Publications

IT has been recently shown that various strains of Streptococcus pyoqenes group A possess a cell-bound haemolysin (CBH) which can be released from the streptococcal cells into the surrounding medium by some surface active materials (Tween 40, Tween 80, Triton) by crystalline albumin, but not by sonlic energy (Ginsburg and Grossowicz, 1957 ; Ginsburg, 1958; Ginsburg and Grossowicz, 1959). This haemolytic factor was designated as streptolysin " D " (SLD) D signifying detergent. SLD is distinguished from streptolysin 0 (SLO) streptolysin S (SLS) (Todd, 1938) and from the intracellular haemolysin (IH) described by Schwab (Schwab, 1956) on the bases of different substrate requirements for formation, sensitivity to U.N. irradiation and to sonic energy (Ginsburg, 1958; Ginsburg and Gros- sowicz, unpublished). Besides haemolysing RBC of various animal species both cell-free and cell- bounid SLD, are also capable of injuring and killing various mamimalian cells in vitro (Ehrlich ascites tumour cells, fibroblasts, amnion cells, leucocytes) (Gins- buirg, 1958 ; Ginsburg and Grossowicz, 1959). The purpose of the present study is to show that Ehrlich ascites tuilour cells damaged by different streptococcal haemolysins may be disintegrated bv various proteolytic enzymes which by themselves are not lethal

1) Defined media which allow heavy growth of 3 strains of group A streptococci have been developed. The medium consists of either a) 21 amino acids, glutamine, 6 vitamins, salts, purines, pyrimidines and glucose or b) 13 amino acids and 4 vitamins. 2) Cysteine is important both as an essential amino acid and as a reducing agent. As an amino acid only a small amount (10 μg ml) is needed and this can be substituted by an equivalent amount of cystine. As a reducing agent it can be replaced by ascorbic acid and less effectively by thiomalic or thioglycollic acids. Concentration of cysteine was critical for initiation of growth from small inocula. With less than 5 × 106 ml cells at least 350 μg ml cysteine HCl are needed for obtaining visible growth. 3) Pyridoxal was necessary in a medium of 13 amino acids and 3 vitamins (nicotinic acid, pantothenate, riboflavin) whereas in a complete medium (22 amino acids) no need for pyridoxal was found. Pyridoxal could be replaced by L- or DL-alanine.

