Small de novo duplication in the repeat region of the TATA-box-binding protein gene manifest with a phenotype similar to variant Creutzfeldt-Jakob disease.

A 20-year-old North American patient developed rapidly progressive cognitive decline and pronounced ataxia, a phenotype compatible with prion disease. No structural changes were found in the PRNP gene, which excludes genetic prion disease, but the patient's PRNP codon 129 Met/Met genotype is known to predispose to variant Creutzfeldt-Jakob disease (vCJD). Further studies identified an expanded allele with 55 CAG/CAA repeats in the TBP gene. The increase of trinucleotide repeat number in the coding region of the TBP gene has previously been associated with spinocerebellar ataxia type 17 (SCA17). The patient's unaffected parents and siblings show normal-size TBP alleles with 37-38 repeats. Haplotype and nucleotide sequence analyses clearly indicate that the mutation has occurred de novo on a paternal chromosome by insertion/duplication of a (CAA)(CAG)(CAA)(CAG)(15) sequence. This report presents a second fully investigated sporadic case of SCA17 occurring as a result of a DNA rearrangement within the polymorphic TBP trinucleotide repeat region. Our findings suggest that patients suspected of vCJD should undergo testing for SCA17, Huntington's disease and other neurodegenerative disorders having phenotypic similarities with vCJD.

[Neuroprotection in acute ischemic stroke. Practicability of guidelines for treatment]. / Neuroprotección en el ictus isquémico agudo. Factibilidad de un protocolo terapéutico.

INTRODUCTION: Fibrinolytic agents are effective in the treatment of acute ischemic stroke. However, logistic and clinical factors limit their use. Neuroprotective drugs pose less risks and can be used even before performance of computed tomography of the brain as they are not detrimental in hemorrhagic stroke. These aspects, in theory, will allow the use of neuroprotective drugs in larger number of patients. OBJECTIVE: To evaluate the feasibility of a neuroprotection protocol and the potential usefulness of citicoline in acute ischemic stroke. PATIENTS AND METHODS: Thirty seven patients admitted with a clinical diagnosis of acute ischemic stroke (later confirmed with computed tomography) received, within 12 hours of onset of symptoms, citicoline 500 mg intravenously in a single bolus daily for 7 days. Neurological outcome in this group was compared with a group of 37 patients admitted during the 6 month period before the initiation of the trial and not treated with citicoline. Groups were matched by National Institute of Health Stroke Scale (NIHSS) on admission. RESULTS: Patients treated with citicoline (aged 69+/-14 years) improved on their NIHSS from admission (5.7+/-4.2) to discharge (4.7+/-4.5), p= 0.015. The control group (aged 60+/-17 years) did not change between admission (5.7+/-4.3) and discharge (5.2+/-3.5), ns. Patients treated within 6 hours of admission (n= 12) had more substantial improvement, from 5.4+/-2.3 on admission to 3.9+/-2.9 at discharge, p= 0.008. There were no differences in vascular risk factor profile between the groups. Citicoline was well tolerated in every subject. CONCLUSIONS: A protocol of acute stroke management using neuroprotective agents presents clear logistic advantages allowing the inclusion of larger number of patients. Citicoline appears as a safe and potentially effective option.

Detection of Helicobacter pylori in human carotid atherosclerotic plaques.

BACKGROUND AND PURPOSE: Several lines of evidence point toward a relationship between infection and atherosclerotic vascular disease. Thus, infection and inflammation often precede ischemic neurological events. Transient alterations in coagulation and direct arterial invasion by certain microorganisms have been reported. Helicobacter pylori infection is the major cause of peptic ulcer disease and appears to be a risk factor for ischemic cerebrovascular disease. However, in contrast to other chronic infectious agents, H pylori has not been consistently isolated from atherosclerotic lesions. METHODS: We investigated the presence of H pylori in 38 atherosclerotic plaques obtained at carotid endarterectomy by using morphological and immunohistochemical techniques and a highly sensitive polymerase chain reaction method. We performed immunohistochemical detection of intercellular adhesion molecule-1, a marker related to inflammatory cell response. We also examined 7 carotid arteries obtained at autopsy from subjects without carotid atherosclerosis. RESULTS: H pylori DNA was found in 20 of 38 atherosclerotic plaques. Ten of the H pylori DNA-positive plaques also showed morphological and immunohistochemical evidence of H pylori infection. None of 7 normal carotid arteries was positive for H pylori. Intercellular adhesion molecule-1 was expressed in 75% of H pylori-positive plaques and in 22% of H pylori-negative plaques. The presence of the microorganism was associated with male sex but was independent of age, vascular risk factor profile, and prior neurological symptoms. CONCLUSIONS: H pylori is present in a substantial number of carotid atherosclerotic lesions and is associated with features of inflammatory cell response. This study provides additional evidence of the relationship between H pylori infection and atherosclerotic disease.

