Surgical management and role of medical therapy in ruptured aneurysmal neurocysticercosis. A case report and review of the literature.

We describe the case of an 80-year-old Hispanic male with an acute subarachnoid hemorrhage (SAH) due to an inflammatory middle cerebral artery (MCA) aneurysm rupture. Two years prior to this episode, the patient had undergone a resection of a left intracranial neurocysticercosis lesion. A current CT, CTA and MRI showed significant SAH, a left MCA aneurysm and a cystic lesion compatible with neurocysticercosis. Intraoperatively, this aneurysm was found to be adjacent to a neurocysticercosis cyst, a diagnosis confirmed by surgical pathology. Only a few cases of subarachnoid hemorrhage due to an inflammatory brain aneurysm have been reported. Due to the associated higher incidence of intraoperative rupture and difficulty clipping, our paper highlights the importance of considering an inflammatory origin in patients with a history of neurocysticercosis and subarachnoid hemorrhage. This is the oldest patient on record reported for this diagnosis and surgery.

Partial caudal duplication in a newborn associated with meningomyelocele and complex heart anomaly.

BACKGROUND: Caudal duplication is a spectrum of rare congenital anomalies with a possible heterogeneous pathogenesis including incomplete separation of monovular twins. METHODS: We report an autopsy case of a full-term infant with incomplete caudal duplication syndrome associated with multiple anomalies. RESULTS: These anomalies included a duplicated penis; double urinary bladder with an attenuated tunica muscularis; duplication of lower bowel with two ilia, appendices and colons; colonic hypogangliosis and left imperforated anus associated with rectourethral fistula. Other anomalies consisted of sacral meningomyelocele, sacral duplication with hypoplastic left sacrum and pelvic bones, muscle atrophy and hypoplasia of the left lower extremity, abnormal lobation of liver with stomach entrapment, omphalocele, and right atrial isomerism syndrome. The complex pattern of anomalies suggests the possibility that partial caudal duplication might be part of the spectrum of conjoined twinning.

Traffic pattern of cystic fibrosis transmembrane regulator through the early exocytic pathway.

The pathway of transport of the cystic fibrosis transmembrane regulator (CFTR) through the early exocytic pathway has not been examined. In contrast to most membrane proteins that are concentrated during export from the ER and therefore readily detectable at elevated levels in pre-Golgi intermediates and Golgi compartments, wild-type CFTR could not be detected in these compartments using deconvolution immunofluorescence microscopy. To determine the basis for this unusual feature, we analyzed CFTR localization using quantitative immunoelectron microscopy (IEM). We found that wild-type CFTR is present in pre-Golgi compartments and peripheral tubular elements associated with the cis and trans faces of the Golgi stack, albeit at a concentration 2-fold lower than that found in the endoplasmic reticulum (ER). delta F508 CFTR, a mutant form that is not efficiently delivered to the cell surface and the most common mutation in cystic fibrosis, could also be detected at a reduced concentration in pre-Golgi intermediates and peripheral cis Golgi elements, but not in post-Golgi compartments. Our results suggest that the low level of wild-type CFTR in the Golgi region reflects a limiting step in selective recruitment by the ER export machinery, an event that is largely deficient in delta F508. We raise the possibility that novel modes of selective anterograde and retrograde traffic between the ER and the Golgi may serve to regulate CFTR function in the early secretory compartments.

Cargo can modulate COPII vesicle formation from the endoplasmic reticulum.

The COPII coat complex found on endoplasmic reticulum (ER)-derived vesicles plays a critical role in cargo selection. We now address the potential role of biosynthetic cargo in modulating COPII coat assembly and vesicle budding. The ER accumulation of vesicular stomatitis glycoprotein (VSV-G), a transmembrane protein, or the soluble PiZ variant of alpha1-antitrypsin, reduced levels of general COPII vesicle formation in vivo. Consistent with this result, conditions that prevent the export of VSV-G from the ER led to a significant inhibition of general COPII vesicle budding from ER microsomes and the export of an endogenous recycling protein p58 in vitro. In contrast, synchronized export of VSV-G stimulated COPII vesicle budding both in vivo and in vitro. Under conditions where VSV-G is retained in the ER, we find that it can to be recovered in pre-budding complexes containing COPII components. These results suggest that the export of biosynthetic cargo is integrated with ER functions involved in protein folding and oligomerization. The ability of biosynthetic cargo to prevent or enhance ER export suggests that interactions of cargo with the COPII machinery contribute to the formation of vesicles budding from the ER.

