Frequency of unexpected red blood cell antibodies in Nanjing

The development of unexpected red blood cell antibodies can significantly complicate transfusion therapy and result in more difficulties in cross-matching of blood. This study aimed to determine the occurrence rate of red blood cell alloimmunization in patients from Nanjing and the surrounding area. The antibody screening tests were carried out on 604 patients in Nanjing Red Cross Blood Center from January 2014 to December 2016, and the results were compiled and statistically analyzed. In the 604 patients, 483 cases revealed autoantibodies with or without underlying alloantibodies, while 121 patients had only alloantibodies in their serum. The overall frequency of alloimmunization was 32.5%. The most frequent antibodies were what against the Rh systerm(72.39%), followed by MN system (25.71%).     

The Prevalence of unexpected antibodies in Saudi's plasma prior blood transfusion and their association with clinical conditions: A cross-sectional study

Unexpected antibodies, also called irregular antibodies, are not known to exist in a person's serum before testing. This research aims to assess the prevalence of unexpected antibodies and their correlation with several clinical conditions. This cross-sectional prospective study, undertaken from June 2019 to June 2020, included ABO, Rh grouping, cross-matching, and antibody screening. Antibody identification was performed only on patients who tested positive in the screening test. From a total of 9764 participants who were screened for unexpected antibodies, 107 (1.1%) tested positive. The Rh blood group system antibodies were the most frequent, particularly anti-D. There was also a significant correlation between the unexpected antibodies and history of transfusion, pregnancy, and autoimmune diseases as P ≤ 0.05. The most prominent unexpected antibodies in the study belong to the Rh system (Anti-D). Moreover, as a result of the strong correlation between the unexpected antibodies as well as the history of transfusion, pregnancy, and autoimmune diseases, the highest safety criteria must be followed during the transfusion of blood to patients with these clinical conditions.     

Ethnic communities in Israel: The genetic blood markers of the Babylonian Jews

One hundred eighty-eight Jewish individuals who either they or whose both parents were born in Iraq were typed for 7 blood groups (ABO, MNS, Rh, Kell, Duffy, P and Kidd), 12 red cell enzyme systems and 2 serum proteins. Iraqi Jews are characterized by a high frequency of A (in ABO), N (in MNS), low cde (Rh) and low Hp-1. Several rare electrophoretic variants were encountered: PGM₁ 6-1, PHI 3-1 and PHI 2-1, and an unidentified AK phenotype. No evidence of Negroid admixture was found in their gene pool. Comparisons with results previously obtained in Iraqi Jews show general similarities in frequencies while comparisons with neighboring non-Jewish populations suggest divergence in most systems investigated. The difficulties of assessing relationships on the basis of a few selected differences and the need for careful interpretations of similarities are emphasized.     

Seroepidemiology of human parechovirus types 1, 3, and 6 in Yamagata,Japan, in 2014

To clarify the seroepidemiology of human parechovirus type 1 (HPeV1), 3 and 6, neutralizing antibodies (NT Abs) were measured in 214 serum specimens collected in 2014 in Yamagata, Japan. The seroprevalence against HPeV1 was 100% in all age groups, while that against HPeV3 and HPeV6 was 79.4% and 66.8%, respectively, overall. The geometric mean titers of NT Abs against HPeV1, 3 and 6 were 755.2, 255.0 and 55.9, respectively, overall. Our findings indicate that HPeV1 is the most prevalent HPeV circulating in Yamagata, followed by HPeV3 and HPeV6.     

Characterization of the Genetic Diversity of Extensively-Drug Resistant Mycobacterium tuberculosis Clinical Isolates from Pulmonary Tuberculosis Patients in Peru

Background

Peru holds the fourth highest burden of tuberculosis in the Americas. Despite an apparently well-functioning DOTS control program, the prevalence of multidrug resistant tuberculosis (MDR-TB) continues to increase. To worsen this situation, cases of extensively drug resistance tuberculosis (XDR-TB) have been detected. Little information exists about the genetic diversity of drug-susceptible vs. MDR-TB and XDR-TB.

