Human spleen inhibitor of leukaemic cell growth

Resumen En este trabajo se describe la purificación de un inhibidor de la síntesis de ARN que afecta secundariamente la síntesis de ADN, y actividad mitótica. El factor ha sido aislado de ocho bazos humanos, comprendiendo dos de enfermos con leucemia mielocítica crónica (LMC) sanas, en los cuales se efectuó la esplenectomía por ruptura traumática del bazo El inhibidor esplénico posee fuerte citotoxicidad sobre células en cultivo provenientes de enfermos con LMC. Estas células tienen el cromosoma de Philadelphia. El inhibidor esplénico tiene un peso molecular de alrededor de 1,000 y es probablaemente un péptido o glicopéptido.     

Purification and partial characterization of a human plasma α1-heteroglycan

Summary A heteroglycan was purified from human plasma and partially characterized in terms of its major properties. It is noteworthy that the carbohydrate content of this blood constituent is unusually high (75%).This study was supported by grants from the National Institutes of Health (GM-10374), US Public Health Service.     

Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4

The African tree Combretum caffrum (Combretacae) has been found to contain a powerful inhibitor of tubulin polymerization (IC50 2-3 microM), the growth of murine lymphocytic leukemia (L 1210 and P 388 with ED50 approximately 0.003 microM and human colon cancer cell lines [(e.g. LoVo (ED50 = 0.005 microgram/ml), HT 29 (ED50 0.02 microgram/ml, Colo 205 (ED50 = 0.07 microgram/ml), DLD-1 (ED50 = 0.005 microgram/ml) and HCT-15 (ED50 = 0.0009 microgram/ml] designated combretastatin A-4 (1c). The structure assigned by spectral techniques was confirmed by synthesis.     

Purification and characterization of bovine pancreatic alpha-amylase

A method for the purification of alpha-amylase from Bovine pancreas homogenate is described. This enzyme has the same molecular weight as the Porcine isoenzymes but its isoelectric point is more basic. Its amino acid composition is similar to that of Porcine, Ovine, Rat and Mouse amylases.     

Structure and function of the type 1 insulin-like growth factor receptor

The type 1 insulin-like growth factor receptor (IGF-1R), a transmembrane tyrosine kinase, is widely expressed across many cell types in foetal and postnatal tissues. Activation of the receptor following binding of the secreted growth factor ligands IGF-1 and IGF-2 elicits a repertoire of cellular responses including proliferation, and the protection of cells from programmed cell death or apoptosis. As a result, signalling through the IGF-1R is the principal pathway responsible for somatic growth in foetal mammals, whereas somatic growth in postnatal animals is achieved through the synergistic interaction of growth hormone and the IGFs. Forced overexpression of the IGF-1R results in the malignant transformation of cultured cells: conversely, downregulation of IGF-1R levels can reverse the transformed phenotype of tumour cells, and may render them sensitive to apoptosis in vivo. Elevated levels of IGF-IR are observed in a variety of human tumour types, whereas epidemiological studies implicate the IGF-1 axis as a predisposing factor in the pathogenesis of human breast and prostate cancer. The IGF-1R has thus emerged as a therapeutic target for the development of antitumour agents. Recent progress towards the elucidation of the three-dimensional structure of the extracellular domain of the IGF-1R represents an opportunity for the rational assembly of small molecule antagonists of receptor function for clinical use.     

Lack of effect of dihydroergotamine on endothelial and smooth muscle cell proliferation and endothelial cell prostanoid production

Summary The most important effect of dihydroergotamine is venoconstriction, but certain metabolic effects and changes in vessel prostanoid activity have also been suggested. In this study endothelial cell production of 6-keto PGF₁ and TxB₂ was quantitated in vitro. No evidence of altered prostanoid production was noted after incubation with dihydroergotamine (exposure ranging from 5×10^–3 to 5×10^–7 g/l). Similarly, no effect of dihydroergotamine on the growth rates of endothelial cells or smooth muscle cells in vitro was documented.     

Lack of effect of dihydroergotamine on endothelial and smooth muscle cell proliferation and endothelial cell prostanoid production

The most important effect of dihydroergotamine is venoconstriction, but certain metabolic effects and changes in vessel prostanoid activity have also been suggested. In this study endothelial cell production of 6-keto PGF1 alpha and TxB2 was quantitated in vitro. No evidence of altered prostanoid production was noted after incubation with dihydroergotamine (exposure ranging from 5 x 10(-3) to 5 x 10(-7) g/l). Similarly, no effect of dihydroergotamine on the growth rates of endothelial cells or smooth muscle cells in vitro was documented.     

