Social Cognition Impairments in Patients with Multiple Sclerosis: Comparison with Grade of Disability.

OBJECTIVES: Social cognitive impairments are an essential aspect of general disability in patients with multiple sclerosis (MS). They can manifest independently or in addition to physical deficits. AIM: To examine the impairment of social cognition and its potential relationship with the grade of disability in MS patients. SETTINGS AND DESIGN: Our study included 17 healthy controls and 36 patients with clinically definite MS (relapsing-remittent form) according to the McDonald Criteria (2010). The patients were divided into two groups - patients with Expanded Disability Status Scale (EDSS) <3.5 (N = 18) and those with EDSS ≥3.5 (N = 18). The neuropsychological battery included empathy assessment (Self-Compassion, "Reading the Mind") and theory of mind tests - ToM (Faux pas, cartoons). RESULTS: We did not register a change in self-assessment empathy in MS. Reading the Mind in Eye test showed a clear tendency for deterioration with increasing physical disability. The statistically significant difference (P < 0.05) between the results of controls and patients with EDSS ≥3.5 was registered. The tests for interpreting stories perceived in an auditory manner ("faux pas") showed a clear trend toward "failure" among patients (P < 0.05). The results of patients with high disability in ToM cartoons task were statistically worse (P < 0.01) both in comparison to those of controls and patients with EDSS <3.5. CONCLUSION: Our study found that, during the course of MS, deterioration of both social cognitive skills and basic cognitive abilities occurs, which is parallel to physical disability.

DNA double-strand breaks cooperate with loss of Ink4 and Arf tumor suppressors to generate glioblastomas with frequent Met amplification.

Glioblastomas (GBM) are highly radioresistant and lethal brain tumors. Ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) are a risk factor for the development of GBM. In this study, we systematically examined the contribution of IR-induced DSBs to GBM development using transgenic mouse models harboring brain-targeted deletions of key tumor suppressors frequently lost in GBM, namely Ink4a, Ink4b, Arf and/or PTEN. Using low linear energy transfer (LET) X-rays to generate simple breaks or high LET HZE particles (Fe ions) to generate complex breaks, we found that DSBs induce high-grade gliomas in these mice which, otherwise, do not develop gliomas spontaneously. Loss of Ink4a and Arf was sufficient to trigger IR-induced glioma development but additional loss of Ink4b significantly increased tumor incidence. We analyzed IR-induced tumors for copy number alterations to identify oncogenic changes that were generated and selected for as a consequence of stochastic DSB events. We found Met amplification to be the most significant oncogenic event in these radiation-induced gliomas. Importantly, Met activation resulted in the expression of Sox2, a GBM cancer stem cell marker, and was obligatory for tumor formation. In sum, these results indicate that radiation-induced DSBs cooperate with loss of Ink4 and Arf tumor suppressors to generate high-grade gliomas that are commonly driven by Met amplification and activation.

HsMCM2/BM28: a novel proliferation marker for human tumors and normal tissues.

HsMCM2/BM28 is a member of the family of minichromosome maintenance (MCM) proteins, which play a critical role in DNA replication by helping to ensure that DNA is replicated once and only once per cell cycle. The association of HsMCM2 with DNA replication suggested to us that it might prove useful as a new marker for cell proliferation. To test this possibility, we employed immunohistochemistry and immunoblotting to study HsMCM2 expression in both normal human tissues and primary human tumors. We found that HsMCM2 was detectable by immunoblotting in 97% of the studied tumors but in only 27% of the corresponding normal tissues. In normal tissues, the immunoblot signal was weaker than in tumors. Immunohistochemistry revealed that in normal tissues HsMCM2 is present only in proliferating cell nuclei. In most cases, tumor cell nuclei produced a stronger HsMCM2 signal than normal proliferating cell nuclei. Comparative studies revealed that antibodies against HsMCM2 stained fewer nuclei than antibodies against proliferating cell nuclear antigen but usually more than antibodies against Ki-67 (another proliferation-related antigen). Thus, the correlations between proliferation and antigenic signal are different for these three proteins. These results indicate that HsMCM2 is, indeed, a novel marker for proliferating cells. Further studies are required to determine whether the fact that HsMCM2 has a different correlation with proliferation and elevated staining intensity in tumor nuclei (compared to nuclei in normal proliferating cells) will permit it to be a more useful diagnostic and prognostic marker than proliferating cell nuclear antigen and Ki-67.

