Thioridazine and EKG anomalies

Summary Acute i.v. infusion but not daily oral administration of thioridazine-HCl in the dog produced EKG anomalies similar to those reported in psychiatric patients taking this drug. Lack of EKG effects after thioridazine-5-sulfoxide infusion and presence of anomalies after thioridazine at equivalent doses suggests further evaluation of the relationship between reported plasma levels of thioridazine and its ring-sulfoxide in association with EKG changes.This study was supported, in part, by a Grant-in-Aid from Boehringer-Ingelheim, Ltd. Sandoz, Inc. kindly provided thioridazine HCl (Mellaril^®) and thioridazine-5-sulfoxide.     

Categorization, anomalies and the discovery of nuclear fission

The characteristics of scientific revolutions and by the same token the question of which events in the history of science deserve the name of revolutionary are controversial themes in the philosophy of science. An issue of disagreement is the question of whether or not events in which only parts of a paradigm are overthrown can truly be called a revolution, or if this term is to be reserved for the developments in which a wholesale replacement of ideas takes place. In this paper Kuhn's latest attempt to state a principle for distinguishing revolutionary developments will be reviewed, and it will be argued that certain developments entailing only partial replacements of the paradigm can be called revolutionary. The discovery of fission will serve as case study to illustrate this idea.     

A similarity-based approach of Kuhn’s no-overlap principle and anomalies

In their book Cognitive Structure of Scientific Revolutions, Hanne Andersen, Peter Barker, and Xiang Chen reconstruct Kuhn’s account of conceptual structure and change, based on the dynamic frame model. I argue against their reconstruction of anomalies and of the no-overlap principle and propose a competing model, based on the similarity relation. First, I introduce the concept of psychological distance between objects, and then I show that the conceptual structure of a theory consists of a set of natural families, separated by a significant empty space. I argue that, in such a conceptual structure, the ES condition, according to which the distance between natural families should be greater than the distance between any two objects belonging to the same natural family, is satisfied. Anomalous objects lead to the violation of this condition. I argue that in a conceptual structure satisfying the ES condition, a similarity relation could be defined, so that natural families would be similarity classes, satisfying the no-overlap principle. In a structure not satisfying this principle, such similarity classes could not be delimited.     

Biomedicine and diseases: the Klippel-Trenaunay syndrome, vascular anomalies and vascular morphogenesis

Vascular morphogenesis is a vital process for embryonic development, normal physiologic conditions (e.g. wound healing) and pathological processes (e.g. atherosclerosis, cancer). Genetic studies of vascular anomalies have led to identification of critical genes involved in vascular morphogenesis. A susceptibility gene, VG5Q (formally named AGGF1), was cloned for Klippel-Trenaunay syndrome (KTS). AGGF1 encodes a potent angiogenic factor, and KTS-associated mutations enhance angiogenic activity of AGGF1, defining ‘increased angiogenesis’ as one molecular mechanism for the pathogenesis of KTS. Similar studies have identified other genes involved in vascular anomalies as important genes for vascular morphogenesis, including TIE2, VEGFR-3, RASA1, KRIT1, MGC4607, PDCD10, glomulin, FOXC2, NEMO, SOX18, ENG, ACVRLK1, MADH4, NDP, TIMP3, Notch3, COL3A1 and PTEN. Future studies of vascular anomaly genes will provide insights into the molecular mechanisms for vascular morphogenesis, and may lead to the development of therapeutic strategies for treating these and other angiogenesis-related diseases, including coronary artery disease and cancer.Received 24 November 2004; received after revision 21 January 2005; accepted 2 March 2005     

Induction of developmental anomalies in mice by maternal stress

Summary The short-time restraint of pregnant mice on day 8 of gestation led to a significant increase of the anomaly rate in fetuses. This effect may be due to stress factors of endocrine origin.The technical assistance of Mrs E. Frei is gratefully acknowledged. Supported by the Swiss National Foundation for Scientific Research.     

Induction of developmental anomalies in mice by maternal stress

The short-time restraint of pregnant mice on day 8 of gestation led to a significant increase of the anomaly rate in fetuses. This effect may be due to stress factors of endocrine origin.     

Concepts, anomalies and reality: a response to Bloor and Fehér

In this article I respond to the defences of the Strong Programme put forward by David Bloor and Márta Fehér in this issue. I dispute the claim that it is attention to only limited parts of the Strong Programme framework that allows me to argue that this approach: (i) leads to weak idealism, (ii) undermines the idea that theories have varying levels of instrumental success, and (iii) challenges the theoretical claims of scientific actors. Rather, I argue that these problematic positions are entailed by the constructionist tenets at the core of the Strong Programme.     

