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Biomedical subjects

M Kubo

Publications and source records attributed to M Kubo.

At least 181 records · Page 10Linked to original sources

Giant cell granulamatous hypophysitis with remarkable uptake on Gallium-67 scintigraphy.

We treated a man with giant cell granulomatous hypophysitis with pituitary enlargement, as seen on magnetic resonance imaging. Endocrinological examination revealed panhypopituitarism and diabetes insipidus. Microscopic examination of the specimen obtained by transsphenoidal pituitary biopsy revealed a granulomatous lesion, composed of epitheliod cells, Langhans' multinucleated giant cells, lymphocytes and other chronic inflammatory cells. On whole body gallium-67 scintigraphy, there was extensive uptake in the pituitary gland. Gallium-67 scintigraphy may greatly aid in the diagnosis of granulomatous hypophysitis.

Adult↗

A novel immunosuppressant, FTY720, increases the efficiency of a superantigen-induced peripheral T-cell deletion whilst inhibiting negative selection in the thymus.

A novel immunosuppressant, FTY720, was generated by chemical modification of ISP-I, an immunosuppressive compound purified from culture filtrates of Isaria sinclairii. FTY720 directly induces apoptotic cell death in lymphocytes, which is believed to be the mechanism by which this drug exerts its immunosuppressive effect. We examined the effect of FTY720 treatment on antigen-induced apoptotic cell death in peripheral T cells and thymocytes. A superantigen, staphylococcus enterotoxin B (SEB), induces T-cell antigen receptor (TCR) Vbeta-specific apoptotic cell death in mature T cells in vivo. In this well-documented experimental system, FTY720 administration significantly enhanced the efficiency of superantigen-induced T-cell deletion. We also determined that apoptotic cell death with DNA fragmentation induced in T-hybridoma cells after stimulation in vitro with anti-TCR antibodies was enhanced in the presence of non-cytolytic doses of FTY720. In sharp contrast, negative selection of T cells in the thymus, another example of antigen-induced apoptosis, was found to be inhibited by FTY720 treatment. A rescue effect was observed on clonal deletion in the H-Y-specific TCRalpha beta transgenic male thymus. In a chicken egg albumin (OVA)-specific TCRalphabeta transgenic system, OVA-induced apoptotic cell death of CD4+CD8+ thymocytes was also inhibited by FTY720 injection. Thus, FTY720 increased the susceptibility of mature T cells to TCR-mediated apoptosis but decreased that of immature thymocytes. The results in this report suggest that the potent immunosuppressive effect of FTY720 is, in part, a result of the augmentation of effects on antigen-induced apoptosis in mature T cells, and that two distinct apoptotic cell death pathways are operating in mature and immature T cells.

Animals↗

Disadvantage of long-term CAPD for preserving cardiac performance: an echocardiographic study.

The indices of cardiac performances were compared between 31 continuous ambulatory peritoneal dialysis (CAPD) and 20 long-term hemodialysis (HD) patients. They were subdivided into three groups according to dialysis duration: L-CAPD (n = 16, mean age and CAPD duration were, respectively, 53 +/- 8 [SD] years and 77 +/- 13 months); S-CAPD (n = 15; 52 +/- 12 years, 28 +/- 12 months); HD (n = 20; 51 +/- 10 years, 162 +/- 52 months). The diabetic HD patients (DM-HD; n = 13; 60 +/- 13 years of age, 22 +/- 11 months) were chosen separately. Thirteen normotensive subjects with normal kidney function (mean age, 57 +/- 9 years) were selected as an age-matched control group. There were no significant differences between groups in age, gender, incidence of original kidney disease, or serum biochemical data. The blood pressure and the cardiothoracic ratio in L-CAPD were highest among groups. The indices of left ventricular (LV) hypertrophy as well as LV performance by means of echocardiography or pulsed Doppler were compared. Among nondiabetic dialysis patients, the calculated LV mass index (LVMI) of 166.4 +/- 84.3 g/m2 and the ratio of the peak atrial filling velocity to the peak diastolic flow velocity of 1.25 +/- 0.4 in L-CAPD were greatest, and the left ventricular fractional shortening (%FS) of 34.2 +/- 10.8% in L-CAPD was smallest. LVMI or %FS of L-CAPD was the same as DM-HD of 161.0 +/- 40.7 g/m2 or 31.6 +/- 8.2%. Possibly, poor control of hypervolemia, which is caused by peritoneal problems induced by either peritonitis or chronic exposure to high-glucose dialysate, causes a substantial cardiac preload leading to incipient cardiac failure in L-CAPD. According to the similar results of L-CAPD and DM-HD, it may be that hypertension, hyperlipidemia, or long-term constant glucose loading of CAPD fluids in addition to impaired glucose tolerance by chronic renal failure is more or less related to the progression of LV hypertrophy and latent cardiac dysfunction in long-term CAPD patients. In this context, CAPD of more than 5 years' duration is disadvantageous for preserving cardiac function as compared with HD.

