Blood Neutrophil-to-Lymphocyte Ratio Predicts Tumor Recurrence in Patients with Hepatocellular Carcinoma within Milan Criteria after Hepatectomy

PURPOSE: The systemic inflammation biomarker, Neutrophil-to-Lymphocyte Ratio (NLR), has been reported as one of the adverse prognostic factors for hepatocellular carcinoma (HCC) patient. The purpose of this study was to evaluate whether NLR could predict the risk of recurrence and death for the HCC patient, according to Milan criteria after hepatectomy. MATERIALS AND METHODS: Retrospective analysis was performed on a database of HCC patients who underwent hepatectomy between March 2001 and December 2011. The cutoff value of NLR was decided by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate regression analyses were performed to identify predictive factors of recurrence and death. RESULTS: A total of 213 patients were included in the present study. The median follow-up period was 48 months. One hundred and seven patients were experienced tumor recurrence; forty of them recurred within 12 months (early recurrence). NLR ≥1.505, albumin ≤3.75 g/dL, microvascular invasion and high grade of cirrhosis were found to be independent factors for adverse recurrence-free survival in multivariate regression analysis. And NLR ≥1.945 was also found as a prognosis factor for early recurrence by univariate regression analysis. CONCLUSION: Elevated preoperative NLR can be easily obtained and reliable biomarker for assessing the tumor recurrence and early recurrence of Milan criteria HCC after the initial hepatectomy.

Variation or newly identified glissonian pedicles between the lateral and medial sections of the liver, using cadaver dissection / 대한외과학회지

PURPOSE: Studies of liver anatomy have developed alongside clinical achievements, as these types of research complement each other. The aim of this study is to determine whether or not the portal vein branches (P4d) in 'Nagino's trisectionectomy' exist, and to examine their characteristics using cadaver dissection. METHODS: From April 2012 to July 2012, 31 adult cadavers were delicately dissected. We defined a 'NewGP' as an extra glissonian pedicle (GP) other than the traditional GPs that supply segments II, III, IVa, and IVb in the ordinary direction, and anatomically located superior to the umbilical fissure (UF). RESULTS: We identified 'NewGPs' based on the UF and UF vein. The incidence of 'NewGPs' was 30/31 (96.8%). The diameter of the 'NewGPs' ranged from 3.5 to 5.6 mm, which was not significantly different from that of traditional GPs (II-, III-, or IV-GP), which have diameters ranging from 3.7 to 9.7 mm. CONCLUSION: We think that the P4d in 'Nagino's trisectionectomy' correspond to the 'IVa NewGP' and the additional pedicle. We believe the clinical significance of the 'NewGP' is to complement the traditional II, III, IVa, and IVb pedicles in supplying the liver.

Epidemiology and Clinical Features of Post-Transplant Bloodstream Infection: An Analysis of 222 Consecutive Liver Transplant Recipients / 감염과화학요법

