Chemokine guidance of central memory T cells is critical for antiviral recall responses in lymph nodes.

A defining feature of vertebrate immunity is the acquisition of immunological memory, which confers enhanced protection against pathogens by mechanisms that are incompletely understood. Here, we compared responses by virus-specific naive T cells (T(N)) and central memory T cells (T(CM)) to viral antigen challenge in lymph nodes (LNs). In steady-state LNs, both T cell subsets localized in the deep T cell area and interacted similarly with antigen-presenting dendritic cells. However, upon entry of lymph-borne virus, only T(CM) relocalized rapidly and efficiently toward the outermost LN regions in the medullary, interfollicular, and subcapsular areas where viral infection was initially confined. This rapid peripheralization was coordinated by a cascade of cytokines and chemokines, particularly ligands for T(CM)-expressed CXCR3. Consequently, in vivo recall responses to viral infection by CXCR3-deficient T(CM) were markedly compromised, indicating that early antigen detection afforded by intranodal chemokine guidance of T(CM) is essential for efficient antiviral memory.

CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation.

Differentiation of naive CD4(+) T cells into T helper (Th) cells is a defining event in adaptive immunity. The cytokines and transcription factors that control Th cell differentiation are understood, but it is not known how this process is orchestrated within lymph nodes (LNs). Here we have shown that the CXCR3 chemokine receptor was required for optimal generation of interferon-γ (IFN-γ)-secreting Th1 cells in vivo. By using a CXCR3 ligand reporter mouse, we found that stromal cells predominately expressed the chemokine ligand CXCL9 whereas hematopoietic cells expressed CXCL10 in LNs. Dendritic cell (DC)-derived CXCL10 facilitated T cell-DC interactions in LNs during T cell priming while both chemokines guided intranodal positioning of CD4(+) T cells to interfollicular and medullary zones. Thus, different chemokines acting on the same receptor can function locally to facilitate DC-T cell interactions and globally to influence intranodal positioning, and both functions contribute to Th1 cell differentiation.

Meniscal extrusion and spontaneous osteonecrosis with root tear of medial meniscus: comparison with horizontal tear.

PURPOSE: The incidence of root tears in patients with spontaneous osteonecrosis of the knee has been studied, but the incidence of spontaneous osteonecrosis of the knee in patients with medial meniscus root tears has not. We assessed the latter incidence and evaluated the characteristics of medial meniscus root tears by comparing clinical status, the degree of osteonecrosis, and meniscal extrusion in patients with horizontal tears. METHODS: Sixty-three patients who were diagnosed with medial meniscus posterior horn tear and treated by arthroscopic surgery between March 2005 and March 2009 were evaluated retrospectively. Patients were divided into 2 groups, the root tear group (R group) and the horizontal tear group (H group). Functional scores and radiography, simple radiography, and magnetic resonance imaging were investigated. RESULTS: No significant differences in age, body mass index, and symptom duration were observed between the 2 groups. The incidence of osteonecrosis was 12 of 36 knees (33.3%) in the R group and 4 of 27 (14.8%) in the H group. The mean absolute extrusion was 4.1 ± 0.7 mm and 3.5 ± 1.4 mm in the R and H groups, respectively (P = not significant). The mean relative percentage of extrusion in the R group (46.1% ± 9.0%) was greater than that in the H group (35.3% ± 13.2%) (P = .01). The degree of osteonecrosis (ellipsoidal volume) was also greater in the R group (423.1 ± 236.7 mm(3)) than that in the H group (175.8 ± 43.6 mm(3)) (P = .03). Though not significant, the visual analog pain score had a tendency to be more severe and knee scores had a tendency to be lower in the R group than in the H group. CONCLUSIONS: Medial meniscus root tears had a greater degree of meniscal extrusion and wider osteonecrosis than horizontal tears of the posterior horn related to loss of the main function of the meniscus. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Cementless total hip arthroplasty in patients with osteonecrosis after kidney transplantation.

This study was to determine the mid- to long-term survivorship of cementless metal-on-metal THA in 52 patients (74 hips) who underwent THA for osteonecrosis of the femoral head with a cementless THA. The mean follow-up was 10.2 years. The mean age at operation was 42.1 years (range, 25-62 years). The survivorship analysis with revision as the end point estimated a 96.6% chance of THA survival during 16.4 years. The average Harris hip score at last follow-up was 89.2 points (range, 74-100). Two patients (two hips) required revision surgery for extensive acetabular osteolysis at 9 years and acetabular liner dissociation at 2 years. The survival rates of cementless THA in these patients are encouraging. However, the possibility of metallic wear related complications are raising concern.

Medial meniscus allograft transplantation using a modified bone plug technique: clinical, radiologic, and arthroscopic results.

