In Vitro Activity of Benzimidazole (SPR719) Against Clinical Isolates of Nontuberculous Mycobacteria With and Without Clarithromycin or Amikacin Resistance

Limited data are available regarding the in vitro activity of SPR719, a derivative of benzimidazole, against diverse nontuberculous mycobacteria (NTM) species. We investigated the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of SPR719 against clinical NTM isolates, including clarithromycin- and amikacin-resistant strains. NTM isolates were obtained from patients with NTM-pulmonary disease caused by various NTM species, including Mycobacterium avium complex, M. abscessus (subspecies abscessus and massiliense), M. kansasii, and M. fortuitum. Regardless of clarithromycin or amikacin resistance, the MIC and MBC values of SPR719 were comparable among these major pathogenic NTM species. In over 70% of the isolates, the MIC values were ≤ 2 µg/mL with MBC values of ≤ 4 µg/mL. The MIC and MBC values of M. kansasii were relatively lower than those of the other species with little difference between them, demonstrating the bactericidal properties of SPR719. The in vitro activity of SPR719 against major clinical NTM species suggests that SPR719 can serve as a novel treatment option for NTM-pulmonary disease.

miR-148a is a downstream effector of X-box-binding protein 1 that silences Wnt10b during adipogenesis of 3T3-L1 cells

Wnt10b, an endogenous inhibitor of adipogenesis, maintains preadipocytes in an undifferentiated state by suppressing adipogenic transcription factors. We have previously demonstrated that Wnt10b transcription during adipogenesis is negatively regulated by X-box-binding protein 1 (XBP1), an important transcription factor of the unfolded protein response. In this report, we demonstrate that XBP1s can directly induce the transcription of microRNA-148a, which in turn mediates the silencing of Wnt10b mRNA during adipogenic differentiation of 3T3-L1 cells. Stability of Wnt10b mRNA was found to be significantly increased by knockdown of XBP1s. Using computational algorithms, a set of microRNAs was predicted to bind Wnt10b mRNA, of which microRNA-148a was selected as a potential target for XBP1s. Our results revealed that microRNA-148a could bind to the 3′UTR of Wnt10b mRNA. Its ectopic expression significantly suppressed both Wnt10b expression and β-catenin activity. When we altered the expression of XBP1 in 3T3-L1 cells, microRNA-148a levels changed accordingly. A potential XBP1 response element was found in the promoter region of microRNA-148a, and XBP1s directly bound to this response element as shown by point mutation analysis and chromatin immunoprecipitation assay. In addition, a microRNA-148a mimic significantly restored adipogenic potential in XBP1-deficient 3T3-L1 cells. These findings provide the first evidence that XBP1s can regulate Wnt10b by a post-transcriptional mechanism through directly inducing microRNA-148a.

miR-148a is a downstream effector of X-box-binding protein 1 that silences Wnt10b during adipogenesis of 3T3-L1 cells

Wnt10b, an endogenous inhibitor of adipogenesis, maintains preadipocytes in an undifferentiated state by suppressing adipogenic transcription factors. We have previously demonstrated that Wnt10b transcription during adipogenesis is negatively regulated by X-box-binding protein 1 (XBP1), an important transcription factor of the unfolded protein response. In this report, we demonstrate that XBP1s can directly induce the transcription of microRNA-148a, which in turn mediates the silencing of Wnt10b mRNA during adipogenic differentiation of 3T3-L1 cells. Stability of Wnt10b mRNA was found to be significantly increased by knockdown of XBP1s. Using computational algorithms, a set of microRNAs was predicted to bind Wnt10b mRNA, of which microRNA-148a was selected as a potential target for XBP1s. Our results revealed that microRNA-148a could bind to the 3′UTR of Wnt10b mRNA. Its ectopic expression significantly suppressed both Wnt10b expression and β-catenin activity. When we altered the expression of XBP1 in 3T3-L1 cells, microRNA-148a levels changed accordingly. A potential XBP1 response element was found in the promoter region of microRNA-148a, and XBP1s directly bound to this response element as shown by point mutation analysis and chromatin immunoprecipitation assay. In addition, a microRNA-148a mimic significantly restored adipogenic potential in XBP1-deficient 3T3-L1 cells. These findings provide the first evidence that XBP1s can regulate Wnt10b by a post-transcriptional mechanism through directly inducing microRNA-148a.

