Alterations in dopaminergic receptors in Huntington's disease.

To detect variations in dopaminergic receptors and cholinergic activity in regions of postmortem Huntington's diseased brains, ³H-spiroperidol binding assays and choline acetyltransferase (ChAc) activities were carried out. A significant reduction in ³H-spiroperidol binding in the caudate nucleus, putamen and frontal cortex of choreic brains was detected which appeared to be due to a decrease in the total number of binding sites rather than to a decrease in affinity of ³H-spiroperidol for the dopaminergic receptor. In choreic brains, there were also significant reductions in ChAc activity in the caudate nucleus and putamen. The decreases of both ³H-spiroperidol binding and ChAc activity in the neostriatum suggest that the dopaminergic receptors are localized postsynaptically on cholinergic interneurons. Dopaminergic receptor alterations in the basal ganglia may be one of the causes of the abnormal motor movements found in HD while alterations of these receptors in the frontal cortex may be associated with the neuronal degeneration found in that area of choreic brains.     

Five 3β, 6α-dihydroxysterols in organ-pipe cactus

The sterol diol fraction from the lipids of organ-pipe cactus, Stenocereus thurberi, was separated into five compounds: macdougallin, peniocerol, cyclostenol, stenocereol and thurberol. The last three compounds have not been described before. All compounds were characterized by physical and spectroscopic properties.     

Crystallographic and molecular-orbital studies on the geometry of antifolate drugs.

In the common dihydrofolate reductase inhibitors an amino substituent replaces the pteridine carbonyl oxygen atom of folates, with altered hydrogen-bonding properties and size. Flexibility in the amino groups could facilitate enzyme binding. Studies of cycloguanil hydrochloride by neutron diffraction show both in-plane and out-of-plane deformation of amino groups. Molecular-orbital calculations ab initio on 2,4-diamino-5-methylpyrimidinium cation confirm that the 4-amino group is readily deformable. The 2,4-diaminoquinazoline structure is reported. Atomic co-ordinates, thermal parameters, bond distances and bond angles for cycloguanil and 2,4-diaminoquinazoline have been deposited as Supplementary Publication SUP 50108 (13 pages) at the British Library Lending Division, Boston Spa. Wetherby, West Yorkshire LS23, 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1978) 169, 5.     

Ontogeny of Daucus carota Infected with Meloidogyne hapla

The ontogeny of carrots (Daucus carota cv. ''Spartan Premium'') grown under greenhouse conditions in pots of organic soil infected with Meloidogyne hapla was influenced detrimentally as early as 4 days after seeding, as determined through analysis of plant surface area, dry weight, fresh weight, net assimilation rate, relative growth rate, and leaf-area ratio. Only 58% of the diseased carrots were suitable for fresh market, compared with 97% of those grown in nematode-free soil. Growth and development of the shoot system (height, surface area, dry weight, and fresh weight) were retarded by M. hapla as early as 12 days after seeding. During the first 12 days after seeding, root dry weight was greater for diseased plants than for controls. Root growth and development (surface area, dry weight, and fresh weight) associated with this nematode, however, were retarded as early as 16 days after seeding. M. hapla caused a delay in the occurrence of 2nd-, 4th-, and 5th-order roots, and an increase in the occurrence of 6th-order roots in infected plants. Parasitized plants had 44% fewer roots (primary through 6th-order) and 50% less total root length.     

Treatmenf of optic neuritis by retrobulbar injection of triamcinolone.

In a single-blind controlled clinical trial patients with optic neuritis caused by demyelination were given a single retrobulbar injection of triamcinolone. Though the treated group showed a trend towards more rapid recovery of vision than the controls, there was no significant difference in visual acuity, colour vision, or visual fields during the first six months after treatment. We conclude that routine use of corticosteroids is not justified in unilateral optic neuritis when vision in the other eye is good. Shortening the period of visual disability in bilateral disease or unilateral disease when vision in the other eye is poor, however, may be justifiable.     

Development of immunoassays for human interleukin 3 and interleukin 4, some of which discriminate between different recombinant DNA-derived molecules

Two panels of hybridomas were produced that secreted monoclonal antibodies (MAbs) against recombinant DNA-derived human interleukin 3 and interleukin 4 (rhIL-3 and rhIL-4). From each panel, sensitive immunoradiometric assays (IRMAs) were developed which were capable of detecting the recombinant molecule used as the immunogen but were unable to recognize natural or other recombinant forms of the same cytokine. Subsequent studies using the MAbs from each panel showed that a number of the MAbs appeared only to recognize that particular recombinant molecule used as immunogen, with little or no binding to other recombinant forms of the molecule. By using MAbs that were found to be unrestricted in their recognition for different recombinant forms of the cytokines, it was possible to develop an IRMA for IL-4 that was capable of detecting natural IL-4 as well as all the recombinant forms equally. An IRMA was also developed for IL-3 but was not of equivalent sensitivity in detecting the different recombinant forms of IL-3 used in the study. The recombinant DNA-derived cytokine molecules used to raise the two panels of MAbs contained amino acid substitutions relative to the natural sequences, and these findings indicate that caution should be exercised when using immunoassays to estimate natural sequence molecules if antibodies raised to modified rDNA-derived molecules are used.