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Biomedical subjects

T Horie

Publications and source records attributed to T Horie.

At least 397 records · Page 22Linked to original sources

Characterization of mucin antigens recognized by monoclonal antibodies raised against human colon cancer cells.

Two monoclonal antibodies, MLS 102, which recognizes cancer-associated mucin antigens, and MLS 103, which recognizes normal mucin, were used to isolate, by immunoaffinity chromatography, the corresponding antigens from cell lysates and spent medium of a human colorectal carcinoma cell line, LS 180. The MLS 102 antigen contained serine, threonine, and proline as major amino acids. The carbohydrate chains of the MLS 102 antigen were composed of O-linked NeuAc alpha 2----6GalNAc (56%), N-acetylgalactosamine (25%), and longer oligosaccharide chains. The MLS 103 antigen differed from the MLS 102 antigen in both amino acid and carbohydrate composition. Most O-linked oligosaccharides of the MLS 103 antigen were longer than the disaccharide found in the MLS 102 antigen. Immunostaining of LS 180 cells using MLS 102 and MLS 103 revealed that the cells are heterogeneous with respect to the expression of the antigens.

Amino Acids↗

Functional T cell subpopulations responsible for hyposecretion of IL-2 in patients with systemic lupus erythematosus.

The ability of T cells to secrete IL-2 in patients with systemic lupus erythematosus (SLE) was investigated. In patients with SLE, impaired IL-2 production by peripheral blood lymphocytes stimulated with mitogens is well known. In this paper, we report that purified T cells stimulated with mitogens, in the presence of Epstein-Barr virus transformed B cells (B-LCL) as an accessory cell, however, could secrete a large quantity of IL-2 as much as normal T cells. In order to study this potential capacity of T cells to secrete IL-2 in patients with SLE, IL-2 secreting T cells were examined. To obtain these cells, T cells were divided into cluster forming cells and noncluster forming cells after short culture of T cells with accessory cells in the presence of Con A. Then the ability of IL-2 production in two kinds of separated T cells was examined. We found that 1) after short culture with B-LCL, the cluster forming T cells could secrete IL-2 when cultured again, but non-cluster forming T cells could not, even in the presence of B-LCL, 2) after short culture with macrophages, in normal donors and SLE patients, noncluster forming T cells were able to secrete a greater amount of IL-2 than cluster forming and undivided T cells when cultured with B-LCL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

In vivo effect of a large amount of allogeneic granulocytes on reconstitution of hemopoietic cells of irradiated mice.

The in vivo effects of allogeneic granulocytes on the reconstitution of splenic and bone marrow CFUs and CFUc numbers were investigated using irradiated mice. When allogeneic granulocytes were intraperitoneally injected into irradiated BDF1 mice (260 rads), the reconstitution of CFUs in both spleen and bone marrow as well as the hematocrit were enhanced, while the reconstitution of splenic or bone marrow CFUc numbers was transiently suppressed and then enhanced. The magnitude of enhancement was dose-dependent. These results suggest that granulocytes injected into irradiated mice might act as enhancing effectors on the in vivo reconstitution of hemopoietic cells.

Animals↗

Expression of a multidrug-resistance gene in human malignant lymphoma and related disorders.

The expression of mdr1 gene was measured to determine whether it plays a role in clinical resistance to chemotherapy of human malignant lymphomas. mdr1 expression was found in 4 of 9 cases resistant to chemotherapy. Expression of mdr1 was not detectable in any of 7 chemotherapy-sensitive tumors. The 2 cases of reactive lymphadenitis and the 3 samples of normal mononuclear cells did not show any expression of mdr1 gene, either. These results indicate that expression of the mdr1 gene is not always detectable in cases of malignant lymphoma resistant to chemotherapy, but the detectable expression of mdr1 gene may predict clinical resistance to chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Syntheses of 5,7,8- and 5,6,7-trioxygenated 3-alkyl-3',4'-dihydroxyflavones and their inhibitory activities against arachidonate 5-lipoxygenase.

