HLA-A*02:687, a novel allele identified by sequence-based typing in cord blood from a Korean woman.

A*02:687 showed one nucleotide difference with A*02:01:01:01 resulting in an amino acid change.

HLA-A*33:102, a novel allele identified by sequence-based typing in cord blood from a Korean woman.

The new allele A*33:102 showed two nucleotide differences with A*33:03:01 in exon 3.

HLA-B*59:09, a novel allele identified by sequence-based typing in a cord blood donated by a Korean woman.

The new allele B*59:09 showed two nucleotide differences with B*59:01:01:01 in exon 3.

Lack of mature lymphocytes results in obese but metabolically healthy mice when fed a high-fat diet.

BACKGROUND/OBJECTIVES: Obesity is characterized by chronic inflammation and immune dysregulation, as well as insulin resistance, but the link between obesity and adaptive immunity remains to be fully studied. METHODS: To elucidate the role of adaptive immunity on body composition, glucose homeostasis and inflammation, recombination-activating gene 1 knockout (Rag1-/-) mice, without mature T-lymphocytes or B-lymphocytes, were maintained on a low- or high-fat diet (LFD and HFD, respectively) for 11 weeks. RESULTS: Rag1-/- mice fed HFD gained significantly more weight and had increased body fat compared with wild type. Downregulation of energy expenditure as well as brown fat uncoupling protein UCP-1 and UCP-3 gene expression were noticed in HFD-fed Rag1-/- mice compared with LFD. HFD mice had significantly decreased energy intake compared with LFD mice, consistent with decreased agouti-related protein and increased pro-opiomelanocortin gene expression levels in the hypothalamus. Moreover, compared with wild type, Rag1-/- mice had lower interleukin (IL)-4 levels, a cytokine recently found to induce browning in white adipocytes, and higher IL-12 levels in HFD-fed Rag1-/- mice. Despite that HFD Rag1-/- mice were more obese, they had similar glucose, insulin and adiponectin levels, while leptin was marginally increased. CONCLUSIONS: Mice with deficiency in adaptive immunity are obese, partly owing to decreased energy expenditure, but are metabolically normal, suggesting that mature lymphocytes have necessary roles in the development of obesity-related metabolic dysregulation.

Estimation of size of cord blood inventory based on high-resolution typing of HLAs.

Methods for estimating the cord blood (CB) inventory size required vary according to the ethnic diversity of the HLA, degree of HLA matching and HLA-typing resolution. We estimated the CB inventory size required using 7190 stored CB units (CBU) and 2450 patients who were awaiting or underwent allogeneic hematopoietic stem cell transplantation. With high-resolution typing of HLA-A, B and DRB1, 94.6% of Korean patients could find CBUs in 100 000 CBUs with a 5/6 match, and 95.7% could find CBUs in 5000 CBUs with a 4/6 match. With low-resolution typing of HLA-A and B and high-resolution typing of leukocyte antigen-DRB1, 95% of patients could find CBUs in 50 000 CBUs with a 5/6 match, and 96.7% could find CBUs in 3000 CBUs  with a 4/6 match. With additional high-resolution typing for HLA-A and B, which could improve transplantation outcome, the size of the CB inventory would need to increase twofold for Koreans.

Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans.

BACKGROUND: Irisin is a recently identified exercise-induced myokine suggested to induce browning of white adipocytes. Deficiency of myostatin, and thus stimulation of muscle growth, has also been reported to induce irisin and its precursor FNDC5 expression in muscle and drive the browning of white adipocytes in mice, implying that irisin may be related to muscle growth in addition to its beneficial effects in adipocytes. In humans, the effect of irisin in muscle hypertrophy as well as adipocyte metabolism has not been fully investigated. METHODS: Primary cultured human myocytes/adipocytes and 3T3-L1 cells were used to examine irisin-regulated gene/protein expression. Lipid accumulation, ATP content, glycolysis, lipolysis and metabolite profile were measured in control and irisin-treated (10 and 50 nM) adipocytes. RESULTS: In human myocytes, FNDC5 mRNA and irisin secretion were increased during myogenic differentiation, along with PGC1α and myogenin expression. Irisin treatment significantly increased insulin-like growth factor 1 and decreased myostatin gene expression through ERK pathway. PGC1α4, a newly discovered PGC1α isoform specifically related to muscle hypertrophy, was also upregulated. In human adipocytes, irisin induced uncoupling protein 1 and consequently increased adipocyte energy expenditure, expression of metabolic enzymes and metabolite intermediates, resulting in inhibition of lipid accumulation. Irisin and FNDC5 treatment also reduced preadipocyte differentiation, suggesting an additional mechanism in suppressing fat mass. CONCLUSIONS: These results suggest that irisin/FNDC5 has a pleiotropic role in muscle and improvement of adipocyte metabolism in humans.

HLA-A, -B and -DRB1 polymorphism in Koreans defined by sequence-based typing of 4128 cord blood units.

