Symptomatic mucoid degeneration of the anterior cruciate ligament

Purpose

Mucoid degeneration of the anterior cruciate ligament (ACL) is a little-known entity. The aim of this study was to detail the clinical, radiological, arthroscopic and pathological findings of this condition and to report clinical outcomes following arthroscopic partial excision of the ACL.

Methods

Between 1999 and 2009, 80 knees in 78 patients were diagnosed as having mucoid degeneration of the ACL based on MRI and clinical findings, and subsequently underwent arthroscopic treatment. Of these, 68 knees in 66 patients, with a median age of 51 years (range, 35–75 years), were followed-up for at least one year.

Results

All patients had insidious onset of knee pain, while 56 knees (82 %) had associated extension deficits and 36 knees (53 %) had restricted flexion. MRI findings typically showed diffuse thickening and increased signal intensity of the ACL. Arthroscopic examination revealed notch impingement and bulging of hypertrophied ACL into lateral compartments. Associated lesions included meniscal tears in 33 knees and chondral lesions of at least Outerbridge grade 2 in 56 knees. All knees underwent arthroscopic partial excision of the hypertrophied ACL, with three undergoing preoperative and 30 undergoing concomitant meniscectomies. Pain relief was achieved in 58 of 62 knees (94 %) following partial excision of the ACL. Extension deficits were normalized in 49 of 56 knees (88 %), and restricted flexion was normalized in 33 of 36 affected knees (92 %). Four knees of four patients had postoperative symptoms of anterior instability.

Conclusions

Pain and limitation of motion due to mucoid degeneration of the ACL can be improved by arthroscopic partial excision of the ACL with or without notchplasty. However, one potential complication is the development of postoperative symptoms of anterior instability.

Level of evidence

Retrospective study, Level IV.     

Less keratinocyte-derived factors related to more keratinocyte apoptosis in depigmented than normally pigmented suction-blistered epidermis may cause passive melanocyte death in vitiligo

Stem cell factor (SCF) of keratinocyte origin regulates melanocyte growth and survival. Deprivation of survival factors causes the apoptosis of melanocytes. Vitiligo often develops following physical trauma, even if this is minor. The exact mechanism of the Koebner phenomenon in vitiligo is unclear. Apoptosis of keratinocytes, which occurs more in depigmented suction-blistered epidermis than in the normally pigmented counterpart, could reduce levels of keratinocyte-derived factors such as SCF and basic fibroblast growth factor (bFGF). Levels of SCF expression were examined in the depigmented and normally pigmented paired epidermis of 19 patients with vitiligo, and bFGF expression in six patients. The expression of SCF (p<0.001) and bFGF was usually reduced in the depigmented compared with the normally pigmented epidermis. Apoptosis of cultured normal human keratinocytes, which was induced by staurosporine, resulted in a concentration-dependent decrease in levels of SCF mRNA and protein. Normal human melanocytes proliferated more in medium containing SCF or keratinocyte (XB-2) feeder than in medium with neither. Deprivation of SCF or keratinocyte feeder in the culture medium induced a marked decrease in melanocytes as a result of apoptosis. Therefore, lower expression of keratinocyte-derived factors, including SCF, in vitiliginous keratinocytes, which could result from keratinocyte apoptosis, might be responsible for passive melanocyte death and may explain the Koebner phenomenon.     

Primary spinal dumbbell-shaped mesenchymal chondrosarcoma located intradurally and extradurally

Mesenchymal chondrosarcomas are rare malignant tumors of the bone and soft tissue. Spinal mesenchymal chondrosarcomas are even rarer and, to the best of our knowledge those that are concomitantly located in the intradural and extradural regions, have never been reported. We report a case of a 25-year-old man with back pain and bilateral progressive weakness of the lower extremities. Magnetic resonance imaging revealed a markedly enhanced dumbbell-shaped mass at the T7 level. The lesion was intradurally located at the left side of the spinal cord, and extended extradurally to the extraforminal space through the T7-8 intervertebral foramen. The tumor was completely excised through a posterior approach. Microscopic examination and immunohistochemical studies confirmed mesenchymal chondrosarcoma. Postoperative radiation therapy and chemotherapy were also performed to prevent local recurrence and metastasis. The patient has been symptom-free for two years after surgery. Herein, we reviewed and discussed the clinical characteristics, treatments, and outcomes of primary intraspinal mesenchymal chondrosarcomas in the literature.     

