• Journal of Life Science
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• v.17 no.7 s.87
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• pp.948-955
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• 2007

Neutrophils play a key role as a first line of defense and are known to acquire the characteristics of dendritic cells (DCs) under the appropriate conditions. The spontaneous apoptosis of neutrophils was delayed by treatment with 4-(2-aminoethyl) benzensulfonylfluoride (AEBSF), a serine protease inhibitor. AEBSF inhibited both caspase-3 and serine protease activities, whereas ZVAD-fmk, a pancaspase inhibitor, inhibited only caspase-3 activity. The life span of neutrophils was prolonged up to 5 days by AEBSF in the presence or absence of granulocyte macrophage colony stimulating factor(CM-CSF). DC surface markers, such as CD80, CD83, and MHC class ll were not expressed on neutrophils treated with AEBSF alone. CM-CSF failed to prolong the survival time of neutrophils up to3 days but increased the expression levels of DC markers on neutrophils in the presence of AEBSF. Expression levels of DC markers were the highest on neutrophils treated with CM-CSF and AEBSF for 3 days. AEBSF and CM-CSF-treated neutrophils stimulated proliferation of T cells in the presence of a superantigen, Staphylococcal enterotoxin B (SEB) but produced $interferon-{\gamma}$ ($IFN{\gamma}$) in the absence of SEB. These results suggest that the inhibition of serine protease activity prolonged the life span of human neutrophils and combined treatment of neukophils with CM-CSF and serine protease inhibitor induced differentiation of neutrophils into DC-like cells.

• Archives of Craniofacial Surgery
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• v.11 no.2
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• pp.95-98
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• 2010

Purpose: CSF (Cerebrospinal fluid) leakage is the most common complication of neurosurgery. Early management with conservative care or surgery must be followed appropriately due to the increased risk of lethal complications, such as meningitis. We report a case of intractable CSF leakage that occurred after a cerebellar tumor resection, which was treated successfully. Methods: A 53-year old male consulted our department for continuous CSF leakage for 3 months after having received conservative care and lumbar drainage. CSF collection was observed in the dead space of the posterior fossa after a cerebellar tumor resection and postoperative radiotherapy. Using a free latissimus dorsi muscle flap, the dead space within the skull was filled and the defects were covered successfully. Results: At 6 weeks after surgery, the follow-up MRI and CT revealed proper coverage and filling in the area where cerebellar tumor had been removed. No CSF leakage was observed at the postoperative 3 month follow-up. Conclusion: Recurrent CSF leakage was treated after cerebellar tumor resection with a relatively satisfactory result. In terms of the patient's treatment, much better results can be achieved by performing dead space filling using a flap with a sufficient size, in addition to coverage of the defects of the dura.

• Clinical and Experimental Pediatrics
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• v.46 no.4
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• pp.345-350
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• 2003

Purpose : Bacterial meningitis is a serious infection of childhood associated with a significant morbidity and mortality. Repeated cerebrospinal fluid(CSF) examination is a useful prognostic indicator and a delayed sterilization is associated with a higher incidence of neurologic abnormalities. In this study we tried to determine the prognostic value of repeated CSF latex agglutination testing. Methods : We retrospectively evaluated 19 patients admitted to Ewha Womans University Mokdong Hospital for bacterial meningitis from January 1997 to June 2002. Bacterial meningitis was confirmed by a positive CSF culture and a positive CSF latex agglutination test. Repeated CSF examinations were done at three, seven, 14, 21 and 28 days after antibiotics therapy. Neuroradiologic studies were performed. Results : The mean age was $10.6{\pm}12.3months$(range; two to 33 months). The male to female ratio was 2.8 : 1. The causative organisms were Haemophilus influenzae type b 57.9%, Group B Streptococcus 21.1%, Streptococcus pneumoniae 15.7% and Escherichia coli 5.3%. Three days after the initiation of antibiotics therapy, repeated CSF latex agglutination tests persisted as positive in nine (47.4%) out of 19 cases, but all CSF cultures became negative. In those cases with negative latex agglutination tests three days after antibiotics therapy, neuroradiologic findings were completely normal. But, in cases with positive latex agglutination tests three days after antibiotics therapy, neuroradiologic abnormalities such as cerebral infarction, encephalomalasia occurred in 44.4%. Conclusion : Repeated CSF latex agglutination testing was valuable as a prognostic factor in bacterial meningitis. Neuroradiologic abnormalities may occur in cases with delayed clearance of CSF latex agglutination tests more often than in cases with negative latex agglutination tests three days after antibiotics therapy.

