Polymorphism of the C-509 gene of TGFB1 and the risk of obliterative atherosclerosis of lower limb arteries

Genetic factors play an important role in the development of obliterative atherosclerosis of arteries in the lower extremities. There are numerous data in the literature on polymorphic variants of the TGFB1 gene associated with the risk of development of cardiovascular diseases, but some of them are contradictory. The present study aimed at elucidating the role ofpolymorphism of509C/T genes of TGFB1 in the development of obliterative atherosclerosis in arteries of the lower extremities. The material included 328 samples of DNA from 203 unrelated subjects of Russian ethnicity residing in Central Russia (177 men and 23 women) with obliterative atherosclerosis of arteries in the lower extremities hospitalized to the Dpt. of Vascular Surgery and 125 age-matched controls. Genotyping of polymorphism of the C-509T (rs1800469) gene of TGFB1 was performed by the PCR-PDRF method with the use of oligonucleotide primers (Sintol Co., Moscow). The patients with obliterative atherosclerosis showed an increased frequency of the occurrence of alternative allele of the C-509T gene of TGFB1 in comparison with control subjects (r=0,0001). Simultaneously, the frequency of homozygous genotypes of wild-type alleles of -509CC decreased (OR=0,58, 95%CI=0,37-0,92, P=0,02) while the frequency of homozygotes with an alternative allele -509TT increased (OR=4,93, 95%CI=5,20-11,03, P=0,00004). The difference in the frequency of heterozygotes 509CT was absent (OR=0,81, 95%CI=0,52-1,27, P=0,35). Thus, polymorphism of the C-509T gene of TGFB1 is a significant predictor ofpredisposition to the development of obliterative atherosclerosis in arteries of the lower extremities.

Download Full-text

Distribution and Severity of Placental Lesions Caused by the Chlamydia abortus 1B Vaccine Strain in Vaccinated Ewes

Pathogens ◽

10.3390/pathogens10050543 ◽

2021 ◽

Vol 10 (5) ◽

pp. 543

Author(s):

Sergio Gastón Caspe ◽

Javier Palarea-Albaladejo ◽

Clare Underwood ◽

Morag Livingstone ◽

Sean Ranjan Wattegedera ◽

...

Keyword(s):

Disease Outbreaks ◽

Principal Component ◽

Placental Pathology ◽

Wild Type ◽

Cell Infiltrate ◽

Chlamydia Abortus ◽

Vaccine Type ◽

The Difference ◽

Enzootic Abortion Of Ewes

Chlamydia abortus infects livestock species worldwide and is the cause of enzootic abortion of ewes (EAE). In Europe, control of the disease is achieved using a live vaccine based on C. abortus 1B strain. Although the vaccine has been useful for controlling disease outbreaks, abortion events due to the vaccine have been reported. Recently, placental pathology resulting from a vaccine type strain (vt) infection has been reported and shown to be similar to that resulting from a natural wild-type (wt) infection. The aim of this study was to extend these observations by comparing the distribution and severity of the lesions, the composition of the predominating cell infiltrate, the amount of bacteria present and the role of the blood supply in infection. A novel system for grading the histological and pathological features present was developed and the resulting multi-parameter data were statistically transformed for exploration and visualisation through a tailored principal component analysis (PCA) to evaluate the difference between them. The analysis provided no evidence of meaningful differences between vt and wt strains in terms of the measured pathological parameters. The study also contributes a novel methodology for analysing the progression of infection in the placenta for other abortifacient pathogens.

Download Full-text

A microfluidic device enabling drug resistance analysis of leukemia cells via coupled dielectrophoretic detection and impedimetric counting

Scientific Reports ◽

10.1038/s41598-021-92647-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yağmur Demircan Yalçın ◽

Taylan Berkin Töral ◽

Sertan Sukas ◽

Ender Yıldırım ◽

Özge Zorlu ◽

...

