Synergistic inhibitory effect of berberine and icotinib on non-small cell lung cancer cells via inducing autophagic cell death and apoptosis.

Resistance to epidermal growth factor receptor-tyrosin kinase inhibitors (TKIs, e.g. icotinib) remains a major clinical challenge. Non-small cell lung cancer patients with wild-type EGFR and/or K-RAS mutation are primary resistance to EGFR-TKIs. Berberine has been found to have potent anticancer activities via distinct molecular mechanism. In this study, we sought to investigate the therapeutic utility of BBR in combination with icotinib to overcome icotinib resistance in NSCLC cells, and explore the molecular mechanism of synergism of icotinib and BBR to EGFR-resistant NSCLC cells. We used the two EGFR-resistant NSCLC cell lines H460 and H1299 for testing the inhibitory effect of icotinib and/or BBR on them. Moreover, xenograft mouse model was applied for assessing the anti-tumor activities of BBR and icotinib in combination. Results showed that BBR and icotinib have a synergistic inhibitory effect on H460 and H1299 cells through induction of autophagic cell death and apoptosis. Accordingly, the anti-cancer effect of BBR plus icotinib was further confirmed in the NSCLC xenograft mouse models. Combination of BBR and icotinib significantly inhibited the protein expression and the activity of EGFR by inducing autophagic EGFR degradation. BBR plus icotinib resulted in intracellular ROS accumulation, which could mediated autophagy and apoptosis and involved in the suppression of cell migration and invasion. In conclusions, combination application of BBR and icotinib could be an effective strategy to overcome icotinib resistance in the treatment of NSCLC.

Knockdown of REV3 synergizes with ATR inhibition to promote apoptosis induced by cisplatin in lung cancer cells.

It has been demonstrated that REV3, the catalytic subunit of the translesion synthesis (TLS) polymerase ζ, play an important role in DNA damage response (DDR) induced by cisplatin, and Ataxia-telangietasia mutated and Rad-3-related (ATR) knase is a central player in activating cell cycle checkpoint, stabilizing replication forks, regulating DDR, and promoting repair of DNA damage caused by cisplatin. Cancer cells deficient in either one of REV3 and ATR are more sensitive to cisplatin. However, whether co-inhibition of REV3 and ATR can further increase sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin is not clear. In this study, we show that REV3 knockdown combined with ATR inhibition further enhance cytotoxicity of cisplatin in NSCLC cells, including cisplatin-sensitive and -resistant cell lines, compared to individual knockdown of REV3 or ATR, which are accompanied by markedly caspase-dependent apoptosis response, pronounced DNA damage accumulation and severe impediment of interstrand crosslink (ICL), and double strand break (DSB) repair. Our results suggest that REV3 knockdown synergize strongly with ATR inhibition to significantly increase sensitivity of cisplatin in NSCLC cells by inhibiting ICL and DSB repair. Thus simultaneously targeting REV3 and ATR may represent one approach to overcome cisplatin resistance and improve chemotherapeutic efficacy in NSCLC treatment.

Synergistic killing effect of paclitaxel and honokiol in non-small cell lung cancer cells through paraptosis induction.

