Immunologic Predictors of Liver Transplantation Outcomes in HIV-HCV Co-Infected Persons

Liver disease is a leading cause of mortality among HIV-infected persons in the highly active anti-retroviral therapy (HAART) era. Hepatitis C Virus (HCV) co-infection is prevalent in, and worsened by HIV; consequently many co-infected persons require liver transplantation (LT). Despite the need, post-LT outcomes are poor in co-infection. We examined predictors of outcomes post-LT. Immunologic biomarkers of immune activation, microbial translocation, and Th1/Th2 skewing were measured pre-LT in participants enrolled in a cohort of HIV infected persons requiring solid organ transplant (HIVTR). Predictive biomarkers were analyzed in Cox-proportional hazards models; multivariate models included known predictors of outcome and biomarkers from univariate analyses. Sixty-nine HIV-HCV co-infected persons with available pre-LT samples were tested: median (IQR) CD4+ T-cell count was 286 (210–429) cells mm^-3; 6 (9%) had detectable HIV RNA. Median (IQR) follow-up was 2.1 (0.7–4.0) years, 29 (42%) people died, 35 (51%) had graft loss, 22 (32%) were treated for acute rejection, and 14 (20%) had severe recurrent HCV. In multivariate models, sCD14 levels were significantly lower in persons with graft loss post-LT (HR 0.10 [95%CI 0.02–0.68]). IL-10 levels were higher in persons with rejection (HR 2.10 [95%CI 1.01–4.34]). No markers predicted severe recurrent HCV. Monocyte activation pre-LT may be mechanistically linked to graft health in HIV-HCV co-infection.     

Human chromosome variation: the discriminatory power of Q-band heteromorphism (variant) analysis in distinguishing between individuals, with specific application to cases of questionable paternity.

The chromosomes from 57 persons were analyzed by means of quinacrine fluorescent staining in order to assess the amount of variation and the discriminatory power of Q-band heteromorphism analysis. Chromosomes 3, 4, 13, 14, 15, 21, 22, and Y of each person were visually compared to those of 56 others, for a total of 1,596 comparisons. No two persons were found to have the same set of variants. The number of differences between chromosomes for each comparison ranged from 2 to 12 out of a possible total of 14 for females and 15 for males. Relatives were also distinguishable, and differences ranged from two to seven. We used the frequency with which each chromosome was useful for telling two people apart, and estimated the probability of finding two persons with the same set of quinacrine variants as .0003. Distinctly different heteromorphisms were found in the 39 unrelated persons for each of the chromosomes examined. In this small population, the number of different sets of variants observed for chromosomes 3, 4, 13, 14, 15, 21, 22, and Y were six, seven, 27, 16, 20, 15, 24, and five, respectively, for a total number of possible combinations of 1.14 X 10(15). As a test of the usefulness of chromosome heteromorphisms in paternity cases, 12 father-mother-child trios of virtually certain paternity, owing to the father-child segregation of a rare structural rearrangement, were coded and recombined at random to produce 120 cases of uncertain paternity. When the code was broken, 108 "alleged fathers" had been excluded correctly and the 12 biological fathers had been included correctly.     

Clinical significance of oxidation and acetylation genetic polymorphism in patients with hyperthyreosis

INTRODUCTION: The relationship between genetically determined polymorphic oxidation and acetylation and susceptibility to some disease was aroused much interest. The aim of our study was to evaluate whether patients with hyperthyreosis differ from healthy persons in their ability to oxidize sparteine and acetylate sulphadimidine as model drugs. Oxidation and acetylation were estimated in 48 patients with hiperthyreosis. MATERIAL AND METHODS: The control group consisted of 160 healthy volunteers for comparison of oxidation phenotype and 60 healthy volunteers for comparison of acetylation phenotype. The phenotyping of oxidation revealed two distinct populations among 40 patients with hyperthyreosis: 38 persons (95%) were extensive metabolizers (EM) of sparteine and 2 persons (5%) was poor metabolizers (PM). In 160 healthy persons (91.2%) were EM and 14 persons (8.8%) were PM. The difference between frequency distribution of PM and EM in healthy persons and in patients with hyperthyreosis was not statistically significant. RESULTS: The phenotyping of acetylation showed among 48 patients with hyperthyreosis 8 persons (13%) were rapid acetylators (RA) and 40 persons (87%) were slow acetylators (SA). In 60 healthy volunteers the phenotype of rapid acetylation was observed in 31 persons (51%) and slow acetylation in 29 persons (49%). Relative risk (odds ratio) of development of thyroid diseases was 5.34 times higher for SA in comparison to RA. The prevalence of SA among patients with hyperthyreosis in comparison to healthy volunteers was statistically significant (p < 0.0002). CONCLUSIONS: The results of our study may suggest that slow acetylation phenotype is associated with increased risk of the development of hyperthyreosis.     

