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INTRODUCTION: Semaphorin-4D (CD100), generated by CD4/CD8 T-cells and its receptor on B cells - CD72, play a role in immune regulation. Both have soluble forms - sCD100/sCD72. METHODS: sCD100 and sCD72 levels were determined by ELISA (MyBioSource, USA). RESULTS: 28 chronic HIV patients and 50 matched healthy volunteers participated in our study. Before treatment, CD4 T-cells counts were 267⯱â¯216â¯cells/mcl and viral load (VL) was 586,675⯱â¯1897,431â¯copies/ml. Two years following HAART, CD4 T-cells counts rose to 475⯱â¯264â¯cells/mcl and VL dropped to 2050⯱â¯10,539â¯copies/ml. CD8 T-cells counts were stable. sCD72 levels prior (4.13⯱â¯2.03â¯ng/ml) and following HAART (3.53⯱â¯2.01â¯ng/ml) were similar to control levels (4.51⯱â¯2.66â¯ng/ml). sCD100 levels before (40.47⯱â¯31.4â¯ng/ml) and following HAART (37.68⯱â¯29.44â¯ng/ml) were significantly lower compared to controls (99.67⯱â¯36.72â¯ng/ml) despite the significant increase in CD4 T-cells counts. CONCLUSIONS: The permanent low levels of the immunoregulator sCD100 suggest a role for CD100 in the immune dysfunction and T cells exhaustion of HIV.
Assuntos
Antígenos CD/sangue , Infecções por HIV/imunologia , Semaforinas/sangue , Adolescente , Adulto , Antígenos CD/fisiologia , Antígenos de Diferenciação de Linfócitos B/sangue , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/imunologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Semaforinas/fisiologia , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Patients with acromegaly (caused by growth-hormone-secreting pituitary adenomas) are at increased risk of hypopituitarism, in particular hypogonadotropic hypogonadism, before and after multimodal therapy. In affected women of reproductive age, fertility is impaired and complex fertility treatments are needed to achieve conception. CASE PRESENTATION: We present the case of a young woman with acromegaly caused by a GH-secreting macroadenoma with suprasellar and bilateral cavernous sinus extension; hypogonadotropic hypogonadism and secondary hypothyroidism were present from the initial evaluation. Neurosurgical intervention was repeatedly recommended but the patient refused it initially; also she was non-compliant to the medical treatment of acromegaly. Transsphenoidal tumor debulking with adjuvant gamma-knife radiotherapy was eventually performed. Following treatment persistent active acromegaly and hypogonadotropic hypogonadism were diagnosed. Under chronic estroprogestative replacement therapy, the patient conceived and delivered a full-term healthy newborn without any complications. Possible mechanisms are discussed. CONCLUSIONS: Secondary hypogonadotropic hypogonadism in pituitary patients, even when considered permanent (after surgery and radiotherapy), can exceptionally allow spontaneous conception and normal course of pregnancy.
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Multiple endocrine neoplasia type 2A (MEN 2A) is a complex autosomal dominant inherited syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and primary parathyroid hyperplasia. In patients with only one or two clinical features, identification of a germline RET(REarranged in Transfection) mutation or the identification of the clinical features of MEN 2A in other first degree relatives is required to make the diagnosis. We present the case of a family with MEN 2A syndrome confirmed by genetic analysis which identified RET gene mutation in 634 codon in father - DV - aged 48 years and also in daughter DM -aged 20 years. The specific feature in this case is that the index case was the daughter (diagnosed and operated for pheochromocytoma at the age of 19 years), the father being diagnosed later with medullary thyroid carcinoma by mutational screening in all family members. This family supports the phenomenon of anticipation, in which severity increases and the age of onset decreases in successive generations, the syndrome being discovered earlier and with a worse prognostic in the daughter.
Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Carcinoma Medular/genética , Neoplasia Endócrina Múltipla Tipo 2a/genética , Mutação , Feocromocitoma/genética , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Adulto , Biomarcadores/metabolismo , Carcinoma Medular/diagnóstico , Carcinoma Medular/cirurgia , Família , Feminino , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/diagnóstico , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Feocromocitoma/diagnóstico , Feocromocitoma/cirurgia , Prognóstico , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Resultado do TratamentoRESUMO
DMBA induced rat mammary tumors were used to study the association of tyrosine protein kinase activity with tumor growth. Pharmacological manipulations of blood prolactin level, by perphenazine and bromocriptine, were used to stimulate or arrest tumor growth, respectively. During perphenazine treatment, a 2-3-fold increase in membranal tyrosine protein kinase activity, measured with angiotensin II as substrate, preceded the 3-4-fold increase in tumor area. At the same time the cAMP-dependent protein kinase activity, measured with kemptide as substrate, did not change.
