Role of glutathione, glutathione S-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines

Spontaneous proliferative liver lesions were found in 15 (13 males and 2 females) of 244 (122 of each sex) transgenic (Tg) mice carrying the human prototype c-H-ras gene (rasH2). The liver lesions included 3 foci of cellular alteration, 1 hepatocellular adenoma, 5 hepatocellular carcinomas, and 4 hepatic hemangiosarcomas in the males and 1 focus of cellular alteration and 1 hepatocellular carcinoma in the females. The mutation patterns of the human and endogenous mouse c-H-ras codon 61 in these proliferative liver lesions were analyzed by DNA amplification using polymerase chain reaction, single-strand conformation polymorphism (PCR-SSCP), and oligonucleotide dot blot hybridization. The hepatocellular carcinomas in 4 males and 1 female contained a point mutation in the mouse c-H-ras gene: 3, 1, and 1 carcinomas had a CAA to AAA transversion at the first base of codon 61, a CAA to CTA transversions, and a CAA to CGA transition at the second base of codon 61, respectively. No point mutations in the human c-H-ras transgene were detected in any hepatocellular carcinoma. All 4 hepatic hemangiosarcomas had a CAG to CTG transversion at codon 61 of the human c-H-ras gene, but no point mutations were detected in codon 61 of the mouse c-H-ras gene. No mutations in human or mouse c-H-ras codon 61 were detected in altered cell foci or hepatocellular adenoma. These results indicate that spontaneous liver tumors in rasH2 Tg mice contain different mutation patterns depending on the histologic type or cell origin of the tumors (i.e., hepatocellular carcinomas or hepatic hemangiosacomas). The absence of similar mutations in foci of cellular alteration and the hepatocellular adenoma suggests that the occurrence of codon 61 point mutations is a late event in the progression of hepatocellular neoplasia in rasH2 Tg mice.     

Bryostatin 1 induces ubiquitin COOH-terminal hydrolase in acute lymphoblastic leukemia cells

It has been previously reported that Bryostatin 1 (Bryo1) induces differentiation of the human acute lymphoblastic leukemia (ALL) cell line, Reh, to a monocytoid B-cell stage. In this study we demonstrate that a novel protein, ubiquitin COOH-terminal hydrolase (UCH-L1), is associated with this differentiation. Reh cells were treated with 200 nmol/l of Bryo1 for 72 h and analyzed for changes in morphology, surface immunophenotype, acid phosphatase and terminal deoxynucleotidyl transferase. Protein patterns of the parent and differentiated cells, by two-dimensional polyacrylamide gel electrophoresis (2D PAGE), were studied. Bryo1-treated cells expressed morphologic, phenotypic and enzymatic features of the monocytoid B-cell stage. The UCH-L1 enzyme (MW-pl 34-5.3) was detected by 2 D PAGE in the differentiated, but not in parent cells. The presence of UCH-L1 in the Bryo1-treated cells was further confirmed by immunoblotting of 2 D PAGE using UCH-L1 polyclonal antibody. Ubiquitin expression was studied in parent and Bryo1-treated cells and was compared with 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated cells. Both agents, TPA and Bryo1, increased the level of ubiquitin expression as detected by flow cytometry. Sodium borohydride, an inhibitor of UCH-L1, inhibited the Bryo1-induced differentiating effect on Reh cells. To date, the mechanism by which Bryo1, exerts its B-cell differentiating effect is not fully understood. This study shows that UCH-L1 expression may play a major role in Bryo1-induced differentiation in pre-B-ALL.     

Adaptive two-loop Voltage-mode control of DC-DC switching converters

A new two-loop control scheme for voltage-mode control (VMC) of dc-dc switching converters is presented. The proposed method adds a high-gain robust loop with two controllers to the conventional VMC loop, achieving an analog "adaptive" loop in which the "equivalent voltage regulator" varies with the changing power stage parameters given as follows: 1) input voltage; 2) load; and 3) component tolerances. The loop significantly improves the disturbance rejection of the control system, i.e., closed-loop output impedance and audiosusceptibility while preserving the stability and the loop gain crossover frequency to a significant extent. Both the small-signal analysis and the experimental results carried out on a buck converter demonstrate the superiority of the proposed scheme with respect to the conventional single loop.     

The contrast enhancement of brain and spinal cord tumors using Gd-DTPA in magnetic resonance tomography with an extra-low magnetic-field intensity

The contrasting agent Gd-DTPA (Magnevist, Schering AG, Germany) was tested when used in magnetic resonance tomography using extra-low (0.04 T) magnetic field intensity in 68 patients with various brain and spine tumors. The agent was injected intravenously in a dose of 0.1 mmol/kg. No complications were found. The tests showed its high efficiency in the diagnosis of brain neoplasms (particularly in malignant intracerebral disorders, meningiomas and neurinomas). Benign astrocytomas induced no noticeable signal intensification on post-contrasting T1-weighed tomograms. In all cases of spinal tumors, the application of Gd-DTPA could specify the extent of tumor invasions, the presence of cysts and identify accessory tumor nodes in one case.     

