Bullae and sweat gland necrosis remain rare cutaneous manifestation, and these conditions can be misdiagnosed as Vibrio vulnificus infections or other soft tissue infections because of their low index of suspicion. A 46-yr-old man with a history of continued alcohol consumption presented with erythematous and hemorrhagic bullous lesions on his left arm. The patient reported that after the ingestion of clams, he slept for 12 hr in a heavily intoxicated state. Then the skin lesions started as a reddish patch that subsequently became hemorrhagic bullae. V. vulnificus infection, cellulitis, and necrotizing fasciitis were considered in initial differential diagnosis. However, on the basis of sweat gland necrosis on histopathologic examinations and negative results on bacterial cultures, we made the diagnosis of bullae and sweat gland necrosis. Therefore, bullae and sweat gland necrosis should also be considered in chronic alcoholic patients who present with bullae and a previous history of unconsciousness.
Alcohol; Bullae and Sweat Gland Necrosis; Sweat Glands; Vibrio vulnificus infection
Acute post-streptococcal glomerulonephritis (PSGN) is characterized by an abrupt onset of edema, hypertension, and hematuria. Life-threatening diffuse alveolar hemorrhage (DAH) is rarely associated with acute PSGN. There have been only two reported cases worldwide, and no case has been reported previously in Korea. Here, we present a patient who clinically presented with pulmonary-renal syndrome; the renal histology revealed post-infectious glomerulonephritis of immune complex origin. A 59-yr-old woman was admitted with oliguria and hemoptysis two weeks after pharyngitis. Renal insufficiency rapidly progressed, and respiratory distress developed. Chest radiography showed acute progressive bilateral pulmonary infiltrates. The clinical presentation suggested DAH with PSGN. Three days after treatment with high-dose steroids, the respiratory distress and pulmonary infiltrates resolved. Electron microscopy of a renal biopsy specimen sample revealed diffuse proliferative glomerulonephritis with characteristic subendothelial deposits of immune complex ("hump"). The renal function of the patient was restored, and the serum creatinine level was normalized after treatment.
Post-Streptococcal Glomerulonephritis; Diffuse Alveolar Hemorrhage
Autologous chondrocyte implantation is an effective treatment for damaged articular cartilage. However, this method involves surgical procedures that may cause further cartilage degeneration, and in vitro expansion of chondrocytes can result in dedifferentiation. Adipose-derived stem cells (ADSCs) may be an alternative autologous cell source for cartilage regeneration. In this study, we developed an effective method for large-scale in vitro chondrogenic differentiation, which is the procedure that would be required for clinical applications, and the subsequent in vivo cartilage formation of human ADSCs (hADSCs). The spheroid formation and chondrogenic differentiation of hADSCs were induced on a large scale by culturing hADSCs in three-dimensional suspension bioreactors (spinner flasks). In vitro chondrogenic differentiation of hADSCs was enhanced by a spheroid culture compared with a monolayer culture. The enhanced chondrogenesis was probably attributable to hypoxia-related cascades and enhanced cell–cell interactions in hADSC spheroids. On hADSCs loading in fibrin gel and transplantation into subcutaneous space of athymic mice for 4 weeks, the in vivo cartilage formation was enhanced by the transplantation of spheroid-cultured hADSCs compared with that of monolayer-cultured hADSCs. This study shows that the spheroid culture may be an effective method for large-scale in vitro chondrogenic differentiation of hADSCs and subsequent in vivo cartilage formation.