Keyword(s):

Drug Resistance ◽

K562 Cells ◽

Leukemia Cells ◽

Drug Resistant ◽

Wild Type ◽

Gene Expressions ◽

Before And After ◽

The Difference ◽

Selection Of ◽

Resistant Cells

AbstractWe report the development of a lab-on-a-chip system, that facilitates coupled dielectrophoretic detection (DEP-D) and impedimetric counting (IM-C), for investigating drug resistance in K562 and CCRF-CEM leukemia cells without (immuno) labeling. Two IM-C units were placed upstream and downstream of the DEP-D unit for enumeration, respectively, before and after the cells were treated in DEP-D unit, where the difference in cell count gave the total number of trapped cells based on their DEP characteristics. Conductivity of the running buffer was matched the conductivity of cytoplasm of wild type K562 and CCRF-CEM cells. Results showed that DEP responses of drug resistant and wild type K562 cells were statistically discriminative (at p = 0.05 level) at 200 mS/m buffer conductivity and at 8.6 MHz working frequency of DEP-D unit. For CCRF-CEM cells, conductivity and frequency values were 160 mS/m and 6.2 MHz, respectively. Our approach enabled discrimination of resistant cells in a group by setting up a threshold provided by the conductivity of running buffer. Subsequent selection of drug resistant cells can be applied to investigate variations in gene expressions and occurrence of mutations related to drug resistance.

Download Full-text

Significant Associations of lncRNA H19 Genotypes with Susceptibility to Childhood Leukemia in Taiwan

Pharmaceuticals ◽

10.3390/ph14030235 ◽

2021 ◽

Vol 14 (3) ◽

pp. 235

Author(s):

Jen-Sheng Pei ◽

Chao-Chun Chen ◽

Wen-Shin Chang ◽

Yun-Chi Wang ◽

Jaw-Chyun Chen ◽

...

Keyword(s):

Confidence Interval ◽

Childhood Leukemia ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Wild Type ◽

Single Nucleotide ◽

Genotypic Distribution ◽

Heterozygous Variant ◽

Significant Difference ◽

The Difference

The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08–2.14, p = 0.0429) and 1.94 (95%CI, 1.15–3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13–1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.

Download Full-text

Place of angiography, oscillography and rheography in the examination of patients with obliterating diseases of the arteries of the lower extremities

Kazan medical journal ◽

10.17816/kazmj62002 ◽

1982 ◽

Vol 63 (3) ◽

pp. 17-19

Author(s):

M. N. Malinovsky ◽

A. A. Zamaletdinov ◽

V. E. Mamaev

Keyword(s):

Research Methods ◽

Lower Limb ◽

Lower Extremities ◽

Functional Changes ◽

Initial Stage ◽

Pharmacological Test ◽

Literary Process

The data of angiographic, oscillographic and rheographic research methods were compared in 63 patients with obliterating diseases of the lower limb arteries. It has been established that arterial oscillography and rheovasography objectively reflect and document the changes occurring in the arterial bed of patients with obliterating endarteritis and atherosclerosis, only when they are used together. The pharmacological test with nitroglycerin makes it possible to differentiate organic and functional changes in the arterial bed only in the initial stage of the disease, in later periods it only helps in predicting the course of the disease. Angiographic methods of examination clarify the diagnosis, localization and length of the literary process.

Download Full-text

128 Differences in PRRSV Resilience for Reproductive Performance Between Landrace and Duroc Sows

Journal of Animal Science ◽

10.1093/jas/skab054.033 ◽

2021 ◽

Vol 99 (Supplement_1) ◽

pp. 18-19

Author(s):

Felipe Hickmann ◽

José Braccini Neto ◽

Luke M Kramer ◽

Kent A Gray ◽

Yijian Huang ◽

...

