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Biomedical subjects

Y Tatsumi

Publications and source records attributed to Y Tatsumi.

At least 37 records · Page 2Linked to original sources

Establishment of a myelodysplastic syndrome (MDS)/secondary AML-derived T lymphoid cell line K2-MDS.

We have established a T lymphoid cell line, K2-MDS, from the peripheral blood mononuclear cells (PBMC) of a patient with acute myeloblastic leukemia (AML) transformed myelodysplastic syndrome (MDS). K2-MDS cells are positive for the expression of CD4, CD5, CD13, CD25, CD71, CD95, HLA-DR and cytoplasmic CD3. Southern blotting analysis shows T cell receptor (TCR) beta chain genes rearrangements, whereas immunoglobulin heavy chain (IgH) genes are not rearranged. Further, the patient PBMC contains TCR beta chain genes rearrangements in the same manner as K2-MDS cells. The data indicate that K2-MDS is a T lymphoid cell line derived from a myelodysplastic clone in the patient PBMC. This new MDS-derived cell line K2-MDS may be a useful in vitro model for studies on the pathogenetic mechanisms leading to MDS.

Acute Disease↗

Gastric cancer presenting with extremely rapid growth: unprecedented morphologic change in a short time and endoscopic estimation of its doubling time.

We encountered a case of gastric cancer that was initially detected as a deep hemorrhagic ulcer without surrounding irregular elevation, followed by rapid protrusion in less than 1 month. Using endoscopic images in the follow-up study, we estimated the doubling time (DT) of this unusual tumor as 9.2 days. Since the doubling time of gastric cancer is generally fairly long due to exfoliation of many cancer cells into the gastric lumen, this cancer presented with extremely rapid growth. Besides, this case reinforces that follow-up study is important in terms of clinical management of ulcerative lesions.

Aged↗

A case of adult-onset Still's disease complicated by non-Hodgkin's lymphoma.

Left cervical lymphadenopathy developed in a 50-year-old male who had a history of adult-onset Still's disease for the preceding 18 months. Still's disease is characterized by rash, fever, and leukocytosis. Lymphadenopathy has been reported in about 60% of the patients, and most histopathologic studies have shown non-specific reactive hyperplasia. However, in this case, an open biopsy of the cervical node revealed a histology of diffuse large B-cell lymphoma. The B-cell malignant lymphoma that developed may have resulted from a sequential progression of a previous stage of benign lymphoproliferative lesion. Our case suggests that the pathophysiology of adult-onset Still's disease involves the stimulation of lymphoid systems to the point of progression towards lymphoma. Malignant lymphoma should be added to the list of life-threatening complications which, although rare, are associated with this disease.

Humans↗

Loss of wild-type carrier-mediated L-carnitine transport activity in hepatocytes of juvenile visceral steatosis mice.

Juvenile visceral steatosis (JVS) mice, which show systemic L-carnitine deficiency, may be an animal model of Reye's syndrome because of its phenotype of fat deposition and mitochondrial abnormalities in the liver. In this study, we compared the characteristics of the L-carnitine transport in isolated hepatocytes from wild-type and JVS mice. The uptake of L-carnitine by wild-type hepatocytes was saturable and the Eadie-Hofstee plot showed 2 distinct components. The apparent Michaelis constant (K(m)) and the maximum transport rate (V(max)) were 4.6 micromol/L and 59.5 pmol/15 min/10(6) cells, respectively, for the high-affinity component, and 404 micromol/L and 713 pmol/15 min/10(6) cells, respectively, for the low-affinity component. The high-affinity L-carnitine uptake occurred via an active carrier-mediated transport mechanism, which is characterized by Na(+)-, energy-, and pH-dependency. On the other hand, the high-affinity uptake was absent in JVS hepatocytes, and the values of K(m) and V(max) for the low-affinity uptake were 475 micromol/L and 557 pmol/15 min/10(6) cells, respectively. The hepatic carnitine transport properties in wild-type hepatocytes were similar to those of high-affinity mouse Octn2-transfected HEK293 cells. This study suggests that Octn2-type carnitine transporter is dysfunctional in hepatocytes of JVS mice.

2,4-Dinitrophenol↗

Pancreatoscopy for the next generation: development of the peroral electronic pancreatoscope system.

