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Biomedical subjects

H Endo

Publications and source records attributed to H Endo.

At least 307 records · Page 17Linked to original sources

Effects of indeloxazine hydrochloride, a cerebral activator, on passive avoidance learning impaired by disruption of cholinergic transmission in rats.

The effect of indeloxazine [(+/-)-2-[(inden-7-yloxy)methyl]morpholine hydrochloride, YM-08054], a cerebral activator, on passive avoidance learning by disruption of cholinergic transmission was investigated in rats. Indeloxazine prolonged the latency for stepping out of an illuminated compartment into a dark compartment, in both mature and aged rats. Disruption of cholinergic transmission was induced by injection of scopolamine, ethylcholine, treatment with aridinium ion (AF64A) and by lesioning the nucleus basalis magnocellularis. The shortened latency in these models was prolonged when indeloxazine was administered before training in doses which did not affect spontaneous movement or the response to pain in mature rats and administration of indeloxazine, immediately after training, also had an ameliorating effect on passive avoidance in the lesioned rats. In biochemical studies, indeloxazine increased the extracellular concentration of acetylcholine in the frontal cortex of mature rats. These results suggest that indeloxazine possesses facilitatory effects on cerebral function, in part due to activation of the central cholinergic system.

Acetylcholine↗

Improved in vitro angiogenesis model by collagen density reduction and the use of type III collagen.

Angiogenesis was examined by a three-dimensional model in vitro, using human umbilical vein endothelial cells (HUVECs) cultured in a collagen gel. An abundant capillary-like network with a lumen structure was identified histologically and shown to have formed at a collagen density of 0.05% or 0.10% instead of 0.15%, for either type I or type III collagen. At the same density, type III collagen induced a capillary-like network with HUVECs at an earlier stage of culture than type I collagen. In a two-dimensional culture, HUVECs were viable and proliferated to a great extent on the culture dish coated with collagen. This was particularly so in the case of type III collagen at lower density (5 ng/cm2). Type III collagen at a sufficiently low density is thus shown useful for studying angiogenesis in vitro. The capillary-like network that formed in the three-dimensional culture appeared somewhat labile, but became stable with the continuous addition of endothelial cell growth supplement and increase in the plating number of HUVECs.

Capillaries↗

Quantitative hepatitis C virus RNA and liver histology in chronic hepatitis C patients treated with interferon alfa.

Seventy patients with hepatitis C virus (HCV) infection received alpha interferon at doses ranging from 3 to 10 million units (MU) daily for eight weeks, three times weekly for 12-24 weeks, or daily and three times weekly for 12-24 weeks. The efficacy of interferon was closely related to the initial blood HCV-RNA values in that these were lower in those who responded completely and partially compared with non-responders. Continuous reductions in HCV-RNA and improvements in the histology activity index score were seen in those who responded completely. In contrast, most of the partial and non-responders remained HCV-RNA positive.

Drug Evaluation↗

In vitro interleukin-5 production of peripheral blood mononuclear cells is increased in patients with asthma.

To determine whether the capacity of interleukin-5 (IL-5) production is increased in patients with asthma, we studied in vitro IL-5 production from peripheral blood mononuclear cells (PBMC) in 27 asthmatics (16 allergic asthmatics and 11 nonallergic asthmatics) and 10 normal subjects. IL-5 production of phytohemagglutinin (PHA)-stimulated PBMC was significantly greater in asthmatics than in normal subjects (p < 0.02). IL-5 production of PBMC by IL-2 stimulation was also significantly increased in asthmatics compared with that of normal subjects (p < 0.05). In contrast, IL-2 production of PHA-stimulated PBMC did not significantly differ between asthmatics and normal subjects. In addition, the number of CD4+ and CD8+ T cells in PBMC or CD4+/CD8+ ratio did not significantly differ between asthmatics and normal subjects, whereas CD25+ T cells were significantly increased in asthmatics compared with those of normal subjects (p < 0.02). Finally, there was no significant correlation between the in vitro IL-5 production of PBMC and blood eosinophil counts in asthmatics and normal subjects. Our results indicate that the capacity of IL-5 production, but not of IL-2 production, is increased in asthmatics. The increased capacity of IL-5 production might be involved in the migration and activation of eosinophils in the airways of asthmatics.

Adolescent↗

Growth hormone-releasing hormone peptide and mRNA are overexpressed in GH-deficient Ames dwarf mice.

