Tumor necrosis after the intra-tumor injection of chemical agents and colloidal radioisotopes

Zusammenfassung Mehrere klinisch wirksame, geschwulsthemmende Stoffe verursachten relativ rasch Nekrosen der Mäusesarkoma-180-Tumoren, wenn sie, entsprechend der klinischen Anwendung von radioaktiven Kolloiden, direkt in den Tumor injiziert wurden. Sowohl unlösliche, wie lösliche Verbindungen ergaben Nekrose. In den Tumor injiziertes 6-Merkaptopurin, Diäthylstilböstrol und -Naphtyl-Stickstoff-Lost verminderten alle bei Ratten das Wachstum des Jensen-Sarkoms.     

Osmotic concentration of the contractile vacuole ofAmoeba proteus following UV-light irradiation

Zusammenfassung Nach UV-Bestrahlung erweist sich die osmotische Konzentration der pulsatilen Vakuolen vonAmoeba proteus als unverändert.     

A Cambrian micro-lobopodian and the evolution of arthropod locomotion and reproduction

The evolutionary success of arthropods, the most abundant and diverse animal group, is mainly based on their segmented body and jointed appendages, features that had evolved most likely already before the Cambrian. The first arthropod-like animals, the lobopodians from the Early Cambrian, were unsclerotized and worm-like, and they had unjointed tubular legs. Here we describe the first three-dimensionally preserved Cambrian lobopodian. The material presented of Orstenotubulus evamuellerae gen. et sp. nov. is the smallest and youngest of a lobopodian known. O. evamuellerae shows strikingly detailed similarities to Recent tardigrades and/or onychophorans in its cellular-structured cuticle and the telescopic spines. It also shows similarities to other, longer known lobopodians, but which are ten times as large as the new form. These similarities include the finely annulated body and legs, which is characteristic also for Recent onychophorans, and paired humps continuing into spines situated dorsally to the leg insertions, a feature lacking in the extant forms. The morphology of O. evamuellerae not only elucidates our knowledge about lobopodians, but also aids in a clearer picture of the early evolution of arthropods. An example is the single ventral gonopore between a limb pair of O. evamuellerae, which indicates that a single gonopore, as developed in onychophorans, tardigrades, pentastomids, myriapods and insects, might represent the plesiomorphic state for Arthropoda, while the paired state in chelicerates and crustaceans was convergently achieved. Concerning life habits, the lateral orientation of the limbs and their anchoring spines of the new lobopodian imply that early arthropods were crawlers rather than walkers.     

OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28

Autosomal dominant optic atrophy (ADOA) is the most prevalent hereditary optic neuropathy resulting in progressive loss of visual acuity, centrocoecal scotoma and bilateral temporal atrophy of the optic nerve with an onset within the first two decades of life. The predominant locus for this disorder (OPA1; MIM 165500) has been mapped to a 1.4-cM interval on chromosome 3q28-q29 flanked by markers D3S3669 and D3S3562 (ref. 3). We established a PAC contig covering the entire OPA1 candidate region of approximately 1 Mb and a sequence skimming approach allowed us to identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases. The gene comprises 28 coding exons and spans more than 40 kb of genomic sequence. Upon sequence analysis, we identified mutations in seven independent families with ADOA. The mutations include missense and nonsense alterations, deletions and insertions, which all segregate with the disease in these families. Because most mutations probably represent null alleles, dominant inheritance of the disease may result from haploinsufficiency of OPA1. OPA1 is widely expressed and is most abundant in the retina. The presence of consensus signal peptide sequences suggests that the product of the gene OPA1 is targeted to mitochondria and may exert its function in mitochondrial biogenesis and stabilization of mitochondrial membrane integrity.     

Regulation of NMDA receptor desensitization in mouse hippocampal neurons by glycine

Responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) are markedly potentiated by nanomolar concentrations of glycine. This is due to the action of glycine at a novel strychnine-resistant binding site with an anatomical distribution identical to that for NMDA receptors, suggesting that the NMDA receptor channel complex contains at least two classes of amino-acid recognition site. Antagonists at the glycine-binding site associated with NMDA receptors act as potent non-competitive antagonists, but do not alter the mean open time or conductance, as estimated by fluctuation analysis. The mechanisms by which glycine acts on NMDA receptors are unknown, but single-channel recording experiments show an increase in opening frequency with no change in mean open time or conductance, suggesting that glycine could regulate transitions to states that are intermediate between binding of NMDA receptor agonists and ion-channel gating. It has been suggested that glycine acts as a co-agonist at the NMDA receptor, and that responses to NMDA cannot be obtained in the complete absence of glycine, but in these experiments the response to NMDA was measured at equilibrium, and it is unlikely that sufficient temporal resolution was achieved to detect rapid alterations in receptor gating. Using a fast perfusion system we find that glycine regulates desensitization at NMDA receptors; this has a major effect on the response to NMDA measured at equilibrium, as would occur with slower applications of agonist. Reduction of NMDA receptor desensitization by glycine provides an example of a novel mechanism for regulation of ion-channel activity.