Hisamitsu Baba

Oncogenic ras induces gastrin/CCKB receptor gene expression in human colon cancer cell lines LoVo and Colo320HSR

Gastrin has the ability to stimulate cell growth in some colorectal cancer cells and some of these cells also express gastrin/CCKB receptors, suggesting that gastrin and its autocrine loop are involved in their proliferation. We previously reported that oncogenic ras induced gastrin gene expression in colon cancer cells. The aim of this study was to investigate whether oncogenic ras also induces gastrin/CCKB receptor gene expression. A transiently transfected activated ras vector stimulated gastrin/CCKB receptor transcriptional activities in both Colo320HSR and LoVo cells, but these ras-increased activities were inhibited by a specific MEK inhibitor, PD98059. An RPA demonstrated that activated ras increased endogenous gastrin/CCKB receptor mRNA levels and PD98059 decreased them in LoVo cells. These findings suggest that oncogenic ras induces gastrin/CCKB receptor gene expression through some intracellular signaling pathways, including MEK, in colon cancer cell lines.

Direct inhibitory effect of amino-terminal parathyroid hormone fragment [PTH(1-34)] on PTH secretion from bovine parathyroid primary cultured cells in vitro

We have examined the possibility of direct inhibitory effect of PTH(1-34) on PTH secretion in bovine parathyroid cells. As low as 10(-12) M PTH(1-34) completely inhibited low calcium (0.5 mM Ca2+)-stimulated PTH secretion by these cells. In the presence of 1.25 mM Ca2+, 10(-12) M PTH(1-34) inhibited PTH secretion by about 14.3% of the basal value, while 10(-11) M or higher concentration of PTH(1-34) showed potent inhibitory effects equivalent to the inhibitory action of high calcium concentration (2.5 mM Ca2+) on PTH secretion. At 2.5 mM Ca2+, as much as 10(-9) M PTH(1-34) failed to inhibit PTH secretion further. These results suggest that PTH(1-34) might directly, not via calcium concentration, inhibit PTH secretion by parathyroid cells and that a cooperative mechanism could exist between calcium and PTH(1-34) to inhibit PTH secretion.

Cost-effectiveness of gargling for the prevention of upper respiratory tract infections

BackgroundIn Japan, gargling is a generally accepted way of preventing upper respiratory tract infection (URTI). The effectiveness of gargling for preventing URTI has been shown in a randomized controlled trial that compared incidences of URTI between gargling and control groups. From the perspective of the third-party payer, gargling is dominant due to the fact that the costs of gargling are borne by the participant. However, the cost-effectiveness of gargling from a societal perspective should be considered. In this study, economic evaluation alongside a randomized controlled trial was performed to evaluate the cost-effectiveness of gargling for preventing URTI from a societal perspective.MethodsAmong participants in the gargling trial, 122 water-gargling and 130 control subjects were involved in the economic analysis. Sixty-day cumulative follow-up costs and effectiveness measured by quality-adjusted life days (QALD) were compared between groups on an intention-to-treat basis. Incremental cost-effectiveness ratio (ICER) was converted to dollars per quality-adjusted life years (QALY). The 95% confidence interval (95%CI) and probability of gargling being cost-effective were estimated by bootstrapping.ResultsAfter 60 days, QALD was increased by 0.43 and costs were

Enhanced aggregation of β-amyloid-containing peptides by extracellular matrix and their degradation by the 68 kDa serine protease prepared from human brain

37.1 higher in the gargling group than in the control group. ICER of the gargling group was

Degrading activity for human parathyroid hormone [PTH-(1–84)] in rat osteoblast-like osteosarcoma cell line UMR106

31,800/QALY (95%CI,

Human brain β-secretase contains heparan sulfate glycoconjugates

1,900–

A serine protease in alzheimer's disease cells cleaves a 16K-peptide with flanking residues upstream to β-amyloid-N-terminus as natural substrate

248,100). Although this resembles many acceptable forms of medical intervention, including URTI preventive measures such as influenza vaccination, the broad confidence interval indicates uncertainty surrounding our results. In addition, one-way sensitivity analysis also indicated that careful evaluation is required for the cost of gargling and the utility of moderate URTI. The major limitation of this study was that this trial was conducted in winter, at a time when URTI is prevalent. Care must be taken when applying the results to a season when URTI is not prevalent, since the ICER will increase due to decreases in incidence.ConclusionThis study suggests gargling as a cost-effective preventive strategy for URTI that is acceptable from perspectives of both the third-party payer and society.

Smoking and Small, Dense Low-Density Lipoprotein Particles: Cross-Sectional Study

To explore whether extracellular matrix components in human brain affect the deposition and aggregation of beta-amyloid containing peptides, human brain samples from patients with sporadic Alzheimers disease and normal aged were analyzed by Western blot analysis. All major beta-amyloid-containing peptides contained epitope(s) which is recognized by anti heparan sulfate antibody. Incubation of brain beta-amyloid-containing peptides with human collagen type IV in neutral pH efficiently generated a high molecular weight aggregated band, approximately 5-fold that of the control sample. We have previously found a serine protease which is capable of cleaving an oligopeptide at the N-terminus of beta-amyloid. In this study, the protease, which also contains heparan sulfate glycoconjugates, degraded the above brain peptides as natural substrates, although with different efficiency. These findings suggest that extra-cellular matrix components affect the processing and aggregation of beta-amyloid-containing peptides in human brain.

Analysis of Delusional Statements from 15 Japanese Cases of ‘Folie à Deux’

The degrading activity for human parathyroid hormone [hPTH-(1-84)] was studied in a rat osteoblast-like osteosarcoma cell line UMR106. At 37 C,UMR106 cells degraded hPTH-(1-84) into fragments in a time-dependent manner, which was shown by a radioimmunoassay with the use of antibody recognizing the C-terminal and middle regions of PTH molecule, whereas the degradation was completely suppressed at 4 C and failed to occur in the absence of the cells. The Lineweaver-Burk plot of this degrading activity at 37 C showed a fairly good linearity and gave a Km value of 5.1 X 10(-7) M. Reverse-phase high-performance liquid chromatography (HPLC) analysis of immunoreactive PTH fragments in the medium disclosed two peaks aside from intact PTH, indicating a limited PTH-hydrolyzing activity of UMR106 cells cleaving the molecule between at least two separate positions. This study suggests the possible involvement of osteoblasts on the metabolism of intact PTH.

Possible involvement of protein' kinase C in parathyroid hormone degradation by osteoblast-like rat osteosarcoma cell line UMR106

Abstract A polyclonal antibody against the 68 kDa β-secretase was established, which recognizes a single 68 kDa band in brain homogenate of Alzheimers disease patients and normal aged. Western analysis revealed that the protease is an acidic glycoprotein with negative charge on its glycoconjugate(s). Sensitiveness to heparitinase and glycopeptidase A indicates that the protease contains asparagine linked oligosaccharide with heparan sulfate moieties. Specific detection of the 68 kDa band in the analysis using anti-heparan sulfate antibody, and its time-course-dependent degradation, also confirm the above results. It seems that, like human blood coagulation factors IXa and XIa, the glycoconjugate(s) attached to the protease interfere with substrate specificity, stability and topological restriction of proteolysis in brain extracellular matrix, where diffuse plaque formation is taking place.