Human leucocyte antigen (HLA) alleles and haplotypes differ significantly among different ethnic groups, and high-resolution typing methods allow for the detection of a wider spectrum of HLA variations. In this study, HLA-A, -B and -DRB1 genotypes were analysed in 4128 cord blood units obtained from Korean women using the sequence-based typing method. A total of 44 HLA-A, 67 HLA-B and 48 HLA-DRB1 most probable alleles were identified. Of these, high-frequency alleles found at a frequency of ≥5% were 6 HLA-A (A*02:01, A*02:06, A*11:01, A*24:02, A*31:01, A*33:03), 5 HLA-B (B*15:01, B*44:03, B*51:01, B*54:01, B*58:01) and 7 HLA-DRB1 (DRB1*01:01, DRB1*04:05, DRB1*07:01, DRB1*08:03, DRB1*09:01, DRB1*13:02, DRB1*15:01) alleles. At each locus, A*02, B*15 and DRB1*04 generic groups were most diverse at allelic level, consisting of 8, 11 and 10 different alleles, respectively. Two- and three-locus haplotypes estimated by the maximum likelihood method revealed 73 A-B, 74 B-DRB1 and 42 A-B-DRB1 haplotypes with frequencies of ≥0.3%. A total of 193 A-B-DRB1 haplotypes found at a frequency of ≥0.1% were presented, and the six most common haplotypes were A*33:03-B*44:03-DRB1*13:02 (4.6%), A*33:03-B*58:01-DRB1*13:02 (3.0%), A*24:02-B*07:02-DRB1*01:01 (2.7%), A*33:03-B*44:03-DRB1*07:01 (2.5%), A*30:01-B*13:02-DRB1*07:01 (2.2%) and A*24:02-B*52:01-DRB1*15:02 (2.1%). Compared with previous smaller scale studies, this study further delineated the allelic and haplotypic diversity in Koreans including low-frequency alleles and haplotypes. Information obtained in this study will be useful for the search for unrelated bone marrow donors and for anthropologic and disease association studies.

Identification of two novel HLA alleles: HLA-DRB1*12:03:03 and HLA-DRB1*13:143.

The novel alleles DRB1*12:03:03 and DRB1*13:143 differ from DRB1*12:03:02 and DRB1*13:02:01 by one nucleotide in exon 2, respectively.

HLA-B*40:179, a novel allele identified by sequence-based typing in cord blood from a Korean woman.

The novel allele B*40:179 showed one nucleotide difference with B*40:01:01 in exon 4.

HLA-A*02:328, a novel allele identified by sequence-based typing in cord blood from a Korean woman.

The novel allele A*02:328 showed one nucleotide difference with A*02:06:01 in exon 3 resulting in an amino acid change at codon 120 from Gly to Arg.

HLA-A*33:25, a novel allele identified by sequence-based typing, is a well-documented allele in Koreans.

The new allele, HLA-A*33:25, differs from A*33:03:01 by one nucleotide substitution in exon 4 (c.778G>A) which results in an amino acid change at codon 236 [GCA→ACA (Ala>Thr)] in ß2-microglobulin-binding domain.

Wrinkling and strain softening in single-wall carbon nanotube membranes.

The nonlinear elasticity of thin supported membranes assembled from length purified single-wall carbon nanotubes is analyzed through the wrinkling instability that develops under uniaxial compression. In contrast with thin polymer films, pristine nanotube membranes exhibit strong softening under finite strain associated with bond slip and network fracture. We model the response as a shift in percolation threshold generated by strain-induced nanotube alignment in accordance with theoretical predictions.

Relationship between the presence of unerupted mandibular third molars and fractures of the mandibular condyle.

Previous studies have shown that the presence of unerupted mandibular third molars predisposes the mandible to angle fractures. This study attempted to relate the presence of unerupted mandibular third molars with the incidence of condyle fractures. The authors compared the proportion of fractures in 439 patients who had unerupted third molars or no unerupted third molars. Fractures at the condylar region showed a significantly higher incidence in patients without unerupted third molars than in those patients with unerupted third molars. This study provides solid clinical evidence to suggest that the removal of unerupted mandibular third molars predisposes the mandible to condyle fractures.

Effect of platelet-rich plasma (PRP) concentration on the viability and proliferation of alveolar bone cells: an in vitro study.

Previous studies have shown that a combination of platelet-rich plasma (PRP) and autogenous bone graft can increase the rate of osteogenesis and enhance bone formation qualitatively. However, contradictory results were reported in a recent animal study. In order to clarify this inconsistency, this study examined the influence of the PRP concentrations on the viability and proliferation of alveolar bone cells in vitro. Bone cells obtained from the alveolar bone chips were exposed to various PRP concentrations. After a culture period of 7 days, cellular viability and proliferation were evaluated by counting the number of cells and a MTT assay. The results showed that the viability and proliferation of alveolar bone cells were suppressed by high PRP concentrations, but were stimulated by low PRP concentrations (1-5%). These in vitro results support the view that variations in the PRP concentrations might influence the bone formation within the PRP-treated bone grafts.

