Monamidocin, a novel fibrinogen receptor antagonist. II. Biological activity and structure-activity relationships.

Monamidocin, a fibrinogen receptor binding inhibitor produced by Streptomyces sp. NR 0637, inhibits the binding of fibrinogen to its receptor with an IC50 of 0.21 microM. It also inhibits ADP-collagen- and thrombin-induced aggregation of human platelet with IC50S of 46, 30, and 77 microM, respectively. To obtain more potent inhibitors, twenty analogs have been synthesized, among which N-[(R)-5-guanidino-2-hydroxypentanoyl]-L-tyrosine is the most potent. It inhibits the binding of fibrinogen to its receptors with an IC50 of 0.022 microM and is about ten times more potent than monamidocin.

Simple synthetic procedure for 2'- and 3'-tetrahydropyranyl ribonucleoside derivatives involving regioselective acylation with acyl chlorides, and synthesis of ribonucleotide oligomers.

Acylation of ribonucleosides through acyl chlorides in pyridine was induced with high regioselectivity under a controlled condition to give the corresponding 2',5'-diacylates in excellent yields and 2'-acylates, depending on the amount of the acyl chlorides used. On the other hand, a treatment of these resulting acylates on a silica gel (Wakogel C-300, Wako Pure Chemical Co. Ltd.) conducted their transformation into the corresponding 3',5'-diacylates or 3'-acylates effectively. These resulting 2',5'- and 3',5'-diacylates were further derived, by the known method, into the 3'- and 2'-O-tetrahydropyran-2-yl ribonucleoside derivatives, respectively, with which some ribonucleotide oligomer syntheses have been performed.

Susceptibility to adjuvant-induced arthritis among germfree, specific-pathogen-free, and conventional rats.

Germfree F344 rats developed severe arthritis with 100% incidence after a single intradermal inection of either squalane containing 0.5 mg of heat-killed Mycobacterium bovis BCG or a water-in-oil emulsion containing 0.2 mg of peptidoglycan derived from Staphylococcus epidermidis. Conventional F344 rats developed less-severe arthritis with 20% incidence for heat-killed BCG and 0% incidence for peptidoglycan. Specific-pathogen-free rats showed an intermediate susceptibility between germfree and conventional rats. Interestingly, both unimmunized specific-pathogen-free and conventional rats. but not unimmunized germfree rats, showed weak delayed-type hypersensitivity reactions to peptidoglycans derived from either S. epidermidis or Lactobacillus plantarum, suggesting that a bacterial flora may furnish a stimulus for induction of cell-mediated immunity to ubiquitous bacterial peptidoglycans. It is thus possible that although a bacterial flora is not necessary for development of adjuvant arthritis, it may have some suppressive effect on the development of the disease in specific-pathogen-free and conventional F344 rats, possibly through modulation of the immune response.

Studies on the use of mumps virus for treatment of human cancer.

Purified mumps virus (Urabe strain) was given mainly by intravenous injection to a total of 200 patients with cancer. The only adverse clinical reaction was transient mild fever in about half the patients. The beneficial clinical effects were as follows; decrease or disappearance of ascites and edema of the lower limbs at high rates (26/37 and 4/4, respectively), usually within a week after treatment: decrease or stoppage of cancerous bleeding in 30 of 35 patients: decrease or disappearance of pain in most of the patients: and tumor regression in 26 patients with cancer of the breast, rectum, ileocaecum, thyroid gland, uterus, skin, etc. Histologically, the virus-treatment caused shrinkage of nuclei and vacuolization of the cytoplasma of tumor cells, but the degenerative changes of tumor cells were not so great as those after chemotherapy or radiotherapy. Infiltration of lymphocytes, fibrosis and collagenesis occurred around tumor tissues, where necrosis or exfoliation of tumor cells was frequently observed.

[Fluctuation and distribution of animal room temperature and the temperature in cages (author's transl)].

The temperature of various positions in an occupied animal room (mice, rats) including inside of cages were measured using a 50 channels thermal data recorder (step time 0.5 sec, 5 min intermittent through 24 hr and continuous) in a summer day. Any short periodical fluctuation of room temperature had practically no influence on the inside temperature of plastic cages. Against small diurnal fluctuations, stable vertical gradients (about 1 degree C between tops and bottoms of racks) were observed among one hour averages of room air temperatures. Air temperature in the cage fluctuated in larger scale. (up to 3 degrees C) For controlling animal room temperature, each of short periodical fractuation, diurnal change and spasal distribution should be separately concerrned.