Methods

Cryopreserved samples of XDR strains from 2007 to 2009 (second semester), were identified and collected. Starting from 227 frozen samples, a total of 142 XDR-TB strains of Mycobacterium tuberculosis complex (MTBC; 1 isolate per patient) were retained for this study. Each strain DNA was analyzed by spoligotyping and the 15-loci Mycobacterial Interspersed Repetitive Unit (MIRU-15).

Results

Among the 142 isolates analyzed, only 2 samples (1.41%) could not be matched to any lineage. The most prevalent sublineage was Haarlem (43.66%), followed by T (27.46%), LAM (16.2%), Beijing (9.15%), and X clade (1.41%). Spoligotype analysis identified clustering for 128/142 (90.1%) isolates vs. 49/142 (34.5%) with MIRUs. Of the samples, 90.85% belonged to retreated patients. The drug resistant profile demonstrated that 62.67% showed resistance to injectable drugs capreomycin (CAP) and kanamycin (KAN) vs. 15.5% to CAP alone and 21.8% to KAN alone. The SIT219/T1 and SIT50/H3 were the most prevalent patterns in our study. The spoligoforest analysis showed that SIT53/T1 was at the origin of many of the T lineage strains as well as a big proportion of Haarlem lineage strains (SIT50/H3, followed by SIT47/H1, SIT49/H3, and SIT2375/H1), as opposed to the SIT1/Beijing strains that did not appear to evolve into minor Beijing sublineages among the XDR-TB strains.

Conclusion

In contrast with other Latin-American countries where LAM sublineage is the most predominant, we found the Haarlem to be the most common followed by T sublineage among the XDR-TB strains.     

MNS16A Tandem Repeats Minisatellite of Human Telomerase Gene and Cancer Risk: A Meta-Analysis

Background

Researchers have provided evidence that telomere dysfunction play an important role in cancer development. MNS16A is a polymorphic tandem repeats minisatellite of human telomerase (hTERT) gene that influences promoter activity of hTERT and thus implicates to relate with risk of several malignancies. However, results on association between MNS16A and cancer risk remain controversial. We therefore conduct a meta-analysis to derive a more precise estimation of association between MNS16A and cancer risk.

Methods

A systematic literature search was conducted by searching PubMed, ISI Web of Knowledge, Human Genome and Epidemiology Network Navigator and Google Scholar digital database for publications on associations between MNS16A and cancer risk. Variants with statistically significant associations by meta-analysis were assessed using Venice criteria.

Results

10 case-control articles enrolling 6101 cases and 10521 controls were brought into our meta-analysis. The relationships were strong epidemiological credibility in cerebral cancer and breast cancer population (P for heterogeneity > 0.1). The cumulative analysis in chronologic order suggested a clear tendency towards a significant association with additional study samples.

Conclusions

The results provided a more accurate depiction of the role of MNS16A in cerebral cancer and breast cancer susceptibility. Additional larger studies were warranted to validate our findings.     

Seroepidemiology of Human Bocaviruses 1 and 2 in China

Seroepidemiology studies had been used to research the newly discovered human bocaviruses (HBoVs). Antibodies against the HBoV1–4 VP2 protein virus-like particles (VLPs) were found to be cross-reactive. The aim of the present study was to characterize the seroprevalence of HBoV1 and 2 among healthy populations in China. Recombinant HBoV1 and 2 VLPs were used to establish enzyme-linked immunosorbent assays (ELISAs) for detection of cross-reactivity between HBoV1 and HBoV2 in 1391 serum samples collected from healthy individuals in China. Of these, 884 samples were collected from Beijing and 507 were from Nanjing. Infection with HBoV1 and 2 was prevalent in healthy Chinese people, with the seroprevalence of HBoV1 and 2 in Beijing at 69.2 (612/884) and 64.4% (569/884), respectively. Highest seroprevalence was observed in 3–5-year-olds. The seroprevalence of HBoV1 was significantly decreased between 10–13-year-olds (80.3%) and 14–20-year-olds (62.3%, p< 0.05). For individuals over 20 years, seroprevalence was relatively constant at about 60%. Similar trends were observed in children from Nanjing, with seroprevalence of HBoV1 and 2 for healthy children at 80.7% (409/507) and 81.3% (412/507), respectively. Moreover, both mouse and human antibodies against HBoV1 and HBoV2 VLPs were found to be cross-reactive and 58.4% (813/1391) serum samples were seropositive for both HBoV1 and HBoV2. This finding suggests HBoV is highly prevalent in China and the antibodies produced as a result of infection with either HBoV1 or HBoV 2 will offer future protection. The cross-reactivity between HBoVs is crucial for accurately determining HBoV seroepidemiology.     

