The novel HLA-C allele, HLA-C*01:02:84 allele, identified in a solid organ transplantation donor.

HLA-C*01:02:84 differs from HLA-C*01:02:01:01 by one synonymous nucleotide substitution in codon 48.

APB-F1, a long-acting feline granulocyte colony-stimulating factor fusion protein, created by exploiting FL335, a chimeric Fab specific for feline serum albumin.

Off-label use of a human granulocyte colony stimulating factor (hG-CSF) has been allowed to treat dogs and cats with neutropenia. However, repeated administration of hG-CSF induces undesirable anti-drug antibody (ADA) responses, implying the necessity of animal-derived G-CSF as a therapeutic reagent, preferably with a long-acting capability. Herein, we generated a recombinant fusion protein by genetically combining FL335, a chimeric Fab specific for feline serum albumin (FSA), and feline G-CSF (fG-CSF), with the ultimate goal of developing a long-acting therapeutic fG-CSF for cats. The resulting FL335-fG-CSF fusion protein, referred to as APB-F1, was produced well as a functional form in a Chinese hamster ovary (CHO) expression system. In in vitro analyses, APB-F1 bound to FSA at high affinity (KD = 400 pM) and possessed 0.78 × 107 U/mg G-CSF biological activity, clearly proving its biological functionality. Pharmacokinetic (PK) and pharmacodynamic (PD) studies using healthy cats revealed that the serum half-life (t1/2) of APB-F1 was increased five times compared with that of fG-CSF (t1/2 = 13.3 h vs. 2.7 h) in subcutaneous (SC) injections. Additionally, APB-F1 induced a profound and sustained increase in white blood cell (WBC) and actual neutrophil count (ANC) up to 10 days, which was far superior to other G-CSF preparations, including filgrastim (Neupogen™) and even pegfilgrastim (Neulasta™). Conclusively, a long-acting fG-CSF with potent in vivo bioactivity was successfully created by using FL335; thus, we provided evidence that our "anti-serum albumin Fab-associated" (SAFA) technology can be applied reliably in developing valuable long-acting biologics in veterinary medicine.

Permeable characteristics of surface film deposited on LiMn2O4 positive electrode revealed by redox-active indicator.

Herein, the ferrocene redox indicator-based surface film characteristics of spinel lithium manganese oxide (LMO) were evaluated. The pre-cycling of spinel LMO generated a film on the LMO surface. The surface film deposited on LMO surface suppresses further electrolyte decomposition, while the penetration of approximately 0.7 nm-sized redox indicator is not prevented. The facile self-discharge of LMO and regeneration current from the ferrocenium molecule was observed from the redox indicator in a specifically designed four-electrode cell. From this electrochemical behavior, a small-sized HF molecule attack on the LMO surface through a carbonate-based electrolyte-derived film is defined; hence, the prevention of small-sized molecules into the deposited surface film is crucial for the enhancement of LiMn2O4-based lithium-ion batteries.

Early bone healing onto implant surface treated by fibronectin/oxysterol for cell adhesion/osteogenic differentiation: in vivo experimental study in dogs.

PURPOSE: This study aimed to evaluate the effects of fibronectin and oxysterol immobilized on machined-surface dental implants for the enhancement of cell attachment and osteogenic differentiation, on peri-implant bone healing in the early healing phase using an experimental model in dogs. METHODS: Five types of dental implants were installed at a healed alveolar ridge in five dogs: a machined-surface implant (MI), apatite-coated MI (AMI), fibronectin-loaded AMI (FAMI), oxysterol-loaded AMI (OAMI), and sand-blasted, large-grit, acid-etched surface implant (SLAI). A randomly selected unilateral ridge was observed for 2 weeks, and the contralateral ridge for a 4-week period. Histologic and histometric analyses were performed for the bone-to-implant contact proportion (BIC) and bone density around the dental implant surface. RESULTS: Different bone healing patterns were observed according to the type of implant surface 2 weeks after installation; newly formed bone continuously lined the entire surfaces in specimens of the FAMI and SLAI groups, whereas bony trabecula from adjacent bone tissue appeared with minimal new bone lining onto the surface in the MI, AMI, and OAMI groups. Histometric results revealed a significant reduction in the BIC in MI, AMI, and OAMI compared to SLAI, but FAMI demonstrated a comparable BIC with SLAI. Although both the BIC and bone density increased from a 2- to 4-week healing period, bone density showed no significant difference among any of the experimental and control groups. CONCLUSIONS: A fibronectin-coated implant surface designed for cell adhesion could increase contact osteogenesis in the early bone healing phase, but an oxysterol-coated implant surface designed for osteoinductivity could not modify early bone healing around implants in normal bone physiology.

Determination of acute leukemia lineage with new morphologic parameters available in the complete blood cell count.

GOALS: Cell population data (CPD) are new morphologic parameters including volume, conductivity, and five light scattering characteristics used for leukocyte classification by an automated hematology analyzer, the UniCel DxH 800. We developed a discriminating CPD model to predict the leukemia lineage during routine complete blood cell count (CBC). PROCEDURES: We analyzed the CPD of 405 blood samples containing more than 10% blasts that were randomly divided into test and validation sets. With the test set, we produced a model for categorizing acute lymphoblastic leukemia (ALL) or acute promyelocytic leukemia (APL), using ranges of the CPD and regarding the remainder as non-APL acute myeloid leukemia. We verified these models against the validation set. RESULTS: In the test set, we formulated a 21-parameter model which identified 43 of 47 ALL cases (91.5% sensitivity) and ruled out 151 of 156 other leukemia cases (96.8% specificity), and a 13-parameter model which distinguished all 10 APL cases (100% sensitivity) and excluded 193 other leukemia cases (100% specificity). In the validation set, the ALL model showed 85.1% sensitivity and 94.2% specificity, and the APL model 100% sensitivity and 100% specificity. CONCLUSIONS: This study demonstrated a new solution for predicting blast lineage using the CPD on a CBC and leukocyte differential.

[A case of ticlopidine induced acute cholestatic hepatitis and pure red cell aplasia].

Ticlopidine inhibits platelet aggregation and provides beneficial secondary prevention of cerebrovascular and coronary artery disease. Frequently reported adverse effects of ticlopidine include diarrhea, nausea, and rash. However, to our knowledge, there are only a few published reports of the simultaneous occurrence of cholestatic hepatitis and pure red cell aplasia. Here we report a patient with simultaneous severe cholestatic hepatitis and pure red cell aplasia associated with ticlopidine. Although these adverse effects are rare, periodic hematological and liver function tests are recommended after starting ticlopidine.

Molecular analysis of X-linked chronic granulomatous disease in five unrelated Korean patients.

Chronic granulomatous disease (CGD) is a fatal genetic disorder in which phagocytes fail to produce antimicrobial superoxide because of NADPH oxidase deficiency. Molecular defects in CYBB gene causing X-linked CGD are responsible for about 70% of all cases. This study was done to confirm genetic defects of CYBB gene in five Korean patients who were highly suggestive of having CGD by clinical history. We performed initial screening for five unrelated Korean patients using single strand conformation polymorphism (SSCP) and then selective sequencing for the regions involving the abnormal bands. Activated NBT tests revealed that all patients were X-linked. SSCP analysis for CYBB gene showed abnormal bands in all patients. The molecular defects of five patients were as follows: c.1663insT, c.1111-1G>T, c.39_40insG, c.927delC and c.434T>C mutation. This result will help the families with prenatal diagnosis or genetic counseling.