[The immunomodulating properties of a glucomacropeptide from whey. I. The stimulation of resistance in mice]. / Imunomodulirashti svoistva na gliukomakropeptid ot surovatka. I. Stimulirane na rezistentnostta pri mishki.

The immunomodulating effect on mice of three products glucomacropeptides obtained from whey with different carbohydrate and peptide components has been studied. After the preliminary application of the preparations at several doses the protective effect in infections with Salmonella typhimurium and Klebsiella pneumoniae increases to different extent. At lower doses fraction 3 increases in vitro the mitogen-induced proliferation of the thymus cells. The phagocytosis of the polymorphonuclear cells on the 24th hour after application of the three preparations is activated. The influence of the structurally different fractions on the immunoprotective effect is discussed.

[Determination of the nucleotide composition of Pasteurella multocida strains]. / Opredeliane nukleotidniia sustav na shtamove Pasteurella multocida.

Studied was spectrophotometrically the nucleotide composition of DNA of Pasteurella multocida strains along with studies on the nucleotide base ratio, the molar relations between nucleotide bases, the guanine/cytosine ratio in percent, and the specificity index adenine-tinin/guanine cytosine. The strains used were isolated from birds with various forms of fowl cholera (acute, atypic, and swelling of the wattles), and from calves with bronchopneumonia. Used were also mutants that were streptomycin dependent, obtained through induction with nitrosoguanidine. Close values were established of the nucleotide bases both with the individual groups of Pasteurella strains and with the mutants and their initial strains. The molar relations showed values around a unit, the guanine/cytosine ratio in percent varied from 40.14 to 43,54 and the specificity index varied from 1.25 to 1.49. Data showed that all studied strains and mutants belonged to one species - Pasteurella multocida, on the one hand, and their grouping could not be made on the basis of their nucleotide composition, on the other - contrary to some other indexes, such as biochemical activity, virulence, and behaviour to specific phages.

[Diagnostic value of the protein antigens of Br. abortus and Yersinia enterocolitica type 9]. / Diagnostichna stoinost na proteinovi antigeni ot Br. abortus i Yersinia enterocolitica tip 9.

Protein antigens were obtained from Br. abortus 99 and Yersinia enterocolitica, type 9, and were titered on guinea-pigs infected with a living culture from these microbes. It was proved that the guinea-pigs infected with Yersinia reacted with a skin-allergic reaction only to an antigen obtained from Yersinia and not from Brucella. Conversely, the animals infected with Br. abortus B-19 reacted during skin treatment only to an allergen from Brucella, but not with an allergen from Yersinia. In a rabbit anti-yersinia serum were proved precipitins through the immunodiffusion test against the protein allergen from Yersinia, whereas no Brucella precipitins were detected with a protein allergen. In anti-Brucella rabbit serum (Brucella amboceptor or agglutinative serum, no precipitins were proved with Brucella and Yersinia protein allergens. In a hiperimmune rabbit serum against Brucella and Yersinia were proved precipitins against a polysaccharide both from Yersinia and Brucella. It was adopted that protein antigens in the case of Brucella and Yersinia were specific and that specificity could be used for differentiation of these two infections.

[Pharmacological studies of 2-methyl-3(2-phenyl-3-methyl-tetrahydrooxazino)-propiophenone hydrochloride and 1-phenoxycarboxy-1-phenyl-2-methyl-3(2-phenyl-3-methyl-tetrahydrooxazino)-propane hydrochloride compounds]. / Farmakologichni prouchvaniia na suedineniiata 2-metil-3(2-fenil-3-metil-tetrakhidrooksazino)-propiofenol khidrokhlorid i 1-fenoksikarboksi-1-fenil-2-metil-3(2-fenil-3-metil-tetrakhidrooksazino)-propan khidrokhlorid.