PURPOSE: Paclitaxel is an anticancer drug for the treatment of non-small cell lung cancer (NSCLC). However, drug-resistance remains a major problem. Honokiol is a natural component which has been found to exhibit anti-tumor activity. Paclitaxel and honokiol have been reported to be able to induce paraptosis. The aim of this study was to investigate whether honokiol can reverse paclitaxel resistance by inducing paraptosis in NSCLC cells. METHODS: NSCLC cell lines H1650 (paclitaxel-sensitive), H1299 and H1650/PTX (intrinsic and acquired paclitaxel-resistant, respectively) were used to assess the cytotoxic effects of paclitaxel and honokiol. Light and transmission electron microscopy were performed to detect cytoplasmic vacuolation. In vitro cell viability and clonogenic survival assays, as well as in vivo xenograft assays were conducted to test synergistic killing effects of paclitaxel and honokiol on NSCLC cells. Western blotting, flow cytometry and immunofluorescence were performed to evaluate paraptosis-regulating mechanisms. RESULTS: We found that combination treatment with paclitaxel and honokiol synergistically killed H1650, H1299 and H1650/PTX cells by inducing paraptosis, which is characterized by cytoplasmic vacuolation. Moreover, paclitaxel/honokiol treatment resulted in a significant growth delay in H1299 xenograft tumors that showed extensive cytoplasmic vacuolation. Mechanistically, proteasomal inhibition-mediated endoplasmic reticulum (ER) stress and unfolded protein responses leading to ER dilation, and the disruption of intracellular Ca2+ homeostasis and mitochondrial Ca2+ overload resulting in mitochondrial disfunction, were found to be involved in paclitaxel/honokiol-induced paraptosis. Cellular protein light chain 3 (LC3) may play an important role in paclitaxel/honokiol induced cytoplasmic vacuolation and NSCLC cell death. CONCLUSIONS: Combination of honokiol and paclitaxel may represent a novel strategy for the treatment of paclitaxel-resistant NSCLC.

Suppression of the FA pathway combined with CHK1 inhibitor hypersensitize lung cancer cells to gemcitabine.

The combination of platinum and gemcitabine is one of the standard regimens in the treatment of advanced lung squamous carcinoma (LSC). Resistance to gemcitabine is main barrier to the successful treatment of LSC. In this study, we showed that suppression of the Fanconi anemia (FA) pathway increased the sensitivity of two LSC cell lines SK-MES-1 and KLN205 to gemcitabine. Moreover, we found that the CHK1 pathway and the FA pathway are functionally compensatory in the repair of DNA damage in the LSC cell lines. Inactivation of one of the two pathways led to DNA damage, triggering compensatory activation of other pathway. Furthermore, we demonstrated that FANCD2 depletion combined with CHK1 inhibitor MK-8776 significantly potentiated the cytotoxicity of gemcitabine to the two LSC cell lines, compared to individual FANCD2 depletion or MK-8776 treatment. The enhanced effect of gemcitabine-chemosensitization was accompanied by loss of DNA repair function and accumulation of DNA single strand breaks and double strand breaks, in parallel with obvious increase of caspase-3 dependent apoptosis. Our results indicate that the enhancement effect of FANCD2 depletion combined with CHK1 inhibitor in sensitizing the LCS cells to gemcitabine supports the FA pathway and CHK1 as two therapeutic targets for improvement of anti-tumor regimens in treatment of LSC.

The functional status of DNA repair pathways determines the sensitization effect to cisplatin in non-small cell lung cancer cells.

PURPOSE: Cisplatin can cause a variety of DNA crosslink lesions including intra-strand and inter-strand crosslinks (ICLs), which are associated with the sensitivity of cancer cells to cisplatin. Here, we aimed to assess the contribution of the Fanconi anemia (FA), homologous recombination (HR) and nucleotide excision repair (NER) pathways to cisplatin resistance in non-small cell lung cancer (NSCLC)-derived cells. METHODS: The expression of FA, HR and NER pathway-associated genes was assessed by RT-qPCR and Western blotting. siRNAs were used to knock down the expression of these genes. CCK-8 and flow cytometry assays were used to assess the viability and apoptotic rate of NSCLC-derived cells, respectively. Immunofluorescence and alkaline comet assays were used to assess the repair of ICLs. RESULTS: We found that acquired cisplatin-resistant NSCLC-derived A549/DR cells exhibited markedly enhanced FA and HR repair pathway capacities compared to its parental A549 cells and another independent NSCLC-derived cell line, Calu-1, which possesses a moderate innate resistance to cisplatin. siRNA-mediated silencing of the FA-associated genes FANCL and RAD18 and the HR-associated genes BRCA1 and BRCA2 significantly potentiated the sensitivity of A549/DR cells to cisplatin compared to A549 and Calu-1 cells, suggesting that the acquired cisplatin resistance in A549/DR cells may be attributed to enhanced FA and HR pathway capacities responsible for ICL repair. Although we found that expression knockdown of the NER-associated genes XPA and ERCC1 sensitized the three NSCLC-derived cell lines to cisplatin, the sensitization effect was more significant in Calu-1 cells than in A549 and A549/DR cells, implying that the innate cisplatin resistance in Calu-1 cells may result from an increased NER activity. CONCLUSIONS: Our results indicate that the functional status of DNA repair pathways determine the sensitivity of NSCLC cells to cisplatin. Direct targeting of the pathway that is involved in cisplatin resistance may be an effective strategy to surmount cisplatin resistance in NSCLC.

