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Biomedical subjects

E Ueda

Publications and source records attributed to E Ueda.

At least 37 records · Page 2Linked to original sources

Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis.

BACKGROUND: Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SACE in this disease has been found. A study of the association of angiotensin II receptor gene polymorphisms with sarcoidosis was therefore undertaken. METHODS: ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls. RESULTS: There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups. Neither AGTR1 nor AGTR2 polymorphisms were associated with sarcoidosis. SACE activity was higher in patients with sarcoidosis with the AGTR1 A/C genotype than in others. However, this tendency was not detected in patients with tuberculosis. CONCLUSIONS: The AGTR1 allele C is associated with high activity of SACE in patients with sarcoidosis. It is another predisposing factor for high levels of SACE in patients with sarcoidosis and is considered to be an independent factor from the ACE D allele for high levels of SACE in sarcoidosis. This fact could be one of the explanations for the increased SACE activity in sarcoidosis.

Analysis of Variance↗

Circulating KL-6 predicts the outcome of rapidly progressive idiopathic pulmonary fibrosis.

Searching for early predictive markers of the therapeutic effects of high-dose corticosteroids ("pulse therapy") on patients with rapidly progressing idiopathic pulmonary fibrosis (IPF), we evaluated 14 such patients, who had received weekly pulse therapy for at least 3 wk. Eight patients responded to the treatment and survived. However, six patients failed to respond, and all of them died within 3 mo after treatment. Serum levels of KL-6 (MUC1 mucin), neutrophil elastase (NE), and lactate dehydrogenase (LDH) were measured before, and at 1 wk and 3 wk after treatment. Levels of KL-6 decreased significantly in patients who lived, whereas KL-6 levels tended to increase in patients who died. The values of NE did not change significantly. LDH levels decreased significantly at 1 wk, and tended to decrease at 3 wk in patients who lived. However, in patients who died, they did not significantly change. At the first cycle of treatment when clinical effects may not be evident, the decrease in KL-6 but not LDH levels was significantly related to a favorable outcome, whereas their increase was related to a poor outcome. Results suggest that monitoring with KL-6 may contribute to early clinical decisions for alternative therapy in the management of rapidly progressing IPF.

Aged↗

KL-6 as a serologic indicator of Pneumocystis carinii pneumonia in immunocompromised hosts.

KL-6, a serum marker for interstitial pneumonitis, was evaluated in patients with Pneumocystis carinii pneumonia (PCP). Patient 1 was a 56-year-old woman with rheumatoid arthritis treated with immunosuppressive drugs and corticosteroids. Patient 2 was a 59-year-old man with a glioblastoma who received anti-cancer drugs and corticosteroids. In both patients, serum KL-6 showed an abnormally high level due to the complication of PCP, and it decreased following successful treatment. These results indicate that PCP is one of the diseases in which serum KL-6 increases.

Antigens↗

[Evaluation of eosinophilic cationic protein levels in patients with eosinophilic pneumonia].

We investigated the significance of eosinophilic cationic protein (ECP) as a biological indicator of disease activity in patients with eosinophilic pneumonia (EP). ECP levels were measured in serum and bronchoalveolar lavage fluid (BALF) samples from patients with EP or other diffuse interstitial lung diseases and from healthy subjects. Also we performed immunohistochemical staining of lung tissue sections from patients with EP using anti-EG 2 antibody, and computed the correlation between the number of EG 2-positive cells in lung tissues and ECP levels in serum and BALF from patients with EP. Levels of ECP in serum and BALF samples from patients with EP were significantly elevated compared to the levels in samples from other interstitial lung-disease patients and healthy subjects. Additionally, changes in serum ECP levels reflected the clinical courses for EP patients. Approximately 90 percent of the infiltrated eosinophils in tissue sections from patients with EP were EG 2-positive and activated. The number of EG 2-positive cells in lung tissues correlated significantly with levels of ECP in serum and BALF samples from patients with EP. These findings suggested that ECP levels in serum and BALF reflect the degree of eosinophil activation in lung tissues and the degree of disease activity in patients with EP. We concluded that ECP may serve as a useful biological indicator in EP.