BACKGROUND: Bloodstream infection (BSI) is a significant cause of morbidity and mortality in liver transplant (LT) recipients. This study aimed to investigate the epidemiology and clinical features of post-transplant BSI in LT recipients. MATERIALS AND METHODS: The microbiology, frequency, and outcome of post-transplant BSI in the first year after LT were retrospectively analyzed in 222 consecutive patients who had received liver transplants at a single center between 2005 and 2011. The risk factors for post-transplant BSI and death were evaluated. RESULTS: During a 1-year period after LT, 112 episodes of BSI occurred in 64 of the 222 patients (28.8%). A total of 135 microorganisms were isolated from 112 BSI episodes including 18 polymicrobial episodes. The median time to BSI onset ranged from 8 days for Klebsiella pneumoniae to 101 days for enterococci, and the overall median for all microorganisms was 28 days. The most frequent pathogens were Enterobacteriaceae members (32.5%), enterococci (17.8%), yeasts (14.0%), Staphylococcus aureus (10.3%), and Acinetobacter baumannii (10.3%); most of them showed resistance to major antibiotics. The major sources of BSI were biliary tract (36.2%), abdominal and/or wound (28.1%), and intravascular catheter (18.5%) infections. The independent risk factors for post-transplant BSI were biliary complications (odds ratio [OR]: 2.91, 95% confidence interval [CI]: 1.29 to 6.59, P = 0.010) and longer hospitalization in the intensive care unit (OR: 1.04, 95% CI: 1.00 to 1.08, P < 0.001) after LT. BSI was an independent risk factor for death (hazard ratio [HR]: 3.92, 95% CI: 2.22 to 6.91, P < 0.001), with a poorer survival rate observed in patients with BSI than in those without BSI (1-year survival rate: 60.0% versus 89.5%, respectively, P < 0.001) after LT. The strongest predictors for death in patients with BSI were hepatocellular carcinoma (HR: 3.82, 95% CI: 1.57 to 9.32, P = 0.003), candidemia (HR: 3.71, 95% CI: 1.58 to 8.71, P = 0.003), polymicrobial bacteremia (HR: 3.18, 95% CI: 1.39 to 7.28, P = 0.006), and post-transplant hemodialysis (HR: 2.44, 95% CI: 1.02 to 5.84, P = 0.044). CONCLUSIONS: BSI was a frequent post-transplant complication, and most of the causative pathogens were multi-drug resistant. Biliary complications and BSIs resulting from biliary infection are major problems for LT recipients. The prevention of BSI and biliary complications is critical in improving prognosis in liver transplant recipients.

Usefulness of the Pinch-Burn-Cut (PBC) technique for recipient hepatectomy in liver transplantation

BACKGROUNDS/AIMS: Surgical bleeding during recipient hepatectomy is a major concern in liver transplantation (LT). Effective intraoperative control of bleeding is necessary. In the Pinch-Burn-Cut (PBC) technique, a small amount of tissue around the dissection plane is pinched with forceps, electocauterized and gently cut. The present study sought to estimate the usefulness of the PBC technique in LT. METHODS: Between June 2007 and December 2010, 123 adult cases underwent LT in our center. Of these, 72 involved a recipient hepatectomy using the PBC technique (PBC group). and 51 involved the conventional technique (non-PBC group). Clinical parameters were compared between two groups. RESULTS: The amount of blood loss and related transfusions were significantly reduced, and the operating time was shorter in the PBC group than in the non-PBC group (p=0.006, p<0.05 and p=0.002, respectively). There was also shorter duration of mechanical ventilation after LT in the PBC group (p=0.017). The incidence of postoperative hemorrhage was lower in the PBC group than in the non-PBC group, but had no statistical significance between two group (19.6% vs. 8.3%, p=0.101). CONCLUSIONS: Our data suggest that the PBC technique is effective for bleeding control during recipient hepatectomy in LT.

Therapeutic effects of recombinant Salmonella typhimurium harboring CCL22 miRNA on atopic dermatitis-like skin in mice

Th-2-biased immune responses are known to play a key role in the pathogenesis of atopic dermatitis. In particular, the macrophage-derived chemokine CCL22 is directly implicated in Th-2-associated skin inflammatory reactions, and its levels are significantly elevated in serum and are correlated with disease severity in atopic dermatitis. In this study, we tested the development of genetic therapeutic options to treat atopic dermatitis using bacteria expressing miRNA. We constructed a recombinant strain of Salmonella typhimurium expressing CCL22 miRNA (ST-miRCCL22) for the in vivo knockdown of CCL22. The CCL22 gene was downregulated with CCL22 miRNA in activated lymphocytes. In mice with a cutaneous disease similar to atopic dermatitis, interleukin-4 was inhibited and interferon-gamma was induced after treatments with ST-miRCCL22. Furthermore, CCL22 levels were suppressed in the atopic mice treated with ST-miRCCL22. These results suggest that ST-miRCCL22 may be an effective genetic agent for treating atopic dermatitis.

