Synthesis and biological activity of Substance P C-terminal hexapeptide and heptapeptide analogues

The analogues [Glu(OBzl)¹¹]SP_6–11 and [Glu(OBzl)¹¹]SP_5–11 of the C-terminal hexapeptide and heptapeptide of Substance P have been synthesized by conventional solution methods. In each analogue the SCH₃ group of Met¹¹ is replaced by the COOCH₂C₆H₅ group. The in vitro activity of both analogues has been determined on three biological preparations: guinea pig ileum (GPI), rat vas deferens (RVD), and rat portal vein (RPV). The selectivity for the different receptors has been studied by utilizing atropine-treated guinea pig ileum (GPI + At). The results showed that both analogues are mainly active on GPI through the NK-1 receptor and that both analogues are equipotent to Substance P.     

Prehospital Thrombolysis in Acute Myocardial Infarction Salvages Myocardium

Early thrombolysis can be given at home, by a medical intensive care unit ambulance team, in the emergency room, or in the coronary care unit. Thrombolysis should be given very early (<2 or 4 hours) and reestablish normal or near normal coronary blood flow. Methods of management include home monitoring of high risk patients with a transtelephonic 12-lead monitor ECG, the management of the patient at home by a trained GP, physician, or medical technician controlled intensive care ambulance team, or a rapid "door to needle" time in the emergency room. Each of these systems requires patient and physician reeducation, to make each group aware of the advantages of early and complete revascularization. An alternative fast track can be provided by immediate percutaneous transluminal coronary angioplasty if the hospital can be prewarned by the physician outside. This article reviews the current published literature and also our experience in 760 patients in Jerusalem. Infarct size, complication rate, and long-term prognosis is related to early complete restoration of coronary blood flow.     

FIELD DESORPTION MASS SPECTROMETRY

In this article we present preliminary results of the application of potassium cationized field desorption mass spectrometry as an additional technique for the elucidation of structure and evaluation of purity of oligopeptides such as C-terminal penta- and hexapeptide analogs of substance P. In the resultant mass spectra both a protonated and a cationized molecular ion, MH+ and MK+respectively, were observed. The m/z values of the two peaks were in agreement with the calculated molecular weights. The ratio between the relative abundancies of these ions (MH+/MK+) was found to be characteristic of the particular peptide and thus useful in the assessment of their purity. Among the 13 peptides studied, only two gave pyroly tic fragmentation leading to a more complex spectra.     

Double Reactivity Against Actin and α-Actinin Defines a Severe Form of Autoimmune Hepatitis Type 1

Anti-filamentous actin antibodies characterize autoimmune hepatitis type 1 (AIH-1). Recently, the binding domain of alpha-actinin on actin was shown to be a predominant epitope. To test this reactivity, an anti-alpha-actinin enzyme-linked immunosorbent assay was developed, and positivity confirmed by Western blot. Anti-alpha-actinin antibody was found in 21/50 (42%) of AIH-1 patients, compared with 52/401 (12.9%) of liver disease control patients, and with 6/200 (6%) of blood donors. Anti-filamentous and anti-alpha-actinin activities were found specifically together in 66% of anti-filamentous-positive AIH-1 patients. This combination of specificities reflected clinical and histological disease activity, short duration and absence of treatment. Finally, using an actin-alpha-actinin complex assay, the binding of anti-filamentous actin to alpha-actinin-binding domain on actin was demonstrated, as well as that of anti-alpha-actinin on the actin-binding domain of alpha-actinin. Thus, the frequent combination of anti-filamentous and anti-alpha-actinin antibodies seems to be the hallmark of activity in AIH-1.     

Antigen Presenting Cells in Human Decidual Tissue: III. Role of Accessory Cells in the Activation of Suppressor Cells

ABSTRACT: Human decidual antigen presenting cells (DAPCs) exposed to fetal cells in vitro induce generation of suppressor T cells among a population of peripheral blood lymphocytes. Human lymphocyte antigen (HLA)-class II positive antigen presenting cells were isolated from early normal human decidual tissue and from peripheral blood (PAPCs) by adhering Ficoll-Pa-que separated cell suspensions to fibronectin. In contrast to PAPCs, DAPCs pulsed with fetal antigens induced a radio-sensitive, Leu 1,2-positive T suppressor cell population. A nylon wool adherent B cell population is required during the in vitro induction of the suppressor cells. These suppressor cells impair primary mitogen and mixed lymphocyte culture (MLC) responses, generation of anti-trinitrophe-nyl (TNP) cytotoxic T lymphocytes, and antibody response of autologous and allogeneic lymphocytes. Only intact viable embryonic cells can effectively confer upon DAPCs the ability to induce T suppressor cells. The T suppressor cell induction by DAPCs primed with fetal antigens is restricted by the major histocompatibility complex. Our results show that the HLA-DR molecules are the most prominent restriction elements.     

Multiple hemangiomata associated with thrombocytopenia: remarks on the pathogenesis of the thrombocytopenia in this syndrome

1. A 13-year-old girl with multiple hemangiomata and thrombocytopeniais described.

2. Complications of surgical treatment included severe bleeding, septicemiaand a fibrinolytic event.

3. Simultaneous platelet counts from the tumor and peripheral blood wereperformed and showed a significantly higher concentration of platelets inthe tumor vessels.

4. With the rise in the platelet count, a decreased platelet fragility as wellas a persistently abnormal prothrombin consumption could be demonstrated.

5. The possible role of the tumor in the pathogenesis of the thrombocytopenia is discussed.

Submitted on December 27, 1957 Accepted on July 14, 1958     

Structure-activity relationship of the ring portion in backbone-cyclic C-terminal hexapeptide analogs of substance P. NMR and molecular dynamics

The conformations of two backbone-cyclized substance P analogs were derived from homo- and heteronuclear NMR measurements and molecular dynamics simulations carried out in DMSO. The analogs contain subtle variations in the ring chemistry and are compared with biologically active analogs previously examined. The correlation between conformation and activity is used to gain insight into the conformational requirements from the pharmacophore.