Role of heme oxygenase-1 in cardiovascular diseases: a novel target for molecular intervention?
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Cardiovascular Diseases↗
Biomedical subjects
K Ohta
Publications and source records attributed to K Ohta.
Ligands for peroxisome proliferator-activated receptor gamma inhibit growth and induce apoptosis of human papillary thyroid carcinoma cells.
Ligands for peroxisome proliferator-activated receptor gamma (PPARgamma) induce apoptosis and exert antiproliferative effects on several carcinoma cell lines. The present study investigates the expression of PPARgamma and the possibility that agonists for PPARgamma also inhibit the growth of human thyroid carcinoma cells. We examined this hypothesis using six cell lines, designated BHP thyroid carcinoma cells, which originated from patients with papillary thyroid carcinoma. RT-PCR analysis revealed that the thyroid carcinoma cell lines BHP2-7, 7-13, 10-3, and 18-21 express PPARgamma. More PPARgamma was expressed in carcinoma than in adjacent normal thyroid tissue in three of six samples of human papillary carcinoma of the thyroid. PPARgamma-positive thyroid carcinoma cells were treated with agonists of PPARgamma, troglitazone, BRL 49653, and 15-deoxy-12,14-prostaglandin J2. Troglitazone (10 micromol/L), BRL 49653 (10 micromol/L), and 15-deoxy-12,14-prostaglandin J2 (1 microg/mL) decreased [(3)H]thymidine incorporation and reduced cell number, respectively, in BHP carcinoma cell lines that expressed PPARgamma. Under low serum conditions, ligands for PPARgamma induced condensation of the nucleus and fragmentation of chromatin into nucleosome ladders. These findings indicate that the death of thyroid carcinoma cells is a form of apoptosis. To investigate the molecular mechanism of the apoptosis, we assessed expression of the apoptosis-regulatory genes bcl-2, bax, and c-myc. Troglitazone significantly increased the expression of c-myc messenger RNA but had no effect on the expression of bcl-2 and bax in thyroid carcinoma cells. These results suggest that, at least in part, the induction of apoptosis in human papillary thyroid carcinoma cells may be due to an increase of c-myc. Troglitazone (500 mg/kg.day) significantly inhibited tumor growth and prevented distant metastasis of BHP18-21 tumors in nude mice in vivo. Taken together, these results suggest that PPARgamma agonist inhibit cell growth of some types of human thyroid cancer.
Animals↗
Galactosyldiacylglycerol, a mammalian DNA polymerase alpha-specific inhibitor from a sea alga, Petalonia bingbamiae.
The glycolipid galactosyldiacylglycerol (GDG), containing C16:0 and C18:1 fatty acids, was isolated from the sea alga Petalonia bingbamiae as a potent inhibitor of the activities of mammalian DNA polymerase alpha (pol. alpha). GDG, however, had no effect on pol. alpha from a fish or a higher plant. The inhibition of pol. alpha by GDG was dose-dependent with an IC50 value of 54 microM. The compound did not influence the activities of other replicative DNA polymerases such as mammalian pol. delta, or repair-related enzymes such as mammalian pol. beta. GDG also did not influence the activities of prokaryotic DNA polymerases such as the Klenow fragment of DNA polymerase I, T4 DNA polymerase, Taq DNA polymerase, DNA polymerases from the higher plant, cauliflower, or DNA metabolic enzymes such as calf thymus terminal deoxynucleotidyl transferase, human immunodeficiency virus type 1 reverse transcriptase and deoxyribonuclease 1. Kinetic analysis of the compound showed that pol. alpha was non-competitively inhibited with respect to both the DNA template and the nucleotide substrate. In this study, we demonstrated the structure-function relationship in the selective inhibition of pol. alpha by the glycolipid group.
Animals↗
Novel retinoidal tropolone derivatives. Bioisosteric relationship of tropolone ring with benzoic acid moiety in retinoid structure.
