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The objective of the present study was to reveal antitumour antibodies in sera of patients with small cell lung cancer (SCLC). The antibodies in sera of patients with SCLC and other tumours were detected by immunoblotting with whole extracts of SCLC cells as the antigen source. Sera of patients with various pulmonological disorders, irradiated during the liquidation of consequences of the Chernobyl nuclear power plant incident (a high-risk group in lung cancer), were also analysed. The present authors' found that SCLC sera contain a set (pattern) of antitumour antibodies which are rarely detected in sera of patients with cancers different from SCLC and very rarely, if ever, present in sera of healthy individuals. The sensitivity and the specificity of the pattern are equal to 80% and 91%, correspondingly. In the high-risk group in lung cancer, the frequencies of the antibodies are somewhat lower than the corresponding values in SCLC sera, but significantly larger than those in healthy sera. The findings of the present study create a basis for clinical application of the antitumour antibodies described.

In cancer, the retinal Ca(2+)-binding protein recoverin is a paraneoplastic antigen, the aberrant expression of which is capable of triggering the appearance of specific autoantibodies in the serum of patients with malignant tumors and the subsequent development of a paraneoplastic syndrome, cancer-associated retinopathy (CAR). The frequency of serum autoantibodies against recoverin (AAR), earlier determined at a rate of 15-20% in lung cancer, is much higher than the frequency of CAR syndrome, which is approximately 1%. In the present study, we estimated for the first time the frequencies of serum AAR in patients with various types of malignancies other than lung cancer. Patient biospecimens were collected to analyze for the presence of AAR. Additionally, various cell lines were cultivated and analyses were performed using Western blotting and RT-PCR. Results showed that in all cases tested, the AAR frequencies did not exceed 10%. Five AAR-positive patients with various types of cancer were available for ophthalmological investigation and only one of these patients had CAR syndrome. This result is consistent with the conclusion made in our previous studies of lung cancer that serum AAR do not necessarily trigger the development of CAR syndrome.

To date, many authors have described the presence of autoantibodies against various neuronal proteins, paraneoplastic antigens (PNA), in a serum of patients with different kinds of malignant tumors located outside the nervous system. These autoantibodies may cross-react with the corresponding PNA or their epitopes present in neurons and thus initiate the development of a variety of neurological disorders, paraneoplastic syndromes (PNS), even though the primary tumor and its metastases have not invaded the nervous system. Cancer-associated retinopathy (CAR) is a rare ocular PNS induced by autoantibodies against several retinal antigens, one of which is a photoreceptor calcium-binding protein, recoverin. Only several CAR patients with a few kinds of cancer (endothelial carcinoma, breast cancer, epithelial ovarian carcinoma) have so far been found to contain autoantibodies against recoverin in their sera. As for lung cancer, the majority of CAR cases mediated by anti-recoverin autoantibodies have been revealed in patients with the most malignant lung cancer, small cell lung carcinoma (SCLC), and only one similar case has been described for a patient with non-small lung carcinoma. The common feature of all these anti-recoverin-positive patients, irrespective of the type of cancer, is the presence of both the CAR syndrome and high titres (as a rule, more than 1:1000) of the underlying autoantibodies in their serum. In this study, we have used recombinant myristoylated recoverin to screen serum samples of 50 patients with SCLC by Western blot and revealed 5 individuals with low titres of anti-recoverin antibodies, who have no manifestation of a loss of vision. To our knowledge, this is the first report on the presence of low titre autoantibodies against recoverin in a serum of patients with cancer, but without visual dysfunction.

Fifty-three patients with lung cancer of different histological types and 72 with other lung diseases were examined by employing the panel containing 5 monoclonal antibodies (MAb) in the indirect immunofluorescence test (IFT). with tissue biopsy specimens, lung cancer could be revealed in 100% of patients with glandular carcinomas and adenocarcinoma of the lung, in 89% of those with small-cell carcinoma, and in 61% with squamous-cell carcinoma. With this, MAb reacted with cancer cellular membranes, by causing their fluorescence and failed to react and to cause the luminescence of inflammation cell membranes, the altered and intact bronchoalveolar epithelium in patients cancer and nontumoral diseases of the lung. IFT with MAb to lung cancerous surface antigens with the cells of tissue biopsy specimens may be a supplementation to cytological studies.

Concanavalin A-induced proliferation of spleen cells of C57B1/6 mice was inhibited by syngeneic normal bone marrow cells. Elimination of Ag-Eb-positive cells by panning was shown to result in markedly reduced inhibitory activity of bone marrow cells. To evaluate the role of Ag-Eb in natural suppressor activity, bone marrow cells were preincubated with different dilutions of MAE-15 monoclonal antibody and then added to spleen cells. The inhibitory effect of bone marrow cells decreased with the increasing concentration of the monoclonal antibody in a dose-dependent manner and nearly disappeared at a concentration of MAE-15 of 150 m micrograms/ml and 300 m micrograms/ml. In control experiments, bone marrow cells were preincubated with antibodies non-reactive with Ag-Eb under the same conditions. It is concluded that the decrease of natural suppressor activity after incubation of bone marrow cells with MAE-15 monoclonal antibody is specific for anti-Ag-Eb antibodies.

