Síndrome de Peutz-Jeghers / Peutz-Jeghers syndrome

Presentamos el caso de un niño de 6 años de edad con lesioneshiperpigmentadas en la región perioral. El padre del pacientehabía sido diagnosticado de síndrome de Peutz-Jeghers (SPJ)mediante un estudio genético. Las lesiones cutáneas, junto conlos antecedentes familiares, fueron la clave para el diagnósticotemprano de la enfermedad. El SPJ es una entidad rara, caracterizadapor la aparición de lentigos periorificiales y póliposgastrointestinales. Histológicamente, estos pólipos son hamartomasque pueden llegar a malignizarse. Además, el SPJ seasocia al desarrollo de tumores extraintestinales (mama, endometrio,ovario, testículo, páncreas...). Por ello, es necesariorealizar un diagnóstico precoz y un control periódico de laspersonas que padecen este síndrome y sus familiares(AU)

We report the case of a 6-year-old child with hyperpigmentedlesions in perioral region. His father had been diagnosed ofPeutz-Jeghers syndrome (PJS) by genetic testing. PJS is a rareentity characterized by the presence of hyperpigmented periorificiallesions and gastrointestinal polyps. Histologically, thesepolyps are hamartomas that can become malignant. Moreover,PJS is associated with the development of nongastrointestinalcancer (breast, endometrium, ovary, testicle, pancreas...). It istherefore necessary to make an early diagnosis and periodicmonitoring of the patients with this syndrome and their families(AU)

Actitud expectante como tratamiento eficaz en un caso de múltiples lesiones por «Molluscum contagiosum» / Attitude expectant as effective treatment in Molluscum contagiosum

El molusco contagioso es una infección cutánea frecuente causada por un virus de la familia de los poxvirus, que afecta principalmente a los niños. La enfermedad puede transmitirse por contacto directo a través de la piel, por fómites contaminados o por autoinoculación. La infección se resuelve habitualmente de forma espontánea en pacientes inmunocompetentes, en un tiempo que puede oscilar entre meses y años. Existe un debate continuo sobre si se debe tratar activamente o mantener una actitud expectante(AU)

Molluscum contagiosum is a common skin infection, caused by a poxvirus, that affect mainly children. The disease can be transmitted by direct contact, fomites, or auto-inoculation. The infection will usually resolve within months or years in people with normal immunity. There has been a continous discussion about whether physicians should treat Molluscum contagiosum actively or not(AU)

Programmed cell death in the development of the vertebrate inner ear.

Programmed cell death is known to be an essential process for accurate ontogeny during the normal development of the inner ear. The inner ear is a complex sensory organ responsible for equilibrium and sound detection in vertebrates. In all vertebrates, the inner ear develops from a single ectodermic patch on the surface of the embryo's head, which undergoes a series of morphological changes to give rise to the complex structure of the adult inner ear. Enlargement and morphogenesis of the inner ear primordium is likely to depend on cellular division, growth, migration, differentiation and apoptosis. Here we describe the regions of programmed cell death that contribute to the final morphological aspect of the adult inner ear. The few studies that focus on the molecules that control this process during inner ear development indicate that the molecules and intracellular signaling pathways activated during the apoptotic response in the inner ear are similar to the previously described for the nervous system. In this review, we will describe some of the growth factors and key pathways that regulate pro- and anti-apoptotic signals and how they cross talk to determine the apoptotic or survival fate of cells in the development of the inner ear.

Granuloma tricorrexico pos varicela-zoster / Tricorrexico granuloma post varicella-zoster

Se han descripto lesiones granulomatosas después de erupciones por virus varicela-zóster. La presencia del virus en estas lesiones se detecta solo durante el mes de evolución y ellas curan espontáneamnete. Se presenta el caso de un noño con granulomas tricorréxico, despues de 6 meses de una infección por este virus, con posterior resolución espontánea y sin partícilas virales en la microscopía electrónica(AU)

Granuloma tricorrexico pos varicela-zoster / Tricorrexico granuloma post varicella-zoster

Se han descripto lesiones granulomatosas después de erupciones por virus varicela-zóster. La presencia del virus en estas lesiones se detecta solo durante el mes de evolución y ellas curan espontáneamnete. Se presenta el caso de un noño con granulomas tricorréxico, despues de 6 meses de una infección por este virus, con posterior resolución espontánea y sin partícilas virales en la microscopía electrónica

A new glucose-6-phosphate dehydrogenase variant with congenital nonspherocytic hemolytic anemia (G6PD Genova). Biochemical characterization and mosaicism expression in the heterozygote.

