Solitary tumours associated with Jaagsiekte retrovirus in sheep are heterogeneous and contain cells expressing markers identifying progenitor cells in lung repair.

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by jaagsiekte sheep retrovirus (JSRV). This study examines immunohistochemically solitary lung nodules considered as early OPA lesions from 11 sheep infected naturally by JSRV. All 11 neoplastic nodules exhibited features of adenocarcinoma and in four of them mesenchymal growth was also observed. Both types of lesion were labelled with antibody specific for JSRV-Env. In two cases infiltrating lymphoreticular cells also contained JSRV-Env. All tumours had a high Ki67 labelling index and variably contained cells expressing CC10 (a marker of Clara cells (CCs)), SPC (a marker of type II pneumocytes), p63 and keratin 14 (markers for stem/progenitor cells of the lung airway epithelia). Tumours with mesenchymal growth had intense expression of vimentin and desmin, weak expression of smooth muscle actin and did not express pancytokeratin and p63. Both epithelial and mesenchymal proliferations did not express the stem cell markers CD90 and CD117, but some tumour infiltrating cells expressed CD133. Solitary OPA tumours can therefore be adenocarcinomas or mixed tumours and have a heterogeneous cellular composition, containing groups of cells expressing markers that characterize local progenitor cells involved in lung repair.

[T-type primary lymphoma of the central nervous system in immunocompetent patients]. / Linfoma primario tipo T del sistema nervioso central en pacientes inmunocompetentes.

INTRODUCTION: The primary lymphoma of the central nervous system is an infrequent neoplasia, which represents 1,5% of all primary neoplasias in adult patients. In the last decade its frequency has increased threefold, both in immunodepressed as well as in immunocompetent patients. The non Hodgkin lymphoma of B cells being the most frequent histological type, the primary T cell lymphoma of the CNS is a rare clinical entity. CASE REPORTS: In this study we present three cases of immunocompetent patients with primary lymphoma of the central nervous system of T cells seen during the 6 last years in our hospital, the diagnostic imaging by computerized tomography and magnetic resonance showed the tumorations, but the definitive diagnosis was by stereotaxic cerebral biopsy. CONCLUSIONS: The lymphomas are radiosensitive to radiotherapy with survivals of approximately 26 months, the combined treatment of surgery and chemotherapy, prior to radiotherapy, may increases survival up to 48 months. Certain aspects of the patient or of the tumor itself are determining factors with respect to the prognosis of survival. We review the relevant literature and study the clinical manifestation, their value of imaging techniques and differential diagnostic and prognosis of survival

Immunohistochemical detection of ribosomal transcription factor UBF and AgNOR staining identify apoptotic events in neoplastic cells of Hodgkin's disease and in other lymphoid cells.

Ribosomal RNA synthesis is a key molecular process for understanding the mechanisms that drive cell proliferation. In this process, the upstream binding factor (UBF) is involved in regulating rDNA transcription at the nucleolus, together with RNA polymerase I. Recently, UBF was demonstrated to be a substrate for selective cleavage by specific proteases during apoptosis. Here we studied the expression of UBF in several cases of Hodgkin's disease (HD) by immunostaining and found it to be absent or clearly diminished in a high proportion of Reed-Sternberg cells and Hodgkin cells compared to small reactive lymphocytes. This result contrasted with labeling of those cells by the AgNOR technique, a marker of cell proliferation dependent on increased amounts of several proteins related to ribosome assembly. Disappearance of UBF and preservation of other NOR proteins is consistent with the pattern of selective proteolysis by caspases described in early stages of apoptosis. This correlates well with our results observed on induction of apoptosis in Jurkat cells treated with anti-FAS/APO-1 serum and with those in aged germinal center B-cells, in which UBF was no longer seen although the staining signal of other NOR proteins was maintained. These results support the concept that the rate of apoptosis is higher in neoplastic cells of HD than in the benign reactive lymphocyte population. Differential proteolysis of NOR proteins, as revealed by double staining of UBF and AgNOR, may prove valuable for identification of early stages of apoptosis in cytological and histopathological samples.

[Oxidative phosphorylation defects with neonatal presentation: review of our caseload]. / Defectos de la fosforilación oxidativa de presentación neonatal: revisión casuística.

