scholarly journals five Int22h Homologous Copies in Association with Intron22 Inversion Type 3

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5033-5033
Author(s):  
Nathalie Lannoy ◽  
Marie Ravoet ◽  
Bernard Grisart ◽  
Mathilde Fretigny ◽  
Cedric R. Hermans
Keyword(s):  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Severe Hemophilia ◽  
Causative Gene ◽  
International Consortium ◽  
Intron 1 ◽  
Intrachromosomal Rearrangement ◽  
Type 3

Abstract Introduction F8 intron22 inversion is the causative gene defect in up to 45% of severe hemophilia A (HA) patients mediated by recombination between three highly homologous copies located in intron 22 (int22h-1) and two other extragenic copies (int22h-2 and int22h-3) positioned more telomerically outside the gene. Intrachromosomal rearrangement between int22h-1 and int22h-3 provide the F8 type 1 inversion while the F8 type 2 inversion could be explained by the participation of the int22-h2 sequence in the homologous recombination. However, a third type, known since 1993*, was explained by the existence of a duplicated copy of int22h-3 or int22h-2 in case of intron22 inversion type 3A or 3B respectively. Methods Three unrelated HA patients with intron22 type 3A/3B were identified by southern blotting. To appreciate the length of the int22h extragenic duplicated, genomic hybridisation was performed using Affimetrix CytoScan High-Density array. Results Breakpoint analyses by CGH-array in all patients show same duplication of approximately 180kb delimited between intron 1 of CLIC2 gene and distal repeat int22h-3reflecting the presence of five genomic int22 copies. A fourth non-hemophiliac case was added since analysis by CGH technique identified duplication delineated by same boundaries. Conclusion This study suggests the existence of genotypes harboring five int22h copies mediated by 180 kb duplication at Xq28 locus probably not associated with HA. We propose that this duplication has happened by tandem inversed duplication. Such genotype is to be considered as polymorphism and could be associated with the two kinds of F8 intron22 inversion type 3 when intrachromosomal recombination has occurred between homologous copies. *Antonarakis SE and the international consortium study. Factor VIII gene inversions in severe hemophilia A: results of an international consortium study. Blood 1995; 86: 2206-2212 Disclosures No relevant conflicts of interest to declare.

Determination of Coagulation Functions and Inhibitory Mechanisms In Acquired Hemophilia A with Type 1 and Type 2 Inhibitors.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3666-3666
Author(s):  
Tomoko Matsumoto ◽  
Keiji Nogami ◽  
Kenichi Ogiwara ◽  
Nobuyuki Tsujii ◽  
Midori Shima
Keyword(s):  
Research Funding ◽  
Hemophilia A ◽  
Hemorrhagic Diathesis ◽  
Severe Hemophilia ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Time To Peak ◽  
Inhibitory Mechanisms