A new deficient variant of glucose-6-phosphate dehydrogenase (G6PD) causing severe congenital nonspherocytic hemolytic anemia (CNSHA) is described. The variant enzyme, characterized by slow electrophoretic mobility, extreme in vivo and in vitro lability, high Km for G6P and strongly acidic pH optimum, appears to be unique, and has been designated G6PD Genova. Investigation of an obligate heterozygote using various cytochemical, biochemical and recombinant-DNA techniques showed G6PD mosaicism in the erythrocytes and leukocytes. Therefore, the presence of a disadvantageous mutation at one Gd locus did not determine selection in favor of the normal allele in the heterozygote's hemopoietic cells.

Catalase and glutathione peroxidase are equally active in detoxification of hydrogen peroxide in human erythrocytes.

Genetic deficiencies of glucose-6-phosphate dehydrogenase (G6PD) and NADPH predispose affected erythrocytes to destruction from peroxides. Conversely, genetic deficiencies of catalase do not predispose affected erythrocytes to peroxide-induced destruction. These observations have served to strengthen the assumption that the NADPH/glutathione/glutathione peroxidase pathway is the principal means for disposal of H2O2 in human erythrocytes. Recently, however, mammalian catalase was found to have tightly bound NADPH and to require NADPH for the prevention and reversal of inactivation by its toxic substrate (H2O2). Since both catalase and the glutathione pathway are dependent on NADPH for function, this finding raises the possibility that both mechanisms destroy H2O2 in human erythrocytes. A comparison of normal and acatalasemic erythrocytes in the present study indicated that catalase accounts for more than half of the destruction of H2O2 when H2O2 is generated at a rate comparable to that which leads to hemolysis in G6PD- deficient erythrocytes.

The function of catalase-bound NADPH.

Catalase (H2O2:H2O2 oxidoreductase, EC 1.11.1.6) is of historical interest for having been the subject of some of the earliest investigations of enzymes. A feature of catalase that has been poorly understood for several decades, however, is the mechanism by which catalase remains active in the presence of its own substrate, hydrogen peroxide. We reported recently that catalase contains tightly bound NADPH. The present study with bovine and human catalase revealed that NADPH both prevents and reverses the accumulation of compound II, an inactive form of catalase that is generated slowly when catalase is exposed to hydrogen peroxide. Since the effect of NADPH occurs even at NADPH concentrations below 0.1 microM, the protective mechanism is likely to operate in vivo. This discovery of the role of catalase-bound NADPH brings a unity to the concept of two different mechanisms for disposing of hydrogen peroxide (catalase and the glutathione reductase/peroxidase pathway) by revealing that both mechanisms are dependent on NADPH.

Primary thrombocythemia: clonal origin of platelets, erythrocytes, and granulocytes in a GdB/GdMediterranean subject.

A patient with primary thrombocythemia, who was heterozygous for glucose-6-phosphate dehydrogenase deficiency (GdB/GdMed), was investigated to test for the clonal origin of this myeloproliferative disorder. In order to assess somatic cell mosaicism in various tissues, we have made use of the different rate of utilization of 2-deoxyglucose-6-phosphate, an analog of glucose-6-phosphate, by normal glucose-6-phosphate dehydrogenase and by the Mediterranean variant: the results demonstrate that essential thrombocythemia is a clonal disease involving the erythrocytic, granulocytic, and megakaryocytic series, without affecting monocytes, T lymphocytes, and non-T lymphocytes.

G6PD Napoli and Ferrara II: two new glucose-6-phosphate dehydrogenase variants having similar characteristics but different intracellular lability and specific activity.