Several tropolone derivatives (4-7) were designed as novel retinoids on the assumption that the tropolone ring may mimic the benzoic acid moiety in retinoid structures, such as Am80 (2). Among the synthesized compounds, 5-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethynyl]tropolone (7a) showed moderate potency as a differentiation-inducer of HL-60 cells. The activities of the tropolones were greatly enhanced in the presence of HX630, an RXR agonist (retinoid synergist).
Benzoates↗
Purification and characterization of an acidophilic xylanase from Aureobasidium pullulans var. melanigenum and sequence analysis of the encoding gene.
An extracellular endo-1,4-beta-xylanase was purified from the culture supernatant of Aureobasidium pullulans var. melanigenum (ATCC 20524) grown on oat-spelt xylan. The purified enzyme showed a single band on SDS-polyacrylamide gel electrophoresis with an apparent M(r) of 24 kDa and had an isoelectric point of 6.7. Xylanase activity was optimal at pH 2.0 and 50 degrees C. The genomic DNA and cDNAs encoding this protein were cloned and sequenced. Southern blot analysis indicated that the xylanase gene (xynI) was present as a single copy in the genome. An open reading frame, consisting of 663 bp, encoded a presumed prepropeptide of 34 amino acids and a mature protein of 187 amino acid. The DNA region encoding the prepeptide was interrupted by a 59-bp intron. A single transcription start point was observed at position -46 (A) from the start codon. The 5'-noncoding region had a putative TATA box at -91 (TATATAA) and two possible CCAAT boxes at -247 (CAAT) and -283 (CCAAT). A cloned xynI cDNA was expressed in Saccharomyces cerevisiae. The deduced amino acid sequence showed 94% identity with that of a previously reported equivalent gene (xynA) encoding a xylanase with an optimal pH of 4.8 from a color variant strain, NRRL Y-2311-1, of A. pullulans. A neighbor-joining tree showed that the Aureobasidium enzymes are closely related to several other family-11 xylanases from black aspergilli and Penicillium purpurogenum.
Journal Article↗
Atopic NC/Nga mice as a model for allergic asthma: severe allergic responses by single intranasal challenge with protein antigen.
Since certain characters of allergic asthma are common with other allergic disorders like atopic dermatitis, the possible relationship in etiology is expected. Herein, we investigated whether NC/Nga mice, an inherent animal model for human atopic dermatitis, are inclined to allergic asthma. A single intranasal challenge of NC/Nga mice immunized with ovalbumin (OVA) resulted in an increase in plasma levels of OVA-specific IgE, and typical pathological aspects of allergic asthma characterized by infiltration of numerous eosinophils, mucus hyper production of bronchial epithelial cells. Moreover, airway hyperresponsiveness to inhaled acetylcholine and marked enhancement of airway resistance after the challenge were observed as compared to control BALB/c mice. Delayed expression of mRNA of eosinophil active chemokines, interleukin-5, eotaxin, macrophage inflammatory protein-1alpha in concert with eosinophilia was determined in the lung of NC/Nga mice. These results suggest that asthmatic responses developed in NC/Nga mice challenged with OVA are very similar to human allergic asthma, and that NC/Nga mice are a useful model to elucidate various aspects of allergic asthma.
Acetylcholine↗
Three patients with isolated adrenocorticotropin deficiency presenting with neuroleptic malignant syndrome-like symptoms.
We report 3 patients with isolated adrenocorticotropin (ACTH) deficiency presenting with neuroleptic malignant syndrome (NMS)-like symptoms. All patients were in their 60's or 70's and showed consciousness disturbance, a high-grade fever, extrapyramydal signs, and muscle enzyme elevations, which met the criteria for NMS. Also, they all showed hyponatremia induced by isolated ACTH deficiency. In addition to the standard therapy for NMS, corticosteroid supplement therapy was effective in all patients. There thus appear to be subjects with isolated ACTH deficiency among patients presenting with NMS-like symptoms, and adrenal and pituitary function should be checked in NMS patients with hyponatremia.
