Potentiation of tumour necrosis factor-mediated cell killing by VP16 on human ovarian cancer cell lines. In vitro results and clinical implications

Synergism between recombinant human tumour necrosis factor (rHuTNF) and DNA topoisomerase II inhibitor VP16 during the killing of cells has been studied in six human ovarian cancer cell lines (A2774, A2780, SW626, IGROV-1, SKOV3, Pa1) and a cervical carcinoma cell line (Me180). Studies were performed using an assay of colony formation inhibition (drug treatment for 1 h) and a growth inhibition assay (continuous exposure for 20 h). Concomitant treatment of cells with VP16+rHuTNF enhanced cell killing in all the cell lines tested--an effect observed in both short- and long-term cytotoxicity assays. This study suggests that the activity of VP16 in ovarian cancer cell lines might be enhanced by rHuTNF in in vitro models.     

Cell density-dependent DNA fragmentation and its suppression by heparin in primary culture of adult rat hepatocytes

We show here that the internucleosomal DNA fragmentation, which is a biochemical hallmark of apoptosis, was induced in a cell density-dependent manner in primary culture of adult rat hepatocytes. This DNA fragmentation could be suppressed by a gene expression inhibitor, indicating the active nature of this process. Moreover, the viability changes in high and low cell density cultures showed a tendency corresponding with the incidence of the DNA fragmentation in them. These results suggest that in hepatocytes there may be a cell density-dependent apoptosis mechanism. In this report, we also show that heparin could suppress this DNA fragmentation with high specificity, and the cell death to some extent.     

A study of phase equilibria of nitrogen for constructing a medium value pressure scale

Translated from Izmeritel'naya Tekhnika, No. 3, pp. 40–42, March, 1993.     

Processing and microstructure of non-oxide ceramic fibres

Research and development efforts on high-temperature, oxidation-resistant fibres have increased over the past decade due to the demand for light-weight, stiff and strong composite materials in aerospace applications. Varieties of ‘high-performance’, continuous, non-oxide fibres with low-density, high tensile strength and tensile modulus have been developed either from organic precursors or via chemical vapour deposition for fabrication of ceramic matrix composites. Fibres derived from polymer precursors (e.g. Nicalon, Tyranno, HPZ) are small in diameter (compared to CVD monofilaments) and are ideally suited for ceramic composites. Processing, microstructural stability and mechanical properties of these newly developed SiC and Si₃N₄ base fibres are briefly reviewed in this paper.     

Difference between human and guinea pig Hageman factors in activation by bacterial proteinases: cleavage site shift due to local amino acid substitutions may determine the activation efficiency of serine proteinase zymogens

Human and guinea pig Hageman factors have been subjected to the action of pseudomonal elastase and serratial E15 proteinase. The pseudomonal elastase cleaved 22-24% of the human molecule at Arg353-Val354, and the remainder at Gly357-Leu358 resulting in the generation of about 20% of potential activity as activated Hageman factor, compared with trypsin activation, while it hydrolyzed Arg340-Ile341 bond in guinea pig molecule and generated about 75% of activity as activated Hageman factor. The serratial proteinase did not hydrolyze the essential cleavage site (Arg353-Val354) of the human zymogen but Gly356-Gly357 (30%) and Gly357-Leu358 (70%) bonds. Both products showed no activity. The guinea pig zymogen, in contrast, was cleaved mostly at Arg340-Ile341 (70%) and less abundantly at Gly344-Leu345 (30%), generating about 85% of the whole potential activity as activated Hageman factor. From the high correspondence between the proportions of activation and of hydrolysis at the essential cleavage site in activation, it was concluded that hydrolysis of the bonds different from the essential bond did not cause activation, even when the spatial separation was only 3 or 4 residues. Considering the amino acid differences between human and guinea pig Hageman factors, -Met351-Thr-Arg-Val-Val-Gly-Gly-Leu-Val-Ala360- and -Leu338-Ser-Arg-Ile-Val-Gly-Gly-Leu-Val-Ala347-, respectively, it was realized that even the minor amino acid substitutions caused the cleavage site shift which resulted in significant differences in activation efficiency of the proteinase zymogens.     