Biomarkers↗

A clinical analysis of the recovery from sensory disturbance after sagittal splitting ramus osteotomy using a Semmes-Weinstein pressure aesthesiometer.

A number of studies of evaluation methods for sensory disturbance after sagittal splitting ramus osteotomy (SSRO) are known. To compare postoperative sensory disturbances among patients in different hospitals, a highly reproducible and standardized sensory test is required. In the present study, we measured the tactile threshold in the region innervated by the mental nerves in 45 patients (90 sides) after SSRO using a Semmes-Weinstein pressure aesthesiometer. The percentage of recovery to the normal level defined by Bell was 72.2% at one week, 82.2% at 4 weeks, and 90.0% at 8 weeks after SSRO. The recovery process was evaluated by classifying the postoperative sensory disturbance into 5 grade levels according to Bell's interpretation scale. The results showed that the SW sensory test is useful for evaluation of the recovery process from sensory disturbance after SSRO. Some improvements of this test were also discussed.

Adult↗

A patient with paroxysmal nocturnal hemoglobinuria bearing four independent PIG-A mutant clones.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by clonal blood cells that are deficient in the surface expression of glycosylphosphatidylinositol-anchored proteins due to somatic mutation in the X-linked gene PIG-A. In some patients, more than one abnormal clone may be present. Analysis of bulk DNA/RNA from granulocytes has been useful in identifying the predominant PIG-A mutation in each patient. However, it is often not useful in determining the presence of minor clones. Many patients have cells with partial deficiency. Here, we analyzed the PIG-A gene in two B-cell lines bearing complete or partial deficiencies, cells of hematopoietic progenitor colonies and peripheral blood granulocytes from the same patient. We found that two B-cell lines had different mutations, the granulocytes contained at least two mutants, and the hematopoietic progenitors contained four mutants. Three of the four were shared by B cells and/or granulocytes whereas the other one was found only in the hematopoietic progenitors. The partial deficiency was caused by a point mutation near an alternative splice site within exon 2 that resulted in partial decreases of activity and quantity of the full-length transcript. These results further show the oligoclonal nature of PNH and differences in extent of expansion among mutant clones.

Alternative Splicing↗

Increased frequency of somatic mutations at glycophorin A loci in patients with aplastic anaemia, myelodysplastic syndrome and paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH), aplastic anaemia (AA) and myelodysplastic syndrome (MDS) are haemopoietic stem cell disorders. These disorders have some features in common, and a percentage of cases progress to acute leukaemia. We speculated that changes in gene stability are involved in the pathogenesis of these haemopoietic stem cell disorders. Therefore we investigated in vivo mutation frequencies in these disorders by erythrocyte glycophorin A (GPA) mutation assay. The assay enumerates NO or NN variant cells in 106 erythrocytes of the MN type using a flowcytometric technique. Patients undergoing chemotherapy known to be at risk of hypermutageneity were also studied. Events exceeding the 95th percentile of healthy donors (> or = 32 and 34 events, respectively for NO and NN variants) were defined as abnormal. Abnormal events in the NO variants were found in three out of seven patients undergoing chemotherapy, two out of nine patients with AA, two out of seven patients with MDS, and four out of nine patients with PNH. Abnormal events in the NN variants were found in three out of seven patients undergoing chemotherapy, two out of nine patients with AA, one out of seven patients with MDS, and two out of nine patients with PNH. These results suggest that not only PIG-A, but also other genes including the GPA gene, are hypermutable in haemopoietic stem cell disorders, and that mutagenic pressure and/or gene instability can contribute to the pathogenesis of these disorders.

Adult↗

Activation of the human transglutaminase 1 promoter in transgenic mice: terminal differentiation-specific expression of the TGM1-lacZ transgene in keratinized stratified squamous epithelia.