Abstract Abstract 3666 Development of factor (F)VIII autoantibody inhibitors results in severe hemorrhagic diathesis known as acquired hemophilia A (AHA). Based on kinetics patterns of FVIII inhibition, these inhibitors are classified into type 1 and type 2 behaviors that inhibit FVIII activity completely and incompletely at saturating concentrations, respectively. We have recently reported on the coagulation functions and inhibitory mechanisms of AHA with type 2 (Blood 2009, 106, Abst), but the mechanism(s) by which hemorrhagic symptoms of AHA are markedly severe are poorly understood. In the present study, we investigated the coagulation function and inhibitory mechanisms for AHA with type 1 as well as type 2. Plasma samples of patients were obtained from congenital severe hemophilia A (S-type; FVIII:C<0.2 IU/dl, FVIII:Ag<1 IU/dl; n=15), AHA with type 1 (<0.2 IU/dl, 3.0±4.2 IU/dl; 167±175 BU/ml; n=9), and AHA with type 2 (2.0±1.9 IU/dl, 12.3±7.5 IU/dl; 202±120 BU/ml; n=8). Thrombin generation test (TGT) was performed using tissue factor (0.5 pM), phospholipids (PL 4 μM), and ellagic acid (0.3 μM). Although FVIII:C in type 1 was similar to that in S-type, TGT parameters in type 1 were significantly decreased than those in S-type and type 2 (type 1/type 2/S-type; ETP: 779±520/1166±880/1125±377 nM×min; Peak thrombin: 37.2±20.1/62.4±35.0/65.0±11.2 nM). Of note, time to peak in both types markedly prolonged compared to that in S-type (type 1/type 2/S-type; 34.7±9.2/31.0±6.8/23.8±4.0 min). Similarly, FXa generation using chromogenic assay were decreased in order of S-type>type 2>type 1, demonstrating that coagulation functions of AHA were much worse than that in congenital severe hemophilia A, and those in type 1 was predominantly lower than those in type 2. Next we compared with inhibitory mechanisms of AHA-type 1 and type 2 inhibitors. The IgGs from AHA's plasmas were immune-purified using protein G-Sepharose. All cases recognized the C2 domain alone, and little recognized other coagulation proteins. Competition binding assays showed that all type 1 competed with anti-C2 mAbESH4 (type 1) by 50–80%, whilst little or slightly competed with anti-C2 mAbESH8 (type 2), and that all type 2 competed with ESH8 by 50–85%, whilst little or mildly competed with ESH4. Type 1 IgGs inhibited the FVIII binding of von Willebrand factor (VWF) and PL by 60–80%, whilst type 2 inhibited both bindings by <5%. In our previous and present studies, a FXa generation assay and SDS-PAGE (and Western blotting) analysis revealed that all type 2 blocked thrombin (and FXa)-catalyzed FVIII activation by 80≂f95% through inhibition of cleavage at Arg372 and Arg1689 in dose- and timed-dependent manners. In contrast, all type 1 did not significantly affect FVIII activation and cleavage by thrombin. It was difficult to evaluate FXa-catalyzed FVIII reaction with type 1, since type 1 inhibited the FVIII-PL binding directly. These findings supported that the inhibitory effects of AHA with type 1 and type 2 on FVIII function were similar to those of ESH4 and ESH8 reported, respectively. Taken together, AHA-type 1 inhibitors interfere FVIII-VWF complexes and inhibit FVIII(a)-PL binding essential for function of tenase complex, whilst type 2 inhibitors decrease FXa generation only through inhibition of thrombin (and FXa)-catalyzed FVIII activation, supporting that these distinct mechanisms of both types result in different serious hemorrhagic symptoms. In addition, we speculate that FVIII(a)-inhibitor complexes might inhibit FIXa-catalyzed FX activation indirectly through steric hindrance, consequently coagulation functions in AHA would be significantly worse than those in congenital severe hemophilia A. Disclosures: Nogami: Bayer hemophilia award program 2009: Research Funding. Ogiwara:Baxter Hemophilia Scientific Research and Education Fund in Japan, 2009: Research Funding.

Molecular analysis of FVIII gene in severe HA patients of Costa Rica

2010 ◽  
Vol 30 (S 01) ◽  
pp. S150-S152
Author(s):  
G. Jiménez-Cruz ◽  
M. Mendez ◽  
P. Chaverri ◽  
P. Alvarado ◽  
W. Schröder ◽  
...  
Keyword(s):  
Factor Viii ◽  
Coagulation Factor ◽  
Costa Rican ◽  
Factor Viii Gene ◽  
Intron 22 Inversion ◽  
Intron 1 ◽  
Polymerase Chain ◽  
Inversion Analysis

SummaryHaemophilia A (HA) is X-chromosome linked bleeding disorders caused by deficiency of the coagulation factor VIII (FVIII). It is caused by FVIII gene intron 22 inversion (Inv22) in approximately 45% and by intron 1 inversion (Inv1) in 5% of the patients. Both inversions occur as a result of intrachromosomal recombination between homologous regions, in intron 1 or 22 and their extragenic copy located telomeric to the FVIII gene. The aim of this study was to analyze the presence of these mutations in 25 HA Costa Rican families. Patients, methods: We studied 34 HA patients and 110 unrelated obligate members and possible carriers for the presence of Inv22or Inv1. Standard analyses of the factor VIII gene were used incl. Southern blot and long-range polymerase chain reaction for inversion analysis. Results: We found altered Inv22 restriction profiles in 21 patients and 37 carriers. It was found type 1 and type 2 of the inversion of Inv22. During the screening for Inv1 among the HA patient, who were Inv22 negative, we did not found this mutation. Discussion: Our data highlight the importance of the analysis of Inv22 for their association with development of inhibitors in the HA patients and we are continuous searching of Inv1 mutation. This knowledge represents a step for genetic counseling and prevention of the inhibitor development.

