Prenatal administration of lipopolysaccharide induces sex-dependent changes in glutamic acid decarboxylase and parvalbumin in the adult rat brain.

RATIONALE: Recent clinical studies suggest GABA-ergic system abnormalities as a neuropathological mechanism of schizophrenia. OBJECTIVES: In the present study, we examined the effect of chronic prenatal lipopolysaccharide (LPS) administration on immunohistochemical changes of glutamate decarboxylase (GAD67) and parvalbumin (PV)-expressing neurons in the medial prefrontal cortex and hippocampus of rats. RESULTS: These data demonstrated that prenatal LPS administration during the final 2 weeks of pregnancy induced schizophrenia-like behavioral symptoms, such as deficits in sensorimotor gating (prepulse inhibition) and impairments in social interactions and exploration, in adult offspring. Moreover, immunohistochemical analysis revealed that in our neurodevelopmental model of schizophrenia, decreases in the total number of PV- and GAD67-positive neurons in the medial prefrontal cortices of adult females prenatally exposed to LPS were observed, whereas these immunochemical changes were primarily detected in the hippocampus of males. Additionally, a decrease in PV-labeled axon terminals of GABA-ergic cells, likely reflecting the perisomatic inhibitory innervation of pyramidal neurons, was observed in the medial prefrontal cortices in both sexes. CONCLUSION: This study provided evidence of a key role for the GABA system in neurodevelopment associated with the etiopathogenesis of schizophrenia and showed that the observed changes are sex-dependent. Moreover, this study is the first to present a model of schizophrenia based on prenatal LPS administration, which not only produced behavioral abnormalities but also changed the cytoarchitecture of the GABA inhibitory system.

Prenatal stress leads to changes in IGF-1 binding proteins network in the hippocampus and frontal cortex of adult male rat.

Depression is a mental disorder of still unknown origin. Currently, much attention is paid to the potential influence of disturbances in the functioning of neurotrophic factors on the onset of this disease. Insulin-like growth factor 1 (IGF-1) is one of the most important growth agents affecting processes that are crucial for brain development. To date, there are no data showing the impact of prenatal stress on the family of six IGF binding proteins (IGFBP 1-6) that regulate IGF-1 bioactivity. The goal of this study was to investigate whether the decreased expression of IGF-1 in the frontal cortex (FCx) and hippocampus (Hp) of adult male rats following a prenatal stress procedure is related to changes in the IGFBP family. Our results show that rats exposed prenatally to stressful stimuli displayed depression-like behavior based on sucrose preference and elevated plus maze tests. In both cases, in the adult rat brain structures that were examined after the prenatal stress procedure, the IGF-1 protein level was reduced. Moreover, we observed changes of varying degrees in the levels of IGFBPs in stressed animals. A decrease in IGFBP-2 and IGFBP-3 accompanied by an increase in the IGFBP-4 concentration in the Hp and the FCx was detected. There were no differences in IGFBP-1 and IGFBP-6 brain levels between the stressed and control animals, whereas IGFBP-5 concentration was decreased in the Hp of prenatally stressed animals. This study demonstrated that stress during pregnancy may lead not only to behavioral disturbances but also to a decrease in IGF-1 level and the dysregulation of the IGF-1 binding protein network in adult rat offspring.

The prevalence of anti-rubella antibodies in women of childbearing age in Poland.

Congenital rubella is a clinically serious problem, which is due to maternal infection with rubella virus during the first trimester of pregnancy. It may result in spontaneous abortion or in fetal infection leading to fetal birth defect. Maternal anti-rubella antibodies have a protective effect and they may prevent congenital rubella. Vaccination of 13-year-old girls in Poland was introduced in 1989. Vaccination coverage is above 95%. The presence of anti-rubella antibodies in maternal blood >15 IU/ml is indicative for immunity to rubella. Thus, the aim of the study was the evaluation of anti-rubella antibody levels in women 15-30 years old. Samples of that sera were collected from six provinces in Poland. We have observed the decrease of anti-rubella antibody titer together with increasing age of tested women. Among 1289 investigated women 135 [10.5%] did not have protective levels of anti-rubella antibodies. We have noticed large decline in protective anti-rubella antibodies in young women (19-22 years of age), who are just entering their prime childbearing years.

