Image-directed percutaneous biopsies with a biopsy gun

Core tissue for histologic study is believed by many pathologists to be more diagnostic than material from needle aspiration. Recently, a biopsy "gun" has been introduced, which simplifies core biopsies. With this device, 182 biopsies of multiple anatomic sites were performed with ultrasonic, computed tomographic, and fluoroscopic guidance and 18-gauge needles. High-quality histopathologic specimens were obtained in 177 of the biopsies, and diagnostic target tissue was obtained in 167. Only three significant complications occurred: one bleeding complication that required transfusion and two cases of pneumothorax that necessitated placement of chest tubes. The biopsy gun eliminated the disjointed movements of conventional "skinny" needle biopsies, and none of the samples demonstrated significant "crush" artifact or obscuring blood, problems that are commonly associated with manual biopsy techniques. Patient discomfort was decreased with this system compared with that of manual biopsies, and the total procedure time was reduced. Because of these distinct advantages, the authors now use the biopsy gun exclusively for all percutaneous biopsies and recommend that other institutions consider the use of this biopsy method.     

新生期大白鼠皮下注射谷氨酸单钠对成年后下丘脑α-促黑素细胞激素神经元免疫反应性的影响

本文用免疫组化方法研究了新生期大白鼠注射谷氨酸单钠(MSG)对成年后下丘脑α-促黑素细胞激素(α-MSH)免疫反应神经元的影响,结果显示MSG处理以后下丘脑弓状核区α-MSII免疫反应神经元减少甚至完全消失,但不影响下丘脑背外侧区的α-MSH神经元群。文中还讨论了这两群α-MSH神经元的生理作用。     

Comparative genomic hybridization of 49 primary retinoblastoma tumors identifies chromosomal regions associated with histopathology,progression, and patient outcome

Forty-nine primary retinoblastoma (Rb) tumors were analyzed by the use of comparative genomic hybridization (CGH), and clinical/histological correlations were performed. Adverse histological factors were present in 13 patients. Chromosomal imbalance was a frequent phenomenon, seen in 96% of the tumors. Gain of 6p represented the most frequent event (69% of the tumors), whereas +1q was observed in 57%, confirming that these abnormalities are key secondary events in retinoblastoma tumor progression. Loss of 13q and 16 was significantly associated with tumors displaying adverse histo-prognostic factors, whereas -16q was significantly associated with tumors without adverse features. In three patients who developed an extra-ocular relapse, the tumors showed -13q and 2/3 had -5q, suggesting that these abnormalities may be associated with metastasis. Children >or= 36 months of age at enucleation tended to have more CGH abnormalities per tumor than children < 12 months (median numbers 11 vs. 3). In addition, +1q, +13q, -16, and -16q were more frequent in children with an older age at enucleation. Identical CGH changes were found in both tumors from one patient with bilateral tumors, suggesting a common origin. It is possible that tumors displaying loss of 13q and 5q indicate those patients who may suffer an adverse outcome and who would require alternative or more intensive therapy. CGH analysis on larger cohorts and in prospective clinical trials will be invaluable in determining whether a genetic classification of retinoblastoma represents a reliable measure of prognosis.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

CTLA-4 is required for the induction of high dose oral tolerance

Mucosal and systemic administrations of high dose antigens induce long- lasting peripheral T cell tolerance. We and others have shown that high dose peripheral T cell tolerance is mediated by anergy or deletion and is preceded by T cell activation. Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) and their counter-receptors CD28/CTLA-4 play pivotal roles in T cell activation and immune regulation. In the present study, we examined the roles of the B7 co-stimulation pathway in the generation of high dose peripheral T cell tolerance. We found that blocking B7:CD28/CTLA-4 interaction at the time of tolerance induction partially prevented T cell tolerance, whereas selective blockade of B7:CTLA-4 interaction completely abrogated peripheral T cell tolerance induced by either oral or i.p. antigens. These results suggest that CTLA-4-mediated feedback regulation plays a crucial role in the induction of high dose peripheral T cell tolerance.      