FUNCTIONAL STATUS AND ADAPTIVE POTENTIAL IN FOREIGN STUDENTS WITH DIFFERENT TYPES OF VEGETATIVE REGULATION DURING TUITION

2020 ◽  
pp. 118-126
Author(s):  
A.M. Satarkulova
Keyword(s):  
Heart Rate ◽  
Foreign Students ◽  
Autonomic Regulation ◽  
The Body ◽  
Functional Changes ◽  
Different Types ◽  
Type 3 ◽  
Adaptive Abilities

The assessment and dynamic control over students’ status is a very important task. It allows timely detection of prenosological status prior to pathology and health maintenance in students. The objective of the paper is to assess the adaptive abilities of the body, to analyze changes in heart rate variability indicators in students with various types of autonomic regulation, to identify prenosological status and precursory pathological symptoms. Materials and Methods. The study enrolled 302 students from India, aged 21.54±1.43. Programming complex «Psychophysiologist» was used to register the main HRV parameters within 5 minutes. Health status was evaluated according to the index of functional changes and the scale of functional states. Results. N.I. Shlyk (2009) distinguished two groups of students with different types of autonomic regulation: type 1 (53 %) with moderate and type 2 (5 %) with marked characteristics of central regulation profile, type 3 (35 %) with moderate and type 4 (7 %) with marked characteristics of autonomous regulation profile. Main parameters of HRV and adaptation potential were defined for each student.All the parameters characterized functional and health status. Conclusions. It was shown that 82 % of trial subjects (type 1), 53 % (type 2), 94 % (type 3) and 95 % (type 4) demonstrated satisfactory adaptation and their physiological processes were at an optimal level. 18 % of students (type 1) demonstrated reduced adaptive abilities of the body. Moreover, they were under moderate stress. 47 % of subjects (type 2) were also under a significant stress, which was proven by excessively high SI, low SDNN and TP, and an increased index of functional changes. 5 % of students (type 4) revealed dysfunctional characteristics in the heart rhythm, peculiar to pathology. Keywords: foreign students, heart rate variability, types of autonomic regulation, adaptation potential, functional status. Оценка состояния студентов и динамический контроль за ним является важной задачей, поскольку позволяет своевременно выявлять у студентов донозологические состояния, предшествующие патологии, и способствовать сохранению здоровья. Цель. Оценка адаптивных возможностей организма, анализ изменений показателей вариабельности сердечного ритма у студентов с различными типами вегетативной регуляции, выявление донозологических состояний и ранних признаков патологии. Материалы и методы. В исследовании участвовало 302 студента в возрасте 21,54+1,43 года из Индии. Регистрировались основные параметры ВСР в течение 5 мин с использованием программно-аппаратного комплекса «Психофизиолог». Состояние и уровень здоровья оценивались по индексу функциональных изменений и шкале функциональных состояний. Результаты. По способу, предложенному Н.И. Шлык, выделены группы студентов с различными типами вегетативной регуляции: I (53 %) и II типы (5 %) – с умеренным и выраженным преобладанием центрального контура регуляции соответственно, III (35 %) и IV типы (7 %) – с умеренным и выраженным преобладанием автономного контура регуляции соответственно. У каждого из студентов определены основные параметры ВСР и адаптационного потенциала, характеризующие функциональное состояние и уровень здоровья. Выводы. Показано, что для 82 % обследуемых с I типом, 53 % со II типом, 94 % c III типом и 95 % с IV типом регуляции характерно состояние удовлетворительной адаптации, физиологические процессы сохраняются на оптимальном уровне. В группе студентов I типа у 18 % студентов адаптивные возможности организма снижены, выявлено состояние умеренного напряжения. У 47 % обследуемых II типа также зафиксировано состояние резко выраженного напряжения, индикатором которого является чрезмерно высокое значение SI, низкие величины SDNN и ТP, повышенное значение индекса функциональных изменений. В группе студентов с IV типом у 5 % учащихсяв регуляции ритма сердца выявлены дисфункциональные признаки, характерные для патологии. Ключевые слова: иностранные студенты, вариабельность сердечного ритма, типы вегетативной регуляции, адаптационный потенциал, функциональное состояние.

POLIOMYELITIS IN CANADIAN ESKIMOS: LABORATORY STUDIES. V. TYPE 1 AND TYPE 3 POLIOMYELITIS ANTIBODY LEVELS IN BAFFIN ISLAND ESKIMOS

1954 ◽  
Vol 32 (1) ◽  
pp. 119-125
Author(s):  
W. Wood ◽  
Eina M. Clark ◽  
F. T. Shimada ◽  
A. J. Rhodes
Keyword(s):  
Medical Records ◽  
Baffin Island ◽  
Tissue Cultures ◽  
Laboratory Studies ◽  
Poliomyelitis Virus ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Type 3