Detection of enterotoxigenic Clostridium perfringens with a duplex PCR.

Two sets of primers designed to detect Clostridium perfringens phospholipase C (plc) and enterotoxin (cpe) genes in a single PCR reaction were applied to a collection of 64 predominantly food poisoning-related C. perfringens isolates. In-vitro enterotoxin synthesis was tested serologically after inducing sporulation. Of the 64 isolates, 26 were clearly enterotoxigenic; 16 were classified as potentially enterotoxigenic only as serological testing did not confirm enterotoxin production. Duplex PCR for diagnosis of enterotoxigenic C. perfringens from vegetative cultures can be a useful tool as fresh isolates often sporulate poorly or not all, giving rise to the possibility of false negative results by serological analysis.

Temporal nucleotide changes in pertactin and pertussis toxin genes in Bordetella pertussis strains isolated from clinical cases in Poland.

Growing number of Bordetella pertussis infections in 1997-1998 in Poland overshadowed the successful national vaccination program. This situation prompted us to investigate if this shift reflects changes in the B. pertussis population. We investigated the possible divergence in genes encoding pertussis toxin subunit 1 (PtxS1) and pertactin (P.69) in B. pertussis population strains during the period of 1960-2000. The pertussis toxin and pertactin variants (ptxS1B and prn1) were found in strains used for production of the whole-cell pertussis vaccine (WCV) production in Poland. Results of the study indicate that the ptxS1A-allele replaced the vaccine variant in 69% in the 1960s, and in 100% in 1990s, and although the prn1-allele was found in all strains from the 1960s and 1970s, after 1995 was gradually replaced by prn2 and prn4 variants. Presumably, vaccination could affect the population structure of B. pertussis in Poland and resulted in antigenic shift in both genes analyzed. Our findings may have implications for the composition of polish WCV and the currently licensed acellular pertussis vaccines.

Vaccination against hepatitis viruses in Poland.

At present, two etiologic varieties of viral hepatitis (VH) can be directly vaccine-preventable: VH type A and VH type B. In addition, VH type D can be prevented indirectly through vaccination against VH-B. The first commercially available vaccine against VH-B appeared in 1981 and was human plasma-derived. After several years, it has generally been replaced by a recombinant type of vaccines. The obvious benefits of vaccination against VH-B prompted its introduction into the national immunization program in Poland in 1989. At that time, vaccination was offered free of charge to high-risk groups: newborns of HBsAg-carrier mothers, health-care workers, students: at medical schools, nursing schools, medical technology schools, and caretakers at institutions for mentally retarded persons. However, similarly to the experiences of other countries, observations in Poland indicated that such a targeted strategy fails to induce major epidemiological changes. In 1989 and in 1993, the incidence of VH-B per 100000 was 40.3 and 34.6, respectively. In addition, during these years, the incidence of V-B per 100000 children aged 0-4 years was 20.0 and 38.4, respectively. It has been decided that vaccination against VH-B will be obligatory for all newborns beginning from 1993. Due to financial constraints, it has been introduced in three phases, and since 1996, all newborns in Poland have been vaccinated. Already in 1993, three additional risk groups have been offered vaccination: patients with chronic diseases, patients awaiting planned surgery, and persons coming into close contact with acute VH-B or chronically HBV-infected individuals. In 1999, the incidence of VH-B per 100000 was 9.1/100000, and it may be assumed that vaccination helped to decrease the incidence of VH-B in Poland. The country experience with vaccination against VH-A is still limited. At present, it is recommended for children and adolescents and people dealing with food distribution, as well as for several other groups of people, such as travellers or long-term visitors (soldiers, missionaries, diplomats) to the endemic regions of the world. It has also been recommended in connection with natural disasters such as floods occurring in a large area of Poland in 1997.