A First Insight on the Population Structure of Mycobacterium tuberculosis Complex as Studied by Spoligotyping and MIRU-VNTRs in Santiago,Chile

Tuberculosis (TB) remains a significant public health problem worldwide, but the ecology of the prevalent mycobacterial strains, and their transmission, can vary depending on country and region. Chile is a country with low incidence of TB, that has a geographically isolated location in relation to the rest of South American countries due to the Andes Mountains, but recent migration from neighboring countries has changed this situation. We aimed to assess the genotypic diversity of Mycobacterium tuberculosis complex (MTBC) strains in Santiago, Chile, and compare with reports from other Latin-American countries. We analyzed MTBC isolates from pulmonary tuberculosis cases collected between years 2008 and 2013 in Central Santiago, using two genotyping methods: spoligotyping and 12-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTRs). Data obtained were analyzed and compared to the SITVIT2 database. Mean age of the patients was 47.5 years and 61% were male; 11.6% were migrants. Of 103 strains (1 isolate/patient) included, there were 56 distinct spoligotype patterns. Of these, 16 strains (15.5%) corresponded to orphan strains in the SITVIT2 database, not previously reported. Latin American and Mediterranean (LAM) (34%) and T (33%) lineages were the most prevalent strains, followed by Haarlem lineage (16.5%). Beijing family was scarcely represented with only two cases (1.9%), one of them isolated from a Peruvian migrant. The most frequent clustered spoligotypes were SIT33/LAM3 (10.7%), SIT53/T1 (8.7%), SIT50/H3 (7.8%), and SIT37/T3 (6.8%). We conclude that LAM and T genotypes are the most prevalent genotypes of MTBC in Santiago, Chile, and together correspond to almost two thirds of analyzed strains, which is similar to strain distribution reported from other countries of Latin America. Nevertheless, the high proportion of SIT37/T3, which was rarely found in other Latin American countries, may underline a specific history or demographics of Chile related to probable human migrations and evolutions.     

Enfermedad hemolítica del feto y del recién nacido por aloanticuerpos contra el antígeno M

There are few case reports of hemolytic disease in fetuses and newborns (HDFN) caused by alloantibodies against the MNS blood group system. The reason for this dearth is that antibodies toward these antigens are usually IgM, which not only cannot cross the placental circulation but also react at temperatures below 37°C. They are, therefore, of minimal clinical importance. Nevertheless, cases have been reported in which the presence of anti-M IgG antibodies caused severe HDFN and even intrauterine death in the presence of maternal-fetal MNS incompatibility indicating that they could have a high clinical impact. The hemolytic pattern observed in these cases is similar to that caused by anti-Kell antibodies. Progressive anemia is mediated and developed through hematopoietic suppression inducing the destruction of bone marrow precursor cells with the resulting absence of reticulocytes in peripheral blood.This occurred in the case of a woman at 38.5 weeks of gestation who showed a discrepancy between direct and reverse blood type determination. A direct Coombs test was performed on the newborn’s blood, which was positive in the absence of maternal-fetal ABO incompatibility. Further tests were performed and anti-M antibodies were found in the maternal serum screening. Our final diagnosis was largely due to discrepancy issues in maternal blood. Although anti-M antibodies do not usually play a significant role in HDFN, this case stresses the importance of identifying the presence of antibodies that can be crucial in preventing HDFN and lead to new recommendations for the screening and prompt treatment of hemolysis in newborns.     