Adrenocorticotropic Hormone↗
Symposium on molecular pathogenesis of respiratory diseases and its clinical implication. 2. Obstructive lung disease.
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Allergens↗
Evaluation of the AMPLICOR CMV, COBAS AMPLICOR CMV monitor and antigenemia assay for cytomegalovirus disease.
The AMPLICOR CMV (qualitative DNA assay by PCR), COBAS AMPLICOR CMV Monitor (quantitative DNA assay by PCR), and antigenemia assay were tested for their ability to diagnose cytomegalovirus (CMV) infection in 115 immunocompromised patients. The AMPLICOR qualitative assay and the antigenemia assay were positive for all nine patients with a clinical diagnosis of CMV disease. The AMPLICOR quantitative assay was negative for one of the nine patients. In 106 patients without CMV disease, the AMPLICOR qualitative test was positive in 22, the quantitative test was positive in 23, and the antigenemia test was positive in 55 patients. The AMPLICOR qualitative and quantitative assays had specificities of 79% and 78% in patients without CMV disease, while that of the antigenemia assay was 48%. Diagnostic efficiencies were 79% for the AMPLICOR qualitative assay, 69% for the AMPLICOR quantitative assay, and 48% for the antigenemia assay. All three tests yielded positive results before, or at the same time as, the onset of CMV disease in most cases, which suggests they can be used to predict disease before the onset of symptoms. During antiviral treatment, test results tended to decrease quantitatively and finally became negative; negative results were followed by remission of symptoms. This suggests that the AMPLICOR quantitative assay and the antigenemia assay could be useful for monitoring therapeutic efficacy. The AMPLICOR qualitative and quantitative assays, as well as the antigenemia assay were considered effective for all of the following: diagnosing CMV disease, predicting the onset of disease, and evaluating the effectiveness of antiviral chemotherapy. The antigenemia assay was at times difficult to perform in the case of severely neutropenic patients, whereas the AMPLICOR assays could be used in such cases.
Antigens, Viral↗
[A case of inoperable advanced gall bladder cancer responding to intra-arterial infusion of 5-fluorouracil (5-FU) and leucovorin (LV)].
The prognosis in cases of inoperable advanced gall bladder cancer is poor. We report here a case of inoperable advanced gall bladder cancer that responded to treatment with continuous intra-arterial infusion of 5-FU and bolus injection of LV for biochemical modulation. The patient was an 81-year-old woman, who visited a nearby clinic with the chief complaints of general fatigue and right lateral abdominal pain. A mass lesion which occupied from the dorsal surface of the liver to the pancreatic head was found by ultrasonography, and she was referred to our hospital for further diagnosis and therapy. The diagnosis was advanced gall bladder cancer of Stage IVa (S2, N3, P0, H0, Hinf1, Dinf1). For the selective arterial infusion of anticancer drugs, the patient underwent intra-arterial cannulation into the common hepatic artery, with a connecting subcutaneous port for arterial infusion therapy. The treatment schedule for 5-FU and LV therapy consisted of continuous infusion of 5-FU of 333 mg/m2 for 72 hr and bolus injection of LV of 20 mg/m2 3 times at 24 hr intervals. This treatment was repeated every 2 weeks. No side effects were observed after the first administration during hospitalization, so the treatment was continued up to 17 times on an outpatient basis. A tumor response was seen in the primary lesion, No. 8 and No. 16 lymph node metastases. A partial response was observed for 13 months and the overall survival was 15 months. These findings may imply that treatment with intra-arterial infusion of 5-FU and LV can be an effective chemotherapy for prolongation of survival in patients with inoperable advanced gall bladder cancer.
Aged↗
[Evaluation of polymerase chain reaction method for monitoring of fungal infection in compromised hosts].
