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1.
BMC Cancer ; 21(1): 295, 2021 Mar 20.
Article in English | MEDLINE | ID: mdl-33743635

ABSTRACT

BACKGROUND: PCNA-associated factor, the protein encoded by the KIAA0101/PCLAF gene, is a cell-cycle regulated oncoprotein that regulates DNA synthesis, maintenance of DNA methylation, and DNA-damage bypass, through the interaction with the human sliding clamp PCNA. KIAA0101/PCLAF is overexpressed in various cancers, including hepatocellular carcinoma (HCC). However, it remains unknown whether KIAA0101/PCLAF overexpression is coupled to gene amplification in HCC. METHODS: KIAA0101/PCLAF mRNA expression levels were assessed by quantitative real-time PCR (qRT-PCR) in 40 pairs of snap-frozen HCC and matched-non-cancerous tissues. KIAA0101/PCLAF gene copy numbers were evaluated by droplet digital PCR (ddPCR) in 36 pairs of the tissues, and protein expression was detected by immunohistochemistry (IHC) in 81 pairs of formalin-fixed paraffin-embedded (FFPE) tissues. The KIAA0101/PCLAF gene copy number alteration and RNA expression was compared by Spearman correlation. The relationships between KIAA0101 protein expression and other clinicopathological parameters, including Ki-67, p53, and HBsAg protein expression in HCC tissues, were evaluated using Chi-square test. RESULTS: Our results demonstrated that KIAA0101/PCLAF mRNA levels were significantly higher in HCC than in the matched-non-cancerous tissues (p < 0.0001). The high KIAA0101/PCLAF mRNA levels in HCC were associated with poor patient survival. The KIAA0101/PCLAF gene was not amplified in HCC, and KIAA0101/PCLAF gene copy numbers were not associated with KIAA0101/PCLAF transcript levels. KIAA0101 protein was overexpressed in the majority of HCC tissues (77.8%) but was not detectable in matched-non-cancerous tissues. Significant correlations between the expression of KIAA0101 protein in HCC tissues and p53 tumor suppressor protein (p = 0.002) and Ki-67 proliferation marker protein (p = 0.017) were found. However, KIAA0101 protein levels in HCC tissues were not correlated with patient age, tumor size, serum AFP level, or the HBsAg expression. CONCLUSIONS: KIAA0101/PCLAF mRNA and protein overexpression is frequently observed in HCC but without concurrent KIAA0101/PCLAF gene amplification. Significant correlations between the expression of KIAA0101 protein and p53 and Ki-67 proteins were observed in this study. Thus, detection of KIAA0101/PCLAF mRNA/protein might be used, along with the detection of p53 and Ki-67 proteins, as potential biomarkers to select candidate patients for further studies of novel HCC treatment related to these targets.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , DNA-Binding Proteins/genetics , Liver Neoplasms/genetics , Carcinoma, Hepatocellular/pathology , DNA Copy Number Variations , Female , Gene Amplification , Gene Dosage , Gene Expression Regulation, Neoplastic , Humans , Ki-67 Antigen/genetics , Liver/pathology , Liver Neoplasms/pathology , Male , Middle Aged , RNA, Messenger/metabolism , Retrospective Studies , Tumor Suppressor Protein p53/genetics
2.
Med Oncol ; 35(10): 127, 2018 Aug 16.
Article in English | MEDLINE | ID: mdl-30116916

ABSTRACT

Approximately 50% of hepatocellular carcinoma (HCC) is attributable to chronic infection with hepatitis B virus (HBV). Serum hepatitis B surface antigen (HBsAg) is an important diagnostic marker of HBV infection, whereas intrahepatic HBV covalently closed circular DNA (cccDNA) is a surrogate marker of HBV persistence. This study aimed to investigate relationships between serum HBsAg, intrahepatic HBsAg, and intrahepatic cccDNA in HBV-associated HCC. Intrahepatic HBsAg was determined by immunohistochemistry in matched non-cancerous and HCC tissues from 88 patients; 56 patients (63.64%) were serum HBsAg positive. In serum HBsAg-positive group, intrahepatic HBsAg was positive staining in 73.2% of non-cancerous tissues, but only in 10.7% of HCC tissues. Significant correlation between serum HBsAg and intrahepatic HBsAg was observed in non-cancerous tissues (p < 0.001), but not in HCC tissues (p = 0.415). Absolute quantification of intrahepatic cccDNA was performed by droplet digital PCR in tissues from 30 patients; 18 patients (60%) were serum HBsAg positive. In serum HBsAg-positive group, intrahepatic cccDNA was detected in 66.66% of non-cancerous tissues, but only in 5.55% of HCC tissue; intrahepatic cccDNA levels in non-cancerous tissues were significantly higher than those in HCC tissues (p < 0.001), and correlated with serum HBsAg (p < 0.01). Significant correlations between intrahepatic HBsAg and intrahepatic cccDNA were found in both non-cancerous tissues (p < 0.01) and HCC tissues (p < 0.05). We concluded that HBV cccDNA and intrahepatic HBsAg in HBV-associated HCC tissues were significantly reduced, as compared with matched non-cancerous tissues. This warrants further investigation into the impacts and the cause(s) of cccDNA reduction in HBV-associated HCC tissues, which might yield novel immune-related therapy for HBV-associated HCC.