Fluorescein and tetramethyl rhodamine as haptens in enzyme immunohistochemistry

Summary Fluorescein (Fl) and tetramethyl rhodamine (Rh) were evaluated as possible candidates for a double hapten sandwich system in enzyme immunohistology. Monoclonal antibodies were raised against Fl and Rh. Their fine-specificity was tested with a competition-like assay. A pair of Mab's was selected for immunohistology in which they functioned as a bridge between Fl/Rh conjugated antibodies and Fl/Rh labeled peroxidase and alkaline phosphatase, respectively. The binding of fluorescein labeled antibodies could be successfully demonstrated in histological slides. A large variability in the efficacy of staining was observed in the case of rhodamine labeled antibodies. The phenomenon is explained by assuming that tetramethyl rhodamine isothiocyanate reacts preferentially with lysine residues near to, or embedded in, hydrophobic regions in a protein. This condition may reduce the accessibility of the Rh moiety for anti-Rh antibodies.Abbreviations AEC 3-amino-9-ethylcarbazole - AP Alkaline phosphatase - BSA Bovine serum albumin - CGG Chicken gamma globulin - c-IF Cytoplasmic immunofluorescence - DAB 3,3-Diamino benzidine HCl - ELISA Enzyme linked immunosorbent assay - Fl Fluorescein - F/P ratio Number of fluorochrome molecules per molecule of protein - Ig Immunoglobulin - Mab Monoclonal antibody - OPD Ortho-phenylenediamine-dihydrochloride - PBS Phosphate buffered saline - PBS-T PBS with 0.2% Tween-20 - PO Peroxidase - RAM/PO Peroxidase labeled rabbit antiserum directed against mouse immunoglobulins - Rh Tetramethyl rhodamine - RT Room temperature In honour of Prof. P. van Duijn     

Characterization of class 1 integrons-mediated antibiotic resistance among calf pathogenic Escherichia coli

Escherichia coli isolates from calf diarrhea cases (n=22) in the Beijing surrounding region in China were characterized for disease serotype, virulence factors, antimicrobial susceptibility pattern and class 1 integrons. 59% (n=13) of the isolates were positive for the int I1 gene. The presence and genetic content of class 1 integrons in 13 E. coli isolates were examined by PCR and sequencing. Sequencing analysis revealed six gene cassettes, which encoded resistance to trimethoprim (dfrA1, dfrA17), aminoglycosides (aadB, aadA1 and aadA5) and chloramphenicol (cmlA). The gene cassette arrays dfrA1-orf (45%) and aadB-orf-cmlA (32%) were most prevalent among these isolates. These data revealed the high prevalence of class 1 integrons among calf pathogenic E. coli isolates in the Beijing surrounding region in China, which may provide important and useful surveillance information reflecting specific antibiotic selective pressure.     

Fluorescein and tetramethyl rhodamine as haptens in enzyme immunohistochemistry

Fluorescein (Fl) and tetramethyl rhodamine (Rh) were evaluated as possible candidates for a double hapten sandwich system in enzyme immunohistology. Monoclonal antibodies were raised against Fl and Rh. Their fine-specificity was tested with a competition-like assay. A pair of Mab's was selected for immunohistology in which they functioned as a bridge between Fl/Rh conjugated antibodies and Fl/Rh labeled peroxidase and alkaline phosphatase, respectively. The binding of fluorescein labeled antibodies could be successfully demonstrated in histological slides. A large variability in the efficacy of staining was observed in the case of rhodamine labeled antibodies. The phenomenon is explained by assuming that tetramethyl rhodamine isothiocyanate reacts preferentially with lysine residues near to, or embedded in, hydrophobic regions in a protein. This condition may reduce the accessibility of the Rh moiety for anti-Rh antibodies.     