Hypothalamic expression of growth hormone-releasing hormone (GHRH) was quantified morphologically in dwarf mice which exhibit spontaneous genetic GH absence. Mouse GHRH mRNA was assessed by in situ hybridization; densitometric evaluation of total mRNA in dwarfs showed levels 2.3-fold higher than in phenotypically normal siblings (p < 0.01); assessment of mRNA per neuron by autoradiographic grain counting indicated a 2.5-fold increase per cell in dwarfs (p < 0.005). GHRH peptide was evaluated immunocytochemically using a new mouse-specific antiserum; numbers of neurons containing detectable levels were 3-fold higher in dwarfs (p < 0.005). The increase in GHRH mRNA corroborates that reported previously in the GH-deficient little mouse, and after hypophysectomy in rats; GHRH peptide increase contrasts with previous reports of the effect of acute GH removal by hypophysectomy, in which GHRH levels fell. The results suggest that chronic GH deficiency is accompanied by increased translation as well as transcription of GHRH.

Animals↗

Natural course of chronic hepatitis C.

We studied 333 chronic hepatitis C patients to evaluate the natural course of this disease. Among 57 patients undergoing serial biopsies, 20 had chronic persistent hepatitis (CPH) at the first biopsy, and 10 of them progressed to chronic active hepatitis (CAH) or liver cirrhosis (LC) after 11 yr. Sixteen patients had CAH 2A, and this progressed to CAH 2B or LC in 10 cases over 9 yr. Among the 21 patients with CAH 2B, progression to LC was noted in 15 after 7 yr. Among the 100 patients observed for over 5 yr, the normalization of liver function for at least 3 yr was seen in only four patients. In two of these four patients, serum HCV-RNA was tested serially. Despite the sustained normalization of alanine aminotransferase levels, HCV-RNA continued to be detectable in one patient. We conclude that many patients with chronic hepatitis C eventually show progression of their disease after a long and symptomless course.

Adolescent↗

Depression of catalase gene expression in the liver of tumor bearing nude mice.

Based on the classical observation that catalase activity is reduced in the liver of a tumor bearing host, we studied this phenomenon from the aspect of gene expression. Northern blot analysis on the livers of mice with a rat tumor showed that the catalase gene expression is lowered in a tumor size-dependent fashion. Decreased gene expression was also seen irrespective of tissue or species origin of tumors transplanted. Removal of the implanted tumor resulted in restoration of the reduced gene message to the normal level. The tumor effect on the catalase gene expression was shown to be controlled at the transcriptional level. These results strongly suggest that the reduction of liver catalase activity in the tumor bearer may be due to down regulation of the catalase gene induced in the liver by a certain humoral factor(s) from the transplanted tumor.

Animals↗

Epidermal growth factor stimulates mouse placental lactogen I but inhibits mouse placental lactogen II secretion in vitro.

This study was undertaken to determine whether epidermal growth factor (EGF) regulates the secretion of mouse placental lactogen (mPL)-I and mPL-II. Primary cell cultures were prepared from placentas from days 7, 9, and 11 of pregnancy and cultured for up to 5 days. Addition of EGF (20 ng/ml) to the medium resulted in significant stimulation of mPL-I secretion by the second day of culture in cells from days 7 and 9 of pregnancy and significant inhibition of mPL-II secretion by the third or fourth day of culture in cells from days 7, 9, and 11. Dose-response studies carried out with cells from day 7 of pregnancy demonstrated that the minimum concentration of EGF that stimulated mPL-I secretion and inhibited mPL-II secretion was 1.0 ng/ml. EGF did not affect the DNA content of the cells or cell viability, assessed by trypan blue exclusion, nor did it have a general effect on protein synthesis. There are three types of PL-containing giant cells in mouse placental cell cultures: cells that contain either mPL-I or mPL-II and cells that contain both hormones. Immunocytochemical analysis and the reverse hemolytic plaque assay indicated that EGF treatment was accompanied by a significant increase in the number of cells that produce mPL-I, but among the PL cells that contained mPL-I, there was no change in the fraction of cells that contained only mPL-I or the fraction that contained both mPL-I and mPL-II. In contrast, EGF treatment did affect the distribution of mPL-II among PL cells. In control cultures, about 75% of the cells that contained mPL-II also contained mPL-I, but in EGF-treated cultures, all of the cells that contained mPL-II also contained mPL-I. These data suggest that EGF regulates mPL-I and mPL-II secretion at least partly by regulating PL cell differentiation.

Animals↗

The primary structure of mouse saposin.

The primary structure of mouse sphingolipid activator protein (saposin) was determined by cDNA sequencing. The amino acid sequence predicted by the cDNA sequence revealed that mouse saposin was highly homologous to human saposin and also to rat sertoli cell glycoprotein. Mouse saposin also has four functional domains, which are structurally similar to each other, and each domain has cysteines, prolines, and a potential glycosylation site at an almost identical position. An amino acid comparison between human and mouse saposins revealed that the similarity was approximately 70%, and human saposin lacks thirty-one amino acids between domains C and D. Heterogeneities of mRNA were found in both the coding and noncoding regions.