ISAba15 Inserted into Outer Membrane Protein Gene carO in Acinetobacter baumannii

We identified ISAba15 inserted into the carO gene in an Acinetobacter baumannii isolate. The insert disrupted the lpxD gene, resulting in colistin resistance in A. baumannii. Persistence in carbapenem resistance in A. baumannii isolates with an intact carO gene indicates that loss of the encoded CarO may play a minor role in carbapenem resistance.

A Novel Frameshift Mutation of Galactosidase-alpha in Fabry Disease Restricted to Dermatologic Manifestations

A 28-year-old Asian male was referred for dermatologic evaluation of diffuse bluish-red maculopapules in the lower trunk and genital regions. There was no family history, and with the exception of dispersed skin lesions and hypohidrosis, no other complaints or symptoms were present. Histological evaluation of the skin lesions revealed angiokeratomas. When this combination of clinical and histological findings is observed, Fabry disease is suspected. Biochemical examination performed for definitive diagnosis did not show any activity of the alpha-galactosidase A enzyme. Through identification of a c.182_183ins(GA) mutation of the GLA gene, Fabry disease was diagnosed. However, there was no particular abnormal finding with regard to the evaluation of non-cutaneous manifestations, a symptom that can occur in the progress of this disease. We reported a case of Fabry disease, restricted to the dermatologic presentation, involving a novel frameshift mutation in the GLA gene.

A Novel Frameshift Mutation of Galactosidase-alpha in Fabry Disease Restricted to Dermatologic Manifestations

A 28-year-old Asian male was referred for dermatologic evaluation of diffuse bluish-red maculopapules in the lower trunk and genital regions. There was no family history, and with the exception of dispersed skin lesions and hypohidrosis, no other complaints or symptoms were present. Histological evaluation of the skin lesions revealed angiokeratomas. When this combination of clinical and histological findings is observed, Fabry disease is suspected. Biochemical examination performed for definitive diagnosis did not show any activity of the alpha-galactosidase A enzyme. Through identification of a c.182_183ins(GA) mutation of the GLA gene, Fabry disease was diagnosed. However, there was no particular abnormal finding with regard to the evaluation of non-cutaneous manifestations, a symptom that can occur in the progress of this disease. We reported a case of Fabry disease, restricted to the dermatologic presentation, involving a novel frameshift mutation in the GLA gene.

Psoriasis Induced by Trastuzumab (Herceptin(R))

Trastuzumab (Herceptin), a humanized monoclonal antibody, is a cancer drug developed to target the human epidermal receptor (HER) 2, which is overexpressed in some cancer cells. Cutaneous side effects, such as folliculitis, xerosis, and alopecia have not been reported with therapies targeting HER2, in spite of the frequent observances of such with the therapies targeting the epidermal growth factor receptor. We experienced a patient in whom psoriasis was triggered by the trastuzumab treatment for breast cancer. She was a 57-year-old woman with erythematous and scaly plaques occurring a few months after starting trastuzumab, with repeated aggravation after the re-administration of trastuzumab for the breast cancer. Histologic examination showed the typical features of psoriasis with parakeratosis, epidermal hyperplasia, elongation of the rete ridges, and a lymphocytic and polymorphonuclear cell infiltrate in the dermis. To the best of our knowledge, this is the first report of psoriasis triggered by trastuzumab treatment for breast cancer.