Stepwise Rehabilitation of the Triple Amputee Combined With Dysfunction of the Sound Limb

To find a multiple amputee more severe than a triple amputee is not easy. This is a report of a 36-year-old patient with right knee disarticulation, left trans-femoral amputation and right elbow disarticulation due to peripheral ischemic necrosis, when he was applied vasopressor in septic shock condition. His left hand was also 2nd, 3rd, 4th, and 5th distal interphalangeal joint disarticulation status, and it was more difficult for him to do rehabilitation program, such as donning and doffing the prostheses. For more efficient rehabilitation training program, we first focused on upper extremities function, since we believed that he might need a walking aid for gait training later. After 13 weeks of rehabilitation program, he has become sit to stand and walk short distance independently with an anterior walker. Although he still needs some assistance with activities of daily living, his Functional Independence Measure score improved from 48 to 90 during the course of 13 weeks.

Characteristics and Surgical Outcome of Macular Holes Developing after Rhegmatogenous Retinal Detachment Repair

PURPOSE: To report the characteristics and surgical outcome of macular holes (MHs) that develop after rhegmatogenous retinal detachment (RRD) repair. METHODS: A retrospective chart review was performed in patients who developed a new full-thickness macular hole after RRD repair between May 2010 and July 2013. For eyes that underwent pars plana vitrectomy with internal limiting membrane peeling and gas tamponade for MH repair, main outcomes included macular attachment status and postoperative visual acuity. RESULTS: Fourteen full-thickness MHs were detected in a series of 2,815 eyes (0.49% prevalence) that had undergone prior RRD surgery. Ten MHs developed after primary vitrectomy and four after scleral bucking surgery. The fovea was detached in eight of the 14 eyes at the time of RRD. Fourteen of 14 eyes were managed by pars plana vitrectomy, internal limiting membrane peeling, and intravitreal gas tamponade, and 12 of 14 eyes achieved MH closure. Mean preoperative Snellen best-corrected visual acuity (BCVA) was 20/63 (+/-0.25). Nine of 14 eyes had an improvement in visual acuity of at least two Snellen lines, and five eyes remained unchanged. CONCLUSIONS: In this small retrospective study, the secondary MHs were found predominantly in foveal detachments after RRD repair, most commonly occurring after primary vitrectomy. In conclusion, the surgical outcome and postoperative visual acuity improvement were satisfactory, although the final BCVA depended on the macular status during the RRD.

Epidemiologic Change of Patients With Spinal Cord Injury

OBJECTIVE: To evaluate the epidemiologic change of patients with spinal cord injury who were admitted to a Rehabilitation Hospital, Yonsei University College of Medicine, during 1987-1996 and 2004-2008. METHODS: Medical records of 629 patients with spinal cord injury admitted to the Rehabilitation Hospital, Yonsei University College of Medicine, from 2004 to 2008 were collected and reviewed retrospectively. RESULTS: The male-to-female ratio decreased to 2.86:1, the mean age at injury increased, nontraumatic etiology increased, traffic accident remained to be the most common in traumatic spinal cord injury, and falling increased significantly. Tumor was the most common etiology in nontraumatic spinal cord injury, tetraplegia and incomplete injuries occurred more than paraplegia and complete injuries, indwelling catheter was the most common voiding method, and the duration of hospitalization decreased. CONCLUSION: Many trends changed in epidemiology of spinal cord injury.