During our study of the action of water-soluble poly-a-amino acids on blood clotting (1), it was observed that the basic poly-amino acids: poly-lysine (2), poly-ornithine (3) and poly-arginine (3), retard fibrinolysis of human clotted blood. A more detailed analysis of this phenomenon was therefore undertaken. Fibrinolytic activity of oxalated human plasma was induced by mixing the plasma with a suspension of ,- hemolytic streptococci (4, 5), by treatment with a cellfree broth containing streptokinase (6), or by shaking the plasma with chloroform (6, 7). The activated plasma was then treated with the poly-amino acids (prepared in this laboratory), and a fibrin clot obtained by the addition of thrombin. The final mixtures were incubated at 370 C for 15-24 hr to determine -if lysis occurred. When the preparations used did not interfere with fibrinolysis, dissolution of the clot occurred. Inhibition of fibrinolysis was indicated by the maintenance of the fibrin clot, obtained as described *above, for 24 hr. A typical experiment with poly-L-lysine and a streptococei-activated plasma is described below. Oxalated human plasma (0.5 ml) was mixed with a suspension of 1-hemolytic streptococci (0.4 ml), and the mixture added to 1 ml saline solution containing 40y poly-L-lysine hydrochloride. Clotting was induced by adding 4 units of bovine thrombin (Upjohn Company) in 0.1 ml saline with vigorous shaking. The clot was incubated at 370 C for 24 hr. No visual change in the clot was observed. In the control experiment where the 1 ml poly-lysine solution was substituted by saline, a complete lysis of the clot was evident within 30 min. The fibrinolytic activity of plasma activated by Ihemolytic streptococci was not inhibited either by the neutral poly-DL-alanine (8) or by the acidic poly-Laspartic (9) and poly-D-glutamic (10) acids up to concentrations of 500y/ml final test mixture. The basic poly-a-amino acids, poly-DL-lysine hydrochloiide (average chain length n = 35) (2), poly-DL-ornithine hydrochloride (n = 30) (3), and poly-DL-arginine sulfate (n = 30) (3), on the other hand, prevented fibrinolysis at concentrations greater than 30y40y/ml test mixture. In the presence of the basic poly-amino acids, fibrinolysis Was inhibited equally well when the streptococcal culture suspension was replaced (in the test mixture) by a cell-free supernatant containing streptokinase. Furthermore, it has been demonstrated that the fibrinolytic activity of chloroform-treated plasma and of menstrual blood was also inhibited by relatively low concentrations of poly-DL-lysine and poly- DL-arginine. It thus seems justified to assume that the basic poly-amino acids are capable of inhibiting hydrolysis of fibrin by plasma fibrinolysin (plasmin) under the experimental conditions used. Preliminary experiments indicated that the average molecular weight of the basic poly-amino acids plays a profound role in ther determination of their antifibrinolytic properties. L-lysine monomer, as well as L-lysyl-L-lysine (11), did not show any antifibrinolytic activity up to a concentration of 750y/ml. A tetra-Llysine showed slight antifibrinolytic activity at 750y/ ml, whereas poly-L-lysine of average chain length n= 7, 35, and 100 showed distinct antifibrinolytic activity at concentrations of 500y, 40y, and 35y/ml test mixture, respectively. No great difference was observed in the antifibrinolytic activity of poly-L-, poly-D-, and poly-DL-lysine of similar average molecular weights. In our previous study on the action of water-soluble poly-amino acids on blood clotting (1), it was demonstrated that the acidic poly-amino acids, poly-D-glutamic acid and poly-L-aspartic acid, as well as heparin, are capable of neutralizing the anticoagulant activity of the basic poly-amino acids. A similar relationship was found to hold for the antifibrinolytic effect of the basic poly-amino acids. Heparin, as well as poly-Laspartic acid (n = 50), was found to obviate the antifibrinolytic activity of poly-lysine. The neutralization of the antifibrinolytic activity of the basic poly-amino acids occurred when approximately equivalent concentrations of the basie -and acidic poly-amino acids were applied. The ability of the basic synthetic peptides to inhibit rev,ersibly the. proteolytic activity of fibrinolysin resembles, the antiproteolytic properties of some natural peptides, such as the pepsin,inhibitor and the' trypsin inhibitors (12). The interaction of the natural as well as the synthetic peptides with the different proteolytic enzymes is probably determined in both cases by some specific groups present in the enzyme and the inhibitor, as well as by the electrostatic forces prevailing between the enzyme and the relatively high molecular weight inhibitor. Further studies with the 'synthetic amino acid polymers may contribute to our basic knowledge of the mode of actlon of naturally naturally occurring polypeptides on enzyme behavior.

abstract

The goal of the present study was to investigate whether spontaneous functional recovery following insult to the language-dominant hemisphere continues in the so-called "chronic stage," and if so, to examine its neuro-functional correlates. We used a longitudinal functional magnetic resonance imaging (fMRI) block design, where each young patient served as his/her own control. Specifically, we examined whether language functions differed significantly in two monitoring sessions conducted years apart, both in the chronic stage, where almost no functional changes are expected. We focused on a unique cohort of young brain damaged patients with aphasiogenic lesions occurring after normal language acquisition, in order to maximize the potential of plasticity for language reorganization following brain damage. The most striking finding was that the linguistic recovery of our patients was significant not just relative to their linguistic scores on initial testing (T1), but also in absolute te

Has the European Union (EU) succeeded in socializing citizens to support the democratic values it claims to promote? On the face of it, the prevailing skepticism precludes any expectation of a successful socialization of EU citizens to the EU values. Yet, according to the socialization hypothesis, citizens' support for these values is expected to increase as countries accumulate more years of the EU membership. Using survey data to isolate distinct dimensions of democratic values, we examine differences among countries in this regard, as well as changes within countries over time. Results confirm the socialization hypothesis, showing that support for democratic [...]

Contributors Abdar, Carmella PhD Among her main areas of expertise are folk art and material culture of Yemenite Jews, mainly rural communities. She has published several articles: “The dress code[...]

Dates based upon notices at the end of sermons on f. 20r (593=1753), 48r (596=1756), 57v (555=1795). ; Ḳaplan, Yaʻaḳov . Lim, ha-Kohen, of Tartu (former owner, per stamp, f. 70v, etc.). ; קפלן, יעקב ב"ר משה ב"ר אליקים לים . הכהן, מתושבי העיר טרטו (בעלים, ע"פ חותמת בדף 07ב, ועוד). ; Reference to Kerem Shelomoh, per J. Brumer's notes. [...]