Comparison of Gene Expression Profiles between Keratinocytes, Melanocytes and Fibroblasts

BACKGROUND: The skin has many important functions such as protection, preservation, temperature regulation, and vitamin D synthesis. It is composed of a variety of cell types including keratinocytes, melanocytes and fibroblasts. OBJECTIVE: We attempted to compare the gene expression profiles between keratinocytes, melanocytes and fibroblast, using cDNA microarray. METHODS: Keratinocytes, melanocytes and fibroblasts were primary cultured from five foreskin specimens. Total RNAs were extracted and pooled to reduce the individual variations, and then used for cDNA microarray. RESULTS: Total 12,028 genes were selected as the reliable genes whose expression was detected in at least one of the three cell types. By comparing the relative expression levels with cutoff limitation as a fourfold change, we obtained 126 fibroblast-specific, 179 keratinocyte-specific and 173 melanocyte-specific genes, many of which are known to be characteristically expressed in each cell type. In addition, we identified many genes whose skin-specific functions have not yet been determined. CONCLUSION: Our data provide important information on which to base further investigation into the specification of skin cell types.

Encephalocraniocutaneous Lipomatosis without Neurologic Anomalies

No abstract available.

Pityriasis rosea-like Drug Eruption Induced by Imatinib Mesylate (Gleevec(TM))

Imatinib mesylate (Gleevec(TM), STI571), a selective inhibitor of BCR-ABL, c-Kit, and platelet-derived factor receptor, has been used to treat chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors. Although its use has been associated with various adverse cutaneous reactions, pityriasis rosea-like drug eruptions are rare. Here, we report a case of pityriasis rosea-like drug eruption that developed following the administration of imatinib mesylate to treat CML.

Can Platelet-rich Plasma Be Used for Skin Rejuvenation? Evaluation of Effects of Platelet-rich Plasma on Human Dermal Fibroblast

BACKGROUND: Autologous platelet-rich plasma has attracted attention in various medical fields recently, including orthopedic, plastic, and dental surgeries and dermatology for its wound healing ability. Further, it has been used clinically in mesotherapy for skin rejuvenation. OBJECTIVE: In this study, the effects of activated platelet-rich plasma (aPRP) and activated platelet-poor plasma (aPPP) have been investigated on the remodelling of the extracellular matrix, a process that requires activation of dermal fibroblasts, which is essential for rejuvenation of aged skin. METHODS: Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were prepared using a double-spin method and then activated with thrombin and calcium chloride. The proliferative effects of aPRP and aPPP were measured by [3H]thymidine incorporation assay, and their effects on matrix protein synthesis were assessed by quantifying levels of procollagen type I carboxy-terminal peptide (PIP) by enzyme-linked immunosorbent assay (ELISA). The production of collagen and matrix metalloproteinases (MMP) was studied by Western blotting and reverse transcriptase-polymerase chain reaction. RESULTS: Platelet numbers in PRP increased to 9.4-fold over baseline values. aPRP and aPPP both stimulated cell proliferation, with peak proliferation occurring in cells grown in 5% aPRP. Levels of PIP were highest in cells grown in the presence of 5% aPRP. Additionally, aPRP and aPPP increased the expression of type I collagen, MMP-1 protein, and mRNA in human dermal fibroblasts. CONCLUSION: aPRP and aPPP promote tissue remodelling in aged skin and may be used as adjuvant treatment to lasers for skin rejuvenation in cosmetic dermatology.

Paraneoplastic Panniculitis in a Patient with Acute Myeloid Leukemia / 대한피부과학회지

Panniculitis generally indicates a group of diseases whose hallmark is fibrous thickening and chronic inflammation of subcutaneous fat. Various factors seem to induce a similar pathological histology, and morphological differences can be found among the patients diagnosed with the same disease. Paraneoplastic causes account for 3~10% of the cases of panniculitis. The commonest causes of cancer associated panniculitis are hematological malignancies and mostly lymphomas. In this case, we confirmed acute myeloid leukemia by a blood test and bone marrow examination, and with considering the clinical aspects and pathological findings of the skin lesion, and we finally diagnosed the patient as having panniculitis, which seems to be related with acute myeloid leukemia. The obvious clinical symptoms or pathophysiological features of this rare type of panniculitis are not yet fully known, and so making the differential diagnosis is needed to distinguish this malady from erythema nodosum, erythema induratum and various connective tissue disorders with accompanying erythematous subcutaneous nodules. We diagnosed this very rare and interesting case of paraneoplastic panniculitis that seemed to be generated from acute myeloid leukemia. We report here on this case and we review the relevant literature.