Broad specificity of virus-specific CD4+ T-helper-cell responses in resolved hepatitis C virus infection

Vigorous virus-specific CD4+ T-helper-cell responses are associated with successful control of hepatitis C virus (HCV) and other human viral infections, but the breadth and specificity of responses associated with viral containment have not been defined. To address this we evaluated the HCV-specific CD4+ T-helper-cell response in HCV antibody-positive persons who lack detectable plasma viremia, and compared this response to that in persons with chronic HCV infection. Peripheral blood mononuclear cells were stimulated with HCV proteins, followed by measurement of HCV-specific CD4+ T-cell responses to a comprehensive set of overlapping HCV peptides by intracellular gamma interferon production. In three persons with resolved HCV infection studied in detail, 13 to 14 epitopes were targeted, but none was recognized by all three. The 37 defined epitopes were predominantly distributed among the HCV proteins core, NS3, NS4, and NS5. In an expanded analysis of responses to these proteins in persons with resolved infection, an average of 10 epitopes was targeted, whereas in persons with chronic viremia never was more than one epitope targeted (P < 0.001). This comprehensive analysis of the breadth and specificity of HCV-specific T-helper-cell responses indicates that up to 14 viral epitopes can be simultaneously targeted by circulating virus-specific CD4+ T helper cells in a controlled human viral infection. Moreover, these data provide important parameters for evaluation of candidate HCV vaccines, and provide rationale for immunotherapy in chronic HCV infection.     

Role of dopamine in the peripheral mechanisms of respiration control

Under clinical conditions, we studied the interaction between dopamine (DA) metabolism and hypoxia stimulationrelated ventilatory responses (HVR) before and after adaptation to periodical hypoxic episodes. Thirty-seven young and elder persons were tested; among elder tested subjects there were patients with Parkinson’s desease treated or not treated with DOPA-DA precursor-containing drugs (levoDOPA/carbiDOPA). We measured the HVR indices and DA and DOPA contents in the venous blood of tested persons before and after a 14-day-long hypoxic training. The highest indices of the ventilation sensitivity to hypoxia together with the lowest above-mentioned chemical indices were observed in young persons. An increase in the DA and DOPA levels in the venous blood were observed concurrently with suppression of the ventilation responses to hypoxic episodes. After a course of periodical hypoxic sessions, we observed in all groups opposite dynamics of DA and DOPA metabolism. An increase in the DA level in young persons and a trend toward its decrease in older healthy persons and parkinsonian patients was nevertheles accompanied by an HVR increase in all groups. Possible relations between the DA metabolism indices and peripheral mechanisms of respiratory control are discussed.     

Efficacy of the per os immunization and reimmunization of man with staphylococcal anatoxin]

By double immunization of 72 persons and single reimmunization of 38 persons per os with tablets containing 100 BU of purified concentrated staphylococcus toxoid (PCST) it was revealed that this immunization was harmless and the immunological response was adequate. The tablets were intended for application through the oral mucosa (oral) or the intestinal tract (enteral); the immunological response depended on the dose of the preparation and the scheme of administration. A high sensitization of healthy persons examined to staphylococcus was found. There was a tendency to reduction of hypersensitivity after the immunization with staphylococcus toxoid (examination in 6 months) and activation of reactions after the antigen administration (examination in 14 days).     

Somatic mutagenesis at T-cell receptor locus in inhabitants of radiation polluted regions as a result of the Chernobyl disaster

