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1.
Trop Anim Health Prod ; 54(5): 310, 2022 Sep 20.
Article in English | MEDLINE | ID: mdl-36123551

ABSTRACT

INTRODUCTION: Gir is a Bos indicus breed originally from India, first imported to Brazil in 1850. High-performance Dairy Gir has been systematically selected in Brazil from its arrival. Since the major phenotypic difference between Gir in India and Brazil is a higher milk production in the former, it is speculated that Brazilian Gir was strategically crossed with Holstein or another Bos taurus to improve milk yield. This study evaluated the purity of Brazilian Gir breed stocks from BASA Farms in Brazil, trying to identify possible admixture events with other cattle breeds based on DNA analysis. MATERIALS AND METHODS: The population included 1061 pure registered individuals genotyped using two commercial platforms with 37 k and 25 k SNPs. Admixture analysis was performed individually to estimate levels of genomic composition derived from six different reference populations, three indicine and three taurine breeds. RESULTS: A Gir ancestry of 99% or higher was found for 94.2% of the population, while the remaining showed levels of non-Gir ancestry up to 6.8%. Only five individuals were identified with possible taurine ancestry, all of them exhibiting levels lower than 2%. The remaining non-Gir ancestry identified was derived from indicine breeds. The levels of admixture observed in the population were from low to non-detectable. No consistent patterns of admixture were observed indicating sustained introgression of taurine lines as means of genetic improvement. CONCLUSION: According to these results, genetic improvement achieved by Brazilian Gir breeders is the result of within-breed selection methods applied intensively over the past five decades, rather than the result from sustained introgression.


Subject(s)
Genomics , Polymorphism, Single Nucleotide , Animals , Brazil , Cattle/genetics , DNA
2.
Anim Genet ; 50(6): 557-568, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31475748

ABSTRACT

Together with their sister subspecies Bos taurus, zebu cattle (Bos indicus) have contributed to important socioeconomic changes that have shaped modern civilizations. Zebu cattle were domesticated in the Indus Valley 8000 years before present (YBP). From the domestication site, they expanded to Africa, East Asia, southwestern Asia and Europe between 4000 and 1300 YBP, intercrossing with B. taurus to form clinal variations of zebu ancestry across the landmass of Afro-Eurasia. In the past 150 years, zebu cattle reached the Americas and Oceania, where they have contributed to the prosperity of emerging economies. The zebu genome is characterized by two mitochondrial haplogroups (I1 and I2), one Y chromosome haplogroup (Y3) and three major autosomal ancestral groups (Indian-Pakistani, African and Chinese). Phenotypically, zebu animals are recognized by their hump, large ears and excess skin. They are rustic, resilient to parasites and capable of bearing the hot and humid climates of the tropics. Many resources are available to study the zebu genome, including commercial arrays of SNP, reference assemblies and publicly available genotypes and whole-genome sequences. Nevertheless, many of these resources were initially developed to support research and subsidize industrial applications in B. taurus, and therefore they can produce bias in data analysis. The combination of genomics with precision agriculture holds great promise for the identification of genetic variants affecting economically important traits such as tick resistance and heat tolerance, which were naturally selected for millennia and played a major role in the evolution of B. indicus cattle.


Subject(s)
Cattle/genetics , Cattle/physiology , Animals , Biological Evolution , Cattle/anatomy & histology , Disease Resistance , Domestication , Ear/anatomy & histology , Fertility , Genetic Variation , Organ Size , Skin/anatomy & histology
3.
Arq. bras. med. vet. zootec. (Online) ; 70(2): 517-524, mar.-abr. 2018. tab
Article in English | LILACS, VETINDEX | ID: biblio-910689

