Disease-free survival in a patient with squamous cell lung carcinoma following complete response with the combination chemotherapy of cisplatin and etoposide

Disease-free survival is reported in a patient with non-small cell lung carcinoma successfully treated with the combination chemotherapy of cisplatin and etoposide (CDDP-ETOP). An 80-year-old woman was diagnosed as having squamous cell carcinoma of the lung with bone metastasis. Chest X-ray showed a tumor (64 x 68 mm in size) in the S1/4 segment of the right lobe, and CT scan revealed no apparent metastasis of hilar lymphnode. In March 1989, the patient achieved a complete response (CR) after two courses of CDDP-ETOP therapy, followed by ETOP(100mg) every two weeks and daily UFT (400 mg) for 10 months. Subsequently, a single course of CDDP-ETOP was administered as a consolidation therapy. The patient is alive with no evidence of recurrent disease for 3 years and half after achieving CR.     

Several reactions of poly(vinyl alcohol)–type acetaldehyde polymer

The preparation of the acetaldehyde polymers (PACH) having a poly(vinyl alcohol)-type structure and the thermal degradation of PACH have been reported previously. This paper will describe detailed aspects of several reactions of PACH. Copolymerization of PACH with toluene diisocyanate (TDI) was performed both thermally and catalytically. When piperidine was used as catalyst, the rate of reaction between PACH and TDI was found to depend on the concentration of both the active hydrogen of PACH and the isocynante group TDI. Acid and alkali treatment of PACH were carried out. On treatment with sulfuric acid, white polymers with good spinnability were obtained. The copolymerization of acetaldehyde with n-butylaldehyde were performed in the presence of sodium amalgam as catalyst. The reaction products were colorless, viscous liquids and assumed from the infrared and NMR spectra, elemental analyses, molecular weight and solubility tests to be aldol condensation-type copolymers.     

New biconically tapered fiber star coupler fabricated by indirect heating method

A new biconically tapered fiber star coupler is developed. The fiber bundle is inserted in a quartz protection tube and the tube is heated with an oxyhydrogen burner while the fibers are twisted and pulled. The tube ends are then sealed with adhesive agent. Excess loss for the new coupler is approximatelylog_{10}mfor input/output fiber port numberm. Furthermore, the coupling ratio is almost independent of wavelength and polarization of incident light. The new fabrication method offers high reproducibility and stability.     

Effect of polyethyleneglycol on polymerization of methyl methacrylate initiated by sodium salt-type macromolecular electrolytes

Summary The effects of polyethyleneglycol (PEG) on the radical polymerizations of methyl methacrylate initiated with the aqueous solutions of such macromolecular electrolytes as sodium polyphenolate and sodium polycarboxylate were studied. PEG was found to promote the polymerizations initiated by such sodium salt-type's macromolecular electrolytes.Vinyl Polymerization. 415.     

A novel mechanism regulates H(2) S and SO(2) production in Saccharomyces cerevisiae

Sulfite (SO(2) ) plays an important role in flavour stability in alcoholic beverages, whereas hydrogen sulfide (H(2) S) has an undesirable aroma. To discover the cellular processes that control SO(2) and H(2) S production, we screened a library of Saccharomyces cerevisiae deletion mutants. Deletion of 12 genes led to increased H(2) S productivity. Ten of these genes are known to be involved in sulfur-containing amino acid metabolism, whereas UBI4 functions in the ubiquitin-proteasome system and SKP2 encodes an F-box-containing protein whose function is unknown. We found that the skp2 mutant accumulated H(2) S and SO(2) , because the adenosylphophosulfate kinase Met14p is a substrate of SCF(Skp2) and more stable in the skp2 mutant than in the wild-type strain. Furthermore, the skp2 mutant grew more slowly than the wild-type strain under nutrient-limited conditions. Metabolome analysis showed that the concentration of intracellular cysteine is lower in the skp2 mutant than in the wild-type strain. The slow growth of the skp2 mutant was due to a lower concentration of intracellular cysteine, because the addition of cysteine suppressed the slow growth. In the skp2 mutant, the cysteine biosynthesis proteins Str2p, Str3p and Str4p are more stable than in the wild-type strain. Moreover, supplementation with methionine, S-adenosylmethionine, S-adenosylhomocysteine and homocysteine also suppressed the slow growth. Overexpression of STR1 or STR4 caused a more severe defect in the skp2 mutant. These results suggest that the balance of methionine and cysteine biosynthesis is important for yeast cell growth. Thus, Skp2p is one of the key components regulating this balance and H(2) S/SO(2) production.     

Stable expression of human homomeric and heteromeric AMPA receptor subunits in HEK293 cells

Human homomeric and heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors (GluRs) were stably expressed in HEK293 cells with cDNAs encoding the flip splice variant of GluR1, GluR2, GluR3, GluR4 subunit, and the GluR1/GluR2, GluR3/GluR2, and GluR4/GluR2 combination. The lethal combination of GluR2 and GluR4 subunits was found in high expression levels of both receptors. The AMPA-evoked current voltage relationships demonstrated the functional channel properties, such as a double rectification in GluR1, GluR3, and GluR4 receptors, and a linear relation in receptors assembled from GluR2 alone and coexpression of GluR2 with the other subunits. All the transfectants exhibited higher selectivity for AMPA than glutamate in dose-dependent current responses. [3H]AMPA binding revealed that the homomeric and heteromeric receptors displayed a single binding site in Scatchard analysis, with dissociation constant (Kd) values in the range of 14.5-49.3 nM. The Bmax values were in the range of 0.57-7.66 pmol/mg protein. The ligand displacement potency for [3H]AMPA binding was CNQX > glutamate > NS257 in all of the transfectants. These results suggest that stable transformants expressing human homomeric and heteromeric AMPA receptors will be useful tools to define selectivity and potential site of action for AMPA receptor modulators.     