Keyword(s):

Reproductive Performance ◽

Mixed Model ◽

Performance Data ◽

The Other ◽

Wild Type ◽

Prrs Virus ◽

The Difference ◽

The Impact

Abstract Studies on differences in resilience to porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) between breeds are scarce in the literature. Thus, the objective of this work was to assess PRRSV resilience in PRRSV wild-type infected sows from two breeds. Farrowing data included 2546 and 2522 litters from 894 Duroc and 813 Landrace sows, respectively, which were housed together and experienced the same PRRSV outbreak. Traits used for this study were number of piglets born alive (NBA), number born dead (NBD), total number born (TNB), and number weaned (NW). The impact of PRRSV infection was evaluated by comparing the reproductive performance of breeds between PRRS phases (pre-PRRS, PRRS, and post-PRRS). PRRS phases were defined based on the reproductive performance data. NBA, NBD, and NW were analyzed as a proportion of TNB using a Poisson mixed model. Pre-defined contrasts were used to evaluate the effect of breed on PRRSV resilience and on return to PRRSV-free performance, representing the differences between breeds for the difference between pre-PRRS and PRRS phases, and pre-PRRS and post-PRRS phases, respectively. There was a significant (P ≤ 0.003) interaction between PRRS phase and breed for all traits, as shown in Table 1. In general, reproductive performance reduced from pre-PRRS to PRRS, and then increased from PRRS to post-PRRS, as expected. The resilience contrast was significant for all traits (P ≤ 0.003). In all cases, the drop in percent reproductive performance from pre-PRRS to PRRS was lower for Duroc than for Landrace, indicating that Duroc sows have greater PRRSV resilience than Landrace sows. The return to PRRSV-free performance contrast had a trending effect for NBD (P = 0.055), and it was not significant for the other traits (P ≥ 0.515). These results indicate that Duroc sows have overall greater phenotypic PRRSV resilience for reproductive performance than Landrace sows.

Download Full-text

Single amino acid substitution of rat MRP2 results in acquired transport activity for taurocholate

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.281.4.g1034 ◽

2001 ◽

Vol 281 (4) ◽

pp. G1034-G1043 ◽

Cited By ~ 31

Author(s):

Kousei Ito ◽

Hiroshi Suzuki ◽

Yuichi Sugiyama

Keyword(s):

Amino Acids ◽

Multidrug Resistance ◽

Amino Acid ◽

Membrane Vesicles ◽

Single Amino Acid ◽

Sf9 Cells ◽

Transport Activity ◽

Wild Type ◽

Cationic Amino Acids ◽

The Difference

Multidrug resistance-associated protein 3 (MRP3), unlike other MRPs, transports taurocholate (TC). The difference in TC transport activity between rat MRP2 and MRP3 was studied, focusing on the cationic amino acids in the transmembrane domains. For analysis, transport into membrane vesicles from Sf9 cells expressing wild-type and mutated MRP2 was examined. Substitution of Arg at position 586 with Leu and Ile and substitution of Arg at position 1096 with Lys, Leu, and Met resulted in the acquisition of TC transport activity, while retaining transport activity for glutathione and glucuronide conjugates. Substitution of Leu at position 1084 of rat MRP3 (which corresponds to Arg-1096 in rat MRP2) with Lys, but not with Val or Met, resulted in the loss of transport activity for TC and glucuronide conjugates. These results suggest that the presence of the cationic charge at Arg-586 and Arg-1096 in rat MRP2 prevents the transport of TC, whereas the presence of neutral amino acids at the corresponding position of rat MRP3 is required for the transport of substrates.

Download Full-text

Interaction between transcriptional activator protein LAC9 and negative regulatory protein GAL80.

Molecular and Cellular Biology ◽

10.1128/mcb.9.7.2950 ◽

1989 ◽

Vol 9 (7) ◽

pp. 2950-2956 ◽

Cited By ~ 17

Author(s):

J M Salmeron ◽

S D Langdon ◽

S A Johnston

Keyword(s):