Studies on the basic immunology of poliomyelitis in Canadian Eskimos have been continued. Some 87 sera collected from Eskimos at Pangnirtung, Baffin Island, have been examined for the presence of Type 1 and Type 3 poliomyelitis antibody by quantitative tests in tissue cultures. The same sera were previously examined for Type 2 antibody by quantitative tests in mice. The results of the three determinations are now presented together for comparison. These sera came from Eskimos aged 2 to 72 years of age. None of the Eskimos showed any evidence of paralysis. Examination of the medical records did not suggest that any paralytic disease had been present in this part of Baffin Island. Very few of the sera showed the presence of poliomyelitis antibody; thus, Type 1 antibody was demonstrated in the sera of 8%, Type 2 antibody in the sera of 9%, and Type 3 antibody in the sera of 14%. No significant number of Eskimos below the age of 45 years had acquired poliomyelitis antibody. The antibody titers mostly ranged between 10−1.0 and 10−2.0, and were significantly lower than the titers customarily found in recently paralyzed cases. These findings suggest that poliomyelitis infection occurred in Pangnirtung Eskimos many years before the date on which the samples were taken (1951). These results point to the worldwide prevalence of the three types of poliomyelitis virus.

Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

2021 ◽  
Vol 47 (02) ◽  
pp. 192-200
Author(s):  
James S. O'Donnell
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Personalized Treatment ◽  
Treatment Plans ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThe biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to > 50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures.

scholarly journals Optimally growing initial errors of El Niño events in the CESM

2021 ◽  
Author(s):  
Hui Xu ◽  
Lei Chen ◽  
Wansuo Duan
Keyword(s):  
El Niño ◽  
El Nino ◽  
Equatorial Pacific ◽  
Initial Error ◽  
Initial Errors ◽  
El Niño Events ◽  
Type 3 ◽  
El Nino Events

AbstractThe optimally growing initial errors (OGEs) of El Niño events are found in the Community Earth System Model (CESM) by the conditional nonlinear optimal perturbation (CNOP) method. Based on the characteristics of low-dimensional attractors for ENSO (El Niño Southern Oscillation) systems, we apply singular vector decomposition (SVD) to reduce the dimensions of optimization problems and calculate the CNOP in a truncated phase space by the differential evolution (DE) algorithm. In the CESM, we obtain three types of OGEs of El Niño events with different intensities and diversities and call them type-1, type-2 and type-3 initial errors. Among them, the type-1 initial error is characterized by negative SSTA errors in the equatorial Pacific accompanied by a negative west–east slope of subsurface temperature from the subsurface to the surface in the equatorial central-eastern Pacific. The type-2 initial error is similar to the type-1 initial error but with the opposite sign. The type-3 initial error behaves as a basin-wide dipolar pattern of tropical sea temperature errors from the sea surface to the subsurface, with positive errors in the upper layers of the equatorial eastern Pacific and negative errors in the lower layers of the equatorial western Pacific. For the type-1 (type-2) initial error, the negative (positive) temperature errors in the eastern equatorial Pacific develop locally into a mature La Niña (El Niño)-like mode. For the type-3 initial error, the negative errors in the lower layers of the western equatorial Pacific propagate eastward with Kelvin waves and are intensified in the eastern equatorial Pacific. Although the type-1 and type-3 initial errors have different spatial patterns and dynamic growing mechanisms, both cause El Niño events to be underpredicted as neutral states or La Niña events. However, the type-2 initial error makes a moderate El Niño event to be predicted as an extremely strong event.

scholarly journals Successful Aging Perception in Middle-Aged Korean Men: A Q Methodology Approach

2021 ◽  
Vol 18 (6) ◽  
pp. 3095
Author(s):  
Mi Hyeon Seong ◽  
Eunyoung Shin ◽  
Sohyune Sok
Keyword(s):  
Successful Aging ◽  
Q Methodology ◽  
Principal Component ◽  
Middle Aged ◽  
Practice Nurses ◽  
Mature Type ◽  
Type 3 ◽  
Family Centered

The purpose of this study is to identify the types of perception of successful aging in middle-aged men and to analyze and describe the characteristics of each type of successful aging perception of middle-aged men in South Korea. This study uses an exploratory study design, applying the Q methodology, which is a subjective research method. The participants were 25 middle-aged men (40 to 60 years old) living in C, Y, and B cities, which were P-samples that were judged to best reveal the successful aging of middle-aged men. In this study, principal component analysis of the PQ method program was used. The five perception types of successful aging among middle-aged men are Type 1 for the “leisure type”, Type 2 for the “mature type”, Type 3 for the “health-oriented type”, Type 4 for the “patriarchal type”, and Type 5 for the “family-centered type”. The mature type had the highest variance among the five types, and the leisure type was the type that showed the second-highest variance. In nursing practice, nurses need to pay attention to the successful aging perceptions of middle-aged Korean men for their successful aging in the future.