Getting into the Golgi.

The intermediate compartment residing between the endoplasmic reticulum (ER) and the Golgi is now recognized to be a dynamic structure that captures cargo released from the ER in COPII vesicular carriers and promotes recycling by COPI vesicular carriers. These and other findings now provide compelling evidence for the importance of this intermediate in balancing anterograde and retrograde flow through the early secretory pathway and in the formation and maintenance of the Golgi stack.

AP-2-containing clathrin coats assemble on mature lysosomes.

Coat proteins appear to play a general role in intracellular protein trafficking by coordinating a membrane budding event with cargo selection. Here we show that the AP-2 adaptor, a clathrin-associated coat-protein complex that nucleates clathrin-coated vesicle formation at the cell surface, can also initiate the assembly of normal polyhedral clathrin coats on dense lysosomes under physiological conditions in vitro. Clathrin coat formation on lysosomes is temperature dependent, displays an absolute requirement for ATP, and occurs in both semi-intact cells and on purified lysosomes, suggesting that clathrin-coated vesicles might regulate retrograde membrane traffic out of the lysosomal compartment.

The organization of endoplasmic reticulum export complexes.

Export of cargo from the ER occurs through the formation of 60-70nm COPII-coated vesicular carriers. We have applied serial-thin sectioning and stereology to quantitatively characterize the three-dimensional organization of ER export sites in vivo and in vitro. We find that ER buds in vivo are nonrandomly distributed, being concentrated in regional foci we refer to as export complexes. The basic organization of an export complex can be divided into an active COPII-containing budding zone on a single ER cisterna, which is adjacent to budding zones found on distantly connected ER cisternae. These budding foci surround and face a central cluster of morphologically independent vesicular-tubular elements that contain COPI coats involved in retrograde transport. Vesicles within these export complexes contain concentrated cargo molecules. The structure of vesicular-tubular clusters in export complexes is particularly striking in replicas generated using a quick-freeze, deep-etch approach to visualize for the first time their three-dimensional organization and cargo composition. We conclude that budding from the ER through recruitment of COPII is confined to highly specialized export complexes that topologically restrict anterograde transport to regional foci to facilitate efficient coupling to retrograde recycling by COPI.

[The valvular apparatus and tissue organization of the endothelium of the thoracic duct]. / Klapannyi apparat i tkanevaia organizatsiia éndoteliia grudnogo protoka.

The structure of ostial valves and valves located along the thoracic duct and of its branches ostial valves and right lymphatic duct ostial valves were studied in 30 experimental outbred dogs and 46 cats. Cryodestruction of thoracic duct was performed in 28 outbred cats. 1, 3, 7 and 14 days later perfusive fixation with intercellular borders impregnation was carried out with simultaneous examination of intact regions of intravalvular segments, cisterna chyli and area of thoracic duct trunks connection with valvular surfaces. Tissue organization in ageing was studied using the intervalvular segment of old animals. Specimens were studied by means of scanning electron microscopy and film preparations of endothelium. Valves, located along the thoracic duct length are bicuspid formations, while ostial ones are falciform and cuneiform respectively in 80 and 20%. Endotheliocytes of cuspids are characterized with high content of microfilaments bundles in the cytoplasm and low content of microvesicles. Cells of the valvular free margin cross the cuspid edge and have adaptive changes preventing their desquamation: fusiform shape, long basal processes and bundles of microfilaments in the cytoplasm. Peculiar "pericyte-like" cells alike with myofibroblasts lie deep in the cuspid thickness close to the sinusal venous side. Fascicles of the duct smooth myocytes reach the base of the valve. Besides, in the ostial valve stroma there is elastic membrane, better displayed along the cuspid venous side. Increased polymorphism and changes of the endotheliocytes metric characteristics were demonstrated in the zones of turbulent lymph flow. Analysis of the newly formed endothelium tissue mosaics allows to reveal mechanisms of monolayer repair: spreading and migration of endotheliocytes on the first day, their proliferation within three days, desquamation of newly formed endotheliocytes and spreading of adjacent cells on later stages.