5,6,7- and 5,7,8-Trioxygenated 3',4'-dihydroxyflavones were derivatized by introducing alkyl groups of various chain lengths at the 3-position of the flavone skeleton. These compounds were tested as inhibitors for arachidonate 5-lipoxygenase purified from porcine leukocytes. Modification of the 3-position with an alkyl group of 6-10 carbons markedly decreased the IC50 values. 3-Hexyl-3',4'-dihydroxy-5,7, 8-trimethoxyflavone inhibited 5-lipoxygenase with an IC50 value of 58 nM. The platelet and leukocyte 12-lipoxygenases, 15-lipoxygenase of reticulocytes, and cyclooxygenase of vesicular gland were inhibited less potently (IC50 = 0.4, 0.4, 2.7, and 30 microM). Thus, the compound was a relatively selective inhibitor for 5-lipoxygenase.

Animals↗

Chronic effects of metoprolol on myocardial beta-adrenergic receptors in doxorubicin-induced cardiac damage in rats.

This study was designed to clarify whether chronic administration of metoprolol had any influence on cardiac beta-adrenergic receptors (BAR) in doxorubicin (DOX)-induced cardiac damage. DOX was injected through the tail vein into rats (3 mg/kg/week, n = 22) for 5 weeks. One week after the final injection, the rats were randomly divided into two groups, M (with metoprolol, 10 mg/kg/day subcutaneously, s.c.; n = 11) and D (without metoprolol; n = 11). After 3-week infusion, plasma norepinephrine (NE) levels and BAR density [[125I]iodocyanopindolol (ICYP) binding on crude membranes] were measured. Left and right ventricular end-diastolic pressure (LVEDP, RVEDP) and myocardial NE levels were also measured, and the results were compared with those from an age-matched control group (C n = 11). Decreased BAR density and increased plasma NE levels were evident in group D, indicating downregulation. In group M, BAR density and plasma NE levels were similar to those in group C. The myocardial NE levels were decreased in group D, but were higher in group M than in group D. The LVEDP and RVEDP were increased in group D, but were almost normal in group M. These results suggest that metoprolol is a promising drug for treatment of DOX-induced cardiac damage.

Animals↗

Protective effect of vitamin A against the methotrexate-induced damage to small intestine: a study on the crypt cells.

Vitamin A (VA) protects the small intestine from the methotrexate (MTX)-induced damage. The in vivo effects of MTX and/or VA on crypt cells of small intestine were investigated using rats orally administered MTX (15 mg/kg body weight) and/or VA (5,000 IU/kg body weight). The thymidine kinase activity of crypt cells separated from villus cells of small intestine of MTX plus VA-treated rats was lower than that from control rats but higher than that from MTX-treated rats. VA-treated rats showed almost the same activity of thymidine kinase as control rats. The amounts of the end products, adenosine monophosphate (AMP) and guanosine monophosphate (GMP), contained in crypt cells of treated rats were determined to investigate the in vivo effects of MTX and/or VA on de novo purine synthesis. MTX treatment significantly decreased the amounts of both AMP and GMP but both amounts were not affected by MTX plus VA treatment. Treatment with VA alone appeared to increase their amounts slightly. Thus, although the oral administration of MTX to rats inhibited DNA synthesis in crypt cells, VA coadministration protected the salvage pathway of pyrimidine synthesis and the de novo purine synthesis in crypt cells.

Animals↗

Impaired tumour necrosis factor-alpha (TNF-alpha) production and abnormal B cell response to TNF-alpha in patients with systemic lupus erythematosus (SLE).

