancers. Grb2 protein, which is the downstream effector of the EGF receptor, acts as an adaptor protein between the EGF receptor and the Ras guanine-nucleotide exchange factor, son of sevenless (Sos) protein. Sos protein regulates the action of Ras protein by promoting the exchange of GDP for GTP. However, the significance of Grb2 and Sos proteins, which is related to EGF-triggered Ras activation, has not been elucidated in human bladder cancer. The aim of the present study is to clarify the significance of these proteins in human bladder cancer cell lines. In the present study, we used four human bladder cancer cell lines (T24, KU-7, UMUC-2, UMUC-6) and two kinds of cultured normal urothelial cells (HMKU-1, HMKU-2) isolated from patients with no malignancy. We examined the expression of EGF receptor, Grb2, and Sos proteins in these cells by Western blot analysis. Furthermore, the bladder cancer cell lines were subjected to sequence analysis to identify a point mutation in the c-H-ras gene at codon 12. There was no marked difference in the expression of the EGF receptor between human bladder cancer cell lines and cultured normal urothelial cells. On the other hand, expression of Grb2 and Sos proteins was substantially increased in all human bladder cancer cell lines examined in comparison with cultured normal urothelial cells, whether codon 12 of H-ras was mutated or not. These results suggest that the amplification of both Grb2 and SOS proteins plays an important role in the carcinogenesis of human bladder cancer.

Adaptor Proteins, Signal Transducing↗

IL-15 expression at human endometrium and decidua.

A large number of natural killer (NK) cells appear in human uterine mucosa during the secretory phase and first trimester pregnancy. We investigated the expression of interleukin (IL)-15, a possible stimulator for these NK cells, in human endometrium and first trimester decidua. Semiquantitative reverse transcriptase-polymerase chain reaction revealed that IL-15 mRNA expression was stronger during the secretory phase and first trimester pregnancy than during the proliferative phase. Immunohistochemistry revealed that immunoreactivity for anti-IL-15 was higher during the secretory phase than it was during the proliferative phase. This was prominent in the perivascular stromal cells around invading spiral arteries during the mid- to late-secretory phase. In first trimester decidua, endothelial cells were also stained as strongly as stromal cells. A membrane-bound IL-15 molecule was detected on the surface of first trimester decidual cells by flow cytometry. Progesterone stimulated the release of soluble IL-15 in the supernatant of cultured decidual cells. These results suggest that IL-15 expression in human uterine mucosa corresponds to the fluctuation of uterine NK cells and that its production is hormonally controlled, especially by progesterone.

Cells, Cultured↗

[A case of primary pulmonary artery myxosarcoma associated with severe pulmonary hypertension].

A 50-year-old man presented with progressive dyspnea on exertion, but with no history of chest pain or syncope. Chronic pulmonary thromboembolism was suspected and he was referred to our hospital. On ausculation, a grade 3 systolic murmur was heard, that was loudest in the fifth intercostal space lateral to the right sternal border. Chest radiography showed mild cardiomegaly and ventilation-perfusion scan revealed absence of perfusion in the left lung and the upper field of the right lung. Contrast-enhanced helical CT showed large mural defects in both main pulmonary arteries, clearly delineated by contrast medium. The left pulmonary artery was nearly completely occluded, and eccentric defects were observed projecting into the lumen of the pulmonary trunk. A tumor originating in the pulmonary artery was suspected, but a definitive diagnosis of the mass could not be made with pulmonary angiography and magnetic resonance imaging. The mean pulmonary arterial pressure was 50 mmHg. Further radiologic examinations failed to reveal the source of the embolus or tumor. It was decided to attempt surgical excision under total cardiopulmonary bypass. At operation, a gelatinous, lustrous, yellowish mass was found partially occluding the right main pulmonary artery and completely occluding the left. The tumor adhered tightly to the intima of the vessel and was inoperable. The patient could not be weaned from percutaneous cardiopulmonary support and died 3 days after surgery. Histologic examination of the excised specimen revealed myxosarcoma.