ABSTRACT

The objective this paper was to evaluate the effect of two categories of beef finished in pasture with supplementation with two herbage allowance on performance, carcass and meat characteristics. Thirty-six Guzera cattle were used, 18 steers and 18 heifers with an initial age of 20 months. There was significant difference in daily weight gain for animal category and the herbage allowance, which were higher in males and animals submitted to high herbage allowance. Steers showed higher final weight, carcass weight and forequarter yield compared with the heifers, although the hindquarter yield was higher in the heifers, however the herbage allowance did not influence these characteristics. There were not statistical differences for carcass yield, ribeye area, backfat thickness and marbling score for the animal categories and herbage allowance. The meat chemical composition of the steers did not differ of the heifers, however, the animals submitted to high herbage allowance was increase in ether extract and pH, decrease in protein percentage. It was concluded that the animal category and the herbage allowance changed the animal performance, improving performance in males and cattle submitted to high herbage allowance.(AU)


O objetivo do presente trabalho foi avaliar o efeito de duas categorias de bovinos terminados em pastagem com suplementação em duas ofertas de forragem no desempenho, na qualidade da carcaça e da carne. Foram utilizados 36 bovinos Guzerá, 18 novilhos e 18 novilhas, com idade inicial de 20 meses de idade. Observou-se diferença significativa no ganho de peso diário para categoria animal e ofertas de forragem, que foram superiores nos machos e nos animais submetidos à oferta alta de forragem. Os novilhos apresentaram maior peso final, peso de carcaça e rendimento de dianteiro em comparação com as novilhas, embora o rendimento do traseiro tenha sido maior para as novilhas, entretanto as ofertas de forragem não influenciaram essas características. Não houve diferenças estatísticas para rendimento de carcaça, área de olho de lombo, espessura de gordura subcutânea e marmorização para categorias de animais e ofertas de forragem. Quanto à composição química, a carne de novilhos não diferiu das novilhas. Os animais submetidos à alta oferta de forragem tiveram aumento no extrato etéreo e pH, redução na porcentagem de proteína. Conclui-se que a categoria animal e os níveis de forragem alteram o desempenho animal, melhorando, assim, o desempenho nos machos e nos bovinos submetidos à alta oferta de forragem.(AU)


Subject(s)
Animals , Cattle , Infant Nutritional Physiological Phenomena , Meat/classification , Pasture/analysis , Cattle , Weight Gain
5.
J Dairy Sci ; 100(7): 5479-5490, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28527809

ABSTRACT

Genomic selection may accelerate genetic progress in breeding programs of indicine breeds when compared with traditional selection methods. We present results of genomic predictions in Gyr (Bos indicus) dairy cattle of Brazil for milk yield (MY), fat yield (FY), protein yield (PY), and age at first calving using information from bulls and cows. Four different single nucleotide polymorphism (SNP) chips were studied. Additionally, the effect of the use of imputed data on genomic prediction accuracy was studied. A total of 474 bulls and 1,688 cows were genotyped with the Illumina BovineHD (HD; San Diego, CA) and BovineSNP50 (50K) chip, respectively. Genotypes of cows were imputed to HD using FImpute v2.2. After quality check of data, 496,606 markers remained. The HD markers present on the GeneSeek SGGP-20Ki (15,727; Lincoln, NE), 50K (22,152), and GeneSeek GGP-75Ki (65,018) were subset and used to assess the effect of lower SNP density on accuracy of prediction. Deregressed breeding values were used as pseudophenotypes for model training. Data were split into reference and validation to mimic a forward prediction scheme. The reference population consisted of animals whose birth year was ≤2004 and consisted of either only bulls (TR1) or a combination of bulls and dams (TR2), whereas the validation set consisted of younger bulls (born after 2004). Genomic BLUP was used to estimate genomic breeding values (GEBV) and reliability of GEBV (R2PEV) was based on the prediction error variance approach. Reliability of GEBV ranged from ∼0.46 (FY and PY) to 0.56 (MY) with TR1 and from 0.51 (PY) to 0.65 (MY) with TR2. When averaged across all traits, R2PEV were substantially higher (R2PEV of TR1 = 0.50 and TR2 = 0.57) compared with reliabilities of parent averages (0.35) computed from pedigree data and based on diagonals of the coefficient matrix (prediction error variance approach). Reliability was similar for all the 4 marker panels using either TR1 or TR2, except that imputed HD cow data set led to an inflation of reliability. Reliability of GEBV could be increased by enlarging the limited bull reference population with cow information. A reduced panel of ∼15K markers resulted in reliabilities similar to using HD markers. Reliability of GEBV could be increased by enlarging the limited bull reference population with cow information.


