Pharmacokinetics and antinociceptive effects of the soluble epoxide hydrolase inhibitor t-TUCB in horses with experimentally induced radiocarpal synovitis.

This study determined the pharmacokinetics, antinociceptive, and anti-inflammatory effects of the soluble epoxide hydrolase (sEH) inhibitor t-TUCB (trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) in horses with lipopolysaccharide (LPS)-induced radiocarpal synovitis. A total of seven adult healthy mares (n = 4-6/treatment) were administered 3 µg LPS into one radiocarpal joint and t-TUCB intravenously (i.v.) at 0 (control), 0.03, 0.1, 0.3, and 1 mg/kg in a blinded, randomized, crossover design with at least 3 weeks washout between. Two investigators independently assigned pain scores (at rest, walk and trot) and lameness scores before and up to 48 hr after t-TUCB/LPS. Responses to touching the joint skin to assess tactile allodynia, plasma, and synovial fluid (SF) t-TUCB concentrations were determined before and up to 48 hr after t-TUCB/LPS. Blood and SF were collected for clinical laboratory evaluations before and up to 48 hr after t-TUCB/LPS. Areas under the curves of pain and lameness scores were calculated and compared between control and treatments. Data were analyzed using repeated measures ANOVA with Dunnett or Bonferroni post-test. p < .05 was considered significant. Data are mean ± SEM. Compared to control, pain, lameness, and tactile allodynia were significantly lower with 1 mg/kg t-TUCB, but not the other doses. For 0.1, 0.3, and 1 mg/kg t-TUCB treatments, plasma terminal half-lives were 13 ± 3, 13 ± 0.5, and 24 ± 5 hr, and clearances were 68 ± 15, 48 ± 5, and 14 ± 1 ml hr-1  kg-1 . The 1 mg/kg t-TUCB reached the SF at high concentrations. There were no important anti-inflammatory effects. In conclusion, sEH inhibition with t-TUCB may provide analgesia in horses with inflammatory joint pain.

Mesenteric vasculitis after G-CSF administration in a severe neutropenic patient with systemic lupus erythematosus.

Granulocyte colony-stimulating factor (G-CSF) is commonly used with neutropenic patients to accelerate recovery. G-CSF is a hematopoietic cytokine that regulates the proliferation and differentiation of neutrophil precursors, and is known as a safe and effective treatment for chemotherapy-induced neutropenia. However, we encountered a case in which a patient with systemic lupus erythematosus (SLE) developed mesenteric vasculitis after G-CSF administration. The patient was a 36-year-old female admitted with fever, arthralgia, and generalized erythematous rash. Despite symptomatic improvement with a high-dose steroid, severe neutropenia persisted for three weeks, precipitating a decision to use G-CSF to enhance recovery. Mesenteric vasculitis developed 15 hours after administration of G-CSF injection. Because the response of immune cells such as neutrophils and T cells is uncontrolled and dysfunctional in patients with lupus, G-CSF therapy should be used with caution.

A novel HLA-B*48 allele, B*48:01:03, identified by sequence-based typing.

A new allele HLA-B*48:01:03 showed one nucleotide difference with B*48:01:01 at codon 269 (CCC->CCT).

Effect of oestrogen on T cell apoptosis in patients with systemic lupus erythematosus.

Defective control of T cell apoptosis is considered to be one of the pathogenetic mechanisms in systemic lupus erythematosus (SLE). Oestrogen has been known to predispose women to SLE and also to exacerbate activity of SLE; however, the role of oestrogen in the apoptosis of SLE T cells has not yet been documented. In this study, we investigated the direct effect of oestrogen on the activation-induced cell death of T cells in SLE patients. The results demonstrated that oestradiol decreased the apoptosis of SLE T cells stimulated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin in a dose-dependent manner. In addition, oestradiol down-regulated the expression of Fas ligand (FasL) in activated SLE T cells at the both protein and mRNA levels. In contrast, testosterone increased FasL expression dose-dependently in SLE T cells stimulated with PMA plus ionomycin. The inhibitory effect of oestradiol on FasL expression was mediated through binding to its receptor, as co-treatment of tamoxifen, an oestrogen receptor inhibitor, completely nullified the oestradiol-induced decrease in FasL mRNA expression. Moreover, pre-treatment of FasL-transfected L5178Y cells with either oestradiol or anti-FasL antibody inhibited significantly the apoptosis of Fas-sensitive Hela cells when two types of cells were co-cultured. These data suggest that oestrogen inhibits activation-induced apoptosis of SLE T cells by down-regulating the expression of FasL. Oestrogen inhibition of T cell apoptosis may allow for the persistence of autoreactive T cells, thereby exhibiting the detrimental action of oestrogen on SLE activity.

