Congenital asplenia and group B streptococcus sepsis in the adult: case report and review of the literature

Asplenia is associated with an increased incidence of fatal and life-threatening sepsis caused by encapsulated pathogens. Isolated congenital asplenia is a very rare condition, with only 33 cases reported in the literature. The authors report another case of this condition complicated by overwhelming Group B streptococcus sepsis secondary to paronychia that was managed successfully.     

Role of the conserved oligomeric Golgi (COG) complex in protein glycosylation

The Golgi apparatus is a central hub for both protein and lipid trafficking/sorting and is also a major site for glycosylation in the cell. This organelle employs a cohort of peripheral membrane proteins and protein complexes to keep its structural and functional organization. The conserved oligomeric Golgi (COG) complex is an evolutionary conserved peripheral membrane protein complex that is proposed to act as a retrograde vesicle tethering factor in intra-Golgi trafficking. The COG protein complex consists of eight subunits, distributed in two lobes, Lobe A (Cog1-4) and Lobe B (Cog5-8). Malfunctions in the COG complex have a significant impact on processes such as protein sorting, glycosylation, and Golgi integrity. A deletion of Lobe A COG subunits in yeasts causes severe growth defects while mutations in COG1, COG7, and COG8 in humans cause novel types of congenital disorders of glycosylation. These pathologies involve a change in structural Golgi phenotype and function. Recent results indicate that down-regulation of COG function results in the resident Golgi glycosyltransferases/glycosidases to be mislocalized or degraded.     

Effects of α-lipoic acid supplementation on maternal diabetes-induced growth retardation and congenital anomalies in rat foetuses

The mechanism of diabetic embryopathy is not known. Excessive reactive oxygen species (ROS) produced in diabetes may be causally related to foetal anomalies. The objective of this study was to determine whether supplementation with the antioxidant lipoic acid (LA) could prevent maternal diabetes-related foetal malformations and intrauterine growth retardation (IUGR) in rats. Pregnant rats were non-treated (Group I) or made diabetic on gestation day (GD) 2 by injecting streptozotocin (Group II). Group III was injected with 20 mg kg^–1 of LA daily starting on GD 6 and continued through GD 19. Group IV was administered only Tris buffer on the corresponding days. Group V was a set of STZ-treated animals, which were supplemented with a daily dose of 20 mg kg^–1 of LA from GD 6 through GD 19. All fetuses were collected on GD 20. Lipoic acid did not affect the blood sugar levels of diabetic animals significantly but improved their body weight gain and reduced food and water consumption. Diabetic group had a high incidence of embryonic resorption, IUGR, craniofacial malformations, supernumerary ribs and skeletal hypoplasia. Lipoic acid significantly reduced these abnormalities. These data support the hypothesis that ROS are causally related to fetal maldevelopment and IUGR associated with maternal diabetes in the rat. They also highlight the possible role of antioxidants in the normal processes of embryo survival, growth and development. (Mol Cell Biochem 261: 123–135, 2004)     

Some Aspects of PCB Metabolism by Horseradish Cells

Transformation of polychlorinated biphenyls was studied using different strains of in vitro cultured cells of horseradish (Armoracia rusticana L.). Time and concentration dependence of this process and production of intracellular and extracellular peroxidases were measured with differentiated shooty teratoma culture K54. The yield of PCB transformation and the viability of the cells were highly dependent on PCB concentration. 100 ppm PCB totally inhibited growth of the cells, and reduced their metabolism of xenobiotics. Experiments with a peroxidase (POX) inhibitor, propylgallate, and a cytochrome P450 inhibitor, aminobenztriazole, indicated the involvement of both enzymatic systems in PCB metabolism.     