In the period of 2001-2004, frequency of cells bearing mutations at T-cell receptor (TCR) locus was assessed in 553 inhabitants of radiation polluted regions of the Russian Federation and 154 unexposed control persons. The inhabitants were divided into three groups according to age at the moment of the Chernobyl disaster and 137Cs pollution density: 1) in utero, 37-555 kBq/m2; 2) 0-14 years old, 20-555 kBq/m2; 3) 18 and more years old, highest 137Cs density (185 more than 555 kBq/m2). The most intense changes of the TCR-mutant cell frequency were observed in the group of persons exposed to ionizing radiation in utero. The mean frequency of the mutant cells was higher in the first group than in age-matched control group by about 1.5-fold: 4.0 x 10(-4) vs 2.7 x 10(-4) accordingly (p < 0.0001). Elevation in the mean TCR-mutant cell frequency was less expressed in group of inhabitants aged 0-14 years at the moment of irradiation start: 1.3-fold increase in comparison to age-matched control (3.8 x 10(-4) vs 2.9 x 10(-4), p = 0.0002). It was not found significant differences in mutant cell frequencies between control group and adults consisting in the third group (18 and more years old at the moment of the Chernobyl accident). The changes of the TCR-mutant cell frequency in persons exposed in pre- and postnatal periods differ not only quantitatively, but qualitatively. In the fist case all persons react to irradiation by increasing number of the TCR-mutant cells in some degree. In the second case - only a part of population. Proportion of reacting persons depends on age at the start of irradiation and, perhaps, on dose absorbed. The TCR-mutant frequency was significantly higher in persons with benign tumors of different localizations and nodules in thyroid gland than in persons without this pathology.     

The prevention of HIV infection and other blood-contact diseases among intravenous narcotic users in Nizhniy Novgorod within the framework of the Harm Reduction program

The results of the development and realization principles of the project on the decrease of harm, envisaging work in three directions (the determination of the technology of using drugs, the exchange of syringes/needles and other accessories, as well as laboratory examination for the presence of antibodies to HIV, hepatitis B and hepatitis C viruses and consultations of narcologists). 1075 injecting drug users took part in this project. Out of 611 participants filling-in the questionnaires, 338 persons underwent tests for HIV and 3 of them were found to be HIV-infected; out of 305 persons screened for the presence of markers of hepatitis B virus, positive results were obtained in 98 (32% of cases); in 218 (65%) out of 335 persons antibodies to hepatitis C virus were found (49 persons, i.e. 14%, had hepatitis C registered in the medical history and in the rest antibodies were detected for the first time). The preventive program of the decrease of harm was assessed as effective.     

Derivation of the short form of the Oral Health Impact Profile in Spanish (OHIP-EE-14)

doi: 10.1111/j.1741‐2358.2012.00613.x
Derivation of the short form of the Oral Health Impact Profile in Spanish (OHIP‐EE‐14) Background and Objective: The Oral Health Impact Profile is the most frequently used and validated of the Oral Health Quality of Life instruments. Several short versions have been developed; and a validation of the OHIP‐49 in Spanish has been published. The objective was to develop the short version of the Oral Health Impact Profile in Spanish (OHIP‐EE‐14). Methods: Cross‐sectional study. One hundred and thirty‐one persons aged ≥60 years attending a social centre for the elderly, residents of a nursing home and persons seeking dental care at a dental school in Mexico City were interviewed and examined. The validity of each of the 49 questions was evaluated, and, to construct the short version, 14 items were selected. The perceived need for dental treatment, number of teeth, presence of coronal caries, root caries, presence of dental plaque and utilisation of removable prosthesis were measured. Internal consistency, repeatability and discriminant validity were calculated. Results: The OHIP‐EE‐14 was reliable (Cronbach’s‐α = 0.918, ICC = 0.825). Significant associations were found between OHIP‐EE‐14 and the number of teeth and perceived need for dental treatment. Conclusions: The OHIP‐EE‐14 is a reliable and valid instrument and can be used in subjects aged 60 years and over from Mexico City.     

Cytogenetic effects of methyl isocyanate exposure in Bhopal

Summary Among human survivors following the methyl isocyanate (MIC) gas tragedy the major complaints have been related to deep-seated suffocation, terrible pain in breathing, and severe ocular irritations. In order to assess the possible genetic effects we have used lymphocyte cultures and screened chromosomes by two techniques; one by looking for chromosomal aberrations and the other by estimating sister-chromatid exchange (SCE) frequencies. Both these paramaters are good indicators of genetic damage in chromosomal DNA. SCE frequencies in lymphocytes have been increased more than three times in MIC-exposed persons. The results were compared to two groups of controls (one group comprising persons present in the same house; the second group of persons were chosen from distant places, 20–50 km away from the incident). Chromosomal breaks have been observed in 10 out of 14 MIC-affected people (71.4%) studied while only 6 out of 28 (21.4%) controls had chromosomal breaks. Some MIC-exposed persons had chromatin bodies in addition to the normal 46 chromosomes. These observations suggest that chromosomal DNA has been damaged.     