Mycobacterium tuberculosis Population in Northwestern Russia: An Update from Russian-EU/Latvian Border Region

This study aimed to characterize the population structure of Mycobacterium tuberculosis in Pskov oblast in northwestern Russia, to view it in the geographical context, to compare drug resistance properties across major genetic families. Ninety M. tuberculosis strains from tuberculosis (TB) patients, permanent residents in Pskov oblast were subjected to LAM-specific IS6110-PCR and spoligotyping, followed by comparison with SITVITWEB and MIRU-VNTRplus databases. The Beijing genotype (n = 40) was found the most prevalent followed by LAM (n = 18), T (n = 13), Haarlem (n = 10), Ural (n = 5), and Manu2 (n = 1); the family status remained unknown for 3 isolates. The high rate of Beijing genotype and prevalence of LAM family are similar to those in the other Russian settings. A feature specific for M. tuberculosis population in Pskov is a relatively higher rate of Haarlem and T types. Beijing strains were further typed with 12-MIRU (followed by comparison with proprietary global database) and 3 hypervariable loci QUB-3232, VNTR-3820, VNTR-4120. The 12-MIRU typing differentiated 40 Beijing strains into 14 types (HGI = 0.82) while two largest types were M2 (223325153533) prevalent throughout former USSR and M11 (223325173533) prevalent in Russia and East Asia. The use of 3 hypervariable loci increased a discrimination of the Beijing strains (18 profiles, HGI = 0.89). Both major families Beijing and LAM had similar rate of MDR strains (62.5 and 55.6%, respectively) that was significantly higher than in other strains (21.9%; P = 0.001 and 0.03, respectively). The rpoB531 mutations were more frequently found in Beijing strains while LAM drug resistant strains mainly harbored rpoB516 and inhA −15 mutations. Taken together with a high rate of multidrug resistance among Beijing strains from new TB cases (79.3% versus 44.4% in LAM), these findings suggest the critical impact of the Beijing genotype on the current situation with MDR-TB in the Pskov region in northwestern Russia.     

Pyrogenic toxins of Staphylococcus aureus in sudden unexpected nocturnal deaths in adults and older children: factors influencing the control of inflammatory responses to toxic shock syndrome toxins

Sudden unexpected nocturnal deaths (SUND) occur in young immigrant workers, mainly from south-east Asia, who are employed in countries such as Singapore and Saudi Arabia. Pyrogenic toxins of Staphylococcus aureus have been identified in two cases of sudden unexpected death in adults in the UK and it has been suggested that these or other toxins with superantigen properties might induce strong inflammatory responses leading to sudden unexpected nocturnal deaths. The objectives of the present study were (1) to assess the levels of antibodies to pyrogenic staphylococcal toxins in the general population, (2) to assess the levels of IgG to the toxins needed to reduce the production of inflammatory mediators by 50% in a model system, (3) to assess in a model system the effects on inflammatory responses to toxic shock syndrome toxin-1 (TSST) of cortisol levels present at night, during the day and under conditions of physiological stress. Enzyme linked immunosorbent assays were used to assess levels of IgG to TSST, staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin C (SEC). Human buffy coats were used to examine the effect of IgG to the toxins for neutralising activity and the effect of cortisol on induction of inflammatory mediators. Tumour necrosis factor alpha (TNF-alpha) was detected by a bioassay with L929 cells, interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured by an enzyme linked immunosorbent assay. IL-6 and TNF-alpha levels elicited by the toxins were not reduced by night time levels of cortisol (5-10 microg dl(-1)) levels. Day time levels of cortisol (10-20 microg dl(-1)) significantly inhibited IL-6 production but not TNF-alpha in responses. Stress levels of cortisol (40 80 microg dl(-1)) significantly reduced all three cytokines earlier than the normal day time levels. The majority of the population tested had sufficient antibodies to reduce TNF-alpha and IL-6 responses elicited by TSST and SEC in the model system. In the age range in which most sudden unexpected nocturnal death cases occur (20-39 years), males had significantly lower levels of IgG to TSST compared with females. If these toxins play a role in precipitating the series of events leading to sudden unexpected nocturnal death, the higher levels of IgG to the toxins observed in females might explain partly the much higher prevalence of these deaths among men in this age range. If inflammatory responses play a role in sudden unexpected nocturnal death, the inability of the night time levels of cortisol to control IL-6 and TNF-alpha in the model system might reflect these interactions in vivo. The methods developed for detection of the toxins in tissue samples and the quantitative IgG assays for anti-toxins can be applied to investigation of SUND victims to test the hypothesis that some of these deaths are precipitated by pyrogenic staphylococcal toxins.     

