Emericid,a new polyether antibiotic fromStreptomyces hygroscopicus (DS 24 367)

Summary Emericid is a new polyether polycyclic ionophore antibiotic excreted byStreptomyces hygroscopicus (DS 24 367). Active in vitro against Gram-positive bacteria, it is ineffective in vivo. At a 0.006–0.02% level in the diet it protects chickens and rabbits against coccidiosis.From a recent paper byN. Otake (Tetrahedron Lett.1970, 4147) emericid and lonomycin would be identical.     

Spécificité de l'action antiphage de substances synthétiques

Summary The effect of synthetic antiphages has been studied against different types of bacteriophage in the same bacterium, in this caseEscherichia coli. Most substances are active only against typesT ₁, 3, 5, 7 (and our type 207) but not against types 2, 4, 6. Others show activity only against type 1 (and our type 207). The antiphage activity of a substance therefore seems to depend upon a specific relationship between its chemical structure and that of the phage type against which it is active.     

De-synthesizing the relative a priori

This paper considers the question whether the notion of the relative apriori, central to Michael Friedman’s transcendentalist programme for philosophy of science, is available also to philosophers who reject appeals to a synthetic a priori. After tracing the rediscovery of the relative a priori and delineating its potential, the question is considered whether Friedman’s arguments against Quinean naturalism and Carnap’s attenuated logicism tell against a conception of philosophy as scientific metatheory that combines logical and empirical inquiries. Finding an opening here it is argued that this conception can also help itself to the notion of a relative a priori which, it is agreed, is central to historically informed theorising about science.     

4-Isothiocyanato-4′-nitrodiphenylamine (C9333-Go/CGP 4540) an anthelminthic with an unusual spectrum of activity against intestinal nematodes,filariae and schistosomes

Summary 4-isothiocyanato-4-nitrodiphenylamine was found to possess activity against intestinal nematodes in mice, against schistosomes in various hosts including primates and against two filarial species in the mongolian jird. Upon administration in a single oral dose it is equally effective againstS. haematobium, S. mansoni andS. japonicum.     

Nosiheptide,a sulfur-containing peptide antibiotic isolated fromStreptomyces actuosus 40037

Summary Nosiheptide (9671 R.P.) isolated fromStreptomyces actuosus 40037 (NRRL 2954) is a sulfur-containing polypeptidic antibiotic, quite different from all the other members of this family. Very active in vitro against gram-positive bacteria, it is inactive in vivo in experimentally infected mice. Not toxic, even at high dose, it may be used as a feed additive for chickens and pigs and it shows a favourable effect on the growth and conversion index.     

Paul Natorp and the emergence of anti-psychologism in the nineteenth century

This paper examines the anti-psychologism of Paul Natorp, a Marburg School Neo-Kantian. It identifies both Natorp’s principle argument against psychologism and the views underlying the argument that give it its force. Natorp’s argument depends for its success on his view that certain scientific laws constitute the intersubjective content of knowledge. That view in turn depends on Natorp’s conception of subjectivity, so it is only against the background of his conception of subjectivity that his reasons for rejecting psychologism make sense. This interpretation of Natorp suggests that attention paid to late nineteenth century theories of subjectivity and philosophy of psychology could improve our understanding of the emergence of anti-psychologism in that period.     

Potentiation of antifungal activity of sesquiterpene dialdehydes against Candida albicans and two other fungi.

The antifungal activity of two drimane sesquiterpene dialdehydes, polygodial (1) and warburganal (2), alone and in combination with several other substances, was examined against three fungi, Candida albicans, Saccharomyces cerevisiae and Pityrosporum ovale employing a broth dilution method. Anethole significantly synergized the activity of the two sesquiterpenoids against C. albicans and S. cerevisiae; however, it had only an additive effect against P. ovale. By contrast, two antioxidants, ascorbic acid (vitamin C) and BHA (butylated hydroxyanisole), noticeably enhanced the activity of the sesquiterpenoids against P. ovale, but had no effect against C. albicans and S. cerevisiae.     

