Parenchymal calcification is associated with the neurological prognosis in patients with congenital rubella syndrome

Congenital rubella syndrome (CRS) results from maternal rubella virus infection in early pregnancy. Abnormal neuroimaging findings have been analyzed in a small number of CRS patients in the past; however, their clinical significance has been poorly addressed. Therefore, we have investigated the neuroimaging findings of 31 patients with CRS from previous studies. The most common finding was parenchymal calcification, which was observed in 18 of 31 patients (58.1%). A multivariable logistic regression model showed that it was associated with psychomotor or mental retardation (p = 0.018), suggesting that parenchymal calcification in CRS could be a prognostic factor.     

Comparison of maxillary stability after Le Fort I osteotomy for occlusal cant correction surgery and maxillary advanced surgery.

OBJECTIVE: To compare postoperative maxillary stability following Le Fort I osteotomy for the correction of occlusal cant as compared with conventional Le Fort I osteotomy for maxillary advancement. STUDY DESIGN: The subjects were 40 Japanese adults with jaw deformities. Of these, 20 underwent a Le Fort I osteotomy and intraoral vertical ramus osteotomy (IVRO) to correct asymmetric skeletal morphology and inclined occlusal cant. The other 20 patients underwent a Le Fort I osteotomy and sagittal split ramus osteotomy (SSRO) to advance the maxilla. Lateral and posteroanterior cephalograms were taken postoperatively and assessed statistically. Thereafter, the 2 groups were followed for time-course changes. RESULTS: There was no significant difference between the 2 groups with regard to time-course changes during the immediate postoperative period. CONCLUSION: This suggests that maxillary stability after Le Fort I osteotomy for cant correction does not differ from that after Le Fort I osteotomy for maxillary advancement.     

Dispersion of Pressure to the Head in Brain/NeuroSurgery

Skin and soft tissue defects are sometimes problematic especially when the defects large, contaminated, irradiated, or poor blood supplied. The human mesenchymal stem cells (hMSCs) are proliferated upon basic fibroblast growth factor (bFGF) stimuli in vitro and in vivo. In this experiment, the skin and soft tissue defects are investigated if the wounds are able to be reepithelialized or accelerated by hMSCs, bFGF and porcine‐derived bilayered skin template.
1.5 × 1.5 cm² nude rat skin and soft tissue defects including panniculus carnosus are excised and 1 × 10⁶ hMSCs and various doses of bFGF (1–100 μg) applied. Before and after normal reepithelialization, the tissues are tested for protein expressions by immunohistochemistry and Western blotting.
The wound sizes are significantly decreased at day 7 with hMSCs with 1, 10, or 100 μg bFGF compared to hMSCs‐alone or medium‐only. All the wounds healed by day 42. 42 Kda and 38 Kda human‐derived pancytokeratin expressions, which do not cross‐react with murine antigens, by Western blotting significantly augmented by 10 μg bFGF compared to hMSCs‐alone. The epidermal immunolocalizations such as integrin α3 and SKALP (Skin‐derived Anti Leukoproteinase) are greatly elevated in time and dose‐dependent manner. Human pan‐cytokeratin expressions are immunoreactive even at day 42.
These data suggest the skin and soft tissue wound healing is accelerated by hMSCs together with bFGF, partly by means of differentiation of hMSCs toward epidermal components.     

Chymase participates in chronic dermatitis by inducing eosinophil infiltration

An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to a mouse ear caused a transient skin swelling, and the repetition of the challenge enlarged the contact dermatitis. The repeated challenge with DNFB also induced eosinophil infiltration on the application site. Administration of a chymase inhibitor significantly inhibited the ear swelling as well as eosinophil accumulation. An intradermal injection of human chymase to the mouse ear also elicited transient skin swelling and eosinophil infiltration, both of which were augmented in proportion to the number of injections. Human serum albumin and heat-inactivated chymase failed to induce such skin reactions, suggesting the participation of proteolytic activity of the enzyme. In addition, chymase stimulated eosinophil migration in vitro in a concentration-dependent manner. Taken together, these observations suggest that mast cell chymase may contribute to development of the DNFB-induced dermatitis, probably by promoting eosinophil infiltration. It is therefore possible that chymase plays a role in pathogenesis of chronic dermatitis such as atopic dermatitis.     

A novel STK11 germline mutation in two siblings with Peutz-Jeghers syndrome complicated by primary gastric cancer

Patients with Peutz-Jeghers syndrome (PJS) are known to be at risk of gastric cancer (GC), and the STK11 gene is a susceptibility gene for PJS. However, as no cases of PJS with GC in which a STK11 germline mutation has been identified have ever been reported and other susceptibility genes have also been suggested to be involved in PJS, the relation between STK11 germline mutations and GC in PJS is still unknown. In this study, we used sequencing analysis to investigate the STK11, CDH1, and TP53 loci for a germline mutation in two siblings with PJS with primary GC. A novel type of the STK11 germline mutation, c.890delG, encoding a truncated protein (p.Arg297fsX38) was identified, but no germline mutations of the CDH1 and TP53 genes were detected. No inactivation of the wild-type allele by somatic mutation or chromosomal deletion or hypermethylation at the 5'-CpG site of STK11 was detected in the GC. This is the first report of a STK11 germline mutation in a PJS patient with GC and should contribute to establishing correlations between the STK11 germline mutations and GC in PJS patients.     