Murine monoclonal antibodies to human small cell lung cancer (SCLC) have been developed and partially characterized. Primary hybridoma clones were screened in the indirect immunofluorescence assay (IFA) on alive H417 cells. Then five clones (IgG1, IgG2a, IgG3 and IgM) non-reactive with normal human bone marrow cells and positively reactive with SCLC tumors were selected. The H417.3 antibody is directed against 47-50kD surface antigens of H417 cells. The antibodies are supposed to be applied for the immunodetection of SCLC metastases to bone marrow and immunotoxin preparations.

The effect of Actinomyces rimosus RNAase on the variolovaccine virus was studied. The inhibitory effect of the Actinomyces rimosus RNAase on the variolovaccine virus reproduction in the tissue culture cells was shown. In the experiments with the use of chick embryons and rabbits this effect was less pronounced. A 10 time increase in the infection multiplicity both in the tissue culture and the chick embryons had no noticeable effect on the level of the virus inhibition. It was supposed that the inhibitory effect of the RNAase on the variolovaccine was associated with impairment of the cell metabolism.

The effect of antibiotic 6734-21 on the viruses of variolovaccine, Herpes simplex, influenza and classical avian plague was studied on various experimental models. Antibiotic 6734-21 inhibited development of the variolovaccine virus in the tissue culture, in chick embryos, in rabbits with variolovaccine infection, as well as the development of the viruses of Herpes simplex, Aueski, and Newcastle diseases in the tissue culture. It had a virulicidic effect on the viruses of variolovaccine, influenza and classical avian plague.

A modification of the microbiological agar-diffusion method for rapid determination of gentamicin, sisomycin and kanamycin levels in the blood serum of patients is described. The decrease in the time for determination of the antibiotic levels in the serum specimens with the modified method was provided by the use of a higher inoculation dose of the test microbe, higher levels of the incubation temperature and an enriched nutrient medium. The assay time was decreased from 18 to 3--4 hours as compared to the routine agar-diffusion method.

The pharmacokinetics of sisomicin was studied on Wistar rats. The antibiotic was used in single or repeated doses of 12.5 and 25 mg/kg. The kinetic data of the antibiotic titration in blood serum within 1 and 24 hours of intramuscular administration of the drug were formalized with the use of a linear two-compartment model. The average values of the elimination constant and the constants of sisomycin transfer from the central compartment into the peripheral one were 0.64, 0.34 and 0.13 hours-1 respectively. The value of the apparent distribution volume in the central compartment was 0.38 ml/kg and that of the stationary and kinetic distribution volumes was 1.37 and 3.06 1/kg respectively. The value of the general clearance was 0.24 1/(kg.hour) and that of the sisomicin half-life was 8.7 hours. Comparison of the antibiotic levels estimated with a model and actually measured in the blood after repeated administrations revealed the drug cumulation. When the antibiotic was used in a dose of 25 mg/kg daily, its cumulation was observed earlier (by the 5th--8th day) than on its use in a dose of 12.5 mg/kg (by the 30th day). Irrespective of the dose, sisomicin cumulation was accompanied by prolongation of the antibiotic half-life in the rats.

The pharmacokinetics of sisomicin administered intramuscularly to rats in daily doses of 12.5 and 25 mg/kg for 30 days was studied. After a single administration of the drug in the above doses the highest and the lowest levels of sisomicin were observed in the kidney cortical layer and liver, respectively. The antibiotic level in the tissues rose with an increase in the antibiotic dose and duration of the drug use. The two-fold rise in the dose resulted in an elevation in the sisomicin level in the kidney cortical layer by 1.7 times, in the medullary layer by 3 times, and in the blood serum, lungs and spleen by 2.3, 1.2 and 1.5 times, respectively. After treatment with a dose of 25 mg/kg for 8 days the antibiotic level in all tissues studied was higher than that after the first administration of the drug: in the cortical and medullary layers of the kidneys by 5-7 times and in the blood serum and other tissues by 1.2-2 times. When sisomicin was used repeatedly in any dose, stabilization of or some decrease in the mean integral concentration of the antibiotic in the kidney cortical layer and a continuous increase of this value with respect to the medullary layer (up to the 30th day) were noted. The difference between the antibiotic levels in the kidney layers after the repeated administration of the drug was less pronounced than that after a single administration of the drug. The cumulation index of sisomicin in the kidney cortical layer persisted at the same level and that in the medullary layer gradually increased. In this connection it is concluded that correlation between the sisomicin nephrotoxic effect and the level of the antibiotic in the kidney cortical layer is more pronounced than that in the medullary layer.

The effect of 9 analogues of distamycin A was studied in a tissue culture with respect to the virus of a smallpox vaccine and classical avian plague. Three analogues of distamycin A (I, VI, VII) were studied in chick embryos with respect to the smallpox and influenza viruses. The analogues were characterized by a loss or decrease of the activity against the smallpox vaccine virus as compared to distamycin A. In contrast to distamycin A analogue VII had an inhibitory effect on influenza infection in chick embryos.