Subject(s)
Genomics/standards , Genotyping Techniques/veterinary , Glycolipids/metabolism , Glycoproteins/metabolism , Milk/metabolism , Polymorphism, Single Nucleotide , Selective Breeding/genetics , Age Factors , Animals , Brazil , Cattle , Dairying , Female , Genetic Markers , Genotype , Genotyping Techniques/methods , Lactation , Lipid Droplets , Male , Oligonucleotide Array Sequence Analysis/veterinary , Pregnancy , Reproducibility of Results
8.
Leukemia ; 30(3): 716-27, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26437781

ABSTRACT

Adult T-cell leukemia (ATL) arises from a human T-cell leukemia virus type I (HTLV-I)-infected cell and has few therapeutic options. Here, we have uncovered a previously unrecognized role for a ubiquitin-editing enzyme A20 in the survival of HTLV-I-infected cells. Unlike in lymphomas of the B-cell lineage, A20 is abundantly expressed in primary ATL cells without notable mutations. Depletion of A20 in HTLV-I-infected cells resulted in caspase activation, cell death induction and impaired tumorigenicity in mouse xenograft models. Mechanistically, A20 stably interacts with caspase-8 and Fas-associated via death domain (FADD) in HTLV-I-infected cells. Mutational studies revealed that A20 supports the growth of HTLV-I-infected cells independent of its catalytic functions and that the zinc-finger domains are required for the interaction with and regulation of caspases. These results indicate a pivotal role for A20 in the survival of HTLV-I-infected cells and implicate A20 as a potential therapeutic target in ATL.


Subject(s)
Caspase 8/genetics , DNA-Binding Proteins/genetics , Fas-Associated Death Domain Protein/genetics , Human T-lymphotropic virus 1/genetics , Intracellular Signaling Peptides and Proteins/genetics , Leukemia-Lymphoma, Adult T-Cell/genetics , Nuclear Proteins/genetics , Adult , Animals , Caspase 3/genetics , Caspase 3/metabolism , Caspase 7/genetics , Caspase 7/metabolism , Caspase 8/metabolism , Cell Death , Cell Line , DNA-Binding Proteins/antagonists & inhibitors , DNA-Binding Proteins/metabolism , Fas-Associated Death Domain Protein/metabolism , Female , Gene Expression Regulation, Leukemic , Genetic Vectors , HEK293 Cells , Host-Pathogen Interactions , Human T-lymphotropic virus 1/pathogenicity , Humans , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Intracellular Signaling Peptides and Proteins/metabolism , Lentivirus/genetics , Leukemia-Lymphoma, Adult T-Cell/metabolism , Leukemia-Lymphoma, Adult T-Cell/pathology , Leukemia-Lymphoma, Adult T-Cell/virology , Mice , Mice, Inbred NOD , Neoplasm Transplantation , Nuclear Proteins/antagonists & inhibitors , Nuclear Proteins/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Signal Transduction , Tumor Burden , Tumor Necrosis Factor alpha-Induced Protein 3
9.
Bone Marrow Transplant ; 51(2): 205-11, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26524263

ABSTRACT

Allogeneic hematopoietic SCT (allo-HSCT) is a curative treatment for aggressive adult T-cell leukemia/lymphoma (ATLL). Considering the dismal prognosis associated with conventional chemotherapies, early application of allo-HSCT might be beneficial for patients with ATLL. However, no previous study has addressed the optimal timing of allo-HSCT from related donors. Hence, to evaluate the impact of timing of allo-HSCT for patients with ATLL, we retrospectively analyzed data from patients with ATLL who received an allo-HSCT from a related donor. The median age was 52 years. Patients were grouped according to the interval from diagnosis to allo-HSCT: early transplant group, <100 days, n=72; late transplant group, ⩾100 days, n=428. The corresponding constituents of disease status were not statistically different between the two groups (P=0.11). The probability of OS in the early transplant group was significantly higher than that in the late transplant group (4-year OS, 49.3% vs 31.2%). Multivariate analysis revealed that late allo-HSCT was an unfavorable prognostic factor for OS (hazard ratio, 1.46; 95% confidence interval (CI), 1.01-2.11; P=0.04). Despite the limitations of a retrospective study, it might be acceptable to consider early application of allo-HSCT for ATLL.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia-Lymphoma, Adult T-Cell/diagnosis , Leukemia-Lymphoma, Adult T-Cell/therapy , Adolescent , Adult , Aged , Allografts , Female , Follow-Up Studies , Humans , Leukemia-Lymphoma, Adult T-Cell/mortality , Male , Middle Aged , Prognosis , Registries , Retrospective Studies , Time Factors
10.
Arq. bras. med. vet. zootec ; 67(4): 1119-1124, July-Aug. 2015. tab
Article in Portuguese | LILACS | ID: lil-759243

