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1.
Ann Hum Biol ; 50(1): 324-331, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37431939

RESUMO

BACKGROUND: The Jomon period of Japan is characterised by a unique combination of sedentary and hunting/gathering lifestyles, spanning for more than 10,000 years from the final Pleistocene to the Holocene. The transition from the preceding Palaeolithic period to the Jomon period is known to have begun with the appearance of pottery usage. However, knowledge of the genetic background of the Jomon people is still limited. AIM: We aimed to determine the population-scale complete mitogenome sequences of the Initial Jomon human remains and compare the occurrence of mitochondrial haplogroups in the Jomon period from temporal and regional perspectives. SUBJECTS AND METHODS: For human remains dated to 8200-8600 cal BP, we determined their complete mitogenome sequences using target enrichment-coupled next-generation sequencing. RESULTS: We successfully obtained the complete mitogenome sequences with high depth of coverage and high concordance on consensus sequences. These sequences differed by more than three bases each, except for two individuals having completely identical sequences. Co-existence of individuals with haplogroups N9b and M7a was first observed at the same archaeological site from the Initial Jomon period. CONCLUSION: The genetic diversity within the population was not found to be low even in the Initial Jomon period.


Assuntos
Arqueologia , Restos Mortais , Humanos , Japão , Sequenciamento de Nucleotídeos em Larga Escala , Conhecimento
2.
Proc Natl Acad Sci U S A ; 115(16): 4128-4133, 2018 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-29610337

RESUMO

The dispersal of modern humans from Africa is now well documented with genetic data that track population history, as well as gene flow between populations. Phenetic skeletal data, such as cranial and pelvic morphologies, also exhibit a dispersal-from-Africa signal, which, however, tends to be blurred by the effects of local adaptation and in vivo phenotypic plasticity, and that is often deteriorated by postmortem damage to skeletal remains. These complexities raise the question of which skeletal structures most effectively track neutral population history. The cavity system of the inner ear (the so-called bony labyrinth) is a good candidate structure for such analyses. It is already fully formed by birth, which minimizes postnatal phenotypic plasticity, and it is generally well preserved in archaeological samples. Here we use morphometric data of the bony labyrinth to show that it is a surprisingly good marker of the global dispersal of modern humans from Africa. Labyrinthine morphology tracks genetic distances and geography in accordance with an isolation-by-distance model with dispersal from Africa. Our data further indicate that the neutral-like pattern of variation is compatible with stabilizing selection on labyrinth morphology. Given the increasingly important role of the petrous bone for ancient DNA recovery from archaeological specimens, we encourage researchers to acquire 3D morphological data of the inner ear structures before any invasive sampling. Such data will constitute an important archive of phenotypic variation in present and past populations, and will permit individual-based genotype-phenotype comparisons.


Assuntos
Evolução Biológica , Orelha Interna/anatomia & histologia , Migração Humana/história , África , Anatomia Comparada , Animais , Cefalometria/métodos , Orelha Interna/diagnóstico por imagem , História Antiga , Projeto Genoma Humano , Humanos , Imageamento Tridimensional , Fenótipo , Primatas/anatomia & histologia , Tomografia Computadorizada por Raios X
3.
Ann Hum Biol ; 47(6): 555-559, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32674620

RESUMO

Ancient human remains have been assigned to their mitochondrial DNA (mtDNA) haplogroups. To obtain efficiently deep and reliable nucleotide sequences of ancient DNA of interest, we achieved target enrichment followed by next-generation sequencing (NGS). Complete mitochondrial genome (mitogenome) sequences were obtained for three human remains from the Iyai rock-shelter site of the Initial Jomon Period in Japan. All the Jomon mitogenomes belong to haplogroup N9b, but no sequences among them were identical. High genetic diversity was clarified even among the Jomon human remains belonging to haplogroup N9b, which has been described as a haplogroup representing the Jomon people.


