Benign neonatal sleep myoclonus: case report and follow-up of four members of an affected family.

Benign neonatal sleep myoclonus (BNSM), characterized by myoclonic jerks of the extremities only in non-REM sleep, occurs in the first months of life with spontaneous disappearance within 3-4 months. We examined five siblings with typical BNSM, at the 3-10 years follow-up neurological examination. Psychomotor development, cognitive functions and EEG were completely normal. These cases confirm that BNSM is a self limited and nonepileptic disorder.     

Percepciones estudiantiles sobre las propiedades del examen clínico objetivo estructurado en Uruguay. Disponiendo un cuestionario válido para analizar la factibilidad del nuevo formato durante la transición curricular

Introduction

Although an objective structured clinical examination (OSCE) format has been applied in Uruguay since 2004, and providing reliable performance measures, perceptions of it properties and level of student satisfaction have not been determined.

Ultrastructural Features of Neuroendocrine Differentiated Carcinomas of the Breast

The ultrastructural patterns of neuroendocrine (NE) differentiated breast carcinomas are analyzed and discussed. Reports in the literature describe wide variations in the size of observed dense-core membrane-bound granules and discrepancies in their interpretation. In the present study 24 cases of breast carcinoma with recognized morphologic, histochemical, and immunocytochemical features of NE tumors were investigated. Five different types of dense-core granules of neurosecretory (NS) type (confirmed by the ultrastructural localization of chromogranin A) and five different cell types were recognized. Some amphicrine cells were found to contain both mucin and NS granules. Another notable ultrastructural feature of breast NE carcinomas was the presence of clear vesicles of presynaptic type, which correlated with expression of synaptophysin.     

Ultrastructural analysis of pancreatic acinar cells from mice fed on genetically modified soybean

No direct evidence that genetically modified (GM) food may represent a possible danger for health has been reported so far; however, the scientific literature in this field is quite poor. Therefore, we investigated the possible effects of a diet containing GM soybean on mouse exocrine pancreas by means of ultrastructural, morphometrical and immunocytochemical analyses. Our observations demonstrate that, although no structural modification occurs in pancreatic acinar cells of mice fed on GM soybean, quantitative changes of some cellular constituents take place in comparison to control animals. In particular, a diet containing significant amount of GM food seems to influence the zymogen synthesis and processing.     

Self class I molecules protect normal cells from lysis mediated by autologous natural killer cells

The surface expression of given HLA class I alleles protects target cells from lysis mediated by natural killer (NK) clones specific for these (or related) alleles. We could define two groups of NK clones specifically recognizing either Cw4 and related C alleles (“group 1”) or Cw3 and related C alleles (“group 2”), respectively. Monoclonal antibodies (mAb) to class I molecules should interfere with the interaction between NK receptors and class I molecules, thus resulting in lysis of protected target cells. However, none of the numerous available mAb to class I molecules had this effect. Therefore, we attempted to select new mAb on the basis of their ability to induce lysis of Cw4- or Cw3-protected lymphoblastoid cell lines by “group 1” or “group 2” NK clones, respectively. From mice immunized with phytohemagglutinin (PHA)-activated lymphocytes expressing either Cw3 or Cw4 alleles, two mAb were selected, the 6A4 (IgG1) and the A6-136 (IgM), on the basis of their ability to induce lysis of protected target cell. Both mAb immunoprecipitated molecules which, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gave two bands of 45 and 12 kDa, typical of the class I heavy chain and β2 microglobulin, respectively. It has been proposed (but not proven), that self major histocompatibility complex class I molecules protect normal cells from autologous NK cell lysis. Thus, we used the 6A4 and A6-136 mAb to assess this possibility directly. Cw4-specific (“group 1”) and Cw3-specific (“group 2”) NK clones were isolated from donors expressing the corresponding (or related) protective C alleles. None of these clones lysed autologous PHA-induced blasts, used as target cells. However, addition of the F(ab′)₂ of 6A4 mAb or the A6-136 mAb resulted in lysis of autologous target cells by “group 1” or “group 2” NK clones, respectively. These data provide direct evidence that the expression of class I molecules protects normal cells from lysis by autologous NK cells.     

Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism

Parkinson's disease (PD) is a progressive neurodegenerative illness associated with a selective loss of dopaminergic neurons in the nigrostriatal pathway of the brain. Despite the overall rarity of the familial forms of PD, the identification of single genes linked to the disease has yielded crucial insights into possible mechanisms of neurodegeneration. Recently, a putative mitochondrial kinase, PINK1, has been found mutated in an inherited form of parkinsonism. Here, we describe that PINK1 mutations confer different autophosphorylation activity, which is regulated by the C-terminal portion of the protein. We also demonstrate the mitochondrial localization of both wild-type and mutant PINK1 proteins unequivocally and prove that a short N-terminal part of PINK1 is sufficient for its mitochondrial targeting.     

Heterogeneous pattern of chromosomal breakpoints involving the MYC locus in multiple myeloma

Chromosomal rearrangements of the MYC locus, which often involve the IG loci, are recurrent events in multiple myeloma (MM) and plasma cell leukemia (PCL). We used dual-color fluorescence in situ hybridization (FISH) to characterize the breakpoint locations of chromosomal translocations/rearrangements involving the MYC locus at 8q24 found in a panel of 14 MM cell lines and 70 primary tumors (66 MM and 4 PCL). MYC locus alterations were observed in 21 cases: MYC/IG (mainly IGH@) fusions in 11 cell lines and three patients (2 MM and 1 PCL), and extra signals and/or abnormal MYC localizations in seven patients (5 MM and 2 PCL). Fourteen of these cases were investigated by FISH analyses by use of a panel of BAC clones covering about 6 Mb encompassing the MYC locus. The breakpoints were localized in a region 100-250 kb centromeric to MYC in four cases, a region 500-800 kb telomeric to the gene in four cases, and regions > or = 2 Mb centromeric or telomeric to MYC in five cases. Two different breakpoints were detected in the KMS-18 cell line, whereas the insertion of a MYC allele was found in a complex t(16;22) chromosomal translocation in the RPMI8226 cell line. Our data document a relatively high dispersion of 8q24 breakpoints in MM.     

Cytotoxic T lymphocyte-associated antigen-4 inhibits integrin-mediated stimulation

The negative role exerted by cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in the regulation of T-cell activity, as induced by T-cell receptor (TCR)/CD3 and CD28 costimulation, has been widely described. In the present work we investigated the role of CTLA-4 in the control of cell activation, as induced by costimulation of the adhesion molecule lymphocyte function-associated antigen-1 (LFA-1) in murine CD4+ T cells. Results show that CTLA-4 engagement inhibits interleukin-2 (IL-2) production, not only when induced by CD3/CD28 costimulation, but also when CD4+ T cells are costimulated by anti-CD3 and anti-LFA-1 monoclonal antibodies (mAbs). LFA-1 has been described to induce Ca2+ mobilization also in the absence of TCR engagement. Moreover, we found that CTLA-4 engagement negatively affects Ca2+ mobilization and NF-AT activation, as induced by LFA-1 engagement alone. PLCgamma1 phosphorylation was also dampened within minutes after CTLA-4 engagement. Altogether these data indicate that through the control of signals induced by different receptors, CTLA-4 could be a global attenuator of T-cell activation.     

Spontaneous Splenic Rupture in a Patient with Acute Lymphoblastic Leukemia of Burkitt Type

We describe a case of spontaneous splenic rupture occurred in a patient with acute lymphoblastic leukemia of Burkitt type before starting cytotoxic chemotherapy. Left hypochondrial pain radiating to the homolateral shoulder was the only clinical symptom. Emergency computed tomography showed splenic laceration and hemoperitoneum. The patient underwent immediate laparotomy with splenectomy and experienced an uneventful postoperative recovery. Eight days after surgery, chemotherapy could be administered and complete remission was achieved. Although spontaneous rupture of the spleen is rare in leukemia and related disorders, this diagnosis should be taken in account also when clinical symptoms are mild. Following immediate operative management, patients may completely recover and receive cytotoxic chemotherapy with substantial possibilities of achieving complete remission.