OBJECTIVES: To define the oxidative phosporilation deficit syndrome in the neonatal in terms of incidence and clinical, biochemical and genetic features. MATERIAL AND METHODS: We report 9 newborns diagnosed as oxidatic phosporilation deficit during the last 8 years in our hospital by means of clinical, metabolic, pathological and molecular studies, among other evaluations. The diagnosis was established based on ensymatic deficit of the respiratory chain, associated with alterations in the mtDNA in one case, and with mitochondrial ultrastructural anomalies in 5 cases. RESULTS: There was an incidence of 1/3.555 newborns and 1/832 newborns admitted in our Neonatal Unit. In four of them there were familial antecedents and polihidramnios in two. Most of them, 8 out of 9, were born at term after a normal pregnancy and delivery, with normal Apgar score and auxological examination. Symptomatology started immediately at the neonatal period as acute neurological damage in most of them. There was a severe evolution as 5 children died and 4 survived with severe damage. All of them had the classical phenotype of early severe encefalopathy, associated with dismorphic features, hypotomía, neurosensorial defects, brain dysgenesis and atrophy, anomalies in the EEG and in 5 of them there were also systemic anomalies, mainly cardiopathy. The most frequent biochemical alteration was a significative increment of the quotient lactate/piruvate. Five patients presented ultrastructural alterations of the mitochondria in thr muscle biopsy but Cox stain was not positive in any case. Three cases has a deficit of the complex IV, e of the complex I-IV, 2 of the complex I and one the complex I-III-IV. Only one patient had multiple deletions in the mtDNA. CONCLUSIONS: Oxidatic phosporilation deficit are frequent and severe diseases of prenatal onset with limited fetal effects, homogeneous clinical phenotype with frequent damage of the central nervous system and variable extraneurological alteration and inconsistent biochemical pattern. Enzymatic studies ar need for making the diagnosis in all suspected cases,

Evidence for a protein related immunologically to the jaagsiekte sheep retrovirus in some human lung tumours.

Human bronchioloalveolar carcinoma (BAC) is a lung cancer, morphologically similar to an endemic contagious lung neoplasm of sheep called sheep pulmonary adenomatosis (SPA) or jaagsiekte. SPA is caused by an exogenous type B/D retrovirus (jaagsiekte sheep retrovirus (JSRV)), which prompted the present study to obtain evidence of a retrovirus in BAC. A panel of 249 human lung tumours, 21 nontumour lung lesions, four normal lung tissues, 23 adenocarcinomas from other organs and a cell line expressing a human endogenous retrovirus protein was examined immunohistochemically using a rabbit antiserum directed against the JSRV capsid protein. Specific staining was detected only in the cytoplasm of recognizably neoplastic cells in the pulmonary alveoli of 39 of 129 (30%) BACs, 17 of 65 (26%) lung adenocarcinomas and two of seven large cell carcinomas. The remaining samples were negative. These results support the hypothesis that some human pulmonary tumours may be associated with a jaagsiekte sheep retrovirus-related retrovirus, warranting further studies.

[McArdle's disease in a 14-year-old girl with fatigability and raised muscle enzymes]. / Enfermedad de McArdle en una niña de 14 años con fatigabilidad y elevación de las enzimas musculares.

INTRODUCTION: McArdle's disease is a disorder of muscle energy metabolism caused by a deficit of muscle phosphorylase. The typical form presents with fatigability muscle cramps and pains triggered by physical exercise. Some cases have few symptoms. We report the case of a 14 year old girl diagnosed on finding a significantly raised CPK, studied following her complaint of fatigability. CLINICAL CASE: A 14 year old girl presented with a CPK of 1,243 UI/l (normal 10-32) which had been requested in view of her fatigability. She had never had cramps, muscle pains or dark urine. Neurological examination was normal. The levels of CPK after intense exercise on the previous days were 7,459 UI/l, and after rest for one week were 283 UI/l (normal 25-230). The ischemic exercise test showed that she was unable to finish the test, with flat lactate and pyruvate curves and markedly raised ammonia (basal 89 and maximum 571 micrograms/dl). On muscle biopsy, the morphology of the striated muscle was seen to be normal and staining for myophosphorylase was negative. CONCLUSIONS: The fluctuations of muscle enzyme levels in relation to exercise orientate the diagnosis towards a disorder of muscle energy metabolism. To detect this, the investigation should be carried out following severe exercise for several days and then compared with a further test after some days of rest. The ischemic exercise test permits identification of defects of glycogenolysis, orientating the choice of suitable histochemical, enzymatic or molecular biological tests.