Anatomical Variation of the Glissonean Pedicle of the Right Liver

PURPOSE: Many studies have been conducted to date regarding whether the right hepatic vein is the accurate border that divides the anterior and posterior section of the right liver. It has been reported that the Glisson pedicle of the right liver may be an anatomical variation that does not have a consistent morphology. We analyzed the relationship between the true borders of the anterior and posterior sections, and the right hepatic vein, based on cadaver dissection and MD-CT image analysis of the anatomical variation of the Glisson pedicle of the right liver. METHODS: Sixteen cadaver livers were available for dissection from the Department of Anatomy, and pre-operative MD-CTs of 20 donor livers who underwent living donor liver transplantation prior to December 2009, were obtained. We analyzed the 3D-relationship between the branches of the Glisson pedicles and the right hepatic vein of the right liver. They were divided into 3 groups according to the sliding pattern of the branches of the Glisson pedicle origin. When all segmental branches of the anterior pedicle arise from the main trunk of the anterior pedicle and all branches of posterior pedicle arise from the main trunk of posterior pedicle, it was designated as Group A (Normal Group). When a portion of the segmental branches of the anterior pedicle arises from the main trunk of the posterior pedicle, it was designated as Group B (Posterior dominant group). When a portion of the branches of the posterior pedicle arises from the main trunk of the anterior pedicle, it was designated as Group C (Anterior dominant group). RESULTS: Among the 16 cadaver liver dissections, 6 cases were in Group A, 5 in Group B, and 3 in Group C. Two cases were excluded from the study because the inferior right hepatic vein was the main draining vein of the right liver. The analysis of preoperative MD-CT of the 20 donor livers showed that there were 13, 4, and 3 patients in Groups A, B, and C, respectively. CONCLUSION: According to Couinaud's theory of anatomy, the right hepatic vein serves as the border between the anterior and posterior sections of the right liver. But, due to the frequent anatomical variations, an adequate understanding of the anatomical variations of the right Glisson pedicle should be necessary for liver surgery.

Living donor liver transplantation for Patients with beyond Milan hepatocellular carcinoma

BACKGROUND: To find the patients who have a significant chance of cure with living donor liver transplantation (LDLT) among the patients suffering with beyond-Milan hepatocellular carcinoma (HCC), we retrospectively analyzed the tumor factors that could affect a good prognosis after LDLT for patients who suffer with beyond Milan HCC. METHODS: Between March 2005 and May 2007, 18 cases of LDLT for beyond Milan HCC were performed. None of the patients had preoperative radiological evidence of vascular invasion. Excluding the 3 cases of in-hospital mortality, we analyzed the survival, the disease-free survival and the prognostic factors for recurrence in 15 beyond Milan HCC patients. The mean follow-up period was 18.8degrees +/- 8.8 months (range: 4-34 months). RESULTS: The two-year survival and disease-free survival rates after LDLT were 61.7% and 31.1%, respectively, in 15 beyond-Milan patients. Among them, 9 patients had recurrence of HCC during follow-up. The one-year survival rate after tumor recurrence was 55.5%. An alphafetoprotein (AFP) level < 400 ng/mL, Edmonson-Steiner histology grade I and II and the presence of graft rejection were analyzed as the good prognostic factors of disease-free survival after LDLT for beyond-Milan HCC (p < .05). The patients with negative preoperative positron emission tomography (PET) findings (n = 5) showed a better prognosis than the PET-positive patients (n = 10) with statistical significance (p = .05). CONCLUSION: Allowing that HCC patients exceed the Milan criteria, we can find the potentially curable candidates for LDLT with using tumor biologic markers such as a serum AFP level < 400 ng/mL, negative PET uptake or low grade histology, as assessed by preoperative needle biopsy. Further investigation is needed to evaluate the relation between graft rejection and tumor recurrence after liver transplantation.