Assuntos
DNA Antigo/análise , DNA Mitocondrial/análise , Genoma Mitocondrial , Arqueologia , Restos Mortais , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Japão
4.
Pediatr Blood Cancer ; 63(2): 234-41, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26469989

RESUMO

BACKGROUND: Advances in cancer immunotherapy in the pediatric field are needed in order to improve the prognosis of children with malignancies. We conducted a prospective phase I/II study of WT1 peptide vaccination for children with relapsed or refractory malignancies. METHODS: The main eligibility criteria were affected tissues or leukemic cells expressing the WT1 gene, and patients (and donors for allogeneic hematopoietic stem cell transplantation) having HLA-A*24:02. Vaccination using the WT1 peptide (CYTWNQMNL), which was modified for higher affinity to this HLA-type molecule with the adjuvant Montanide ISA51, was performed weekly 12 times. RESULTS: Twenty-six patients were enrolled and 13 (50.0%) completed the vaccination 12 times. Evidence for the induction of WT1-specific cytotoxic T-lymphocyte (CTL) responses without severe systemic side effects was obtained. Two out of 12 patients with bulky disease exhibited a transient clinical effect (one mixed response and one stable disease), three out of six patients with minimal residual disease achieved transient molecular remission, and five out of eight patients without a detectable level of the molecular marker, but with a high risk of relapse, had the best outcome of long-term continuous complete remission. CONCLUSIONS: WT1 vaccination is a safe immunotherapy and induced WT1-specific CTL responses in children; however, as a single agent, vaccination only provided patients in remission, but with a high risk of relapse, with "long-term benefits" in the context of its use for relapse prevention. WT1 peptide-based treatments in combination with other modalities, such as anti-tumor drugs or immunomodulating agents, need to be planned.


Assuntos
Vacinas Anticâncer/uso terapêutico , Neoplasias/terapia , Peptídeos/uso terapêutico , Proteínas WT1/imunologia , Proteínas WT1/uso terapêutico , Adjuvantes Imunológicos , Adolescente , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Manitol/administração & dosagem , Manitol/análogos & derivados , Neoplasias/genética , Ácidos Oleicos/administração & dosagem , Peptídeos/imunologia , Reação em Cadeia da Polimerase , Linfócitos T Citotóxicos/imunologia
5.
Am J Phys Anthropol ; 159(3): 523-33, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26537028

RESUMO

OBJECTIVES: In paleodemography, the Bayesian approach has been suggested to provide an effective means by which mortality profiles of past populations can be adequately estimated, and thus avoid problems of "age-mimicry" inherent in conventional approaches. In this study, we propose an application of the Gompertz model using an "informative" prior probability distribution by revising a recent example of the Bayesian approach based on an "uninformative" distribution. METHODS: Life-table data of 134 human populations including those of contemporary hunter-gatherers were used to determine the Gompertz parameters of each population. In each population, we used both raw life-table data and the Gompertz parameters to calculate some demographic values such as the mean life-span, to confirm representativeness of the model. Then, the correlation between the two Gompertz parameters (the Strehler-Mildvan correlation) was re-established. We incorporated the correlation into the Bayesian approach as an "informative" prior probability distribution, and tested its effectiveness using simulated data. RESULTS: Our analyses showed that the mean life-span (≥ age 15) and the proportion of living persons aging over 45 were well-reproduced by the Gompertz model. The simulation showed that using the correlation as an informative prior provides a narrower estimation range in the Bayesian approach than does the uninformative prior. CONCLUSIONS: The Gompertz model can be assumed to accurately estimate the mean life-span and/or the proportion of old people in a population. We suggest that the Strehler-Mildvan correlation can be used as a useful constraint in demographic reconstructions of past human populations.