• Applied Microscopy
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• v.40 no.2
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• pp.73-80
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• 2010

Liver regeneration is a result of highly coordinated proliferation of hepatocytes and nonparenchymal liver cells. Partial hepatectomy (PH) is the most often used stimulus to study liver regeneration because, compared with other methods that use hepatic toxins, it is not associated with the tissue injury and inflammation, and the initiation of the regenerative stimulus is precisely defined. Granulocyte macrophage-colony stimulating factor (GM-CSF), which is a cytokine able to regulate the proliferation and differentiation of epithelial cells, was first identified as the most potent mitogen for bone marrow. Particularly, rrhGM-CSF, which is highly glycosylated and sustained longer than any other types of GM-CSF in the blood circulation, was specifically produced from rice cell culture. In this experiment, effects of rrhGM-CSF administration were evaluated in the regenerating liver after 78% PH of rats. Morphological changes induced by PH were characterized by destroyed hepatocyte plate around the central vein and enlarged nuclear cytoplasmic ratio and increased hepatocytes with two nuclei. And then, proliferation of liver cells (parenchymal and nonparenchymal) and rearrangement of plates and lobules seemed to be carried out during liver regeneration. These alterations in the experimental group preceded those of the control. Since proliferating cell nuclear antigen (PCNA) is known to be a nuclear protein maximally elevated in the S phase of proliferating cells, the protein was used as a marker of liver regeneration after PH in rats. PCNA levels by western blot analysis and immunohistology were compared between the two groups. PCNA protein expression of two groups at 12 hr and 24 hr after injury showed similar pattern. The protein expression showed the peak at 3 days in both groups, however, the protein level of the experimental group was higher than that of the control. On immunohistochemical observations, the reaction product of PCNA was localized at the nuclei of proliferating cells and the positive reaction in experimental group at 3 days was clearly stronger than that in control group. The results by Western blotting and immunohistology for PCNA showed similar pattern in terms of the protein levels. In conclusion, rrhGM-CSF administration during liver regeneration after 78% PH accelerated breakdown and restoration of the hepatic plate and expression of PCNA. These results suggest that rrhGM-CSF might play an important role during liver regeneration in rats.

• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.286-291
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• 1994

The mutagenicity of DA-3030(rhG-CSF)was studied by reverse mutation test, chromosome aberration test and micronucleus test. The reverse mutatuon test in bacteria was performed using salmonella typhimurium strain TA100, TA98, TA1535 and TA1537 with rhG-CSF in any of the concentrations(150, 75, 37.5, 18.75, 9.375 and 4,6875 $\mu\textrm{g}$/plate), no increase in the number of revertant colonies in each strain was observed, irrespective of treatment with the metabolic activation system(S-9 mix) The chromosome aberration test was carried out using CHL cells, cell line from chinese hamster lung. With 4 doses(75, 37.5, 18.75 and 9.375 $\mu\textrm{g}$/ml) of rhG-/CSF the cells were treated for 24 or 48 hours in the direct method or for 6 hours followed by 18 hour-expression time in the metabolic activation method. Results of the study showed, by the direct method or metabolic activation method, no trend toward increase in the number of aberrant metaphase. The micronucleus test was carried out using ICR mice at the age of 8 weeks. Three doses(862.5, 1725 and 3450 $\mu\textrm{g}$/kg) of DA-3030 were admintstered intraperitoneally with single shot and bone marrow cells were sampled at 24 hours after administration. Neither the number of polychromatic erythrocytes with micronuclei nor the ratio of normochromatic erythrocytes to polychromatic erythrocytes increased singinficantly in each dose, compared with a vehicle control. These results indicate that rhG-CSF has not mutagenic potential under the condiions.

• Journal of Korean Neurosurgical Society
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• v.58 no.1
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• pp.1-8
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• 2015

Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques.