Despite promising results from the therapeutic use of stem cells for treating ischemic diseases, the poor survival of cells transplanted into ischemic regions is one of the major problems that undermine the efficacy of stem cell therapy. Cord blood mononuclear cells (CBMNCs) are an alternative source of mesenchymal stem cells (MSCs) without disadvantages, such as the painful and invasive harvesting procedure, of MSCs derived from bone marrow or adipose tissue. In the present study, we investigated whether the angiogenic efficacy of cord blood mesenchymal stem cells (CBMSCs) can be enhanced by grafting as spheroids in a mouse hindlimb ischemia model. Human CBMSC (hCBMSC) spheroids were prepared by using the hanging-drop method. Mouse hindlimb ischemia was induced by excising the femoral artery and its branches. After surgery, the animals were divided into no-treatment, dissociated hCBMSC, and spheroid hCBMSC groups (n=8 per group) and received corresponding hCBMSC treatments. After surgery, the ischemic hindlimbs were monitored for 4 weeks, and then, the ischemic hindlimb muscles were harvested for histological analysis. Apoptotic signaling, angiogenesis-related signal pathways, and blood vessel formation were investigated in vitro and/or in vivo. The transplantation of hCBMSCs as spheroids into mouse ischemic hindlimbs significantly improved the survival of the transplanted cells by suppressing apoptotic signaling while activating antiapoptotic signaling. Furthermore, the transplantation of hCBMSCs as spheroids significantly increased the number of microvessels and smooth muscle α-actin-positive vessels in the ischemic limbs of mice, and attenuated limb loss and necrosis. Human CBMNC can be considered an alternative source of MSC, and spheroid-based hCBMSC delivery can be considered a simple and effective strategy for enhancing the therapeutic efficacy of hCBMSCs.
There is as yet no effective and safe treatment for vitiligo. One percent pimecrolimus cream, a topical calcineurin inhibitor, has been tried for the treatment of vitiligo, with its therapeutic efficacy having mostly been reported in non-segmental vitiligo. However, questions about the therapeutic efficacy of 1% pimecrolimus cream have remained unanswered regarding segmental vitiligo.
The aim of this study was to study the therapeutic efficacy and safety of 1% pimecrolimus cream for segmental childhood vitiligo.
Nine childhood patients with segmental vitiligo were treated with 1% pimecrolimus cream twice daily for three months, after which good responders were scheduled to continue with the 1% pimecrolimus cream monotherapy. The efficacy and safety of this treatment were determined by the levels of repigmentation, initial response time and the presence of adverse events including burning, dryness, stinging and itching.
Four of nine patients achieved mild to moderate responses after three months of treatment and thus continued with treatment. Among these four patients, three achieved an excellent response and one patient achieved a moderate response, with a mean treatment duration of 7.3 months. Transient local burning sensation was the most common adverse event. In comparison with the patients with poor response, those patients with good response showed a shorter disease duration (8.5±10.5 mo vs. 13.4±10.1 mo), more frequent facial involvement (4/4 patients vs. 3/5 patients) and earlier initial response after treatment (1.0±0.0 mo vs. 2.0±1.0 mo).
This study suggests that 1% pimecrolimus cream is an effective and well-tolerated treatment for segmental childhood vitiligo.
The underlying mechanism of atopic dermatitis (AD) exacerbated by Staphylococcus aureus has not been established. However, we demonstrated recently that the majority of S. aureus strains colonized in the skin of Korean AD patients carried genes encoding staphylococcal enterotoxin A (SEA) and/or toxic shock syndrome toxin-1 (TSST-1).
To clarify the role of staphylococcal superantigen, SEA in AD.
With the lesional skin of 9 AD patients and normal looking skin of one healthy adult, we examined first the expression of SEA, staphylococcal enterotoxin B (SEB), and TSST-1 using immunohistochemical analysis. In addition, we investigated the effects of SEA on the expression of inflammation-related adhesion molecules and cytokines in human HaCaT keratinocytes and Human Umbilical Vein Endothelial Cells (HUVECs) by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent assay.
Staphylococcal protein A (SPA) and SEA were detected with increased immunoreactivity in AD patients. However, TSST-1 showed mild-to-moderate immunoreactivity in AD patients, whereas SEB was minimally detected. In the double immunofluorescence investigation, SEA and SPA were well co-localized. SEA induced upregulation of adhesion molecules and elicited inflammatory responses in HaCaT keratinocytes and HUVECs.
This study demonstrates the importance of SEA as an immunoinflammatory triggering factor of AD in Koreans.