Amantadine and Zanamivir Resistance of Influenza A/H3N2 Viruses Isolated in Korea, 2002/03~2003/04

To investigate the emergence and prevalence of antiviral resistance, we analyzed influenza A/H3N2 viruses isolated in Korea during 2002/03 to 2003/04 season by genetic and phenotypic assay. For the genetic analysis to the amantadine, an M2 protein inhibitor, the M gene was amplified by RT-PCR and regions corresponding to the amino acid at positions 27, 30, and 31 were amplified by nested PCR with size of 154 bp, 95 bp, and 153 bp fragments, respectively. A total of 3 of 31 (9.7%) viruses were found to be mutated by restriction fragment length polymorphism (RFLP) with Sca I and sequence analysis, showing the single amino acid change (Ser to Asn) at position 31. Also it was observed that their growths in Madin-Darby Canine Kidney (MDCK) cells were unaffected by amantadine (up to 1 microgram/ml) in both plaque assay and WST-1 assay, confirming that these viruses were resistant against amantadine. We also examined the resistant pattern against zanamivir, a neuraminidase inhibitor, for 15 Korean influenza A/H3N2 viruses isolated in 2002~2003 season. Sequence analysis showed that there were no genetic changes of NA genes including R292K, K274Y, R152K, and E119V which were related to resistance against the neuraminidase inhibitor. In the NA inhibition assay to zanamivir, Korean isolates were found to be sensitive, ranging from 0.17 nM to 1.77 nM in 50% inhibitory concentration (IC(50)). These results suggest that monitoring for the antiviral resistance should be intensified and maintained to provide guideline for prophylaxis and treatment of influenza in Korea.

Reconstruction of the Middle Hepatic Vein in Right Lobe Living Donor Liver Transplantation: The Experience at Ajou University Hospital

Reconstruction of the middle hepatic vein (MHV) tributaries, in modified right lobe grafts, appears to be effective for solving the congestion problem of the right paramedian sector (segment V, VIII). Various methods have been proposed to maintain efficient graft outflow for right lobe grafts without the middle MHV by centers with a high volume of procedures. Since December 2005, we adopted the bench procedure for reconstruction of a modified right lobe graft into the shape of an extended right lobe graft with a venous pouch to form a common trunk between the MHV (or newly reconstructed MVH) and right hepatic vein (RHV) using a cryoperserved aortic patch or bovine pericardium. Before December 2005, the graft RHV and MVH were anastomosed to the recipients' RHV and MHV/left hepatic vein. In this study, we compared the results of these two different methods (23 recipients of the direct and separate anastomosis, group A; 40 recipients of formation of a common outflow trunk, group B). The two groups were comparable in terms of preoperative parameters. Compared with group A, the middle hepatic vein patency length in group B was much better (p = 0.000). The necessity of metallic stenting due to early occlusion of the hepatic vein was significantly decreased in Group B (Group A; 5/21 vs. Group B; 2/40, p = 0.042). However, 1-year patient and graft survival was not different between the two groups (p = 1.000). Our procedure for constructing a modified right lobe graft into an anatomical figure with the extension of the right lobe graft and reconstruction of a wider outflow tract might provide an effective functioning liver mass and help to improve the outcomes in these patients.

The Effect of Preoperative Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma

OBJECTIVE: To evaluate the impact of preoperative transarterial chemoembolization (TACE) for the treatment of patients undergoing curative liver resection for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Preoperative TACE was performed in 164 of 339 HCC patients that had a curative resection and follow-up. Retrospective clinico-pathological analysis was performed with regard to the safety and response to treatment, early and late incidence and the pattern of recurrence as well as survival. RESULTS: For 159 patients in the TACE group (96.9%), TACE was performed preoperatively only once. The mean waiting time from TACE to resection was 19.5 days. There was no difference in the operative time, postoperative mortality and duration of hospital stay after resection between the two groups (patients that underwent TACE and patients that did not undertake the procedure). Ed-highlight-you did not define the two groups-is the above description in parentheses accurate? Microvascular invasion was significantly decreased in the TACE group (p < 0.01) and complete necrosis of the tumor was induced in 21 patients (12.8%) of the TACE group. Early and late recurrence patterns were not different between patients in the two groups. Overall survival and disease-free survival rate was not different between patients in both groups. However, the 3 year disease-free survival rate was significantly improved in the TACE group (p = 0.04) and the 3 year disease-free survival rate was also improved (p = 0.06), especially for patients with AJCC stage I or II. Multivariate analysis showed microvascular invasion, large tumor size, the presence of daughter nodules, gross portal invasion, Child classification and histological stage of cirrhosis to be risk factors for HCC recurrence and poor survival. CONCLUSION: Preoperative TACE is a safe procedure and can improve early postoperative recurrence and survival, especially in stage I or II HCC patients.