Assuntos
Neoplasias Mamárias Experimentais/enzimologia , Proteínas Quinases/metabolismo , 9,10-Dimetil-1,2-benzantraceno , Angiotensina II/metabolismo , Animais , Divisão Celular , AMP Cíclico/farmacologia , Feminino , Neoplasias Mamárias Experimentais/patologia , Membranas/enzimologia , Oligopeptídeos/metabolismo , Perfenazina/farmacologia , Prolactina/sangue , Proteínas Tirosina Quinases , Quercetina/farmacologia , RatosRESUMO
ABSTRACT Grapevine virus A (GVA) is implicated in the etiology of the rugose wood disease. The coat protein (CP) and the putative movement protein (MP) genes of GVA were cloned and expressed in Escherichia coli and used to produce antisera. Both the CP and the MP were detected with their corresponding antisera in GVA-infected Nicotiana benthamiana. The MP was first detected at an early stage of the infection, 6 to 12 h after inoculation, and the CP was detected 2 to 3 days after inoculation. The CP and MP were detected by immunoblot analysis in rugose wood-affected grapevines. The MP could be detected in GVA-infected grapevines that tested negative for CP, both with CP antiserum and with a commercially available enzyme-linked immunosorbent assay kit. The study shows that detection of the nonstructural MP may be an effective means for serological detection of GVA infection in grapevines.
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Somatotroph and thyrotroph pituitary cells share a common precursor cell expressing the transcription factor Pit1 in ontogeny. Cells expressing both thyrotropin (TSH) and growth-hormone (GH) are found in adult rat pituitary and in human pituitary adenomas in acromegaly, and these tumors contain both thyrotropin-releasing hormone (TRH) and the TRH receptors (TRHR). It has been shown that stimulation of TSH expression in primary hypothyroidism promotes changes suggestive of somatotroph to thyrotroph cell transdifferentiation. We tested this hypothesis and the role of TRH in experimental primary hypothyroidism in rats. Adult female Long-Evans rats, 6 months old, were administered the antithyroid drug methimazole (0.1% w/v) in the drinking water for 42 days. Animals were sacrificed by perfusion fixation under anaesthesia at weekly intervals and pituitary tissue processed in acrylic resin for immunofluorescence and immuno-electronmicroscopy for TSH, GH and TRHR. In the hypothyroid rat pituitary immunofluorescent somatotrophs were greatly reduced in number and gradually replaced by thyrotrophs during methimazole administration. Colocalization of GH and TSH in the same cell was noted. Immunoelectronmicroscopy demonstrated the development of enlarged thyrotrophs with dilated rough endoplasmic reticulum containing an electron-dense material and intracisternal granules, both of which are immunoreactive for TSH ('thyroidectomy cells'). The somatotrophs showed reduced GH immunoreactivity and also the presence of TSH-type, small-size secretory granules. This suggests that the greatly increased number of TSH-cells in methimazole-induced-hypothyroidism is due, at least partially, to the transdifferentiation of somatotroph into thyrotroph cells. TRHR immunofluorescence was expressed in many somatotrophs in normal rat pituitary and unlike immunoreactive GH, its expression was enhanced during hypothyroidism. The number of TRHR-immunoreactive cells increased in parallel with the number of TSH-immunoreactive cells. This indicates a role for TRH stimulation in the transdifferentiation process. Taken together, these data suggest that, in addition to the cell mutation mechanism involving an early totipotential progenitor cell, transdifferentiation of existing somatotroph cells also plays a part in the pathogenesis of multihormonal GH-secreting adenomas.
Assuntos
Diferenciação Celular/fisiologia , Hipotireoidismo/metabolismo , Hipófise/citologia , Receptores do Hormônio Liberador da Tireotropina/metabolismo , Animais , Feminino , Hormônio do Crescimento/metabolismo , Humanos , Imuno-Histoquímica , Microscopia Imunoeletrônica , Hipófise/fisiologia , Ratos , Ratos Long-Evans , Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/metabolismoRESUMO
Tyrosine protein kinase activity was measured in membranes from DMBA-induced mammary tumors, with Angiotensin II as substrate. The apparent Km for the peptide was 3.3 mM. This enzymatic activity is inhibited by Ca+2; Mn+2 can replace Mg+2 with an increase in the Km for ATP from 47 /microM to 172 microM. The enzymatic activity was not affected by cyclic AMP but was inhibited in dose dependent manner by quercetin, a bioflavonoid which is known to inhibit proliferation of malignant cells in vitro.