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Biomedical subjects

M Hara

Publications and source records attributed to M Hara.

At least 217 records · Page 12Linked to original sources

[Myelodysplastic syndrome associated with polymyalgia rheumatica].

A 69-year-old man was referred to us because of severe pain in both girdles. A diagnosis of polymyalgia rheumatica was made, and low-dose prednisolone therapy (20 mg/d) was started. The patient's muscle pain disappeared after 3 weeks. After 5 months of therapy, pancytopenia became prominent. A marrow aspirate smear showed hypercellularity, trilineage dysplasia, and 7% blasts. The clinical diagnosis was myelodysplastic syndrome, subtype refractory anemia with excess of blasts. In elderly patients presenting with polymyalgia rheumatica, an underlying hematologic malignancy should always be looked for when the disease demonstrates clinical signs inconsistent with typical polymyalgia rheumatica.

Aged↗

KL-6 as a novel serum marker for interstitial pneumonia associated with collagen diseases.

OBJECTIVE: To investigate the diagnostic value of the serum concentrations of KL-6, a mucinous glycoprotein expressed on type II pneumocytes, for interstitial pneumonia (IP) in various collagen diseases. METHODS: Serum KL-6 levels were measured by ELISA. RESULTS: The mean values and the positive rates of serum KL-6 levels for patients with rheumatoid arthritis, systemic sclerosis, or polymyositis/dermatomyositis with IP were significantly higher than those without IP. Sensitivity, specificity, positive and negative predictive values of serum KL-6 level for IP associated with collagen diseases were 60.7, 98.9, 97.4, and 77.1%, respectively. The mean serum KL-6 level of patients with active IP was significantly (p = 0.0001) higher than that of patients with inactive IP. Serum KL-6 levels increased with the deterioration of IP, while the successful treatment of IP resulted in a significant decrease of these levels. CONCLUSION: Serum KL-6 concentration levels are a useful marker for diagnosis and evaluation of the disease activity of IP associated with collagen diseases.

Adult↗

[A case of Sjögren's syndrome and systemic sclerosis complicated with acute pancreatitis].

We report a case of Sjögren's syndrome (SS) and systemic sclerosis (SSc) complicated with acute pancreatitis. A 51-year-old woman had been diagnosed as SS in 1973. She noticed Raynaud's phenomenon in 1977. In 1988, interstitial pneumonia (IP) was pointed out and she was treated with methylprednisolone (mPSL) pulse therapy. Prednisolone (PSL) was gradually tapered to 3-5 mg daily and she visited our outpatient clinic in 1995. On her first admission to our hospital in 1996, she showed xerostomia, keratoconjunctivitis sicca, sclerotic skin changes of her distal extremities and face, thickening of her sublinguinal frenulum, and regurgitative esophagitis. She was positive with anti-SS-A and SS-B antibodies. She was diagnosed as SS and SSc. Radiographic and laboratory data also established the diagnosis of inactive IP, renal tubular acidosis (RTA) and chronic renal failure (CRF). In April 30th 1997, she was admitted to our hospital again with complaints of dyspnea, dysesthesia, epigastralgia and petechia. Active IP and mononeuritis multiplex were diagnosed, and petechia was considered to be associated with vasculopathy. Her serum amylase level was 891 mU/ml on admission and spontaneously increased to 2440 mU/ml on May 12th along with increase of fibrinogen degradation product, D-dimer and alpha 2 plasmin-plasmin inhibitor complex levels. Ultrasonography depicted swelling of her pancreatic head and the diagnosis of acute pancreatitis was made. She was treated with protease inhibitors and intravenous hyperalimentation for acute pancreatitis. mPSL pulse therapy (500 mg/day for 3 days) was instituted for IP and mononeuritis multiplex on May 22, followed by 50 mg of daily PSL. While IP and mononeuritis multiplex gradually improved by the high-dose steroid therapy, serum amylase level raised to more than 4293 mU/ml, suggesting the modification of pancreatitis by the treatment with steroid. Since she did not respond to the conservative therapy for acute pancreatitis, she was treated with plasmapheresis, which turned out to be very effective. However, she was suffered from fungal pneumonia and died of respiratory failure. As far as we know, only three cases of SS with acute pancreatitis have been reported so far. The immunopathological mechanisms of development of acute pancreatitis in our case, especially focusing on the significance of microvasculopathy and hypercoagulability, were discussed.

