Successful outcome after resection of pancreatic cancer with a solitary hepatic metastasis

The presence of hepatic metastasis in pancreatic cancer has generally been considered to be a contraindication for surgery. However, the present case survived seven years after concomitant resection of pancreatic cancer and hepatic metastasis. This shows that hepatic metastasis may be a strong predictor of poor survival, but not a determinant of noncurability. Surgical resection may be an option for highly selected patients with pancreatic cancer complicated with hepatic metastasis.     

Differences in expression patterns of cathepsin C/dipeptidyl peptidase I in normal,pathological and aged mouse central nervous system

Cathepsin C (CC) (EC 3.4.14.1, dipeptidyl peptidase I) is a lysosomal cysteine protease that is required for the activation of several granule‐associated serine proteases in vivo. CC has been shown to be constitutively expressed in various tissues, but the enzyme is hardly detectable in central nervous system (CNS) tissues. In the present study, we investigated the regional and cellular distribution of CC in normal, aging and pathological mouse brains. Immunoblotting failed to detect CC protein in whole brain tissues of normal mice, as previously described. However, low proteolytic activity of CC was detected in a brain region‐dependent manner, and granular immunohistochemical signals were found in neuronal perikarya of particular brain regions, including the accessory olfactory bulb, the septum, CA2 of the hippocampus, a part of the cerebral cortex, the medial geniculate, and the inferior colliculus. In aged mice, the number of CC‐positive neurons increased to some extent. The protein level of CC and its proteolytic activity showed significant increases in particular brain regions of mouse models with pathological conditions – the thalamus in cathepsin D‐deficient mice, the hippocampus of ipsilateral brain hemispheres after hypoxic–ischemic brain injury, and peri‐damaged portions of brains after penetrating injury. In such pathological conditions, the majority of the cells that were strongly immunopositive for CC were activated microglia. These lines of evidence suggest that CC is involved in normal neuronal function in certain brain regions, and also participates in inflammatory processes accompanying pathogenesis in the CNS.     

Hydroxyapatite Affects the Physicochemical Properties of Contemporary One-Step Self-Etch Adhesives

The study aimed to evaluate the influence of the manipulation surfaces on the physical properties of one-step self-etch adhesives (1-SEAs). Scotchbond Universal (SBU), Clearfil Universal Bond Quick ER (UBQ), and an experimental adhesive (UBQ_exp) were manipulated on different surfaces: manufacturer’s Teflon-based dispensing dish (TD) or hydroxyapatite plate (HA). After manipulation of the adhesives, the pH of each 1-SEA was measured. Samples of each adhesive/manipulation surface were prepared and subjected to water sorption (WS)/solubility (SL) and flexural strength tests. The modulus of elasticity (E) was measured in dry and wet conditions before and after 24 h water storage, and the percentage of variation of E (ΔE) was calculated. Results were analyzed using the t-test with Bonferroni corrections (α = 0.05). When adhesives were manipulated on the HA plate, there was a significant increase in the adhesives’ pH. WS and SL of all 1-SEAs decreased when the HA was used. Only SBU showed higher flexural strength when manipulated on the HA compared to the manipulation on TD under dry and wet conditions. For each 1-SEA, the use of HA resulted in significantly higher E in dry and wet conditions. ΔE of all adhesives was smaller with the manipulation on HA than on TD. It was concluded that the manipulation of 1-SEA on a hydroxyapatite plate considerably affected the adhesives’ properties.     

Antitumor activity of FTC-092, a masked 5-trifluoromethyl-2′-deoxyuridine derivative

Summary 1-(3-O-Benzyl-2-deoxy--d-ribofuranosyl)-5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione (FTC-092), a fluorinated pyrimidine derivative, appeared to be effective against various transplantable tumors in mice following oral administration, and its activity was superior to that of several other antitumor fluorinated pyrimidines. The ED₅₀ value for FTC-092 the dose effective in achieving 50% inhibition of tumor growth against the solid form of sarcoma 180 was 13.3 mg/kg daily, whereas those for 5-trifluoromethyl-2-deoxyuridine (CF₃dUrd), the parent compound of FTC-092, for 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur, FT), the prodrug of 5-fluorouracil (FUra), and for FUra were 64.1, 122, and 28 mg/kg daily, respectively. The therapeutic indices (LD₁₀/ED₅₀) of FTC-092, CF₃dUrd, FT, and FUra were 4.39, 1.7, 1.35, and 1.65, respectively. FTC-092 itself is not an active agent. After it has been absorbed from the gastrointestinal tract, FTC-092 undergoes a gradual biotransformation, mainly via the action of liver microsomes, releasing CF₃dUrd over a long period. The levels of CF₃dUrd in the stomach and small intestine of mice after the oral administration of FTC-092 were undetectable, whereas those following the administration of CF₃dUrd at the same dose were high for a period of several hours. In contrast, the CF₃dUrd level generated in plasma after the administration of FTC-092 remained at a high level for a longer period than did that observed on the administration of CF₃dUrd. The low levels of CF₃Urd measured in stomach and small-intestine tissues and the maintenance of CF₃dUrd in blood over long periods after the administration of FTC-092 are features that favor the possible clinical application of FTC-092.Abbreviations used FTC-092 1-(3-O-benzyl-2-deoxy--d-ribofuranosyl)-5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione - CF₃dUrd 5-trifluoromethyl-2-deoxynridine - FT 1-(2-tetrahydrofuryl)-5-fluorouracil - FUra 5-fluorouracil - F₃Thy 5-trifluorothymine - ILS increase in life span     