Two new glucose-6-phosphate dehydrogenase (G6PD, D-glucose 6-phosphate: NADP oxido reductase, E.C. 1.1.1.49) variants, designated G6PD Napoli and G6PD Ferrara II, are described in propositi from two unrelated families. Characterization side by side of the two variants according to W.H.O. recommendations reveals minor differences which are mostly related to utilization of artificial substrates (increased in both cases as compared with normal G6PD type B). Other properties, which are not significantly distinctive between the two variants, are an enzyme activity amounting to nearly 20% of normal, a decreased electrophoretic mobility, decreased Km values for glucose-6-phosphate and NADP, normal thermostability and biphasic pH curves. However, marked differences emerged between the two variants and between either variant and G6PD B as well, when a number of microtechniques were used. These were: (1) the half-lives of G6PD Napoli and G6PD Ferrara II are 16 and 29 d, respectively, while that of G6PD B is 63 d; (2) the specific activities, measured by a method involving direct estimation of G6PD protein on sodium dodecyl sulphate polyacrylamide gel electrophoretic tracings, are 166 I.U./mg (G6PD Napoli) and 59 I.U./mg (G6PD Ferrara II), as compared with normal value of 180 I.U./mg (G6PD B). On the whole, these findings allow the conclusion that the deficiency of catalytic activity is related to an accelerated though distinctive decay of both mutant enzyme proteins within the affected erythrocytes and that a significant impairment of catalytic efficiency is also involved, as a result of the underlying structural mutation in the case of G6PD Ferrara II.

2-deoxy-glucose-6-phosphate utilization in the study of glucose-6-phosphate dehydrogenase mosaicism.

The electrophoretic difference between normal glucose-6-phosphate dehydrogenase (G6PD) and two common variants (G6PD A and G6PD A-) has made the G6PD enzyme system very useful for genetic studies and for investigation on the clonal origin of tumors. This approach has not been possible for another common variant, G6PD mediterranean, which has a normal electrophoretic pattern. The different utilization of 2-deoxy-glucose-6-phosphate (2dG6P), an analog of the normal substrate, by the normal enzyme and the Mediterranean variant, allows a convenient determination of the degree of mosaicism in mononuclear cells from heterozygotes.

Favism: erythrocyte metabolism during haemolysis and reticulocytosis.

The reduced activity of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate; NADP+ 1-oxidoreductase; G6PF) in Mediterranean erythrocytes explains the precarious equilibrium of the hexose monophosphate pathway (HMP) and the susceptibility of these cells to haemolytic agents. G6PD-deficient erythrocytes, in steady-state conditions, have a low NADPH/NADP+ ratio, thus allowing the HMP to operate at its maximal intracellular rate and to compensate the intrinsic erythrocyte enzyme deficiency. Studies started soon after accidental intake of fava beans by sensitive G6PD-deficient subjects demonstrate a decrease of both NADPH/NADP+ ratio and reduced glutathione. The metabolic effects induced by fava beans may be attributed to oxidative stress probably associated with an inhibitor effect of some unknown metabolite on the HMP. The availability of erythrocytes from subjects recovering from haemolysis with high reticulocyte counts and increased G6PD activity, provides new information on the rate of synthesis as well as on the in vivo decay of the mutant enzyme. Correlation of G6PD activity to reticulocyte count and extrapolation to an ideally homogenous population of reticulocytes reveal that the mutant enzyme is synthesized at a nearly normal rate. Furthermore, the present correlation allows an estimate of the in vivo half-life of Mediterranean G6PD. The rate of decline of about 8 d observed in this study well correlates to the intracellular metabolic aspects of G6PD Mediterranean erythrocytes.

Effect of haemolysis on the hexose monophosphate pathway in normal and in glucose-6-phosphate dehydrogenase-deficient erythrocytes.

The hexose monophosphate pathway of human glucose-6-phosphate dehydrogenase (EC 1.1.1.49) - deficient erythrocytes is under a severe and unexplained restraint (Gaetani, G.D., Parker, J.C. and Kirkman, H.N. (1974) Proc. Natl. Acad. Sci. U.S. 71, 3584-3587). In this study the hexose monophosphate pathway activity and the NADPH level of normal and glucose-6-phosphate dehydrogenase-deficient erythrocytes were measured soon after haemolysis. The results indicate a prompt increase in 14CO2 evolution and a rise in MADPH levels. Since, in this study, the concentration of the haemolysate is comparable to that of intact erythrocytes, the relief of the restraint on glucose-6-phosphate dehydrogenase through dilution-dependent dissociation from inactivator or inhibitor is excluded. The possibility that the intracellular restraint may result from compartmentalization of glucose-6-phosphate dehydrogenase and substrates or from properties of the intact membrane of the erythrocytes is suggested.