Acute Disease↗

[A case of acute pulmonary embolism fourteen days after hysterectomy].

We describe a 54-year-old female with acute pulmonary embolism. She showed a syncope attack and hypotension fourteen days after hysterectomy for uterine cancer. Preoperative echocardiogram revealed that thrombus in the right atrium was coming and going through the tricuspid valve. Emergent pulmonary embolectomy through the sternotomy under cardiopulmonary bypass was performed 4.5 hours after the diagnosis without homologous blood transfusion. Postoperative perfusion scintigram 20 days after the operation showed normal filling of the both lungs except for the localized defect at the distal portion of the right middle lobe. The patient was discharged on the 22nd postoperative day and she has been followed up with anticoagulation therapy. It is essential that we have the opportunity to salvage an otherwise helpless situation by a high index of suspicion and a prompt surgical intervention.

Acute Disease↗

Detection and investigation of Campylobacter jejuni by polymerase chain reaction-restriction fragment length polymorphism analysis.

A molecular typing approach for Campylobacter jejuni with restriction fragment length polymorphism (RFLP) analysis of the flagellin gene flaA in C. jejuni, was generated and studied. Using polymerase chain reaction (PCR)-RFLP with the restriction endonuclease Mbo I, it was demonstrated that C. jejuni could be divided into four types. Genotypic analysis of C. jejuni by PCR-RFLP is a valuable technique for epidemiological typing.

Animals↗

[A case of amyopathic dermatomyositis with rapidly progressive interstitial pneumonia].

We report here a case of interstitional pneumonia (IP) associated with amyopathic dermatomyositis (DM). In August, 1998, a 53-year-old Japanese man was admitted to our hospital because of fever, polyarthritis and erythematous heliotrope eruption and Gottron's sign without any symptom of myositis. Serum CK level and EMG were normal. Jo-1 antibody was negative. Chest computed tomography (CT) revealed IP at both lung base areas. The patient was diagnosed as amyopathic DM with IP. When IP rapidly progressed, methylprednisolone pulse therapy and oral high dose prednisolone were not effective. High-dose intravenous cyclophosphamide seemed to be transiently effective, but oral cyclosporine A was not effective. The patient was died of respiratory failure in October 1998. During the course, we measured serum levels of LDH, sIL-2 R, s-ICAM-1 and KL-6, KL-6 could be a sensitive parameter of IP activity.

Antigens↗

Epidermal sphingomyelins are precursors for selected stratum corneum ceramides.

Epidermal ceramides (Cer) comprise a heterogeneous family of seven species, including two unique omega-hydroxylated Cer, that are key components of the stratum corneum (SC) intercellular lamellar membranes responsible for the epidermal permeability barrier. Although both glucosylceramide (GlcCer) and the phospho-sphingolipid sphingomyelin (SM) are potential precursors of SC Cer, based on reported chemical structures of epidermal GlcCer and SC Cer, it is assumed that all major subfractions of SC Cer are generated from lamellar body-derived GlcCer. Yet, we and others have shown that SM-derived Cer are required for normal barrier homeostasis. Moreover, two pools of SM, one from plasma membrane, the other from lamellar body-derived contents, are potentially available for Cer production. To clarify the role of SM as a potential precursor of bulk or specific SC Cer, we compared Cer moieties in epidermal SM, Cer generated from epidermal SM by sphingomyelinase treatment, Cer within SC, and Cer that persist in Gaucher SC, where GlcCer cannot generate Cer due to an absence of beta-glucocerebrosidase. Using gas chromatography-mass spectrometry, fast atom bombardment-mass spectrometry, and nuclear magnetic resonance for Cer characterization, epidermal SM comprise three major subfractions with distinctive amide-linked (N-acyl) fatty acid (FA) compositions: that is, either long-chain FA (SM-1; C(22;-26)), short-chain FA (SM-2; primarily C(16)), and short-chain alpha-hydroxy FA (SM-3; C(16;-18)). In contrast, only trace quantities of omega-hydroxy FA were present. For each SM subfraction, the sphingoid base was either sphingosine or sphinganine, but phytosphingosine was not detected. Comparison of these SM with corresponding sphingomyelinase-generated epidermal Cer and SC Cer revealed that the Cer moieties of SM-1 and SM-3 are equivalent to Cer 2 (NS) and Cer 5 (AS), respectively. Moreover, both Cer 2 and Cer 5 occurred in Gaucher SC, whereas other Cer subfractions did not occur. These results indicate that two epidermal SM, that is, SM-1 and SM-3, are important precursors of two corresponding Cer in mammalian SC, that is, Cer 2 and Cer 5, but other Cer species, including the omega-hydroxy Cer species, do not derive from SM.

