Brain abscesses developing at the site of intracerebral hemorrhage are very rare. We report a 78-... more Brain abscesses developing at the site of intracerebral hemorrhage are very rare. We report a 78-year-old man who had a left frontal lobe hemorrhage resulting in right hemiparesis. At that time, he also had a urinary tract infection. Three weeks later, his right hemiparesis worsened and motor aphasia developed. Brain MRI and contrast-enhanced CT revealed a brain abscess in the same region as the earlier hemorrhage. The patient recovered after drainage of the abscess and treatment with antibiotics. Although very rare, an abscess can develop at the site of an earlier intracerebral hemorrhage.
Although gouty arthritis is a common metabolic disorder, and the gouty tophi may be deposited in ... more Although gouty arthritis is a common metabolic disorder, and the gouty tophi may be deposited in the joints and juxtaarticular connective tissue, its affliction of the axial spine is relatively rare. We present therefore a rare case of lumbosacral extradural spinal gout. The patient had a long history of peripheral polyarticular gout without regular medical control. The clinical manifestation was subacute left radiculopathy which mimicked an infectious process. Surgical decompression was performed and the histopathological examination showed tophaceous gout deposition. The clinical, radiological and pathological features are discussed. If a gout patient develops symptoms indicative of spinal cord compression, spinal gout should be included in differential diagnosis.
Die Hirnmetastasen gehoren zu den gefurchteten Komplikationen des Mammakarzinoms [8, 29, 31, 32].... more Die Hirnmetastasen gehoren zu den gefurchteten Komplikationen des Mammakarzinoms [8, 29, 31, 32]. Die Hirnmetastasen von Mammakarzinomen werden heute wegen der Erfolge der Kombinationsbehandlung des Mammakarzinoms selbst und der damit verbundenen langeren Uberlebenszeit haufiger gesehen als fruher [24, 25, 26, 35, 36]. Trotz dieser Haufigkeitszunahme ist unser Wissen uber die Ergebnisse der neurochirurgischen Behandlung der zerebralen Metastasen des Mammakarzinoms noch gering. Ziel dieser Arbeit ist, folgende Fragen zu untersuchen: Welche Charakteristika haben diese Patientinnen aus neurochirurgischer Sicht? Welchen Erfolg hat die operative Behandlung dieser zerebralen Metastasen? Was sind die Operationsindikationen und die prognostisch bedeutsamen Faktoren?
Journal of Cancer Research and Practice, Jun 1, 2016
Background: To assess postoperative rhinological complaints, length of hospital stay and complica... more Background: To assess postoperative rhinological complaints, length of hospital stay and complications related to endoscopic, endonasal trans-sphenoidal procedures. Patients and methods: From May 2001 through May 2007, a retrospective analysis was conducted on a series of 39 patients that underwent endonasal surgery and 9 patients that had craniotomy removal of pituitary tumors. Questionnaires were filled out at both 2 weeks and 3 months after surgery, most of which were completed in the outpatient department if the patient was discharged. Nasal packing lasted for 72 h in 29 patients, but not in the last 10 patients. Results: Of the 12 patients with preoperative headache, 50% had complete resolution, 33% had partial resolution and 17% reported no change. The frequency of rhinological complaints declined between the two questionnaires (p < .001). After 3 months, 64e84% of patients had no rhinological complaints, while 2.5% had severe complaints. Of the 9 patients with complications, rhinological complaint severity was similar to those without complications (p < .001). Conclusions: The direct endonasal trans-sphenoidal approach for pituitary fossa tumor is associated with a rapid rhinological recovery, shorter hospital stay and a low occurrence of serious long-term sinonasal complaints.
Journal of Neuropathology and Experimental Neurology, May 1, 1993
Human neuroblastoma cells, LAN, were used to study the phosphorylation and dephosphorylation of t... more Human neuroblastoma cells, LAN, were used to study the phosphorylation and dephosphorylation of tau proteins.
Objective: The value of methylprednisolone (MP) treatment in acute traumatic spinal cord injury (... more Objective: The value of methylprednisolone (MP) treatment in acute traumatic spinal cord injury (SCI) remains controversial. We attempted to evaluate the utilization of resources, motor function recovery and adverse effect after the use of MP. Methods: We compared 13 demographic and clinical characteristics between MP and non-MP treatment groups in 110 patients with acute traumatic SCI treated in hospitals between June 1st, 2000 and May 31st, 2001, and analyzed 10 short-term outcome variables. These demographic and clinical characteristics included age, cause of injury, number of associated injuries, Revised Trauma Score, Glasgow Coma Scale, mean blood pressure, level/completeness and pattern of SCI, number and types of spinal surgeries, frequency of rehabilitation therapy and the time interval between trauma and admission. Results: The MP (64.5%) and non-MP (35.5%) treatment groups showed no significant differences in all characteristics except the time interval between trauma and admission (P=0.024). MP treatment was associated with a higher frequency of infectious complications (P=0.038), but there was no difference between the two treatment groups in other outcome parameters. The results of analysis stratified by dosage of MP showed that the length of ICU stay (P=0.021) and the number of tracheostomies (P=0.005) and pneumonia cases (P=0.004) were increased significantly in the standard dose group. Conclusions: Although the rate of infection had risen in patients receiving MP, the steroid treatment did not significantly increase utilization of resources during hospitalization and appeared safe in terms of mortality. However, it had not been proven to improve motor function recovery.
