Immunoglobulin G4-Related Kidney Disease with Membranous Proliferative Glomerulonephritis Presenting with a Renal Pelvic Mass / 대한내과학회지

Immunoglobulin G4 (IgG4)-related kidney disease is a chronic immune-mediated fibro-inflammatory disorder characterized by multiple organ infiltration with IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis or tumefactive lesions. Previous studies have explored IgG4-related kidney disease, increasing our understanding of its clinical manifestations, and pathological and radiologic findings. However, IgG4-related kidney disease can be misdiagnosed since it mimics malignancies. We report a case of a 77-year-old Korean man diagnosed with IgG4-related kidney disease with membranous proliferative glomerulonephritis, presenting with a renal pelvic mass suspected of being malignant.

Immunoglobulin G4-Related Kidney Disease with Membranous Proliferative Glomerulonephritis Presenting with a Renal Pelvic Mass / 대한내과학회지

Immunoglobulin G4 (IgG4)-related kidney disease is a chronic immune-mediated fibro-inflammatory disorder characterized by multiple organ infiltration with IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis or tumefactive lesions. Previous studies have explored IgG4-related kidney disease, increasing our understanding of its clinical manifestations, and pathological and radiologic findings. However, IgG4-related kidney disease can be misdiagnosed since it mimics malignancies. We report a case of a 77-year-old Korean man diagnosed with IgG4-related kidney disease with membranous proliferative glomerulonephritis, presenting with a renal pelvic mass suspected of being malignant.

The nature of triple-negative breast cancer classification and antitumoral strategies

Identifying the patterns of gene expression in breast cancers is essential to understanding their pathophysiology and developing anticancer drugs. Breast cancer is a heterogeneous disease with different subtypes determined by distinct biological features. Luminal breast cancer is characterized by a relatively high expression of estrogen receptor (ER) and progesterone receptor (PR) genes, which are expressed in breast luminal cells. In ~25% of invasive breast cancers, human epidermal growth factor receptor 2 (HER2) is overexpressed; these cancers are categorized as the HER2 type. Triple-negative breast cancer (TNBC), in which the cancer cells do not express ER/PR or HER2, shows highly aggressive clinical outcomes. TNBC can be further classified into specific subtypes according to genomic mutations and cancer immunogenicity. Herein, we discuss the brief history of TNBC classification and its implications for promising treatments.

The nature of triple-negative breast cancer classification and antitumoral strategies

Identifying the patterns of gene expression in breast cancers is essential to understanding their pathophysiology and developing anticancer drugs. Breast cancer is a heterogeneous disease with different subtypes determined by distinct biological features. Luminal breast cancer is characterized by a relatively high expression of estrogen receptor (ER) and progesterone receptor (PR) genes, which are expressed in breast luminal cells. In ~25% of invasive breast cancers, human epidermal growth factor receptor 2 (HER2) is overexpressed; these cancers are categorized as the HER2 type. Triple-negative breast cancer (TNBC), in which the cancer cells do not express ER/PR or HER2, shows highly aggressive clinical outcomes. TNBC can be further classified into specific subtypes according to genomic mutations and cancer immunogenicity. Herein, we discuss the brief history of TNBC classification and its implications for promising treatments.

Peritoneal Fluid Cytology of Disseminated Large Cell Neuroendocrine Carcinoma Combined with Endometrioid Adenocarcinoma of the Endometrium

No abstract available.

Epstein-Barr virus-positive mucocutaneous ulcer colliding with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (malt lymphoma) that developed in the palatine tonsils of an immunocompetent patient after gastric lymphoma relapse

No abstract available.

Cocaine- and Amphetamine-Regulated Transcript (CART) Peptide Plays Critical Role in Psychostimulant-Induced Depression

Cocaine- and amphetamine-regulated transcript (CART) peptide is a widely distributed neurotransmitter expressed in the central nervous systems. Previously, several reports demonstrated that nucleus accumbal-injected CART peptide positively modulated behavioral sensitization induced by psychostimulants and regulated the mesocorticolimbic dopaminergic pathway. It is confirmed that CART peptide exerted inhibitory effect on psychostimulant-enhanced dopamine receptors signaling, Ca2+/calmodulin-dependent kinase signaling and crucial transcription factors expression. Besides modulation of dopamine receptors-related pathways, CART peptide also exhibited elaborated interactions with other neurotransmitter receptors, such as glutamate receptors and γ-aminobutyric acid receptors, which further account for attribution of CART peptide to inhibition of psychostimulant-potentiated locomotor activity. Recently, CART peptide has been shown to have anxiolytic functions on the aversive mood and uncontrolled drug-seeking behaviors following drug withdrawal. Moreover, microinjection of CART peptide has been shown to have an anti-depressant effect, which suggests its potential utility in the mood regulation and avoidance of depression-like behaviors. In this review, we discuss CART pathways in neural circuits and their interactions with neurotransmitters associated with psychostimulant-induced depression.