Transglutaminase 1 (TGase 1) is a tissue-specific enzyme which is expressed in the keratinized stratified squamous epithelia and which catalyzes straightepsilon-(gamma-glutamyl) lysine cross-links of proteins to form the cell envelope at the periphery of cornified cells. A transient expression assay using a luciferase reporter gene linked to the 2.5 kb 5' upstream region of the human TGase 1 gene (TGM1) showed phorbol ester-responsive promoter activity in cultured normal human keratinocytes. To assess its promoter activity in vivo, we generated transgenic mice expressing the Escherichia coli beta-galactosidase gene (lacZ) directed by the 5' upstream region. beta-Galactosidase histochemistry revealed that the TGM1-lacZ transgene was expressed in terminally differentiating keratinocytes in upper layers of stratified squamous epithelia in embryonic, neonatal and adult transgenic mice. The expression pattern was similar to that of endogenous TGase 1 mRNA detected by in situ hybridization. Furthermore, topical application of a phorbol ester to adult tail skin enhanced expression of the transgene as well as TGase 1 mRNA in the epidermis. Thus, the 2.5 kb 5' upstream sequence of TGM1 includes elements regulating tissue- and terminal differentiation-specific gene expression in stratified squamous epithelia.

Animals↗

Utility of hyaluronic acid in pleural fluid for differential diagnosis of pleural effusions: likelihood ratios for malignant mesothelioma.

The level of hyaluronic acid (HA) was determined in the pleural fluid of 99 patients, including 19 with malignant mesothelioma, 27 with lung cancer, 1 with breast cancer, 1 with mediastinal tumor and 51 with non-malignant diseases. With a cut-off level at 100 micrograms/ml, the pleural fluid concentration of HA was high in 36.8% of patients (7 of 19) with malignant mesothelioma and 1.3% of patients (1 of 80) with lung cancer and other malignant and non-malignant diseases. The mean concentration of pleural fluid HA was significantly higher in patients with mesothelioma than in those with lung cancer and other malignant and non-malignant diseases. The pre-test probability of MM was 5.9% in this series. The LRs for > or = 100, 50-99 and < or = 49 micrograms/ml are 28.3, 3.3 and 0.5, respectively; these put the post-test probabilities at 64, 17 and 3%, respectively. Indeed, in cases of uncommon disease such as MM, the post-test probability is low even if the cut-off level of HA is > or = 100 micrograms/ml. The discrimination between malignant mesothelioma and lung cancer needs special attention. In these two diseases, the LRs of MM for pleural fluid CEA > 30, 10-30 and < 10 ng/ml were 0.2, 1.9 and 2.4, respectively. The pre-test probability of MM for HA > or = or 100 micrograms/ml is 64%. Furthermore, because the LR for CEA is < 10 ng/ml, the post-test probability is 81%. When the combination of two markers is considered, the high level of HA and the low level of CEA may be useful for the differential diagnosis of MM from pleuritis carcinomatosa.

Biomarkers, Tumor↗

A new type of illegitimate recombination is dependent on restriction and homologous interaction.

Illegitimate (nonhomologous) recombination requires little or no sequence homology between recombining DNAs and has been regarded as being a process distinct from homologous recombination, which requires a long stretch of homology between recombining DNAs. Under special conditions in Escherichia coli, we have found a new type of illegitimate recombination that requires an interaction between homologous DNA sequences. It was detected when a plasmid that carried 2-kb-long inverted repeats was subjected to type II restriction in vitro and type I (EcoKI) restriction in vivo within a delta rac recBC recG ruvC strain. Removal of one of the repeats or its replacement with heterologous DNA resulted in a reduction in the level of recombination. The recombining sites themselves shared, at most, a few base pairs of homology. Many of the recombination events joined a site in one of the repeats with a site in another repeat. In two of the products, one of the recombining sites was at the end of one of the repeats. Removal of one of the EcoKI sites resulted in decreased recombination. We discuss the possibility that some structure made by homologous interaction between the long repeats is used by the EcoKI restriction enzyme to promote illegitimate recombination. The possible roles and consequences of this type of homologous interaction are discussed.

Base Sequence↗

Serial computed tomographic evaluation in desquamative interstitial pneumonia.