Adult↗

Antinociceptive and anti-inflammatory activities of limonin isolated from the fruits of Evodia rutaecarpa var. bodinieri.

Antinociceptive and anti-inflammatory effects of limonin isolated from the dried fruits of Evodia rutaecarpa var. bodinieri were investigated. Oral administration of 30 or 100 mg/kg limonin significantly decreased the frequency of licking and biting behavior within a unit of time at the late phase without affecting that of the early phase in the formalin test. Limonin inhibited the rise of vascular permeability induced by acetic acid and the increase of paw edema induced by carrageenin. Limonin also showed inhibitory effects on bradykinin-induced paw edema and arachidonic acid-induced ear swelling. These results suggest that limonin possesses an antinociceptive effect and the effect may be accompanied by an anti-inflammatory action, and that the antinociceptive activity in Evodiae Fructus is partially attributable to limonin.

Analgesics↗

Requirement for p56(lck) tyrosine kinase activation in Th subset differentiation.

The lymphocyte-specific protein tyrosine kinase p56(lck) (Lck) is well documented with regard to its role in regulating T cell activation and thymocyte development through delivery of signals via the mature alphabeta TCR as well as the pre-TCR. Little is known, however, about the role of Lck in Th cell subset differentiation in the periphery. Here, we assess the requirement for tyrosine kinase activation of Lck in Th1 and Th2 cell differentiation by using a dominant-negative Lck (DLGKR) transgenic (Tg) mice under the control of a lck distal promoter that directs high expression in mature T cells, in which splenic CD4 T cells developed normally. This Tg mouse provides a good experimental model system to investigate the roles of Lck in mature T cell function in vivo. We show that the catalytically inactive Lck protein at about twice-normal concentrations inhibits Th2 subset differentiation in vivo and in vitro, whilst leaving the maturation of the other T cell subset, Th1, intact. These data indicate a requirement for Lck activity in Th2 cell differentiation, and a differential dependence for Lck activity between Th2 and Th1 cell differentiation.

Amino Acid Sequence↗

Successful use of single-lumen, urokinase immobilized femoral catheters as a temporary access for haemodialysis.

METHODS: Placement of a femoral vein catheter as a temporary vascular access for haemodialysis was conducted and the indications, catheter patency rate, and incidence of catheter-related infections were examined. An urokinase immobilized femoral vein catheter (UIFC) is a soft polyurethane single-lumen catheter 2.7 mm in diameter and 22 cm in length which needs no heparin infusion (Japan Shawood Co., Ltd., Tokyo; Unitica Co., Ltd., Hyogo, Japan). A soft silicon rubber was attached to the tip of the catheter in order to avoid excessive bleeding during insertion. Aseptic adhesive wound dressing was employed at the exit-site which was cleansed with popidone-iodine and renewed at each dialysis session. RESULTS: Eighty-one UIFCs were used for haemodialysis in 64 patients (acute renal failure: 11; vascular access trouble: 53; initiation of chronic dialysis: 17). The average age of the patients was 58 +/- 13 years, ranging from 26 to 80 years. The mean duration of catheter indwelling was 22.4 +/- 13.1 days. An adequate blood flow of 180-200 ml/min was obtained through UIFC and returned to another peripheral vein punctured at each dialysis session. Unexplained fever occurred in four cases while the UIFC was in place (4.9%) but culture of either blood or the catheter tip was negative for bacteria. The catheter was removed immediately and fever subsided in all cases. The overall catheter survival rate was 84% at 34 days calculated using the Kaplan-Meier method. Catheter insertion was easy to perform and no serious complications such as pulmonary embolism or septicaemia occurred. CONCLUSION: Our modified type of UIFC is very useful as a temporary access for haemodialysis with a very low incidence of catheter-related infections and no need for heparinization. Excellent catheter patency was maintained with the plug system and careful dressing techniques without unnecessary bleeding during catheter care.

