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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 505 records · Page 28Linked to original sources

Nasal lesions induced by intranasal administration of benzaikonium chloride in rats.

We investigated the lesions of nasal cavity mucous membrane caused by administration of 0.01, 0.05 and 0.10 w/v% Benzalkonium chloride (BZC) solutions in the nasal cavity of rats. No BZC-induced symptoms or nasal lesions were seen in the 0.01 w/v% BZC-treated group. On the other hand, BZC-induced symptoms such as nasal sound and rubbing the nose with forelegs were observed in the 0.05 and 0.10 w/v% BZC-treated groups. Additionally, BZC-induced lesions, including epithelial desquamation, inflammation and edema, occurred in the anterior nasal cavity in the 0.05 and 0.10 w/v% BZC-treated groups, but these lesions were confined to the dorsal meatus and the adjacent nasal septum. These results indicate that 0.01 w/v% BZC solution has no effect on the nasal cavity mucous membrane. However, 0.05 and 0.10 w/v% BZC solutions induce lesions in the nasal cavity mucous membrane due to their irritating effect.

Administration, Intranasal↗

Wegener's granulomatosis with dural involvement as the initial clinical manifestation.

We treated a patient with an atypical presentation of Wegener's granulomatosis (WG) with dural involvement as the initial clinical manifestation. A 37-year-old man had a dural lesion without lower respiratory tract or renal manifestations in the initial clinical course. His only initial symptom was headache, and at disease onset computed tomography (CT) and magnetic resonance imaging (MRI) of the head revealed bilateral abnormal subdural masses. The diagnosis of WG was made based on the results of needle biopsy of the nasal polyps and the finding of positive circulating antineutrophil cytoplasmic antibodies (c-ANCA). He achieved remission on daily prednisone and cyclophosphamide with the later addition of sulfamethoxazole-trimethoprim.

Adult↗

Rapid uptake and phosphorylation of D-mannose, and limited D-mannose 6-phosphate isomerization in the glycolytic pathway of bloodstream forms of Trypanosoma brucei gambiense.

Bloodstream forms of the parasitic protozoa Trypanosoma brucei gambiense derive all of needed energy through an unusual glycolysis. In an earlier study, we showed that D-mannose specifically inhibited the growth of bloodstream forms of T. b. gambiense. We investigated D-mannose transport into the T. b. gambiense bloodstream forms and its metabolism in the initial phase of the glycolytic pathway. D-Mannose was transported rapidly into the bloodstream forms of T. b. gambiense (K(m) = 378 microM), and D-glucose competitively inhibited D-mannose uptake. D-Mannose and D-glucose are transported into bloodstream trypanosomes by the same carrier. Hexokinase from the bloodstream trypanosomes could convert D-mannose to D-mannose 6-phosphate (K(m) = 155.8 microM; Vmax = 0.93 mumol/min/mg protein); with kinetic properties very similar to D-glucose phosphorylation (K(m) = 199.4 microM; Vmax = 1.15 mumol/min/mg protein). D-Mannose 6-phosphate could be further metabolized in the glycolytic pathway. However, the metabolic rate was extremely slow, and D-mannose 6-phosphate accumulated in the glycosomes. D-Mannose may cause growth inhibition of bloodstream trypanosomes through an extremely high concentration of D-mannose 6-phosphate in the glycosomes.

Animals↗

[Quantitative analysis of the gustatory evoked potentials in the guinea pig].

Gustatory evoked potentials were studied in anesthetized guinea pigs to develop an objective and quantitative taste examination for patients with taste disorders. A positive wave was recorded by the application of NaCl, HCl or quinine hydrochloride solution. There was little difference in latency, duration and waveform among these three solutions. No apparent change in activity was seen after the application of sucrose solution or distilled water. The gustatory evoked potentials that excluded the influence of the trigeminal nerve innervating the tongue surface were able to be reproducibly recorded on either the cortical surface or the skull surface. There was a linear relationship between logarithmic values of potential amplitude and those of taste solution concentration. Therefore, it is suspected that the quantitative evaluation of taste detection is possible by measuring the taste solution concentration-potential amplitude relationship.