BACKGROUND: Desquamative interstitial pneumonia (DIP) may represent the early stage and usual interstitial pneumonia (UIP) the late stage of the same disease. The purpose of this study was to evaluate the computed tomographic (CT) features of DIP, to evaluate the changes in pattern and extent of disease over time, and to determine whether the appearances of DIP on the CT scan change to those of UIP during follow up. METHODS: Sequential CT evaluation was conducted on eight patients with DIP over a mean (SD) follow up period of 3.2 (1.3) years (range 1.6-6.5). The relative extents of ground glass and honeycombing were determined from serial CT scans. Changes in the extent and appearance of the disease were examined in paired anatomically comparable CT sections. RESULTS: Common features on the CT scans of patients with DIP were a homogeneous increase in lung attenuation (n = 5), linear areas of attenuation (n = 5), relatively well preserved lung architecture (n = 5), and the presence of small cysts (n = 6). Uncommon features were architectural distortion (n = 3), and traction bronchiectasis (n = 1). In six patients with DIP with cystic spaces these did not change with time in three cases, in two they regreased, and in one patient they increased. Open lung biopsy samples from patients with DIP with many cystic lesions showed dilated alveolar ducts and bronchioles and/or pulmonary cysts, as well as numerous macrophage-filled air spaces and mild fibrosis, but no typical honeycomb cysts were seen. CONCLUSIONS: Some of the microcysts in DIP are different from the honeycomb cysts seen in UIP, and some of the cysts seen in patients with DIP resolve with time. DIP does not progress to UIP in the short term.

Biopsy↗

[Chronic eosinophilic pneumonia successfully treated with suplatast tosilate].

The patient was a 45-year-old woman in whom a chest X-ray film obtained on admission showed bilateral infiltrative shadows. A chest CT scan revealed areas of consolidation and ground-glass opacities. Examination of bronchoalveolar lavage fluid revealed many eosinophils, and specimens obtained by transbronchial lung biopsy showed thickened alveolar septa with infiltration of eosinophils. The numbers of eosinophils and the level of IgE in blood were low. The radiographic appearance improved after administration of suplatast tosilate. The level of interleukin 5 was high both in plasma and in bronchoalveolar lavage fluid before treatment, but the level of IL-5 in plasma was low after suplatast tosilate was given. Suplatast tosilate, which suppresses the production of cytokines, may be useful in patients with chronic eosinophilic pneumonia.

Anti-Allergic Agents↗

[High levels of elastolytic activity in bronchoalveolar lavage fluid from a patient with idiopathic interstitial pneumonia].

A 63-year-old female with acure exacerbution of idiopathic interstitial pneumonia (IIP) showed high levels of elastolytic activity in bronchoalveolar lavage fluid (BALF). She was admitted to our hospital with progressive dyspnea. Arterial blood gas analysis and pulmonary function tests were abnormal. Examination of the bronchoalveolar lavage fluid revealed an increased numbers of neutrophils. Despite the administration of corticosteroids, the patient died of respiratory failure. A high level of elastolytic activity was present in the BALF. Western immunoblot analysis, using an anti-alpha 1-protease inhibitor (PI) antibody, revealed a truncated alpha 1-PI in the BALF. These findings suggest that an imbalance between protease and PI in the lower respiratory tract contribute to lung tissue damage in patients with IIP.

Bronchoalveolar Lavage Fluid↗

[The clinical efficacy of imipenem/cilastatin sodium in orthopedic infections and drug levels in the bone tissue].

We evaluated the clinical efficacy of imipenem/cilastatin sodium (IPM/CS--a carbapenem antibiotic) against orthopedic infections, and the drug levels of the bone tissues were determined. The clinical efficacies for 6 patients in the infection group were good in 3 cases, and fair in the other 3; giving an efficacy rate of 50%. Bacteriologically, 8 strains were isolated from patients with the infection and an eradication rate of 87.5% was obtained upon the treatment. In 39 patients that were given the drug prophylactically, no postoperative infections occurred. Mean IPM levels in the bone and the bone marrow at 1 hour after administration in 5 patients of the prophylactic group were 17.3 micrograms/ml and 5.9 micrograms/g, respectively. The ratio of concentrations the bone to those in the bone marrow was 34.6%. The results of this study suggest that IMP/CS reaches to the bone tissue providing sufficient concentrations and that the drug is efficacious for the prophylaxis and the treatment of orthopedic infections.

Adolescent↗

The eta isoform of protein kinase C mediates transcriptional activation of the human transglutaminase 1 gene.