Outflow Reconstruction using Cryopreserved Aortic Patch in Right Lobe Living Donor Liver Transplantation

METHODS: Living donor liver transplantation (LDLT) using a right lobe graft has been widely used to compensate for the cadaveric organ shortage. Successful reconstruction of the middle hepatic vein (MHV) is required to provide an adequate functional volume in LDLT with using the right lobe. We describe herein a new technique using a cryo-preserved aortic patch for outflow reconstruction of the right lobe graft with or without MHV. METHODS: From November 2005 through March 2006, 20 adult patients who received a right lobe graft (n=10) or an extended right lobe graft (n=10) for LDLT were included. During the bench procedure of the right lobe graft, we reconstructed the new MHV with using cryopreserved veins just like the MHV of the extended right lobe graft, and we then made a venous pouch to form a common trunk between the MHV (or new MHV) and the RHV of the right lobe graft with using a cryopreserved aortic patch. During graft implantation, anastomosis of an outflow tract was made between the venous pouch of the graft and the common trunk of recipient's RHV-MHV-LHV. One week following the transplantation, measurement of the pressure gradient between the MHV and IVC was done, as well as performing regular follow-up 3D-CT scans and liver function tests. RESULTS: The mean pressure gradient between the reconstructed MHV and the recipient's IVC was 2.3+/-1.2mmHg, and in all cases, the serial liver function tests showed gradual improvement as the days progressed post-operatively. There was no evidence of hepatic venous congestion of the graft and/or obstruction of the reconstructed MHVs according to the serial postoperative follow-up images of the Doppler US and MD-CT. CONCLUSION: We suggest that reconstructing the outflow tract with a cryopreserved aortic patch is a good alternative technique for preventing anterior segment congestion in LDLT with using a right lobe graft with or without MHV.

Brain Metastases Developed in Advanced Colorectal Cancer Patients who Underwent Multi-drug Chemotherapy

PURPOSE: Brain metastasis from colorectal cancer is a rare clinical condition. We have experienced five cases of brain metastases in a relatively short period of time during extensive chemotherapy for advanced colorectal cancer. To examine whether this phenomenon is a simple coincidence or there is a correlation with prolongation of life span in patients with stage IV colorectal cancer, we analysed five patients with brain metastases. METHODS: The case histories of 47 patients with unresectable systemic metastases who had undergone sequential chemotherapy (FOLFOX and FOLFIRI) in Ajou University Hospital from August 2002 to December 2004 were reviewed and analyzed for clinical characteristics. The sites of unresectable metastases were the liver (n=28), the lung (n=28), and the paraaortic nodes (N=6). Diagnostic criteria of unresectable metastasis were multiple or bilobar lesions in hepatic metastasis and multilobar involvement in pulmonary metastasis. RESULTS: There was no complete remission. Partial remission was noted in 31.9% of the patients and stable disease in 8.5%. Sequential chemotherapy showed no effect in 59.6% of the patients. Brain metastases occurred in five patients (10.6%). Accompanying metastases were found in the lung (n=4), the liver (n=3), the paralortic lymph nodes (n=2), and bone (n=1). Four patient (21.0%) were noted in the response group. The mean interval from primary cancer surgery to the diagnosis of brain metastasis was 27.5 (20~44) months. From the start of chemotherapy, brain metastasis was diagnosed at an average of 10.5 (8~16) months. Metastasectomies were performed in three patients, and stereotaxic radiosurgery was performed in two patients. One patient died with the disease, and four patients have been alive with the disease for more than six months. CONCLUSIONS: It is still unclear whether the increasing incidence of brain metastasis is related with prolongation of life expectancy in patients with stage IV colorectal cancer. However, about half of the stage IV colorectal cancer patients were found to obtain meaningful survival benefits by sequential chemotherapy, and 20% of chemo- responders showed brain metastases. Therefore, we conclude that the increasing incidence of brain metastasis seems to correlate with prolongation of life expectancy in stage IV colorectal cancer.