Atopic dermatitis; Staphylococcal enterotoxin A; Staphylococcus aureus
Tinea incognito (TI) is a dermatophytic infection which has lost its typical clinical appearance because of improper use of steroids or calcineurin inhibitors. The incidence of TI is increasing nowadays. We conducted retrospective review on 283 patients with TI from 25 dermatology training hospitals in Korea from 2002-2010 to investigate the demographical, clinical, and mycological characteristics of TI, and to determine the associated risk factors. More than half (59.3%) patients were previously treated by non-dermatologists or self-treated. The mean duration of TI was 15.0 ± 25.3 months. The most common clinical manifestations were eczema-like lesion, psoriasis-like, and lupus erythematosus-like lesion. The trunk and face were frequently involved, and 91 patients (32.2%) also had coexisting fungal infections. Among 67 isolated strains, Trichophyton rubrum was the most frequently detected (73.1%). This is the largest study of TI reported to date and the first investigational report concerning TI in Korea. We suggest that doctors should consider TI when a patient has intractable eczema-like lesions accompanied by tinea pedis/unguium. Furthermore, there should be a policy change, which would make over-the-counter high-potency topical steroids less accessible in some countries, including Korea.
Calcineurin Inhibitor; Dermatophytoses; Korea; Steroid; Tinea; Tinea Incognito
Pseudomembranous necrotizing bronchial aspergillosis (PNBA) is a rare form of invasive aspergillosis with a very poor prognosis. The symptoms are non-specific, and the necrotizing plugs cause airway obstruction. Atelectasis and respiratory failure can be the initial manifestations. Recently, we treated an immunocompromised patient with PNBA, who presented with a sudden onset of atelectasis and acute respiratory failure. There were no preceding signs except for a mild cough and one febrile episode. Bronchoscopy revealed PNBA, and Aspergillus nidulans was cultured from the bronchial wash.
Aspergillosis; Pneumonia; Neutropenia
Extranodal natural killer (NK)/T-cell lymphoma is a subtype of lymphoma that is derived from NK cells. It is considered as an aggressive form of non-Hodgkin's lymphoma because of frequent relapses and resistance to treatment. Relapsed NK/T-cell lymphoma often follows a fulminant course that is refractory to conventional chemotherapy treatment.
Several patients with extranodal NK/T-cell lymphoma showed long-term survival in spite of frequent relapses. Thus, the medical records of patients diagnosed with extranodal NK/T-cell lymphoma from 1995 to 2007 were reviewed and assessed.
Of the 140 cases reviewed, 6 were selected (4.29%). Each of these patients had a minimum of 3 relapses or disease progression during the follow-up period, and their median overall survival was 66 months (range, 42-89 months). They were grouped according to the atypical clinical behavior observed: (1) repeated relapses or progression (≥3 times) during follow-up; and (2) long-term survival of more than 40 months, as the longest overall survival median was previously considered at approximately 40 months. The clinicopathological and laboratory characteristics of these patients were similar to those of other extranodal NK/T-cell lymphoma patients. However, 5 of the studied cases involved relatively lower expression of the proliferation-related antigen Ki-67 (<40-50%), indicating less proliferative activity. Clinically, they showed delayed relapse for at least 20 months after the initial complete remission.
Our observations suggest that the clinical behavior of some extranodal NK/T-cell lymphoma patients differs from the typical clinical course.
Extranodal NK/T-cell lymphoma; Relapse; Survival; Indolent
The osseointegration around titanium mini-implants installed in macroporous biphasic calcium phosphate (MBCP) blocks was evaluated after incubation with recombinant human bone morphogenetic protein-2 (rhBMP-2) in an ectopic subcutaneous rat model.
Mini-implants (φ1.8×12 mm) were installed in MBCP blocks (bMBCPs, 4×5×15 mm) loaded with rhBMP-2 at 0.1 mg/mL, and then implanted for 8 weeks into subcutaneous pockets of male Sprague-Dawley rats (n=10). A histomorphometric analysis was performed, and the bone-to-implant contact (BIC) and bone density were evaluated.
Significant osteoinductive activity was induced in the rhBMP-2/bMBCP group. The percentage of BIC was 41.23±4.13% (mean±standard deviation), while bone density was 33.47±5.73%. In contrast, no bone formation was observed in the bMBCP only group.