BACKGROUND: To improve visualization of the pancreatic duct with a pancreatoscope, we have developed the smallest known electronic endoscope, that is, the peroral electronic pancreatoscope. METHODS: This instrument (2.1 mm, external diameter) was developed with a 50k-pixel interline charge coupled device. A peroral fiberoptic pancreatoscope was used as control, connected to a video converter. The visibility of both systems was studied with a test chart. The model pancreatic duct, the oral mucosa, and the pancreatic ducts of a healthy control subject and patients with chronic pancreatitis were examined with both systems. RESULTS: The smallest visible interval (with a 5 mm distance between the object and the distal end of the endoscope) was 0.07 mm with the peroral electronic pancreatoscope and 0.2 mm with the peroral fiberoptic pancreatoscope. The electronic instrument produced better images of the model pancreatic duct than the fiberoptic endoscope. A clear image of the small vessels of the oral mucosa was obtained with the electronic but not with the fiberoptic instrument. The fine vessel network of the pancreatic duct was visualized only with the electronic instrument; pancreatic duct stones and rough-surfaced pancreatic duct were shown more precisely with the electronic endoscope. CONCLUSIONS: The peroral electronic pancreatoscope provides images of the fine detail of the pancreatic duct and will contribute to the diagnosis of pancreatic diseases.

Calculi↗

High inducibility of heat shock protein 72 (hsp72) in peripheral blood mononuclear cells of aplastic anaemia patients: a reliable marker of immune-mediated aplastic anaemia responsive to cyclosporine therapy.

To better characterize immunologic aberrations in aplastic anaemia (AA), we examined peripheral blood mononuclear cells (PBMC) of 67 patients with AA and other patients with various haematological diseases for the expression of heat shock protein 72 (hsp72), which is inducible in lymphocytes by various stressors including antigenic stimulation. When freshly obtained PBMC were examined using flow cytometry, the proportion of cells expressing hsp72 in cytoplasm was significantly higher in allogeneic marrow transplant recipients (22 +/- 15%, mean +/-standard deviation (SD)) and AA patients (17 +/- 21%) than in normal individuals (6 +/- 3%). When PBMC were tested after heat treatment, only the proportion of hsp72+ cells of AA patients (37 +/- 30%) was significantly higher than that of the normal control (17 +/- 11%). Dual fluorescence analysis of the PBMC revealed that the majority of hsp72+ cells was CD3+. For 28 untreated AA patients, the proportion of hsp72+ cells in those who later responded to cyclosporine (CyA) (62 +/- 24%) was higher than that in non-responders (19 +/- 13%). Immunoblotting analysis revealed predominant expression of hsp72 in T cells. These findings indicate that high inducibility of hsp72 in PBMC by heat treatment is an immunologic aberration characteristic of CyA-responsive AA and that this simple test may be useful for identifying a subset of AA patients responsive to immunosuppressive therapy.

Adolescent↗

IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases.

Using the suppression subtractive hybridization technique, we isolated a novel kinase, IKK-i, whose message is drastically induced by lipopolysaccharide (LPS) in the mouse macrophage cell line RAW264. 7. The predicted protein contains the kinase domain in its N-terminus, which shares 30% identity to that of IKK-alpha or IKK-beta. The C-terminal portion contains a leucine zipper and a potential helix-loop-helix domain, as in the case of IKK-alpha and IKK-beta. IKK-i is expressed mainly in immune cells, and is induced in response to proinflammatory cytokines such as tumor necrosis factor-alpha, IL-1 and IL-6, in addition to LPS. Overexpression of wild-type IKK-i phosphorylated serine residues Ser32 and Ser36 of IkappaB-alpha (preferentially Ser36), and significantly stimulated NF-kappaB activation. These results suggest that IKK-i is an inducible IkappaB kinase which may play a special role in the immune response.

Amino Acid Sequence↗

In vivo cisplatin resistance depending upon canalicular multispecific organic anion transporter (cMOAT).

The in vitro sensitivities to cisplatin of AH66 and AH66F cells, a variant obtained from AH66 cells, were very similar, when assayed in a medium containing 5% fetal bovine serum (FBS), whereas in the in vivo experiments AH66F cells were sensitive and AH66 cells were highly resistant to cisplatin. In this study, we examined the mechanism of the in vivo cisplatin resistance of AH66 cells. The in vitro cisplatin sensitivity of AH66 cells was lowered by changing FBS to 5% ascites fluid (ASF) in the assay medium and the sensitivity in FBS by treatment with buthioninesulfoximine (BSO). The sensitivity of AH66F cells was not changed by these treatments. Moreover, after culture in 5% ASF for 48 h, the accumulation of cisplatin in AH66 cells was decreased and the efflux of cisplatin from the cells was accelerated. The accumulation of cisplatin in AH66 cells in ASF was increased by pretreatment with BSO, sodium azide or probenecid. Then, we examined the expression of the glutathione (GSH) conjugate efflux pump family. Among them, only the expression of canalicular multispecific organic anion transporter (cMOAT) in AH66 cells was decreased by culture in FBS and enhanced by ASF. These results suggest that some substances contained in ASF enhanced the expression of cMOAT in the plasma membrane of AH66 cells and this transporter actively extruded cisplatin-GSH conjugate from the cells. Consequently, AH66 cells afford a cisplatin-resistant tumor in the host.

