Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

PURPOSE: Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. MATERIALS AND METHODS: Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated. RESULTS: A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p < 0.001), and the median overall survival (OS) of the high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 months vs. 15.5 months, p < 0.001). Results of multivariate analyses showed significant association of high Romo1 expression with both poor PFS (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.71 to 4.44) and poor OS (HR, 3.99; 95% CI, 2.36 to 6.74). Results of the subgroup analysis showed a similar association regardless of tumor histology. Romo1 expression showed no association with any clinical parameter including age, sex, smoking status, stage, differentiation, or tumor histology. CONCLUSION: Romo1 overexpression was associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting.
Biomarkers ; Carcinoma, Non-Small-Cell Lung* ; Disease-Free Survival ; Drug Therapy* ; Humans ; Immunohistochemistry ; Lung Neoplasms ; Multivariate Analysis ; Platinum ; Prognosis ; Reactive Oxygen Species* ; Smoke ; Smoking

Implant prostheses were classified into screw-retained prosthesis and cement-retained prosthesis by their method of retaining, and there is screw and cement retained implant prosthesis (SCRP) which has been made reflecting the strengths of these two. The advantages of the SCRP technique are easy retrievability and passive fit of implant prostheses. However, the occlusal screw holes of implant prostheses can be thought as a disadvantage with respect to esthetics and occlusion. Inappropriately positioned implants also limited the use of the SCRP technique. The present study is reporting about the case where nine implants (US II, OSSTEM, Seoul, Korea) were placed in maxilla and eight in mandible respectively in fully edentulous patients. Then, the cement-retained prosthesis was applied for the part in which the screw hole positioned improperly, and screw-retained prosthesis for properly positioned implants so that the combined screw-cement prosthesis has been produced where the satisfying result has shown in both function and esthetics. Three-year follow-up has been done for the patient.
Denture, Partial, Fixed ; Esthetics ; Follow-Up Studies ; Humans ; Mandible ; Maxilla ; Prostheses and Implants

Paraneoplastic limbic encephalitis (PLE) is a rare syndrome characterized by memory impairment, affective and behavioral disturbances and seizures. Among many different neoplasms known to cause PLE, small cell lung cancer (SCLC) is the most frequently reported. The pathogenesis is not fully understood but is believed to be autoimmune-related. We experienced a patient with typical clinical features of PLE. A 67-year-old man presented with seizure and disorientation. Brain magnetic resonance imaging demonstrated high signal intensity in the bilateral amygdala and hippocampus in flair and T2-weighted images suggestive of limbic encephalitis. Cerebrospinal fluid tapping revealed no evidence of malignant cells or infection. Positron emission tomography/computed tomography showed a lung mass with pleural effusion and a consequent biopsy confirmed the diagnosis of PLE associated with SCLC. The patient was subsequently treated with chemotherapy and neurologic symptoms gradually improved.
Aged ; Amygdala ; Biopsy ; Brain ; Electrons ; Hippocampus ; Humans ; Limbic Encephalitis ; Lung ; Lung Neoplasms ; Magnetic Resonance Imaging ; Memory ; Neurologic Manifestations ; Paraneoplastic Syndromes ; Pleural Effusion ; Seizures ; Small Cell Lung Carcinoma

Bronchial carcinoid tumors are relatively uncommon neoplasms that are considered to be malignant tumors of low to intermediate grade. They are classified by pathologic features as typical or atypical carcinoids and have distinctly different prognoses and therapeutic options. Surgery is the treatment of choice in typical and atypical carcinoid tumors but the approach has been changing. Recently, several studies have described experiences using other technologies as adjuncts to bronchoscopic resection, technologies such as laser and cryotherapy with curative intent in endoluminal typical carcinoids. Here we present a case of atypical bronchial carcinoid that was treated with bronchoscopic cryotherapy.
Bronchoscopy ; Carcinoid Tumor ; Cryotherapy ; Prognosis

A 35-year-old man, previously hepatitis B surface antigen (HBsAg) carrier, presented with gross hematuria and heavy proteinuria that he had been suffering from for 1 month. Serum creatinine was 4.4 mg/dL. Renal biopsy showed pauci-immune crescentic glomerulonephritis. He received plasmapheresis and was treated with high-dose steroids and cyclophosphamide. Lamivudine was started for the prevention of hepatitis B virus (HBV) activation. Serum creatinine and proteinuria were ameliorated one week after the treatment. There was no sign of HBV activation after six months of treatment. We report a case of rapidly progressive glomerulonephritis in a HBV carrier successfully treated with high dose immunosuppressive therapy and prophylactic lamivudine.
Adult ; Biopsy ; Creatinine ; Cyclophosphamide ; Glomerulonephritis ; Hematuria ; Hepatitis ; Hepatitis B ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Humans ; Lamivudine ; Plasmapheresis ; Proteinuria ; Steroids ; Stress, Psychological

The EGFR plays an essential role in goblet cell hyperplasia and mucus hypersecretion. EGFR has an intrinsic tyrosine kinase activity that, when activated, induces the production of MUC5AC through the signaling kinase cascade in the airway epithelium. We have investigated the effects of an EGFR tyrosine kinase inhibitor, gefitinib, on ovalbumin (OVA)-induced, allergic inflammation in airway epithelia of mice. OVA-sensitized mice were pretreated with gefitinib at two different doses (12.5 and 50 mg/kg) and then challenged with OVA. The OVA challenge increased the total cell count and eosinophil count in bronchoalveolar lavage fluid (BALF), as well as the concentrations of T-helper2 (Th2) cytokines, such as IL-4 and IL-13, overall eosinophil recruitment in the lung tissue and airway hyperresponsiveness (AHR). Pretreatment with gefitinib reduced the inflammatory cell counts and released cytokine concentrations (IL-4 and IL-13) in BALF, as well as eosinophil recruitment in the lungs and AHR, in a dose-dependent manner. This was associated with decreased EGFR and Akt phosphorylation. We showed that gefitnib inhibits EGFR and phosphoinositol 3'-kinase (PI3K)/Akt activation which were activated in OVA sensitized mice. These findings suggest that inhibitors of the EGFR cascade may have a role in the treatment of asthma.
Animals ; Antineoplastic Agents/*therapeutic use ; Bronchoalveolar Lavage Fluid/cytology ; Cytokines/biosynthesis ; Enzyme Activation ; Eosinophils/cytology ; Goblet Cells/pathology ; Inflammation/drug therapy/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Quinazolines/*therapeutic use ; Receptor, Epidermal Growth Factor/*antagonists & inhibitors/metabolism ; Respiratory Hypersensitivity/*drug therapy/etiology/metabolism ; Respiratory Mucosa/drug effects/pathology