scholarly journals The Effect of Coronal Implant Design and Drilling Protocol on Bone-to-Implant Contact: A 3-Month Study in the Minipig Calvarium

Materials ◽  
2021 ◽  
Vol 14 (10) ◽  
pp. 2645
Author(s):  
Omer Cohen ◽  
Dieter D. Bosshardt ◽  
Evegeny Weinberg ◽  
Gil Slutzkey ◽  
Ofer Moses
Keyword(s):  
Implant Design ◽  
Drill Diameter ◽  
Bone To Implant Contact ◽  
Type 3

Stress concentrated at an implant’s neck may affect bone-to-implant contact (BIC). The objective of this study was to evaluate four different implant neck designs using two different drilling protocols on the BIC. Methods: Ninety-six implants were inserted in 12 minipigs calvarium. Implants neck designs evaluated were: type 1–6 coronal flutes (CFs), 8 shallow microthreads (SMs); type 2–6 CFs,4 deep microthreads (DMs); type 3–4 DMs; type 4–2 CFs, 8 SMs. Two groups of forty-eight implants were inserted with a final drill diameter of 2.8 mm (DP1) or 3.2 mm (DP2). Animals were sacrificed after 1 and 3 months, total-BIC (t-BIC) and coronal-BIC (c-BIC) were evaluated by nondecalcified histomorphometry analysis. Results: At 1 month, t-BIC ranged from 85–91% without significant differences between implant types or drilling protocol. Flutes on the coronal aspect impaired the BIC at 3 m. c-BIC of implant types with 6 CFs was similar and significantly lower than that of implant types 3 and 4. c-BIC of implant type 4 with SMs was highest of all implant types after both healing periods. Conclusions: BIC was not affected by the drilling protocol. CFs significantly impaired the -BIC. Multiple SMs were associated with greater c-BIC.

scholarly journals Challenge of diabetes mellitus and researchers’ contributions to its control

2021 ◽  
Vol 19 (1) ◽  
pp. 614-634
Author(s):  
Ayodele T. Odularu ◽  
Peter A. Ajibade
Keyword(s):  
Diabetes Mellitus ◽  
Medical Records ◽  
Diabetes Type ◽  
Future Studies ◽  
The Past ◽  
Significant Events ◽  
Review Study ◽  
Type 3

Abstract The aim of this review study was to assess the past significant events on diabetes mellitus, transformations that took place over the years in the medical records of treatment, countries involved, and the researchers who brought about the revolutions. This study used the content analysis to report the existence of diabetes mellitus and the treatments provided by researchers to control it. The focus was mainly on three main types of diabetes (type 1, type 2, and type 3 diabetes). Ethical consideration has also helped to boost diabetic studies globally. The research has a history path from pharmaceuticals of organic-based drugs to metal-based drugs with their nanoparticles in addition to the impacts of nanomedicine, biosensors, and telemedicine. Ongoing and future studies in alternative medicine such as vanadium nanoparticles (metal nanoparticles) are promising.

Research on Effect of Alloy Elements on Equilibrium and Properties of Ni-Cr-Co Type Nickel-Based Superalloy

2016 ◽  
Vol 849 ◽  
pp. 513-519
Author(s):  
Qing Quan Zhang ◽  
Ming Yang Li ◽  
Ran Wei ◽  
Hui Yun Wu ◽  
Zhen Rui Li
Keyword(s):  
High Temperature ◽  
Room Temperature ◽  
High Temperature Strength ◽  
Nickel Based Superalloy ◽  
Type 3 ◽  
Room Temperature Strength ◽  
Super Alloy ◽  
Type Nickel

Ni-Cr-Co type Nickel-based super alloy Inconel 740H was studied. The effect of Nb, Al and Ti on the equilibrium of this alloy was analyzed by JMatPro software. The amount of Ti and Nb should be controlled by 1.50wt.%, and meanwhile, Al should be 1.0-2.0wt.%. If Mo and W were added the amount of Mo should be in the range of 1.0-2.0wt. %, and W should be about 1.0wt.%. Based on these results, three types of new alloys were designed, which contain Ni-Cr-Co-Mo type (1#), Ni-Cr-Co-W type (2#) and Ni-Cr-Co-Mo-W type (3#). Compared with the Ni-Cr-Co type Inconel 740H alloy, the room temperature strength, high temperature strength and high temperature durable performance of the three new alloys improved, which can provide the evidence and reference to optimize the chemical composition of Inconel 740H alloy, i.e., adding 1.50wt.% Mo and 1.0wt.% W individually or together.

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