The control of hematopoiesis and leukemia: from basic biology to the clinic.

Hematopoiesis gives rise to blood cells of different lineages throughout normal life. Abnormalities in this developmental program lead to blood cell diseases including leukemia. The establishment of a cell culture system for the clonal development of hematopoietic cells made it possible to discover proteins that regulate cell viability, multiplication and differentiation of different hematopoietic cell lineages, and the molecular basis of normal and abnormal blood cell development. These regulators include cytokines now called colony-stimulating factors (CSFs) and interleukins (ILs). There is a network of cytokine interactions, which has positive regulators such as CSFs and ILs and negative regulators such as transforming growth factor beta and tumor necrosis factor (TNF). This multigene cytokine network provides flexibility depending on which part of the network is activated and allows amplification of response to a particular stimulus. Malignancy can be suppressed in certain types of leukemic cells by inducing differentiation with cytokines that regulate normal hematopoiesis or with other compounds that use alternative differentiation pathways. This created the basis for the clinical use of differentiation therapy. The suppression of malignancy by inducing differentiation can bypass genetic abnormalities that give rise to malignancy. Different CSFs and ILs suppress programmed cell death (apoptosis) and induce cell multiplication and differentiation, and these processes of development are separately regulated. The same cytokines suppress apoptosis in normal and leukemic cells, including apoptosis induced by irradiation and cytotoxic cancer chemotherapeutic compounds. An excess of cytokines can increase leukemic cell resistance to cytotoxic therapy. The tumor suppressor gene wild-type p53 induces apoptosis that can also be suppressed by cytokines. The oncogene mutant p53 suppresses apoptosis. Hematopoietic cytokines such as granulocyte CSF are now used clinically to correct defects in hematopoiesis, including repair of chemotherapy-associated suppression of normal hematopoiesis in cancer patients, stimulation of normal granulocyte development in patients with infantile congenital agranulocytosis, and increase of hematopoietic precursors for blood cell transplantation. Treatments that decrease the level of apoptosis-suppressing cytokines and downregulate expression of mutant p53 and other apoptosis suppressing genes in cancer cells could improve cytotoxic cancer therapy. The basic studies on hematopoiesis and leukemia have thus provided new approaches to therapy.

High-level production of recombinant human lysosomal acid alpha-glucosidase in Chinese hamster ovary cells which targets to heart muscle and corrects glycogen accumulation in fibroblasts from patients with Pompe disease.

Infantile Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme. We constructed a plasmid containing a 5'-shortened human acid alpha-glucosidase cDNA driven by the cytomegalovirus promoter, as well as the aminoglycoside phosphotransferase and dihydrofolate reductase genes. Following transfection in dihydrofolate reductase-deficient Chinese hamster ovary cells, selection with Geneticin, and amplification with methotrexate, a cell line producing high levels of the alpha-glucosidase was established. In 48 hr, the cells cultured in Iscove's medium with 5 mM butyrate secreted 110-kDa precursor enzyme that accumulated to 91 micrograms.ml-1 in the medium (activity, > 22.6 mumol.hr-1.ml-1). This enzyme has a pH optimum similar to that of the mature form, but a lower Vmax and Km for 4-methylumbelliferyl-alpha-D-glucoside. It is efficiently taken up by fibroblasts from Pompe patients, restoring normal levels of acid alpha-glucosidase and glycogen. The uptake is blocked by mannose 6-phosphate. Following intravenous injection, high enzyme levels are seen in heart and liver. An efficient production system now exists for recombinant human acid alpha-glucosidase targeted to heart and capable of correcting fibroblasts from patients with Pompe disease.

The Importance of the First Psychotherapy Case in the Development of the Therapist's Professional Self as Viewed Through the Lens of Self Psychology

This paper explores the gap in the literature between what is herein referred to as the "first psychotherapy case" and its impact on the development of the trainee psychotherapist's professional self. The self psychology concepts of identity development, selfobject needs and fulfillment, narcissism, shame, countertransference, and structuralization are incorporated into the theoretical framework from which this developmental milestone is viewed. The theory's emphasis on early experiences and the development of self highlight the distinctiveness of the first case for the therapist. The beginning psychotherapy case poses a unique context for selfobject experiences and the developing self, involving both the therapist's presumably mature needs (assuming an existing cohesive nuclear self) and more infantile needs as the professional, peripheral self develops. As a result, the potential and important implications for the psychotherapist, the patient, training implications for the supervisor, and the ensuing treatment through termination are identified. The intent is to shed light on an area that is understudied thus far, and to begin a conversation as to why and how the impact of the first case on the psychotherapist should be examined. Implications, limitations, and ideas for future exploratory and qualitative research are also discussed.