[Use of electrophoresis in polyacrylomide gel (SDS_PAGE) for evaluating IgG structure--the main component of human intravenous immunoglobulin]. / Zastosowanie elektroforezy w zelu poliakryloamidowym (SDS-PAGE) do oceny struktury czasteczek IgG--glównego skladnika preparatów ludzkich immunoglobulin do stosowania dozylnego.

For the assessment of the structure of IgG particles in the immunoglobulin preparation for intravenous use (Bioglobulin) electrophoresis in polyacrylamide gel (SDS-PAGE) was applied in place of filtration on Sephadex G-200 gel. The method serves for determination of the molecular weight of polypeptide chains under conditions of reduction. The method is rapid, sensitive and of high resolution. Six batches of the preparation were examined finding that IgG monomers and dimers accounted for over 90%, with IgG aggregates about 3% and degradation products about 1%. The obtained values comply with the recommendation of the WHO and requirements in the latest edition of Europea Pharmacopaes.

Molecular epidemiology survey of toxinogenic Clostridium perfringens strain types by multiplex PCR.

Toxin genotypes of 95 C. perfringens strains collected within a 45-year period were analysed by a multiplex PCR. A set of primers designed for 4 different genes encoding the alpha, beta, epsilon, and iota toxins was used in a single reaction with a sensitivity of gene detection of 200 fg for DNA extracted from pure culture. Most of the strains (97%) conformed to the A biotype, and the remaining to the C or E biotypes. For biotype determination, seroneutralization of lethality in mice was performed by intravenous injection. Toxin phenotype and genotype profile were concordant in 94% of strains. Our results documented the presence of rare toxin genotypes of C. perfringens in a Polish geographical region and indicated the suitability of multiplex PCR as a method supplementing classical techniques and providing better insight into the prevalence of toxinogenic C. perfringens strains.

Linker histones play a role in male meiosis and the development of pollen grains in tobacco.

To examine the function of linker histone variants, we produced transgenic tobacco plants in which major somatic histone variants H1A and H1B were present at approximately 25% of their usual amounts in tobacco chromatin. The decrease in these major variants was accompanied by a compensatory increase in the four minor variants, namely, H1C to H1F. These minor variants are smaller and less highly charged than the major variants. This change offered a unique opportunity to examine the consequences to a plant of major remodeling of its chromatin set of linker histones. Plants with markedly altered proportions of H1 variants retained normal nucleosome spacing, but their chromosomes were less tightly packed than those of control plants. The transgenic plants grew normally but showed characteristic aberrations in flower development and were almost completely male sterile. These features correlated with changes in the temporal but not the spatial pattern of expression of developmental genes that could be linked to the abnormal flower phenotypes. Preceding these changes in flower morphology were strong aberrations in male gametogenesis. The earliest symptoms may have resulted from disturbances in correct pairing or segregation of homologous chromosomes during meiosis. No aberrations were observed during mitosis. We conclude that in plants, the physiological stoichiometry and distribution of linker histone variants are crucial for directing male meiosis and the subsequent development of functional pollen grains.

[Coexpression of CD4 and CD8 antigens and the appearance of HLA-DR and CD25 receptors on lymphocytes as markers of immune activation in patients with HIV infection]. / Wspólwystepowanie receptora CD4 i CD8 oraz obecnosc receptorów HLA-DR i CD25 na limfocytach jako wskaznik pobudzenia ukladu immunologicznego u osób zakazonych HIV.

Results of quantitative determinations of peripheral blood lymphocytes presenting CD4 or simultaneously CD4 and CD8 antigens as well as HLA-DR and CD25 antigens in patients with different clinical stages of CD4+ and CD4+CD8+ cells were observed. The fall of CD4+CD8+ lymphocytes percentage was slight in the initial stages of infection but more sharp during the full-blown AIDS. The percentage of HLA-DR positive cells was higher in seropositive patients in comparison with controls and increased with the progression of HIV infection into AIDS. The CD25 expression was also higher in HIV-infected patients, however, it decreased in patients with late stages of AIDS. The observed disturbances could be caused by the direct destruction by replicating HIV or by severe abnormalities of immune system function.