Sero-prevalence of RBC alloantibodies among Han and minority patients in Xinjiang

The aim of the study was to examine the sero-prevalence and frequency of red blood cell (RBC) alloantibodies (RAAbs) and to investigate the risk factors for producing RAAbs among the Han and Uyghurs in Xinjiang. The RBC antibody screening test and identification were conducted for 45,163 Han and 70,633 Uyghurs admitted to the First Affiliated Hospital of Xinjiang Medical University from October 2010 to December 2014. RBC alloantibodies against the Rh antigens were the most frequent, including anti-E(21.7% in the Han, 21.6% in Uyghurs) and anti-D(18.5% in the Han, 18.2% in Uyghurs). Notably, the sero-prevalence of anti-K and anti-Fy^a was also high in Xinjiang. Transfusion and pregnancy were risk factors among both the Han and Uyghurs; furthermore, Uyghurs had a higher sero-prevalence of RBC antibodies compared to that of Han because of a higher incidence of these risk factors. We concluded that RBC alloantibodies against the Rh factor showed the highest frequency, and antibodies against Asian-related high-frequency antigens, including Fy^a and low-frequency antigens, such as K were notably high in Xinjiang.     

Studies of the genetic susceptibility of individuals to infection with influenza viruses

Summary Nearly three and a half thousand sera obtained from various populations were tested serologically to obtain evidence of past infection with influenza A viruses that were prevalent from 1947 to 1972.No significant difference was found between the distributions of the levels of these antibodies of individuals of blood groups A and 0, A₁ and 0, Rh (D+) and Rh (D-) and MM, MN and NN.The significance of these findings is discussed.     

Clonal Expansion of Both Modern and Ancient Genotypes of Mycobacterium tuberculosis in Southern Taiwan

We present the first comprehensive analysis of Mycobacterium tuberculosis isolates circulating in the Kaohsiung region of southern Taiwan. The major spoligotypes found in the 224 isolates studied were Beijing lineages (n = 97; 43.3%), EAI lineages (n = 72; 32.1%) and Haarlem lineages (n = 18; 8.0%). By 24 MIRU-VNTR typing, 174 patterns were identified, including 24 clusters of 74 isolates and 150 unique patterns. The combination of spoligotyping and 12-MIRU-VNTR revealed that 129 (57.6%) of the 224 isolates were clustered in 18 genotypes. Moreover, 63.6% (7/11) of infected persons younger than 30 years had a Beijing strain, which could suggest recent spread among younger persons by this family of TB strains in Kaohsiung. Among the 94 Beijing family (SIT1, SIT250 and SIT1674) isolates further analyzed for SNPs by mass spectrometry, the most frequent strain found was ST10 (n = 49; 52%), followed by ST22 (n = 17; 18%) and ST19 (n = 11; 12%). Among the EAI-Manila family isolates analyzed by region deletion-based subtyping, the most frequent strain found was RD type 1 (n = 63; 87.5%), followed by RD type 2 (n = 9; 12.5%). In our previous study, the proportion of modern Beijing strains (52.5%) in northern Taiwan was significantly higher than the proportion of EAI strains (11%). In contrast, in the present study, EAI strains comprised up to 32% of Beijing strains in southern Taiwan. In conclusion, both ‘modern’ (Beijing) and ‘ancient’ (EAI) M. tuberculosis strains are prevalent in the Kaohsiung region, perhaps suggesting that both strains are somehow more adapted to southern Taiwan. It will be interesting to investigate the dynamics of the lineage composition by different selection pressures.     

Dyslipoproteinemia in an inbred rat strain with spontaneous chronic progressive nephrotic syndrome.

