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.     

Isolation and structure of Phomin

Zusammenfassung Aus Kulturen einesPhoma spec. (Stamm S 298) (Fungi imperfecti) wurde das neue cytostatisch wirksame Antibioticum Phomin isoliert. Auf Grund seiner chemischen und physikalischen Eigenschaften wird ihm die Strukturformel1 erteilt.     

Serotonin,a strong inhibitor of the autocatalytic activation of trypsinogen

Zusammenfassung Eine Reihe von Alkylaminen wurden auf ihren hemmenden Einfluss auf die Trypsinogenaktivierung untersucht. Hierbei erwies sich Serotonin als der stärkste Hemmstoff, gefolgt von Tryptamin und Butylamin. Die Hemmung der autokatalytischen Aktivierung war bedeutend stärker ausgeprägt als die Hemmung der Aktivierung durch Enterokinase.

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This study was supported by US Public Health Service grant HE-06350.     

Purification of platelet-derived endothelial cell growth inhibitor and its characterization as transforming growth factor-beta type 1.

In 1986, Brown and Clemmons (Proc. natl Acad. Sci. USA 83 (1986) 3321) showed that platelets contain a substance, platelet-derived growth inhibitor (PDGI), that inhibits in vitro endothelial cell replication. Although platelets are rich in transforming growth factor beta (TGF-beta), PDGI was considered not to be related to TGF-beta, on the basis of its reported properties (extraction from platelets at neutral pH, binding to heparin-Sepharose). However, we purified PDGI to near homogeneity and showed that on the basis of HPLC retention behavior, in vitro growth inhibitory activities with several cell types, receptor binding, and immunoneutralization of growth inhibitory activity with specific anti-TGF-beta type 1 antibodies, PDGI is most probably identical with TGF-beta type 1.     

Isolation of maridomycins and structure of maridomycin II

Zusammenfassung Das ausStreptomyces hygroscopicus isolierte neue Makrolid Maridomycin II lässt sich mit Säure Mycarcose und Mycaminose spalten. Auf Grund der Oxidation ins Carbomycin sowie der spektroskopischen Daten wurde die Struktur als II erklärt.

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The authors are greatly indebted to Dr.F. A. Hochstein of Chas Phizer & Co., Inc., for valuable gifts of carbomycin and carbomycin B.

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Detailed microbiological and isolation studies will be published in J. Antibiotics (Tokyo).     

Isolation of maridomycins and structure of maridomycin II

Zusammenfassung Das ausStreptomyces hygroscopicus isolierte neue Makrolid Maridomycin II lässt sich mit Säure Mycarcose und Mycaminose spalten. Auf Grund der Oxidation ins Carbomycin sowie der spektroskopischen Daten wurde die Struktur als II erklärt.     

Isolation and structure of N α -formyl melittin

Zusammenfassung Bienengift wurde durch Gelfiltration in seine Komponenten aufgetrennt. Aus der Melittinfraktion wurde neben Melittin eine elektrophoretisch langsamer wandernde Komponente isoliert, die als N -Formyl-Melittin identifiziert wurde. Diese Struktur wurde auch durch Synthese bestätigt.

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Peptide Synthese XLVIII. 4th Communications on melittin.     

Isolation of plant growth regulators fromPseudomonas amygdali

Summary Trans-zeatin and indole-3-acetic acid were isolated, as the main components of the cytokinin and indole mixtures respectively from culture filtrates ofPseudomonas amygdali, the causal agent of hyperplastic bacterial canker of almond.     

Epicatechin can cause the seedling growth inhibitor,nagilactone E,to induce growth stimulation

Summary A possible new role for the flavonoid (–)-epicatechin (II) is described. It has no growth effects on its own, but when it is added to lettuce and rice seeds together with the known seedling growth inhibitor nagilactone E (I), the growth inhibitor activity ofI can cease and growth stimulation can be observed.     

Regulation of cell growth

Posters

Regulation of cell growth     

Isolation and structure of caerulein,an active decapeptide from the skin ofHyla caerulea

Riassunto Vengono descritti i procedimenti che hanno permesso di giungere all'isolamento e al chiarimento della struttura della caeruleina, decapeptide attivo della pelle dellaHyla caerulea. Vengono messi in luce gli stretti rapporti di struttura esistenti fra la caeruleina e le gastrine, soprattutto le gastrine-II, e fra la caeruleina e la colecistochinina-pancreozimina.

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Supported in part by a grant from the Consiglio Nazionale delle Ricerche, Roma.     

Isolation and structure of 2,4-dihydroxy-3,5,6-trimethylbenzoic acid fromMortierella ramanniana

Zusammenfassung Aus KulturenMortierella ramanniana var.angulispora (Naumov) Linnemann wurde 2,4-dihydroxy-3,5,6-trimethylbenzoesäure isoliert. Auf Grund seiner chemischen und physikalischen Eigenschaften wird ihm die Strukturformel I erteilt.     

Nerve growth factor: structure and function

Neurotrophins are critical for the development and maintenance of the peripheral and central nervous system. These highly homologous, homodimeric growth factors control cell survival, differentiation, growth cessation, and apoptosis of sensory neurons. The biological functions of the neurotrophins are mediated through two classes of cell surface receptors, the Trk receptors and the p75 neurotrophin receptor (p75NTR). Nerve growth factor (NGF), the best characterized member of the neurotrophin family, sends its survival signals through activation of TrkA and can induce cell death by binding to p75NTR. Recent domain deletion and mutagenesis studies have identified the membrane-proximal domain of the Trks as necessary and sufficient for ligand binding. Crystal structures of this domain of TrkA, TrkB, and TrkC, and an alanine scanning analysis of this domain of TrkA and TrkC have allowed identification of the ligand-binding site. The recent crystal structure of the complex between NGF and the ligand-binding domain of TrkA defines the orientation of NGF in the signaling complex, and eludicates the structural basis for binding and specificity in the family. Further structural work on NGF-TrkA-p7SNTR complexes will be necessary to address the many remaining questions in this complex signaling system.     

Antizyme inhibitor: mysterious modulator of cell proliferation

In contrast to the considerable interest in the oncogene ornithine decarboxylase (ODC) and in the family of antizymes with regard to cell proliferation and tumorigenesis, the endogenous antizyme inhibitor (AZI) has been less well studied. AZI is highly homologous to the enzyme ODC but does not possess any decarboxylase activity. Elevated ODC activity is associated with most forms of human malignancies. Antizymes bind ODC, inhibit ODC activity and promote the ubiquitin-independent degradation of ODC. Consequently they are proposed as tumor suppressors. In particular, the most studied member of the antizyme family, antizyme 1, has been demonstrated to play a role in tumor suppression. AZI inactivates all members of the antizyme family, reactivates ODC and prevents the proteolytic degradation of ODC, which may suggest a role for AZI in tumor progression. Received 9 December 2005; received after revision 13 April 2006; accepted 1 June 2006