[Design of Novel Carboxamides of Eremomycin and Vancomycin with 4- or 3-Amino Methyl Phenyl Boric Acid and Their Investigation].

Amidation of the end carboxyl group of eremomycin and vancomycin by pinacolinic 4- or 3-amino methyl phenyl boron acids esters in the presence of the condensing reagent PyBOP resulted in formation of novel carboxamides of the antibiotics (IIIa-VIa). After elimination of the pinacolinic group under mild hydrolysis in weak acid aqueous medium there formed the respective derivatives with a residue of the nonprotected boric acid (III-VI). It was shown that the activity of the 4-substituted derivatives of the borole-containing eremomycin and vancomycin practically was the same as that of the initial antibiotics, while higher than that of the respective 3-substituted derivatives of the borole-containing derivatives against 8 strains of grampositive bacteria.

[The characteristics of the clinical course of lymphosarcomas in conformity with the morphological variants of the WHO and Working Formulation classifications]. / Osobennosti klinicheskogo techeniia limfosarkom v sootvetstvii s morfologicheskimi variantami klassifikatsii VOZ i rabochei formulirovki.

Histological and cytological preparations of the lymph nodes, spleen, bone marrow and other tumors from 140 patients with different variants of lymphosarcomas were subjected to a comparative clinicomorphological analysis. The data obtained were correlated to the WHO classification and the working formulation of non-Hodgkin's lymphomas intended for clinical use. It has been found desirable that the working formulation may be used for predicting the disease course and elaboration of the programs of lymphosarcoma treatment.

[Production and antineoplastic activity of new asymmetric azines on the rubomycin base]. / Poluchenie i protivoopukholevaia aktivnost' novykh nesimmetrichnykh azinov na osnove rubomitsina.

New alkulidene hydrazones of rubomycin (daunorubicin) with the linear or branched chain of the carbon atoms were studied: rubomycin 13-(hexylidene-2")-hydrazone, rubomycin 13-(heptylidene-3")-hydrazone and rubomycin 13-(4"-methylpentylidene-2")-hydrazone. Alkylidene hydrazones of the formamidine derivatives were also studied: 13:cyclohexylidene hydrazone of 3'-desamino-3'-dimethylformamidine rubomycin and 13-(5"-oxypentyliden-2") hudrazone of 3'-desamino-3'-dimethylformamidine rubomycin. The latter two alkylidene hydrazones were modified twice. It was found that after a single intravenous administration to tumor-free mice the new substance had the same or lower toxicity as compared to that of rubomycin. Antitumor activity of the substances against lymphosarcoma LIO-I was studied comparatively with that of the initial rubomycin. It was shown that the molecule modification at C-13, as well as simultaneous modification at C-13 and the sugar amino group resulted in lowering of the antitumor activity in comparison to that of the starting rubomycin.

[Beta-glucuronidase activity and the cellular ultrastructure of the lymph nodes in malignant non-Hodgkin lymphomas]. / Aktivnost' beta-gliukuronidazy i ul'trastruktura kletok limfaticheskikh uzlov pri zlokachestvennykh nekhodzhkinskikh limfomakh.

Lymphoid elements from lymph nodes of malignant non-Hodgkin's lymphomas were studied by the methods of beta-glucuronidase cytochemistry, scanning, and transmission electron microscopy. The number of lysosomes, more prominent in nonmature variants, was found to decrease.

[Comparative experimental studies of the combined use of vaccines, interferon and interferon inducers in neurovirus infections]. / Sravnitel'nye issledovaniia po éksperimental'nomu izucheniiu sochetannogo primeneniia vaktsin, interferona i induktorov interferona pri nekotorykh neirovirusnykh infektsiiakh.

Comparative investigations of the combined use of vaccines and interferon in tick-borne encephalitis, herpes, and acute encephalomyelitis of man showed that up to 78% of animal protection against 10--50 LD50 of intraperitoneally inoculated viruses could be achieved. Vaccination alone provided up to 56% survival of the infected mice, while administration of interferon subcutaneously or intraperitoneally in a dose of 800 units (53,300 units per 1 kilo body weight) 18--20 hours before virus gave a survival rate of 36%. The use of vaccine in combination with an interferon inducer, phage of f2 RNA, in tick-borne encephalitis gave up to 75% survival of the infected mice. Four hours after administration, interferon could be detected in mouse sera in a concentration up to 640 units/ml which in immune mice accumulated more rapidly and remained at a higher level 18 hours after inoculation of the inducer.