Animals↗

[Smoldering leukemia with CD7.CD34(+), immunoglobulin heavy chain rearrangement (+) and hypoplastic marrow with myelofibrosis].

A 63-year-old male was admitted because of pneumonia. Peripheral blood findings showed pancytopenia with increase of blasts. A bone marrow specimen showed hypocellular marrow with increase of blasts. The blasts were positive for CD7, CD34, and HLA-DR and negative for other lymphoid antigens and myeloid antigens involving myeloperoxidase. Rearrangement of immunoglobulin heavy chain was demonstrated by Southern blotting analysis. T cell receptor beta, T cell receptor gamma and immunoglobulin light chain rearrangement were negative. A diagnosis of stem cell leukemia was made. In vitro, the blasts did not respond to recombinant human granulocyte colony-stimulating factor (rhG-CSF), cytarabine (Ara-C) and all-trans retinoic acid (ATRA). However, in the blasts of culture without cytokeins, CD33 expression was newly induced. Remission was not obtained by chemotherapies with cyclophosphamide, etoposide, prednisolone and Ara-C. Four months later, marrow specimens showed hypoplasty with myelofibrosis. One year later, the blasts showed CD33 expression with negative myeloperoxidase. The leukemia was transformed to minimally differentiated myeloid leukemia from stem cell leukemia. This condition was thought to be "smoldering leukemia" because of the slow development and refractoriness to chemotherapy. Nineteen months later the patient died due to respiratory failure by pneumonia and pulmonary bleeding despite therapy.

Acute Disease↗

[A case of primary malignant melanoma of the esophagus].

A case of primary and malignant melanoma of the esophagus was reported. A 64-year-old male complaining of discomfort of anterior chest pain was admitted to our hospital for operation. Findings of upper G-1 X-ray and endoscopic examination revealed suspiciously malignant melanoma. Subtotal thoracic esophagectomy with R III dissection was performed. Operative findings included A0 N2 Pl0 M0 Stage III. Macroscopically it showed black-grayish colored polypoid tumors, 7 cm in size. The typical finding of junctional activity adjacent to the tumor mass and melanocytes were microscopically found. The patient received postoperative systemic chemotherapy, but was died of multiple liver and bone metastases 125 days after surgery. Malignant melanoma of the esophagus has extremely poor prognosis and none of effective therapies has been reported.

Esophageal Neoplasms↗

[Renal cell carcinoma in acquired cystic disease of kidney (ACDK) manifested by spontaneous renal rupture: a case report].

We report a case of renal cell carcinoma in acquired cystic disease of the kidney (ACDK) presenting with a spontaneous renal rupture. A 41-year-old man on chronic hemodialysis for 16 years was referred to our hospital with sudden left back pain. On arrival, the patient was in a state of hemorrhagic shock but his general condition improved by conservative therapy. Computed tomography demonstrated a left renal rupture as well as bilateral ACDK. Although there was no definite evidence of a renal tumor, a left radical nephrectomy was performed one week later. The resected kidney contained a yellowish-brown tumor of 5.5 x 5.0 x 4.5 cm in size. Pathological examination revealed renal cell carcinoma, cystic type, clear cell subtype, pT2pN0M0. He has been free of recurrence for 3 months.

Adult↗

Increased alanine uptake and lipid synthesis from alanine in isolated hepatocytes of Wistar-Kyoto fatty rats: an inhibitory effect of biguanides.

To examine the pathophysiological characteristics of non-insulin-dependent diabetes mellitus, alanine metabolism in isolated hepatocytes of male Wistar-Kyoto (WKY) fatty rats (genetically obese and hyperglycemic) and their lean littermates was investigated. The effects of glucagon and the biguanides, metformin and buformin, on alanine metabolism were also studied by measuring alanine uptake and lipid synthesis from alanine. WKY fatty rats showed higher plasma insulin and lipid concentrations than lean rats at 5 as well as at 12 weeks of age. Alanine uptake into hepatocytes was increased in fatty rats only at 12 weeks of age compared with lean rats. Lipid synthesis from alanine in hepatocytes was increased in fatty rats at 5 and 12 weeks of age compared with lean rats. Glucagon increased alanine uptake into hepatocytes but did not affect lipid synthesis from alanine in both fatty and lean rats. Low concentrations (0.1 mM) of biguanides decreased lipid synthesis from alanine only in fatty rats without inhibiting alanine uptake into hepatocytes. These observations suggest that lipid synthesis from alanine in hepatocytes of WKY fatty rats is accelerated prior to the onset of diabetes mellitus, which might be associated with the development of diabetes, and that an inhibitory effect on increased lipid synthesis is one of the pharmacodynamic actions of biguanides.