Animals↗

Stabilization of liposomal membranes by thermozeaxanthins: carotenoid-glucoside esters.

Thermozeaxanthins (TZS) are novel carotenoid-glucoside esters existing in the cell membranes of the thermophilic bacterium, Thermus thermophilus. The effect of TZS on membrane permeability was studied by measuring the leakage of the fluorescent dye from calcein-entrapped large unilamellar liposomes (LUVs). The LUVs were composed of a small portion (0.2-1.0 mol%) of TZS and phosphatidylcholine (PC) of various length and saturation degree of hydrocarbon chains. Incorporation of TZS in egg PC LUVs stabilized the liposomes in the temperature range from 30 to 80 degrees C, as only 2.6% of the entrapped calcein leaked out in contrast to 10% release from the egg PC liposomes without TZS. LUVs composed of dipalmitoylphosphatidylcholine (DPPC) or dioleoylphosphatidylcholine (DOPC) were stabilized by the incorporation of TZS at a temperature below 30 degrees C. Inclusion of TZS in LUVs composed of dimyristoylphosphatidylcholine, whose hydrocarbon chains are shorter than both DPPC and DOPC, did not stabilize the liposomes. About 90% of the entrapped dye was lost indicating defects of the liposomal membranes. Matching of the lipid bilayer thickness with the molecular length of TZS in the bilayers is discussed.

Carotenoids↗

Mast cells cause apoptosis of cardiomyocytes and proliferation of other intramyocardial cells in vitro.

BACKGROUND: Mast cells are multifunctional cells containing various mediators such as cytokines, proteases, and histamine. They are found in the human heart and have been implicated in ventricular hypertrophy and heart failure. However, their roles in pathogenesis of these diseases are unknown. METHODS AND RESULTS: Cultured cardiomyocytes from neonatal rats were incubated with mast cell granules (MCGs) for 24 hours. The highest concentration of diluted MCGs caused the death of approximately 70% of cardiomyocytes. This cell death was proved to be apoptosis, as quantified by electron microscopy and biochemical criteria. MCG-mediated cytotoxicity was prevented by pretreatment of MCGs with protease inhibitors or a neutralizing antibody against rat mast cell chymase 1 (RMCP 1). RMCP 1 by itself was proved to induce cell death of cardiomyocytes. These results suggest that RMCP 1 contained in MCGs causes the death of cardiomyocytes. In contrast, MCGs induced the proliferation of intramyocardial cells other than myocytes. RMCP 1 was also proved to induce their proliferation. CONCLUSIONS: Mast cells cause apoptosis of cardiomyocytes and proliferation of other intramyocardial cells via the activity of RMCP 1. Our results suggest that mast cell chymase may play a role in the progression of heart failure, because loss of cardiomyocytes and proliferation of nonmyocardial cells exaggerate its pathophysiology.

Animals↗

FTY720, a new immunosuppressant, promotes long-term graft survival and inhibits the progression of graft coronary artery disease in a murine model of cardiac transplantation.