Regulation of biosynthesis and phosphorylation of P210 protein during differentiation induction of K 562 cells

The changes of P210^bcr/abl and other tyrosine phosphorylated proteins in K562 cells during growth and differentiation were studied by metabolic labeling with ³²PO₄ and immunoprecipitation with anti-phosphotyrosine sera. The anti-phosphotyrosine sera recognized P210^bcr/abl and other phosphoproteins with mol wt of 150, 115, 100, 70 and 64 kD. The 2-day incubation of K562 cells with inducers for differentiation, hemin, sodium butyrate and TPA, decreased the level of P210^bcr/abl protein and other phosphoproteins. Inhibitors of tyrosine protein kinase, amiloride and genistein, also reduced the phosphorylation of P210^bcr/abl protein and other substrates, but did not induce differentiation of the cells. Although most of these additives inhibited the cell growth, cytotoxic agents such as adriamycin, vincristine and Ara-C did not affect the level of P210^bcr/abl protein. The experiments using ³⁵S-methionine labeled cells and the immunoprecipitation with anti-abl sera suggested that reduced biosynthesis but not dephosphorylation of P210^bcr/abl protein mainly accounted for the reduction of P210^bcr/abl protein reacting to anti-phosphotyrosine sera in differentiation-induced cells. These results indicate that the reduction of P210^bcr/abl protein synthesis plays some roles in cellular differentiation of K562 cells.     

The clinical application of surface pH measurements to longitudinally assess white spot enamel lesions

Objectives

Means of objectively assessing white spot enamel lesions (WSEL) are critical for determining their potential activity and monitoring the success of preventive treatments. The aim of this study was to determine whether surface pH measurements of WSEL changed during a preventive course of care designed to remineralize the lesions.

Methods

Eight healthy subjects (1 male and 7 females) with at least one WSEL were recruited (19–64 years). Each subject was placed on a preventive treatment program including the daily application of a CPP-ACP paste (MI paste, GC Corp., Japan) with custom fitted trays for more than 6 months. The surface pH values of sound enamel and WSEL were monitored for up to 2 years using a micro-pH sensor. The visual appearance of the WSEL was monitored via digital photography, and images were analyzed qualitatively on a 5-point scale to assess the success of the remineralization preventive program. The relationship between the qualitative assessment of WSEL appearance and the WSEL pH was investigated using a Spearman's rho non-parametric correlation.

Results

The surface pH of the WSEL was different to that of the sound enamel surrounding it in all patients at all times. All lesions showed visual improvement as the treatment period progressed. The pH of the WSEL increased towards that of sound enamel over the course of treatment significantly correlating with the visual improvement of the lesion (rho = 0.63, p < 0.0001).

Conclusions

The clinical assessment of WSEL surface pH changes with time may have utility as an additional objective measure for the assessment of WSEL activity.     

Baicalin induces apoptosis via mitochondrial pathway as prooxidant

Baicalin is a flavonoid and a major component of a herbal medicine, Sho-saiko-to, which is commonly used for treatment of chronic hepatitis in Japan and China. Flavonoids including baicalin have been reported to not only function as anti-oxidants but also cause cytotoxic effect. We investigated the mechanism of baicalin-induced cytotoxicity in leukemia-derived T cell line, Jurkat cells. When cells were cultured with 50-200 microg/ml baicalin for 6h, caspase-3 was activated and then cells fell into apoptosis. Induction of apoptosis by baicalin was accompanied with the marginal generation of intracellular reactive oxygen species (ROS), the increase of the cytosolic fractions of cytochrome c, and the disruption of mitochondrial transmembrane potential (DeltaPsi(m)) prior to the activation of caspase-3. The pre-culture with 5 mM of buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, facilitated baicalin-induced disruption of DeltaPsi(m) and induction of apoptosis. The pre-culture with N-benzyloxycarbonyl-valyl-alanyl-aspartyl fluoromethylketone (Z-VAD-fmk), a pan-caspase inhibitor, partially suppressed the induction of apoptosis. On the other hand, baicalin showed little toxic effect on peripheral blood mononuclear cells (PBMCs) from healthy volunteers. These results indicate that baicalin acts as a prooxidant and induces caspase-3 activation and apoptosis via mitochondrial pathway.     

The gene encoding CD23 leukocyte antigen (FCE2) is located on human chromosome 19

Using Southern blot analysis of DNAs from human×rodent cell hybrids, we have mapped the CD23 leukocyte antigen gene (FCE2) to human chromosome 19.     

Observation on the effects of Chinese medicine zhenxuanyin for improving cerebral blood flow in rats with cerebral ischemia.

Zhenxuanyin [symbol: see text] is composed of pure Chinese medicinal herbs, such as gastrodia tuber, poria cocos, ligusticum wallichii etc. 4-verssel occlusion (4VO) model rats were reperfused after 30 minutes' complete occlusion, and Zhenxuanyin was administered 3 times a day. 24 hours later, 123I-IMP uptake in the brain was evaluated as an index of cerebral blood flow (CBF). The results show that Zhenxuanyin (0.03 g/kg, 0.3 g/kg, 1 g/kg, or 3 g/kg a day) can greatly improve the blood flow in the main cerebral regions, and 0.3 g/kg can increase cerebral blood flow (CBF) to the normal level.