Chronic Disease↗

WRM-1 activates the LIT-1 protein kinase to transduce anterior/posterior polarity signals in C. elegans.

During C. elegans development, Wnt/WG signaling is required for differences in cell fate between sister cells born from anterior/posterior divisions. A beta-catenin-related gene, wrm-1, and the lit-1 gene are effectors of this signaling pathway and appear to downregulate the activity of POP-1, a TCF/LEF-related protein, in posterior daughter cells. We show here that lit-1 encodes a serine/threonine protein kinase homolog related to the Drosophila tissue polarity protein Nemo. We demonstrate that the WRM-1 protein binds to LIT-1 in vivo and that WRM-1 can activate the LIT-1 protein kinase when coexpressed in vertebrate tissue culture cells. This activation leads to phosphorylation of POP-1 and to apparent changes in its subcellular localization. Our findings provide evidence for novel regulatory avenues for an evolutionarily conserved Wnt/WG signaling pathway.

Amino Acid Sequence↗

Detection of DNA abnormalities by arbitrarily primed PCR fingerprinting: amplification of the MDM2 gene in a mediastinum fibrosarcoma.

Arbitrarily primed PCR (AP-PCR) fingerprinting method is easy and useful for analysis of genetic alterations in anonymous chromosomal regions. We applied this technology to analysis of DNA from human primary cancers and found amplification of a DNA fragment in a mediastinum fibrosarcoma. PCR-based analysis of radiation hybrid panels following cloning and nucleotide sequence determination of the fragment revealed that it was derived from a region of chromosome 12q13-q15. In this region, the MDM2 and IFNG genes were noted as known genes that could be involved in human carcinogenesis. Southern blot analysis of genomic DNA of the tumor revealed the amplification of the MDM2 gene together with the fragment locus, but not the IFNG gene. Our results demonstrated that detection of DNA alterations by AP-PCR fingerprinting without any previous knowledge of the genes and subsequent analysis of radiation hybrid panels could lead to easy identification of candidates for genes involved in carcinogenesis.

Base Sequence↗

Structure of the immediate early gene of canine herpesvirus.

The nucleotide sequence of the immediate early (IE) gene of canine herpesvirus was determined. This gene was located in the inverted repeat regions, encoding a polypeptide of 1,383 amino acids. The predicted amino acid sequence was most closely related to that of the feline herpesvirus 1 IE protein among those of other alphaherpesviruses. DNA binding and transcriptional activation domains were found in the IE protein. A spliced region of the IE gene transcript was determined in its 5' non-coding region.

Amino Acid Sequence↗

MOM-4, a MAP kinase kinase kinase-related protein, activates WRM-1/LIT-1 kinase to transduce anterior/posterior polarity signals in C. elegans.

In C. elegans, a Wnt/WG-like signaling pathway down-regulates the TCF/LEF-related protein, POP-1, to specify posterior cell fates. Effectors of this signaling pathway include a beta-catenin homolog, WRM-1, and a conserved protein kinase, LIT-1. WRM-1 and LIT-1 form a kinase complex that can directly phosphorylate POP-1, but how signaling activates WRM-1/LIT-1 kinase is not yet known. Here we show that mom-4, a genetically defined effector of polarity signaling, encodes a MAP kinase kinase kinase-related protein that stimulates the WRM-1/LIT-1-dependent phosphorylation of POP-1. LIT-1 kinase activity requires a conserved residue analogous to an activating phosphorylation site in other kinases, including MAP kinases. These findings suggest that anterior/posterior polarity signaling in C. elegans may involve a MAP kinase-like signaling mechanism.

Amino Acid Sequence↗

The JIP group of mitogen-activated protein kinase scaffold proteins.

Activation of the c-Jun NH(2)-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases is mediated by a protein kinase cascade. This signaling mechanism may be coordinated by the interaction of components of the protein kinase cascade with scaffold proteins. The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates signaling by the mixed-lineage kinase (MLK)-->MAP kinase kinase 7 (MKK7)-->JNK pathway. The scaffold proteins JIP1 and JIP2 interact to form oligomeric complexes that accumulate in peripheral cytoplasmic projections extended at the cell surface. The JIP proteins function by aggregating components of a MAP kinase module (including MLK, MKK7, and JNK) and facilitate signal transmission by the protein kinase cascade.