Sequential coupling between COPII and COPI vesicle coats in endoplasmic reticulum to Golgi transport.

COPI and COPII are vesicle coat complexes whose assembly is regulated by the ARF1 and Sar1 GTPases, respectively. We show that COPI and COPII coat complexes are recruited separately and independently to ER (COPII), pre-Golgi (COPI, COPII), and Golgi (COPI) membranes of mammalian cells. To address their individual roles in ER to Golgi transport, we used stage specific in vitro transport assays to synchronize movement of cargo to and from pre-Golgi intermediates, and GDP- and GTP-restricted forms of Sar1 and ARF1 proteins to control coat recruitment. We find that COPII is solely responsible for export from the ER, is lost rapidly following vesicle budding and mediates a vesicular step required for the build-up of pre-Golgi intermediates composed of clusters of vesicles and small tubular elements. COPI is recruited onto pre-Golgi intermediates where it initiates segregation of the anterograde transported protein vesicular stomatitis virus glycoprotein (VSV-G) from the retrograde transported protein p58, a protein which actively recycles between the ER and pre-Golgi intermediates. We propose that sequential coupling between COPII and COPI coats is essential to coordinate and direct bi-directional vesicular traffic between the ER and pre-Golgi intermediates involved in transport of protein to the Golgi complex.

Heterogeneity of smooth muscle cells in embryonic human aorta.

Cellular composition of aortas from 5- to 12-week and 18- to 28-week-old human embryos were investigated using immunocytochemistry, scanning and transmission electron microscopy. The aorta of the 5- to 12-week-old embryos consisted of three sublayers differing in cellular composition. The inner sublayer adjacent to the endothelium contained round and ovoid cells with synthetic phenotype. In the intermediate sublayer, spindle-like cells ultrastructurally similar to smooth muscle cells were found. Cells of the outer sublayer resembled fibroblasts or poorly differentiated mesenchymal cells. There were not definite morphological borders between sublayers. In the 18- to 28-week-old embryo aorta the intima was separated from media by internal elastic lamina. Intimal and innermost medial cells had predominately stellate shape and synthetic phenotype. The outer part of media contained spindle-like cells that had well developed contractile structures. Both the 5- to 12-week-old and the 18- to 28-week-old embryo aortic cells were positively stained for alpha-actin and myosin and negatively stained for macrophage antigens. Thus, the majority of embryo aortic cells appeared smooth muscle cells, however there was a regional difference in shape and synthetic state of these cells.

[The hemodynamic effect on the spatial organization of atherosclerotic lesions in the human aorta. Topical differences in the fatty streaks and in the lipofibrous and fibrous plaques]. / Vliianie gemodinamiki na prostranstvennuiu organizatsiiu ateroskleroticheskikh porazhenii aorty cheloveka. Topicheskie otlichiia v lipidnykh polosakh, lipofibroznykh i fibroznykh bliashkakh.

By means of light microscopy of whole-mounted membranous preparations and scanning electron microscopy differences of the three-dimensional organization in the fatty streaks, lipo-fibrous and fibrous plaques in proximal, distal and central parts were investigated. It was revealed that the central parts of the atherosclerotic lesions have a more mature character than the proximal and, especially, distal parts of the plaques. This phenomenon is accounted for by a progressive growth of the plaques along blood flow in distal direction due to the changes in hemodynamics.

[The hemodynamic effect on the spatial organization of atherosclerotic lesions in the human aorta. Plaques at the sites of arterial branching]. / Vliianie gemodinamiki na prostranstvennuiu organizatsiiu ateroskleroticheskikh porazhenii aorty chelovka. Bliashki v mestakh vetvleniia arterii.

By means of light microscopy of whole-mounted membranous preparations and scanning electron microscopy differences of the three-dimensional organization in the macroscopically intact and atherosclerotic human aortic intima in the sites of intercostal artery ostium were investigated. It was shown that the process of atherogenesis begins in the lateral areas and later involves the site of the entry. The flow divider does not contain lipids and resembles fibrous cap of the plaque. Such differences in the three-dimensional organization are accounted for by the local hemodynamic properties.