Aristotle on the infallibility of normal observation

Whereas it is well established that Aristotle allowed the possibility of error in some observations, it is often held that he was an infallibilist with respect to normal observational beliefs. We shall argue against this interpretation of Aristotle, and in particular show that it is not implicit in his view that observation is the ‘ultimate arbiter of truth’.     

Nematodes and the spleen: An immunological relationship

Despite being a major organ of the immune system, the spleen's role in resisting, controlling or simply ameliorating nematode infections has been neglected. A review of both filarial and gastrointestinal nematodes suggests that though it is difficult to fully assess or quantify the organ's importance in vivo, the spleen is prominent in acting against nematode parasites in mammals. One manifestation of this is that transfer of lymphocytes from the spleen of immunised individuals can protect recipients against the disease. Expansion of splenic lymphoid tissue also alludes to its activity during nematode infection. There is a considerable need for investigation of the spleen under natural conditions as well as much more rigorously controlled experiments even in mammals besides birds and other vertebrates.     

Deviant encodings and Turing’s analysis of computability

Turing’s analysis of computability has recently been challenged; it is claimed that it is circular to analyse the intuitive concept of numerical computability in terms of the Turing machine. This claim threatens the view, canonical in mathematics and cognitive science, that the concept of a systematic procedure or algorithm is to be explicated by reference to the capacities of Turing machines. We defend Turing’s analysis against the challenge of ‘deviant encodings’.     

Lactoferrin

Lactoferrin (LF) is a member of the transferrin family that is expressed and secreted by glandular epithelial cells and is found in the secondary granules of neutrophils. Originally viewed as an iron-binding protein in milk, with bacteriostatic properties, it is becoming increasingly evident that LF is a multifunctional protein to which several physiological roles have been attributed. These include regulation of iron homeostasis, host defense against a broad range of microbial infections, anti-inflammatory activity, regulation of cellular growth and differentiation and protection against cancer development and metastasis. While iron binding is likely central to some of the biological roles of LF, other activities, including specific interactions with mammalian receptors and microbial components, also contribute to the pleoitropic functional nature of this protein. In this article, recent advances in the understanding of these functions at the cellular and molecular level are discussed.     

Quantum metaphysical indeterminacy and the ontological foundations of orthodoxy

This paper develops quantum state individualism, a fundamental ontology for what is usually known as ‘orthodox quantum mechanics.’ The central import of this ontology is that allows for a systematic evaluation of some of the main conclusions of the recent literature on quantum metaphysical indeterminacy. In particular, quantum state individualism supports the ‘gappy’ version of Jessica Wilson's determinable-based account of metaphysical indeterminacy; it implies that fundamental reality is perfectly precise; and third, it provides a non-disjunctive definition of determinables and thereby shields Wilson's account against the charge that it requires either a departure from classical logic or a revision of the quantum formalism.     

Selenoprotein P

Selenoprotein P (SeP) is an extracellular, monomeric glycoprotein containing up to 10 selenocysteine residues in the polypeptide chain. It is ubiquitously expressed in mammalian tissues, and in human plasma it accounts for at least 40% of the total selenium concentration. SeP binds to heparin and cell membranes, and is associated with endothelial cells. SeP in human plasma protects against peroxynitrite-mediated oxidation and reduces phospholipid hydroperoxide in vitro, in accordance with the presumption that it has a function as an extracellular oxidant defense. Immunochemical assays have demonstrated that its concentration in plasma varies much with selenium intake, but other factors also have an influence.     