ABSTRACT

O objetivo do trabalho foi estimar os parâmetros genéticos das características de crescimento da raça Suffolk, a fim de fornecer subsídio para a definição de estratégias de seleção para programas de melhoramento genético. Os dados analisados, coletados entre os anos de 2007 a 2009, são referentes a ovinos da raça Suffolk oriundos de uma propriedade localizada no Estado de São Paulo, Brasil, participante do programa de melhoramento genético Ovigol, conduzido pela empresa Aries Reprodução e Melhoramento Genético Ovino Ltda. em parceria com a empresa AbacusBio Limited, da Nova Zelândia. As características avaliadas foram: peso ao nascer (PN), ganho de peso pré-desmame (GPP) e peso ao desmame (PD), com número de registro de 1.039, 636 e 649 animais, respectivamente. Para análise estatística, utilizou-se o procedimento GLM do programa computacional SAS; para a consistência do pedigree e para as estimativas dos parâmetros genéticos, os programas computacionais utilizados foram Relax2: pedigree analysis program e o WOMBAT, respectivamente. O modelo linear geral incluiu sexo, grupo de contemporâneos (tipo de parto e ano de nascimento), covariável idade ao desmame (GPP e PD) com efeito quadrático, efeito genético aditivo direto, efeito de ambiente permanente materno e efeito residual. As herdabilidades para PN, GPP e PD foram 0,06, 0,42 e 0,37, respectivamente. As correlações genéticas entre PN e GPP, PN e PD e GPP e PD foram -0,10, -0,03 e 0,97, respectivamente. Na população estudada, as características GPP e PD, apresentam altas respostas à seleção, ao contrário do PN. As características PN e GPP são suficientes para compor um índice de seleção, sendo aconselhável o monitoramento do PN na fase inicial do programa.


The aim of this study was to estimate genetic parameters for growth of Suffolk, in order to provide a basis for the definition of selection strategies for breeding programs. The data analyzed are for Suffolk sheep, collected between years 2007 to 2009, from a property located in the State of São Paulo - Brazil, a participant in the Ovigol breeding program conducted by the company (Aries Reproduction and Breeding Sheep Ltd.) in partnership with (AbacusBio) New Zealand Limited. The evaluated characteristics were: birth weight (PN), weight gain pre-weaning (GPP) and weaning weight (PD), with registration number 1039, 636 and 649 respectively. For statistical analysis we used the GLM procedure of SAS software, for the consistency of pedigree and genetic parameter estimates software Relax2: pedigree analysis program and WOMBAT, respectively, were used. The general linear model included sex, contemporary group (type of birth and year of birth), covariate age at weaning (GPP and PD) with a quadratic effect, direct genetic effect, maternal permanent environmental effect and residual effect. Heritability estimates for PN, PD and GPP were 0.06, 0.42 and 0.37, respectively. Genetic correlations between PN and GPP, and PN and PD and GPP were -0.10, -0.03 and 0.97, respectively. In the study population characteristics GPP and PD have a high response to selection, unlike the PN. The GPP and PN characteristics are enough to make a selection index, it is advisable to monitor the PN in the initial phase of the program.