Background: Meningioma is one of the most common primary brain neoplasms with poor outcomes. The ... more Background: Meningioma is one of the most common primary brain neoplasms with poor outcomes. The present study was aimed to determine clinical and surgical characteristics of intracranial meningiomas associated with tumor recurrence and complications. Methods: A total of 138 patients undergoing surgical resection of intracranial meningiomas between Jan 2003 and Dec 2014 were included and followed for the period of at least 12 months. The demographic and clinical characteristics possibly associated with tumor recurrence were assessed, including age, gender, clinical symptoms, pathology data, tumor parameters, preoperative and postoperative Karnofsky Performance Scale (KPS), complications and recurrence rate. Results: One hundred and twenty one lesions were benign (classified as Grade I) and 17 were atypical/ malignant (classified as Grade II/III). The patients were of a mean age of 60.5 years and a mean follow-up duration of 36.8 months (range, 16.3e62.9 months). The 1, 3, 5-year recurrence/tumor enlargement rates were 3.4%, 7.2%, and 15.7%, respectively. In multivariate analysis, symptoms of disturbance of consciousness and palpable cranial mass were associated with increased recurrence/tumor enlargement. In addition, patients with Simpson grade IV were more likely to have recurrence/tumor enlargement. Conclusion: The pattern of intracranial meningioma in this series is typical to other studies. Presenting symptoms is suggested to be predictive of recurrence.
Aging is a complex biological process. A study of pyrroline-5-carboxylate reductase 1 (PYCR1) def... more Aging is a complex biological process. A study of pyrroline-5-carboxylate reductase 1 (PYCR1) deficiency, which causes a progeroid syndrome, may not only shed light on its genetic contribution to autosomal recessive cutis laxa (ARCL) but also help elucidate the functional mechanisms associated with aging. In this study, we used RNA-Seq technology to examine gene expression changes in primary skin fibroblasts from healthy controls and patients with PYCR1 mutations. Approximately 22 and 32 candidate genes were found to be up-and downregulated, respectively, in fibroblasts from patients. Among the downregulated candidates in fibroblasts with PYCR1 mutations, a strong reduction in the expression of 17 genes (53.1%) which protein products are localized in the extracellular space was detected. These proteins included several important ECM components, periostin (POSTN), elastin (ELN), and decorin (DCN); genetic mutations in these proteins are associated with different phenotypes of aging, such as cutis laxa and joint and dermal manifestations. The differential expression of ten selected extracellular space genes was further validated using quantitative RT-PCR. Ingenuity Pathway Analysis revealed that some of the affected genes may be associated with cardiovascular system development and function, dermatological diseases and conditions, and cardiovascular disease. POSTN, one of the most downregulated gene candidates in affected individuals, is a matricellular protein with pivotal functions in heart valvulogenesis, skin wound healing, and brain development. Perturbation of PYCR1 expression revealed that it is positively correlated with the POSTN levels. Taken together, POSTN might be one of the key molecules that deserves further investigation for its role in this progeroid neurocutaneous syndrome.
We report a case of subdural metastasis in which the clinical features and associated images mimi... more We report a case of subdural metastasis in which the clinical features and associated images mimic chronic subdural hematoma. Despite a known history of systemic metastasis of adenocarcinoma, the initial diagnosis and treatment were directed toward chronic subdural hematoma. During burr-hole operation, the subdural space was found to be filled will solid tumor rather than chronic hematoma. Pathology examination confirmed metastatic adenocarcinoma. The patient received subsequent whole brain irradiation and died 3 months after operation. Similar situations have rarely been reported in the literature. CT and MRI with enhancement can be adequate tools for differential diagnosis. On the other hand, chronic subdural hematoma may be a presentation of dural metastasis or a target of metastasis. We conclude that if a patient has history of cancer, subdural metastasis should be considered and brain CT or MRI be performed with contrast enhancement when making differential diagnosis of subdura...
s-14th World Congress on Disaster and Emergency Medicine sl3 guidelines represent the first natio... more s-14th World Congress on Disaster and Emergency Medicine sl3 guidelines represent the first national, evidence-based standards for pediatric disaster and terrorism preparedness. The methodology used to develop the guidelines and recommendations in the current report was one of a previously validated, evidenced-based, consensus process used in prior studies, supplemented by a modified Delphi approach for topic selection. Experts from multiple disciplines and areas of expertise involved in the planning for and care of children during times of disaster and/or terrorist events were convened for the discussion. There were several goals of this process: 1. To build collaboration among individuals with expertise in pediatrics, pediatric emergency medicine, pediatric critical care, pediatric surgery, and emergency management (including disaster planning, management, and response); 2. To review and summarize the existing data on the needs of children in disaster planning, preparation, and response; 3. To develop evidence-based guidelines and recommendations on the needs of children in disasters, and develop evidence-based consensus guidelines for dealing with the gaps in the evidence; and 4. To create a research agenda to address knowledge gaps based on the limited data that exist on the needs of children in disasters. The final recommendations of the conference focused on three major areas: (1) emergency and prehospital care; (2) hospital care; and (3) terrorism preparedness and response, including biological terrorism, chemical terrorism, radiological terrorism, physical protection, decontamination, and the Strategic National Stockpile (SNS).