Differential sensitivity to photohemolysis of erythrocytes enriched with some liposome-carried substances

The sensitivity of human erythrocytes to photohemolysis sensitized by addition of protoporphyrin IX can be selectively affected by their enrichment with substances carried by cationic liposomes. In particular the enrichment which superoxide dismutase is accompanied by a copper-related greater sensitivity toward photohemolysis, as observed in the Down's syndrome (mongolism). Instead it is possible to protect the erythrocytes against the phototoxic effect of protoporphyrin by enrichment with small amounts of beta-carotene.     

Epigenetic tinkering and evolution: is there any continuity in the role of cytosine methylation from invertebrates to vertebrates?

The function of DNA methylation has been investigated in depth in vertebrate and plant genomes, establishing that it is involved in gene silencing and transposon control. Data regarding insect methylation, even if still scanty, apparently argue against evolutionary conservation of DNA methylation functions. Cytosine methylation, therefore, proves to be an epigenetic tool repeatedly used to accomplish different functions in different taxa according to a sort of epigenetic tinkering occurring during evolution.     

Ureido-ethyl-imidazolines active against autochthonous diethylnitrosamine-induced epidermoid,papillary and adenocarcinomatous tumors of the respiratory tract of Syrian hamsters and against human bronchogenic carcinomas in nu/nu mice

Summary The detection of a new class of tumor inhibiting substances is described. Employing a chemical reaction discovered several years ago, a series of imidazolinylureas were prepared. It was found that some compounds of this group were active against diethylnitrosamine (DENA)-induced tumours in hamsters. CGP 15 720 A (1-{2-[2-(4-pyridyl)-2-imidazoline-l-yl]-ethyl}-3-(4-carboxy-phenyl)urea,Xb), the most active compound at present, was developed through a series of structural variations. CGP 15 720 A inhibits significantly in oral or parenteral treatment with well tolerated doses (10–30 mg/kg) the progressive growth of autochthonous, DENA-induced papillary, epidermoid and adenocarcinomatous tumors of the respiratory system in Syrian hamsters and prolongs significantly the survival. The substance also inhibits significantly the growth of 2 poorly differentiated human epidermoid or anaplastic bronchogenic carcinomas in nu/nu Balb/c mice and prolongs the mean survival time. In these mice, the substance is also active against the rodent ascites tumors Ehrlich carcinoma, CrSa 180 and Yoshida Sa AH 66, although it is only marginally active or inactive against these tumors in normal mice or rats. — In the therapeutic trials, hamsters tolerated the highest dose administered for 4 weeks, 1000 mg/kg p.o., without signs or symptoms of toxicity.Editorial remarks. There is still an urgent medical need for effective and welltolerated drugs for the treatment of the most common forms of cancer, such as bronchial carcinoma, or for post-operative prophylaxis against relapse and metastasis. — The old-established screening method based on rapidly proliferating acute transplantable lymphatic leukemias in the mouse that is applied in the major cancer research centers has certainly achieved some measure of clinical success, inasmuch as the mean duration of survival of patients with acute lymphatic leukemia has increased from 3 months to about 6 years and similar activity has been found in some rapidly proliferating lymphomas, sarcomas and teratomas.The authors were convinced, however, that chemotherapeutic agents effective against lung cancer could only be found with the help of new specific animal models. They developed a model of an autochthonous tumor in the hamster, applied it in extensive series of experiments, and succeeded in synthesizing and identifying a group of compounds that were both effective and well tolerated. They describe the synthesis and biological activity of CGP 15 720, the compound with the highest therapeutic index and an apparently non-cytotoxic mode of action.     

Wirkung eines tumorhemmenden Stoffes,des Triäthylenmelamins,auf das Wachstum von Fremdkörpergranulom und Tumor

Summary The action of Triethylenmelamine, an anti-tumour substance, was investigated on tumourgrowth and on development of the foreign body granuloma comparatively.It was found that this substance induces in both cases a similar dosis-dependent inhibition of growth.As the inhibiting action of Triethylenmelamine can even be demonstrated on rapidly growing normal tissues, it is questionable whether the antagonistic action against tumour can be designed as tumour-specific.