Assuntos
Teorema de Bayes , Demografia/métodos , Modelos Estatísticos , Paleontologia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Am J Phys Anthropol ; 161(1): 170-80, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27346085

RESUMO

Recent theoretical progress potentially refutes past claims that paleodemographic estimations are flawed by statistical problems, including age mimicry and sample bias due to differential preservation. The life expectancy at age 15 of the Jomon period prehistoric populace in Japan was initially estimated to have been ∼16 years while a more recent analysis suggested 31.5 years. In this study, we provide alternative results based on a new methodology. The material comprises 234 mandibular canines from Jomon period skeletal remains and a reference sample of 363 mandibular canines of recent-modern Japanese. Dental pulp reduction is used as the age-indicator, which because of tooth durability is presumed to minimize the effect of differential preservation. Maximum likelihood estimation, which theoretically avoids age mimicry, was applied. Our methods also adjusted for the known pulp volume reduction rate among recent-modern Japanese to provide a better fit for observations in the Jomon period sample. Without adjustment for the known rate in pulp volume reduction, estimates of Jomon life expectancy at age 15 were dubiously long. However, when the rate was adjusted, the estimate results in a value that falls within the range of modern hunter-gatherers, with significantly better fit to the observations. The rate-adjusted result of 32.2 years more likely represents the true life expectancy of the Jomon people at age 15, than the result without adjustment. Considering ∼7% rate of antemortem loss of the mandibular canine observed in our Jomon period sample, actual life expectancy at age 15 may have been as high as ∼35.3 years.


Assuntos
Dente Canino/anatomia & histologia , Polpa Dentária/anatomia & histologia , Expectativa de Vida/história , Adolescente , Adulto , Determinação da Idade pelos Dentes , Antropologia Física , Demografia , História Antiga , Humanos , Japão , Funções Verossimilhança , Pessoa de Meia-Idade , Adulto Jovem
7.
Clin Immunol ; 160(2): 255-60, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26172957

RESUMO

We herein describe a case of a 17-year-old boy with intractable common warts, short stature, microcephaly and slowly-progressing pancytopenia. Simultaneous quantification of T-cell receptor recombination excision circles (TREC) and immunoglobulin κ-deleting recombination excision circles (KREC) suggested very poor generation of both T-cells and B-cells. By whole exome sequencing, novel compound heterozygous mutations were identified in the patient's DNA ligase IV (LIG4) gene. The diagnosis of LIG4 syndrome was confirmed by delayed DNA double-strand break repair kinetics in γ-irradiated fibroblasts from the patient and their restoration by an introduction of wild-type LIG4. Although the patient received allogeneic hematopoietic stem cell transplantation from his haploidentical mother, he unfortunately expired due to an insufficiently reconstructed immune system. An earlier definitive diagnosis using TREC/KREC quantification and whole exome sequencing would thereby allow earlier intervention, which would be essential for improving long-term survival in similar cases with slowly-progressing LIG4 syndrome masked in adolescents.


Assuntos
Anormalidades Craniofaciais/genética , DNA Ligases/genética , Transtornos do Crescimento/genética , Síndromes de Imunodeficiência/genética , Microcefalia/genética , Pancitopenia/genética , Imunodeficiência Combinada Severa/genética , Adolescente , DNA Ligase Dependente de ATP , Humanos , Masculino
8.
Am J Phys Anthropol ; 156(3): 482-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25388672

RESUMO

Evolutionary and functional significance of the human chin has long been explored from various perspectives including masticatory biomechanics, speech, and anterior tooth size. Recent ontogenetic studies have indicated that the spatial position of internally forming anterior teeth partially constrains adult mandibular symphyseal morphology. The present study therefore preliminarily examined the size and placement of developing anterior teeth in immature Neanderthal mandibles of Dederiyeh 1 and 2, compared with similarly-aged modern humans (N = 16) and chimpanzees (N = 7) whose incisors are comparatively small and large among extant hominids, respectively. The Dederiyeh 1 mandible is described as slightly presenting a mental trigone and attendant mental fossa, whereas Dederiyeh 2 completely lacks such chin-associated configurations. Results showed that, despite symphyseal size being within the modern human range, both Dederiyeh mandibles accommodated overall larger anterior dentition and displayed a remarkably wide bicanine space compared to those of modern humans. Dederiyeh 2 had comparatively thicker deciduous incisor roots and more enlarged permanent incisor crypts than Dederiyeh 1, but both Dederiyeh individuals exhibited a total dental size mostly intermediate between modern humans and chimpanzees. These findings potentially imply that the large deciduous/permanent incisors collectively distended the labial alveolar bone, obscuring an incipient mental trigone. It is therefore hypothesized that the appearance of chin-associated features, particularly of the mental trigone and fossa, can be accounted for partly by developmental relationships between the sizes of the available mandibular space and anterior teeth. This hypothesis must be, however, further addressed with more referential samples in future studies.