Background-Effective immunosuppression is a critical determinant of organ and patient survival in cardiac transplantation. The present study was designed to determine the potency of FTY720, a new synthesized immunosuppressant, and examine its clinical potential as an immunosuppressant. Methods and Results-Hearts of DBA/2 mice were transplanted heterotopically in C57BL/6 mice. Recipients were treated with oral FTY720 in doses of 0.3, 1, 3, or 10 mg. kg(-1). d(-1) or with 40 mg. kg(-1). d(-1) of cyclosporin A (CsA) as a comparative treatment. The median graft survival time (MST) was significantly prolonged by treatment with FTY720 10 mg. kg(-1). d(-1). MST was not prolonged by FTY720 1 mg. kg(-1). d(-1) or CsA. However, FTY720 1 mg. kg(-1). d(-1) combined with CsA 40 mg. kg(-1). d(-1) resulted in a significant prolongation of MST. Histopathological studies performed 5 days after transplantation demonstrated remarkable suppression of inflammatory response by treatment with FTY720 10 mg. kg(-1). d(-1). Interleukin (IL)-2 and interferon (IFN)-gamma production was not suppressed; however, cytotoxic T lymphocyte activity was strongly suppressed in vitro. In addition, IL-2-stimulated T-cell proliferation and class I and class II MHC antigen expression on IFN-gamma-stimulated macrophages were strongly inhibited by FTY720. Histopathological studies 60 days after transplantation (DBA/2-B10.D2) demonstrated a beneficial effect on graft atherosclerosis. Conclusions-FTY720 promoted long-term cardiac graft survival and strongly inhibited the progression of graft atherosclerosis. These observations suggest that FTY720 has a promising clinical potential in cardiac transplantation.

Animals↗

Decreases in Ikaros activity correlate with blast crisis in patients with chronic myelogenous leukemia.

Gene targeting studies in mice have shown that the lack of Ikaros activity leads to T-cell hyperproliferation and T-cell neoplasia, establishing the Ikaros gene as a tumor suppressor gene in mice. This prompted us to investigate whether mutations in Ikaros play a role in human hematological malignancies. Reverse transcription-PCR was used to determine the relative expression levels of Ikaros isoforms in a panel of human leukemia/lymphoma cell lines and human bone marrow samples from patients with hematological malignancies. Among the cell lines examined, only BV-173, which was derived from a chronic myelogenous leukemia (CML) patient in lymphoid blast crisis, overexpressed the dominant-negative isoform, Ik-6. In 9 of 17 samples of patients in blast crisis of CML, Ikaros activity had been reduced either by drastically reducing mRNA expression (4 of 17) or by overexpressing the dominant-negative isoform Ik-6 (5 of 17). Significantly, expression of Ikaros isoforms seemed normal in chronic phase CML patients and patients with other hematological malignancies. In some cases, overexpression of the dominant-negative Ik-6 protein was confirmed by Western blot analysis, and Southern blot analysis indicated that decreases in Ikaros activity correlated with a mutation in the Ikaros locus. In summary, these findings suggest that a reduction of Ikaros activity may be an important step in the development of blast crisis in CML and provide further evidence that mutations that alter Ikaros expression may contribute to human hematological malignancies.

Adult↗

Low-Temperature Synthesis of Nanometer-Sized Crystalline TiO2 Particles and Their Photoinduced Decomposition of Formic Acid.

Anatase TiO2 particles with an average size of 2.7 nm in an as-grown state were obtained below 373 K from an H2O-EtOH mixed solution of TiOSO4 by a facile liquid phase method. The volume ratio of H2O to EtOH was revealed to be the key for crystallinity of the particles. The as-grown particles prepared from the H2O-EtOH solution (H2O/EtOH (mL/mL) = 150/100) showed a high photoreactivity in the TiO2 photoinduced decarboxylation of HCOOH under a deaerated condition. In contrast, under an aerated condition, the rate of the reaction increased with an increase in calcining temperature (Tc) due to the improvement of anatase crystallinity, going through a maximum at Tc = 873 K. Copyright 1999 Academic Press.

Journal Article↗