Astrocyte–neuron interactions in neurological disorders

Astrocytes have long been considered as just providing trophic support for neurons in the central nervous system, but recently several studies have highlighted their importance in many functions such as neurotransmission, metabolite and electrolyte homeostasis, cell signaling, inflammation, and synapse modulation. Astrocytes are, in fact, part of a bidirectional crosstalk with neurons. Moreover, increasing evidence is stressing the emerging role of astrocyte dysfunction in the pathophysiology of neurological disorders, including neurodegenerative disease, stroke, epilepsy, migraine, and neuroinflammatory diseases.     

Vaginal treatment with a prostaglandin F2 alpha derivative (alfaprostol) for inducing labor in pregnancy at term

The effectiveness and acceptability of Alfaprostol (an analog of PGF2 alpha) in inducing labor were assessed in 20 pregnant women at term. All subjects had no spontaneous uterine activity before treatment and the mean (M +/- SE) Bishop score was 2.45 +/- 0.21. The drug was administered by vaginal route at the dose of 10 mg every 3 hours. Regular uterine contractions appeared in all patients and delivery occurred in 85% of the patients after a mean time of 9h50min +/- 0h55min following the start of treatment. The mean dose of Alfaprostol utilized to achieve delivery was 29.4 +/- 2.0 mg. No major side effects were noted in the mothers and their fetuses at any time during treatment. Two patients exhibited vomiting. The Apgar score of all newborns at birth was 8 or more. These results suggest the usefulness of Alfaprostol to induce labor in pregnant women at term, as it has oxytocic activity without adverse effects on either the mother or the fetus.     

Ecology of bdelloids: how to be successful

Bdelloids inhabit many different environments. The entire taxon is an order belonging to the phylum Rotifera. In spite of its wide distribution, it has a very uniform morphology, suggesting that natural selection has had almost no effect on its morphological characteristics.This paper reviews the geographical and ecological distributions of bdelloids and their ability to tolerate different conditions is discussed. Two characteristics account for the wide distribution of bdelloids, parthenogenetic reproduction and their ability to withstand unfavorable conditions through anhydrobiosis. The former is an apomictic thelytoky which may ensure genetic homogeneity within clones. However, evidence which suggests variability among and within parthenogenetic clones is discussed. Some recent experimental evidence indicates that anhydrobiosis does not affect the life history of the surviving individuals. The effects of anhydrobiosis on bdelloid populations are considered.     

Adoptive immunity in mice challenged with L1210/DTIC clones

Summary New antigenic specificities, not detectable on parental cells, have been induced by many investigators in mouse lymphomas by treatment with the antitumor agent 5(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC). The antigens are transmissible, after withdrawal of the drug treatment, as an inheritable character. The mechanism of induction, the molecular nature, and the number of the new antigenic specificities have not been completely elucidated. Four clones from murine leukemia L1210 isolated and expanded in vitro were treated in vivo with DTIC and the new sublines were studied in detail. The four drug-treated sublines studied exhibited strong immunogenicity since they were rejected by syngeneic animals. Immunosuppressed animals challenged with 10⁷ A/DTIC or P/DTIC cells were reciprocally protected by the adoptive transfer of spleen cells from donors that had rejected a lethal challenge of A/DTIC or P/DTIC clones. In a similar fashion, the adoptive transfer of spleen cells obtained from animals that had rejected the Q/DTIC or the R/DTIC clones protected immunosuppressed mice challenged with Q/DTIC or R/DTIC cells. No antitumor activity was observed in cross-protective schedules other than those indicated. It was been concluded that (a) the L1210 leukemia line does not have antigenic cells, (b) four DTIC-treated clone sublines were rejected by compatible hosts, and (c) two mutually exclusive sets of antigens were expressed in four antigenic clone sublines.Research supported in part by P.F.O. Contract Grant from C. N. R., Rome, Italy     

Autoradiographic localization of vasoactive intestinal polypeptide receptors in the rat mesenteric vascular tree

By the use of combined in vitro radioreceptor binding and autoradiographic techniques, we analyzed the pharmacological properties and the anatomical localization of the vasoactive intestinal polypeptide (VIP) receptor in rat superior mesenteric artery and in medium and small mesenteric artery branches. 125I-VIP was bound by sections of rat superior mesenteric artery in a manner consistent with the labeling of specific VIP receptors, with Kd and Bmax values of 0.23 nM and 0.71 pmol/mg protein respectively. Inhibition of 125I-VIP binding with VIP and related peptides gives the following rank order of potency: VIP greater than peptide histidine methionine greater than secretin. Light microscope autoradiography reveals specific VIP binding sites within the medial layer of superior mesenteric artery and its branches. Medium and small sized vessels are richer in 125I-VIP binding sites than the larger ones.     