Assuntos
Queixo/anatomia & histologia , Incisivo/anatomia & histologia , Mandíbula/anatomia & histologia , Homem de Neandertal/anatomia & histologia , Animais , Antropologia Física , Cavernas , Humanos , Síria
9.
Am J Phys Anthropol ; 158(2): 185-197, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26249757

RESUMO

OBJECTIVES: We describe a new computer reconstruction to obtain complete anatomical information of the ecto- and endocranium from the imperfectly preserved skull of the Neanderthal Amud 1. MATERIALS AND METHODS: Data were obtained from computed tomography scans of the fossil cranium. Adhesive and plaster were then virtually removed from the original specimen, and the fragments comprising the fossil cranium were separated. These fragments were then mathematically reassembled based on the smoothness of the joints. Both sides of the cranium were reassembled separately, and then aligned based on bilateral symmetry and the distance between the mandibular fossae obtained from the associated mandible. The position of the isolated maxilla was determined based on the position of the mandible that was anatomically articulated to the mandibular fossae. To restore missing basicranial and damaged endocranial regions, the cranium of Forbes' Quarry 1 was warped onto that of La Chapelle-aux-Saints 1, and the resulting composite Neanderthal cranium was then warped onto the reconstructed Amud 1 by an iterative thin-plate spline deformation. RESULTS: Comparison of the computer reconstruction with the original indicated that the newly reconstructed Amud 1 cranium was slightly shorter and wider in the anteroposterior and mediolateral directions, respectively, suggesting that it was relatively more brachycephalic. The endocranial volume was estimated to be 1,736 cm3 , which was quite similar to the original estimated value of 1,740 cm3 . DISCUSSION: This new computer reconstruction enables not only measurement of new cranial metrics, but also inclusion of the Amud 1 specimen in three-dimensional geometric morphometric analyses that were previously difficult due to its incompleteness. Am J Phys Anthropol 158:185-197, 2015. © 2015 Wiley Periodicals, Inc.

10.
Pediatr Int ; 57(6): 1178-81, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26711919

RESUMO

Here we report a case of aggressive neuroendocrine tumor (NET), which is an extremely rare secondary solid tumor that occurs after allogeneic hematopoietic cell transplantation (allo-HSCT). A patient with chronic active Epstein-Barr virus infection received allo-HSCT from an HLA-DR two allele-mismatched unrelated donor. Four years later, he developed NET with multiple metastases. He received thoraco-abdominal irradiation as a conditioning regimen, and developed repeated episodes of intestinal graft-versus-host disease, for which he received long-term immunosuppressive therapy. Although these factors may be potential contributing factors to the development of secondary NET, the exact pathogenesis remains unclear.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Infecções por Vírus Epstein-Barr/cirurgia , Doença Enxerto-Hospedeiro/complicações , Segunda Neoplasia Primária , Tumores Neuroendócrinos/etiologia , Adulto , Evolução Fatal , Humanos , Masculino , Tumores Neuroendócrinos/diagnóstico , Transplante Homólogo
11.
Biol Blood Marrow Transplant ; 20(2): 214-21, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24188918