Effects of Calcium on the Epidermis in a Skin Organ Culture / 대한피부과학회지

BACKGROUND: Calcium plays a role in the proliferation and differentiation of keratinocytes. In a normal situation, the calcium concentration forms a gradient across the epidermal layers. Calcium is sparse in the basal layer and spinous layer. Skin organ culture is a useful model for conducting research on various aspects of skin biology. Skin organ culture systems are used for defining factors that affect homeostasis when elucidating the modulatory effects of biologic response modifiers, drugs and physical agents on the skin and also when studying complex aspects of cutaneous biology in normal and diseased skin. OBJECTIVE: In this study, we investigated the effects of extracellular calcium on the epidermis in a skin organ culture. METHODS: We compared the skin organ culture patterns under various culture conditions (calcium 0.1, 0.7, 1.4 and 2.0 mM). RESULTS: H&E staining showed different phenotypes according to the calcium concentration and IHC also showed different phenotyes compared to that of keratin 10, involucrin, filaggrin, loricrin and PCNA. CONCLUSION: As a result, we concluded that the calcium gradient is also an important factor in skin organ culture to maintain the vivo-like environment and the appropriate calcium concentration is 1.4 mM.

The Beneficial Effect on the Early Lumbar Stabilization Exercise after Microdiscectomy

OBJECTIVE: The purpose of this study was to investigate the effect of early 3-D lumbar stabilization exercise to patients with chronic lumbago after microdiscectomy. METHOD: From March 2006 to January 2008, 234 patients(male: 104, female: 130) who underwent lumbar microdis- cectomy were performed CENTAUR lumbar stabilization exercise at 7days postoperatively, CENTAUR was used to measure strength of stabilization muscle. RESULT: As a result after lumbar stabilization exercise for 8weeks, lumbar muscular strength increased by 24% averagely at 8 angles(0 degrees, +45 degrees, -45 degrees, +90 degrees, -90 degrees, +135 degrees, -135 degrees, 180 degrees;+ clockwise, - counterclockwise)(p<0.05). It was possible for the microdiscectomy patients to practice lumbar stabilization exercise at 7days postoperatively. CONCLUSION: The early lumbar stabilization exercise was good effect on the muscular strength after microdiscectomy.

Branchio-Oto-Renal Syndrome / 대한피부과학회지

Branchio-oto-renal (BOR) syndrome is a rare congenital anomaly that is characterized by preauricular pits, branchial fistula and hearing impairment and it is often combined with renal anomalies. BOR syndrome is inherited in an autosomal dominant mode and the mutations of two genes, EYA1 and SIX1, have been identified. We experienced a case of a 14-year-old female who complained of bilateral neck openings and hearing loss that were found at birth the girl's family had a familial tendency for these features. A skin biopsy from the cervical lesion showed the characteristic features of branchial fistula. We report here on a case of BOR syndrome and we review the relevant literature.

A Case of Isolated Plexiform Neurofibroma in a Patient with Myasthenia Gravis

We report a case of an isolated plexiform neurofibroma occurring in a patient with myasthenia gravis. A 48-year-old man presented with asymptomatic skin-colored nodules on the tip of his 4th finger. Microscopically, a plexiform neurofibroma was identified located in the dermis that appeared to originate from small superficial nerves. He had a 20-year history of treated myasthenia gravis; otherwise, his personal and family histories were unremarkable. Given that myasthenia gravis is a disorder of the peripheral nerves, plexiform neurofibromas could be associated with myasthenia gravis. However, the development of an isolated plexiform neurofibroma in a case of myasthenia gravis has not yet been reported. The occurrence of a neurofibromas in a patient with myasthenia gravis suggests a link in the pathogenesis of these two diseases.