Animals↗

Adhesive interaction of highly malignant hepatoma AH66F cells with mesothelial cells.

We investigated the mechanism of adhesion of highly malignant ascites hepatoma AH66F cells to mesothelial cells. The adhesion rate of AH66F cells to mesentery-derived mesothelial cells (M-cells) was about 46% at 37 degrees C, but it decreased to about 27% at 4 degrees C. The adhesion rate of AH66F cells was about 25% in the presence of leukocyte function-associated antigen 1 (LFA-1) mAb at both 4 C and 37 C. When M-cells were treated with hyaluronidase, the AH66F/M-cell adhesion was decreased to half at 37 degrees C and had nearly disappeared at 4 degrees C. The residual adhesion of AH66F cells to M-cells treated with hyaluronidase almost disappeared in the presence of LFA-1 mAb. AH66F cells strongly adhered to a hyaluronate (HA)-coated plate, but not to a bovine serum albumin-coated plate. AH66F cells expressed a CD44 molecule (a HA receptor) in the plasma membrane, with a molecular size of about 85 to 90 kDa, corresponding to the CD44H isoform. These results indicated that the adhesion of AH66F cells to mesothelial cells is composed of pathways of CD44/HA and LFA-1/ICAM-1.

Animals↗

Synthesis and antifungal activities of (2R,3R)-2-aryl-1-azolyl-3-(substituted amino)-2-butanol derivatives as topical antifungal agents.

2-Aryl-1-azolyl-3-(substituted amino)-2-butanol derivatives I were prepared by ring-opening reaction of epoxides II with excess amine, and their antifungal activities were evaluated as topical agents. Azolyl-cyclic amine derivatives with a methylene group showed extremely strong activity with a broad spectrum in vitro. In general, anti-Trichophyton mentagrophytes activities of most of the topical antifungal agents are substantially reduced by addition of keratin (a major constituent of the keratinized tissue). However, the triazole derivative (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidino)-1-(1H-1,2 ,4- triazol-1-yl)-2-butanol ((-)-40, KP-103) showed very little deactivation by addition of keratin. This biological characteristic of triazole derivative (-)-40 resulted in excellent therapeutic efficacy on dermatophytosis superior to that of the corresponding imidazole derivative ((-)-41).

Animals↗

A novel lipopolysaccharide inducible C-C chemokine receptor related gene in murine macrophages.

To identify genes induced in activated macrophages, we screened a cDNA library prepared from the lipopolysaccharide (LPS)-treated cell line, RAW264, using the suppression subtractive hybridization technique. One of the clones isolated was dramatically induced by LPS in macrophages. The predicted protein sequence of this gene contains the domain unique to seven transmembrane receptors, and shows similarity with mouse C-C chemokine receptor 5 (CCR5). Therefore, we designated it LPS inducible C-C chemokine receptor related gene (L-CCR). Northern blot analysis revealed that L-CCR was specifically expressed in differentiated macrophages after LPS stimulation. These results show that L-CCR is a novel C-C chemokine receptor related gene induced by LPS in macrophages and may play an important role in inflammatory responses.

Amino Acid Sequence↗

Analysis of the 13C-urea breath test for detection of Helicobacter pylori infection based on the kinetics of delta-13CO2 using laser spectroscopy.

We have previously reported on laser spectroscopy as a simple alternative to mass spectrometry. To validate a simplified 13C-urea breath test (UBT) with laser spectroscopy for the detection of Helicobacter pylori in clinical use, we evaluated the optimal time of breath sample collection. The 13C-UBT was carried out on each of 102 infected and 70 non-infected subjects (32 without eradication and 38 after eradication therapy). Breath samples were taken at five time points within 60 min followed by 100 mg of 13C-urea administration. The ratio of 13CO2 to 12CO2 was measured using laser spectroscopy and the recovery of tracer in the exhaled breath was calculated. Results were compared with histological and culture examinations of gastric biopsies to establish the infection status. For statistical evaluation of 13C-UBT, the optimal timing of breath sample collection was examined on the basis of the kinetics of delta-13CO2. In 32 H. pylori-negative patients (without therapy), the mean +/- 2SD of delta-13CO2 was at its minimum 20 min after urea ingestion whereas in H. pylori-positive patients, the mean +/- SD delta-13CO2 was maximum at 20 min. In addition, receiver operating characteristic (ROC) curve analysis showed that the cut-off value was estimated between 2.5-3.0 per mil (%0) at 20 min before therapy. Based on the histology and culture results, the sensitivity, specificity and positive and negative predictive values were 98.0%, 100%, and 94.1%, respectively. In conclusion, 13C-UBT with laser spectroscopy is a non-invasive, simple, sensitive and specific test to determine H. pylori status. Our findings suggest that in clinical use, measurements made at 20 min after substrate administration could be recommended for most sensitive and specific 13C-UBT results.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Antipyretic activity of gingyo-san, a traditional medicine, in influenza virus-infected mice.