Copy number variation of CCL3L1 influences asthma risk by modulating IL-10 expression

BackgroundCopy number of Chemokine ligand 3-like 1 (CCL3L1) is associated with various immune disorders. This study was conducted to assess the role of CCL3L1 in asthma by both association analyses of human subjects and in vitro functional analyses.MethodsWe analyzed the copy number of the CCL3L1 gene in 533 Korean subjects (372 controls and 161 asthma patients) by real-time PCR, and investigated the effect of recombinant CCL3L1 protein on THP-1 human monocytic cells that were stimulated with house dust mite extract.ResultsThe mean copy number of CCL3L1 in asthma subjects was significantly lower than that of control subjects (3.18 vs. 3.75, p = 0.001). A low copy number of ≤ 1 was significantly associated with increased asthma risk with an odds ratio of 2.47, and a high copy number of ≥ 5 was associated with decreased asthma risk with an odds ratio of 0.40. Subjects with ≤ 1 copy of CCL3L1 had significantly lower mRNA levels of CCL3L1 in peripheral blood cells, and significantly higher serum IgE levels (p < 0.05). In the house dust mite extract-simulated THP-1 monocytic cells, CCL3L1 protein dose-dependently up-regulated the expression of IL-10, an anti-inflammatory cytokine.ConclusionCopy number of CCL3L1 may influence asthma risk by modulating IL-10 expression.     

Molecular characterization of rare G12P[6] rotavirus isolates closely related to G12 strains from the United States, CAU 195 and CAU 214

Two human G12 rotaviruses, CAU 195 and CAU 214, were isolated from South Korea using cell culture and characterized on the basis of sequence divergence in the VP7, VP4, and NSP4 genes. Phylogenetic analysis of the VP7 gene sequences indicated that these strains clustered into lineage III and were most closely related to G12 rotaviruses isolated in the United States. The VP4 and NSP4 gene sequences showed that two strains belonged to the P[6]-Ia lineage and genotype [B]. This finding provides information that can be used to evaluate G12 strains and aid in the development of effective vaccines in the future.     

Three-dimensional cancer-bone metastasis model using ex-vivo co-cultures of live calvarial bones and cancer cells

One of the major limitations of studying cancer-bone metastasis has been the lack of an appropriate ex-vivo model which can be used under defined conditions that simulates closely the in vivo live bone microenvironment in response to cancer-bone interactions. We have developed and utilized a three-dimensional (3D) cancer-bone metastasis model using free-floating live mouse calvarial bone organs in the presence of cancer cells in a roller tube system. In such co-cultures under hypoxia and a specifically defined bone remodeling stage, viz., resorption system, cancer cells showed a remarkable affinity and specificity for the “endosteal side” of the bone where they colonize and proliferate. This was concurrent with differentiation of resident stem/progenitor cells to osteoclasts and bone resorption. In contrast, under bone formation conditions this model revealed different pathophysiology where the breast cancer cells continued to induce osteoclastic bone resorption whereas prostate cancer cells led to osteoblastic bone formation. The current 3D model was used to demonstrate its application to studies involving chemical and biochemical perturbations in the absence and presence of cancer cells and cellular responses. We describe proof-of-principle with examples of the broad versatility and multi-faceted application of this model that adds another dimension to the ongoing studies in the cancer-bone metastasis arena.     

Stimulation parameter optimization for functional electrical stimulation assisted gait in human spinal cord injury using response surface methodology

BACKGROUND: The aims of this study were to identify the reflex moment induced by flexion withdrawal reflex and to optimize stimulation parameters for restoring swing motion with respect to initial kinematic conditions in human with spinal cord injury. METHODS: The influence of hip position and passive movement in the reflex moment were tested in six subjects with chronic spinal cord injury. The two-dimensional dynamic models consisted of thigh, shank and foot segments were developed to compute the swing-phase response and the response surface method was also used to optimize stimulation parameters for restoration of gait by functional electrical stimulation. FINDINGS: At three different hip positions, significant linear relationship was found between the reflex moment and hip angle (P < 0.05) and hip movement also increased the reflex moment compare to isometric conditions. The hip and knee flexion velocities significantly contributed to the hip and knee flexion angle during the swing-phase (P < 0.05) and increase of initial joint velocity resulted in a decrease of the burst frequency and duration time for optimal swing motion in spinal cord injured patients. INTERPRETATION: From dynamic simulation, we concluded that optimal solutions of pulse amplitude, frequency and duration time of burst for electrical stimulation assisted gait were influenced by initial kinematic conditions at toe-off. The reflex model and the results of this study can be applied to the design and control strategies of neuroprosthetic devices using functional electrical stimulation for spinal cord injured patients.     