Subject(s)
Animals , Genetic Enhancement , Genetic Fitness , Sheep/growth & development , Sheep/genetics , Models, Genetic , Chromosome Mapping/veterinary
11.
J Dairy Sci ; 98(7): 4969-89, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25958293

ABSTRACT

Genotype imputation is widely used as a cost-effective strategy in genomic evaluation of cattle. Key determinants of imputation accuracies, such as linkage disequilibrium patterns, marker densities, and ascertainment bias, differ between Bos indicus and Bos taurus breeds. Consequently, there is a need to investigate effectiveness of genotype imputation in indicine breeds. Thus, the objective of the study was to investigate strategies and factors affecting the accuracy of genotype imputation in Gyr (Bos indicus) dairy cattle. Four imputation scenarios were studied using 471 sires and 1,644 dams genotyped on Illumina BovineHD (HD-777K; San Diego, CA) and BovineSNP50 (50K) chips, respectively. Scenarios were based on which reference high-density single nucleotide polymorphism (SNP) panel (HDP) should be adopted [HD-777K, 50K, and GeneSeek GGP-75Ki (Lincoln, NE)]. Depending on the scenario, validation animals had their genotypes masked for one of the lower-density panels: Illumina (3K, 7K, and 50K) and GeneSeek (SGGP-20Ki and GGP-75Ki). We randomly selected 171 sires as reference and 300 as validation for all the scenarios. Additionally, all sires were used as reference and the 1,644 dams were imputed for validation. Genotypes of 98 individuals with 4 and more offspring were completely masked and imputed. Imputation algorithms FImpute and Beagle v3.3 and v4 were used. Imputation accuracies were measured using the correlation and allelic correct rate. FImpute resulted in highest accuracies, whereas Beagle 3.3 gave the least-accurate imputations. Accuracies evaluated as correlation (allelic correct rate) ranged from 0.910 (0.942) to 0.961 (0.974) using 50K as HDP and with 3K (7K) as low-density panels. With GGP-75Ki as HDP, accuracies were moderate for 3K, 7K, and 50K, but high for SGGP-20Ki. The use of HD-777K as HDP resulted in accuracies of 0.888 (3K), 0.941 (7K), 0.980 (SGGP-20Ki), 0.982 (50K), and 0.993 (GGP-75Ki). Ungenotyped individuals were imputed with an average accuracy of 0.970. The average top 5 kinship coefficients between reference and imputed individuals was a strong predictor of imputation accuracy. FImpute was faster and used less memory than Beagle v4. Beagle v4 outperformed Beagle v3.3 in accuracy and speed of computation. A genotyping strategy that uses the HD-777K SNP chip as a reference panel and SGGP-20Ki as the lower-density SNP panel should be adopted as accuracy was high and similar to that of the 50K. However, the effect of using imputed HD-777K genotypes from the SGGP-20Ki on genomic evaluation is yet to be studied.


Subject(s)
Cattle/genetics , Genotype , Oligonucleotide Array Sequence Analysis/veterinary , Polymorphism, Single Nucleotide , Animals , Female , Male , Oligonucleotide Array Sequence Analysis/methods
14.
Arq. bras. med. vet. zootec ; 66(4): 1139-1146, 08/2014. tab, graf
Article in Portuguese | LILACS | ID: lil-722570

ABSTRACT

Objetivou-se avaliar a aplicação da metodologia de modelos lineares mistos em características de escores visuais por meio de simulação, considerando-se duas estruturas populacionais (com e sem seleção), dois níveis de herdabilidade (0,1 e 0,4) e quatro níveis de conectabilidade (8, 20, 38 e 60 por cento). As populações com e sem seleção estavam constituídas por 6660 e 3360 animais, respectivamente, dos quais os últimos 2460 animais tinham fenótipo para o escore visual. Assumiu-se uma variável contínua adjacente ao escore visual, a partir da qual foram definidos os intervalos correspondentes a cada categoria de escore visual. O processo de simulação foi feito por meio do software R, e a estimação de parâmetros e predição de valores genéticos pelo software Wombat, sob modelo animal, considerando-se modelos com e sem efeitos fixos. Os critérios de avaliação foram: o erro quadrático médio (EQM) para a herdabilidade e as correlações de Spearman entre os valores genéticos verdadeiros e preditos. As estimativas da herdabilidade apresentaram-se próximas do valor verdadeiro nos cenários sem seleção (0,084-0,101 e 0,367-0,389), no entanto este resultado não ocorreu quando houve seleção, pois a herdabilidade apresentou-se subestimada (0,032 e 0,278). As correlações apresentaram-se maiores nos cenários sem seleção e com herdabilidade de 0,4 (0,86-0,89). Em todos os cenários simulados, a inclusão do efeito fixo no modelo melhorou as estimativas de herdabilidade e as correlações entre os valores genéticos verdadeiros e preditos. O nível de conectabilidade afetou a correção dos efeitos fixos feita pela atribuição dos escores. Em conclusão, a metodologia dos modelos lineares mistos pode ser utilizada na estimação de parâmetros e predição de valores genéticos de escores visuais em populações sem seleção, entretanto não se apresenta adequada em populações sob seleção...