This model represents a more standardized tool for analyzing osseointegration and bone healing along the implant surface and in bMBCPs that excludes various healing factors derived from selected animals and defect models.
Animals; Dental implants; Osseointegration
Interdigitating dendritic cell sarcoma (IDCS) is a very rare and aggressive neoplasm that arises from antigen presenting cells. IDCS usually involves lymph nodes; however, extra-nodal involvement has also been reported. Because a consistent standard therapy for IDCS has not been established to date, we report a case of the successful treatment of disseminated IDCS using ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine). A 64-year-old man was diagnosed with IDCS on the basis of immunohistochemical findings of a biopsy specimen of the inferior nasal concha. Immunohistochemical staining showed a positive reaction for CD68, leukocyte common antigen, and S-100 protein, but a negative reaction for CD34, CD1a, and CD21. Imaging studies showed cervical and axillary lymphadenopathies, subcutaneous nodules, and a soft tissue lesion in the nasal cavity. Treatment with the ABVD regimen resulted in complete remission after 8 cycles of chemotherapy.
IDCS; ABVD chemotherapy; Complete remission
Bone morphogenetic protein-2 (BMP-2) is used to promote bone regeneration. However, the bone regeneration ability of BMP-2 relies heavily on the delivery vehicle. Previously, we have developed heparin-conjugated fibrin (HCF), a vehicle for long-term delivery of BMP-2 and demonstrated that long-term delivery of BMP-2 enhanced its osteogenic efficacy as compared to short-term delivery at an equivalent dose. The aim of this study was to compare the bone-forming ability of the BMP-2 delivered by HCF to that delivered by clinically utilized BMP-2 delivery vehicle collagen sponge. An in vitro release profile of BMP-2 showed that HCF released 80% of the loaded BMP-2 within 20 days, whereas collagen sponge released the same amount within the first 6 days. Moreover, the BMP-2 released from the HCF showed significantly higher alkaline phosphatase activity than the BMP-2 released from collagen sponge at 2 weeks in vitro. Various doses of BMP-2 were delivered with HCF or collagen sponge to mouse calvarial defects. Eight weeks after the treatment, bone regeneration was evaluated by computed tomography, histology, and histomorphometric analysis. The dose of BMP-2 delivered by HCF to achieve 100% bone formation in the defects was less than half of the BMP-2 dose delivered by collagen sponge to achieve a similar level of bone formation. Additionally, bone regenerated by the HCF-BMP-2 had higher bone density than bone regenerated by the collagen sponge-BMP-2. These data demonstrate that HCF as a BMP-2 delivery vehicle exerts better osteogenic ability of BMP-2 than collagen sponge, a clinically utilized delivery vehicle.
bone morphogenetic protein 2; collagen; drug delivery systems; fibrin; osteogenesis
DNA methylation may regulate gene expression by restricting the access of transcription factors. We have previously demonstrated that GATA-1 regulates the transcription of the CCR3 gene by dynamically interacting with both positively and negatively acting GATA elements of high affinity binding in the proximal promoter region including exon 1. Exon 1 has three CpG sites, two of which are positioned at the negatively acting GATA elements. We hypothesized that the methylation of these two CpGs sites might preclude GATA-1 binding to the negatively acting GATA elements and, as a result, increase the availability of GATA-1 to the positively acting GATA element, thereby contributing to an increase in GATA-1-mediated transcription of the gene. To this end, we determined the methylation of the three CpG sites by bisulfate pyrosequencing in peripheral blood eosinophils, cord blood (CB)-derived eosinophils, PBMCs, and cell lines that vary in CCR3 mRNA expression. Our results demonstrated that methylation of CpG sites at the negatively acting GATA elements severely reduced GATA-1 binding and augmented transcription activity in vitro. In agreement, methylation of these CpG sites positively correlated with CCR3 mRNA expression in the primary cells and cell lines examined. Interestingly, methylation patterns of these three CpG sites in CB-derived eosinophils mostly resembled those in peripheral blood eosinophils. These results suggest that methylation of CpG sites at the GATA elements in the regulatory regions fine-tunes CCR3 transcription.