Subject(s)
Carcinoma, Hepatocellular/blood , DNA, Circular/blood , Hepatitis B Surface Antigens/blood , Hepatitis B virus/isolation & purification , Hepatitis B/blood , Liver Neoplasms/blood , Adult , Carcinoma, Hepatocellular/diagnosis , Female , Hepatitis B/diagnosis , Humans , Liver Neoplasms/diagnosis , Male , Middle Aged
3.
Ann Hepatol ; 15(1): 47-52, 2016.
Article in English | MEDLINE | ID: mdl-26626640

ABSTRACT

BACKGROUND AND STUDY AIMS: Chronic liver disease (CLD) can cause hepatopulmonary syndrome (HPS), defined as triad of liver disease, hypoxemia, and intrapulmonary vascular dilation (IPVD). The aim of this study was to determine the evidence of IPVD in a cohort of pediatric patients with CLD pre- and post-liver transplantation (LT). MATERIAL AND METHODS: All pediatric patients with CLD listed for LT were studied. Pulse oxygen saturation (SpO(2)), technetium-99m-labeled macroaggregated albumin ((99m)Tc- MAA) perfusión scan (positive test: uptake of the isotope ≥ 6% in the brain), and echocardiography with saline bubble test (SBT) were performed. SBT was re-evaluated at 3-6 months after LT. Grading of SBT included grade 0 (no bubble), I (1-9 bubbles), grade II (10-20 bubbles), and grade III (> 20 bubbles). RESULTS: Eighteen patients, median age 22.5 months (8-108), were enrolled. Most had biliary atresia (77.8%). Pre-LT, all patients had SpO(2) of 100% and none had positive (99)mTc- MAA perfusion scan. Two patients (11%) had negative SBT (grade 0), 1 (5.5%) had grade I, 3 (16.5%) had grade II, and 12 (67%) had grade III, respectively. Post-LT SBT became negative in all survivors (n = 16), (p = 0.0001). CONCLUSIONS: Most cirrhotic children in this cohort study had evidence of IPVD by positive SBT. However, none of these met the criteria for diagnosis of HPS. This evidence of IPVD subsided after LT.


Subject(s)
Hepatopulmonary Syndrome/etiology , Liver Cirrhosis/surgery , Liver Transplantation , Pulmonary Artery/physiopathology , Vasodilation , Age Factors , Child , Child, Preschool , Chronic Disease , Echocardiography , Female , Hepatopulmonary Syndrome/diagnosis , Hepatopulmonary Syndrome/physiopathology , Humans , Infant , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Male , Oximetry , Perfusion Imaging/methods , Predictive Value of Tests , Pulmonary Circulation , Radiopharmaceuticals/administration & dosage , Risk Factors , Sodium Chloride/administration & dosage , Technetium Tc 99m Aggregated Albumin/administration & dosage , Treatment Outcome
4.
Hepatol Int ; 10(3): 518-24, 2016 May.
Article in English | MEDLINE | ID: mdl-26462482

