New bone induction by demineralized bone matrix in immunosuppressed rats.

Subcutaneous implantation of demineralized bone matrix (DBM) initiates a sequence of developmental events which culminate in endochondral bone formation. To test the effects of T-cell deficiency on new bone formation, the morphology of DBM-induced bone was examined in rats thymectomized at three weeks of age and in thymectomized or nonthymectomized rats lethally irradiated and reconstituted with syngeneic bone marrow. At 24 days after implantation, bone induction in control rats was appropriate for their age, while thymectomized-irradiated-reconstituted rats and thymectomized rats had significantly more new bone and larger bone marrow space than the controls. In non-thymectomized, irradiated and reconstituted rats, bone induction occurred in only 25% of the animals, compared to 95% in other groups.     

Identical point mutations of PMP-22 in Trembler-J mouse and Charcot-Marie-Tooth disease type 1A.

We have investigated the peripheral myelin protein gene, PMP-22, in a family with Charcot-Marie-Tooth disease type 1A (CMT1A). The DNA duplication commonly found in CMT1A was absent in this family, but strong linkage existed between the disease and the CMT1A marker VAW409R3 on chromosome 17p11.2. We found a point mutation in PMP-22 which was completely linked with the disease. The mutation, a proline for leucine substitution in the first putative transmembrane domain, is identical to that recently found in the Trembler-J mouse. The presence of this PMP-22 defect in this CMT1A family and the location of PMP-22 within the DNA duplication associated with CMT1A suggest that both structural alteration and overexpression of PMP-22 may lead to the disease.     

NMR study of parallel-stranded tetraplex formation by the hexadeoxynucleotide d(TG4T).

Multistranded DNA structures based upon guanine association have been proposed to be important in the structure of chromosome telomeres and in immunoglobulin class switching. Nucleic acids containing runs of guanine bases form a number of structures in vitro, including fold-back structures (Fig. 1a) and parallel-stranded quadruplex structures in DNA and RNA. The features of fold-back structures have now been determined at high-resolution. The different structures are probably based on a tetrad of hydrogen-bonded guanine bases (Fig. 1b), with buffer conditions and sequence effects mediating isomerization between the different forms. Here we use NMR spectroscopy to investigate the solution structure of the complex formed by the hexadeoxynucleotide d(TG4T) in the presence of sodium ions. We have observed the formation of a parallel-stranded quadruplex containing hydrogen-bonded tetrads of guanine. The parallel-stranded form differs significantly from the fold-back form, with individual nucleotide conformations being closer to those of B-form DNA.     

Quantification of the disorder in network-modified silicate glasses.

Local order in silicate glasses has been observed by many experimental techniques to be similar to that in crystalline materials. Details of the intermediate-range order are more elusive, but essential for understanding the lack of long-range symmetry in glasses and the effect of composition on glass structure. Two-dimensional 17O dynamic-angle-spinning nuclear magnetic resonance experiments reveal intermediate-range order in the distribution of inter-tetrahedral (Si-O-Si) bond angles and a high degree of order in the disposition of oxygen atoms around the network-modifying cations.     

Capillary electrophoresis: the promise and the practice.

The field of capillary electrophoresis has undergone rapid development over the past 10 years. Many advances have been made, but there are still some problems that must be addressed before the technique can reach its full potential.     

Immunospecific inhibition of nerve conduction by T lymphocytes reactive to basic protein of myelin

Experimental autoimmune encephalomyelitis (EAE) induced by immunization to the basic protein of central nervous system myelin (BP) is a paralytic disease in which T lymphocytes attack the individual's own central nervous system. As the target is in white matter, EAE has been considered an experimental model of some aspects of human disease such as multiple sclerosis. To investigate whether autoimmune T lymphocytes could produce paralysis, we studied the effects on the electrophysiology of isolated nerves produced by T-lymphocyte lines reactive specifically to BP or other antigens. We now report that propagation of action potentials evoked by electrical stimulation was blocked by incubating optic nerves with specific anti-BP T cells. This blockade could be reversed for up to two hours by removing the anti-BP line cells from the optic nerve. The anti-BP line cells had no effect on conduction along allogeneic optic nerves or syngeneic peripheral nerves. This indicates that disruption of the function of myelin in neuroimmunological disease may result from an immunologically specific interaction between autoimmune T lymphocytes and myelin antigens.     

Septation and fragmentation inOedogonium mitochondria as different and independent effects of dimethyl sulfoxide (DMSO) treatment

Summary Oedogonium cardiacum Wittrock, a filamentous green alga, was treated with DMSO. The substance induced active swelling and fragmentation of mitochondria at both 5 and 7.5%. Septa were observed at 7.5% only and were not identical with the fragmentation sites. Thus it is concluded that internal partition by septa is not a prerequisite for mitochondrial fragmentation or division.Acknowledgment. This work was supported by the Österreichische Nationalbank, Jubiläumsfondsprojekt No. 1927.     

Viral transduction of c-myc gene in naturally occurring feline leukaemias

Feline leukaemia virus (FeLV) is epidemiologically associated with induction of the majority of lymphoid tumours of the domestic cat. However, about one-third of these tumours are devoid of exogenous virus or show evidence of virus integration only after tumour outgrowth. To help define the genetic mechanisms of feline lymphomagenesis we have explored here the possibility that cellular oncogenes (c-onc genes) are rearranged in tumour cell DNA. Of 16 FeLV-positive T-cell tumours among 31 naturally occurring lymphomas, 2 showed evidence of recombinant FeLV proviruses containing myc oncogene sequences. One of the two produced a transmissible myc-containing FeLV. In both cases c-myc and its surrounding DNA appeared unaltered. We believe that the association of myc with FeLV may result in its activation and play a part in the development of a significant fraction of cat T-cell lymphomas. Our findings contrast with studies of experimental induction of chicken lymphoma, in which myc activation occurs by retrovirus promoter insertion near c-myc (refs 3-5), rather than by incorporation into virus.     

Structure-dependent,selective localization of chlorinated xenobiotics in the cerebellum and other brain structures

Summary Remarkable regional distribution patterns of some chlorinated xenobiotics in the CNS are described.We thank Dr Åke Bergman, Wallenberg Laboratory, University of Stockholm, Stockholm, for the synthesis of compounds IV and V. The studies were supported by the Swedish Work Environment Fund (grants nos 73/169 and 74/181) and by the Research Committee of the National Swedish Environment Protection Board (grant no. 7-27/79).