Transglutaminase 1 (TGase 1) is expressed during the terminal differentiation of keratinized squamous epithelium to form cornified cell envelope in differentiated keratinocytes by the epsilon-(gamma-glutamyl) cross-linking reaction. The gene for human TGase 1 is responsible for autosomal recessive lamellar ichthyosis, a severe hereditary keratinizing disorder of the skin. We examined the transcriptional activity of the gene in FRSK, rat keratinocytic cells, transfected with the luciferase reporter gene under control of the 5' upstream region of human TGase 1 gene. Transfection of the reporter gene with an expression vector for the eta isoform of novel protein kinase C (nPKCeta), as well as exposure to 12-0-tetradecanoylphorbol-13-acetate, markedly increased the luciferase activity in FRSK, but not in HT-1080 fibrosarcoma cells, although exogenous nPKCeta was expressed in both. The induction was suppressed by deleting the TGase 1 upstream sequence from -95 to -67 and by deleting the kinase domain from exogenous nPKCeta. In comparison with other PKC isoforms, nPKCeta most effectively induced the luciferase activity. We suggest that nPKCeta, an epithelium-specific isoform of PKC, mediates the activation of the TGase 1 transcription.

Animals↗

Analysis of PIG-A gene in a patient who developed reciprocal translocation of chromosome 12 and paroxysmal nocturnal hemoglobinuria during follow-up of aplastic anemia.

The relationships between paroxysmal nocturnal hemoglobinuria (PNH), aplastic anemia (AA), and myelodysplastic syndrome (MDS) are not clear. Here we describe a patient, J20, who developed a reciprocal translocation of chromosome 12 and PNH during follow-up of AA. All metaphases in CD59-deficient bone marrow mononuclear cells had the translocation, whereas none of the CD59-deficient cells had it, indicating that the PNH clone coincided with a cell population bearing the chromosomal aberration. We found a somatic single-base deletion mutation in the PIG-A gene of this patient's peripheral blood cells. This is the first patient with PNH with a PNH clone containing a chromosomal translocation.

Adult↗

[Two cases of von Recklinghausen's disease with diffuse pulmonary changes].

Two patients with von Recklinghausen's disease had diffuse pulmonary diseases. The pulmonary diseases were interstitial fibrosis and emphysematous bullae. In case 2, examination of a specimen obtained by transbronchial lung biopsy revealed fibrotic interstitial thickening and adenomatous hyperplasia. Diffuse pulmonary abnormalities in von Recklinghausen's disease have been said to be fibrotic changes and emphysematous changes, as shown in roentgenograms in these two cases. The biopsy specimen obtained in case 2, however, revealed fibrotic changes only, which could not be distinguished from findings in cases of idiopathic interstitial pneumonia. In case 2, bronchoalveolar lavage fluid was also examined but it did not reveal any unique features of von Recklinghausen's disease. Since 1978, von Recklinghausen's disease has been diagnosed 10 times in our hospital, but diffuse pulmonary diseases was seen in only two of those 10 cases.

Adult↗

[KL-6 in patients with interstitial pneumonitis].

Levels of KL-6 are high in serum and in bronchoalveolar lavage fluid (BALF) from patients with interstitial pneumonitis. To examine the usefulness of the KL-6 level as a marker of disease activity in interstitial pneumonitis, KL-6 was measured in serum and in BALF from patients with this disease. Correlations between KL-6 levels and the number of cells in BALF and between KL-6 levels and pulmonary function were computed. Serum KL-6 levels were abnormally high and correlated with the number of lymphocytes in BALF in patients with interstitial pneumonitis. Furthermore, changes in serum KL-levels reflected clinical coursed in these patients. KL-6 levels in BALF were very high and correlated with the total number of cells, and with the numbers of lymphocytes, neutrophils, and eosinophils in BALF. KL-6 levels in serum and in BALF correlated significantly with %VC, %DLco, and %DLco/VA. These results suggest that KL-6 levels in serum and in BALF reflect the degree of alveolitis and of deterioration of pulmonary function in these patients, and that KL-6 is a useful indicator of disease activity in interstitial pneumonitis.

Antigens↗