Defectos de la fosforilación oxidativa de presentación neonatal: revisión casuística / Oxidative phosphorilation defects with neonatal presentation: review of our experience

Objetivos: Definir el síndrome de déficit de la fosforilación oxidativa neonatal, en función de su incidencia, características perinatales, clínicas, bioquímicas y genéticas. Material y métodos : Se revisan los casos de 9 recién nacidos catalogados como déficit de la fosforilación oxidativa en los últimos 8 años en nuestro centro, mediante valoración clínica, metabólica, histopatológica, enzimática y molecular, además de otras evaluaciones. El diagnóstico se estableció en función del déficit enzimático de la cadena respiratoria, asociado a alteraciones del ADNmt en un caso, y en cinco a anomalías ultraestructurales mitocondriales. Resultados La incidencia fue de 1/3.555 y de 1/832 recién nacidos ingresados en nuestra unidad neonatal. Cuatro tenían antecedentes familiares positivos, y dos polihidramnios. La mayoría (8/9) fueron recién nacidos a término, de embarazo y parto normales, con Apgar y somatometría también normales. La clínica se inició en el período neonatal inmediato, como sufrimiento neurológico agudo en la mayoría. La evolución fue grave (5 fallecieron y 4 sobreviven gravemente afectados). Todos presentaban un fenotipo clínico de encefalopatía grave precoz, asociada a dismorfia, hipotonía, alteraciones neurosensoriales, atrofia y disgenesia cerebral, electroencefalograma patológico, y en 5 de ellos, además, a anomalías viscerales (principalmente cardiopatía). La alteración bioquímica más frecuente fue un aumento significativo del cociente lactato/piruvato. Cinco pacientes presentaron alteraciones ultraestructurales mitocondriales en la biopsia muscular pero la tinción de Cox no resultó claramente patológica en ningún caso. Tres tenían un déficit del complejo IV, tres de I-IV, dos del I y uno del I-III-IV. Sólo en un paciente se detectaron deleciones múltiples del ADNmt. Conclusiones Se trata de enfermedades frecuentes y graves, de comienzo prenatal con escasa repercusión fetal, fenotipo clínico homogéneo con afectación predominante del SNC y extraneurológica variable, y perfil bioquímico inconstante. El diagnóstico exige el estudio enzimático de la cadena respiratoria en todos los casos sospechosos (AU)

[Progressive myoclonic epilepsy as a sign of a late form of Alpers syndrome]. / Epilepsia mioclónica progresiva como manifestación de una forma tardía de síndrome de Alpers.

INTRODUCTION: Progressive cerebral polidystrophy or Alpers syndrome is a clinico-pathological picture, with no specific biological marker, characterized by involvement mainly of the cerebral grey matter and which shows clinically as a rapidly progressive encephalopathy with intractable seizures, usually myoclonic. The typical picture starts, after a normal neonatal period, during the first two years of life. CLINICAL CASE: A boy who after some previous difficulty with school-work presented with epilepsy at the age of 10 years and when he was 11 years old had a sudden illness with intractable seizures and severe neurological deterioration with spastic-dystonic tetraparesia, absence of visual function and minimal social contact to vocal or tactile stimuli. He had had a previously normal brother who died at the age of seven years during status epilepticus. Skin and muscle biopsies showed increase in the number and size of the mitochondria. Study of the respiratory chain in muscle showed a partial deficit in the activity of cytochrome C oxidase. CAT scanning showed marked generalized atrophy after four years. CONCLUSIONS: This case fulfils the criteria for Alpers syndrome established by Adams and Lyon in 1996. We consider that in the context of Alpers syndrome ultrastructural changes in the mitochondria of skin and muscle and partial deficit of enzyme activity of the IV complex of the respiratory chain should be evaluated. We emphasize the late presentation of Alpers syndrome, which has rarely been reported in the literature.

[Demyelinating pseudotumoral lesion prior to a primary cerebral lymphoma]. / Lesión pseudotumoral desmielinizante previa a linfoma cerebral primario.

INTRODUCTION: Some case of demyelinating pseudotumoral lesions preceding the appearance of primary cerebral lymphoma have been reported. The relation between the two conditions is not known. We report the case of a woman in whom a demyelinating pseudotumoral lesion had been diagnosed on biopsy and who developed a primary cerebral lymphoma 13 months later. CLINICAL CASE: In October 1997 a 38 year old woman presented with a secondarily generalized focal motor seizure. Neuroimaging showed a left frontal tumour with marked oedema and uptake of contrast medium. Based on the clinicoradiological suspicion of a primary cerebral tumour or metastasis, treatment was started with dexamethasone. Approximately two weeks later a stereotaxic biopsy was done, in which there was demyelination with conservation of the axons and perivascular inflammatory infiltration with polyclonal T and B lymphocytes. The diagnosis was 'a pseudotumoral form of a demyelinating disease'. Thirteen months later the patient had episodes of falling to the floor, followed by subsequent slight confusion and difficulty in speaking. On neuroimaging studies (cerebral CAT and MR) there was a tumour of the left basal ganglia, considerable oedema and homogeneous marking following the injection of contrast. Anatomopathological study of the lesion showed a B cell lymphoma. CONCLUSION: In cases of pseudotumoral demyelinating lesions the possibility of a primary cerebral lymphoma of the central nervous system must be remembered.