This study aimed to evaluate the application of linear mixed models methodology using simulated data for trait visual scores, two population structures (with and without selection), two levels of heritability (0.1 and 0.4) and four levels of connectability (8, 20, 38 and 60 percent) were examined. Populations with and without selection consisted of 6,660 and 3,360 animals respectively, of which, the last in 2460 had score visual phenotypes. The scores were simulated with an underlying normal distribution from which intervals were defined corresponding to each category of the visual scores. The simulation process was performed in software R, to estimate genetic parameters and predict breeding values through software Wombat using animal model, considering models with and without fixed effects. The evaluation criteria were: the mean squared error (EQM) for heritability and Spearman correlations between true and predicted breeding values. Estimates of heritability showed close to the true value in scenarios without selection (0.084-0.101 and 0.367-0.389), however when selection was applied heritability was underestimated (0.032 and 0.278). Consistent with heritability, the correlations were higher for the scenarios without selection and with heritability of 0.4 (0.86-0.89). In all scenarios simulated the inclusion of fixed effects in the model improved the estimates of heritability and correlations between true and predicted breeding values. The level of connectability affected the correction of fixed effects done by allocating visual scores. The linear mixed model methodology can be used in the estimation of genetic parameters and predicted breeding values for visual scores in populations without selection, however, is not suiting in populations under selection...


Subject(s)
Animals , Cattle , Cattle/classification , Heredity , Linear Models , Templates, Genetic , Forecasting/methods , Software
15.
Spinal Cord ; 52(10): 729-33, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24777166

ABSTRACT

OBJECTIVE: Magnetic resonance imaging (MRI) is useful in diagnosing spontaneous spinal epidural hematoma (SSEH). The purpose of the present study is to determine whether apparent diffusion coefficient (ADC) values could determine severity of spinal cord damage and predict functional recovery in SSEH. METHODS: The study involved four consecutive patients with SSEH (two men and two women: aged 21-76 years). Using axial slices, ADC values were determined in four separate regions of the spinal cord. These areas were classified into the following three groups based on findings in T2-weighted images: normal T2 intensity; persistent T2 abnormality; and temporary T2 abnormality. ADC values among different groups were compared. The relationship between preoperative ADC values and neurological grades were also evaluated. RESULTS: ADC values in normal T2 areas were 0.89 ± 0.10 × 10(-3) mm(2) s(-1), whereas those for the persistent T2 abnormality group were significantly lower (0.63 ± 0.14 × 10(-3)). In a patient who was Frankel A on admission and in the follow-up, the ADC value was as low as 0.41 × 10(-3). Functional recovery was also limited in the spinal cord segments with lower ADC values. In the temporary T2 abnormality group, ADC values were significantly higher (1.05 ± 0.10 × 10(-3)). CONCLUSIONS: In SSEH, if MRI demonstrated T2-hyperintensity with lower ADC values, patients may suffer from irreversible spinal cord damages. ADC values of the spinal cord can be added as a new factor that reliably indicated the severity of spinal cord damage and predicted functional recovery.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Hematoma, Epidural, Spinal/pathology , Recovery of Function , Spinal Cord/pathology , Adult , Aged , Female , Hematoma, Epidural, Spinal/diagnosis , Humans , Image Interpretation, Computer-Assisted/methods , Male , Middle Aged , Predictive Value of Tests , Prognosis , Severity of Illness Index , Young Adult
16.
Blood Cancer J ; 3: e159, 2013 Nov 15.
Article in English | MEDLINE | ID: mdl-24241399