Quantitation of whole blood Epstein-Barr virus DNA is useful for assessing treatment response in patients with non-Hodgkin's lymphoma.

INTRODUCTION: Epstein-Barr virus (EBV) is a well-known tumorigenic virus and is associated with lymphoproliferative disorders. Quantitations of EBV viral loads in plasma and peripheral blood mononuclear cells have been reported to be useful biomarkers for monitoring Hodgkin's lymphoma and EBV-associated non-Hodgkin lymphoma (NHL). METHODS: In the present study, whole blood specimens were used to determine quantitatively EBV viral loads, which were then compared with clinical data. Using real-time quantitative polymerase chain reaction (RQ-PCR), EBV-DNA was monitored in whole blood samples from patients with NHL (n = 61) at the time of diagnosis, relapse, and follow-up. RESULTS: A statistically significant correlation was observed between positive EBV viral load and extranodal involvement in diffuse large B-cell lymphoma at the time of diagnosis or relapse (n = 29, P = 0.009). In patients who were serially checked for EBV-DNA levels (n = 16), viral load was found to fall to undetectable levels during complete remission. On the contrary, progressive disease and relapse were found to be associated with sustained or elevated EBV-DNA levels. CONCLUSION: These results suggest that whole blood EBV-DNA quantitation might be of value as a convenient biomarker for therapeutic responsiveness of NHL.

Safety of extended endoscopic mucosal resection and endoscopic submucosal dissection following the Japanese Gastric Cancer Association treatment guidelines.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are widely performed. Indications for these procedures have been extended in Korea and Japan. The aim was to evaluate whether these extended indications are safe. METHODS: All patients who had surgery for early gastric cancer at Seoul National University Bundang Hospital between May 2003 and December 2007 were identified from a prospective database. Lymph node status was examined in patients who met extended indications for EMR and had undergone surgical resection. RESULTS: Of patients with mucosal cancers, 129 met extended indications for EMR or ESD and three (2.3 per cent) had lymph node metastasis. Of the 52 submucosal cancers meeting extended indications for EMR or ESD, two (4 per cent) had lymph node metastasis. Differentiated mucosal cancers without ulcer formation did not have lymph node metastasis, irrespective of size. CONCLUSION: Extending the indications for EMR and ESD according to the Japanese Gastric Cancer Association guidelines carries an increased risk of lymph node metastasis. For cancers meeting these criteria, treatment by gastric resection with lymph node dissection should still be considered. A well differentiated mucosal cancer of any size without ulceration may be considered as an extended indication for EMR or ESD.

Effective screening of informative single nucleotide polymorphisms using the novel method of restriction fragment mass polymorphism.

Restriction fragment mass polymorphism (RFMP) was applied to pooled DNA for selecting informative single nucleotide polymorphisms (SNPs). A total of 225 coding non-synonymous SNPs (cnSNPs) from immunomodulating genes known to be involved in the pathogenesis of asthma were selected from the National Center for Biotechnology Information's (NCBI) SNP database (dbSNP). DNA samples from 200 healthy Koreans were pooled, amplified by polymerase chain reaction, digested with restriction enzymes and the fragments analysed by mass spectrometry. Only 30 of the 225 cnSNPs (13.3%) were informative, i.e.had a minor allele frequency>10%. The percentage of informative cnSNPs varied according to the validation status of the dbSNP, being 42.3% (22/52) when validated by multiple submissions and frequency data, 8.7% (2/23) when validated by multiple submissions alone and 9.1% (3/33) when validated by frequency data alone. Most of the 112 unvalidated cnSNPs were not informative. In conclusion, the RFMP method using pooled DNA is useful in selecting informative SNPs, as also is validation status in the dbSNP.

Location of nerve entry points of flexor digitorum profundus.

The aim of this study was to elucidate the anatomical location of nerve entry points of Flexor digitorum profundus (FDP) and its implications for non-surgical neurolysis. A total of 21 amputated forearms of 11 Korean fresh cadavers were dissected. Two transverse x-axes joined the medial and lateral epicondyles and the radial and ulnar styloid processes. The longitudinal y-axis joined the midpoints of the proximal and distal transverse x-axes. The locations of the points were marked relative to the forearm length (x) and forearm width (y). The number of nerve entry points from median nerve and ulnar nerve were average 3.91 +/- 0.62 (range 3-5, median 4) and 2.14 +/- 0.65 (range 1-3, median 2) respectively. Most (82.9%) nerve entry points of FDP from the median nerve were within two circles, with 15 mm diameter. The two circles were on medial 1/10 of forearm width from the y-axis, and on proximal 1/3 (1:2) and 2/5 (2:3) of forearm length on x-axis. Most (80.0%) nerve entry points of the ulnar nerve innervating FDP were within a 15 x 30 mm rectangle. Its center was located at +26.5% on x-axis and -36.0% on y-axis. The nerve entry points used to be selected in performing non-surgical neurolysis with either ethyl alcohol (50%) or phenol (5-12%).