PURPOSE: To determine clinical, radiologic, and arthroscopic results of our meniscus allograft transplantation (MAT) by use of modified bone plug technique, which permits easy passage of the allograft by reducing the size of the posterior bone plug. METHODS: From December 2004 to December 2008, 22 consecutive patients (20 men and 2 women) with a mean age of 35.9 years underwent medial MAT with the modified bone plug method. The Lysholm score and International Knee Documentation Committee subjective knee score were documented. Joint space narrowing and Kellgren-Lawrence grade changes were evaluated on radiographs, and graft healing status, arthrosis changes in cartilage, and meniscal extrusion were investigated by magnetic resonance imaging (MRI). RESULTS: The mean follow-up was 24.9 months. The mean Lysholm score improved significantly, from 68.2 to 89.7 (P = .002). The International Knee Documentation Committee subjective knee score improved significantly, from 60.3 to 85.4 (P = .003). Joint space narrowing was insignificant, and arthrosis progression was observed in 3 of 22 cases (13.6%) on radiographs. On MRI, complete healing of the grafts was observed in 18 cases (100%), 15 cases (83.3%), and 17 cases (94.4%) at the anterior root, posterior root, and meniscal rim, respectively. Mean meniscal extrusion was 4.35 ± 1.76 mm, and arthrosis progression was observed in 4 of 18 cases (22.2%). During second-look arthroscopy, complete healing of the grafts was observed in 11 cases (100%), 9 cases (81.8%), and 10 cases (90.9%) at the anterior root, posterior root, and meniscal rim, respectively. Cartilage degeneration was advanced in 4 cases (36.4%). No significant correlations were found between meniscal extrusion and other outcomes. CONCLUSIONS: Our modified bone plug method was an effective surgical method. MRI and second-look arthroscopic examinations showed sound evidence of graft healing. Meniscal extrusion was observed in most cases but was not correlated with other clinical and radiologic outcomes. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Sesamoid arthritis mimicking trigger thumb.

This article presents a case of undiagnosed sesamoid arthritis with coexisting trigger thumb. A 25-year-old woman presented with a 2-year history of metacarpophalangeal joint pain and triggering of the thumb. She was a right-handed bank employee and recalled a trivial thumb sprain. The pain improved slightly while on medication, but the triggering recurred 1 month after the steroid injection. Six months after the first visit, she underwent A1 pulley release surgery for the triggering without a more detailed evaluation such as radiographs or sonographs. Intraoperatively, no definite abnormalities in the fibrous flexor sheath or flexor tendon were observed. The triggering resolved, but the pain persisted. One month postoperatively, a repeat physical examination was performed, and the painful region was localized to the radial sesamoid area. Radiography was then performed, which showed joint space narrowing of the sesamoid metacarpal head and sclerotic changes and spur formation on the metacarpal head. An additional diagnosis of sesamoid arthritis of the thumb was made and the pain finally resolved as a result of the sesamoidectomy. Orthopedic surgeons often overlook pathologies around the metacarpophalangeal joint, especially those related to triggering. A high index of suspicion and clinical findings consistent with intermittent mechanical obstruction and tenderness in the palmar aspect of the metacarpophalangeal joint warrant inclusion of sesamoid arthritis as a differential diagnosis for metacarpophalangeal joint pathology. Detailed physical examinations should be performed and proper radiographs taken in all patients with tenderness in the metacarpophalangeal joint even if triggering of the thumb is present.

Comprehensive analysis of microRNA-mRNA co-expression in circadian rhythm.

To investigate the potential role of microRNA (miRNA) in the regulation of circadian rhythm, we performed microarray-based expression profiling study of both miRNA and mRNA in mouse liver for 48 h at 4-hour intervals. Circadian miRNA-mRNA target pair is defined as the pair both elements of which show circadian expression patterns and the sequence-based target relationship of which can be predicted. Circadian initiators, Clock and Bmal1, showed inversely correlated circadian expression patterns against their corresponding miRNAs, miR-181d and miR-191, targeting them. In contrast, circadian suppressors, Per, Cry, CKIe and Rev-erba, exhibited positively correlated circadian expression patterns to their corresponding miRNAs. Genomic location analysis revealed that intronic region showed higher abundance of cyclic than non-cyclic miRNAs targeting circadian genes while other (i.e., 3-UTR, exon and intergenic) regions showed no difference. It is suggested that miRNAs are involved in the regulation of peripheral circadian rhythm in mouse liver by modulating Clock:Bmal1 complex. Identifying specific miRNAs and their targets that are critically involved in circadian rhythm will provide a better understanding of the regulation of circadian- clock system.

Inhibition of ERK-MAP kinase signaling by RSK during Drosophila development.

Although p90 ribosomal S6 kinase (RSK) is known as an important downstream effector of the ribosomal protein S6 kinase/extracellular signal-regulated kinase (Ras/ERK) pathway, its endogenous role, and precise molecular function remain unclear. Using gain-of-function and null mutants of RSK, its physiological role was successfully characterized in Drosophila. Surprisingly, RSK-null mutants were viable, but exhibited developmental abnormalities related to an enhanced ERK-dependent cellular differentiation such as ectopic photoreceptor- and vein-cell formation. Conversely, overexpression of RSK dramatically suppressed the ERK-dependent differentiation, which was further augmented by mutations in the Ras/ERK pathway. Consistent with these physiological phenotypes, RSK negatively regulated ERK-mediated developmental processes and gene expressions by blocking the nuclear localization of ERK in a kinase activity-independent manner. In addition, we further demonstrated that the RSK-dependent inhibition of ERK nuclear migration is mediated by the physical association between ERK and RSK. Collectively, our study reveals a novel regulatory mechanism of the Ras/ERK pathway by RSK, which negatively regulates ERK activity by acting as a cytoplasmic anchor in Drosophila.

Bronchobiliary fistula after radiofrequency thermal ablation of hepatic tumor.

A broad spectrum of complications can occur after radiofrequency (RF) ablation of hepatic tumors, even though it has been accepted as a safe and effective technique for unresectable hepatic tumors. Recently, the rare complication of brochobiliary fistula was encountered after RF ablation in a patient with a metastatic tumor from stomach cancer. It was assumed to have developed from collateral damage to the adjacent diaphragm and lung base as well as biloma formation at the ablation zone. Symptomatic improvement was achieved by conservative management with an external drainage catheter, but the fistula was still persistent on a 2-month follow-up image.