Papillary fibroelastoma of the heart

BACKGROUND: Fibroelastoma is a rare cardiac tumor that was originally described typically from autopsy findings. Thanks to improved imaging modalities, such tumors are today relatively easy to detect and therefore are actively searched for in patients with unclear embolic events. We present the cases of 2 patients recently treated in our clinic and review the recent literature pertaining to fibroelastomas. METHODS AND RESULTS: An electronic PubMed search revealed 186 cases reported between 1994 and 2003. Ninety-seven percent of the reported fibroelastomas were diagnosed in living patients in their fourth and fifth decades of life. The majority (86%) were symptomatic, with stroke, transient ischemic attack, myocardial infarction, and angina pectoris being the most commonly described. Echocardiography was the typical diagnosis modality. Surgical resection was completed in 95% of the cases. CONCLUSIONS: Although cardiac papillary fibroelastomas are rare and benign tumors, they cannot be considered as harmless endothelial lesions, because related embolic events are frequent and primarily involve adults in their active period of life. Echocardiography must therefore consider fibroelastoma in the differential diagnosis of every unclear systemic embolic event, especially because surgical resection can be considered as curative.

Chronic stimulation of the globus pallidus internus for treatment of non-dYT1 generalized dystonia and choreoathetosis: 2-year follow up

OBJECT: The authors studied the long-term efficacy of deep brain stimulation (DBS) of the posteroventral lateral globus pallidus internus up to 2 years postoperatively in patients with primary non-DYT1 generalized dystonia or choreoathetosis. The results are briefly compared with those reported for DBS in DYT1 dystonia (Oppenheim dystonia), which is caused by the DYT1 gene. METHODS: Enrollment in this prospective expanded pilot study was limited to adult patients with severely disabling, medically refractory non-DYT1 generalized dystonia or choreoathetosis. Six consecutive patients underwent follow-up examinations at defined intervals of 3 months, 1 year, and 2 years postsurgery. There were five women and one man, and their mean age at surgery was 45.5 years. Formal assessments included both the Burke-Fahn-Marsden dystonia scale and the recently developed Unified Dystonia Rating Scale. Two patients had primary generalized non-DYT1 dystonia, and four suffered from choreoathetosis secondary to infantile cerebral palsy. Bilateral quadripolar DBS electrodes were implanted in all instances, except in one patient with markedly asymmetrical symptoms. There were no adverse events related to surgery. The Burke-Fahn-Marsden scores in the two patients with generalized dystonia improved by 78 and 71% at 3 months, by 82 and 69% at 1 year, and by 78 and 70% at 2 years postoperatively. This was paralleled by marked amelioration of disability scores. The mean improvement in Burke-Fahn-Marsden scores in patients with choreoathetosis was 12% at 3 months, 29% at 1 year, and 23% at 2 years postoperatively, which was not significant. Two of these patients thought that they had achieved marked improvement at 2 years postoperatively, although results of objective evaluations were less impressive. In these two patients there was a minor but stable improvement in disability scores. All patients had an improvement in pain scores at the 2-year follow-up review. Medication was tapered off in both patients with generalized dystonia and reduced in two of the patients with choreoathetosis. All stimulation-induced side effects were reversible on adjustment of the DBS settings. Energy consumption of the batteries was considerably higher than in patients with Parkinson disease. CONCLUSIONS: Chronic pallidal DBS is a safe and effective procedure in generalized non-DYT1 dystonia, and it may become the procedure of choice in patients with medically refractory dystonia. Postoperative improvement of choreoathetosis is more modest and varied, and subjective ratings of outcome may exceed objective evaluations.

Serine residues 1177/78/82 of the insulin receptor are required for substrate phosphorylation but not autophosphorylation

Serine residues of the human insulin receptor (HIR) may be phosphorylated and negatively regulate the insulin signal. We studied the impact of 16 serine residues in HIR by mutation to alanine and co-overexpression in human embryonic kidney (HEK) 293 cells together with the docking proteins insulin receptor substrate (IRS)-1, IRS-2, or (SHC) Src homologous and collagen-like. As a control, IRS-1 was also cotransfected with an HIR with a juxtamembrane deletion (HIR delta JM) and therefore not containing the domain required for interaction with IRS-1. Coexpression of HIR with IRS-1, IRS-2, and SHC strongly enhanced tyrosine phosphorylation of these proteins. A similar increase in tyrosine phosphorylation was observed in cells overexpressing IRS-1, IRS-2, or SHC together with all HIR mutants except HIR delta JM and a mutant carrying exchanges of serines 1177, 1178, and 1182 to alanine (HIR1177/78/82), although this mutant showed normal autophosphorylation. Analysis of total cell lysates with anti-phosphotyrosine antibodies showed that in addition to the overexpressed substrates, other cellular proteins displayed reduced levels of tyrosine phosphorylation in these cells. To study consequences for phosphatidylinositol 3-kinase (PI 3-kinase) activation, we established stable NIH3T3 fibroblast cell lines overexpressing wild-type HIR, HIR1177/78/82, and other HIR mutants as the control. Again, HIR1177/78/82 showed normal autophosphorylation but showed a clear decrease in tyrosine phosphorylation of endogenous IRS-1 and activation of PI 3-kinase. This decrease in kinase activity also occurred in an in vitro kinase assay towards recombinant IRS-1. Finally, we performed a separation of the phosphopeptides by high-performance liquid chromatography and could not detect any differences in the profiles of HIR and HIR1177/78/82. In conclusion, we have defined a region in HIR that is important for substrate phosphorylation but not autophosphorylation. Therefore, this mutant may provide new insights into the mechanism of kinase activation and substrate phosphorylation.