The presence of protein aggregates or inclusion bodies in the neurons or glial cells is one of th... more The presence of protein aggregates or inclusion bodies in the neurons or glial cells is one of the pathological hallmarks of neurodegenerative diseases, such as tauopathy in Alzheimer's diseases (AD). Infectious agents or unknown etiological factors may cause de novo misfolding of peptides or proteins to form proteinaceous seeds or oligomers. These protein seeds lead to self-propagation of pathologic aggregates that impair neuronal functions at different brain regions for causing specific neurological diseases. 1 Substantial evidence reveals that tumor suppressor WW domain-containing oxidoreductase, designated WWOX, FOR or WOX1, controls protein aggregation in the human brain. 2 Downregulation of WWOX appears to start in the middle ages that leads to the slow progression of neurodegeneration. 2 WWOX is a multi-functional molecule involved in cell signaling, cancer progression, metabolic disorders, and neural diseases. 2 When WWOX protein is totally lost due to alteration of WWOX/Wwox gene such as missense or nonsense mutation and deletion, neural disorders, and metabolic diseases occur in vivo, including ataxia, epilepsy, dementia, neurodegeneration, growth retardation, abnormal HDL lipid metabolism, and early death. 2,3 WWOX blocks neurodegeneration by binding tau and tau-hyperphosphorylating enzymes GSK3β, ERK, and JNK1, (refs 4-6) and promotes neuronal differentiation. 5 WWOX interacts with ERK and JNK1 via its N-terminal first WW domain, but binds tau and GSK3β via C-terminal short-chain alcohol dehydrogenase/reductase (SDR) domain. 4,5 A portion of WWOX is in the mitochondria, so as to maintain the normal cell physiology. The SDR domain appears to have a key role in the mitochondrial homeostasis. 4-6 WWOX is frequently downregulated in the AD hippocampi. 2,4 This downregulation results in spontaneous relocation of TGFβ1-induced antiapoptotic factor 1 (TIAF1) and TRAPPC6AΔ (trafficking protein particle complex 6A delta, TPC6AΔ) to the mitochondria and both proteins become aggregated (see Figure 1). 6,7 These aggregated proteins activate caspases, which leads to
Globoid cell leukodystrophy (GLD) is an autosomal recessive, lysosomal storage disease caused by ... more Globoid cell leukodystrophy (GLD) is an autosomal recessive, lysosomal storage disease caused by deficiency of the enzyme galactocerebrosidase (GALC). The absence of GALC activity leads to the accumulation of the toxic substance psychosine and the preferential loss of myelinating cells in the central and peripheral nervous systems. Profound demyelination, astrogliosis and axonopathy are the hallmarks of the pathogenesis of GLD, and cerebellar ataxia is one of the dominant manifestations in adolescents and adults affected with GLD. To date, studies regarding cerebellar degeneration in GLD are limited. In this study, the efficacy of cerebellum-targeted gene therapy on the cerebellar neuropathology in twitcher mice (a murine model of GLD) has been validated. We observed degeneration of Purkinje cells, Bergmann glia, and granule cells in addition to astrocytosis and demyelination in the cerebellum of the twitcher mice. Ultrastructural analysis revealed dark cell degeneration and disintegration of the cellular composition of Purkinje cells in untreated twitcher mice. In addition, the expressions of neurotrophic factors CNTF, GDNF and IGF-I were up-regulated and the expression of BDNF was down-regulated. Intracerebellar-mediated gene therapy efficiently corrected enzymatic deficiency by direct transduction to Purkinje cells and cross-correction in other cell types in the cerebellum, leading to the amelioration of both neuroinflammation and demyelination. The population, dendritic territory, and axonal processes of Purkinje cells remained normal in the cerebellum of treated twitcher mice, where radial fibers of Bergmann glia spanned the molecular layer and collateral branches ensheathed the dendritic processes of Purkinje cells. Moreover, the aberrant expressions of neurotrophic factors were mitigated in the cerebellum of treated twitcher mice, indicating the preservation of cellular function in addition to maintaining the neuronal architecture. The life span of the treated twitcher mice was significantly prolonged and their neurobehavioral performance was improved. Taken together, our findings underscore the complexity of cerebellar neurodegeneration in GLD and highlight the potential effectiveness of gene therapy in mitigating neuropathological deficits in GLD and other neurodegenerative disorders in which Purkinje cells are involved.
Self-aggregation of transforming growth factor β (TGF-β)1-induced antiapoptotic factor (TIAF1) is... more Self-aggregation of transforming growth factor β (TGF-β)1-induced antiapoptotic factor (TIAF1) is known in the nondemented human hippocampus, and the aggregating process may lead to generation of amyloid β (Aβ) for causing neurodegeneration. Here, we determined that overexpressed TIAF1 exhibits as aggregates together with Smad4 and Aβ in the cancer stroma and peritumor capsules of solid tumors. Also, TIAF1/Aβ aggregates are shown on the interface between brain neural cells and the metastatic cancer cell mass. TIAF1 is upregulated in developing tumors, but may disappear in established metastatic cancer cells. Growing neuroblastoma cells on the extracellular matrices from other cancer cell types induced production of aggregated TIAF1 and Aβ. In vitro induction of TIAF1 self-association upregulated the expression of tumor suppressors Smad4 and WW domain-containing oxidoreductase (WOX1 or WWOX), and WOX1 in turn increased the TIAF1 expression. TIAF1/Smad4 interaction further enhanced Aβ...