Diagnosis of fungal infections in compromised hosts has been difficult because of insufficient sensitivity and specificity of conventional methods such as culturing and serum testing. Therefore, antifungal agents are usually started in febrile patients who are resistant to antibiotics even if these monitoring tests were negative. In this study, therefore, in order to increase the reliability of these monitoring, polymerase chain reaction (PCR) methods for detection of blood fungus were also performed in compromised hosts including 14 patients with hematological malignancies and one with solid tumor who were undergoing chemotherapies. From these patients, total of 56 peripheral blood samples was collected periodically, irrespective of the presence of infectious signs. At each time point of venopuncture, status of the patient was allocated to one of the followings: A, receiving an intravenous antifungal therapy because of sustaining fever which had not responded to prior antibiotic therapies and also positive for culturing and/or serum beta-D-glucan tests; B, receiving an additional intravenous antifungal therapy but negative for culturing and serum-tests; C, febrile but not yet receiving any intravenous fungal therapy; D, afebrile status. During the study, 10 blood samples from 3 patients were allocated in group A, and one sample of them was positive while remaining 9 were all negative for PCR. Six samples from 4 patients were in group B, and one was PCR positive while remaining 5 were negative. Fifteen samples from 7 patients were in group C, and 3 were positive and 12 were negative for PCR. Twenty-five samples were in group D, and 5 were positive and 20 were negative for PCR. Thus, the results from fungal PCR in these patients were in some case showed discrepancies from those expected from the clinical course and/or conventional monitoring tests. Further evaluation of fungal PCR may gain insight into the more precise diagnosis of fungal infection in these patients.
Adult↗
[CD13- and CD33-negative acute myelocytic leukemia (FAB classification; M2) with morphological changes and CD13 expression on recurrence].
A 42-year-old man was diagnosed as having acute myelocytic leukemia in July 1998. The leukemic cells tended to be differentiated, and on the basis of positive peroxidase staining, this case was considered to be AML (M2) according to the FAB classification. t(8;21)(q22;q22) chromosomal abnormality was observed, but surface antigen analysis revealed no expression of either CD13 or CD33, a finding characteristic of myelocytic leukemia. Combination chemotherapy resulted in complete remission, and allogeneic bone marrow transplantation was performed with donor cells from the patient's sister. Unfortunately, however, the patient died about 18 months after the onset of leukemia. Comparison of the findings at recurrence with those at initial diagnosis revealed morphological changes in non-differentiated immature cells (AML-M1) and CD13 surface antigen expression. This was considered to be a rare case of AML with neither CD13 nor CD33 expression at onset, but with CD13 expression at recurrence.
Adult↗
[Neoadjuvant chemotherapy for advanced gastric cancer].
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Antineoplastic Combined Chemotherapy Protocols↗
[Roles of clinical laboratory monitoring in bone marrow and peripheral blood stem cell transplantation].
Hematopoietic stem cell transplantation(HSCT) increase the chances of cure of many hematological malignancy. The clinical laboratory plays a major role in support of HSCT. Both transplantation-specific laboratory test(tissue typing, assessment of graft viability/rejection, evaluation of minimal residual disease, and measurement of immunosuppressive drugs) and routine clinical laboratory tests(biochemical, hematological, serological, urinary, bacteriological, and physiological examinations) are significant. Hematopoietic stem cells(HSC) are usually assessed as CD34+ cells, while immature cells determined by automated hematology analyzers can simply evaluate HCS. These automated immature cell counts are earlier markers of engraftment following transplantation than the traditional indicators(neutrophils and platelets). After transplantation, infections, regimen-related toxicities, graft-versus host disease, veno-occlusive disease, and thrombotic microangiopathy are the serious complications, which are causes of expected mortality and morbidity in HSCT. Clinical laboratory monitoring may contribute early diagnosis and treatment of the complications, resulting in prevention of the adverse events.
Bone Marrow Transplantation↗
[Health status and lifestyle issues of homeless people in Sapporo city, 2000].
