Combination cytotoxic effects of cis-diamminedichloroplatinum(II) and 5-fluorouracil with and without leucovorin against human non-small cell lung cancer cell lines

Both cisplatin (CDDP) and leucovorin (LV) have been shown to enhance cytotoxicity of 5-fluorouracil (FUra) against murine and human neoplasms by increasing intracellular reduced folate concentrations. We were interested in their use in a combination to inhibit non-small cell lung cancer (NSCLC) cell growth and therefore conducted an in vitro study to investigate the cytotoxic activities of combinations of CDDP plus FUra, with and without LV (20 microM), against seven NSCLC cell lines. A tetrazolium assay with application of the classical isobole method was used to test drug combinations. We found that LV enhanced FUra but not CDDP cytotoxicity and that the degree of enhancement was negatively correlated with the effect of FUra. There was an overall additive combination effect of CDDP plus FUra, although there may be synergy at higher effect levels. There was synergy to a combination of CDDP, FUra, and LV, presumably primarily related to the synergistic effects of adding LV to FUra. In summary, LV and CDDP enhanced FUra cytotoxicity in a complementary fashion and there was clear synergy of a combination of CDDP, FUra, and LV against a panel of NSCLC cell lines. Our in vitro results provide a rationale for controlled clinical studies of this three-drug regimen in patients with NSCLC.     

Control-canonical-form method applied to generating systems to improve dynamic stability characteristics

Contents The control-canonical-form (CCF) method is introduced for the purpose of applying it to high-order state-space single-input single or multiple-output (SISO or SIMO) and multiple-input multiple-output (MIMO) linear time-invariant system models to determine closed-loop systems (i.e. design robust controllers) from which enchanced dynamic stability characteristics and overall performance of these systems is achieved. The method has been applied successfully to a SISO 6th-order linearized state-space open-loop model (representing a simplified hydro power system), and to a MIMO 8th-order linearized state-space open-loop model (representing an 87.5 kVA synchronous machine with conventional exciter supplying power to an electric utility system through an interconnection network)

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Anwendung der kanonischen Form der Zustandsrückführung auf Erzeugersysteme zur Verbesserung der dynamischen Stabilitätseigenschaften

Übersicht Die Methode der kanonischen Form wird auf lineare zeitinvariante Systeme höherer Ordnung im Zustandsraum angewendet, die eine oder mehrere Eingangsgrößen bei einer oder mehreren Ausgangsgrößen aufweisen. Damit werden robuste Regler entworfen, welche die dynamische Stabilität und das gesamte Betriebsverhalten verbessern. Die Methode wurde erfolgreich auf ein linearisiertes Modell sechster Ordnung mit einem Eingang und einem Ausgang angewendet, das vereinfachend eine Wasserkraftanlage darstellt; außerdem auf ein linearisiertes Zustandsmodell achter Ordnung einer Synchronmaschine 87,5kVA mit konventioneller Erregung, die über ein Verbindungsnetzwerk in das öffentliche Netz einspeist.

     

Ultrastructural and immunocytochemical features of a case of neuroendocrine carcinoma developing in a prior ileostomy site

A patient who developed a mixed neuroendocrine carcinoma and adenocarcinoma at the site of a previous long-standing ileostomy is reported. The neuroendocrine features are documented by both ultrastructural and immunocytochemical findings. Carcinoma arising in an ileostomy site is rare but has been recorded in patients with long-standing ileostomies after colectomy for chronic inflammatory bowel disease, as in this patient. Neuroendocrine carcinoma developing in this setting apparently has not been described before, however.     

Primary cell culture of human type II pneumonocytes: maintenance of a differentiated phenotype and transfection with recombinant adenoviruses

Studies of the regulation of surfactant lipoprotein metabolism and secretion and surfactant protein gene expression have been hampered by the lack of a cell culture system in which the phenotypic properties of type II cells are maintained. We have developed a primary culture system that facilitates the maintenance of a number of morphologic and biochemical properties of type II pneumonocytes for up to 2 wk. Cells were isolated by collagenase digestion of midgestation human fetal lung tissue that had been maintained in organ culture in the presence of dibutyryl cyclic AMP (Bt2cAMP) for 5 days. The isolated cells were enriched for epithelial components by treatment with DEAE-dextran, plated on an extracellular matrix (ECM) derived from Madin-Darby canine kidney (MDCK) cells, and incubated at an air/liquid interface in a minimal amount of culture medium containing Bt2cAMP. The cell cultures were comprised of islands of round epithelial-like cells containing numerous dense osmiophilic granules, surrounded by sparse spindle-shaped cells with the appearance of fibroblasts. Ultrastructural examination revealed that the osmiophilic granules had the appearance of lamellar bodies, the distinguishing feature of type II pneumonocytes. Additionally, the cultures maintained elevated levels of SP-A gene expression for up to 2 wk. The expression of mRNAs encoding SP-A, SP-B, and SP-C were regulated in the cultured cells by glucocorticoids and cyclic AMP in a manner similar to that observed in fetal lung tissue in organ culture. The differentiated phenotype was most apparent when the cells were cultured at an air/liquid interface. In order to utilize the cultured type II cells for study of the effects of overexpression of various proteins and for promoter analysis, it is of essence to transfect DNA constructs into these cells with high efficiency. Unfortunately, we found the cells to be refractory to efficient transfer of DNA using conventional methods (i.e., lipofection, electroporation, or calcium phosphate-mediated transfection). However, replication-defective recombinant human adenoviruses were found to provide a highly efficient means of introducing DNA into the type II pneumonocytes. Furthermore, we observed in type II cell-enriched cultures infected with recombinant adenoviruses containing the lacZ gene under control of a cytomegalovirus promoter, that beta-galactosidase was expressed uniformly in the islands of type II cells and surrounding fibroblasts. By contrast, in cultures infected with recombinant adenoviruses containing the human growth hormone (hGH) gene under control of the SP-A gene promoter and 5'-flanking region, hGH was expressed only in the type II cells. Thus, this culture system provides an excellent means for identifying genomic elements that mediate type II cell-specific gene expression.     