Adaptor Proteins, Signal Transducing↗

Detection of canine herpesvirus DNA in the ganglionic neurons and the lymph node lymphocytes of latently infected dogs.

To determine the site of latent infection of canine herpesvirus (CHV), tissues from dogs convalescent from acute infection with CHV were examined for the presence of viral genome DNA by the nested polymerase chain reaction. CHV DNA was detected in the trigeminal ganglia and the retropharyngeal lymph nodes. In situ hybridization study of the tissues revealed that CHV genome persisted in the nuclei of ganglionic neurons and lymphocytes.

Animals↗

Differences in receptor specificity between Newcastle disease viruses originating from chickens and waterfowl.

We compared the receptor specificity of Newcastle disease viruses from a variety of avian species, including chickens and wild waterfowl, using hemagglutination tests with erythrocytes from different animal species. All isolates from wild waterfowl agglutinated horse erythrocytes, while the chicken isolates did not. The results showed that the receptor specificity of Newcastle disease viruses is different, depending on the avian species from which the viruses are isolated.

Animals↗

Replacement of internal protein genes, with the exception of the matrix, in equine 1 viruses by equine 2 influenza virus genes during evolution in nature.

To establish the evolutionary association between the equine 1 H7 HA and M genes, phylogenetic analyses of the six internal gene segments of equine 1 influenza viruses (H7N7 subtype) were performed using partial nucleotide sequences. The results demonstrated that five internal genes (PBI, PB2, PA, NP and NS) of equine 1 viruses isolated after 1964 were replaced by those of equine 2 H3N8 viruses. However, the M gene was maintained during the evolution of these equine 1 viruses. These findings suggest a functional association between equine H7 HA and M gene products, most likely M2 protein.

Animals↗

Serum 2-hydroxyestradiol 17-sulphate in pregnancy.

2-Hydroxyestradiol 17-sulphate (2-OH E2-17-S) is a catecholized form of sulphated estrogen. In vitro studies showed that its antioxidative effect is almost equal to that of free catecholestrogens, such as 2-OH E2 or 4-OH E2 and alpha-tocoferol, but the existance of 2-OH E2-17-S in human serum has not yet been made clear. 2-OH E2-17-S strongly antagonizes lipid peroxidation, and so it may play an important role in pregnancy, for example as an anti-oxidant in pregnancy-induced hypertension (PIH). The serum level of 2-OH E2-17-S was measured during mid to late pregnancy by a direct radioimmunoassay (RIA) without hydrolysis. The serum levels at 28-31 weeks, 32-35 weeks and 36-40 weeks of gestation were 4.68+/-0.93 (mean+/-SE), 8.38+/-1.21 and 18.31+/-3.41 nmol/l, respectively. The serum level in PIH cases at 36-40 weeks (4.64+/-1.29 nmol/l) was significantly lower than that in normal pregnancy. The 2-OH E2-17-S level in umbilical arteries was significantly higher than that in maternal peripheral vein. These results suggest that the feto-placental unit plays an important role in catecholizing E2-17-S to 2-OH E2-17-S, which may act as an antioxidant in pregnancy.

Estradiol↗

Prediction of life expectancy in patients with primary pulmonary hypertension. A retrospective nationwide survey from 1980-1990.