We examined the TNF-alpha activity in culture supernatants of monocytes isolated from the peripheral blood of patients with SLE and of normal individuals. The monocytes from patients with SLE stimulated with silica particles, lipopolysaccharide or Staphylococcus aureus Cowan 1 secreted significantly lower amounts of TNF-alpha than did normal monocytes. A decreased TNF mRNA expression was observed in peripheral blood mononuclear cells stimulated by mitogens from patients with SLE. Furthermore, we examined the effect of recombinant TNF-alpha (rTNF-alpha) on the B cell function in SLE patients. rTNF-alpha inhibited the spontaneous B cell proliferation of SLE, but tended to enhance the normal B cell proliferation. Spontaneous IgM production from SLE B cells was inhibited by rTNF-alpha, but that from normal B cells was not. Spontaneous IgG production was unaffected by rTNF-alpha. Also, rTNF-alpha did not affect the viability of B cells. These findings suggest that an impaired TNF-alpha production and an abnormal B cell response to TNF-alpha play a role in the immunological dysfunction in patients with SLE.

B-Lymphocytes↗

Mechanism of calcium ionophore and phorbol ester-induced T-cell activation. Accessory cell requirement for T-cell activation.

We examined the role of monocytes in T-cell activation induced by phorbol myristate acetate (PMA) and calcium ionophore ionomycin. Depletion of monocytes from peripheral blood mononuclear cells (PBMC) was associated with the loss of interleukin-2 (IL-2) production, IL-2 receptor (IL-2R) expression and proliferation, in response to either PMA or ionomycin. Addition of monocytes to highly purified T cells resulted in the complete reconstitution of IL-2 production, IL-2R expression and proliferation by PMA-stimulated lymphocytes. Exogenous IL-2, but not interleukin-1 (IL-1), could reconstitute the T-cell responsiveness. Addition of monocytes to highly purified T cells stimulated with ionomycin resulted in partial reconstitution of IL-2 production, IL-2R expression and proliferation. Similarly, the addition of exogenous IL-2 to ionomycin-stimulated T cells only partially reconstituted the response compared with PBMC. These results suggest that monocyte-T-cell interactions contribute to IL-2 production and IL-2R expression and are crucial events for PMA-induced T-cell proliferation. With ionomycin, monocytes play a role, in part, in inducing IL-2 production, IL-2R expression and proliferation. However, IL-2 is not a sufficient signal to induce T-cell proliferative response to ionomycin, suggesting that an IL-2-independent mechanism may exist in ionomycin-induced T-cell proliferation.

Cell Division↗

Effects of irradiation on marrow stromal cells with respect to committed granulocyte-macrophage progenitor cells.

The effects of irradiation on the growth regulatory function of marrow stromal cells (MSC), and on the committed granulocyte-macrophage progenitor cells (GM-CFC), were investigated using a liquid culture system. CSF activity in the supernatant of irradiated MSC (0-900 rads) increased markedly with the increase of MSC irradiation dose. CSF-inhibitory activity in the supernatant of irradiated MSC (0-900 rads) also increased with the increase of MSC irradiation dose. Furthermore, the activity of exogenous CSF added to the supernatant of 900 rad-irradiated MSC was lost more slowly than that of non-irradiated MSC. These data suggest that irradiation affected CSF production, inhibitor production and consumption of CSF by MSC.

Animals↗

Correlations between IL-2 enhancing activity and clinical parameters in patients with rheumatoid arthritis and systemic lupus erythematosus.

In a previous paper (Tomura, K. et al. Tohoku J. Exp. Med., 1989, 159, 171-183), we discovered IL-2 enhancing factor(s) designated B cell derived-growth enhancing factor-2 (BGEF-2), which enhanced IL-2 dependent cell proliferation, and reported that BGEF-2 was produced by B cells of the patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) only when they were in the active stage of the disease. In this paper, we studied relationship between each IL-2 enhancing activity from B cell supernatant of the patients with these diseases and clinical parameters. IL-2 enhancing activities did not correlate with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), but correlated with plasma concentrations of gamma-globulin from the patients with RA and SLE in the active stages. IL-2 enhancing activities correlated with hypocomplementemia and leukocytopenia in the patients with SLE, and also correlated with RAHA titer in the patients with RA. Moreover, on several patients with RA or SLE in the active stages, diminution of IL-2 enhancing activity was found when they were in the remission stage after treatments. These findings suggested that IL-2 enhancing activity (i.e., BGEF-2 activity) correlated with activity of these diseases and supported the hypothesis that BGEF-2 played an important role in the polyclonal B cell activation and autoantibody production in patients with these diseases.