Purification and partial characterization of two lectins fromMomordica charantia

Summary 2 different lectins have been purified from the seeds ofMomordica charantia by gel-filtration and ion-exchange chromatography. These 2 lectins appear to be composed of 2 subunits of 26,000 daltons. Protein fraction I, but not II, showed agglutinating activity toward human type-O red blood cells. The amino acid compositions and amino-terminal sequences of these two homologous proteins are quite different.Acknowledgment. The skillful assistance of Ms M. Diane Forde is greatly acknowledged. Part of this work was supported by NIH grants CA18621 and AI09810 when the author was at Mount Sinai School of Medicine.     

The pattern of endothelial cell boundaries in regenerated aortae.

The pattern of endothelial cell boundaries in the regenerated aorta was shown to differ greatly from that of control specimens as seen in silver stained preparations under the scanning electron microscope.     

Morphine as inhibitor of prostaglandin E1 in the isolated guinea-pig intestine

Zusammenfassung Es wird gezeigt, dass Analgetika vom Morphintypus die am isolierten Meerschweinchen-dünndarm nach Zugabe von Prostaglandin E₁ erfolgenden Kontraktionen ähnlich wie die durch Arachidonsäure (-peroxid) erzeugten Kontraktionen in spezifischer Weise zu antagonisieren vermögen.     

Purification and partial characterization of lysozyme from mouse small intestine

Summary Lysozyme was isolated from the small intestine of mice by combined ion-exchange and molecular sieve chromatography. This lysozyme differs from that isolated from the urine of mice with monocytoma in amino acid composition, and migration rate in cellulose acetate electrophoresis. As intestinal lysozyme originates at least in part from the Paneth cell, our results point towards the existence of isozymes of lysozymes in mice.Acknowledgments. Supported by grant No. 20159 from the Fonds voor Wetenschappelijk Geneeskundig Onderzoek, Brussel, Belgium. We should like to thank Mrs.Parein for skillful technical assistance.     

Spatially defined oxygen gradients and vascular endothelial growth factor expression in an engineered 3D cell model

Tissue hypoxia results in rapid angiogenesis in vivo, triggered by angiogenic proteins, including vascular endothelial growth factor (VEGF). Current views of tissue viability are founded on whether ‘deeper-lying’ cells receive sufficient nutrients and oxygen for normal activity and ultimately survival. For intact tissues, levels of such essential nutrients are governed by micro-vascular perfusion. However, there have been few effective quantitatively defined 3D models, which enable testing of the interplay or interdependence of matrix and cell density, and path diffusion on oxygen consumption in vitro. As a result, concepts on cell vulnerability to low oxygen levels, together with the nature of cellular responses are ill defined. The present study has adapted a novel, optical fibre-based system for in situ, real-time oxygen monitoring within three-dimensionally-spiralled cellular collagen constructs, which were then unfurled to enable quantitative, spatial measurements of VEGF production in different parts of the same construct exposed to different oxygen levels. A VEGF response was elicited by cells exposed to low oxygen levels (20 mmHg), primarily within the construct core. Received 3 August 2007; received after revision 24 October 2007; accepted 29 October 2007 An erratum to this article is available at .     

Vermipodia - a new type of cell process.

A new kind of cell process is described in leukemic cells in two cases of histiocytic malignancies. They were evident both with light microscopy and scanning electron microscopy. As they have a tubular, worm like appearance, the name vermipodia has been given to them.     

Regulation of the type III InsP3 receptor and its role in beta cell function

The type III inositol 1,4,5-trisphosphate receptor (InsP3R) is an important intracellular calcium (Ca2+) release channel in the pancreatic beta cell. Pancreatic beta cells secrete insulin following a characteristic change in membrane potential that leads to an increase in cytoplasmic Ca2+. Both extracellular Ca2+ and Ca2+ mobilized from InsP3-sensitive stores contribute to this increase. RIN-m5F cells, an insulin-secreting beta cell line, preferentially express the type III InsP3R. These cells have been useful in determining the regulatory properties of the type III InsP3R and the role of this isoform in an intact cell. The type III InsP3R is ideal for signal initiation because high cytoplasmic Ca2+ does not inhibit its activity. Altered insulin secretion, the result of changes in Ca2+ handling by the beta cell, has significant clinical consequences.