Rats of the Milan Normotensive Strain (MNS) develop a dyslipoproteinemia that is associated with a spontaneous, age-dependent and slowly progressive nephropathy characterized by proteinuria and hypoalbuminemia (nephrotic syndrome). We assumed that the MNS strain might be a suitable model for studying the features of nephrotic dyslipoproteinemia and its relationship with proteinuria, hypoalbuminemia, and hepatic apolipoprotein production. Plasma lipoproteins were investigated in MNS rats at various ages (4-48 weeks) and in another rat strain (Milan Hypertensive Strain, MHS), genetically related to MNS but free of nephropathy, that was used as control. In MNS rats, abnormal proteinuria was detectable at 20 weeks and increased 2-fold up to 34 weeks with no reduction of plasma albumin (compensated stage). During this stage we found increased levels of plasma cholesterol (+ 34%), high density lipoprotein-1 (HDL1) (+ 73%), and HDL2 (+ 31%) that were positively correlated with proteinuria but not with plasma albumin. The later stage (34-48 weeks) (nephrotic stage) was characterized by a further increase of proteinuria, moderate hypoalbuminemia (- 25%), a 2-fold increase of plasma cholesterol, triacylglycerols, low density lipoprotein (LDL), and HDL1, and a 1.2-fold increase of HDL2. In this stage the levels of LDL, HDL1, and HDL2 were positively correlated with proteinuria, and negatively correlated with plasma albumin. The most striking change in apolipoproteins was a progressive increase of the relative content of apoA-I in HDL (in 48-week-old MNS rats the A-I/E ratio was 3-fold that found in MHS rats) that was associated with a similar increase of plasma apoA-I. None of these lipoprotein changes were observed in age-matched MHS rats. At the end of the compensated stage, the hepatic levels of A-I, B, A-II, and albumin mRNA were 5.3-, 3.5-, 1.3-, and 2.0-fold, respectively, those found in age-matched MHS rats. During the nephrotic stage, albumin mRNA continued to increase, whereas A-I, B, and A-II mRNAs decreased toward the levels found in age-matched MHS rats. Thus, nephrotic dyslipoproteinemia in MNS rats starts to develop in the compensated stage before the onset of hypoalbuminemia, is characterized by an early elevation of HDL1 + HDL2, and is associated with an increased content of hepatic mRNAs of some apolipoproteins, especially apoA-I. The slow progression of nephrotic syndrome with the long-standing proteinuria and no reduction in plasma albumin renders the MNS strain the most suitable animal model for the study of the effect of proteinuria on plasma lipoprotein metabolism.     

北京地区宫颈癌HPV16上游调控序列、E6、E7癌基因序列初步分析

为检测HPV16上游调控序列(Upstream regulatory region, URR)、E6、E7癌基因变异在北京地区宫颈癌患者癌组织中的分布特征, 探讨该地区宫颈癌发生同HPV16变异株间的相关性, 文章以提取的31例HPV16检测阳性宫颈癌组织DNA为模板, 设计针对性引物扩增URR、E6、E7 3个目的片段, PCR产物直接测序并通过GenBank对比分析变异和分支鉴定情况。在所分析的宫颈癌组织中, URR是突变频率最高的片段, 其次为E7, 最保守的序列为E6。共发现热突变位点8个, 分别为URR序列上G7521A(100%)、C7435G(96.77%)、C24T(45.16%)、A7729C(45.16%)、G7839A(45.16%); E6序列上T178G(41.94%); E7序列上A647G(45.16%)、T846C(45.16%)。HPV16分支分布频率最广的是As型(54.84%), 其次为E型(45.16%)。研究结果提示, HPV16URR序列上G7521A、A7729C、G7839A, E6序列上T178G、T350G, E7序列上A647G、G658A等位点的变异可能与病毒致癌潜能及宫颈癌的发生相关。北京地区宫颈癌患者中As和E型可能是两种最主要的HPV16分支, 这有可能会为HPV疫苗的研制和感染治疗提供有价值的信息。As型和E型病毒在不同年龄组和不同肿瘤分期组的患者中分布频率有差异, 这可能会为揭示宫颈癌年轻化趋势提供新的线索。