[The anti-idiotypic response to the experimental administration of the inactivated or live influenza virus]. / Antiidiotipicheskii otvet na vvedenie inaktivirovannogo ili zhivogo virusa grippa v éksperimente.

The injection of inactivated and live influenza virus into rabbits induces the formation of anti-idiotypic antibodies, appearing after anti-influenza hemagglutinins, in the blood. The presence of immune complexes antibody--anti-idiotypic antibody in the blood of the animals has been established. The booster immunization of the animals with influenza virus antigens produces a rise in the levels of both idiotypic and anti-idiotypic antibodies. The injection of autologous anti-idiotypic globulin into the primed animals ensures the induction of idiotypic and anti-idiotypic revaccinal reactions.

[The antigenic characteristics of influenza A viral strains circulating synchronously in 2 separated areas (the CzSFR--Saint Petersburg)]. / Antigennaia kharakteristika shtammov virusa grippa A, tsirkulirovavshikh sinkhronno na dvukh otdalennykh territoriiakh (ChSFR--Sankt-Peterburg).

A comparative study of the antigenic characteristics of influenza A (H1N1) and A (H3N2) virus strains isolated during the same epidemic season, 1989-1990, in St. Petersburg and CzSFR was carried out by routine serological methods and by cross-challenge of immunized mice. Antigenic differences were found only among serosubtype A (H1N1) strains isolated in different areas. The study was carried out in connection with potential occurrence of influenza epidemic outbreaks from local sources.

Molecular hybridization with DNA probes as a laboratory diagnosis test for influenza viruses: further investigations on the possibilities of the method.

The possibilities of the molecular hybridization test, i.e. test, i.e. using neuraminidase probes of different subtypes for subtype specific detection of influenza, as well as different probes (PA, M, NP) for type A specific detection of influenza viruses in infected cells were shown. The results of molecular hybridization in washings' analyses from patients during the outbreaks give us an opportunity to make some conclusions about the usefulness of the method in epidemic control of influenza morbidity.

Immunogenicity of a chromatographically concentrated influenza vaccine.

The immunogenicity of the Czechoslovak-made commercial vaccine Adinvira as well as that of the chromatographically concentrated vaccine Leningrad of Soviet origin was evaluated in an immunization project. The both vaccines were well tolerated after administration, the Soviet-made Leningrad brand featuring greater efficiency in eliciting an antibody response against influenza virus haemagglutinin.

[Molecular hybridization of nucleic acids as a method for the laboratory diagnosis of influenza in model experiments on cell cultures and in research on nasopharyngeal smears obtained from patients]. / Molekuliarnaia gibridizatsiia nukleinovykh kislot kak metod laboratornoi diagnostiki grippa v model'nykh éksperimentakh na kul'turakkh kletok i pri issledovanii nosoglotochnykh smyvov, poluchennykh ot bol'nykh.

DNA probes containing the nucleotide sequences of the conservative genes of influenza A virus (matrix, nucleoprotein and acidic polymerase genes) show their specificity with respect to the RNA of influenza A viruses in mammal tissue cell cultures (continuous spaniel kidney cell culture and primary calf kidney cell culture). The minimal amount of infected monolayer cells, permitting the detection of viral RNA, is 10(3). The results obtained in the study of nasopharyngeal washings make it possible to recommend the method of molecular hybridization for use in the epidemiological analysis in addition to virological and serological tests. The method of hybridization permits the detection of virus-specific RNA in the allantoic fluid of chick embryos in subculturing the materials under study even in those cases when hemagglutinating influenza virus cannot be isolated.