Correlation between the differences in the free energy change and conformational energy in the folded state of hen lysozymes with Gly-Pro and Pro-Gly sequences introduced to the same site

We suggested for the introduction of a prolyl residue into a protein that if the N-terminus residue is glycine, an unfavorable interaction in the folded state caused by the introduction of the prolyl residue can be substantially avoided by use of mutant lysozymes in which Gly-Pro and Pro-Gly sequences are introduced to positions 101-102 in the loop region of the lysozymes [Ueda, T., Tamura, T., Maeda, Y., Hashimoto, Y., Miki, T., Yamada, H., and Imoto, T. (1993) Protein Eng. 6, 183-187]. In order to determine whether or not the information obtained is applicable to other regions, we prepared mutant lysozymes with Gly-Pro and Pro-Gly sequences at position 47, which is located in the beta-sheet, positions 70-71, which are located in the loop, positions 117-118, which are located in the beta-turn, and positions 121-122, which are located in the 3(10)-helix. The free energy changes of the native and mutant lysozymes for unfolding were determined at pH 5.5 and 35 degrees C. However, a mutant lysozyme with the Gly-Pro sequence was not always stabler than that with the Pro-Gly sequence at the same site. On the other hand, in order to determine whether or not strain caused by these sequences exists in the folded or unfolded state, the structures of these mutant lysozymes were determined by use of energy minimization. On comparison of the differences in the free energy change between the mutant lysozymes with Gly-Pro and Pro-Gly sequences at the same site with those in their total local conformational energies, it was found there is a good correlation between them. Therefore, it was suggested that the difference in total local conformational energy caused by the introduction of a Gly-Pro or Pro-Gly sequence could be estimated by use of the energy minimized structure. Moreover, the correlation indicated that the differences in the free energy change between Gly-Pro and Pro-Gly lysozymes may be reflected by the differences in the total local conformational energies in their folded state. It was suggested that the energy levels in the unfolded states of mutant lysozymes with Gly-Pro and Pro-Gly sequences at the same site in a Gdn-HCl solution were almost identical.     

Network-Based Predictions and Simulations by Biological State Space Models: Search for Drug Mode of Action

Since time-course microarray data are short but contain a large number of genes, most of statistical models should be extended so that they can handle such statistically irregular situations. We introduce biological state space models that are established as suitable computational models for constructing gene networks from microarray gene expression data. This chapter elucidates theory and methodology of our biological state space models together with some representative analyses including discovery of drug...     

The cell cycle, including the mitotic cycle and organelle division cycles, as revealed by cytological observations

It is generally believed that the cell cycle consists essentially of the mitotic cycle, which involves mitosis and cytokinesis. These processes are becoming increasingly well understood at the molecular level. However, successful cell reproduction requires duplication and segregation (inheritance) of all of the cellular contents, including not only the cell-nuclear genome but also intracellular organelles. Eukaryotic cells contain at least three types of double membrane-bounded organelles (cell nucleus, mitochondria and plastids), four types of single membrane-bounded organelles (endoplasmic reticulum, Golgi apparatus, lysosomes and microbodies) and the cytoskeleton, which comprises tubulin-based structures (including microtubules, centrosome and spindle) and actin microfilaments. These membrane-bounded organelles cannot be formed de novo and daughter organelles must be inherited from parent organelles during cell cycle. Regulation of organelle division and its coordination with the progression of the cell cycle involves a sequence of events that are subjected to precise spatio-temporal control. Considering that the cells of higher animals and plants contain many organelles which tend to behave somewhat randomly, there is little information concerning the division and inheritance of these double- and single-membrane-bounded organelles during the cell cycle. Here, we summarize the current cytological and morphological knowledge of the cell cycle, including the division cycles of seven membrane-bounded and some non-membrane-bounded organelles. The underlying mechanisms and the biological relevance of these processes are discussed, particularly with respect to cells of the primitive alga Cyanidioschyzon merolae that have a minimum of organelles. We discuss unsolved problems and future perspectives opened by recent studies.     

Construction of a plasmid vector for the regulatable high level expression of eukaryotic genes in Escherichia coli: an application to overproduction of chicken lysozyme

A novel expression vector pKPl500 for synthesizing unfused proteinin Escherichia coli was constructed. pKP1500 perserves the tacpromoter, the lacZ SD sequence, unique restriction sites (EcoRI,SmaI, BamHI, SalI, PstI and HindIII) and the rrnB terminatorsof pKK223-3, but the replication origin is replaced with thatof pUC9. Construction of this plasmid is based upon the observationthat the copy number control of pUC9 is temperature dependent.At 28°C, the copy number of pKP1500 is less than 25 perchromosome, approximately the same copy number as that of pKK223-3,which contains the replication origin of pBR322, whereas at42°C, the copy number increases about 10 times and reachesup to 230 copies per chromosome. The main advantage of thissystem is that the temperature-dependent copy control and regulatableexpression of the tac promoter make cells car rying pKPl500derivatives stable against selective pressure by detrimentaloverproduction of foreign proteins at a low temperature andpermits high expression of cloned DNAs at a high temperature.When chicken lysozyme cDNA carrying the initiation codon (ATG)immediately upstream from the Lys¹ codon was inserted downstreamfrom the tac promoter and the SD sequence, the pKP1500 derivativeproduced lysozyme at about 25% of the total cellular proteins.This value is more than 10 times higher than that obtained withthe pKK223-3 derivative carrying the same lysozyine cDNA. Bycomparison, the expression of eukaryotic genes from the tacpromoter reported by others has usually been less than a few% of the total cellular protein. pKPl500 would therefore beuseful for the high level production of unfused proteins fromeukaryotic cDNAs in E. coli.