Aging↗

PET imaging of brain tumor with [methyl-11C]choline.

UNLABELLED: This article describes a new method of [11C]choline synthesis for intravenous injection. We aimed at the utilization of this compound for brain tumor imaging with PET. METHODS: After [11C]carbon dioxide production in a cyclotron and the subsequent [11C]methyl iodide synthesis, [methyl-11C]choline was synthesized by the reaction of [11C]methyl iodide with "neat" dimethylaminoethanol at 120 degrees C for 5 min. Purification was achieved by evaporation of the reactants followed by passage of the aqueous solution of the product through a cation-exchange resin cartridge. The time required for overall chemical processing, excluding the cyclotron operation, was 15 min. Radiochemical yield was > 98%. Radiochemical purity was > 98%. Chemical purity was > 90% (dimethylaminoethanol was the only possible impurity). Specific radioactivity of the product was > 133 GBq/mumol. The whole body distribution was examined in rabbits with PET. Clinical studies were performed in patients with brain tumor using PET after intravenous injection of 370 MBq of [11C]choline. RESULTS: In rabbits,[11C]choline was taken up from blood by various tissues very rapidly, and the radioactivity remaining in blood became almost negligible 5 min after intravenous injection. Taking advantage of this characteristic, we obtained stable tissue distribution images of human brain using PET. In patients with brain tumor, PET produced clearly delineated positive images of the tumors. CONCLUSION: Carbon-11-choline can be used for obtaining clear images of brain tumor in PET.

Adenoma↗

[Surgical revision of failed filtering bleb with mitomycin C].

The revision of a failed filtering bleb using mitomycin C was performed in 40 eyes (28 eyes with primary open angle glaucoma and 12 eyes with secondary open angle glaucoma) in which the previous trabeculectomy using 5-fluorouracil had failed to control intraocular pressure (IOP). Presurgical IOP ranged from 21 approximately 36 mm Hg (average: 24.7 mmHg) with the maximum tolerable antiglaucoma medication. The follow-up period was at least 2 years (24 approximately 60, mean: 39.8 months). Mitomycin C (0.04%, 5 ml, 5 min) was applied under the subconjunctival space. After rinsing, the wall of the scarred bleb was incised in cases with a localized bleb, or the margin of the scleral flap was incised in cases without a filtering bleb. The conjunctival wound was closed with 10-0 Nylon sutures. IOP control under 21 mmHg was achieved in 53.4% without medication and in 60.2% with or without medication at 60 months. After repeating the same procedure, IOP control was obtained in 82.2% with or without medication at 60 months. The success rate in secondary open angle glaucoma was less than in primary open angle glaucoma. Complications such as flattening of the anterior chamber requiring reformation (8%), choroidal detachment (8%), hyphema (5%), and hypotonic maculopathy (5%) were less than after trabeculectomy but conjunctival wound separation (5%) occurred little more frequently.

Adult↗

Cloning and biological activity of murine oncostatin M.

Oncostatin M (OSM) is a member of the interleukin-6/leukemia inhibitory factor (LIF) family cytokines. While human OSM (hOSM) has been characterized, the murine counterpart had not been isolated. We cloned a murine OSM (mOSM) cDNA as a gene that is induced in hematopoietic cells by a subset of cytokines including IL-3, GM-CSF and Epo. Identity of mOSM was based on overall homology to hOSM and chromosomal gene localization. Human OSM is known to exhibit biological activities similar to LIF, because they share the same functional receptor composed of the LIF receptor and gp130. As compared to hOSM, however, a 1000-fold higher concentrations of mOSM was required to stimulate proliferation of LIF-dependent murine DA1a cells, differentiation of M1 macrophage cells, and inhibition of ES cell differentiation. On the other hand, mOSM inhibited growth of NIH3T3 cells at a 1000-fold lower concentration than that of hOSM. These results indicate that mOSM functions through a receptor which is distinct from that of the LIF receptor. Studies on the physiological role of OSM is underway.