RESUMO

Chronic Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases represented by chronic active Epstein-Barr virus infection are lethal but are curable with several courses of chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Recently, we reported that reduced-intensity conditioning (RIC) provided better outcomes than myeloablative conditioning because RIC was less toxic. However, it was unclear whether cord blood transplantation (CBT) works in the context of RIC. We retrospectively analyzed 17 patients who underwent RIC followed by bone marrow transplantation (RIC-BMT) and 15 patients who underwent RIC followed by CBT (RIC-CBT). The representative regimen was fludarabine and melphalan based. The overall survival rates with RIC-BMT and RIC-CBT were 92.9% ± 6.9% and 93.3% ± 6.4%, respectively (P = .87). One patient died of lung graft-versus-host disease after RIC-BMT, and 1 patient died of multiple viral infections after RIC-CBT. Although cytotoxic chemotherapy was also immunosuppressive and might contribute to better donor cell engraftment after RIC-HSCT, the rate of engraftment failure after RIC-CBT was still higher than that after RIC-BMT (not significant); however, patients who had experienced graft failure were successfully rescued with a second HSCT. Unrelated cord blood can be an alternative source for RIC-HSCT if a patient has no family donor.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Transtornos Linfoproliferativos/terapia , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Infecções por Vírus Epstein-Barr/virologia , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Recém-Nascido , Células Matadoras Naturais , Masculino , Adulto Jovem
12.
Pediatr Hematol Oncol ; 31(8): 754-64, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25325678

RESUMO

BACKGROUND: Patients with advanced malignancies in non-complete remission (CR) have a dismal prognosis after HLA-matched hematopoietic stem cell transplantation (HSCT). T-cell-replete HLA-haploidentical HSCT has remarkable anti-leukemia/tumor effects on these patients, but also a high risk of severe/extensive graft-versus-host disease (GHVD). Post-transplantation cyclophosphamide (PTCY) is regarded as a GVHD-specific immunosuppressant in adults, but its feasibility is unknown in children. METHODS: We performed a prospective feasibility study of PTCY at 50 mg/kg on day 3 for children with advanced leukemias or malignant solid tumors: refractory to chemotherapy or relapsed after conventional allogeneic HSCT. Conditioning consisted of fludarabine (180 mg/m2) and melphalan (140-210 mg/m2). RESULTS: Long-term engraftments were achieved in 11 patients (73.3%) after bone marrow transplantation (BMT, n = 13) or peripheral blood (PB) stem cell transplantation (n = 2). The incidence of severe acute GHVD was 25.0% and that of extensive chronic GVHD 0.0% after evaluable BMT. CR was achieved in 6/15 and partial response in 4/15 as the best response. Finally, 11/15 experienced disease progression/relapse, 2/15 suffered treatment-related mortality without evidence of disease, and 2/15 are alive in continuous CR. CONCLUSIONS: PTCY is feasible in children; however, for a better outcome in such patients with advanced malignancies, some modifications are anticipated.


Assuntos
Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Neoplasias/terapia , Transplante de Células-Tronco de Sangue Periférico , Criança , Ciclofosfamida/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Haploidia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Teste de Histocompatibilidade , Humanos , Imunossupressores/administração & dosagem , Japão , Masculino , Neuroblastoma/sangue , Neuroblastoma/complicações , Neuroblastoma/terapia , Estudos Prospectivos , Transplante Homólogo
13.
Pediatr Blood Cancer ; 60(8): E60-2, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23468187

RESUMO

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) in children is one of the highest-risk ALL groups. Improved outcome in combination with imatinib has been reported. However, intensive chemotherapy or myeloablative conditioning followed by hematopoietic stem cell transplantation (HSCT) can be associated with significant adverse late effects. We report a case series of five children with Ph + ALL underwent reduced-intensity allogeneic HSCT (RIST) after induction and consolidation in chemotherapy combined with imatinib. Four of the five patients remain first complete remission for a median of 3.1 years after RIST. These results are preliminary, but suggest the feasibility and effectiveness of RIST with imatinib.