ABSTRACT

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with a very poor outcome. However, several studies have shown a progress in the treatment. To evaluate the effect of the progress in the treatment of ATLL in a whole patient population, we used vital statistics data and estimated age-adjusted mortality and trends in the mortality from 1995 to 2009. Since allogeneic hematopoietic stem-cell transplantation (allo-HSCT) has been introduced as a modality with curative potential during study period, we also evaluated the association of the annual number of allo-HSCT and the trend of the mortality of ATLL. Endemic (Kyushu) and non-endemic areas (others) were evaluated separately. Significance in the trend of mortality was evaluated by joinpoint regression analysis. During the study period, a total of 14 932 patients died of ATLL in Japan, and mortality decreased significantly in both areas (annual percent change (95% confidence interval (CI)): Kyushu, -3.1% (-4.3, -1.9); others, -3.4% (-5.3, -1.5)). This decreasing trend in mortality seems to be associated with an increase in the number of allo-HSCTs (Kyushu, R-squared=0.70, P=0.003; and others, R-squared=0.55, P=0.058). This study reveals that the mortality of ATLL is now significantly decreasing in Japan and this decreasing trend might be associated with allo-HSCT.

17.
Leukemia ; 26(6): 1238-46, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22289924

ABSTRACT

Cell adhesion molecule 1 (CADM1/TSLC1) was recently identified as a novel cell surface marker for adult T-cell leukemia/lymphoma (ATLL). In this study, we developed various antibodies as diagnostic tools to identify CADM1-positive ATLL leukemia cells. In flow cytometric analysis, the percentages of CD4(+)CADM1(+) double-positive cells correlated well with both the percentages of CD4(+)CD25(+) cells and with abnormal lymphocytes in the peripheral blood of patients with various types of ATLL. Moreover, the degree of CD4(+)CADM1(+) cells over 1% significantly correlated with the copy number of the human T-lymphotropic virus type 1 (HTLV-1) provirus in the peripheral blood of HTLV-1 carriers and ATLL patients. We also identified a soluble form of CADM1 in the peripheral blood of ATLL patients, and the expression levels of this form were correlated with the levels of soluble interleukin 2 receptor alpha. Moreover, lymphomas derived from ATLL were strongly and specifically stained with a CADM1 antibody. Thus, detection of CD4(+)CADM1(+) cells in the peripheral blood, measurement of serum levels of soluble CADM1 and immunohistochemical detection of CADM1 in lymphomas would be a useful set of markers for disease progression in ATLL and may aid in both the early diagnosis and measurement of treatment efficacy for ATLL.


Subject(s)
Cell Adhesion Molecules/metabolism , HTLV-I Infections/diagnosis , Immunoglobulins/metabolism , Leukemia-Lymphoma, Adult T-Cell/diagnosis , Leukemia-Lymphoma, Adult T-Cell/metabolism , Tumor Suppressor Proteins/metabolism , Adult , Case-Control Studies , Cell Adhesion Molecule-1 , Cell Adhesion Molecules/immunology , DNA, Viral/genetics , Disease Progression , Flow Cytometry , HTLV-I Infections/genetics , HTLV-I Infections/virology , Human T-lymphotropic virus 1/genetics , Humans , Immunoenzyme Techniques , Immunoglobulins/immunology , Leukemia-Lymphoma, Adult T-Cell/virology , Lymphocytes/cytology , Lymphocytes/metabolism , Proviruses/genetics , Real-Time Polymerase Chain Reaction , Viral Load
18.
Bone Marrow Transplant ; 46(1): 116-8, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20400987