Depression and Quality of Life in Patients within the First 6 Months after the Spinal Cord Injury

OBJECTIVE: To evaluate the severity of depression, degree of life satisfaction, level of stress, and resilience among patients in the first 6 months after a spinal cord injury (SCI). METHOD: 36 patients with SCI were asked to fill out questionnaires concerning Beck Depression Inventory (BDI), World Health Organization Quality of Life Questionnaire-BREF, Stress Response Inventory, and Connor-Davidson resilience scale. All patients had experienced an SCI within the last 6 months before the commencement of this study. RESULTS: In our study, the patients who experienced the SCI within the last six months had a higher rate of depression (63.9%) and a higher overall level of depression (13.8 points). The unmarried group had a significantly higher quality of life (QOL; p<0.05) when compared with the married group. In the motor complete group, severity of depression and level of stress were higher, whereas QOL was lower than the motor incomplete group (p<0.05). The mean American Spinal Injury Association (ASIA) Motor Score (AMS) was much higher in the non-depressive group (p<0.05) when compared with the depressive group. CONCLUSION: We found the patients within six months after SCI injury had higher rate of depression and higher overall level of depression. Also, patients with motor complete injury had affected significantly on depression, QOL and stress. We found the married patients had poorer QOL and depressive group had lower AMS score of lower extremity. Therefore, there should be emphasis of psychological care who have motor complete injury and are married during the early stage.

Cerebral Air Embolism during Open Heart Surgery with Cardiopulmonary Bypass: A Case Report

Cerebral air embolism is an unusual event that is mainly an iatrogenic cause, such as open heart surgery. We present a case of cerebral air embolism in a patient undergoing ASD patch repair with cardiopulmonary bypass. He had a status epilepticus, loss of consciousness and marked left limb weakness immediately after the operation. Diffusion-weighted MRI with angiography showed acute infarction in right entire hemisphere with patent internal carotid and intracranial arteries, and glucose PET brain scan showed severe decreased uptakes in right hemisphere. He recovered markedly with mild motor impairment of left upper and lower limbs in the 6 months after onset.

Obturator Prosthesis for Velopharyngeal Insufficiency after Treatment of Soft Palate Cancer: A Case Report

Velopharyngeal insufficiency after surgical resection of soft palate cancer can be troublesome. This report concerns a male suffered from severe dysphagia following combined treatment for soft palate cancer. Sequential videofluoroscopic swallowing studies (VFSS) were used to assess his swallowing function and plan the interventional strategies. Initial VFSS showed huge nasal regurgitation, increased oral transit time, residues in oral cavity, delayed swallowing reflex, pharyngeal residue, impaired laryngeal elevation, and aspiration in semisolid and liquid trials. Obturator prosthesis was fabricated to minimize velopahryngeal insufficiency. After application of obturator prosthesis, swallowing dysfunction in oral and pharyngeal stages was markedly improved. Nasal regurgitation was not shown. Oral residue, oral transit time in oral stage also improved. Residue on vallaculae and pyriform sinuses decreased in pharyngeal stage. Aspiration also decreased. We reported successful obturator prosthesis application with sequential changes of clinical and VFSS findings in our case.

