Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain proteins

During ageing of the human brain, and particularly in senile dementia of the Alzheimer type (AD), many neurones progressively accumulate abnormal cytoplasmic fibres, called paired helical filaments (PHF). Each such fibre consists of a pair of intermediate (10 nm) filaments twisted into a double helix with a periodicity of 160 nm. PHF accumulate in large perikaryal masses, called neurofibrillary tangles, and are also found in degenerating cortical neurites that form neurite plaques. The density of PHF-containing neurites and cell bodies correlates with the degree of dementia and the extent of loss of cholinergic neurotransmitter function in AD. Recently, we demonstrated that PHF from human cerebral cortex are large, rigid polymers with unusual molecular properties, including insolubility in SDS, urea and other denaturing solvents and apparent resistance to protease digestion. These properties have so far prevented complete purification and analysis of the constituents of PHF. Based on their insolubility, we have developed a new method of preparing highly enriched PHF fractions and have raised an antiserum that is highly specific for PHF. We report here that this antiserum specifically labels PHF, free of any associated normal fibrous proteins and, unexpectedly, it reacts with neither neurofilaments nor any other normal cytoskeletal protein in brain sections or on immunoblotted gels. These anti-PHF antibodies have been used for the specific detection of Alzheimer-type PHF and in the search for cross-reacting antigens in various tissues, and are suitable for immunoaffinity purification of PHF. Our results indicate that PHF contain determinants that are not shared with normal neuronal fibrous proteins.     

Calcitonin-like peptide in the shrimpPalaemon serratus (Crustacea,Decapoda) during the intermolt cycle

Summary A molecule immunologically related to salmon calcitonin has been detected in the hemolymph of the shrimpPalaemon serratus. Its concentration varies inversely with the calcium level during the molt cycle; a maximum (14 ng/ml) is found in the post-molt stage and a minimum (0.5 ng/ml) during the premolt stage.     

Inhibition of pathogenic effect of effector T cells by specific suppressor T cells during influenza virus infection in mice

Mice infected with an aerosol of influenza type A virus, or immunized with purified UV-inactivated whole virus or with viral subunits, develop a transient delayed-type hypersensitivity (DTH) which peaks 5-7 days after immunization. The intensity of DTH is greatly enhanced and sustained when mice are pretreated with cyclophosphamide. The reaction is maximal 24 h after elicitation, has classical tuberculin-type histology and is transferable by immune H-21 region restricted Lyt-1+2- T cells (Td) but not by immune serum. These Td cells not only fail to protect mice against influenza virus infection, but increase the mortality rate due to influenzal pneumonia following challenge with homologous lethal virus. On the other hand, antigen-specific suppressor T (Ts) cells which inhibit DTH are readily generated during influenza virus infection, and are detectable for at least 40 days thereafter. The ease with which they are induced and maintained during the infection may be of evolutionary advantage. In support of this, we now report that these Ts cells can reverse the pathogenic effect of Td cells thereby demonstrating a beneficial influence of Ts cells in a viral disease.     

Comparative distribution of vasoactive intestinal polypeptide (VIP), substance P and PHI in the enteric sphincters of the cat

Summary In the feline gastrointestinal tract, the neuropeptides, substance P, VIP and PHI were investigated by specific radioimmunoassays and immunocytochemistry. The concentrations of all 3 peptides and the level of peptidergic innervation were significantly less in the anal sphincter than elsewhere, whereas no significant differences were seen between other sphincter and non-sphincter regions.     

Sliding movement of single actin filaments on one-headed myosin filaments

The myosin molecule consists of two heads, each of which contains an enzymatic active site and an actin-binding site. The fundamental problem of whether the two heads function independently or cooperatively during muscle contraction has been studied by methods using an actomyosin thread, superprecipitation and chemical modification of muscle fibres. No clear conclusion has yet been reached. We have approached this question using an assay system in which sliding movements of fluorescently labelled single actin filaments along myosin filaments can be observed directly. Here, we report direct measurement of the sliding of single actin filaments along one-headed myosin filaments in which the density of heads was varied over a wide range. Our results show that cooperative interaction between the two heads of myosin is not essential for inducing the sliding movement of actin filaments.     

Low-molecular-weight proteinase inhibitor in human plasma inhibiting papain and trypsin activity

Summary A low-molecular-weight proteinase inhibitor was isolated from human plasma on the basis of its papain-inhibiting capacity. The isolated fraction demonstrated inhibitory activity against papain and trypsin activity and the molecular weight was estimated to be approximately 3200 by gel-filtration.     

Evidence for no relationship of the pineal activity with the neonatal shrinkage of Leydig cells in the rat

Summary The collective volume of Leydig cells in prenatally pinealectomized newborn rats declined as sharply as in intact newborn rats. Also, the collective volume in pups born in the dark declined in a fashion similar to that in pups born in the light. The results indicate that neither the pineal gland nor the light is responsible for the neonatal shrinkage of Leydig cells.This study was supported in part by a Grant-in Aid for Scientific Research (No. 548067) from the Ministry of Education, Science and Culture of Japan.     

Lipid peroxidation in rabbit reticulocytes

Summary Lipid peroxides in rabbit erythrocytes and plasma were determined while anemia was induced by daily bleeding. They increased as reticulocytes increased and returned to normal with the morphological transformation to mature cells.This work was supported in part by a grant-in-aid from the Japan Medical Research Foundation and a grant-in-aid (project No. 56570363) from the Ministry of Education, Science and Culture of Japan.     

The phorbol ester TPA induces metamorphosis in Red Sea coral planulae (Cnidaria: Anthozoa)

Controlled experiments on the metamorphosis of marine invertebrate larvae require artificial inducers. These inducers can be used for studying the involvement of known signal transduction pathways in settlement and metamorphosis. The ability of the tumor-promoting phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) to induce metamorphosis in planulae of the Red Sea soft coral speciesHeteroxenia fuscescens, Xenia umbellata, Dendronephthya hemprichii, Litophyton arboreum andParerythropodium fulvum fulvum, and the stony coralStylophora pistillata, was examined by using various concentrations of TPA. The chemical induced metamorphosis in all six species. The effect was unspecific and concentration-related. For all the corals except forX. umbellata the highest mean percentages of metamorphosis were obtained with 8.1×10^–7–10^–9 M TPA. ForX. umbellata, the percentage of metamorphosis was lower, and was obtained within a wider TPA concentration range. The present results, along with previous studies on Hydrozoa and Scyphozoa, demonstrate that TPA is the first common artificial inducer for these classes of Cnidaria. TPA is known to activate the enzyme protein kinase C (PKC) and therefore plays an important role in studying the phosphatidylinositol signal transduction system. Evidence for the involvement of this pathway in triggering metamorphosis has already been reported for Hydrozoa and Scyphozoa. Our results suggest that PKC is also involved in initiating metamorphosis in Anthozoa.