Gingyo-san is composed of 10 crude drugs and used as a traditional antipyretic medicine for the treatment of the common cold and influenza virus infection. In a murine intranasal influenza infection model, fever produced by the infection has been demonstrated to be reduced by suppressing interferon-induced interleukin (IL)-1 alpha production. Thus, we focused on the serum level of IL-1 alpha which produces such novel antipyretic activity, and evaluated the relationship between defervescence and the suppression of IL-1 alpha production by Gingyo-san in influenza virus-infected mice. Fever was produced in the infected mice 33-44 h after infection. Oral administration of a hot water-extract of Gingyo-san (8.9-12.5 mg/0.25 ml/mouse x 3 per day) significantly reduced fever production and suppressed the rise in IL-1 alpha production to the level in uninfected mice. No apparent toxicity by Gingyo-san was observed in infected mice. When the hot water-extract of each 10 of the crude components of Gingyo-san (an unknown amount extracted from 6.25 mg/0.25 ml/mouse x 3 per day for Saigae Tataricae Cornu and 3.5 mg/0.25 ml/mouse x 3 per day for the other 9) was orally administered to infected mice, 6 showed significant antipyretic activity. Of these 6, Saigae Tatricae Cornu significantly suppressed the rise in IL-1 alpha production to the basal level while the other 5 did not affect serum IL-1 alpha. Thus, of the 10 crude components of Gingyo-san, Saigae Tataricae Cornu simultaneously exhibited antipyretic and IL-1 alpha-regulatory activities. The novel antipyretic action of Gingyo-san may be mainly mediated by Saigae Tataricae Cornu which regulates the elevated serum IL-1 alpha level produced by influenza infection.

Analgesics, Non-Narcotic↗

[The chemical structure of new substance as the metabolite of baicalin and time profiles for the plasma concentration after oral administration of sho-saiko-to in human].

Baicalin (BG) is one of the major components of Sho-Saiko-To. We found a new substance as the metabolite of BG in human plasma after oral administration of Sho-Saiko-To. The metabolite was identified as baicalein 6-O-sulfate (BS) by comparing its retention time in HPLC and electrospray ionization mass spectra (ESI-MS)/MS methods with that of an authentic sample. Time profiles for the plasma concentrations of BS and BG after oral administration of Sho-Saiko-To (EK-9) at a daily dose (6 g), were investigated in 14 healthy male volunteers. The determination for the concentrations of BS and BG in human plasma was developed by the HPLC method using electrochemical detector (ECD). Each 1 ml of the plasma specimen was used for the solid phase extraction. The calibration curves of BS and BG showed a good linearity between 5 and 300 ng/ml. The quantitative limits of BS and BG in human plasma were 5 ng/ml. Using this method, BS was detected after 1 h, reached a maximum level at 5 h and then decreased to the level less than the quantitative limit after 36 h, and the plasma level of BS showed a slight peak at 24 h. BG was detected after 1 h, reached a maximum level at 5 h and then decreased to the level less than the quantitative limit after 36 h, and the plasma level of BG showed two peaks at 12 h and 24 h.

Administration, Oral↗

Irsogladine maleate may preserve gastric mucosal hydrophobicity against ethanol in phospholipids independent way in rats.

Irsogladine maleate (IM) has been used as a mucosal protective agent, whose action is partially explained as enhancement of mucosal blood flow, increase of cellular cyclic AMP and facilitation of gap-junctional intercellular communication. Effect of IM on rat gastric mucosal hydrophobicity, one of the mucosal barrier properties, was investigated, in comparison with that of 16,16-dimethyl prostaglandin E2 (dmPGE2). IM alone had no effect on mucosal hydrophobicity and mucosal phospholipids content. dmPGE2 alone did not change mucosal hydrophobicity significantly, but remarkably increased mucosal surface-active phospholipids. Intragastric administration of absolute ethanol significantly decreased gastric mucosal hydrophobicity and mucosal phospholipids content. IM could prevent the decrease in mucosal hydrophobicity by ethanol, maintaining the surface mucus gel layer and mucosal surface phospholipids almost as non-damaged control levels, whereas dmPGE2 also prevented the decrease in mucosal hydrophobicity by ethanol, with the surface epithelium being partially exfoliated and mucosal surface-active phospholipids showing remarkable enhancement. These results suggest that IM may preserve gastric mucosal hydrophobicity against ethanol, not through enhancement of mucosal phospholipids content like prostaglandin, but possibly through its reported stabilization action to the epithelial cell lining, which may preserve the surface epithelium with the mucous gel layer containing surface-active phospholipids, a possible origin of mucosal hydrophobicity.

Animals↗