The role of a small transforming growth factor beta (TGF-β)-induced TIAF1 (TGF-β1-induced antiapo... more The role of a small transforming growth factor beta (TGF-β)-induced TIAF1 (TGF-β1-induced antiapoptotic factor) in the pathogenesis of Alzheimer's disease (AD) was investigated. TIAF1 physically interacts with mothers against DPP homolog 4 (Smad4), and blocks SMAD-dependent promoter activation when overexpressed. Accordingly, knockdown of TIAF1 by small interfering RNA resulted in spontaneous accumulation of Smad proteins in the nucleus and activation of the promoter governed by the SMAD complex. TGF-β1 and environmental stress (e.g., alterations in pericellular environment) may induce TIAF1 self-aggregation in a type II TGF-β receptor-independent manner in cells, and Smad4 interrupts the aggregation. Aggregated TIAF1 induces apoptosis in a caspase-dependent manner. By filter retardation assay, TIAF1 aggregates were found in the hippocampi of nondemented humans and AD patients. Total TIAF1-positive samples containing amyloid β (Aβ) aggregates are 17 and 48%, respectively, in the...
... [ ] 9.K. Goel, YE Kim, TH Lim, ³An analytical investigation of the ... J. Spinal Disord. Tech... more ... [ ] 9.K. Goel, YE Kim, TH Lim, ³An analytical investigation of the ... J. Spinal Disord. Tech., 2004 (In press) [19]CK Cheng, WJ Chen, CS Chen, SC Chueh, CC Wang, ³Failure analysis of pedicle screw breakage on spinal instrumentation´. Med. ... [27]DY Cho, WR Liau, WY Lee, JT Liu ...
Tumor suppressor WWOX inhibits cancer growth and retards Alzheimer’s disease (AD) progression. Su... more Tumor suppressor WWOX inhibits cancer growth and retards Alzheimer’s disease (AD) progression. Supporting evidence shows that the more strongly WWOX binds intracellular protein partners, the weaker is cancer cell growth in vivo. Whether this correlates with retardation of AD progression is unknown. Two functional forms of WWOX exhibit opposite functions. pY33-WWOX is proapoptotic and anticancer, and is essential for maintaining normal physiology. In contrast, pS14-WWOX is accumulated in the lesions of cancers and AD brains, and suppression of WWOX phosphorylation at S14 by a short peptide Zfra abolishes cancer growth and retardation of AD progression. In parallel, synthetic Zfra4-10 or WWOX7-21 peptide strengthens the binding of endogenous WWOX with intracellular protein partners leading to cancer suppression. Indeed, Zfra4-10 is potent in restoring memory loss in triple transgenic mice for AD (3xTg) by blocking the aggregation of amyloid beta 42 (Aβ42), enhancing degradation of agg...
doi: 10.3389/fonc.2013.00043 Tumor suppressorWWOX and p53 alterations and drug resistance in glio... more doi: 10.3389/fonc.2013.00043 Tumor suppressorWWOX and p53 alterations and drug resistance in glioblastomas
Primary central nerve system lymphoma (PCNSL) represents approximately 1% of all intracranial neo... more Primary central nerve system lymphoma (PCNSL) represents approximately 1% of all intracranial neoplasms. Although an early and reliable diagnosis of PCNSL is important to rapidly initiate optimal therapy, atypical cases complicate the differential diagnosis by clinicians and radiologists. Here, we report a 48-year-old male patient of PCNSL with tumoral bleeding and ocular involvement. He suffered from progressive blurred vision and was diagnosed with brain tumoral bleeding at the right temporal lobe. The pathological report showed diffuse large B-cell lymphoma after he received brain surgery. The postoperative course was uneventful. The present case reconfirms the importance of imaging study and clinical presentation in diagnosis of PCNSL, and that histopathologic examination following brain biopsy is necessary for a correct diagnosis.
Dysfunction of mitochondria causes defects in oxidative phosphorylation system (OXPHOS) and incre... more Dysfunction of mitochondria causes defects in oxidative phosphorylation system (OXPHOS) and increased production of reactive oxygen species (ROS) triggering the activation of the cell death pathway that underlies the pathogenesis of aging and various diseases. The process of autophagy to degrade damaged cytoplasmic components as well as dysfunctional mitochondria is essential for ensuring cell survival. We analyzed the role of autophagy inpatient-specific induced pluripotent stem (iPS) cells generated from fibroblasts of patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with well-characterized mitochondrial DNA mutations and distinct OXPHOS defects. MELAS iPS cells recapitulated the pathogenesis of MELAS syndrome, and showed an increase of autophagy in comparison with its isogenic normal counterpart, whereas mitophagy is very scarce at the basal condition. Our results indicated that the existence of pathogenic mtDNA alone in mitochondri...