The authors used the compounds 2-methyl-3)2-phenyl-3-methyl tetrahydroxasino)-propiophenone hydrochloriad (code PsI) and 1-phenoxycarboxy-1-phenyl-2-methyl-3 (2-phenyl-3-methyl-tetrahydroxasino-propan hydrochlorid(code P3) and carried out the following studies: influence of tripamine, corasol and strichnine seizures 1-phenoxycarboxy--1-phenyl-2-methyl--3 (2-phenyl--3-methyl-tetrahydroxasino) propar hydrochlor (Code P8) in white mice, effect on the hypertensive action of reserpine in white rats, investigations on the analeptic action in urethanized cats as well as on the analgetic effect, examined both by the test of "hot plate" and the method of Hendreshot-Forsaith. The examined compounds, administered in a dose of 1/6 of LD50, showed analgetic effect weaker than that of the preparations Morphinum hydrochloricum and Analigin, but their analeptic effect was less manifested that of of corasol. Similar to MAO-inhibitor-oproniazid although in smaller degree the compound PS1 potentiated tripamine seizures and inverted the hypotensive effect of Reserpine into hypertensive.

[Live vaccine against salmonellosis in swine]. / Zhiva vaksina sreshtu salmoneloza po svinete.

A live vaccine was produced against salmonellosis in pigs, using a mutant strain 3--297 of Salmonella cholerae suis. The vaccine proved fully innocuous at the rate of 1 cm3 to guinea pigs and at 2-5 ml to pigs, and 15 days following injection the vaccinal strains was no longer isolated from the test animals. Guinea pigs injected singly at the rate of 1cm3 of the vaccine and infected on the 12th day with a pathogenic Salmonella cholerae suis strain died up to 12 per cent (the control ones up to 91 per cent). Pigs vaccinated singly or twice at the rate of 2 cm3 and infected on the 20th day (i/v) with a pathogenic strain of Salmonella cholerae suis died up to 14 per cent (the control ones up to 80 per cent).

[Production of live attenuated vaccine against colibacillosis in pigs]. / Vurkhu poluchavaneto na zhiva atenuirana vaksina sreshtu kolibakterioza po prasetata.

Two strains of beta-hemolytic Escherichia coli, p-0141 and i-0149 were used to obtain mutant E. coli organisms with unchanged cultural, morphological, biochemical, and serological properties. The mutants proved apathogenic for albino mice at intravenous injection of a 6-hour broth culture at the rate of 0.3 cm3 or an endotoxin in the same dose. Neither were they enteropathogenic for pigs when inoculated into intestinal segments. They could be used as vaccinal strains.

[Experimental transmission of antibiotic resistance in chicks]. / Eksperimentalno prenasiane na antibiotichna ustoichivost pri pileta.

Multi-drug resistance of Salmonella heidelberg was transmitted to normal intestinal flora (E. coli organisms were resistant to ampicillin, streptomycin, tetracycline, erythromycin, and oleandomycin. The donor strains of Salmonella heidelberg used in the experiment was a carrier of the following nine markers of resistance: ampicillin, streptomycin, chloramphenicol, kanamycin, neomycin, novobiocin, tetracycline, erythromycin, and oleandomycin. The donor strains of Salmonella heidelberg used in the experiment was a carrier of the following nine markers of resistance: ampicillin, streptomycin, chloramphenicol, kanamycin, neomycin, novobiocin, tetracycline, erythromycin, and oeandomycin, novobiocin, tetracycline, erythromycin, and oleandomycin. The resistance to drugs was transmitted with the oral administration of the donor strain at the preliminary neutralization of the action of hydrochloric acid in the stomah secretion through sodium bicarbonate (1 cm3 of a 10 per cent sol.) an hour prior to feeding the birds with Salmonella heidelberg (1 cm3 of 10(10). In other experiments carboneum tetrachloratum was injected at rates of 0.08 to 0.15 cm3 (acocrting with the body weight of birds) one day prior to infection, followed by the administration of 0.20 to 0.40 cm3 of a 2 per cent solution of omnopon. Escherichia coli organisms acquired new markers of resistance--to chloramphenicol, kanamycin, neomycin and novobiocin. The level of resistance proved equal with that to the donor strain. A total of 1.8 to 5.4 per cent of the intestinal E. coli investigated proved to be carriers of the indicated markers of resitance. Highest level in acquiring markers of multi-drug resistance (13 per cent) showed E. coli organisms isolated from the liver of birds injected additionally with C. tetrachloratum omnopon.