Serum enzymes and HBsAg in families with viral hepatitis

Examinations of all families affected with viral hepatitis confirmed by enzyme screening tests by means of incubation and also by the test for HBAgs were carried out in a town district in the course of 7 years. 1. After triple biochemical examinations repeated always after 14 days, changes in the serum enzymes (SGPT, ALD, LDH) were stated in 15% cases from the total of 4328 persons from 1332 families. In the control group no changes were found. 2. From the number of 2215 persons from 726 families 32% were HBAgs-positive in CFT. Simultaneous evidence of HBAgs and enzymes changes were stated in 162 persons (7,4%). 3. Changes in the enzymes as well as simultaneous evidence of HBAgs were especially stated in children. Findings of HBAgs alone prevailed in the adults (P greater than 0,001).     

Epidemiology of disaster. The Donner Party (1846-1847)

I examined the pattern of mortality in the Donner Party, a group of emigrants who became trapped with inadequate food stores in the winter snows of the Sierra Nevada mountains in 1846-1847. The party consisted of 90 persons; the median age was 19.5 years (range, 1 to 70), 55 (61%) were male, and 72 (80%) were traveling with family members. Of the 90 persons, 42 (47%) died. Multivariate regression analysis indicated that age was the most important mortality risk factor. The lowest mortality (10%) was seen in the 6- to 14-year age group, and the highest was for persons younger than 6 years (relative risk = 6.6; 95% confidence interval [CI], 2.3 to 9.6) and persons 35 years or older (relative risk = 8.4; 95% CI, 3.4 to 10.2). Persons traveling without other family members had a relative risk of 2.0 (95% CI, 1.0 to 2.5). Men and boys were also at increased risk (relative risk = 2.0; 95% CI, 1.0 to 2.9). These factors can identify persons at increased risk for mortality in nutritionally stressed populations, and efforts to maintain intact family structures may improve survival.     

Study of the effect of the sera of patients with rheumatism on the blast transformation in the mixed lymphocyte culture]

The authors studied the influence of the blood sera of 23 patients suffering from rheumatism on blast-transformation of lymphocytes obtained from healthy persons, in mixed cultures: 4 sera stimulated it, 5--depressed, and 14 produced no effect. Among patients whose sera depressed the blast-transformation persons with a more severe cardiovascular insufficiency prevailed. The content of IgG, IgM and alpha2-globulins in these sera was greater.     

Human acrocentric chromosomal associations in old age

Associations of satellite chromosome fibres of acrocentric chromosomes of the DD, GG and DG types were studied in persons aged from 80 to 114 years. It was found that the value of P (probability of joining of satellite fibres of two chromosomes in a group) is considerably less than the corresponding value for persons aged from 20 to 48 years. It is supposed that the decrease of the frequency of association at senile age is caused by heterochromatization of satellite fibres in the 13th and 14 chromosome pairs.     

Antibiotic resistance of Lactobacillus strains]

One hundred and thirty six Lactobacillus strains isolated from poultry and 23 Lactobacillus strains isolated from long-living persons were tested for their antibiotic sensitivity. Occurrence of some type determinants of resistance to aminoglycoside antibiotics and tetracyclines in the Lactobacillus strains resistant to these antibiotics was studied. The majority of the strains from the both collections were resistant to aminoglycosides (73 and 79 per cent, respectively). The isolates from the poultry were characterized by multiple resistance. The isolates from the long-living persons were most frequently resistant to one of two antibiotics. All the tested Lactobacillus strains isolated from the long-living persons were sensitive to tetracyclines. The species composition of the isolates was different. The antibiotic-resistant strains were detected in all the species involved in the study. By hybridization of Lactobacillus colonies with the probes containing various genes of the resistance it was shown that in 14 per cent of the antibiotic-resistant strains belonging to Lactobacillus the antibiotic resistance was controlled by the genes homologous to resistance genes widely distributed in gramnegative organisms. This indicated a possible wide exchange and heterologous expression of the antibiotic resistance determinants between microorganisms of various taxonomic groups.     