Recent developments in the synthesis and discovery of oligosaccharides and glycoconjugates for the treatment of disease

The development of the first automated oligosaccharide synthesizer, along with new methods for screening carbohydrate ligand arrays is likely to lead to a rapid acceleration in both our ability to synthesize these molecules, and understand the roles of oligosaccharides and glycoconjugates in biology. Consequently we may uncover new avenues for therapeutic intervention more rapidly. These recent developments are very important since our understanding of the role of glycoconjugates in nature has traditionally fallen far behind that of the other biopolymers such as proteins and nucleic acids as the formation of, for example, glycosylated proteins is not template driven. The chemical synthesis of oligosaccharides and glycoconjugates has provided us with new potential cancer vaccines, antibiotics and new biotechnological tools. Glycobiologists have employed many such tools to uncover new signalling roles for oligosaccharides and glycoconjugates. In this review we aim to highlight some emerging methods for glycoconjugate assembly and screening, and discuss innovative approaches to glycoconjugate based drug design and delivery, all of which are, and will continue to be, fruitful avenues for medicinal chemistry research.     

A new curvature technique calculation for surface tension contribution in PLIC-VOF method

The volume of fluid (VOF) methods have been used for numerous numerical simulations. Among these techniques used to define the moving interface, the piecewise linear interface reconstruction (PLIC-VOF) is one of the most accurate. A study of the superficial tension impact on two-phase flow with free surface is presented. A new method based on direct staggered grid is developped to include surface tension in PLIC-VOF. The new numerical curvature calculation method doesn't need smoothed colour function and leads to less “spurious current”. This technique is applied to the calculus of surface tension force in the case of the rise of air bubble in viscous liquid and the fall of liquid drop in the same liquid on free surface. Droplets, thin layer and capillarity waves are observed after the free surface rupture for different Bond number. The influence of surface tension calculus is then obvioused and when the drop hit the free surface, wavelets propagate toward the virtual boundaries imposed.     

Poly-(L-lactic) acid membranes in palatal surgery in beagle dogs: clinical and histologic evaluation

This article reports on the histologic findings from a larger study that was designed to investigate whether the attachment of scar tissue to underlying bone, which is normally found after palatal surgery, can be prevented by using biodegradable poly-(L-lactic) acid membranes. Von Langenbeck's procedure was simulated in 12-week-old beagle dogs without clefts. In one group normal wound healing was allowed. In two groups, membranes were inserted immediately after surgery or 3 weeks thereafter. Sham and control groups were also included. Histologic evaluation was carried out at regular intervals. Reports have been published on other aspects, such as clinical wound healing, contraction and maxillary arch development in beagle dogs following this treatment. After direct implantation of membranes, wound healing was retarded. Disintegration of the membranes started soon after implantation and remaining particles were surrounded by a fibroblastic sheath and a fibrous capsule. At sites where membrane particles persisted, attachment of the scar tissue to the underlying bone by Sharpey's fibers was prevented.     

Neurotoxic effects of sodium nitroprusside in rat hippocampal slices

The effect of a permanent transection on myelin gene expression in a regenerating sciatic nerve and in an adult sciatic nerve was compared to establish the degree of axonal control exerted upon Schwann cells in each population. First, the adult sciatic nerve was crushed, and the distal segment allowed to regenerate. At 12 days post-crush, the sciatic nerve was transected distal to the site of crush to disrupt the Schwann cell-axonal contacts that had reformed. Messenger RNA (mRNA) levels coding for five myelin proteins were assayed in the distal segment of the crush-transected nerve after 9 days and were compared to corresponding levels in the distal segments of sciatic nerves at 21 days post-crush and 21 days post-transection using Northern blot and slot-blot analysis. Levels of mRNAs found in the distal segment of the transected and crush-transected nerve suggested that Schwann cells in the regenerating nerve and in the mature adult nerve are equally responsive to axonal influences. The crush-transected model allowed the genes that were studied to be classified according to their response to Schwann cell-axonal contact. The levels of mRNAs were 1) down-regulated to basal levels (P0 and MBP mRNAs), 2) down-regulated to undetectable levels (myelin-associated glycoprotein mRNAs), 3) upregulated (mRNAs encoding 2'3'-cyclic nucleotide phosphodiesterase and beta-actin), or 4) not stringently controlled by the removal of Schwann cell-axonal contact (proteolipid protein mRNAs). This novel experimental model has thus provided evidence that the expression of some of the important myelin genes during peripheral nerve regeneration is dependent on continuous signals from the ingrowing axons.     

Downhole Upgrading of Extra-heavy Crude Oil Using Hydrogen Donors and Methane Under Steam Injection Conditions

An extra-heavy crude oil underground upgrading process is described which involves the downhole addition of a hydrogen donor additive under steam injection conditions (280-315°C and residence times of at least 24-h). Laboratory experiments showed a 4° increase in the API gravity (from 9 to 12°) of the upgraded product, a two-fold reduction in the viscosity and, an approximately 8% decrease in the asphaltene content with respect to the original crude. Further increases on the temperature led to products with improved properties reaching 15°API at 315°C. It was found that the presence of the natural formation (catalysts) and methane (natural gas) is necessary to enhance the properties of the upgraded crude oil. From GC and GC-MS results a reaction pathway is proposed that involves hydrogen transfers from tetralin to the extra-heavy crude oil resulting in the formation of 1,2-dihydronaphthalene. This compound is then transformed into naphthalene, further upgrading of crude oil through hydrogen donation. The results of the experiments carried out in the presence and absence of the mineral formation and with an inert solid (SiC) strongly indicate that the former acts as a catalyst and not as a heat transfer matrix. Isotopic labeling studies (CD₄ and ¹³CH₄) give evidences that, most probably, methane is involved in the upgrading reactions.