Transplantation of cultured bone marrow stromal cells to improve peripheral nerve regeneration.

The role of cultured bone marrow stromal cells (BMSCs) in peripheral nerve regeneration was examined using an established rabbit peroneal nerve regeneration model. A 15-mm peroneal nerve defect was bridged with a vein filled with BMSCs (1 x 10(6)), which had been embedded in collagen gel. On the contralateral side, the defect was bridged with a vein filled with collagen gel alone. When the regenerated tissue was examined 4, 8 and 12 weeks after grafting, the number and diameter of the myelinated fibers in the side with the BMSCs were significantly higher than in the control side without the BMSCs. This demonstrates the potential of using cultured BMSCs in peripheral nerve regeneration.

Management of mandibular angle fractures using the mandibular angle reduction forceps.

The aim of this study was to determine whether or not the use of the mandibular angle reduction forceps decreases the incidence of post-operative complications. Forty-six patients, who presented with mandibular angle fractures with a displacement or dislocation, were randomly divided into two treatment groups. Both groups underwent an open reduction with a single upper border miniplate and screw fixation. For 23 patients, the mandibular angle reduction forceps was used to aid in fracture reduction, and for 23 patients, the reduction of the fracture was achieved using IMF. The post-reduction radiographs showed that the reduction forceps group had a higher proportion of precise anatomic alignment of fracture than those in the IMF group. In addition, the former group showed a lower rate of post-operative complications, as compared to the latter group. This study found that the use of the mandibular angle reduction forceps is an important factor for decreasing the incidence of post-surgical complication.

An in vitro evaluation of miniplate fixation techniques for fractures of the atrophic edentulous mandible.

This study was undertaken to evaluate the biomechanical stability of various miniplate fixation techniques in varying degrees of atrophy and to determine optimal fixation techniques for fractures of the atrophic edentulous mandible. A total of 78 bovine ribs were randomly divided into 13 groups of six each; one non-atrophic group and twelve atrophic groups. Each one of the 13 sets of six ribs was formed based on the vertical dimension (40, 20, 15 or 10 mm) and osteotomized. The segments so produced were then reduced and fixed using various miniplate fixation techniques. The stability of various miniplate fixations in ribs showing varying degrees of atrophy (10, 15 and 20 mm) was compared with that of one miniplate fixation in non-atrophic ribs (40 mm), used as a standard. Atrophic groups utilizing single miniplate were significantly less stable than the non-atrophic group, whereas atrophic groups fitted with double miniplates, such as two 4-hole or two 6-hole miniplates, were significantly more stable than the non-atrophic group. The two miniplate fixation technique is recommended for the provision of adequate fracture site stability when open reduction is indicated in cases of atrophic edentulous mandibular fractures.

Microneural anastomosis using cyanoacrylate adhesives.

We have developed a reliable method of microneural anastomosis using cyanoacrylate adhesives. This method involves overlapping the epineuriums of the two nerve ends and then applying two or three microdrops of cyanoacrylate adhesive on the surface of the epineurium just where the epineuriums overlap. The sciatic nerves of Sprague-Dawley rats were transected and repaired either with 10-0 nylon sutures or by using the described method. Histological evaluation showed no significant difference in the outcome of nerve regeneration between the two groups. It was concluded that the cyanoacrylate repair deserves to be considered as an alternative to the conventional suture technique in microneural anastomosis.

Effect of platelet-rich plasma on bone regeneration in autogenous bone graft.

In this study, we evaluated the effect of platelet-rich plasma (PRP) on bone regeneration in an autogenous bone graft in a canine model. The mandibular premolar teeth had been bilaterally extracted previously, and the ridges had been allowed to heal for 3 months. After this period, continuity resection was performed on both sides of the mandible. One defect (the PRP group) was reconstructed with the original particulate bone mixed with PRP. As a control, the contralateral defect (non-PRP group) was reconstructed with the original particulate bone alone. Biopsies after 6 weeks showed lower levels of bone formation in the PRP group than in the non-PRP group, and fluorescence microscopy revealed a delay in the remodelling of grafts loaded with PRP. These findings suggest that the addition of PRP does not appear to enhance new bone formation in autogenous bone grafts.

Computed tomographic findings of the fractured mandibular condyle after open reduction.

The purpose of this study was to evaluate the long-term radiological results obtained with open reduction and fixation of unilateral mandibular condyle fractures in 10 patients. CT images taken at the end of the follow-up period (average of 22 months, range 7 to 33 months), were traced and digitized, and the position and morphology of the fractured condylar process was statistically compared with those of the contralateral non-fractured condylar process in the coronal, transverse and sagittal planes. Little difference was observed in the position or morphology of the condylar process in the operated and non-fractured joints. This study shows that it is possible to anatomically reduce fractured condyles, and thereby to avoid postoperative disadvantageous joint changes.