Transcriptional Activation ◽

Kluyveromyces Lactis ◽

Regulatory Protein ◽

Wild Type ◽

Galactose Metabolism ◽

Metabolism Regulation ◽

Transcriptional Activator Protein ◽

The Difference ◽

Carboxy Terminal

In Saccharomyces cerevisiae, transcriptional activation mediated by the GAL4 regulatory protein is repressed in the absence of galactose by the binding of the GAL80 protein, an interaction that requires the carboxy-terminal 28 amino acids of GAL4. The homolog of GAL4 from Kluyveromyces lactis, LAC9, activates transcription in S. cerevisiae and is highly similar to GAL4 in its carboxyl terminus but is not repressed by wild-type levels of GAL80 protein. Here we show that GAL80 does repress LAC9-activated transcription in S. cerevisiae if overproduced. We sought to determine the molecular basis for the difference in the responses of the LAC9 and GAL4 proteins to GAL80. Our results indicate that this difference is due primarily to the fact that under wild-type conditions, the level of LAC9 protein in S. cerevisiae is much higher than that of GAL4, which suggests that LAC9 escapes GAL80-mediated repression by titration of GAL80 protein in vivo. The difference in response to GAL80 is not due to amino acid sequence differences between the LAC9 and GAL4 carboxyl termini. We discuss the implications of these results for the mechanism of galactose metabolism regulation in S. cerevisiae and K. lactis.

Download Full-text

NEXT AND LONG-TERM RESULTS OF X-RAY ENDOVASCULAR INTERVENTIONS IN TREATMENT OF CHRONIC CRITICAL ATHERODIABETIC ISCHEMIA OF LOWER EXTREMITIES

Journal of the Grodno State Medical University ◽

10.25298/2221-8785-2020-18-6-710-715 ◽

2020 ◽

Vol 18 (6) ◽

pp. 710-715

Author(s):

N. N. Ioskevich ◽

◽

L. F. Vasilchuk ◽

P. E. Vankovich ◽

S. P. Antonenko ◽

...

Keyword(s):

Lower Limb ◽

Type I Diabetes ◽

Lower Extremities ◽

Limb Ischemia ◽

Type I ◽

Critical Ischemia ◽

Lower Limb Ischemia ◽

X Ray ◽

Endovascular Interventions

Background. The treatment of chronic critical ischemia of the lower extremities with their combined atherodiabetic lesion is one of the far from the resolved problems of modern surgery. Aim of the study. Analysis of the results of X-ray endovascular interventions in patients with critical lower limb ischemia due to atherodiabetic lesions of the femoral-popliteal-tibial segment. Material and methods. We analyzed the results of REVS in 60 patients with diabetes mellitus with critical ischemia of the lower extremities due to infra-anginal atherosclerotic occlusions with a follow-up period of up to 5 years from the moment of the manipulation. Results. The total shelf life of the lower limb after REVV was 492.4 ± 10.1 days. Out of 26 amputations performed, balloon angioplasty was performed in 18 cases and stenting in 8 cases. In individuals with type I diabetes, the duration of painless period was 415.4 ± 5.1 days, and the total shelf life of the leg was 465.4 ± 4.3 days. In type II diabetes, these indicators were, respectively, 181.4 ± 4.4 days and 317.8 ± 6.7 days. In the group of patients with type I diabetes, the lower limb was saved in 55.6% of cases (in 20 out of 36 patients), and in type II diabetes - in 58.3% (in 14 out of 24 people). Conclusions. The presence of simultaneously obliterating atherosclerosis and diabetes mellitus in patients leads to a combined atherodiabetic lesion of the arterial bed, including infra-anginal arteries. X-ray endovascular interventions (balloon angioplasty and stenting) on the arterial femoral-popliteal-tibial segment are a rather effective method of eliminating chronic critical lower limb ischemia, which allows preserving the lower limb in 56.7% patients with a follow-up period of up to 5 years from the date of surgery. Improving the results of X-ray endovascular interventions in case of chronic critical atherodiabetic lower limb ischemia requires a comprehensive study of the possible causes of occlusions of reconstructed arterial segments (blood coagulation potential, non-optimal processes in the intervention zone).