Mite and cockroach allergens activate protease-activated receptor 2 and delay epidermal permeability barrier recovery

Protease-activated receptor-2 (PAR-2) is known to be involved in epidermal permeability barrier function homeostasis. PAR-2 activation occurs after barrier disruption and further activation of PAR-2 by activating peptide significantly delays barrier recovery rate. Cockroach and house dust mite allergens, both known to be associated with the development of asthma, allergic rhinitis, and atopic dermatitis, have protease activity, which can activate PAR-2. In this study, we investigated the effects of both allergens on the epidermal barrier function as well as on the epidermal calcium gradient. Both allergens, when topically applied on the barrier-disrupted site, increased protease activities in the epidermis and delayed barrier recovery and lamellar body secretion in murine skin. The topical application of PAR-2-specific antagonist or protease inhibitors normalized the barrier recovery. Cockroach allergens induced intracellular calcium oscillations in cultured human keratinocytes through PAR-2-involved pathway, which was confirmed by desensitization protocol. Abnormal calcium ion distribution after barrier disruption was also observed in allergens-applied skin. These results suggest that allergens with protease activity can influence the epidermal permeability barrier homeostasis through PAR-2 activation and consequent modulation of the calcium ions in skin.     

K6PC-5, a sphingosine kinase activator, induces anti-aging effects in intrinsically aged skin through intracellular Ca2+ signaling

BACKGROUND: Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, regulates multiple cellular responses such as Ca(2+) signaling, growth, survival, and differentiation. Because sphingosine kinase (SK) is the enzyme directly responsible for the production of S1P, many factors have been identified that regulate its activity and subsequent S1P levels. To date, there are no reports to demonstrate a chemically induced, direct activation of SK. OBJECTIVE: Here we have studied the effects of K6PC-5 as a newly synthesized SK activator on fibroblast proliferation in both human fibroblasts and aged mouse skin. To demonstrate that K6PC-5 has S1P-mediated action mechanism in fibroblasts, we have measured SK-dependent intracellular Ca(2+) signaling. METHODS: Fibroblasts were cultured primarily from human foreskin and were used to study the effect of K6PC-5 and S1P on intracellular Ca(2+) signaling and fibroblast proliferation. Changes in intracellular Ca(2+) were detected by fluorescence with fura-2/AM. To study skin anti-aging effects of K6PC-5, we used intrinsically aged hairless mice (56 weeks old). RESULTS: K6PC-5 promoted fibroblast proliferation and procollagen production in human fibroblasts significantly. K6PC-5 induced intracellular Ca(2+) concentration ([Ca(2+)](i)) oscillations in human fibroblasts. Both dimethylsphingosine and dihydroxysphingosine, SK inhibitors, and the transfection of SK1-siRNA blocked the K6PC-5-induced increases in [Ca(2+)](i), an effect independent of the classical PLC/IP(3)-mediated pathway. The K6PC-5-induced [Ca(2+)](i) oscillations were dependent on thapsigargin-sensitive Ca(2+) stores and Ca(2+) entry. Topical application of K6PC-5 for 2 weeks to intrinsically aged hairless mice enhanced fibroblast proliferation, collagen production, and eventually increased dermal thickness (10%). K6PC-5 also promoted specific epidermal differentiation marker proteins, including involucrin, loricrin, filaggrin, and keratin 5, without any alterations on epidermal barrier function. CONCLUSION: These results suggest that K6PC-5 acts to regulate fibroblast proliferation through intracellular S1P production, and can further promote keratinocyte differentiation. We anticipate that the regulation of S1P levels may represent a novel approach for the treatment of skin disorders, including skin aging.