Brain abscesses developing at the site of intracerebral hemorrhage are very rare. We report a 78-... more Brain abscesses developing at the site of intracerebral hemorrhage are very rare. We report a 78-year-old man who had a left frontal lobe hemorrhage resulting in right hemiparesis. At that time, he also had a urinary tract infection. Three weeks later, his right hemiparesis worsened and motor aphasia developed. Brain MRI and contrast-enhanced CT revealed a brain abscess in the same region as the earlier hemorrhage. The patient recovered after drainage of the abscess and treatment with antibiotics. Although very rare, an abscess can develop at the site of an earlier intracerebral hemorrhage.
Although gouty arthritis is a common metabolic disorder, and the gouty tophi may be deposited in ... more Although gouty arthritis is a common metabolic disorder, and the gouty tophi may be deposited in the joints and juxtaarticular connective tissue, its affliction of the axial spine is relatively rare. We present therefore a rare case of lumbosacral extradural spinal gout. The patient had a long history of peripheral polyarticular gout without regular medical control. The clinical manifestation was subacute left radiculopathy which mimicked an infectious process. Surgical decompression was performed and the histopathological examination showed tophaceous gout deposition. The clinical, radiological and pathological features are discussed. If a gout patient develops symptoms indicative of spinal cord compression, spinal gout should be included in differential diagnosis.
Die Hirnmetastasen gehoren zu den gefurchteten Komplikationen des Mammakarzinoms [8, 29, 31, 32].... more Die Hirnmetastasen gehoren zu den gefurchteten Komplikationen des Mammakarzinoms [8, 29, 31, 32]. Die Hirnmetastasen von Mammakarzinomen werden heute wegen der Erfolge der Kombinationsbehandlung des Mammakarzinoms selbst und der damit verbundenen langeren Uberlebenszeit haufiger gesehen als fruher [24, 25, 26, 35, 36]. Trotz dieser Haufigkeitszunahme ist unser Wissen uber die Ergebnisse der neurochirurgischen Behandlung der zerebralen Metastasen des Mammakarzinoms noch gering. Ziel dieser Arbeit ist, folgende Fragen zu untersuchen: Welche Charakteristika haben diese Patientinnen aus neurochirurgischer Sicht? Welchen Erfolg hat die operative Behandlung dieser zerebralen Metastasen? Was sind die Operationsindikationen und die prognostisch bedeutsamen Faktoren?
Journal of Cancer Research and Practice, Jun 1, 2016
Background: To assess postoperative rhinological complaints, length of hospital stay and complica... more Background: To assess postoperative rhinological complaints, length of hospital stay and complications related to endoscopic, endonasal trans-sphenoidal procedures. Patients and methods: From May 2001 through May 2007, a retrospective analysis was conducted on a series of 39 patients that underwent endonasal surgery and 9 patients that had craniotomy removal of pituitary tumors. Questionnaires were filled out at both 2 weeks and 3 months after surgery, most of which were completed in the outpatient department if the patient was discharged. Nasal packing lasted for 72 h in 29 patients, but not in the last 10 patients. Results: Of the 12 patients with preoperative headache, 50% had complete resolution, 33% had partial resolution and 17% reported no change. The frequency of rhinological complaints declined between the two questionnaires (p < .001). After 3 months, 64e84% of patients had no rhinological complaints, while 2.5% had severe complaints. Of the 9 patients with complications, rhinological complaint severity was similar to those without complications (p < .001). Conclusions: The direct endonasal trans-sphenoidal approach for pituitary fossa tumor is associated with a rapid rhinological recovery, shorter hospital stay and a low occurrence of serious long-term sinonasal complaints.
Journal of Neuropathology and Experimental Neurology, May 1, 1993
Human neuroblastoma cells, LAN, were used to study the phosphorylation and dephosphorylation of t... more Human neuroblastoma cells, LAN, were used to study the phosphorylation and dephosphorylation of tau proteins.
Objective: The value of methylprednisolone (MP) treatment in acute traumatic spinal cord injury (... more Objective: The value of methylprednisolone (MP) treatment in acute traumatic spinal cord injury (SCI) remains controversial. We attempted to evaluate the utilization of resources, motor function recovery and adverse effect after the use of MP. Methods: We compared 13 demographic and clinical characteristics between MP and non-MP treatment groups in 110 patients with acute traumatic SCI treated in hospitals between June 1st, 2000 and May 31st, 2001, and analyzed 10 short-term outcome variables. These demographic and clinical characteristics included age, cause of injury, number of associated injuries, Revised Trauma Score, Glasgow Coma Scale, mean blood pressure, level/completeness and pattern of SCI, number and types of spinal surgeries, frequency of rehabilitation therapy and the time interval between trauma and admission. Results: The MP (64.5%) and non-MP (35.5%) treatment groups showed no significant differences in all characteristics except the time interval between trauma and admission (P=0.024). MP treatment was associated with a higher frequency of infectious complications (P=0.038), but there was no difference between the two treatment groups in other outcome parameters. The results of analysis stratified by dosage of MP showed that the length of ICU stay (P=0.021) and the number of tracheostomies (P=0.005) and pneumonia cases (P=0.004) were increased significantly in the standard dose group. Conclusions: Although the rate of infection had risen in patients receiving MP, the steroid treatment did not significantly increase utilization of resources during hospitalization and appeared safe in terms of mortality. However, it had not been proven to improve motor function recovery.