DNA methylation; eosinophils; GATA-1; receptors, CCR3; transcription factor; transcriptional activation
Eosinophils arise from hematopoietic CD34+ stem cells in the bone marrow. They acquire IL-5Rα on their surface at a very early stage during eosinophilopoiesis, and differentiate under the strong influence of interleukin (IL)-5. They then exit to the bloodstream, and enter the lung upon exposure to airway inflammatory signals, including eotaxins. In inflamed tissues, eosinophils act as key mediators of terminal effector functions and innate immunity and in linking to adaptive immune responses. Transcription factors GATA-1, CCAAT/enhancer-binding protein, and PU.1 play instructive roles in eosinophil specification from multipotent stem cells through a network of cooperative and antagonistic interactions. Not surprisingly, the interplay of these transcription factors is instrumental in forming the regulatory circuit of expression of eosinophil-specific genes, encoding eosinophil major basic protein and neurotoxin, CC chemokine receptor 3 eotaxin receptor, and IL-5 receptor alpha. Interestingly, a common feature is that the critical cis-acting elements for these transcription factors are clustered in exon 1 and intron 1 of these genes rather than their promoters. Elucidation of the mechanism of eosinophil development and activation may lead to selective elimination of eosinophils in animals and human subjects. Furthermore, availability of a range of genetically modified mice lacking or overproducing eosinophil-specific genes will facilitate evaluation of the roles of eosinophils in the pathogenesis of asthma. This review summarizes eosinophil biology, focusing on development and regulation of eosinophil-specific genes, with a heavy emphasis on the causative link between eosinophils and pathological development of asthma using genetically modified mice as models of asthma.
Asthma; CCR3; eosinophils; eotaxin; GATA-1; IL-5
Bilateral quadriceps tendon rupture is an unusual injury, but may be encountered in patients with various chronic diseases after minor trauma. This article presents a case of bilateral quadriceps tendon rupture of a 38-year-old woman with chronic renal failure. Surgical repair was performed using a bone tunnel technique with a nonabsorbable suture and a suture anchor. Postoperative magnetic resonance imaging confirmed complete healing of the repair site, and clinically active extension with 120 degrees of range of motion was achieved.
Quadriceps tendon; Bilateral rupture; Chronic renal failure; Primary repair
In previous studies, psoriasis has been reported to be associated with metabolic syndrome.
The purpose of this study was to evaluate risk factors for metabolic syndrome in psoriasis patients and to compare the prevalence of metabolic syndrome in psoriasis and control groups.
All patients (n=490) and controls (n=682) were investigated for cardiovascular risk factors, including central obesity, hypertension, fasting plasma glucose levels, and blood levels of triglycerides and high-density lipoprotein (HDL).
We found no statistical association between psoriasis and the prevalence of metabolic syndrome when controlling for age and gender. Among individual components of metabolic syndrome, only increased triglyceride levels was significantly prevalent in patients psoriasis. The incidence of other factors such as central obesity, hypertension, fasting plasma glucose and HDL in the psoriasis group were similar to or lower than those in the control group. Although psoriasis patients with metabolic syndrome had severe and large plaque-type psoriasis, the association of metabolic syndrome with the severity or clinical subtype of psoriasis was not significant after adjusting for age and gender.
Our results suggest that there is no close correlation between psoriasis and metabolic syndrome in Korean patients.
Cardiovascular risk; Metabolic syndrome; Psoriasis
An 82-year-old woman presented with a four-month history of an ulcerative plaque overlying her left neck. This lesion had developed as a subcutaneous nodule, gradually increased in size, and evolved into ulcers. Before visiting our Dermatology clinic, the patient had been diagnosed as having a bacterial abscess, but treatments with antibiotics were unsuccessful. The presence of a purulent discharge and prominent ulceration caused further confusion as bacterial abscess, and radiologic evaluation on computed tomography also led to the possibilities of secondary lesions from an abscess or malignancy. However, the characteristic appearance of her lesion allowed us to discern cutaneous tuberculosis, especially scrofuloderma. Based on clinical examinations, staining for acid-fast bacilli, and positive findings of polymerase chain reaction, a quick diagnosis of scrofuloderma was made. After that, she was treated successfully with anti-tuberculosis therapy and the ulcer healed. Our case highlights the problem of delayed diagnosis of scrofuloderma presenting as a bacterial abscess. In conclusion, having a high index of suspicion is needed to diagnose cutaneous tuberculosis correctly.