A case of adult T-cell leukemia/lymphoma in Korea

No abstract available.

Bosentan and Rifampin Interactions Modulate Influx Transporter and Cytochrome P450 Expression and Activities in Primary Human Hepatocytes

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with 20 μM bosentan+200 μM rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by SA-β-gal staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.

Human Herpes Virus 8/Epstein-Barr Virus–Copositive, Plasmablastic Microlymphoma Arising in Multicentric Castleman's Disease of an Immunocompetent Patient

No abstract available.

Unmasking Granulomatous Pneumocystis jirovecii Pneumonia with Nodular Opacity in an HIV-Infected Patient after Initiation of Antiretroviral Therapy

Pneumocystis jirovecii pneumonia (PJP) in patients with HIV infection can, in rare cases, present with pulmonary nodules that histologically involve granulomatous inflammation. This report describes an intriguing case of granulomatous PJP with pulmonary nodules after commencing antiretroviral therapy (ART) in an HIV-infected patient without respiratory signs or symptoms. Diagnosis of granulomatous PJP was only achieved through thoracoscopic lung biopsy. This case suggests that granulomatous PJP should be considered in the differential diagnosis of pulmonary nodules in HIV-infected patients for unmasking immune reconstitution inflammatory syndrome manifestation after initiation of ART.

Primary Pulmonary Amyloidosis with Mediastinal Lymphadenopathy

We report a case of inadvertent hoarseness after surgery for primary pulmonary amyloidosis. A 55-year-old male was transferred to our facility due to a lung mass. Chest computed tomography revealed a solitary pulmonary nodule. Positron emission tomography-computed tomography showed fluorodeoxyglucose uptake in the main mass and in the mediastinal lymph nodes. To confirm the pathology of the mass, wedge resection and thorough lymph node dissection were performed via video-assisted thoracic surgery (VATS). No complications except for hoarseness were observed; hoarseness developed soon after surgery and lasted for 3 months. The main mass was diagnosed as amyloidosis, but this was not found in the lymph nodes. In conclusion, VATS wedge resection for peripheral amyloidosis is a feasible and safe procedure. However, mediastinal lymph node dissection is not recommended unless there is evidence of a clear benefit.

Vitamin C Stimulates Epidermal Ceramide Production by Regulating Its Metabolic Enzymes

Ceramide is the most abundant lipid in the epidermis and plays a critical role in maintaining epidermal barrier function. Overall ceramide content in keratinocyte increases in parallel with differentiation, which is initiated by supplementation of calcium and/or vitamin C. However, the role of metabolic enzymes responsible for ceramide generation in response to vitamin C is still unclear. Here, we investigated whether vitamin C alters epidermal ceramide content by regulating the expression and/or activity of its metabolic enzymes. When human keratinocytes were grown in 1.2 mM calcium with vitamin C (50 mug/ml) for 11 days, bulk ceramide content significantly increased in conjunction with terminal differentiation of keratinocytes as compared to vehicle controls (1.2 mM calcium alone). Synthesis of the ceramide fractions was enhanced by increased de novo ceramide synthesis pathway via serine palmitoyltransferase and ceramide synthase activations. Moreover, sphingosine-1-phosphate (S1P) hydrolysis pathway by action of S1P phosphatase was also stimulated by vitamin C supplementation, contributing, in part, to enhanced ceramide production. However, activity of sphingomyelinase, a hydrolase enzyme that converts sphingomyelin to ceramide, remained unaltered. Taken together, we demonstrate that vitamin C stimulates ceramide production in keratinocytes by modulating ceramide metabolic-related enzymes, and as a result, could improve overall epidermal barrier function.