A Novel Enhanced Green FluorescentProtein-Expressing NOG Mouse for Analyzingthe Microenvironment of Xenograft Tissues

The interaction between transplanted cells and host tissues is important for the growth and maintenance of transplanted cells. To analyze the mechanisms of these interactions, a systemic fluorescent protein-expressing mouse is a useful recipient. In this study, we generated a novel NOG strain, which strongly expresses enhanced green fluorescent protein (EGFP; PgkEGFP-NOG), especially in the liver, kidney, gastrointestinal tract, and testis. Because the host tissues expressed EGFP, xenotransplanted human cancer cells were clearly identified as EGFP-negative colonies in PgkEGFP-NOG mice. Immunohistochemical analysis revealed that EGFP-expressing stromal tissues formed a complicated tumor microenvironment within xenograft tissues. Moreover, a similar microenvironment was observed in human iPS cell-derived teratomas. Collectively, these results indicated that a suitable microenvironment is essential for the growth and maintenance of xenotransplanted cells and that PgkEGFP-NOG mice represent a useful animal model for analyzing the mechanisms of microenvironment formation.     

Reducing acetylated tau is neuroprotective in brain injury

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Congenital anomalies

Over the past decade, amniotic fluid-derived stem cells have emerged as a novel, experimental approach for the treatment of a wide variety of congenital anomalies diagnosed either in utero or postnatally. There are a number of unique properties of amniotic fluid stem cells that have allowed it to become a major research focus. These include the relative ease of accessing amniotic fluid cells in a minimally invasive fashion by amniocentesis as well as the relatively rich population of progenitor cells obtained from a small aliquot of fluid. Mesenchymal stem cells, c-kit positive stem cells, as well as induced pluripotent stem cells have all been derived from human amniotic fluid in recent years. This article gives a pediatric surgeon’s perspective on amniotic fluid stem cell therapy for the management of congenital anomalies. The current status in the use of amniotic fluid-derived stem cells, particularly as they relate as substrates in tissue engineering-based applications, is described in various animal models. A roadmap for further study and eventual clinical application is also proposed.     

Quantitative proteomic profiling identifies global protein network dynamics in murine embryonic heart development

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Characterization of a caveolin‐1 mutation associated with both pulmonary arterial hypertension and congenital generalized lipodystrophy

Congenital generalized lipodystrophy (CGL) and pulmonary arterial hypertension (PAH) have recently been associated with mutations in the caveolin‐1 ( CAV1 ) gene, which encodes the primary structural protein of caveolae. However, little is currently known about how these CAV1 mutations impact caveolae formation or contribute to the development of disease. Here, we identify a heterozygous F160X CAV1 mutation predicted to generate a C‐terminally truncated mutant protein in a patient with both PAH and CGL using whole exome sequencing, and characterize the properties of CAV1 , caveolae‐associated proteins and caveolae in skin fibroblasts isolated from the patient. We show that morphologically defined caveolae are present in patient fibroblasts and that they function in mechanoprotection. However, they exhibited several notable defects, including enhanced accessibility of the C‐terminus of wild‐type CAV1 in caveolae, reduced colocalization of cavin‐1 with CAV1 and decreased stability of both 8S and 70S oligomeric CAV1 complexes that are necessary for caveolae formation. These results were verified independently in reconstituted CAV1 ^?/? mouse embryonic fibroblasts. These findings identify defects in caveolae that may serve as contributing factors to the development of PAH and CGL and broaden our knowledge of CAV1 mutations associated with human disease.      

Birth rate and mortality rate of infants with congenital malformations of the limbs in the Awajishima free-ranging group of Japanese monkeys (Macaca fuscata)

The birth rate and mortality rate of infants with congenital malformations of the limbs were examined in the Awajishima free-ranging group of Japanese macaques (Macaca fuscata). Of the 606 infants born between 1978 and 1995, 86 (14.2%) were malformed. The male-female ratio did not differ between malformed and normal infants. Most kin-groups included females who gave birth to malformed infants at least once. The mortality rate within the first year after birth for malformed infants (28.2%) was significantly higher than that for normal infants (10.0%). However, this indicates that more than 70% of malformed infants were able to survive for the first year of life, even though they were unable to cling to their mothers ventrum due to their limb deformities. This finding indicates that maternal care-taking is sufficient to enable malformed infants to survive during the early stages of development and that clinging by the infant is not necessary for the display of maternal care. Am. J. Primatol. 42:225–234, 1997. © 1997 Wiley-Liss, Inc.