[Presence of autoantibodies in patients infected with HIV]. / Wystepowanie autoprzeciwcial u osób zakazonych HIV.

The presence of serum autoantibodies directed against single-stranded DNA (ssDNA), RNA, histones, nuclear antigen SS-A, mitochondria and cardiolipin were investigated in 30 HIV-negative drug addicts (from years 1986-87), 30 addicts actually infected with HIV and 31 AIDS patients presenting with clinical symptoms indicating autoimmune disorders. Positive results were found in 12 (40%) drug addicts from years 1986-87, 5 (16.7%) actually infected and 16 (51.6%) AIDS patients. Autoantibodies were more often detectable in patients with thrombocytopenia 8/12 (66.7%) than in remaining 8 out of 19 subjects (42.1%) who presented dermatitis, hepatitis, pancarditis, ulcerative colitis and polyneuropathy. The prevalence of autoantibodies in all investigated groups were significantly higher than in controls-1/20 (3.3%).

[The effect of discontinuing intravenous opiate injections and methadone treatment on the status of the immune system in narcotic abusers with HIV]. / Wplyw przerwania dozylnego stosowania opiatów i zastosowania leczenia metadonem na stan ukladu immunologicznego u narkomanów zakazonych HIV.

The effect of discontinuation of injecting drug use and administration of methadone was investigated in 43 HIV-infected drug abusers. In 20 (46.5%) out to them an improvement in the immune status as measured by CD4+ lymphocyte percentage and CD4/CD8 lymphocyte ratio was observed, while remaining 23 persons (53.5%) showed stable or decreasing values of both parameters. In the control group which consisted of 23 persons who continued injecting drug use, only 3 (13%) out of the showed increase in the CD4+ lymphocyte percentage and CD4/CD8 lymphocyte ratio. It seems that discontinuation of injecting drug use may improve the function of immune system in HIV-infected drug addicts and could be an important factor in the approach for treatment of these patients.

[Antibody avidity in diagnosis of toxoplasmosis]. / Oznaczanie widnosci przeciwcial w diagnostyce toksoplazmozy.

The sequential changes in avidity of antibodies to Toxoplasmosis gondii were investigated. The values of avidity were observed to be significantly lower in serum samples drawn in early stages of infection than 3-4 months later and increasing with time of duration of the infection. A correlation was found between antibody avidity and antibody level measured in international units (IU/l), whereas, no correlation was observed between avidity, IU/l and antibody titers.

[Occurrence of free receptor for interleukin 2 in serum and quantitative determinations of CD25+ in patients infected with HIV]. / Wystepowanie wolnego receptora dla interleukiny 2 w surowicy oraz oznaczenia ilosciowe limfocytów CD25+ u pacjentów zakazonych HIV.

Serum soluble interleukin 2 receptor (sIL-2R) concentration and the percentage of lymphocytes presenting this receptor (CD25+) were investigated in 28 asymptomatic HIV carriers or patients with lymphadenopathy only and in 15 AIDS patients. The levels of sIL-2R were found to be higher in AIDS patients (mean 1060 U/ml) than in persons during the initial stages of infection (mean 750 U/ml) or controls (mean 470 U/ml). No significant differences in the quantity of CD25+ lymphocytes between these groups were observed, with the means of 1.0; 1.3 and 1.1, respectively. However, a decrease in percentage of these cells were found in patients with advanced HIV infection. Since sIL-2R is regarded as a marker of immune system activation its detection could be helpful in the assessment of the immune status impairment in HIV infected patients.

[Occurrence of autoimmune phenomena in persons infected with HIV.I. Pathogenetic aspects]. / Wystepowanie zjawisk autoimmunologicznych u osób zakazonych HIV. I. Aspekty patogenetyczne.

Autoimmune mechanisms presumably involved in the pathogenesis of HIV infection and AIDS are presented. The possible role of similarity between antigens of the major histocompatibility complex and viral antigens in the development of immune system impairment are discussed.