Assuntos
Antineoplásicos/administração & dosagem , Benzamidas/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Cromossomo Filadélfia , Piperazinas/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pirimidinas/administração & dosagem , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Mesilato de Imatinib , Masculino , Indução de Remissão , Transplante Homólogo
14.
Am J Hum Genet ; 85(4): 528-35, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19804850

RESUMO

Shovel shape of upper incisors is a common characteristic in Asian and Native American populations but is rare or absent in African and European populations. Like other common dental traits, genetic polymorphisms involved in the tooth shoveling have not yet been clarified. In ectodysplasin A receptor (EDAR), where dysfunctional mutations cause hypohidrotic ectodermal dysplasia, there is a nonsynonymous-derived variant, 1540C (rs3827760), that has a geographic distribution similar to that of the tooth shoveling. This allele has been recently reported to be associated with Asian-specific hair thickness. We aimed to clarify whether EDAR 1540C is also associated with dental morphology. For this purpose, we measured crown diameters and tooth-shoveling grades and analyzed the correlations between the dental traits and EDAR genotypes in two Japanese populations, inhabitants around Tokyo and in Sakishima Islands. The number of EDAR 1540C alleles in an individual was strongly correlated with the tooth-shoveling grade (p = 7.7 x 10(-10)). The effect of the allele was additive and explained 18.9% of the total variance in the shoveling grade, which corresponds to about one-fourth of the heritability of the trait reported previously. For data reduction of individual-level metric data, we applied a principal-component analysis, which yielded PC1-4, corresponding to four patterns of tooth size; this result implies that multiple factors are involved in dental morphology. The 1540C allele also significantly affected PC1 (p = 4.9 x 10(-3)), which denotes overall tooth size, and PC2 (p = 2.6 x 10(-3)), which denotes the ratio of mesiodistal diameter to buccolingual diameter.


Assuntos
Receptor Edar/genética , Variação Genética , Dente/anatomia & histologia , Alelos , Feminino , Genoma , Genótipo , Humanos , Japão , Masculino , Modelos Genéticos , Reação em Cadeia da Polimerase , Polimorfismo Genético , Análise de Componente Principal , Análise de Regressão , Dente/fisiologia
15.
Rinsho Ketsueki ; 53(3): 361-6, 2012 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-22499056

RESUMO

A 22-year-old man with chronic active Epstein-Barr virus infection underwent allogeneic bone marrow transplantation (allo-BMT) from an HLA two allele-mismatched unrelated donor. Ten months after allo-BMT, he developed protein-losing enteropathy following a respiratory syncytial virus infection. A diagnosis of a recurrent type of acute graft-versus-host disease (GVHD) was made based on the histopathological findings, such as the infiltration of T lymphocytes into the superficial epithelium and crypts, and apoptotic bodies in crypts. Although methylprednisolone (mPSL: 10 mg/kg) administration for two consecutive days improved gastrointestinal symptoms, acute pancreatitis and severe depression developed in association with corticosteroid treatment. Reduction of mPSL and administration of infliximab (5 mg/kg/dose, 3 times) resulted in rapid improvement of depression and pancreatitis without aggravating intestinal GVHD. Recent studies have demonstrated that tumor-necrosis-factor (TNF)-α is associated with not only GVHD but also depression and acute pancreatitis. In the present case, anti-TNF-α treatment enabled us to reduce corticosteroid dose without aggravating GVHD, which suggests that this approach might be effective for the treatment of depression and acute pancreatitis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Metilprednisolona/efeitos adversos , Terapia de Alvo Molecular , Fator de Necrose Tumoral alfa , Doença Aguda , Transplante de Medula Óssea , Infecções por Vírus Epstein-Barr/terapia , Gastroenteropatias/etiologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Infliximab , Masculino , Metilprednisolona/administração & dosagem , Pancreatite/tratamento farmacológico , Pancreatite/etiologia , Recidiva , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
16.
JASA Express Lett ; 2(4): 045203, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-36154226