3T3 Cells↗

[The essential region of CD40 cytoplasmic domain for signal transduction in WEHI231 cells].

Ligation of surface immunoglobulin M (IgM) induced cell death and this was blocked by CD40-mediated signal in a mouse B cell line, WEHI231. In order to define which region of CD40 and how CD40-mediated signal are involved in the blocking of IgM-induced cell death, we generated several human CD40 transfectants. We demonstrated that a 10-amino acid segment in the conserved cytoplasmic region of CD40-mediated rescue from IgM-induced cell death and was involved in the activation of c-Jun aminoterminal kinase (JNK). In addition, the same segment was also important for CD40-mediated activation of extracellular signal-regulated protein kinase 2 (ERK2). Moreover, tumor necrosis factor receptor-associated factor (TRAF) 2 and 3 could bind to the same segment of CD40.

Amino Acid Sequence↗

Inhibitory effect of circulating egg antigens on Schistosoma japonicum egg-induced granuloma formation.

Schistosoma japonicum produces an enormous quantity of eggs during infection. This study was conducted to examine the effect of egg-derived antigens on the development of granuloma formation around S. japonicum eggs in the livers of mice. When soluble egg antigen (SEA) (75 micrograms/mouse/day) was injected 3-4 times via a vein into mice implanted with laid eggs, the magnitude of tissue lesion was drastically inhibited when assessed at maximal occurrence (14 days after implantation of eggs), whereas adult worm antigen (AWA), rabbit hyperimmune serum against SEA, or bovine serum albumin (BSA) did not show any effect on either the cellularity or the magnitude. In contrast to intravenous injection, there was no effect from subcutaneous injections of SEA. When serum taken from heavily infected mice or rabbit was transferred, there was a considerable extent of inhibition. In addition, an immune complex fraction of infected rabbit serum was found to have a stronger inhibitory effect than the supernatant fraction. This study indicates that the amount of egg-derived circulating antigens has a crucial effect on the development of schistosome granuloma formation.

Animals↗

Antithrombotic and hemorrhagic effects of DX-9065a, a direct and selective factor Xa inhibitor: comparison with a direct thrombin inhibitor and antithrombin III-dependent anticoagulants.

(+)-2S-2-[4-[[(3S)-1-Acetimidoyl-3- pyrrolidinyl]oxy]phenyl]-3-[7-amidino-2-naphthyl]propanoic acid hydrochloride pentahydrate (DX-9065a) is an antithrombin III (AT III)-independent and selective inhibitor of activated blood coagulation factor X (FXa). The aim of the present study was to compare the antithrombotic and hemorrhagic effects of DX-9065a with a direct thrombin inhibitor and AT III-dependent anticoagulants in rat models of thrombosis and bleeding. Rats were administered intravenously DX-9065a (0.1-1 mg/kg/h), argatroban (0.1-1 mg/k/h), low molecular weight heparin (25-100 anti-XaU/kg/h), unfractionated heparin (25-100 anti-XaU/kg/h) or Orgaran (30-300 anti-XaU/kg/h) for 1 h. DX-9065a dose-dependently inhibited both thrombus formation and elevation in plasma thrombin-AT III complex (TAT) level in a copper wire-inserted arteriovenous (AV) shunt model in rats. The dose required for 50% inhibition of thrombus formation was 0.27 mg/kg/h. DX-9065a did not prolong transection bleeding time up to 7.78 mg/kg/h. Argatroban and AT III-dependent anticoagulants also inhibited both thrombus formation and TAT elevation, but prolonged bleeding time at a slightly higher dose than the effective dose. These results suggest that direct and selective inhibition of factor Xa by DX-9065a is preferable for the treatment of thrombosis in the aspect of lack of compromising primary hemostasis.

Animals↗