Bacterial abscess; Scrofuloderma
Lichens striatus (LS) is an acquired, self-limiting inflammatory dermatosis that follows the lines of Blaschko. The etiology of the eruption is unknown, but several theories have been proposed with focus on environmental factors, viral infection, cutaneous injury, hypersensitivity, and genetic predisposition. We describe a 19-year-old woman who developed a unilateral linear eruption 17 months after allogenic peripheral blood stem cell transplantation. Histopathology revealed features, which were consistent with LS. To the best of our knowledge, our patient is the first case describing the appearance of LS occurring after allogenic stem cell transplantation. We speculate that this condition represents an unusual form of localized, chronic graft-versus-host disease.
Graft-versus-host disease; Lichen striatus; Pathogenesis; Stem cell transplantation
Purpose: A fluorogenic peptide probe-immobilized diagnostic kit was used to analyze MMP activity in the synovial fluids (SFs) from patients with osteoarthritis (OA) and acute inflammatory conditions of the knee joint.
Methods: The MMP diagnostic kit containing a polymer-conjugated MMP probe immobilized on a 96-well plate was utilized for high-throughput screening of MMP activity in SFs from OA patients (n = 33) and patients with acute inflammatory conditions of the knee joint (n = 5).
Results: Compared to SF from OA patients, SF from patients with acute inflammatory conditions of the knee joint presented stronger NIR fluorescent signals. In gelatin zymography, most samples from patients with acute inflammatory conditions of the knee joint also displayed 92 kDa (pro-form) MMP-9 and faint 84 kDa (active form) MMP-9, while SF from OA patients did not display detectable MMP-9 activity .
Conclusion: The presence of a strong fluorescence signal from the MMP diagnostic kit corresponded well with patients with acute inflammatory conditions of the knee joint. The results suggest that our MMP diagnostic kit can be useful in differentiation between early stages of OA and acute inflammatory conditions of the knee joint.
Matrix metalloproteinases; Osteoarthritis; Synovial fluid; Diagnostic kit; Acute inflammatory conditions of the knee joint
To determine if exogenously injected bone marrow derived platelet-rich plasma (PRP) plus bone morphogenetic protein (BMP)-2 could accelerate the healing of bone-tendon junction injuries and increase the junction holding strength during the early regeneration period.
A direct injury model of the bone-tendon junction was made using an Achilles tendon-calcaneus bone junction in a rabbit. In the PRP/BMP-2/fibrin group, 0.05 mL of bone marrow derived PRP and 100 ng/mL of BMP-2 both incorporated into 0.1 mL of fibrin glue were injected into Achilles tendon-calcaneus bone junctions. The effect of the intervention was tested by comparing the results of an intervention group to a control group. The results of biomechanical testing, and histological and gross analyses were compared between the 2 groups at the following time points after surgery: 2 weeks, 4 weeks, and 8 weeks.
Histologic examinations showed that woven bone developed in tendon-bone junctions at 2 weeks after surgery in the PRP/BMP-2/fibrin group. Mechanical test results showed no significant difference between the PRP/BMP-2/fibrin and control groups at 2 and 4 weeks after surgery, but the mean maximal load in the PRP/BMP-2/fibrin group was significantly higher than in the control group (p < 0.05) at 8 weeks after surgery.
Bone marrow derived PRP and BMP-2 in fibrin glue accelerated healing in a rabbit model of tendon-bone junction injury.
Bone-tendon junction; Achilles tendon; Bone marrow derived platelet rich plasma; Bone morphogenetic protein