Posterior circulation ischemic stroke in Korean population.

To understand the characteristics of posterior circulation ischemic stroke (PCS) in the Korean population better, we retrospectively reviewed the data from the Hallym Stroke Registry (HSR). We analyzed the demographic features, risk factors, stroke subtypes, lesion distributions and clinical outcomes of 591 consecutive patients with PCS, enrolled in HSR between January 1996 and July 2002. PCS was 39.8% of all ischemic strokes. Mean age of PCS patients was 63.4 years and 55.7% were men. Hypertension was the most common risk factor (69.9%). However, potential cardioembolic sources were found only in 11.0%. The most frequent stroke subtype was large artery disease (50.0%), followed by small vessel disease (33.8%). Only 5.2% of patients were classified as affected with cardioembolism. The most common location of infarcts was in the middle territory (36.5%), followed by distal (28.1%), proximal (19.0%), and multiple territories (16.4%). The hospital mortality rate (4.1%) and discharge outcome of PCS were comparable with those of the anterior circulation stroke (ACS). In conclusion, the etiology and lesion topography of PCS in the Korean population appeared to be different from those of the Caucasians.

Novel HLA-Cw*06 allele, Cw*0612, identified by sequence-based typing.

In this report, we describe the identification of an human leucocyte antigen-Cw*06 (HLA-Cw*06) nucleotide sequence variant, a new HLA-Cw*0612. The new allele was detected during routine HLA typing by high-resolution sequence-based typing. Allele Cw*0612 showed one nucleotide difference with Cw*0602 at codon 153 (GCG-->ACG) resulting in an amino acid change from alanine to threonine.

Novel HLA-Cw*01 allele, Cw*010203, identified by sequence-based typing*.

In this report, we describe the identification of an human leucocyte antigen-Cw*0102 (HLA-Cw*0102) nucleotide sequence variant, a new HLA-Cw*010203, in a case - control study by using sequence-based typing. Allele HLA-Cw*010203 showed one nucleotide difference with HLA-Cw*010201 by a silent substitution at codon 130 (CTG-->CTA).

Novel HLA-A*11 allele, A*1120, identified by sequence-based typing.

In this report, we describe the identification of a human leucocyte antigen-A*11 (HLA-A*11) nucleotide sequence variant, a new HLA-A*1120 by using sequence-based typing (SBT). The new allele was detected during routine HLA typing by high-resolution SBT. Allele A*1120 showed one nucleotide difference with A*110101 at codon 152 (GCG-->GAG) resulting in an amino acid change from alanine to glutamate. Residue 152 is located on alpha(2)-helix of HLA class I molecule and involved in peptide binding by constructing E pocket of peptide-binding groove, implying that the change of the residue 152 would affect the binding affinity of peptides to A*1120 allele.

Novel HLA-A*31 allele, A*3111 identified by sequence-based typing.

In this report, we describe the identification of an HLA-A*31 nucleotide sequence variant, a new HLA-A*3111, in three members of a Korean family by using sequence-based typing (SBT). The new allele was detected during routine HLA typing by high-resolution SBT. Allele A*3111 showed one nucleotide difference with A*310102 at codon 165 (GTG-->CTG) resulting in an amino acid change from valine to leucine (V165L). Serologic reactivity was shorter than normally expected.

Influence of mismatching of HLA cross-reactive groups on cadaveric kidney transplantation.

Finding fully HLA-matched recipients for a given donor is not practical due to the allelic diversity of the loci. Cross-reactive group (CREG) matching has been considered a feasible alternative to HLA matching. However, the true efficacy of CREG matching in cadaveric kidney transplantation is controversial. Using conventional HLA and CREG classifications proposed by Rodey and McKenna, we counted the number of mismatches for 319 patients who received cadaver kidney transplants between 1992 and 2003 at Asan Medical Center in Korea. When we compared transplants with four or fewer HLA-A, -B, and -DR antigen mismatches with those with five or more, we observed a significant difference in 5-year survival rate (88.5% versus 78.6%; P = .0189). Transplants with no or one HLA-DR mismatch had a significantly better 5-year survival rate than those with two HLA-DR mismatches (87.9% versus 80.0%; P = .0469). Among transplants with one or two HLA-DR mismatches, transplants with zero or one CREG mismatch showed better 5-year graft survival rate than those with two or more CREG mismatches (89.4% versus 79.8%; P = .0415) only in McKenna's CREG classification. These results suggest that the impact of CREG mismatches on graft survival may depend on CREG classification and on the distribution of HLA-DR mismatches.