A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease

OBJECT: The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. METHODS: Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. RESULTS: Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. CONCLUSIONS: This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

Activity of the glycosylating enzyme, core 2 GlcNAc (beta1,6) transferase, is higher in polymorphonuclear leukocytes from diabetic patients compared with age-matched control subjects: relevance to capillary occlusion in diabetic retinopathy

The exact mechanism for capillary occlusion in diabetic retinopathy is still unclear, but increased leukocyte-endothelial cell adhesion has been implicated. We examined the possibility that posttranslational modification of surface O-glycans by increased activity of core 2 transferase (UDP-Glc:Galbeta1-3GalNAcalphaRbeta-N-acetylglucoaminyltr ansferase) is responsible for increased adhesion of leukocytes to vascular endothelium in diabetes. The mean activity of core 2 transferase in polymorphonuclear leukocytes isolated from type 1 and type 2 diabetic patients was higher compared with age-matched control subjects (1,638 +/- 91 [n = 42] vs. 249 +/- 35 pmol x h(-1) x mg(-1) protein [n = 24], P = 0.00013; 1,459 +/- 194 [n = 58] vs. 334 +/- 86 [n = 11], P = 0.01). As a group, diabetic patients with retinopathy had significantly higher mean activity of core 2 transferase compared with individuals with no retinopathy. There was a significant association between enzyme activity and severity of retinopathy in type 1 and type 2 diabetic patients. There was a strong correlation between activity of core 2 transferase and extent of leukocyte adhesion to cultured retinal capillary endothelial cells for diabetic patients but not for age-matched control subjects. Results from transfection experiments using human myelocytic cell line (U937) demonstrated a direct relationship between increased activity of core 2 transferase and increased binding to cultured endothelial cells. There was no relationship between activity of core 2 transferase and HbA(1c) (P = 0.8314), serum advanced glycation end product levels (P = 0.4159), age of the patient (P = 0.7896), and duration of diabetes (P = 0.3307). On the basis that branched O-glycans formed by the action of core 2 transferase participate in leukocyte adhesion, the present data suggest the involvement of this enzyme in increased leukocyte-endothelial cell adhesion and the pathogenesis of capillary occlusion in diabetic retinopathy.

Organic nitrogen and organic phosphorus concentrations bays of the White Sea

Concentrations of organic and mineral nitrogen and phosphorus in waters from different types of bays were determined during summer of 1987. Content of organic nitrogen in surface waters reached 80-97% of total; content of mineral phosphorus was 60-100%. Concentrations of N_org and P_org in deep waters decreased to 70 and 40%, respectively. Distribution of organic matter in the bays was controlled by river run-off.

Cenozoic planktonic foraminifera of the Falkland Plateau and Argentine Basin

Sites 511 and 512 (Falkland Plateau) and 513 (Argentine Basin) penetrated calcareous-siliceous oozes of the middle and upper Eocene and lower Oligocene with rather numerous planktonic foraminifers. Upper Oligocene, Miocene, Pliocene, and Quaternary sections are composed mostly of siliceous sediments (Sites 511-514) where planktonic foraminifers are rare or absent. High-latitude planktonic foraminifers of the Austral Province are characterized by impoverished assemblages - only representatives of Globigerina, Globigerinita, Globorotaloides, and Globorotalia with a rounded peripheral margin are found. In the Paleogene, these species are supplemented, in lesser amounts, by representatives of Globigerapsis, Acarinina, Pseudogloboquadrina, Pseudohastigerina, and Chiloguembelina. Assemblages of planktonic foraminifers have low stratigraphic resolution, especially in the upper Oligocene-Quaternary. This reflects the generally deteriorating Cenozoic climate, which evinced a sharp change in the upper Oligocene that is connected with initiation of the circum-Antarctic current near the Paleogene/Neogene boundary. Comparison of Paleogene and Neogene planktonic foraminifers of the South Atlantic (Falkland Plateau, Argentine Basin, 46-51°S) and the North Atlantic (Rockall Plateau, 55-56°N) indicates that the South Atlantic climate was much colder than that of the same latitudes of the North Atlantic. Paleogene oozes of the Falkland Plateau rest unconf ormably on Maestrichtian sediments and in their turn are overlain unconformably by Neogene-Quaternary oozes. Cenozoic sections are stratigraphically discontinuous: periods of intensive biogenic sedimentation resulting in a thick succession of sediments alternated with periods of nondeposition and strong erosion that resulted in hiatuses and unconformities. In the Argentine Basin, Oligocene calcareous-siliceous oozes rest on basalts of the oceanic basement; they are replaced upward in the section by Neogene-Quaternary siliceous oozes with some hiatuses. Planktonic foraminifers here clearly demonstrate the processes of oceanic subsidence and CCD fluctuations as well as Polar Front migrations during Cenozoic time. Fifty species of planktonic foraminifers are discussed and illustrated.

(Table 1.4) Ratios of petrogenic components in glassy and crystalline basalts from the north part of the Bougault anomaly, Mid-Atlantic Ridge 15°N

Structure and composition of sub-surface bottom sediments from the southwest Barents Sea have been under study. The study has revealed heterogeneity of sediment structure resulted from temporal irregularity and variability of sedimentation processes. The study of the heavy minerals from 0.1-0.01 mm grain size fraction has shown prevalence of green hornblende, epidote, garnet, and ilmenite in all types of sediments; these minerals are the basis of terrigenous-mineralogical province. At the same time in different areas local terrigenous-mineralogical associations have been identified. Clay mineral composition of in the sediments was quite uniform: biotite, chlorite, hydromica, smectite. Despite this, a number of features indicating initial stages of clay mineral transformation has been identified. Differences in material composition and structure of the studied sediments are associated with rapid change in paleogeographic situation on the land - ice cover melting on the Kola Peninsula and subsequent Holocene climatic situation.