Screening for proteins with polyglutamine expansions in autosomal dominant cerebellar ataxias

Expansion of trinucleotide CAG repeats coding for polyglutamine has been implicated in five neurodegenerative disorders, including spinocerebellar ataxia (SCA) 1 and SCA3 or Machado-Joseph disease (SCA3/MJD), two forms of type I autosomal dominant cerebellar ataxias (ADCA). Using the 1C2 antibody which specifically recognizes large polyglutamine tracts, particularly those that are expanded, we recently reported the detection of proteins with pathological glutamine expansions in lymphoblasts from another form of ADCA type I, SCA2, as well as from patients presenting with the distinct phenotype of ADCA type II. We now have screened a large series of patients with ADCA or isolated cases with cerebellar ataxia, for the presence of proteins with polyglutamine expansions. A 150 kDa SCA2 protein was detected in 16 out of 40 families with ADCA type I. This corresponds to 24% of all ADCA type I families, which is much more frequent than SCA1 in this series of patients (13%). The signal intensity of the SCA2 protein was negatively correlated to age at onset, as expected for an expanded and unstable trinucleotide repeat mutation. The disease segregated with markers closely linked to the SCA2 locus in all identified SCA2 families. In addition, a specific 130 kDa protein, which segregated with the disease, was detected in lymphoblasts of patients from nine families with ADCA type II. It was also visualized in the cerebral cortex of one of the patients, demonstrating its translation in the nervous system. Finally, no new disease-related proteins containing expanded polyglutamine tracts could be detected in lymphoblasts from the remaining patients with ADCA or isolated cases with cerebellar ataxia.      

Three-dimensional modeling of the anatomy of the heart and great vessels

Summary The anatomic constraints imposed on a total artificial heart (TAH) require specific anatomic studies. A thoracic anatomic study was performed with a scanning device equipped with three-dimensional (3-D) reconstruction software on 15 male patients, between the ages of 41 to 63 years (52 ± 6 years). All were candidates for heart transplantation. The 3-D reconstructions of the cardiovascular structures obtained from surgical anatomy data specific to TAH implantation allowed a volumetric measurement of these structures. A modeling diagram of these structures permitted reproducible quantitative measurements of the 35 geometrical parameters which characterized shape, orientation, and position of these structures within the thorax. Most of the measured parameters were characterized by low variability (coefficient of variation from 10 to 25%).

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Modélisation tridimensionnelle de l'anatomie du cur et des gros vaisseaux

Résumé Les contraintes anatomiques imposées au cur artificiel total (CAT) nécessitent des études anatomiques spécifiques. Une étude anatomique thoracique a été réalisée avec un scanner doté d'un logiciel de reconstruction tridimensionnelle (3-D) chez 15 patients, tous de sexe masculin, agés de 41 à 63 ans (52 ± 6 ans), et candidats à une transplantation cardiaque. Les reconstructions 3-D des structures cardio-vasculaires réalisées selon les données de l'anatomie chirurgicale propre à l'implantation du CAT ont permis la mesure volumétrique de ces structures. Un schéma de modélisation de ces structures a permis des mesures quantitatives reproductibles de 35 paramètres géométriques caractéristiques de la forme, de l'orientation, de la position de ces structures dans le thorax. Les résultats de ces mesures ont pu être exprimés en termes statistiques. La plupart des paramètres mesurés étaient caractérisés par une faible variabilité (coefficients de variations de 10 à 25%).

     

Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes

Friedreich ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the frataxin gene. In order to unravel frataxin function we developed monoclonal antibodies raised against different regions of the protein. These antibodies detect a processed 18 kDa protein in various human and mouse tissues and cell lines that is severely reduced in Friedreich ataxia patients. By immunocytofluorescence and immunocytoelectron microscopy we show that frataxin is located in mitochondria, associated with the mitochondrial membranes and crests. Analysis of cellular localization of various truncated forms of frataxin expressed in cultured cells and evidence of removal of an N-terminal epitope during protein maturation demonstrated that the mitochondrial targetting sequence is encoded by the first 20 amino acids. Given the shared clinical features between Friedreich ataxia, vitamin E deficiency and some mitochondriopathies, our data suggest that a reduction in frataxin results in oxidative damage.