Survey on the Diagnostic Process of Amyotrophic Lateral Sclerosis

OBJECTIVE: To emphasize the need for precise diagnosis of amyotrophic lateral sclerosis (ALS), a progressive and degenerative disease of upper and lower motor neurons that often present initially with weakness at the upper or lower extremities, and frequently misdiagnosed as myelopathy, radiculopathy, peripheral neuropathy or arthropathy that may ultimately lead to unnecessary treatments including surgical procedures. METHOD: We retrospectively reviewed medical records of 331 ALS patients who visited our hospital between 1998 and 2008. Symptoms at onset, progression of disease, radiologic findings, surgeries prior to diagnosis of ALS, outcome after surgery or conservative treatments, and electrodiagnostic study results were reviewed. RESULTS: Among the 331 patients with ALS, 34 (10.3%) had a history of surgical procedure and 37 (11.1%) underwent conservative treatment prior to diagnosis of ALS. 34 patients with a mean disease duration at diagnosis of 20.0+/-14.9 months, had surgery for symptoms that were later attributable to ALS. In 30 of the 34 patients, symptoms did not resolve after the intervention. 37 patients with a mean disease duration at diagnosis of 16.6+/-14.3 months, underwent conservative treatments such as physical therapy prior to diagnosis of ALS. Only in one patient (2.7%), symptoms improved after conservative treatment. CONCLUSION: In the absence of a single confirmatory study for the diagnosis of ALS, clinical findings may be misinterpreted, leading to an erroneous diagnosis. Therefore, closer and more careful follow-up is necessary for patients with limb weakness in the absence of sensory symptoms, or bulbar abnormalities such as dysarthria and dysphagia.

Neural Substrates of Motor Learning

Motor Learning is a relatively permanent change in the capability for skilled motor performance as a result of practice or experience. Rehabilitation is fundamentally a process of relearning. With advanced neuro-imaging, the roles of brain areas related to motor learning have been revealed. However, results of a single study represent only parts of a puzzle of the neuronal changes underlying motor learning. The neural substrates of motor learning with a combined view of functional imaging data were reviewed.

Plasma Neuron-specific Enolase and Glutamic Acid Level in Acute Ischemic Stroke

PURPOSE: We studied the plasma neuron-specific enolase (NSE) and glutamic acid levels as a marker of the severity of acute ischemic stroke (AIS). METHODS: We enrolled 93 patients who visited to the emergency department from April to September, 2005. The AIS patients included those who visited the emergency department within 24 hours due to ischemic stroke symptoms. The AIS patients was subclassified according to large-vessel, small-vessel, cardioembolic, or unclassified infarction. RESULTS: The plasma NSE and glutamic acid level were 15.1+/-7.9 ng/ml and 204.5+/-86.5 nM/ml, respectively, in the AIS patients. Plasma NSE and Glutamic acid in the was higher than reference range (NSE 0-12 ng/ml, Glutamic acid 0-130 nM/ml). According to the type of infarction, no differences were observed in the plasma NSE and glutamic acid levels. CONCLUSION: In cases of AIS, NSE and glutamic acid have no statistical usefulness in classifying the type of infarction. However, the value of plasma NSE and glutamic acid levels have statistical usefulness in deciding on the existence or nonexistence of an AIS.

Preventable Trauma Deaths Rates and Management Errors in Emergency Medical System in Korea

PURPOSE: The objectives of this study were 1) to estimate the preventable death rate in emergency medical system in Korea 2) to determine factors that affect preventability of trauma deaths 3) to identify management errors involved in preventable deaths. METHODS: The records of a 202 patients who died in the emergency departments or shortly after admission due to trauma at nine hospitals in three regions between from July 1, 2003, to June 30, 2004 were retrospectively reviewed by nine board certified physicians in emergency medicine using professional panel study methodology. Each panelist independently reviewed prehospital records, medical records, x-ray films, and inter-hospital transfer records using a structured survey format and preventability was determined by a unanimous agreement rule. The management errors that contributed to a preventable death were determined and classified as "structure-related"and "process-related"errors. RESULTS: Preventable deaths related to all management errors account for 39.6% of all trauma deaths. Whereas, 25.7% of preventable deaths were related to management errors in the studied hospitals. The preventability of trauma deaths were determined by the cause of death and the severity of injury. A total of 389 management errors are identified. Management errors occurred mostly in emergency departments (51.1%) and, in prehospital delivery (21.8%). Most of these errors were found to be processrelated (81.2%) rather then structure-related (18.8%). CONCLUSION: Preventable death rates in Korea are higher than other developed countries, which implies there is much to be improved in the quality of emergency medical services. We found this to be true especially, for processrelated errors, which need to be regularly assessed, and policy established that reduces preventable deaths.