Adult↗

MUC-1 mucin expression in invasive areas of intraductal papillary mucinous tumors of the pancreas.

The expression of MUC-1 mucin (membrane-associated mucin) and MUC-2 mucin (secretory mucin) were immunohistochemically examined in 46 invasive ductal carcinomas (IDC) and 16 intraductal papillary mucinous tumors (IPMT) of the pancreas. Intraductal papillary mucinous tumors usually reveal expansive growth. However, of the 16 IPMT examined in the present study, three showed an invasive growth pattern, which was similar to 'mucinous carcinoma', around the non-invasive growth areas. Of 46 IDC, MUC-1 mucin detected by monoclonal antibodies, DF3 and MY.1E12, was expressed in 44 cases (96%) and in 45 cases (98%), respectively, whereas MUC-2 mucin detected by polyclonal antibody, anti-MRP, was not expressed in any of the cases (0%). In contrast, in the non-invasive growth areas of the 16 IPMT, MUC-1 mucin detected by DF3 and MY.1E12 was expressed in four cases (25%) and in six cases (38%), respectively, whereas MUC-2 mucin detected by anti-MRP was expressed in 13 cases (81%). The invasive growth areas of the three IPMT showed positive expression of MUC-1 mucins detected by DF3 and MY.1E12, although the non-invasive growth areas showed negative expression of MUC-1 mucins, except for their focal positive expression in one of the three cases. These findings indicate that the invasive growth areas of IPMT acquire a characteristic of MUC-1 mucin expression that is usually seen in IDC.

Biomarkers, Tumor↗

Baicalin and baicalein, constituents of an important medicinal plant, inhibit intracellular Ca2+ elevation by reducing phospholipase C activity in C6 rat glioma cells.

Glial cells have a role in maintaining the function of neural cells. This study was undertaken to clarify the effects of baicalin and baicalein, flavonoids isolated from an important medicinal plant Scutellariae Radix (the root of Scutellaria baicalensis Georgi), on glial cell function using C6 rat glioma cells. Baicalin and baicalein caused concentration-dependent inhibition of a histamine-induced increase in intracellular Ca2+ concentrations ([Ca2+]i). The potency of baicalein was significantly greater than that of baicalin. The noradrenaline- and carbachol-induced increase in [Ca2+]i was also inhibited by baicalein and both drugs inhibited histamine-induced accumulation of total [3H]inositol phosphates, consistent with their inhibition of the increase in [Ca2+]i. These results suggest that baicalin and baicalein inhibit [Ca2+]i elevation by reducing phospholipase C activity. The inhibitory effects of baicalin and baicalein on [Ca2+]i elevation might be important in the interpretation of their pharmacological action on glial cells, such as inhibition of Ca2(+)-required enzyme phospholipase A2.

Animals↗

Analysis of inhibitory effects of scutellariae radix and baicalein on prostaglandin E2 production in rat C6 glioma cells.

Inhibitory mechanism of the water extract of Scutellariae Radix on prostaglandin E2 (PGE2) release was examined in C6 rat glioma cells. Scutellariae Radix reduced a Ca2+ ionophore A23187-induced PGE2 release by inhibition of arachidonic acid (AA) liberation. Sho-saiko-to and San'o-shashin-to, which contain Scutellariae Radix, also inhibited PGE2 release. A23187 caused phosphorylation of mitrogen-activated protein kinase (MAPK), resulting in activation of cytosolic phospholipase A2 (cPLA2). Scutellariae Radix and baicalein inhibited the phosphorylation of MAPK. Baicalein, but not baicalin, inhibited A23187-induced PGE2 release. These results suggest that baicalein in Scutellariae Radix reduces AA liberation through the inhibition of the MAPK-cPLA2 pathway.