Effect of postmenopausal hormone replecement therapy on leptin level and body composition / 대한산부인과학회잡지

OBJECTIVE: To compare the women who use postmenopausal hormone replacement therapy to never user for the serum leptin level and degree of obesity, then evaluate the precausing factor of postmenopausal obesity. METHOD: We checked the serum leptin level, blood chemistry and body composition in three groups, two groups are postmenopause groups which is HRT user (n=125) and HRT never user (n=194), and the other is premenopause groups(n=82). We used SPSS and Excel for analyzed the difference between the groups. RESULT: BMR is decreased after menopause, body fat ratio, abdominal fat ratio, BMI, leptin, sugar, and cholesterol level are increased after menopause. There is no difference between the postmenopausal HRT group and non-HRT group in body fat composition, abdominal fat ratio, BMI,BMR,AMC and leptin levels. Serum sugar level shows positive correlation with the leptin level in pre and postmenopausal women after exclude the effect of body fat ratio. Serum estradiol and leptin level shows positive correlation.(correlation coefficient 0.68 in postmenopausal non-HRT group and 0.735 in postmenopausal HRT group). CONCLUSION: Serum estradiol and sugar level have some correlation with leptin level and leptin resistance in postmenopausal women, and decreased estradiol level caused obesity through increased leptin resistance.

Therapeutic Effects of Low Energy Laser on Acute Phase of Herpes Zoster / 대한피부과학회지

BACKGROUND: Herpes zoster(HZ), caused by reactivation of latent varicella-zoster virus, is manifested by dermatomal distribution of skin rashes, acute pain and post-herpetic neuralgia by pathologic involvement of the sensory ganglia. Low-energy laser(LEL) deliver a small amount of energy without elevation of the tissue temperature. LEL is reported to have various biologic effects such as anti-inflammatory, analgesic, regenerative, antiallergic, immunocorrective, and antibacterial effects. OBJECTIVE: We attempted to evaluate the therapeutic effect of LEL on an acute phase of HZ. METHODS: A total of 60 patients with acute HZ were enrolled in the study. The control group(30 patients) received medications including analgesics, antihistamine, and topical care without LEL irradiation. The experimental group(30 patients) were irradiated with LEL daily for 7 days in addition to the same kinds of medications for the control group. The efficacy of LEL irradiation for HZ was assessed by analyzing changes in skin rashes, pain scores, and postherpetic neuralgia.

Brainstem Infarction Following Snake Bite

Bleeding complications of central nervous system following snake bite are well known. However, nonhemorrhagic manifestations such as ischemic stroke are extremely rare. As far as we know, only four such instances involving middle cerebral artery territory have ever been reported in the literature up to now. A 53-year-old farmer noted right side motor weakness and severe dysarthria 3 hours after a snake bite on right middle finger. Magnetic resonance T2WI showed high signal intensity on left pontine region extending to basal surface and bilateral tegmentum of the pons. He had neither atherogenic risk factors nor cardiogenic embolic sources. Laboratory findings were within normal limits except for mild consumptive coagulopathy. Cerebral angiogram revealed abrupt occlusion of proximal basilar artery. We report a case of brainstem infarction caused by a Korean viper (Agkistrodon blomhoffii brevicaudus) bite and discuss possible mechanisms for cerebral infarction.

Serum Neopterin in Head Injury

Cell-mediated immunity frequently becomes impaired after major trauma. To investigate the immune response of the head injury, the authors measured the level of the serum neopterin, which represents the index of macrophage activation, in 53 head-injured patients. In the injured group the serum neopterin level was 5.4+/-3.1 nmol/l and slightly higher than that of the normal control group, 4.4+/-1.0 nmol/1. In the group of the patients with the Glasgow Coma Scale(GCS) 3-9, the level was significantly higher than the group GCS 10-15. The differences were not significantly related to the age or the presence of intracranial hematoma. It is conceivable that head injury will change the patient's immune response and it may be influenced by neural control.