Primary pulmonary hypertension (PPH) is a progressive disease of unknown etiology usually followed by death within 5 years after diagnosis. Although heart-lung or lung transplantation is now offered to patients with advanced PPH, adequate criteria assessing an accurate prediction of life expectancy in PPH has been difficult to establish. The aims of this study were to identify the characteristic features associated with a poor prognosis in patients with PPH, and to attempt to establish an individual prognostic index that predicts with great accuracy survival or death of PPH after one year, thereby helping to define criteria for patient selection for transplantation. In 1991, a retrospective nation-wide survey on PPH was conducted in Japan, and the clinical and cardiorespiratory variables of 223 PPH cases (female; 144, male; 79) in the period from 1980-1990 were obtained. The mean pulmonary arterial pressure (PPA) was 57.5+/-17.2 mm Hg (mean+/-SD), and the overall median survival time was 32.5 months since the first diagnostic catheterization. The characteristic features of 61 patients who died within one year of catheterization (Nonsurvivors group) were compared to 141 patients who survived one year or more from the time of catheterization (Survivors group). Among several clinical and cardiorespiratory variables, heart rate, PPA, right atrial pressure (PRA), stroke volume index (SI), pulmonary vascular resistance, and partial pressure of carbon dioxide (PaCO2) were significantly different between the two groups. As the independent factors, PPA, PRA, SI, and PaCO2 were selected for the multiple logistic analysis. Using a 0.7 probability cut-point to separate Nonsurvivors from Survivors, 84.6% of Nonsurvivors and Survivors could be correctly predicted from this logistic regression equation. Predictive equations like the present preliminary one can be used in the future to better assess life expectancy in patients with PPH in whom transplantation will be considered.

Adolescent↗

[Investigation of pulmonary hemodynamics and chest X-ray findings in patients with pulmonary tuberculosis sequelae and obstructive ventilatory impairment].

We investigated pulmonary hemodynamics and chest X-ray findings to explore significance of obstructive ventilatory impairment in patients with pulmonary tuberculosis sequelae. One hundred and two patients underwent examinations of blood gases, spirometry, and right cardiac catheterization. The patients were divided into two groups, according to forced expiratory volume in one second as the percentage of forced vital capacity (FVC), which was expressed as FEV1%. Group A (n = 38) had FEV1% of 55% or lower and Group B (n = 64), FEV1% above 55%. First, the values of blood gases and hemodynamics were compared between the two groups, regarding the percent predicted value of FVC as a covariate. Secondly, between 26 of Group A and 42 of Group B, the change of pulmonary arteriolar resistance (PAR) before and after 100% oxygen breathing for 10 minutes was compared. These comparisons were made by exploratory data analysis. Lastly, we described every case with five items of chest X-ray findings and the extent of each finding we had defined. The items were emphysematous change; fibrosis, bronchiectasis and/or cavity; pulmonary resection and/or atelectasis; pleural thickening; and thoracoplasty. We explored X-ray findings influenced on airway obstruction by ridit (abbreviation for "relative to an identified distribution") analysis, taking smoking status into consideration. The results were as follows. (1) The patients of Group A tended to show severer hypoxemia and tissue hypoxia than the patients of Group B. (2) The patients of Group A tended to show worse values of pulmonary hemodynamics than the patients of Group B. Under an even level of the arterial oxygen tension that was 60 Torr or lower, pulmonary artery mean pressure was higher in Group A than in Group B. (3) PAR after oxygen breathing was less likely to decrease in Group A than in Group B. (4) As any mean ridit was standardized and adjusted to 0.5 in Group B, every mean ridit of "emphysematous change" in Group A was the largest-0.63 in non-smokers, 0.74 in ex-smokers and 0.70 in current smokers. Therefore, "emphysematous change" was more influenced on airway obstruction than any other finding because of the largest mean ridit. We conclude as follows. Pulmonary hypertension is more serious in patients suffering from severe airway obstruction with pulmonary tuberculosis sequelae, and it may be attributable to reduction in capacity of anatomical pulmonary vascular bed rather than hypoxic pulmonary vasoconstriction. Pathological changes such as "emphysematous change" on the radiograph might be considered as an important cause of obstructive ventilatory impairment.

Adolescent↗

[Pulmonary hemodynamic and gas exchange effects of various oxygen concentrations in patients with severe pulmonary hypertension primarily affecting the pulmonary vasculature].