Download Full-text

Association between family history and the onset age of essential hypertension in Han population in Shanghai China

10.21203/rs.2.11431/v1 ◽

2019 ◽

Author(s):

li anle ◽

Qian Peng ◽

Yue Qin Shao ◽

Yi Ying Zhang ◽

Fang Xiang

Keyword(s):

Essential Hypertension ◽

Family History ◽

Genetic Factors ◽

Nuclear Family ◽

Age Of Onset ◽

Control Group ◽

Case Group ◽

Onset Age ◽

Han Population ◽

The Difference

Abstract Importance Genetic factors are important influencing factors of essential hypertension, and family history (FH) is an important marker of genetic factors. Objective To explore the association between family history and the onset age of essential hypertension in Han population in Shanghai China. Methods According to l:l matched pairs design，342 precursor of hypertension and 342 controls were selected and investigate their nuclear family members in the case-control study. The diagnostic information of hypertension in all relatives of these two groups was investigated. The method of genetic epidemiology research was used to explore the effect of family history. Results The average prevalence of hypertension was 23.32%. The prevalence of hypertension of first-degree relatives was 33.99%; the prevalence of second- degree relatives was 17.60%; the prevalence of third-degree relatives was 13.51%. All prevalence of hypertension of case group relatives were significantly higher than that of control group relatives. The average onset age in population with positive FH is 48.74±11.16 years old, and the average onset age in population with negative FH is 54.38±9.87 years old. The difference about two FH groups showed statistically significant (t=4.589, P<0.001). The average onset age of offspring with father, mother, grandpa, grandma, maternal grandpa or maternal grandma positive was respectively 48.42± 11.16, 49.16±11.12, 39.55±11.95, 39.88±11.90, 43.67±9.77 or 43.64±10.21 years old; and the average onset age of children with father, mother, grandpa, grandma, maternal grandpa or maternal grandma negative was respectively 51.90± 10.81, 51.17±11.04, 51.07±10.59, 51.08±10.60, 50.50±11.09 or 50.57±11.06 years old. The difference about two groups showed statistically significant. Conclusion Family history has a positive effect on the occurrence of hypertension, and lead to earlier age of onset of offspring. The effects are different among parent and grandparent in Han in Shanghai China.

Download Full-text

THE EFFECTS OF HETEROZYGOSITY CHANGES ON VIABILITY IN DROSOPHILA MELANOGASTER

Genetics ◽

10.1093/genetics/70.4.595 ◽

1972 ◽

Vol 70 (4) ◽

pp. 595-610

Author(s):

Ray Moree

Keyword(s):

Drosophila Melanogaster ◽

Genetic Background ◽

Laboratory Strain ◽

Theoretical Expectation ◽

Wild Type ◽

Small Deviations ◽

The Third ◽

The Difference

ABSTRACT The viability effects of chromosomes from an old and from a new laboratory strain of D. melanogaster were studied in eight factorial combinations and at two heterozygosity levels. The combinations were so constructed that heterozygosity level could be varied in the third chromosomes of the carriers of a homozygous lethal marker, in the third chromosomes of their wild-type segregants, and in the genetic backgrounds of both. Excluding the effect of the marker and the exceptional outcomes of two of the combinations, and taking into account both large and small deviations from theoretical expectation, the following summary is given as the simplest consistent explanation of the results: 1) If total heterozygosities of two segregant types tend toward equality their viabilities tend toward equality also, whether background heterozygosity is high or low; if background heterozygosities is higher the tendency toward equality is slightly greater. 2) If total heterozygosity of two segregant types are unequal the less heterozygous type has the lower viability; the difference is more pronounced when background heterozygosity is low, less when it is high. 3) Differences between segregant viabilities are correlated with differences between the total heterozygosities of the two segregants; genetic background is effective to the extent, and only to the extent, that it contributes to the magnitude of this difference. This in turn appears to underlie, at least partly, the expression of a pronounced interchromosomal epistasis. Thus in this study viability is seen to depend upon both the quantity and distribution of heterozygosity, not only among the chromosomes of an individual but among the individuals of a given combination as well.

Download Full-text