Influence of total surface area of core material on yield of deposited coacervate

The neuronal cytoskeleton is one of the most profoundly altered organelles in late life neuro-degenerative disorders that are characterized by progressive impairments in cognitive abilities. The elucidation of the protein building blocks of these organelles as well as advances in understanding how these proteins become altered in Alzheimer's disease (AD) and other less common dementing illnesses, i.e., diffuse Lewy body disease (DLBD) or the Lewy body variant of AD (LBVAD), will provide insights into the molecular basis of these disorders. Within, we review evidence that normal adult human tau is abnormally phosphorylated and converted into the subunits of AD paired helical filaments (PHFs), and that Lewy bodies (LBs) represent accumulation of altered neurofilament (NF) triplet subunits. Although the precise biological consequences of PHF and LB formation in neurons is unknown, growing evidence suggests that the formation of PHFs and LBs from normal neuronal cytoskeletal proteins could have deleterious effects on neuronal function and survival. Finally, insights into the composition of PHFs and LBs could lead to the development of novel strategies for the timely and accurate diagnosis of AD, DLBD and the LBVAD.     

Some features of the chemical transformation of a highly exothermic ore concentrate-based mixture in a combustion wave

Use of inexpensive ore concentrates as initial components in SHS metallurgy [1–3] brings about some specific features in the process and the properties of the materials obtained. Ore reagents contain a considerable amount of impurities (Al₂O₃, SiO₂, Fe₂O₃) that decrease the energetics of SHS systems and the temperature and the rate of combustion and create the limits of combustion and phase separation. In addition, the impurities participate in chemical reactions and enter the desired product. In many cases the presence of silicon, iron, and aluminum in a cast product does not prevent use of this product for practical purposes.Institute of Metallurgy, Academy of Sciences of the Republic of Georgia, Tbilisi. Institute of Structural Macrokinetics, Russian Academy of Sciences, Chernogolovka. Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 65, No. 5, pp. 613–616, November, 1993.     

Modified hippocampal long-term potentiation in PKC gamma-mutant mice

Calcium-phospholipid-dependent protein kinase (PKC) has long been suggested to play an important role in modulating synaptic efficacy. We have created a strain of mice that lacks the gamma subtype of PKC to evaluate the significance of this brain-specific PKC isozyme in synaptic plasticity. Mutant mice are viable, develop normally, and have synaptic transmission that is indistinguishable from wild-type mice. Long-term potentiation (LTP), however, is greatly diminished in mutant animals, while two other forms of synaptic plasticity, long-term depression and paired-pulse facilitation, are normal. Surprisingly, when tetanus to evoke LTP was preceded by a low frequency stimulation, mutant animals displayed apparently normal LTP. We propose that PKC gamma is not part of the molecular machinery that produces LTP but is a key regulatory component.     

Erythroid potentiating activity of tissue inhibitor of metalloproteinases on the differentiation of erythropoietin-responsive mouse erythroleukemia cell line, ELM-I-1-3, is closely related to its cell growth potentiating activity

The erythroid-potentiating activity (EPA) of the tissue inhibitor of metalloproteinase-1 (TIMP-1) was re-examined using ELM-I-1-3, a mouse erythroleukemia cell line, which responded well to erythropoietin. Depletion of pre-existing TIMP-1 from fetal calf serum in culture medium using monoclonal antibody suppressed erythropoietin-induced differentiation as measured by the induction of hemoglobin, commitment assay and globin mRNAs. The removal of TIMP-1 also suppressed the proliferation of ELM-I-1-3 as measured by cell number and de novo DNA synthesis. These changes were reversed by the addition of purified TIMP-1 to the culture medium. Anti-TIMP-1 antibody also blocked both hexamethylene bisacetamide (HMBA)-induced erythroid differentiation and the proliferation of both ELM-I-1-3 and Friend erythroleukemia cells. Considering previous reports analyzing the chemical induction of Friend mouse erythroleukemia cell differentiation, our results suggest that erythropoietin- or HMBA-induced erythroid differentiation might also be coupled with cell proliferation. Our 3H thymidine-uptake experiment shows that TIMP-1 removal was also effective in the inhibition of cell growth of various other cell lines in addition to erythroleukemia cell lines. These results suggest that EPA action of TIMP-1 on erythroid leukemia cell lines is closely related to its activity to promote the cell growth of various cell lines and cells including erythroleukemia cell lines.