Urinary elastase 1 in chronic pancreatic disease

Serum and urine elastase 1, its renal output and clearance and urinary gamma-glutamyltransferase and ribonuclease excretions were measured in 16 patients with pancreatic cancer, 23 with chronic pancreatitis and in 22 healthy controls in order to evaluate elastase 1 plasma-urine transfer in chronic pancreatic disease and to investigate any factors that might influence the clearance of this enzyme. In an additional group of 17 patients with different pancreatic diseases the serum molecular size distribution of elastase 1 after chromatography was ascertained. An increased urinary elastase 1 output was found in 4/16 patients with pancreatic cancer and in 6/23 with chronic pancreatitis. No correlation was found between circulating elastase 1 and its urinary output; a negative correlation was detected between the serum levels of this enzyme and its clearance. The excretion of ribonuclease and gamma-glutamyltransferase was correlated with elastase 1 output and clearance. While the majority of elastase 1 in serum was accounted for by high molecular forms, probably the expression of complexes with serum inhibitors, free circulating enzyme was present in all patients with high serum elastase 1. Our findings suggest that elastase 1 urinary excretion increases in some patients with chronic pancreatic disease regardless of the neoplastic or inflammatory nature of the illness. Although the availability of different amounts of ultrafiltrable enzyme may play a role in influencing elastase 1 plasma-urine transfer, renal tubular damage appears to be the most important factor influencing the increase in the urinary output of elastase 1.     

Structure and activity of proteins from pathogenic fungi Phytophthora eliciting necrosis and acquired resistance in tobacco

The phytopathogenic fungi Phytophthora cryptogea and Phytophthora capsici cause systemic leaf necrosis on their non-host tobacco; in culture they release proteins, called cryptogein and capsicein, which elicit similar necrosis. In addition, both proteins protect tobacco against invasion by the pathogen Phytophthora nicotianac, the agent of the tobacco black shank, that is unable to produce such an elicitor. Cryptogein causes visible leaf necrosis starting at about 1 microgram/plant, whereas 50-fold as much capsicein is required for the same reaction. Capsicein induces protection even in near absence of leaf necrosis. The activities of both elicitors are eliminated upon pronase digestion. They are proteins of similar Mr (respectively 10,323 and 10,155) and their complete amino acid sequences were determined. They consist of 98 residues, with some internal repetitions of hexapeptides and heptapeptides. 85% identity was observed between both sequences: only two short terminal regions are heterologous, while the central core is entirely conserved. Secondary structure predictions, hydropathy and flexibility profiles differ only around position 15 and at the C-terminus; these modifications could play a role in the modulation of their biological activities. After a search of the sequence data bases, they appear to be novel proteins.     

Characterization of two glycoproteins of human pancreatic juice: P35, a truncated protease E and P19, precursor of protein X

Four glycoproteins were separated by SDS-polyacrylamide gel electrophoresis of proteins of human pancreatic juice devoid of free proteolytic activity. The two low molecular weight glycoproteins were isolated and characterized. Protein P19, the precursor family of protein X, was analyzed by its carbohydrate content which seemed to play an important role in protein solubility at pH 8.0. Protein P35 was found to be a Con A-binding protein rich in mannose. Its N-terminal amino acid sequence covering 33 residues revealed a strong homology with human protease E without the dipeptide Val-Val. Is P35 a protein homologous to the subunit III of bovine procarboxypeptidase A?     

Role of class II histocompatibility antigens in Staphylococcus aureus protein A-induced activation of human T lymphocytes

The capacity of peripheral blood monocytes and B lymphocytes to support staphylococcal protein A (SpA)-induced proliferation of autologous and allogeneic T cells, as well as the role of major histocompatibility complex (MHC) class I and II molecules in this activation process, were investigated. Highly purified peripheral T lymphocytes did not proliferate in response to SpA, but their response was reconstituted by both irradiated (or mitomycin C-treated) monocytes and B lymphocytes. The effect of B cells on the SpA-induced T-cell response could not be explained by a contamination of residual accessory cells because long-term continuous B-cell lines restored SpA-induced T-cell DNA synthesis as effectively as did monocytes. Support of SpA responsiveness by B cells could not be accounted for by polyclonal binding of SpA to cell surface immunoglobulins, since the ability of SpA-unreactive and SpA-reactive B cells was comparable. The cells from two human leukemic lines--K562 and Raji--showed the same ability in supporting the pokeweed mitogen-induced T-cell response, but the class II-positive Raji cells were much more effective than class II-negative K562 cells in restoring the T-cell responsiveness to SpA. Monoclonal antibodies specific for monomorphic determinants of MHC class II antigens, as well as their F(ab')2 fragments, consistently inhibited the SpA-induced proliferative response, whereas antibodies specific for MHC class I antigens were without effect. The antibodies specific for class II antigens appeared to act at the level of accessory cell, since pretreatment with these antibodies inhibited the ability of SpA-pulsed monocytes or Raji cells to present SpA to autologous or allogeneic T lymphocytes, respectively. These data indicate that either monocytes or normal and lymphoblastoid B cells can act as accessory cells for the proliferative response of human T cells to soluble SpA and that monomorphic determinants of MHC class II molecules play an important role in this activation process.     

1,4-Thiomorpholine-3,5-dicarboxylic acid, a novel cyclic imino acid detected in bovine brain

Gas-liquid chromatography of enriched bovine brain extract revealed the occurrence of several sulfur-containing compounds. By co-chromatography with authentic product and by mass-spectrometric analysis, one of these compounds has been identified as 1,4-thiomorpholine-3,5-dicarboxylic acid (TMDA). The possible derivation of TMDA from lanthionine is discussed. This represents the second S-containing cyclic amino acid so far discovered in a mammalian brain whose physiological significance has not yet been explored.