Pelvic Exenteration as the Treatment for Recurrent or Locally Advanced Rectal Cancer

PURPOSE: The purpose of this study is to evaluate the value of pelvic exenteration (PE) for recurrent or locally advanced rectal cancer. METHODS: This retrospective study analyzed 20 patients who underwent PE for rectal cancer from June 1994 to October 2003 in Ajou University Hospital. The surgical severity, the postoperative complications, and the survival rate were analyed based on the medical records. RESULTS: The mean operation time was 221.5+/-93.0 minutes, the mean blood loss 750.5+/-223.3 cc, and the mean transfusion amount RBC 6.5+/-4.3 units. Operative mortality was 5% (1/20). A bleeding-associated complication was noted in one patient who underwent a reoperation for hemostasis. Other minor complications were small bowel obstruction (n=3), abdominal wound infection (n=5), vesicocutaneous fistula (n=2), delayed healing of the perineal wound (n=10). The overall 5-year survival rate was 52.6% (10 of 19 patients, excluding the operative mortality case). CONCLUSIONS: Our study showed acceptable surgical severity and postoperative complications and a favorable 5-year survival rate (> or =50%) for pelvic exenteration as a treatment for recurrent or locally advanced rectal cancer. With strictly selected patients, PE may be one of the treatment options for recurrent or locally advanced rectal cancer.

A case of reactive airway dysfunction syndrome due to chlorine gas exposure / 천식및알레르기

The reactive airway dysfunction syndrome (RADS), a subset of irritant-induced asthma, has been described following exposure to various irritant gas. We describe a case of RADS occuring following a single exposure to high levels of chlorine gas in the workplace. No documented pre-existing respiratory illness and atopy was identified. Cough, dyspnea, and wheezing were developed with the single accidental exposure to chlorine gas and methacholine provocation test was positive. He was completely recovered with the treatment of corticosteroid and oxygen therapy.

The relationship between airway remodeling and transforming growth factor-beta1 and basic fibroblast growth factor expression in bronchoalveolar lavage cells from asthmatics / 천식및알레르기

BACKGROUND AND OBJECTIVE: Airway wall remodeling such as epithelial shedding, increased basement membrane thickness, subepithelial fibrosis is established pathological features in asthma. However the pathogenesis of this structural alteration is not well understood. In other chronic inflammatory diseases, fibrotic change occurs usually and the growth factor for fibroblast is particulary important. Our purpose was to study whether transforming growth factor-beta1 (TGF- beta1) and basic fibroblast growth factor (bFGF) were related to airway remodeling. METHODS: In asthmatics (n=24) and non-asthma controls (n=4), epithelial shedding and basement membrane thickness were measured by hematoxylin-eosin stain and the degree of subepithelial fibrosis was measured by Masson-trichrome stain. TGF- beta1 and bFGF positive cells were measured in BAL fluid by immunocytochemical stain using monoclonal antibody. RESULTS: Epithelial shedding (20.00 +/- 11.55% vs 49.77 +/- 30.80%, P<0.01) and basement membrane thickness (8.25 +/- 2.63 micrometer vs 13.50 +/- 4.36 micrometer, P<0.05) were significantly increased in asthmatics than controls. And the degree of subepithelial fibrosis in asthmatics had increased tendency as compared with controls (52.5 +/- 12.56 micrometer vs 117.05 +/- 63.73 micrometer, P=0.06). The degree of epithelial shedding was significantly increased in severe asthmatics as compared with controls, mild and moderate asthmatics (31.25 +/- 26.96% vs 65.42 +/- 27.59%, P<0.05) and basement membrane thickness was significantly increased in moderate, severe asthmatics as compared with controls (8.25 +/- 2.63 micrometer vs 14.50 +/- 4.85 micrometer, P<0.05) but the degree of subepithelial fibrosis according to clinical severity was statistically insignificant. TGF- beta1 expression in asthmatics was significantly higher than control group (0.00 +/- 0.00% vs 13.13 +/- 22.35%, P<0.05), and bFGF expression had increased tendency in asthmatics but statistically insignificant. There was no significant correlation between the degree of basement membrane thickness, subepithelial fibrosis and TGF- beta1 or bFGF expression in BAL cells from asthmatics. Severity of asthma, duration of asthma, FEV1, and PC20 were not correlated with TGF- beta1 or bFGF expression. CONCLUSION: We showed that bronchial epithelial shedding, basement membrane thickening and subepithelial fibrosis were observed in asthmatics, and the expression of TGF- beta1 was increased in asthmatics. These results suggested that TGF- beta1 might be related to the airway remodeling. But the direct correlation between TGF- beta1 or bFGF expression in BAL cells and the degree of airway remodeling was not observed. Further studies on other growth factors, TGF- beta1 and bFGF expression in bronchial mucosal tissue and time sequence of cytokine expression on airway remodeling should be needed.