RESUMO

The speech production capability of sibilant fricatives of early hominin was assessed by interpolating the modern human vocal tract to an Australopithecine specimen based on the jawbone landmarks, and then simulating the airflow and sound generation. The landmark interpolation demonstrates the possibility to form the sibilant groove in the anterior part of the oral tract, and results of the aeroacoustic simulation indicate that the early hominins had the potential to produce the fricative broadband noise with a constant supply of airflow to the oral cavity, although the ancestor's tongue deformation ability is still uncertain, and the results are highly speculative.


Assuntos
Hominidae , Animais , Humanos , Som , Espectrografia do Som/métodos , Fala , Medida da Produção da Fala/métodos
17.
Int J Hematol ; 115(3): 406-413, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35028882

RESUMO

The prognosis of relapsed/refractory (R/R) pediatric acute leukemia is extremely poor. We retrospectively reviewed 20 consecutive pediatric patients with R/R acute leukemia who underwent a first HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning (haplo-RIC-PBSCT) with very low-dose antithymocyte globulin (ATG) between 2012 and 2019. Of these 20 patients, 7 patients had acute lymphoblastic leukemia, and 13 had acute myeloid leukemia. At the time of haplo-RIC-PBSCT, 15 patients had active disease. The median follow-up duration for survivors was 56 months (range 22-108 months). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, short-term methotrexate, methylprednisolone, and ATG 1.25 mg/kg on day-2. The 2-year cumulative incidence of transplant-related mortality and relapse were 5.0% [95% confidence interval (CI) 0.7-30.5%)] and 57.8% (95% CI 37.4-79.6%), respectively. Among the 20 patients, 16 (80.0%) developed grade III-IV acute GVHD, and 2 developed severe chronic GVHD. The 2-year event-free survival and overall survival rates were 40.0% (95% CI 19.3-60.0%) and 50.0% (95% CI 27.1-69.2%), respectively. Although the sample size is small, the survival outcomes of the present study are encouraging.


Assuntos
Soro Antilinfocitário/administração & dosagem , Antígenos HLA/genética , Haploidia , Leucemia Mieloide Aguda/cirurgia , Transplante de Células-Tronco de Sangue Periférico/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Condicionamento Pré-Transplante/métodos , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Lactente , Leucemia Mieloide Aguda/mortalidade , Masculino , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
18.
J Gen Virol ; 92(Pt 5): 1032-1043, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21248177

RESUMO

Polymorphisms in Epstein-Barr virus (EBV) latent genes can identify virus strains from different human populations and individual strains within a population. An Asian EBV signature has been defined almost exclusively from Chinese viruses, with little information from other Asian countries. Here we sequenced polymorphic regions of the EBNA1, 2, 3A, 3B, 3C and LMP1 genes of 31 Japanese strains from control donors and EBV-associated T/NK-cell lymphoproliferative disease (T/NK-LPD) patients. Though identical to Chinese strains in their dominant EBNA1 and LMP1 alleles, Japanese viruses were subtly different at other loci. Thus, while Chinese viruses mainly fall into two families with strongly linked 'Wu' or 'Li' alleles at EBNA2 and EBNA3A/B/C, Japanese viruses all have the consensus Wu EBNA2 allele but fall into two families at EBNA3A/B/C. One family has variant Li-like sequences at EBNA3A and 3B and the consensus Li sequence at EBNA3C; the other family has variant Wu-like sequences at EBNA3A, variants of a low frequency Chinese allele 'Sp' at EBNA3B and a consensus Sp sequence at EBNA3C. Thus, EBNA3A/B/C allelotypes clearly distinguish Japanese from Chinese strains. Interestingly, most Japanese viruses also lack those immune-escape mutations in the HLA-A11 epitope-encoding region of EBNA3B that are so characteristic of viruses from the highly A11-positive Chinese population. Control donor-derived and T/NK-LPD-derived strains were similarly distributed across allelotypes and, by using allelic polymorphisms to track virus strains in patients pre- and post-haematopoietic stem-cell transplant, we show that a single strain can induce both T/NK-LPD and B-cell-lymphoproliferative disease in the same patient.