Background: Meningioma is one of the most common primary brain neoplasms with poor outcomes. The ... more Background: Meningioma is one of the most common primary brain neoplasms with poor outcomes. The present study was aimed to determine clinical and surgical characteristics of intracranial meningiomas associated with tumor recurrence and complications. Methods: A total of 138 patients undergoing surgical resection of intracranial meningiomas between Jan 2003 and Dec 2014 were included and followed for the period of at least 12 months. The demographic and clinical characteristics possibly associated with tumor recurrence were assessed, including age, gender, clinical symptoms, pathology data, tumor parameters, preoperative and postoperative Karnofsky Performance Scale (KPS), complications and recurrence rate. Results: One hundred and twenty one lesions were benign (classified as Grade I) and 17 were atypical/ malignant (classified as Grade II/III). The patients were of a mean age of 60.5 years and a mean follow-up duration of 36.8 months (range, 16.3e62.9 months). The 1, 3, 5-year recurrence/tumor enlargement rates were 3.4%, 7.2%, and 15.7%, respectively. In multivariate analysis, symptoms of disturbance of consciousness and palpable cranial mass were associated with increased recurrence/tumor enlargement. In addition, patients with Simpson grade IV were more likely to have recurrence/tumor enlargement. Conclusion: The pattern of intracranial meningioma in this series is typical to other studies. Presenting symptoms is suggested to be predictive of recurrence.
Aging is a complex biological process. A study of pyrroline-5-carboxylate reductase 1 (PYCR1) def... more Aging is a complex biological process. A study of pyrroline-5-carboxylate reductase 1 (PYCR1) deficiency, which causes a progeroid syndrome, may not only shed light on its genetic contribution to autosomal recessive cutis laxa (ARCL) but also help elucidate the functional mechanisms associated with aging. In this study, we used RNA-Seq technology to examine gene expression changes in primary skin fibroblasts from healthy controls and patients with PYCR1 mutations. Approximately 22 and 32 candidate genes were found to be up-and downregulated, respectively, in fibroblasts from patients. Among the downregulated candidates in fibroblasts with PYCR1 mutations, a strong reduction in the expression of 17 genes (53.1%) which protein products are localized in the extracellular space was detected. These proteins included several important ECM components, periostin (POSTN), elastin (ELN), and decorin (DCN); genetic mutations in these proteins are associated with different phenotypes of aging, such as cutis laxa and joint and dermal manifestations. The differential expression of ten selected extracellular space genes was further validated using quantitative RT-PCR. Ingenuity Pathway Analysis revealed that some of the affected genes may be associated with cardiovascular system development and function, dermatological diseases and conditions, and cardiovascular disease. POSTN, one of the most downregulated gene candidates in affected individuals, is a matricellular protein with pivotal functions in heart valvulogenesis, skin wound healing, and brain development. Perturbation of PYCR1 expression revealed that it is positively correlated with the POSTN levels. Taken together, POSTN might be one of the key molecules that deserves further investigation for its role in this progeroid neurocutaneous syndrome.
We report a case of subdural metastasis in which the clinical features and associated images mimi... more We report a case of subdural metastasis in which the clinical features and associated images mimic chronic subdural hematoma. Despite a known history of systemic metastasis of adenocarcinoma, the initial diagnosis and treatment were directed toward chronic subdural hematoma. During burr-hole operation, the subdural space was found to be filled will solid tumor rather than chronic hematoma. Pathology examination confirmed metastatic adenocarcinoma. The patient received subsequent whole brain irradiation and died 3 months after operation. Similar situations have rarely been reported in the literature. CT and MRI with enhancement can be adequate tools for differential diagnosis. On the other hand, chronic subdural hematoma may be a presentation of dural metastasis or a target of metastasis. We conclude that if a patient has history of cancer, subdural metastasis should be considered and brain CT or MRI be performed with contrast enhancement when making differential diagnosis of subdura...
s-14th World Congress on Disaster and Emergency Medicine sl3 guidelines represent the first natio... more s-14th World Congress on Disaster and Emergency Medicine sl3 guidelines represent the first national, evidence-based standards for pediatric disaster and terrorism preparedness. The methodology used to develop the guidelines and recommendations in the current report was one of a previously validated, evidenced-based, consensus process used in prior studies, supplemented by a modified Delphi approach for topic selection. Experts from multiple disciplines and areas of expertise involved in the planning for and care of children during times of disaster and/or terrorist events were convened for the discussion. There were several goals of this process: 1. To build collaboration among individuals with expertise in pediatrics, pediatric emergency medicine, pediatric critical care, pediatric surgery, and emergency management (including disaster planning, management, and response); 2. To review and summarize the existing data on the needs of children in disaster planning, preparation, and response; 3. To develop evidence-based guidelines and recommendations on the needs of children in disasters, and develop evidence-based consensus guidelines for dealing with the gaps in the evidence; and 4. To create a research agenda to address knowledge gaps based on the limited data that exist on the needs of children in disasters. The final recommendations of the conference focused on three major areas: (1) emergency and prehospital care; (2) hospital care; and (3) terrorism preparedness and response, including biological terrorism, chemical terrorism, radiological terrorism, physical protection, decontamination, and the Strategic National Stockpile (SNS).