Amino Acid Sequence↗

Crescentic glomerulonephritis due to rifampin treatment in a patient with pulmonary atypical mycobacteriosis.

A 64-year-old male was treated continuously with rifampin, isoniazid and streptomycin for pulmonary atypical mycobacteriosis, Mycobacterium kansasii. Five weeks after beginning the treatment, the patient suddenly developed acute renal failure. A renal biopsy showed crescentic lesions characteristic of rapidly progressive glomerulonephritis with moderate interstitial changes. Serum antirifampin antibody was detected, and the cessation of rifampin treatment was followed by a rapid spontaneous recovery of the patient's renal function. This is, to our knowledge, the first case of rapidly progressive crescentic glomerulonephritis associated with rifampin treatment where circulating antirifampin antibody is demonstrated and the renal function spontaneously improved after discontinuing rifampin treatment.

Antibiotics, Antitubercular↗

Effects of Sho-saiko-to, San'o-shashin-to and Scutellariae Radix on intracellular Ca2+ mobilization in C6 rat glioma cells.

Glial cells are able to support neurons physically and functionally. The present study was undertaken to determine the effects of Kampo medicines on glial cell function, especially Ca2+ mobilization. C6 rat glioma cells expressed H1-histamine, muscarinic cholinergic and adrenergic alpha1-receptors, stimulation of which resulted in phosphoinositide hydrolysis and increase in intracellular Ca2+ concentrations ([Ca2+]i). The water extracts of Sho-saiko-to and San'o-shashin-to, Kampo medicines which contain Scutellariae Radix (Ogon, the root of Scutellaria baicalensis GFORGI), inhibited histamine (100 microM)-induced increase in [Ca2+]i in a concentration-dependent manner. The water extract of Scutellariae Radix potently decreased [Ca2+]i in a concentration-dependent manner. Sho-saiko-to, San'o-shashin-to and Scutellariae Radix significantly inhibited histamine-induced accumulation of total [3H]inositol phosphates, consistent with their inhibition of the increase in [Ca2+1]i. These results suggest that Sho-saiko-to, San'o-shashin-to and Scutellariae Radix inhibit Ca2+ mobilization mediated via an inhibition of phospholipase C. The inhibitory effect may be important in interpreting the pharmacological actions of above Kampo medicines.

Animals↗

Studies on Kochiae Fructus. V. Antipruritic effects of oleanolic acid glycosides and the structure-requirement.

We examined the antipruritic effects of various oleanolic acid glycosides from natural medicines such as Kochiae Fructus (the fruit of Kochia scoparia SCHRAD.) and Momordicae Radix (the roots of Momordica cochinchinensis SPRENG.) using a compound 48/80-induced pruritic model in mice. Oleanolic acid 3-O-monodesmosides showed an antipruritic effect, while oleanolic acid 3,28-O-bisdesmosides and their common sapogenol oleanolic acid lacked the activity. This evidence indicated that the 3-O-glycoside moiety and the 28-carboxyl group in oleanolic acid glycosides were essential for exhibiting the antipruritic effect. Furthermore, it was found that the 3-O-glucuronides showed more potent activity than the corresponding 3-O-glucosides.

Animals↗

Studies on Alismatis Rhizoma. II. Anti-complementary activities of methanol extract and terpene components from Alismatis Rhizoma (dried rhizome of Alisma orientale).