Salud comunitaria y acción social en el control epidemiológico del tracoma infantil, España (1932-1939)

En el contexto de la endemia tracomatosa que afectó a diversas regiones españolas hasta la década de 1960, se analizan los determinantes epidemiológicos del tracoma infantil y su abordaje desde el modelo de asistencia preventiva que encerraba el concepto de salud comunitaria que se perfiló en el período de entreguerras. La detección precoz de casos, unida a actividades preventivas, educativas, terapéuticas y de inspección, como las que llevaron a cabo las enfermeras visitadoras, contribuyeron al control de la enfermedad. Los resultados reafirman la validez de las estrategias de intervención horizontal de mejora de las condiciones higiénicas y de los factores medioambientales que explicaban la prevalencia del tracoma.

El profesorado de Educación Primaria ante las TIC: realidad y retos

A partir de diversos estudios de caso se plantea una aproximación a la utilización por parte del profesorado de Infantil y Primaria en diversos centros de enseñanza de la Comunidad Autónoma de la Región de Murcia de las tecnologías de la información y la comunicación. Los resultados señalan que pese a la alta valoración por el profesorado de las TIC como herramienta didáctica en el aula y la progresiva dotación de recursos tecnológicos en los centros educativos en los últimos diez años, la utilización de las TIC por el profesorado aún es escasa. Los motivos principales señalados son las dificultades para la formación en el uso de las nuevas tecnologías y el excesivo tiempo que conlleva la preparación de materiales didácticos.

Hemangioma da Infância

Os hemangiomas infantis são os tumores mais comuns da infância, ocorrendo em cerca de 3 a 10% das crianças com ida- de inferior a um ano de idade, com predomínio no sexo feminino. Apesar da frequência destes tumores, a sua patogénese permanece pouco compreendida e a melhor abordagem terapêutica é controversa. Têm uma história natural de crescimento rápido durante a primeira infância, seguida de involução gradual, muitas vezes levando à regressão completa. Devido à sua involução espontânea, a maioria dos hemangiomas infantis não requerem qual- quer intervenção. No entanto, em 10 a 15% dos casos é necessário tratamento devido às possíveis complicações locais, compromisso fisiológico ou estético a longo prazo elevado ou risco de vida.

Hemangiomatose neonatal difusa : caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.

Syphilis et mariage /

Includes bibliographical references.

Survey of cripples in New York City /

Report of the Committee on Survey of Cripples of the Conference on Cripples held in New York on Apr. 4, 1919.

On the wasting diseases of infants and children /

Includes index.

Leçons théoriques et cliniques sur la syphilis et les syphilides.

Microfilmed for preservation

Les maladies des enfants.

Bibliographic notes and references throughout text.

Inherited copper toxicosis with emphasis on copper toxicosis in Bedlington terriers

Canine copper toxicosis is an important inherited disease in Bedlington terriers, because of its high prevalence rate and similarity to human copper storage disease. It can lead to chronic liver disease and occasional haemolytic anaemia due to impaired copper excretion. The responsible gene for copper toxicosis in Bedlington terriers has been recently identified and was found not to be related to human Wilson's disease gene ATP7B. Although our understanding of copper metabolism in mammals has improved through genetic molecular technology, the diversity of gene mutation related to copper metabolism in animals will help identify the responsible genes for non-Wilsonian copper toxicoses in human. This review paper discusses our knowledge of normal copper metabolism and the pathogenesis, molecular genetics and current research into copper toxicosis in Bedlington terriers, other animals and humans. (C) 2004 Elsevier GmbH. All rights reserved.

CRIANÇAS DESPROTEGIDAS E SEU IMAGINÁRIO A RESPEITO DE DEUS: abstração de imagens de Deus refletidas em representações gráficas.

Este trabalho é uma interpretação do imaginário a respeito de Deus, revelado por um grupo de crianças desprotegidas. Obter-se uma representação desse imaginário, tarefa difícil, foi o primeiro passo da investigação. A partir da prática do desenho, considerado como forma capaz de oferecer indicações seguras para busca de traços de personalidade, adicionada às interpretações verbais, realizadas pelas crianças; imagens foram se revelando e concretizando o desejado imaginário. A explicitação dos mecanismos de produção de sentidos das imagens fundamentou-se em dois diferentes níveis de interpretação teórica: a primeira, subsidiada por propostas psicológicas e psicanalíticas, permitiu a interpretação dos traços e cores, nos desenhos, como indicadores de sentimento. A segunda, baseada na Teologia Sistemática: a simbologia segundo Tillich, oportunizou a identificação de símbolos relacionados ao Divino, dos quais um, pela sua presença nas duas expressões: pictórica e verbal, foi considerado o símbolo, ou, a figura simbólica de Deus, manifestada pelas crianças. O desenvolvimento do trabalho abarca os seguintes tópicos: realidade contextual das crianças, a perda como uma característica marcante nas crianças, o imaginário infantil, síntese tradicional das interpretações que as crianças fazem a respeito de Deus, significações das expressões pictóricas, revelação simbólica como representação da pessoa de Deus, imaginada, experiências religiosas de fé das crianças, para com a pessoa de Deus, por elas revelada. Considerando-se que nenhuma análise é acabada, no final do trabalho encontram-se algumas perspectivas oriundas do seu interior, substituindo qualquer conclusão.(AU)