ABSTRACT

We have previously conducted clinical trials of allogeneic hematopoietic SCT with reduced-intensity conditioning regimen (RIC) for adult T-cell leukemia/lymphoma (ATLL)-a disease caused by human T-lymphotropic virus type 1 (HTLV-1) infection and having a dismal prognosis. Long-term follow-up studies of these trials revealed that 10 of the 29 patients have survived for a median of 82 months (range, 54-100 months) after RIC, indicating a possible curability of the disease by RIC. However, we have also observed that the patterns of post-RIC changes in HTLV-1 proviral load over time among the 10 survivors were classified into three patterns. This is the first report to clarify the long-term outcomes after RIC for ATLL patients.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia-Lymphoma, Adult T-Cell/therapy , Transplantation Conditioning , Aged , Female , Follow-Up Studies , Human T-lymphotropic virus 1/isolation & purification , Humans , Karnofsky Performance Status , Leukemia-Lymphoma, Adult T-Cell/virology , Limit of Detection , Male , Middle Aged , Proviruses/isolation & purification , Remission Induction , Survival Analysis , Transplantation, Homologous , Viral Load
19.
Acta Neurochir Suppl ; 103: 57-60, 2008.
Article in English | MEDLINE | ID: mdl-18496946

ABSTRACT

Spontaneous dissections of cerebral and cervical artery are relatively uncommon lesions in Japan. Although reported cases of cerebral and cervical arterial dissection are gradually increasing, natural history and optimal treatment remain unclear. The purpose of this study was to clarify the clinical features, natural history, and optimal treatment for patients suffering from non-hemorrhagic cerebral arterial dissection. Fifty-four males and 14 females with cerebral or cervical arterial dissection were treated between January 1998 and December 2003 at the Stroke Center, Sendal Medical Center in Japan. Although most patients suffering from non-hemorrhagic cerebral arterial dissection recover well by conservative treatments, some cases require surgical treatment if they are complicated by enlargement of aneurysms, cerebral ischemia due to bilateral vertebral arterial dissection.


Subject(s)
Aortic Dissection/epidemiology , Aortic Dissection/therapy , Vertebral Artery Dissection/epidemiology , Vertebral Artery Dissection/therapy , Adult , Aged , Aged, 80 and over , Aortic Dissection/diagnostic imaging , Aortic Dissection/pathology , Cerebral Angiography/methods , Female , Humans , Japan/epidemiology , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed/methods , Vertebral Artery Dissection/diagnostic imaging , Vertebral Artery Dissection/pathology
20.
Bone Marrow Transplant ; 41(12): 1029-35, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18332910

ABSTRACT

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven effective in adult T-cell leukemia/lymphoma (ATL) patients. To study the graft-versus-ATL (Gv-ATL) effects after allo-HSCT, we analyzed 21 ATL patients who had been treated at our hospital. Of these, 18 had acute-, 2 had lymphoma- and 1 had chronic-type ATL; at allo-HSCT, seven patients were in CR, one was in PR, five had stable disease (SD) and eight had progressive disease (PD). Disease state after allo-HSCT was CR in 14, PR in 3, SD in 1 and PD in 3 patients. Among 15 patients who survived longer than 100 days, ATL relapsed in 10 patients, skin relapsed in 9 patients and 5 had relapsed on the skin alone. After we discontinued immunosuppressant therapy in these 10 patients, 8 manifested GVHD; ATL was ameliorated to CR in 6 patients. Donor lymphocytes were infused into two patients who did not show GVHD; one obtained CR. In five patients with skin relapse alone, four patients achieved CR following the discontinuation of the immunosuppressants. Our results demonstrate that relapse of ATL after allo-HSCT tends to develop on skin, and Gv-ATL effects played a critical role in the outcome of allo-HSCT for ATL.


Subject(s)
Graft vs Leukemia Effect , Hematopoietic Stem Cell Transplantation/methods , Leukemia-Lymphoma, Adult T-Cell/therapy , Adult , Cohort Studies , Disease-Free Survival , Drug Administration Schedule , Female , Graft vs Host Disease/drug therapy , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Kaplan-Meier Estimate , Leukemia-Lymphoma, Adult T-Cell/pathology , Male , Middle Aged , Recurrence , Retrospective Studies , Skin Diseases/pathology , Transplantation, Homologous
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