A methanol extract (TMe-ext) from the dried rhizome of Alisma orientale was screened for anti-complementary activity in experimental models. In the animal models, it was found that TMe-ext inhibits zymosan-induced hind paw edema in rats and zymosan-activated rat serum (ZAS)-induced vascular permeability in mice. TMe-ext showed an inhibitory effect on complement-induced hemolysis through both the classical pathway and the alternative pathway. And TMe-ext inhibited hypotonic shock-induced hemolysis, but this effect was weak compared with the anti-complementary activities of TMe-ext. Four triterpenes (alisol A, alisol A monoacetate, alisol B and alisol B monoacetate) isolated from the rhizome also inhibited the complement-induced hemolysis through the classical pathway, but two sesquiterpenes (alismol and alismoxide) were ineffective. These results indicate that Alismatis Rhizoma shows anti-complementary activity, and its anti-complementary components are partially attributable to the terpene components mentioned above.

Animals↗

New antidiabetic compounds, mangiferin and its glucoside.

Mangiferin (MF) and its glucosides (mangiferin-7-O-beta-glucoside) (MG) isolated from Anemarrhena asphodeloides Bunge rhizome, were tested for their antidiabetic activity in KK-Ay mice, an animal model of non-insulin-dependent diabetes mellitus (NIDDM). MF and MG lowered the blood glucose level of KK-Ay mice after oral administration. However, no affect on the blood glucose level in normal mice was seen, indicating that MF and MG are useful in treating NIDDM. In addition, MF or MG improved hyperinsulinemia in KK-Ay mice. From these findings, it seems likely that MF and MG exert their its antidiabetic activity by increasing insulin sensitivity.

Animals↗

Application of tumbling melt granulation (TMG) method to prepare controlled-release fine granules.

The tumbling melt granulation (TMG) method was applied to prepare controlled-release fine granules of diltiazem hydrochloride (DH). The entire process, from the preparation of the cores by the adherence of DH to the sucrose crystal to the subsequent coating of the controlled-release layer, was performed without using any solvent. A mixture of meltable material, talc, and ethylcellulose was used for the controlled-release layer and controlled-release fine granules approximately 400 microns in diameter were obtained with excellent producibility. The dissolution rate of DH from these fine granules was similar to that of a once-a-day dosage form obtained in the market; further, the dependency of the dissolution profile on pH of the media was less. Thus, it was concluded that this TMG method was very useful for preparing not only controlled-release beads of granule size (usually 500 to 1400 microns) but also fine granules.

Delayed-Action Preparations↗

Novel indole S,O-bisdesmoside, calanthoside, the precursor glycoside of tryptanthrin, indirubin, and isatin, with increasing skin blood flow promoting effects, from two Calanthe species (Orchidaceae).

The methanolic extracts from Calanthe discolor LINDL. and C. liukiuensis SCHLTR. were found to exhibit hair restoring and skin blood flow promoting activities. Through bioassay-guided separation using the skin blood flow increasing effect, a novel indole S,O-bisdesmoside, calanthoside, was isolated together with three new components, glucoindican, calaliukiuenoside, and calaphenanthrenol, and known compounds such as tryptanthrin, indirubin, isatin, and indican. The structures of the new compounds were determined on the basis of physicochemical and chemical evidence and they showed an activating effect on skin blood flow. In addition, it was found that enzymatic hydrolysis of calanthoside with beta-glucosidase furnished tryptanthrin together with a small amount of indirubin and isatin, whereas indirubin and isatin were obtained from calanthoside by acid hydrolysis. Based on their contents in the fresh and dried plant, calanthoside may be a common genuine glycoside of tryptanthrin, indirubin, and isatin in the plant.

Animals↗

Need for aromatic residue at position 115 for proteolytic activity found by site-directed mutagenesis of tryptophan 115 in thermolysin.

In thermolysin, tryptophan 115 seems to be at the S2 subsite. Trp-115 was replaced with tyrosine, phenylalanine, leucine, and valine during site-directed mutagenesis in order to evaluate the role of Trp-115 in the proteolytic activity of thermolysin. The mutant enzymes with Tyr-115 or Phe-115 had as much proteolytic activity as the wild-type enzyme, but the other two mutant enzymes had no activity. We found earlier that the substitution of Trp-115 with alanine, glutamic acid, lysine, and glutamine causes the enzyme to lose all activity, so an aromatic amino acid at position 115 seems to be essential for thermolysin.

Escherichia coli↗