Further Survey of Aflatoxin M1 in Milk Powders by ELISA

A survey of AFM₁ residues in 58 commercial milk powder samples was carried out using an enzyme‐linked immunosorbent assay (ELISA) based on a monoclonal antibody against aflatoxin M₁ (AFM₁). The samples were collected from the USA (10), China (28), Italy (14), New Zealand (3) and Poland (3). The ELISA was performed without the need for clean‐up procedures. The data revealed that 4 (US), 21 (Chinese) and 1 (Polish) samples were positive for AFM₁, with an average of 95.5, 102.8 and 85.0 pg g^‐1 of the AFM₁respectively.     

Preparation of poly(L-lactic acid) and poly(DL-lactic-co-glycolic acid) foams by use of ice microparticulates

Biodegradable foams of poly(L-lactic acid) (PLLA) and poly(DL-lactic-co-glycolic acid) (PLGA) for tissue engineering were fabricated by a porogen-leaching technique using ice microparticulates as the porogen material. PLLA or PLGA solution in chloroform was mixed with ice microparticulates. The mixtures were frozen by being placed in molds in liquid nitrogen and freeze-dried to form the foams. Scanning electron microscopic observation of the PLLA and PLGA foams showed that evenly distributed and interconnected pore structures were formed in these foams. The porosity and surface area of the foams increased with an increase in the weight fraction of the ice microparticulates, while the median pore size remained unchanged. The pore structures of the foams could be manipulated by controlling processing variables such as the size and weight fraction of the ice microparticulates and polymer concentration.     

Pseudotype hepatitis C virus enters immature myeloid dendritic cells through the interaction with lectin

Dendritic cells (DC) are the most potent antigen-presenting cells that regulate immune responses. One of the mechanisms for hepatitis C virus (HCV) persistence is the ability of HCV to suppress DC function. Direct HCV infection to blood DC has been implicated for DC dysfunction. To clarify the susceptibility of each DC subset to HCV, we used pseudotype vesicular stomatitis virus (VSV) coated with chimeric HCV envelope glycoproteins (E1 and E2). We demonstrate that pseudotype VSV enters myeloid DC (MDC) but not plasmacytoid DC (PDC). The highest efficiency of pseudotype VSV entry to MDC was observed when MDC were cultured with GM-CSF. Such efficiency decreased when MDC are matured with the treatment of IL-4, CpG oligodeoxynucleotide, or CD40 ligand. Mannan inhibited pseudotype VSV entry to MDC, but Ca(2+) chelators failed to do so. These results show that pseudotype VSV possessing HCV-E1 and E2 enters immature MDC through the interaction with lectins in a Ca(2+)-independent manner.     

Culturing of skin fibroblasts in a thin PLGA-collagen hybrid mesh

A thin biodegradable hybrid mesh of synthetic poly(DL-lactic-co-glycolic acid) (PLGA) and naturally derived collagen was used for three-dimensional culture of human skin fibroblasts. The hybrid mesh was constructed by forming web-like collagen microsponges in the openings of a PLGA knitted mesh. The behaviors of the fibroblasts on the hybrid mesh and PLGA knitted mesh were compared. The efficiency of cell seeding was much higher and the cells grew more quickly in the hybrid mesh than in the PLGA mesh. The fibroblasts in the PLGA mesh grew from the peripheral PLGA fibers toward the centers of the openings, while those in the hybrid mesh also grew from the collagen microsponges in the openings of the mesh resulting in a more homogenous growth. The proliferated cells and secreted extracellular matrices were more uniformly distributed in the hybrid mesh than in the PLGA mesh. Histological staining of in vitro cultured fibroblast/mesh implants indicated that the fibroblasts were distributed throughout the hybrid mesh and formed a uniform layer of dermal tissue having almost the same thickness as that of the hybrid mesh. However, the tissue formed in the PLGA mesh was thick adjacent to the PLGA fibers and thin in the center of the openings. Fibroblasts cultured in the hybrid mesh were implanted in the back of nude mouse. Dermal tissues were formed after 2 weeks and became epithelialized after 4 weeks. The results indicate that the web-like collagen microsponges formed in the openings of the PLGA knitted mesh increased the efficiency of cell seeding, improved cell distribution, and therefore facilitated rapid formation of dermal tissue having a uniform thickness. PLGA-collagen hybrid mesh may be useful for skin tissue engineering.     

Preservation of pancreas in the University of Wisconsin solution supplemented with AP39 reduces reactive oxygen species production and improves islet graft function

Ischemia-reperfusion injury (IRI) results in increased rates of delayed graft function and early graft loss. It has recently been reported that hydrogen sulfide (H₂S) protects organ grafts against prolonged IRI. Here, we investigated whether the preservation of pancreas in University of Wisconsin (UW) solution supplemented with AP39, which is a mitochondrial-targeted H₂S donor, protected pancreatic islets against IRI and improved islet function. Porcine pancreata were preserved in the UW solution with AP39 (UW + AP39) or the vehicle (UW) for 18 h, followed by islet isolation. The islet yields before and after purification were significantly higher in the UW + AP39 group than in the UW group. The islets isolated from the pancreas preserved in UW + AP39 exhibited significantly decreased levels of reactive oxygen species (ROS) production and a significantly increased mitochondrial membrane potential as compared to the islets isolated from the pancreas preserved in the vehicle. We found that the pancreas preserved in UW + AP39 improved the outcome of islet transplantation in streptozotocin-induced diabetic mice. These results suggest that the preservation of pancreas in UW + AP39 protects the islet grafts against IRI and could thus serve as a novel clinical strategy for improving islet transplantation outcomes.