OBJECTIVE: To clarify the health status and lifestyle issues of homeless people in Sapporo city, voluntary "health consultations and medical examinations" were carried out near an emergency kitchen. METHODS: The voluntary activities were held in a park near the shelter tents of homeless people seven times from December 1999 to December 2000. The homeless people who consulted us, medical doctors, were asked detailed questions about past history, present illness, subjective symptoms, lifestyles and so on, and were examined for their blood pressure and urinary parameter. RESULTS: A total of 60 homeless people, including 59 men and 1 woman, were consulted and examined, Fifty-seven percent of them were 50 years old of older, and 30% had been homeless for less than half a year. Forty percent had some dental problems, 28% suffered neck stiffness, and 27% back pain. The medical examination found 53% of them to be hypertensive and 26% to be diabetic. Twenty-five percent had meals only once a day, 55% had meat or fish in their diet not more than twice a week and 57% had vegetables in their diet not more than twice a week. Forty-two percent slept not more than 5 hours a day, 13% often drank alcohol in the daytime, and 83% were smokers. CONCLUSION: The present results suggest that lifestyle-related chronic diseases are more significant problems among homeless people in Sapporo city than common infectious diseases such as tuberculosis or dysentery, probably because it is colder and therefore there are fewer homeless people in Sapporo city than in other major cities in Japan such as Tokyo and Osaka. Further studies of the homeless people living in such a cold environment are warranted to develop better health policies for them in the context of their social and economical determinants. In addition, it is important to establish a more reliable registration system for these people in order to plan and provide a comprehensive social and health support network as needed.
Adult↗
[Two cases of alveolar hemorrhage due to inhalation of detergent aerosol].
We report on two cases of alveolar hemorrhage after inhalation of detergent aerosol. Case 1: A 54-year-old woman was referred to our hospital with a complaint of hemoptysis. She used a spray type detergent for ventilation fan cleaning, and recognized hemoptysis later for eight hours. She had mild anemia and severe hypoxemia, and chest radiographs and CT films infiltrative shadows were recognized predominantly in the right middle, left lingual lower lobes. Case 2: A 22-year-old woman was admitted to our hospital complaining of bloody sputum and dyspnea. She had used a spray-type detergent for bathroom cleaning intermittently for one week. Between the beginning of this activity and the seventh day, cough and dyspnea developed. Chest radiographs and CT films disclosed diffuse infiltrative shadows in both lung fields. In both cases, the condition was diagnosed by bronchoalveolar lavage as alveolar hemorrhage. In case 2, a transbronchial lung biopsy specimen revealed alveolitis without vasculitis or capillaritis. Both the clinical symptoms and the CT images were improved by steroid administration. The steroid dosage was decreased gradually and stopped, but there was no relapse of the hemoptysis. Neither patient was positive for antinuclear antibodies or antibodies against the cytoplasm of granulocytes. Urinalysis showed no pathological findings. Since the hemoptysis appeared after inhalation of a detergent aerosol, it was possible that inhalation was the cause of the hemorrhage.
Adult↗
[Chronological changes of lacunar infarctions on fluid-attenuated inversion recovery magnetic resonance images].
In 26 patients with lacunar syndromes, emergence of new lacunar infarctions were identified within 13 days from onset by diffusion-weighted magnetic resonance images. The identified lacunar infarctions were repeatedly imaged using fluid-attenuated inversion recovery (FLAIR) sequence up to 600 days from onset. On FLAIR images taken by 23 days from onset, lacunar infarctions showed homogeneous hyperintensity. On the later FLAIR images beyond 25 days from onset they were observed as heterogeneously hyperintense lesions in half of the patients. In the other patients, lacunar infarctions were observed as hypointense areas with a hyperintense rim beyond 41 days from onset, which indicates cystic transformation with surrounding gliosis. These FLAIR images of lacunar infarction differ from those of dilated perivascular space which is observed as an area of simple hypointensity.
Adult↗
[Ectopic ADH producing tumor].
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Adolescent↗