Poorly Differentiated Thyroid Carcinoma with Gross Internal Jugular Vein Invasion and Multiple Lung Metastases / 대한갑상선학회지

A rare case of poorly differentiated thyroid carcinoma (PDTC) with gross intraluminal invasion to the internal jugular vein whose clinical manifestation was multiple lung metastases is described. A 66-year-old man was referred to the outpatient clinic of the Department of Internal Medicine, hemato-oncology subdivision for multiple lung nodules found by his regular health check-up. These lung nodules showed variable sizes with irregular shapes, and typical distributions throughout the parenchyma, which were consistent with metastatic nodules. Ultrasonography revealed a 4.5 cm sized hypoechoic mass with irregular shape in his left thyroid lobe and a huge thrombus in the left internal jugular vein. PDTCs associated with gross intraluminal invasion to the great cervical vein and multiple lung nodules as their first clinical manifestation are extremely rare. We would emphasize the importance of preoperative detailed evaluation of the disseminated disease by ultrasonography in suspected patients.

Measurement of Human Cytochrome P450 Enzyme Induction Based on Mesalazine and Mosapride Citrate Treatments Using a Luminescent Assay

Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their inter-assay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.

Mixed gonadal dysgenesis in 45,X Turner syndrome with SRY gene

Turner syndrome is the most common chromosomal disorder in girls. Various phenotypic features show depending upon karyotype from normal female through ambiguous genitalia to male. Usually, Turner girls containing 45,X/46,XY mosaicism, or sex-determining region Y (SRY) gene may have mixed gonadal dysgenesis with various external sexual differentiation. We experienced a short statured 45,X Turner girl with normal external genitalia. Because SRY gene was positive, laparoscopic gonadectomy was performed. The dysgenetic gonads revealed bilateral ovotesticular tissues. The authors report a mixed gonadal dysgenesis case found in clinical 45,X Turner patient with positive SRY gene. Screening for SRY gene should be done even the karyotype is 45,X monosomy and external genitalia is normal.

Characterization of Two Novel mAbs Recognizing Different Epitopes on CD43

JL1, a specific epitope on CD43, is a potential biomarker for the diagnosis of acute leukemia. Although qualitative assays for detecting leukemia-specific CD43 exist, there is a need to develop quantitative assays for the same. Here, we developed two novel monoclonal antibodies (mAbs), 2C8 and 8E10, recognizing different epitopes on CD43. These clones are capable of pairing with YG5, another mAb against JL1 epitope, because they were selectively obtained using sandwich ELISA. Antigens recognized by 2C8 and 8E10 were confirmed as CD43 by western blotting using the CD43-hFC recombinant protein. When expression on various leukemic cell lines was investigated, 2C8 and 8E10 displayed a disparity in the distribution of the epitope. Enzyme assays revealed that these mAbs recognized a sialic acid-dependent epitope on CD43. Using normal thymus and lymph node paraffin-embedded tissues, we confirmed a difference in the epitopes recognized by the two mAbs that was predicted based on the maturity of the cells in the tissue. In summary, we developed and characterized two mAbs, 2C8 and 8E10, which can be used with YG5 in a sandwich ELISA for detecting leukemia-specific CD43.

Infratentorial and Intraparenchymal Subependymoma in the Cerebellum: Case Report

Subependymomas are rare benign tumors located in the ventricular system. Intraparenchymal subependymoma is extremely rare; only 6 cases have been reported, and all were located in the supratentorial region. We describe a case of infratentorial, intraparenchymal subependymoma in a 28-year-old man with intermittent headache. Imaging revealed a well-demarcated cystic and solid cerebellar mass near the fourth ventricle. The mass had a microcystic component and calcification without contrast enhancement. Complete surgical excision was performed, and histopathology confirmed a subependymoma.

Localized Thymic Amyloidosis Presenting with Myasthenia Gravis: Case Report

A mediastinal mass was incidentally found on chest radiography in a 46-yr-old woman who had had myasthenia gravis (MG) for 2 months. Computed tomography revealed a 4-cm in size, well-defined, and lobulating mass with nodular calcification that was located in the thymus. Microscopically, the mass consisted of diffuse amorphous eosinophilic materials. These deposits exhibited apple-green birefringence under polarized light microscopy after Congo red staining. Immunohistochemical analysis revealed that they were positive for both kappa and lambda light chains and negative for amyloid A. A diagnosis of localized primary thymic amyloidosis was finally made. After thymectomy, the symptoms of MG were controlled with reduced corticosteroid requirements. Localized thymic amyloidosis associated with MG has not been reported to date.