The presence of protein aggregates or inclusion bodies in the neurons or glial cells is one of th... more The presence of protein aggregates or inclusion bodies in the neurons or glial cells is one of the pathological hallmarks of neurodegenerative diseases, such as tauopathy in Alzheimer's diseases (AD). Infectious agents or unknown etiological factors may cause de novo misfolding of peptides or proteins to form proteinaceous seeds or oligomers. These protein seeds lead to self-propagation of pathologic aggregates that impair neuronal functions at different brain regions for causing specific neurological diseases. 1 Substantial evidence reveals that tumor suppressor WW domain-containing oxidoreductase, designated WWOX, FOR or WOX1, controls protein aggregation in the human brain. 2 Downregulation of WWOX appears to start in the middle ages that leads to the slow progression of neurodegeneration. 2 WWOX is a multi-functional molecule involved in cell signaling, cancer progression, metabolic disorders, and neural diseases. 2 When WWOX protein is totally lost due to alteration of WWOX/Wwox gene such as missense or nonsense mutation and deletion, neural disorders, and metabolic diseases occur in vivo, including ataxia, epilepsy, dementia, neurodegeneration, growth retardation, abnormal HDL lipid metabolism, and early death. 2,3 WWOX blocks neurodegeneration by binding tau and tau-hyperphosphorylating enzymes GSK3β, ERK, and JNK1, (refs 4-6) and promotes neuronal differentiation. 5 WWOX interacts with ERK and JNK1 via its N-terminal first WW domain, but binds tau and GSK3β via C-terminal short-chain alcohol dehydrogenase/reductase (SDR) domain. 4,5 A portion of WWOX is in the mitochondria, so as to maintain the normal cell physiology. The SDR domain appears to have a key role in the mitochondrial homeostasis. 4-6 WWOX is frequently downregulated in the AD hippocampi. 2,4 This downregulation results in spontaneous relocation of TGFβ1-induced antiapoptotic factor 1 (TIAF1) and TRAPPC6AΔ (trafficking protein particle complex 6A delta, TPC6AΔ) to the mitochondria and both proteins become aggregated (see Figure 1). 6,7 These aggregated proteins activate caspases, which leads to
Globoid cell leukodystrophy (GLD) is an autosomal recessive, lysosomal storage disease caused by ... more Globoid cell leukodystrophy (GLD) is an autosomal recessive, lysosomal storage disease caused by deficiency of the enzyme galactocerebrosidase (GALC). The absence of GALC activity leads to the accumulation of the toxic substance psychosine and the preferential loss of myelinating cells in the central and peripheral nervous systems. Profound demyelination, astrogliosis and axonopathy are the hallmarks of the pathogenesis of GLD, and cerebellar ataxia is one of the dominant manifestations in adolescents and adults affected with GLD. To date, studies regarding cerebellar degeneration in GLD are limited. In this study, the efficacy of cerebellum-targeted gene therapy on the cerebellar neuropathology in twitcher mice (a murine model of GLD) has been validated. We observed degeneration of Purkinje cells, Bergmann glia, and granule cells in addition to astrocytosis and demyelination in the cerebellum of the twitcher mice. Ultrastructural analysis revealed dark cell degeneration and disintegration of the cellular composition of Purkinje cells in untreated twitcher mice. In addition, the expressions of neurotrophic factors CNTF, GDNF and IGF-I were up-regulated and the expression of BDNF was down-regulated. Intracerebellar-mediated gene therapy efficiently corrected enzymatic deficiency by direct transduction to Purkinje cells and cross-correction in other cell types in the cerebellum, leading to the amelioration of both neuroinflammation and demyelination. The population, dendritic territory, and axonal processes of Purkinje cells remained normal in the cerebellum of treated twitcher mice, where radial fibers of Bergmann glia spanned the molecular layer and collateral branches ensheathed the dendritic processes of Purkinje cells. Moreover, the aberrant expressions of neurotrophic factors were mitigated in the cerebellum of treated twitcher mice, indicating the preservation of cellular function in addition to maintaining the neuronal architecture. The life span of the treated twitcher mice was significantly prolonged and their neurobehavioral performance was improved. Taken together, our findings underscore the complexity of cerebellar neurodegeneration in GLD and highlight the potential effectiveness of gene therapy in mitigating neuropathological deficits in GLD and other neurodegenerative disorders in which Purkinje cells are involved.
Self-aggregation of transforming growth factor β (TGF-β)1-induced antiapoptotic factor (TIAF1) is... more Self-aggregation of transforming growth factor β (TGF-β)1-induced antiapoptotic factor (TIAF1) is known in the nondemented human hippocampus, and the aggregating process may lead to generation of amyloid β (Aβ) for causing neurodegeneration. Here, we determined that overexpressed TIAF1 exhibits as aggregates together with Smad4 and Aβ in the cancer stroma and peritumor capsules of solid tumors. Also, TIAF1/Aβ aggregates are shown on the interface between brain neural cells and the metastatic cancer cell mass. TIAF1 is upregulated in developing tumors, but may disappear in established metastatic cancer cells. Growing neuroblastoma cells on the extracellular matrices from other cancer cell types induced production of aggregated TIAF1 and Aβ. In vitro induction of TIAF1 self-association upregulated the expression of tumor suppressors Smad4 and WW domain-containing oxidoreductase (WOX1 or WWOX), and WOX1 in turn increased the TIAF1 expression. TIAF1/Smad4 interaction further enhanced Aβ...