Immunochemical study of protein anomalies in platelets of patients with Glanzmann's thrombasthenia and Bernard-Soulier syndrome]

Crossed immunoelectrophoresis of "Triton X-100" solubilized proteins from (125I) iodinated normal and abnormal (Bernard-Soulier and thrombasthenic) platelets was performed using rabbit antibodies raised against whole, normal platelets. In Bernard-Soulier platelets neither of the two surface oriented forms of GP I, glycocalicin and glycoprotein Ib (band 13) were detected. In two patients with type I thrombasthenia, the most prominent precipitate (No. 16) and platelet fibrinogen (No 24) were not detected whereas in one patient with type II thromblasthenia, fibrinogen was normally detected and the amount of protein 16 was around 15% of the normal level. The alloantibody IgG L..., able to induce a "thrombasthenic-like" reactivity in normal human platelets, has been shown to be directed against protein 16.     

The effects of cocaine in the production of cardiovascular anomalies inβ-Adrenoreceptor stimulated chick embryos

Summary Cocaine potentiates the effects of epinephrine and norepinephrine in terms of aortic arch malformation in embryonic chicks. Cocaine itself induces aortic arch malformations when administered in large doses.This study was supported by grant No. HL 18050, National Heart and Lung Institute, National Institutes of Health, Bethesda, Maryland.     

草地与农牧交错带退化生态系统重建及防治途径

草地不仅是草地畜牧业的基地，而且在生态环境保护与建设方面的作用尤为重要。草原与农牧交错带，即不同于西部牧区，也不同于东部农区。根据它在地理、气候、农林牧产业结构、生态、经济、文化、社会等方面具有自己独特地位的实际情况，因地制宜提出了相应之对策，为国家在西部大开发和草地与农牧交错带生态环境的恢复提供科学依据。     

Telomeres and meiosis in health and disease

Beyond their role in replication and chromosome end capping, telomeres are also thought to function in meiotic chromosome pairing, meiotic and mitotic chromosome segregation as well as in nuclear organization. Observations in both somatic and meiotic cells suggest that the positioning of telomeres within the nucleus is highly specific and believed to be dependent mainly on telomere interactions with the nuclear envelope either directly or through chromatin interacting proteins. Although little is known about the mechanism of telomere clustering, some studies show that it is an active process. Recent data have suggested a regulatory role for telomere chromatin structure in telomere movement. This review will summarize recent studies on telomere interactions with the nuclear matrix, telomere chromatin structure and factors that modify telomere chromatin structure as related to regulation of telomere movement.     

Telomeres and meiosis in health and disease

Telomeres are important segments of chromosomes that protect chromosome ends from nucleolytic degradation and fusion. At meiosis telomeres display an unprecedented behavior which involves their attachment and motility along the nuclear envelope. The movements become restricted to a limited nuclear sector during the so-called bouquet stage, which is widely conserved among species. Recent observations suggest that telomere clustering involves actin and/or microtubules, and is altered in the presence of impaired recombinogenic and chromosome related functions. This review aims to provide an overview of what is currently known about meiotic telomere attachment, dynamics and regulation in synaptic meiosis.     

Telomeres and meiosis in health and disease

Telomeres are important segments of chromosomes that protect chromosome ends from nucleolytic degradation and fusion. At meiosis telomeres display an unprecedented behavior which involves their attachment and motility along the nuclear envelope. The movements become restricted to a limited nuclear sector during the so-called bouquet stage, which is widely conserved among species. Recent observations suggest that telomere clustering involves actin and/or microtubules, and is altered in the presence of impaired recombinogenic and chromosome related functions. This review aims to provide an overview of what is currently known about meiotic telomere attachment, dynamics and regulation in synaptic meiosis.     

Telomeres and meiosis in health and disease

The aim of this review is threefold. First, we want to report on recent observations on the role of telomeres in the alignment of homolog and non-homologues in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe and the relationship of early telomere clustering to later recombination events. Second, we compare the similarities and differences between synaptic and asynaptic yeasts. Third, we report on the increasing evidence of the effect of meiosis on telomeric sequences that suggest an induction of a specific form of recombination processes termed telomere rapid deletion.     

Models and structures: Phenomenological and partial

In a recent paper, Suárez and Cartwright (2008) return to the example of London and London's construction of a model for superconductivity and raise a number of concerns against the account of this construction presented in French and Ladyman (1997) and elsewhere. In this discussion note, we examine the challenge they raised and offer our responses.