Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumour growth rate but cause weight loss and shortened survival in syngeneic mice

HuIL-6 cDNA, cloned into a neomycin resistant conferring expression vector, BMGNeo, was transfected into Lewis Lung Carcinoma (LLC) cells. LLC cells (5 x 10(6) ml-1) transfected with IL-6 cDNA (LLC-IL6) secreted IL-6 into the culture supernatant at a concentration of 9.9 ng ml-1 within 48 h. When 1,000,000 of untransfected LLC, BMGNeo vector transfected LLC (LLC-Neo) or LLC-IL6 cells were transplanted into C57BL/6 mice subcutaneously, the mean +/- s.d. of survival times of these mice were 33.3 +/- 9.7, 34.3 +/- 7.1 and 17.0 +/- 3.1 days, respectively. The survival time of LLC-IL6 cells transplanted mice was significantly shorter than that of LLC (P < 0.01) or LLC-Neo (P < 0.01) cells transplanted mice without a measurable difference of tumour size. Plasma concentration of IL-6 steadily increased in LLC-IL6 transplanted mice. Body weight and serum albumin were significantly lower in LLC-IL6 transplanted mice than in LLC transplanted mice. Mouse IL-1 alpha and mouse TNF-alpha were not detected in the plasma of LLC-IL6 transplanted mice. These data suggested that secretion of IL-6 from LLC cells was unable to alter net tumour growth rate but rather caused a state similar to cachexia without detectable increase of IL-1 alpha and TNF-alpha in the plasma. This state may be responsible for the shortened survival of LLC-IL6 tumour-bearing mice.     

Microstructure development of steel during severe plastic deformation

The microstructure development during plastic deformation was reviewed for iron and steel which were subjected to cold rolling or mechanical milling (MM) treatment, and the change in strengthening mechanism caused by the severe plastic deformation (SPD) was also discussed in terms of ultra grain refinement behavior. The microstructure of cold-rolled iron is characterized by a typical dislocation cell structure, where the strength can be explained by dislocation strengthening. It was confirmed that the increase in dislocation density by cold working is limited at 10¹⁶m⁻², which means the maximum hardness obtained by dislocation strengthening is HV3.7 GPa. However, the iron is abnormally work-hardened over the maximum dislocation strengthening by SPD of MM because of the ultra grain refinement caused by the SPD. In addition, impurity of carbon plays an important role in such grain refinement: the carbon addition leads to the formation of nano-crystallized structure in iron.     

Evaluation of blue-chitin column, blue-rayon hanging, and XAD-resin column techniques for concentrating mutagens from two Japanese rivers

Highly mutagenic water of the Katsura River, Kyoto, and moderately mutagenic water of the Asahi River, Okayama, were used to evaluate the efficacy of three concentration techniques, the blue-chitin column, the blue-rayon hanging, and the XAD-2 column. These two river waters have been shown to exhibit high mutagenicity in the assay with Salmonella typhimurium TA98 with metabolic activation. With this assay as a measure, two water samples from the Katsura, collected on different dates, and a sample from the Asahi were submitted to the column concentration techniques, blue-chitin and XAD-2. Blue-chitin was more efficient than XAD-2 for all of these samples: e.g., for one Katsura sample, the mutagenicity found was 913 +/- 53 (mean +/- SD, n = 3) revertants/500 ml with blue-chitin, and 419 +/- 129 (n = 3)/500 ml with XAD-2. Blue rayon (0.5 g) hung in the Asahi for 24 h gave 563 +/- 74 (n = 3) revertants, while the water spot-sampled at the start of the hanging showed 253 +/- 10 (n = 3) revertants per 5 liter with the blue-chitin column technique. We conclude that for quantitative measurement of the "Salmonella TA98 +/- S9' mutagens in these rivers, the blue-chitin column is more efficient and accurate than the XAD-2 column and that for judging the presence of mutagens, the blue-rayon hanging is the most sensitive and convenient among the three methods examined.     