Adult↗

Bialaphos poisoning with apnea and metabolic acidosis.

A 64-year-old man with ethanol intoxication, ingested a bottle of Herbiace (100 ml, 32 w/v% of bialaphos, CAS #35597-43-4, Meiji Seika Kaisha, Tokyo, Japan). He had severe metabolic acidosis and was treated with infusions of sodium bicarbonate and furosemide, plus gastric lavage and enema. The metabolic acidosis improved 15 hours after treatment but nystagmus, apnea and convulsions were progressive. Although his sensorium was clear, spontaneous respirations were not observed for 64 hours. The electroencephalographic findings of atypical triphasic waves and slow waves suggest a unique response to bialaphos poisoning. His clinical course indicates that the management of apnea is critically important to recovery from bialaphos poisoning.

Acidosis↗

Biliary excretion of bile acid conjugates in a hyperbilirubinemic mutant Sprague-Dawley rat.

The hepatic transport of bile acid conjugates was studied in the Eisai hyperbilirubinuria rat, a Sprague-Dawley mutant rat with conjugated hyperbilirubinemia. Serum bile acid levels were increased, bile acid-independent bile flow was decreased and biliary glutathione concentrations were markedly decreased in the Eisai hyperbilirubinuria rat. Biliary excretion of sulfobromophthalein was markedly impaired and almost no glutathione conjugate was excreted in the bile of the Eisai hyperbilirubinuria rat. Biliary excretion of lithocholate-3-O-glucuronide and lithocholate-3-sulfate in the Eisai hyperbilirubinuria rat was markedly delayed, whereas that of lithocholate was only slightly delayed. After [14C]chenodeoxycholate infusion (1 mumol/min/100 gm for 60 min), the increases in bile flow and biliary excretion of isotope in the Eisai hyperbilirubinuria rat were not so prominent as those observed in control rats, and the glucuronide of chenodeoxycholate, which constituted about 15% of biliary chenodeoxycholate in control rats, was not observed in the Eisai hyperbilirubinuria rat. Initial uptake of lithocholate and its glucuronide and sulfate by isolated hepatocytes was not impaired in the Eisai hyperbilirubinuria rat; the profiles of cytosolic bile acid binding proteins in Eisai hyperbilirubinuria rat liver were identical to those in control liver. These data indicate that the Eisai hyperbilirubinuria rat has excretory impairment of organic anions, bile acid glucuronide and sulfate and that it has characteristics very similar to those of the hyperbilirubinemic mutant Wistar rats TR- and GY.

Animals↗

[Upper airway finding on CT scan with and without nasal CPAP in obstructive sleep apnea patients].

The area of upper airway (from the nasopharynx to the hypopharynx) was measured by means of computed tomography (CT) scan in 15 confirmed cases of obstructive sleep apnea (OSA) and in 4 normal controls while they were awake. The minimum cross-sectional area (MA) of the upper airway was 14.7 +/- 20.0 mm2 in OSA patients and 80.0 +/- 33.1 mm2 in normal controls and the difference was statistically significant (p less than 0.01). In OSA patients, MA did not correlate with age, body weight, apnea index, desaturation index, mean nadir-SO2 and lowest SO2. MA was also measured with OSA patients while nasal continuous positive airway pressure (NCPAP) of 10 cmH2O was applied and it was found that MA was significantly widened when NCPAP therapy was performed. We conclude that upper airway narrowing is consistent finding in OSA patients but the degree of narrowing does not correlate with parameters of apnea and gas exchange during sleep, and NCPAP is effective to widen the area of upper airway in OSA patients.