High Frequencies of the CCR2b-64I and SDF1-3'A Mutations with HIV Infection in Koreans

BACKGROUND: Host genetic polymorphisms in the HIV-1 co-receptor CCR5 and CCR2b and SDF-1, ligand for co-receptor CXCR4, have been known to be associated with the resistance of HIV infection and/or the delayed disease progression in HIV-infected patients. METHODS: We examined the frequencies of SDF1-3'A and CCR2b-64I alleles of 354 Koreans including 100 HIV-uninfected persons, 13 discordant spouses of HIV-infected persons, and 241 HIV-infected persons. The genotyping assays of SDF1 and CCR2b genes were carried out by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequencies of CCR2b-64I and SDF1-3'A alleles in Koreans were very high compared with Caucasians and blacks. Observed frequencies of CCR2b-64I and SDF1-3'A allelic variants were 25.1% and 28.7%, respectively. The frequency of the CCR2b-64I allele in Koreans was 2~4 times higher than those of other ethnic groups with the exception of Asian. The frequencies of CCR2b-64I and SDF1- 3'A genotypes did not show the significant difference between HIV-infected and uninfected Koreans. However, the prevalence of CCR2b-64I genotype of the LTNP group was about two times higher than that of the remainder group (P < 0.05). Four (45%) out of 9 LTNPs (long-term nonprogressors) showed having the SDF1-3'A allele and 7 (78%) out of 9 LTNPs carried the CCR2b-64I allele. 3 (33%) out of 9 LTNPs had both SDF1-3'A and CCR2b-64I alleles. But none of 5 RPs (rapid progressors) appeared to have both SDF1-3'A and CCR2b-64I alleles. CONCLUSION: The different genetic backgrounds in study populations may affect the disease progression and the AIDS epidemic in each country. Further studies need to define whether high frequencies of CCR2b-64I and SDF1-3'A allelic variants may affect the HIV disease progression.

Analysis of Viral Phenotype (SI / NSI) and V3 Domain Amino Acid Sequence in the Various HIV - 1 Subtype Isolates

No abstract available.

Anti-inflammatory Effects of Pentoxifylline and Neutrophil Elastase Inhibitor on Lipopolysaccharide-Induced Acute Lung Injury In Vitro / 결핵

BACKGROUND: Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. METHODS: To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1,1:1,1:5,0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as will as mRNA expressions of TNF-α, inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. RESULTS: (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. The effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to expaerimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of TNF-α, MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of TNF-αand IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL-β and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed atrend to attenuate LPS-induced mRNA expressions of TNF-α and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. CONCLUSION: These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.