Peroxiredoxin 2 as a chemotherapy responsiveness biomarker candidate in osteosarcoma revealed by proteomics

Purpose : We aimed to identify novel chemotherapy responsiveness biomarkers for osteosarcoma (OS) by investigating the global protein expression profile of 12 biopsy samples from OS patients. Experimental design : Six patients were classified as good responders and six as poor responders, according to the Huvos grading system. The protein expression profiles obtained by 2‐D DIGE consisted of 2250 protein spots. Results : Among them, we identified 55 protein spots whose intensity was significantly different (Bonferroni adjusted p‐value<0.01) between the two patient groups. Mass spectrometric protein identification demonstrated that the 55 spots corresponded to 38 distinct gene products including peroxiredoxin 2 (PRDX 2). Use of a specific antibody against PRDX 2 confirmed the differential expression of PRDX 2 between good and poor responders, while PRDX 2 levels as measured by Western blotting correlated highly with their corresponding 2‐D DIGE values. The predictive value of PRDX 2 expression was further confirmed by examining an additional four OS cases using Western blotting. Conclusions and clinical relevance : These results establish PRDX 2 as a candidate for chemotherapy responsiveness marker in OS. Measuring PRDX 2 in biopsy samples before treatment may contribute to more effective management of OS.     

Deformation-induced martensitic transformation behavior in cold-rolled and cold-drawn type 316 stainless steels

We investigate deformation-induced martensitic transformation behavior in cold-rolled and cold-drawn specimens of type 316 stainless steel. Deformation-induced martensite preferentially nucleates at the twin boundary between the austenite matrix and a deformation twin. In the cold-rolled specimen, martensite formed at the twin boundary has a Kurdjumov–Sachs (K–S) relationship with both the austenite matrix and the deformation twin (“double K–S relationship”). In the cold-drawn specimen, two kinds of deformation twins with different twin planes are typically formed, and therefore deformation-induced martensites are formed where the deformation twin boundaries intersect: martensite thus has an imperfect “triple K–S relationship” with the austenite matrix and the two deformation twins. The complicated crystallographic orientation relationship between austenite and martensite grains strongly restricts the formation of some variants of deformation-induced martensites. Because of the difference in number of nucleation sites in the cold-drawn and cold-rolled specimens, martensitic transformation is more enhanced in the former than in the latter.     

Arrhythmogenic right ventricular cardiomyopathy underlies syndrome of right bundle branch block, ST-segment elevation, and sudden death

In all experimental mammals tested (rats, dogs, primates), intramuscular injections of the oil-soluble antimalarial artemisinin derivatives artemether and arteether have produced an unusual pattern of selective damage to brain stem centers predominantly involved in auditory processing and vestibular reflexes. Artesunate, the most widely used of these compounds, is a water soluble hemisuccinate derivative given parenterally either by intravenous or intramuscular injection. The neurotoxic potential of parenteral artesunate and artemether was compared in a murine model. Adult Swiss albino mice were assigned randomly to 28-day regimens of intramuscular artemether or artesunate in doses ranging from 30 to 100 mg/kg/day. At 30 mg/kg/day, no abnormalities were detected with either drug. At 50 mg/kg/day, abnormalities were observed in six of 12 artemether recipients and two of 12 artesunate recipients. These were reversible in all but one (artemether) mouse. At 100 mg/kg/day, eight of 36 artemether recipients, two of 36 artesunate recipients, and one of 18 control mice died. All but four surviving mice in the artemether group (86%) showed obvious and usually irreversible abnormalities of balance and equilibrium, whereas only four artesunate recipients (11%) exhibited abnormalities, and these were reversible in each case (P < 0.001). At this dose the relative risk (95% confidence interval) for death or disability was 5.3 (2.6-11.2) for artemether recipients. Intramuscular artemether is significantly more neurotoxic than intramuscular artesunate in this murine model.