Adult↗

Decrease in the specific forms of cytochrome P-450 in liver microsomes of a mutant strain of rat with hyperbilirubinuria.

Eisai-hyperbilirubinuria rats (EHBR) is a mutant originated from Sprague Dawley rats. The activities of UDP-glucuronyltransferase and drug metabolizing enzymes in EHBR were compared with those in Sprague Dawley rats as the control. The activity of aniline hydroxylase was significantly increased in liver microsomes of EHBR whereas the activity of ethylmorphine N-demethylase was found to be significantly decreased in EHBR as compared to control rats. In addition, the activity of testosterone 7 alpha-hydroxylase was increased in EHBR whereas the activity of testosterone 6 beta-hydroxylase was significantly decreased in EHBR as compared to control rats. Western blot analysis of liver microsomes of EHBR with antibodies to P-450IA2, P-450IIB1, P-450IIC11 and P-450IIIA2 showed that the amounts of P-450IIB1 and P-450IIIA2 in liver microsomes were significantly lower in EHBR than in control rats. These results indicated the form-specific alteration in the amounts of cytochrome P-450 in liver microsomes of EHBR.

Aniline Hydroxylase↗

[Effects of nasal continuous positive airway pressure (NCPAP) on nocturnal renal function in obstructive sleep apnea syndrome (OSAS)].

Nocturnal renal function was examined in 8 patients with obstructive sleep apnea syndrome (OSAS) and the effects of nasal CPAP (NCPAP) on renal function were also studied. Nocturia was observed more than twice in all cases when no treatment was performed, but it disappeared after initiation of NCPAP. Fractional nocturnal urine volume and creatinine clearance decreased significantly from 1.36 +/- 0.15 ml/min to 0.75 +/- 0.20 ml/min (p less than 0.01) and from 116.8 +/- 46.5 ml/min to 101.1 +/- 33.0 ml/min (p less than 0.05), respectively, after initiation of NCPAP. Although the serum Na and creatinine did not change following NCPAP, the urine Na and creatinine changed significantly after NCPAP therapy. The serum renin, aldosterone, and ADH did not change after NCPAP therapy. The significant positive correlation (p less than 0.05) between the fractional nocturnal urine volume and DI, and also significant inverse correlation (p less than 0.05) between the fractional urine volume and %FRC were observed. These results suggest that the abnormal renal function seen in cases of OSAS is related to the hypoxemia during sleep. It was concluded that the nocturnal renal function in cases of OSAS was different from those in normal controls and NCPAP therapy induced the recovery of these abnormalities.

Creatinine↗

Age-related changes in various hemopoietic progenitor cells in senescence-accelerated (SAM-P) mice.

The effect of aging process on the hemopoietic system in senescence-accelerated (SAM-P) mice with respect to numbers of hemopoietic progenitor cells was investigated. The numbers of femoral granulocyte-macrophage colony-forming cells (CFU-GM), mast cell progenitors (mast colony-forming units, CFU-Mast), erythroid burst-forming units (BFU-E), and erythroid colony-forming units (CFU-E) in old mice (30-35 weeks old) decreased to 96%, 81%, 83%, and 87% of those of young mice (8-12 weeks old), respectively. The numbers of femoral fibroblast colony-forming cells (CFU-F) in old mice increased to 315% of those of young mice. The numbers of splenic CFU-GM, CFU-Mast, BFU-E, and CFU-E in old mice decreased to 7%, 43%, 25%, and 40% of those of young mice, respectively. In contrast, significant changes in these progenitor cells were not observed in the bone marrow. These findings suggest that the effect of the aging process on hemopoietic tissues in SAM-P mice is predominantly in the spleen.

Aging↗