Assuntos
Infecções por Vírus Epstein-Barr/virologia , Antígenos Nucleares do Vírus Epstein-Barr/genética , Herpesvirus Humano 4/classificação , Herpesvirus Humano 4/genética , Polimorfismo Genético , DNA Viral/química , DNA Viral/genética , Genótipo , Herpesvirus Humano 4/isolamento & purificação , Humanos , Filogeografia , Análise de Sequência de DNA , Proteínas da Matriz Viral/genética
19.
Proc Natl Acad Sci U S A ; 105(37): 13764-8, 2008 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-18779579

RESUMO

From birth to adulthood, the human brain expands by a factor of 3.3, compared with 2.5 in chimpanzees [DeSilva J and Lesnik J (2006) Chimpanzee neonatal brain size: Implications for brain growth in Homo erectus. J Hum Evol 51: 207-212]. How the required extra amount of human brain growth is achieved and what its implications are for human life history and cognitive development are still a matter of debate. Likewise, because comparative fossil evidence is scarce, when and how the modern human pattern of brain growth arose during evolution is largely unknown. Virtual reconstructions of a Neanderthal neonate from Mezmaiskaya Cave (Russia) and of two Neanderthal infant skeletons from Dederiyeh Cave (Syria) now provide new comparative insights: Neanderthal brain size at birth was similar to that in recent Homo sapiens and most likely subject to similar obstetric constraints. Neanderthal brain growth rates during early infancy were higher, however. This pattern of growth resulted in larger adult brain sizes but not in earlier completion of brain growth. Because large brains growing at high rates require large, late-maturing, mothers [Leigh SR and Blomquist GE (2007) in Campbell CJ et al. Primates in perspective; pp 396-407], it is likely that Neanderthal life history was similarly slow, or even slower-paced, than in recent H. sapiens.


Assuntos
Evolução Biológica , Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Fósseis , Hominidae/anatomia & histologia , Hominidae/crescimento & desenvolvimento , Adulto , Animais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Tamanho do Órgão , Parto , Federação Russa , Esqueleto , Crânio/anatomia & histologia , Síria
20.
Pediatr Int ; 53(6): 1010-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21810148

RESUMO

BACKGROUND: Herpesviruses cause life-threatening diseases after hematopoietic stem cell transplantation (HSCT). It is necessary that viral diseases are identified early and safely diagnosed. The purpose of this study was to evaluate the efficacy of multiplex polymerase chain reaction (PCR) for qualitative detection of the six herpesviruses simultaneously: herpes simplex virus type 1 and type 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus (EBV) and human herpesvirus 6B. METHODS: Multiplex PCR was applied to patients with various clinical manifestations including central nervous system, cutaneous and mucosal complications after allogeneic HSCT, and the data were retrospectively analyzed. RESULTS: Patients positive for cytomegalovirus in peripheral blood by multiplex PCR might need pre-emptive treatment, but a positive result for EBV had no specific correlation with EBV-associated post-transplant lymphoproliferative disease, and positive result for human herpesvirus 6B failed to show any clinical significance. The multiplex PCR was safe and helpful to diagnose viral diseases of local regions, for example, the central nervous system, skin and mucosa. CONCLUSIONS: It may be worthwhile to survey the six herpesviruses with multiplex PCR after HSCT.


Assuntos
DNA Viral/análise , Transplante de Células-Tronco Hematopoéticas , Infecções por Herpesviridae/diagnóstico , Herpesviridae/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Infecções por Herpesviridae/transmissão , Infecções por Herpesviridae/virologia , Humanos , Lactente , Recém-Nascido , Masculino , Período Pós-Operatório , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto Jovem
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