Efficacy of Aquacell(R) Dressing in Partial Thickness Burn Patients

In partial thickness burn injuries, silver sulfadiazine cream 1%(SSD, Silvadene(R)) is the most commonly used topical agent worldwide. But silver sulfadiazine cream 1% has no exudate absorption property. Usually after escar is removed from wound surface, Silvadene(R) is changed to saline wet gauze dressing to promote epithelization. Aquacel(R)(ConvaTec, UK) is a 100% sodium carboxymethylcellulose Hydrofiber material. It absorbs exudates directly into the hydrofibers by vertical wicking which allows rapid uptake of liquid into the fibers. The absorbed exudate fluid can be distributed to the entire dressing rather than just over the wound surface, which results in larger fluid absorption capacity. From April, 2003 to July, 2004 a study was done with 40 patients who had variable partial thickness burns. Aquacel(R) dressing was compared in 21 cases to silver sulfadiazine cream 1% and saline wet gauze dressings in 19 cases. In the Aquacel(R) cases, the average healing time on the face was 5.36+/-1.69 a day; on the hands was 8.46+/-2.15 a day; and, on the neck was 6.0+/-2.0 a day. With the Silvadene(R) and Saline wet gauze dressing, the average healing time on the face was 6.44+/-1.74 a day; on the hands was 13.79+/-5.35 a day; and, on the neck was 11.17+/-3.31 a day. As a result, the Aquacel(R) group showed a shorter healing time compared to the Silvadene(R) and saline wet gauze dressing group and patients were satisfied because of less pain and improved comfort. In conclusion, Aquacel(R) is a better choice for partial thickness burn injuries because of shorter healing time, less pain and more confortable dressing.

Immunohistochemical Study for Expression of cFos, pERK1/2 and pAkt Proteins in a Macrosphere Animal Model for Permanent Focal Brain Ischemic Injury

PURPOSE: Recently, a new animal model for permanent focal brain ischemia using macrospheres was developed wherein the hypothalamic area was free from ischemic injury. The purpose of this study was to evaluate spatiotemporal changes in the expressions of cFos, pERK, and pAkt proteins in the macrosphere model. METHOD: Three or four macrospheres were injected into the internal carotid artery after ligation of the external carotid artery to induce permanent focal brain ischemic injury. RESULT: Twenty-four hours after macrosphere injection, 2,3,5-Triphenyltetrazlium (TTC) staining showed a marked ischemic injury in the blood supply territory of the middle cerebral artery, for example, the cerebral cortex and striatum. Furthermore, TUNEL staining revealed apoptotic cell death in the ischemic injury region of the cerebral cortex and striatum. Expression of the cFos protein was significant in the penumbral zone, but not in the ischemic core of the cortex and striatum, two and six hours after ischemic insult. A transient prominent expression of the pERK1/2 protein was noted in the penumbral zone of the cortex and striatum two hours after injection of macrospheres. In contrast, there was a strong immunoreactivity for the pAkt protein in the ischemic core, but not in the penumbral zone of the cortex and striatum, six hours after ischemic injury. CONCLUSION: The above results suggest that early expressions of cFos, pERK1/2, and pAkt proteins take part in different signaling cascades for cell survival or death in macrosphere animal model of permanent focal brain ischemic injury.

Effects of TGF-beta, GM-CSF, and PDGF on Proliferation and Expression of Cytokine and Metalloproteinase Genes in Rheumatoid Synovial Cells / 대한면역학회지