The Levels of Interferon-gamma, Interleukin-2 Receptor, Interleukin-6 and Interleukin-10 in the patients with Malignant Pleural Effusion, Tuberculosis Effusion, Parapneumonic Effusion, and Lung Emphysema? / 결핵

BACKGROUND: Cytokines are chemical mediators that control and modulate many infalmmatory processes. They work in different fashions in a variety of diseases. Discriminating between malignant effusion, tuberculous effusion, and parapneumonic effusion are crucial from the clinical view-point in Korea. In the current study, interferon-gamma(INF-γ), soluble interleukin-2 receptor(IL-2R), interleukin-6(IL-6) and interleukin-10(IL-10) were measured for this purpose. METHODS: Pleural fluids from patients with malignant disease, tuberculosis, parapneumonic effusion and lung empysema were collected and gauged using commercial ELISA kits. RESULTS: 34 patients were enrolled in this study. among these 15 cases were malignant effusions, 12 were tuberculosis pleurisy and 7 were paraneumonic effusion and lung empyema. The levels of cytokines measured in this study were as follows, in order of frequency, malignant effusion, tuberculous effusion, parapneumonic effusion and lung empyema. The levels of INF-γ were higher in tuberculous effusion than in malignant or parapneumonic effusion(295.5±585.5 vs. 16.7±50 vs. 10.0±0 pg/ml, p>0.05). The levels of IL-2R were higher in tuberculous effusion than in malignant or parapneumonic effusion(7423.5±3752.8 vs. 3247.4±1713.3 vs. 3790.2±3201.1 pg/ml, p<0.05). No significant differences were found in the levels of IL-6 between the groups(600±12.8 pg/ml in malignant effusion, 556.4±161.7 pg/ml in tuberculous effusion, 514.4±224.8 pg/ml in parapneumonic effusion). IL-10 levels were higher in parapneumonic effusion than in malignant or tuberculous effusions(98.4±141.7 vs. 28.2±55.5 vs. 11.3±11.7 pg/ml, p<0.05). CONCLUSION: These results suggest that the measurement of IL-2R levels in pleural fluids may be a useful means of differentiating between tuberculous effusion and pleural effusions of other origins, and that the measurement of IL-10 levels in pleural fluids may be useful to differentiate between parapneumonic effusion and pleural effusions of other origins.

The Altered Pattern of CD28 Expression on T Cell Subsets in HIV-Infected Koreans / 대한면역학회지

The CD8(+)CD28(+) T cells have known to mediate major histocompatibility complex class I-restricted cytolysis and to secret an HIV-1 inhibitory factor. As HIV infection lead to dramatic changes within the cellular immune system, the cellular cytotoxicities decrease in the duration of the HIV infection. To determine the importance of the cellular cytotoxicities in long-term nonprogression, we tried to compare CD28 expression on total T, CD4(+) T, and CD8(+) T cells as one of methods for cellular cytotoxicity measurements between long-term nonprogressor and normal person or between long-term nonprogressor and rapid progressor. The median percentages and counts of CD4(+) T cells of the norrnal, the long-term nonprogressor, and the rapid progressor groups were 39.9 and 0.96 * 10(9) cells/L, 24.6 and 0.58 * 10(9) cells/L, 9.9 and 0.15 * 10 cells/L, respectively. As a result of comparison of the cells having CD28 surface molecules on CD8(+) T cells in the long-term nonprogressor and the rapid progressor group, they showed over 5 times lower than that in the normal group. Especially, the long-term nonprogressor regarded to the healthy HIV-infected patient showed much lower CD28 expression on total T, CD4(+) T, and CD8(+) T cells than those of the normal person. The proportions of CD4'CD28 T and CD3CD28 T cell subsets showed the significant difference between the LTNP and the RP group. In conclusion, although HIV-infected patients were LTNPs having the steady CD4(+) T cell counts and no clinical symptoms, we suggested that HIV led to abnormality within the lymphocyte subsets such as the altered expression of CD28 molecules on various T cell subsets and this result would cause deficiency of host immune function and failure of control of HIV replication by anergy in T cell subsets.