Amino Acid Sequence↗

Beneficial effects of dietary intervention on serum lipid and apolipoprotein levels in obese children.

Effects of weight reduction on serum levels of lipids and apolipoproteins were measured in 13 obese children (seven girls, six boys). Mean weight loss of 8.4% of the initial body weight was achieved after 4 weeks of energy intake restriction and exercise. Serum total cholesterol (5.46 +/- 1.01 mmol/L) and triglyceride (2.08 +/- 0.52 mmol/L) levels were significantly high compared with control values before treatment and were significantly reduced to 4.32 +/- 0.75 and 1.31 +/- 0.42 mmol/L, respectively, after treatment. Serum high-density lipoprotein cholesterol level (1.03 +/- 0.23 mmol/L) was significantly low and unchanged after treatment (0.94 +/- 0.25 mmol/L). Serum apolipoprotein A-I level (0.039 +/- 0.009 mmol/L or 111 +/- 0.26 g/L) was normal before treatment and significantly reduced, to 0.032 +/- 0.007 mmol/L or 0.92 +/- 0.19 g/L, after weight reduction. Serum apolipoprotein B level (0.00019 +/- 0.00007 mmol/L or 1.07 +/- 0.21 g/L) was significantly high before treatment and decreased to the normal range after treatment (0.00014 +/- 0.0009 mmol/L or 0.76 +/- 0.24 g/L). The ratio of apolipoprotein B to apolipoprotein A-I (1.09 +/- 0.29) was significantly high on admission and decreased significantly to 0.64 +/- 0.12 after treatment. Serum apolipoprotein E level (0.0014 +/- 0.0006 mmol/L or 0.05 +/- 0.02 g/L) was normal and decreased to 0.0008 +/- 0.0002 mmol/L or 0.03 +/- 0.01 g/L after treatment. In conclusion, weight reduction achieved by energy intake restriction and exercise had beneficial effects on serum lipid and apolipoprotein concentrations for the prevention of future atherosclerosis.

Adolescent↗

Nerve growth factor receptor gene expression in human peripheral blood lymphocytes in aging.

Nerve growth factor (NGF) has a modulating effect on immune function, which may occur as a consequence of binding to the NGF receptor (NGF-R). To determine if mRNA for the gene coding for p75NGFR (low affinity NGF-R) is present in lymphocytes, Northern blot analysis of mRNA from human peripheral blood lymphocytes (PBL) and purified T lymphocytes was initiated using cDNA probe for human p75NGFR. p75NGFR mRNA was present in PBL and T lymphocytes, and the mRNA in response to phytohemagglutinin stimulation showed maximum levels at 14 hr of stimulation. p75NGFR mRNA content when analyzed in PBL and T cells from volunteers of various ages showed that p75NGFR mRNA expression does not change with the age of the cell donor.

Adult↗

Production of interleukin 8 by cultured synovial cells in response to interleukin 1 and tumor necrosis factor.

Both interleukin 1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) stimulated the production of interleukin 8 (IL-8) by synovial cells in time and dose dependent manners. Enhanced chemotactic activity of polymorphonuclear cells (PMN) in culture supernatants of synovial cells was neutralized with anti-IL-8 antibody, thus showing synovial cells to be capable of secreting IL-8 which may contribute to PMN accumulation in rheumatoid inflamed joints.

Cells, Cultured↗

Hepatitis type C virus infection in patients with type B chronic liver disease.

Anti-c100-3 (Ortho) was determined in the sera of 152 patients with HBs antigen-positive chronic liver diseases to assess coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Eleven patients (7.2%) were positive for anti-c100-3. Anti-CP-9 (Okamoto) and HCV-RNA (RT-PCR) were also examined in these 11 patients. Anti-CP-9 was detected in 7 patients and HCV-RNA was detected in all 11 patients. Four of the 11 anti-c100-3-positive patients were positive for HBe antigen (HBeAg) and others were negative. In 8 of the 11 patients, HCV was suspected to be superinfected by blood transfusion. In HBeAg-positive patients, serum glutamic pyruvic transaminase (SGPT) was elevated in relation to active replication of HBV shown by DNA-polymerase activity. The histological findings showed chronic active hepatitis, with or without cirrhosis. On the other hand, in HBeAg-negative patients, SGPT fluctuated without evidence of active replication of HBV. Active inflammation in the liver was observed in 3 of 5 HBeAg-negative patients by liver biopsy. These findings suggest that HBV might play an important role in chronic active inflammation in HBeAg-positive patients coinfected with HCV, and that HCV might be responsible for continuous inflammation in HBeAg-negative patients coinfected with HCV.

Adult↗