[Methodological aspects of studying chemical preparations in a model of experimental influenzal infection]. / Metodicheskie aspekty izucheniia khimiopreparatov na modeli éksperimental'noi grippoznoi infektsii.

Some methodologic approaches have been developed permitting most exhaustive characterization of antiviral and antitoxic activity of drugs in mice infected with toxigenic and nontoxigenic influenza A virus strains.

[Purification of a corpuscular influenza vaccine by means of immunoaffinity chromatography]. / Ochistka korpuskuliarnoi grippoznoi vaktsiny metodami immunoaffinnoi khromatografii.

Two immunoaffinity chromatographic methods for the purification of corpuscular influenza vaccine from the admixture of chick embryo components have been examined. The isolation of the virus on immobilized antiviral antibodies has proved to be unsuitable for preparative purposes. The method for the purification of the vaccine from ovalbumin with the use of immobilized anti-ovalbumin antibodies has proved to be highly effective. When introduced into guinea pigs in 3 injections, the vaccine purified by immunosorption has been found to produce no anaphylactic reactions.

[Immunobiological characteristics of impurities in corpuscular influenza vaccines]. / Immunobiologicheskaia kharakteristika primesnykh komponentov korpuskuliarnykh grippoznykh vaktsin.

Admixtures of free antigens have been shown to play the main role in the anaphylactogenic danger of vaccines. The immunogenic and anaphylactogenic action of such antigenic admixtures in corpuscular influenza vaccine can be observed after the immunization of animals in 2 or 3 injections. Host antigens incorporated into viral particles induce no anaphylactic reaction in guinea pigs after their immunization in 3 injections.

[Analysis of the immunochemical purity of modern influenza vaccines]. / Analiz immunokhimicheskoi chistoty sovremennykh grippoznykh vaktsin.

Corpuscular influenza vaccines have been found to contain chick embryo antigens differing from ovalbumin in their antigenic, immunogenic, and allergenic properties. The study has revealed that host antigens are present in vaccines in the form of free contaminants and as substances incorporated into viruses. The vaccine prepared by the method of sorption-elution on red blood cells with subsequent gel chromatography is characterized by the highest antigenic purity.

[Method for the cross protection of mice in studying the antigenic variability of the influenza virus]. / Metodika perekrestnoi zashchity myshei v izuchenii antigennoi izmenchivosti virusa grippa.

A modification of the method of cross protection of mice was developed for the study of influenza virus antigenic drift. This modification does not require a pre-adaptation of the virus to mouse lungs. The experiments of cross protection of immune animals carried out by the modified method demonstrated antigenic variability of the influenza A virus strains (H3N2) isolated in 1968-1983. Immunologically significant differences between influenza A/Hong Kong/68/ and A/Victoria/36/72 virus strains were detected. Subsequently, with isolation of more influenza virus strains immunologically significant differences were found between A/Victoria/36/72 and A/Leningrad/42/75 (an analogue of A/Scotland/840/74) strains, A/Leningrad/42/75 and A/Leningrad/399/76 (an analogue of A/Victoria/3/75) strains. The differences between influenza A/Texas/1/77 and A/Leningrad/527/80 (an analogue of A/Bangkok/1/79), A/Leningrad/385/80 (an analogue of A/Bangkok/1/79), and A/Leningrad/50/83, (an analogue of A/Philippines/2/82) strains were not immunologically significant.

[Cellular immune reactions to the multiple administration of a chromatographic inactivated influenza vaccine in an experiment]. / Kletochnye immunnye reaktsii na mnogokratnoe vvedenie inaktivirovannoi grippoznoi khromatograficheskoi vaktsimy v éksperimente.

The administration of inactivated chromatographic influenza vaccine to mice in three injections induced the formation of the pronounced clone of antigen-reactive lymphocytes, detected in the leukocyte blast transformation test. Slight fluctuations in the phytohemagglutinin level and lipopolysaccharide response in mice subjected to multiple immunization with the inactivated vaccine indicated that this preparation produced no damaging effect on the T- and B-lymphocyte populations.