The prevalence of helicobacteriosis in regions of Siberia based on serological study data

687 adults in 5 regions of Siberia and 79 children and young persons in Novosibirsk were examined. IgG antibodies to H. pylori in their blood sera were determined with the use the enzyme immunoassay. The detection rate of antibodies among the adult population varied within 70-87%, depending on the region, being somewhat lower among the population north of latitude 60 degrees (75%) in comparison with the population residing south of this latitude (86%, p < 0.001). In Novosibirsk the number of seropositive persons was found to be unrelated to sex, age and clinical manifestations of digestive tract diseases. A high detection rate of antibodies to H. pylori was registered in persons aged 25-34 years with a minor increase in older age groups. In children the detection rate increased with age: 29% in children of 5-10 years old and 56% in children 11-14 years old. By the age of 15 more than a half of the children had antibodies.     

Investigation of asymptomatic visceral leishmaniasis cases using western blot in an endemic area in Turkey

In Turkey, Leishmania infantum is responsible for human visceral leishmaniasis (VL), which is seen mainly in the Aegean, Mediterranean, and Central Anatolia Regions. This study aimed to determine asymptomatic infections in an endemic area of VL in Turkey using the western blot technique. A total of 82 persons including children and adults were chosen randomly in Denizli province which is one of the endemic sites for VL. Serum samples were collected and screened using indirect immunofluorescent test (IFAT), enzyme-linked immunosorbent assay (ELISA) and western blot (WB). One year later, 35 of the 82 persons were sampled and screened serologically for the second time. Seven out of 82 samples were found to be positive by western blot analysis with the presence of 14 and/or 18 kDa bands. Two of these seven sera were also positive by IFAT, but only one of these two was positive by ELISA. Only one person showing seropositivity with all three tests had clinical symptoms and was diagnosed as VL with the presence of amastigotes in bone marrow aspirate. Because six people, including the one found to be seropositive in all two tests, had no clinical symptoms, they were accepted as asymptomatic carriers. The ratio of asymptomatic infection was calculated as 7.41% (6/81) in the region. In the second sampling, the western blot revealed antibodies against the same antigens in all seven subjects. Our findings showed that the presence of antibodies against 14 and 18 kDa antigens are important for the diagnosis of symptomatic and asymptomatic infections. Western blot was found to be effective in the detection of asymptomatic persons in the epidemiological studies in endemic areas.     

Populational polymorphisms in silver staining of nucleolus organizer regions (NORs) in human acrocentric chromosomes

Summary The Ag stainability of the nucleolus organizer region (NOR) was studied in the acrocentric chromosomes identified by Q banding of cultured lymphocytes in 41 karyotypically normal persons (33 males and 8 females) originating from southeast Estonia. The data obtained are compared with those established earlier for a combined Vienna-Ulm population of 51 karyotypically normal persons (see Mikelsaar et al., 1977a). Significant differences between the two populations in the frequency and patterns of Ag-positive NORs were found. The following findings were most striking: the frequency of Ag-positive NORs in chromosome 14 and in the totals was significantly lower in the Estonian population than in the Vienna-Ulm population (P<0.01). The average modal number of Ag-positive NORs per individual was 7.8 in the Estonian population and 8.7 in the Vienna-Ulm sample (P<0.01). If the data of the two populations were combined the frequency of positive NORs was significantly (P<0.05) lower in chromosome 22 than in 13,15, and 21, but not 14.     

Occurrence of antibodies to type 2 herpes simplex virus in the sera of town population.

In order to obtain a more detailed knowledge of the ecology of genital herpesvirus in Czechoslovak geographic and socioeconomic conditions, a total of 1 246 sera of town population, collected by the method of random selection from persons of different age groups in the town of Ostrava were examined in microneutralization reaction for antibodies to type 2 and type 1 herpes simplex virus. Antibodies to HSV-1 were present even in the youngest age groups 0--4 and 5--9 and positive findings in the older age groups ranged from 52 to 82% while antibodies to type 2 herpesvirus were found for the first time at the age of 14 (in one case); in adult persons they occurred in 17--26%. The mentioned results correspond to the sexual manner of transmission of genital herpesvirus and are in keeping with published findings.     

Sequential staining for G- and C-banding of chromosomes in the analysis of the morphology of the short arms of human acrocentric chromosomes]

Sequential staining for G- and C-banding of acrocentric chromosomes of 8 persons showed that the large heterochromatin region occurred more frequently in chromosome 15 than in chromosomes 13 and 14, and in chromosome 22 more frequently than in chromosome 21. There proved to be no correlation between the size of the heterochromatic region and the short arm of the acrocentric chromosomes. The frequency of occurrence of the satellites in the 8 persons was approximately the same for all the acricentric pairs. The C-banded satellite region of the homologous chromosomes is often heteromorphic.