The aim of this study was to evaluate pulmonary hemodynamic and gas exchange response to oxygen inhalation in patients with severe pulmonary hypertension primarily affecting the pulmonary vasculature. This study included 7 patients with primary pulmonary hypertension (PPH), 11 with pulmonary hypertension related to collagen vascular diseases (CoPH), and 18 with chronic thromboembolic pulmonary hypertension (CTEPH). All patients had mean pulmonary arterial pressure (PPAm) of greater than 25 mm Hg. We divided the patients into two groups: a PPH + CoPH group comprising the 7 PPH and 11 CoPH patients, and the CTEPH group. We measured cardiopulmonary variables after 10 min inhalation of various oxygen concentrations (FiO2 0.24, 0.28, 0.4, 1.0). In the PPH + CoPH group, PPAm significantly decreased after the inhalation of oxygen concentrations of 40% or more. This was associated with a significant reduction in pulmonary arteriolar resistance (PAR), and suggested active pulmonary vasodilation was caused by oxygen inhalation. In the CTEPH group, on the other hand, PPAm significantly decreased after the inhalation of oxygen concentrations of 28% or more, apparently in association with a significant fall of cardiac output. However, PAR was unchanged regardless of the inspired oxygen concentration, indicating an absence of pulmonary vasodilation in the CTEPH group. When breathing room air, 7 patients in the PPH + CoPH group (38.9%) and 10 in the CTEPH group (55.6%) demonstrated mixed venous oxygen tension (PvO2) values of less than 35 Torr. Extra attention should be paid to PvO2 when administering oxygen therapy to patients with severe pulmonary hypertension.

Collagen Diseases↗

[Investigation of pulmonary hemodynamics and chest X-ray findings in hypercapnic patients with pulmonary tuberculosis sequelae].

We investigated pulmonary hemodynamics and chest X-ray findings to explore pathophysiological significance of chronic hypercapnia in patients with pulmonary tuberculosis sequelae. One hundred and seven patients underwent examinations of blood gases and right cardiac catheterization. The patients were divided into two groups, according to arterial carbon dioxide tension under room air breathing (PaCO2). Group I (n = 35) was defined as 45 Torr or lower of PaCO2, and Group II (n = 72) was the hypercapnic group whose PaCO2 was over 45 Torr. In addition, spirometry was done in 34 patients of Group I and 68 of Group II. First, the values of blood gases, spirometry and pulmonary hemodynamics were compared between the two groups. Secondly, between 22 of Group I and 50 of Group II, the values of pulmonary arteriolar resistance (PAR) before and after 100% oxygen breathing for 10 minutes were compared. These comparisons were made by exploratory data analysis. Lastly, we described in all cases with five items of chest X-ray findings and the extent of each finding we had defined. The items were emphysematous change; fibrosis, bronchiectasis, and/or cavity (hereafter abbreviated as "fibrosis"); lung resection and/or atelectasis; pleural thickening; and thoracoplasty. We explored the items of X-ray findings which may relate to hypercapnia by ridit (abbreviation for "relative to an identified distribution") analysis. The results were as follows. (1) Hypercapnic patients tended to have severer restrictive ventilatory impairment and hypoxemia. Under an even level of arterial oxygen tension (PaO2), tissue oxygenation was not poorer in Group II than in Group I. (2) Hypercapnic patients tended to have more unfavorable pulmonary hemodynamics. More than half of them had pulmonary hypertension defined as 20 mmHg or higher of pulmonary artery mean pressure (PAm). Under an even level of PaO2, PAm was higher in Group II. Although 34 patients of Group II showed PaO2 over 60 Torr, 23 of them had pulmonary hypertension. (3) PAR after oxygen breathing was more likely to decrease in Group II than in Group I. (4) As any mean ridit was standardized and adjusted to 0.5 in Group I, the maximum was the mean ridit of "pleural thickening" (= 0.67), next "fibrosis" (= 0.65) in Group II. The above two items of X-ray findings, in which each mean ridit was higher than in any other item, were more influential on hypercapnia. We conclude as follows. (1) Pulmonary hypertension is severer in hypercapnic patients with pulmonary tuberculosis sequelae; it may be mainly attributable to hypoxic pulmonary vasoconstriction. (2) An important cause of chronic hypercapnia may be pathological changes such as "pleural thickening" and "fibrosis" seen on the radiogram.

Adult↗