The role of a small transforming growth factor beta (TGF-β)-induced TIAF1 (TGF-β1-induced antiapo... more The role of a small transforming growth factor beta (TGF-β)-induced TIAF1 (TGF-β1-induced antiapoptotic factor) in the pathogenesis of Alzheimer's disease (AD) was investigated. TIAF1 physically interacts with mothers against DPP homolog 4 (Smad4), and blocks SMAD-dependent promoter activation when overexpressed. Accordingly, knockdown of TIAF1 by small interfering RNA resulted in spontaneous accumulation of Smad proteins in the nucleus and activation of the promoter governed by the SMAD complex. TGF-β1 and environmental stress (e.g., alterations in pericellular environment) may induce TIAF1 self-aggregation in a type II TGF-β receptor-independent manner in cells, and Smad4 interrupts the aggregation. Aggregated TIAF1 induces apoptosis in a caspase-dependent manner. By filter retardation assay, TIAF1 aggregates were found in the hippocampi of nondemented humans and AD patients. Total TIAF1-positive samples containing amyloid β (Aβ) aggregates are 17 and 48%, respectively, in the...
... [ ] 9.K. Goel, YE Kim, TH Lim, ³An analytical investigation of the ... J. Spinal Disord. Tech... more ... [ ] 9.K. Goel, YE Kim, TH Lim, ³An analytical investigation of the ... J. Spinal Disord. Tech., 2004 (In press) [19]CK Cheng, WJ Chen, CS Chen, SC Chueh, CC Wang, ³Failure analysis of pedicle screw breakage on spinal instrumentation´. Med. ... [27]DY Cho, WR Liau, WY Lee, JT Liu ...
Tumor suppressor WWOX inhibits cancer growth and retards Alzheimer’s disease (AD) progression. Su... more Tumor suppressor WWOX inhibits cancer growth and retards Alzheimer’s disease (AD) progression. Supporting evidence shows that the more strongly WWOX binds intracellular protein partners, the weaker is cancer cell growth in vivo. Whether this correlates with retardation of AD progression is unknown. Two functional forms of WWOX exhibit opposite functions. pY33-WWOX is proapoptotic and anticancer, and is essential for maintaining normal physiology. In contrast, pS14-WWOX is accumulated in the lesions of cancers and AD brains, and suppression of WWOX phosphorylation at S14 by a short peptide Zfra abolishes cancer growth and retardation of AD progression. In parallel, synthetic Zfra4-10 or WWOX7-21 peptide strengthens the binding of endogenous WWOX with intracellular protein partners leading to cancer suppression. Indeed, Zfra4-10 is potent in restoring memory loss in triple transgenic mice for AD (3xTg) by blocking the aggregation of amyloid beta 42 (Aβ42), enhancing degradation of agg...
doi: 10.3389/fonc.2013.00043 Tumor suppressorWWOX and p53 alterations and drug resistance in glio... more doi: 10.3389/fonc.2013.00043 Tumor suppressorWWOX and p53 alterations and drug resistance in glioblastomas
Primary central nerve system lymphoma (PCNSL) represents approximately 1% of all intracranial neo... more Primary central nerve system lymphoma (PCNSL) represents approximately 1% of all intracranial neoplasms. Although an early and reliable diagnosis of PCNSL is important to rapidly initiate optimal therapy, atypical cases complicate the differential diagnosis by clinicians and radiologists. Here, we report a 48-year-old male patient of PCNSL with tumoral bleeding and ocular involvement. He suffered from progressive blurred vision and was diagnosed with brain tumoral bleeding at the right temporal lobe. The pathological report showed diffuse large B-cell lymphoma after he received brain surgery. The postoperative course was uneventful. The present case reconfirms the importance of imaging study and clinical presentation in diagnosis of PCNSL, and that histopathologic examination following brain biopsy is necessary for a correct diagnosis.
Dysfunction of mitochondria causes defects in oxidative phosphorylation system (OXPHOS) and incre... more Dysfunction of mitochondria causes defects in oxidative phosphorylation system (OXPHOS) and increased production of reactive oxygen species (ROS) triggering the activation of the cell death pathway that underlies the pathogenesis of aging and various diseases. The process of autophagy to degrade damaged cytoplasmic components as well as dysfunctional mitochondria is essential for ensuring cell survival. We analyzed the role of autophagy inpatient-specific induced pluripotent stem (iPS) cells generated from fibroblasts of patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with well-characterized mitochondrial DNA mutations and distinct OXPHOS defects. MELAS iPS cells recapitulated the pathogenesis of MELAS syndrome, and showed an increase of autophagy in comparison with its isogenic normal counterpart, whereas mitophagy is very scarce at the basal condition. Our results indicated that the existence of pathogenic mtDNA alone in mitochondri...
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Papers by Ming-Fu Chiang