[Pathomorphological characteristics of the experimental infection in animals infected with viruses of the rabies antigenic group]. / Patomorfologicheskie osobennosti éksperimental'noi infektsii u zhivotnykh, zarazhennykh virusami antigennoi gruppy beshenstva.

Comparison of pathomorphological lesions in the brains of white mice inoculated with viruses isolated in Africa from shrews, in America from bats, in Czechoslovakia from rodents (6 strains) and classified into the rabies group, with those observed in the same animal species infected with street rabies virus and virus of human acute encephalomyelitis (HAE) established the peculiar features of the reactive processes distinguishing these infections from each other. In contrast to the reactions after inoculation with street rabies virus and HAE, 24 hours after inoculation of white mice with Lagos bat, Ib An 27 377, 297 BF, 548 BF, 808 BF, 482 SG, 598 SG, and 638 SG strains hemorrhagic foci were observed; within 48 hours multiple perivascular cuffs were formed in the brain, and degeneration of the Ammon horn down to its disappearance and formation of multiple voids in the brain tissue were observed. Cytoplasmic inclusions in neurons of the cerebrum cortex and Ammon horn in the form of small paired formations with a pinpoint basophilic granule inside could be detected 24 hours postinfection. Later in the disease, the number of inclusions found diminished sharply.

[Chronic encephalomyelitis in white rats and guinea pigs]. / Khronicheskii éntsefalomielit u belykh krys i morskikh svinok

During a 2-year observation of white rats and guinea pigs infected with human acute encephalomyelitis virus a typical picture of the disease was observed with exacerbations and remissions quite characteristic of chronic forms of multiple encephalomyelitis and multiple sclerosis of man. The presence of the virus in animals and marked pathomorphological lesions in the central nervous system were shown not to prevent remissions. The evidence of association of chronic infection with long-term viremia is also important.

[Study of the antigenic relationship of different strains of the rabies group viruses]. / Izuchenie antigennogo rodstva raznykh shtammov virusov gruppy beshenstua

In neutralization tests in animals close antigenic relationship between human virus of acute encephalomyelitis (AEM) and viruses (297 and 598 SG strains) isolated from wild rodents in Czechoslovakia was first established. At the same time, poor antigenic relationship of human AEM virus to viruses isolated in Africa from bats (Lagos bat) and from shrews (YbAn 27377) was demonstrated. Certain differences in the antigenic properties of viruses isolated in Africa and in Czechoslovakia were found. These studies indicate the existence of many varieties in the rabies virus group. Ferther accumulation of data concerning different viruses of the rabies group is necessary as they may be helpful for elucidation of the pathology of certain neuroinfections due to viruses of this group as well as for creation of the necessary collection of the investigated strains for preparation of rabies vaccines.

[Study of viremia in experimental neuroviral infections]. / Izuchenie virusemii pri eksperimental'nykh infektsiiakh

Study of viremia in susceptible experimental animals showed all the blood fractions to take part in the infectious process both in acute diseases and in the chronic course of infections caused by various neuroviruses. Thus in animals infected with human acute encephalomyelitis, tick-borne encephalitis, lymphocytic choriomeningitis viruses viremia was observed throughout the entire short period of infection terminating fatally, as a rule. In such cases viremia was of a mixed character, the viruses being found in all blood fractions. The intensity of viremia and the degree of involvement of plasm and blood cell elements into the infectious process may depend upon the animal species, virus strains, form of the disease (acute, chronic). In chronic encephalomyelitis in rats and guinea pigs infected with human acute encephalomyelitis virus viremia are observed for two years (the observation period). In chronic encephalomyelitis blood cells were more actively involved in the infectious process. Virus was found in leukocytes and erythrocytes more frequently than in plasm, though the total amount of virus in the blood was much lower than that in the acute form of this disease. Sequential multiple passages of AEM virus from the blood to the brain in experiments with some strains resulted in intensive viremia thereby demonstrating the possibility of AEM adaptation to the blood tissue.