Progressive scoliosis with vertebral rotation after lumbar intervertebral disc herniation in a 10-year-old girl

A case report of a 10-year old girl with a herniated disc is presented. The most significant symptoms were progressive scoliosis with a flat back and paravertebral muscle spasm. An absent H reflex on the left and an increased latency of the somatosensory-evoked potentials of the left posterior tibial nerve were found. The computed tomographic scan of the lumbar spine showed a large central left-sided disc protrusion at the L5-S1 level. Our case presents the youngest patient with documented intervertebral disc herniation and the only one with severe scoliosis and vertebral rotation. The curve was not structural because it improved with surgery and an orthosis was not necessary.     

Loudness balance between acoustic and electric stimulation by a patient with a multichannel cochlear implant

Estimates of loudness balance were obtained for acoustically and electrically presented 250 Hz sine signals from a patient who uses the Ineraid multichannel cochlear implant. Acoustic and electric loudness matching was possible because the patient evidenced a 25 dB HL threshold at 250 Hz in his nonimplanted ear. The level of the electrical stimulus in microamperes required for a balance of loudness grew linearly with equal increments in decibels for the acoustic stimulus. These data, in concert with the very limited data from previous studies, provide a rationale for using a logarithmic transformation of acoustic to electric intensity in signal processors for cochlear implants.     

Alignment of fluorescent molecules vapour-deposited on to highly oriented PTFE substrates

The alignment of six fluorescent materials (p-terphenyl, p-quaterphenyl, p-quinquephenyl, diphenylstilbene, 1,4-bis(2-methylstyryl)benzene, and 1,4-bis-2-(5-phenyloxazolyl)benzene) grown from the vapour phase on to friction-deposited, highly oriented poly(tetrafluoroethylene) (PTFE) films was studied. The dichroic ratio of the fluorescent films produced was determined by polarized spectroscopic fluorescence measurements, and the crystallographic orientation of these materials was determined by transmission electron microscopy. The measured dichroic ratios ranged from 1.7 for diphenylstilbene to 5.0 for the p-quaterphenyl film. Electron diffraction patterns revealed that five of the fluorescent materials grew epitaxially on the single crystal-like PTFE films, the fluorescent crystals adopting particular orientations with respect to the crystallographic planes of PTFE. On the other hand, crystals of 1,4-bis-2-(5-phenyloxazolyl) benzene aligned in a fibre pattern, apparently by a grapho-epitaxial mechanism.     

Statistical studies of branched ester latex and paint properties

Vinyl versatate, butyl acrylate and 2-ethylhexyl acrylate were compared as comonomer, for colloid-stabilized vinyl acetate latex polymers to assess their impact on latex coating properties. Vinyl versatate afforded advantages in scrub resistance, gloss, hydrophobicity and higher glass transition temperatures. Butyl acrylate developed better wet adhesion efficiency, gel content and hiding efficiency. 2-Ethylhexyl acrylate offered performance comparable to butyl acrylate in hiding efficiency, lowering copolymer glass transition temperatures, and gloss development. Combinations of these monomers, in many instances, afforded a better balance of performance properties than individual monomers alone. In the subject study, a simplex-centroid design was utilized to statistically map polymer compositions for determining the effect of comonomer composition on latex and paint film properties. In addition to developing contour maps of polymer and paint properties as a function of composition, a technique for studying structure-property relationships is presented.     

Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog

An early step in the development of vertebrae, ribs, muscle, and dermis is the differentiation of the somitic mesoderm into dermomyotome dorsally and sclerotome ventrally. To analyze this process, we have developed an in vitro assay for somitic mesoderm differentiation. We show that sclerotomal markers can be induced by a diffusible factor secreted by notochord and floor plate and that heterologous cells expressing Sonic hedgehog (shh/vhh-1) mimic this effect. In contrast, expression of dermomyotomal markers can be caused by a contact-dependent signal from surface ectoderm and a diffusible signal from dorsal neural tube. Our results extend previous studies by suggesting that dorsoventral patterning of somites involves the coordinate action of multiple dorsalizing and ventralizing signals and that a diffusible form of Shh/Vhh-1 mediates sclerotome induction.