To investigate effects of cytokines on rheumatoid synovial cells, proliferation and expression of cytokine and metalloproteinase genes were studied with the primary culture of rheumatoid synovial cells which was treated with TNF-alpha, GM-CSF, TGF-alpha, PDGF and IL-B. By [3H] thymidine incorporation assay, TGF-beta and PDGF increased proliferation of synovial cells by 1.5 and 2.5 folds respectively. Cytokine gene expression was assessed by RT-PCR. Rheumatoid synovial cells expressed constitutively TGF-beta and IL-B at a high level and IL-1B, GM-CSF, and MIP-1a at a relatively low level. TGF-beta, GM-CSF and PDGF increased IL-B expression. Expression of pro-inflammatory cytokines and chemokines was increased by GM-CSF and PDGF. Both GM-CSF and PDGF increased the expression of IL-1B, GM-CSF MIP-la and IL-8. In addition, GM-CSF enhanced expression of TNF-alpha. Stromelysin and collagenase are the major proteinases responsible for destruction ot joints in rheumatoid arthritis (RA). These genes were expressed constitutivefy in rheumatoid synovial cells. In summary, PDGF and GM-CSF may piay an important role by inducing or increasing expression of IL-1B, TGF-beta and PDGF by increasing proliferation of rheumatoid synovial cells.

IL-4 inhibits proliferation of renal carcinoma cells by increasing the expression of p21WAF1 and IRF-1

Interleukin (IL)-4 inhibits proliferation of several human cancer cell lines in vitro. Although IL-4 is known to regulate proliferation of lymphocytes by modulating p27KIP1 expression, the mechanism involved in the IL-4-induced growth inhibition of nonhematopoietic cancer cells has not been fully elucidated. Previously, we reported that IL-4 suppressed proliferation of human renal cell carcinoma (RCC) cell lines in vitro. Here, we show that IL-4 inhibits cell cycle progression at the G1 phase in Caki-1 cells by increasing the expression of p21WAF1 and interferon regulatory factor (IRF)-1, and decreasing the cyclin dependent kinase (CDK) 2 activity. Up-regulation of p21WAF1 and IRF-1 expression is transcriptional, but independent of p53. The levels of p21WAF1 and IRF-1 proteins were enhanced as early as 1 h after IL-4 treatment. CDK2 activity started to decline at 4 h after IL-4 treatment, and by 24 h, was ~50% of the control. Neither the protein expressions of p27KIP1 and p16INK4a, nor the phosphorylation level of pRb was changed. The importance of p21WAF1 and IRF-1 in the growth inhibition induced by IL-4 was confirmed by antisense oligonucleotide transfection. Both of p21WAF1 and IRF-1 antisense oligonucleotides prevented IL-4-mediated growth inhibition by ~30% compared to the respective sense oligonucleotides. In summary, our study indicated that p21WAF1 and IRF-1 mediate the growth inhibitory effect of IL-4 in human RCC cells.

Plasma Homocysteine Level and Blood Coagulation Factors in Acute Ischemic Cerebral Stroke

PURPOSE: We studied the plasma homocysteine level and coagulation factors such as fibrinogen and antithrombin III (ATIII) in acute cerebral infarction (ACI). METHODS: We enrolled 222 patients who visited our emergency department from March 1, 2003, to August 31, 2003. The ACI patient group included those who visited the emergency department within 24 hours due to cerebral infarction symptoms and included 115 patients the control group included those visited the emergency department due to minor trauma (CRAMS score>9) and include 56 patients in the homocysteine control group and 51 in the fibrinogen and ATIII group. ACI patient group was subclassified according to great artery, small artery, or cardioembolic cerebral infarction. RESULTS: The plasma homocysteine level, the fibrinogen, and ATIII were 16.3+/-7.9 micrommol, 283.2+/-60.1 mg/dl, 87.3+/-25.8%, respectively, in the ACI patient group and 9.6+/-4.0 micrommol, 245.3+/-62.2 mg/dl, 109.8+/-14.7% in the control group. The values of plasma homocysteine and fibrinogen in the was higher than it was in the control group. The value of ATIII in the ACI patient group was lower than it was in the control group. In according to cerebral infarction type, no differences were observed in the plasma homocyteine, fibrinogen, and ATIII. CONCLUSION: In cases of acute cerebral infarction, fibrinogen and ATIII have no statistical usefulness in classifying the type of cerebral infarction. However, the value of plasma homocysteine, fibrinogen, and ATIII have statistical usefulness in deciding on the existence or nonexistence of an acute cerebral infarction.