• The Journal of Korean Medicine
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• v.24 no.3
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• pp.145-154
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• 2003

Background : Production of cytokines by bronchial epithelial cells may contribute to the local accumulation of inflammatory cells in patients with bronchial asthma. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of asthma. Objective : We aimed to identify the dose-dependent inhibitory effects of Lonicerae Flos and Paeoniae Radix on the mRNA expression of IL-6, IL-16, and GM-CSF involved in the asthma model. Materials and Methods : In the study BEAS-2B cell lines, human epithelial cells were used. These cells were stimulated with tumor necrosis factor $(TNF)-\alpha$ for artificial inflammatory expression. ${\beta}-actin$ messenger RNA (mRNA) was used for internal standard. After 24 hours of Lonicerae Flos, Paeoniae Radix, total cellular RNAs were collected treating RNA zol directly on the living cells. Then the transcriptional activities of IL-6, 16, GM-CSF were measured by RT- PCR with electrophoresis. Results : In the Lonicerae Flos study, the mRNA expression of IL-6, IL-16 and GM-CSF was showed no inhibitory effect compared to the control group in all concentrations. In the Paeoniae Radix study, the mRNA expression of IL-6, IL-l6 and GM-CSF was showed no inhibitory effect compared to the control group in all concentrations. Conclusion : This study shows that Lonicerae Flus and Paeuniae Radix have no inhibitory effects on the mRNA expression of IL-6, IL-16 and GM-CSF in BEAS-2B cell lines, human epithelial cells. Advanced studies are required to investigate the other mechanisms of inhibitory effect by Lonicerae Flus and Paeoniae Radix in the asthma model.

• Journal of Korean Neurosurgical Society
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• v.38 no.1
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• pp.1-11
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• 2005

Objective : The purpose of this study is to evaluate the correlation of the ICAM-l levels in serum and CSF with cerebral vasospasm in early aneurysmal subarachnoid hemorrhage [SAH] patients. Methods : A prospective analysis was performed in thirty consecutive patients who underwent early surgery for intracranial aneurysmal SAH. The serum and CSF were obtained daily through the indwelling arterial lines and intraoperative ventriculostomy, or cisternal drain for 4 consecutive days after surgery. The ICAM-1 levels in serum and CSF samples were measured via quantitative enzyme-linked immunosorbent assay. Results : The mean concentration of serum in aneurysmal SAH patients was 207.89ng/ml compared with 132.25ng/ml in controls. The mean concentration of CSF in aneurysmal SAH patients was 76.39ng/ml compared with 3.96ng/ml in controls. There were no significant differences between serum and CSF ICAM-1 level with regards to clinical characteristics in patients with aneurysmal SAH [P>0.05]. However, CSF ICAM-1 levels increased significantly in patients with vasospasm compared with those without vasospasm [P<0.05]. Conclusion : The major result of this study shows that ICAM-1 is increased in CSF after early aneurysmal SAH and that this increase in ICAM-1 has correlation with cerebral vasospasm. Further study is needed to determine whether ICAM-1 levels may be indicator in the pathogenesis of important events leading to cerebral vasospasm.

• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.316-322
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• 1997

CJ-50001 is a recombinant granulocyte-colony stimulating factor (rG-CSF) synthesized by recombi-nant DNA technology using E. coli as an expression system. The general pharmacological properties of CJ-50001 were evaluated in mice, rats, dogs and isolated guinea pig ileum. The doses are 100, 300 and 1, 0007g/kg, i.v. for mice and rats, 1, 10 and 100$\mu$g/kg, 1.v. for dogs and 1 and 10$\mu$g/ml for isolated guinea pig ileum. Intravenous administration of CJ-50001 at this dose range did not affect general behavior, central nervous system, smooth muscles, gastrointestinal system, cardiovascular and respiratory system and water and electro-lytes excretion. In summary, CJ-50001 had no harmful pharmacological erect in these studies even up to the 200-fold expected clinical dose, 2507g/man.

• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.256-259
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• 1994

This study was performed to evaluate the acute toxicity of DA-3030(granulocyte-colony stimulating factor, G-CSF) in mice and rats via intragastrical and intravenous routes. DA-3030(G-CSF) in the acute toxicity study did not induce any toxic signs in the mice and rats in mortalities, clinical findings, body weights and gross findings. It is suggested that LD$_{50}$ values in mice and rats would be >13, 800 $\mu\textrm{g}$/kg in the oral route and >6, 900 $\mu\textrm{g}$/kg in the intravenous route.e.