ABSTRACT

BACKGROUND/AIM: Liver cirrhosis is associated with several cardiac abnormalities. There have been few studies of these abnormalities in cirrhotic children post-liver transplantation (LT). The purpose of this study was to evaluate cardiac abnormalities in cirrhotic children pre- and post-LT. METHODS: All cirrhotic children <15 years of age on a waiting list for LT underwent pre-LT echocardiography to evaluate left ventricular (LV) dimension, mass, and function. Repeated studies were performed at 1-2 and 3-6 months post-LT. RESULTS: A total of 20 cirrhotic children (median age 21.5 months [8-108 months], 11 female [55 %]) were enrolled in the study. Most patients had biliary atresia (75 %) and decompensated cirrhosis, with a median pediatric end-stage liver disease score of 19.5 (14-28). Two patients subsequently died, at 1 and 4 months post-LT. Echocardiography was re-evaluated in 17 and 18 patients at 1-2 months and 3-6 months post-LT, respectively. Prior to transplant, most patients had cardiac abnormalities, including LV enlargement (50 %), increased LV mass (95 %), abnormal LV geometry (95 %), hyperdynamic LV systolic function (60 %), LV diastolic dysfunction (60 %), and high cardiac index (75 %). At 3-6 months post-LT, no significant decrease in cardiac abnormalities was noted; however, cardiac parameters including LV dimension in diastole index and z-score, LV mass index, and relative wall thickness were significantly decreased. CONCLUSIONS: Most cirrhotic children had cardiac abnormalities, including LV enlargement, increased LV mass, abnormal LV geometry, and LV dysfunction. These abnormalities tended to improve post-LT. We suggest that echocardiography should be performed in all cirrhotic children.


Subject(s)
Heart Diseases/etiology , Liver Cirrhosis/complications , Liver Transplantation , Child , Child, Preschool , Echocardiography , End Stage Liver Disease/complications , End Stage Liver Disease/surgery , Female , Heart Diseases/diagnostic imaging , Heart Ventricles/diagnostic imaging , Humans , Infant , Liver Cirrhosis/surgery , Liver Transplantation/adverse effects , Male , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology
5.
Biomed Res Int ; 2015: 171845, 2015.
Article in English | MEDLINE | ID: mdl-26436086

ABSTRACT

Epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase receptor, plays important roles in various cancers. In nonsmall cell lung cancer (NSCLC), EGFR mutations cluster around the ATP-binding pocket (exons 18-21) and some of these mutations activate the kinase and induce an increased sensitivity to EGFR-tyrosine kinase inhibitors. Nevertheless, data of EGFR mutations in HCC are limited. In this study, we investigated EGFR expression by immunohistochemistry and EGFR mutations (exons 18-24) by PCR cloning and sequencing. EGFR overexpression in HCC and matched nontumor tissues were detected in 13/40 (32.5%) and 10/35 (28.6%), respectively. Moreover, missense and silent mutations were detected in 13/33 (39.4%) and 11/33 (33.3%) of HCC tissues, respectively. The thirteen different missense mutations were p.L730P, p.V742I, p.K757E, p.I780T, p.N808S, p.R831C, p.V851A, p.V897A, p.S912P, p.P937L, p.T940A, p.M947V, and p.M947T. We also found already known SNP, p.Q787Q (CAG>CAA), in 13/33 (39.4%) of HCC tissues. However, no significant association was detected between EGFR mutations and EGFR overexpression, tissue, age, sex, tumor size, AFP, HBsAg, TP53, and Ki-67. Further investigation is warranted to validate the frequency and activity of these missense mutations, as well as their roles in HCC tumorigenesis and in EGFR-targeted therapy.


Subject(s)
Carcinoma, Hepatocellular/genetics , ErbB Receptors/genetics , Exons/genetics , Liver Neoplasms/genetics , Mutation, Missense/genetics , Base Sequence , DNA Mutational Analysis , Electrophoresis, Agar Gel , Female , Humans , Immunohistochemistry , Male , Middle Aged , Molecular Sequence Data
6.
Biomed Res Int ; 2015: 381602, 2015.
Article in English | MEDLINE | ID: mdl-25695068

ABSTRACT

Hepatocellular carcinoma (HCC) is the leading cause of cancer death in men worldwide owing to limited insights into pathogenesis and unsatisfactory efficacy of current therapies. HER2 and TOP2A genes are coamplified in breast and some other cancers. In this study, we investigated gene aberrations of HER2 and TOP2A and protein expressions of HER2, TOP2A, Ki-67, and p53 in tumor and matched nontumor tissues, as well as their associations with clinicopathological features. Gene aberrations were evaluated by FISH and protein expressions by IHC. Neither HER2 overexpression nor HER2 gene amplification was observed in both tumor tissues and matched nontumor tissues. By contrast, TOP2A overexpression was detected in 72.5% of tumor tissues but not detected in matched nontumor tissues. However, TOP2A gene amplification was not observed in both tumor and matched nontumor tissues. TOP2A overexpression was significantly associated with HCC tumor tissues (P < 0.001), hepatitis B surface antigen (HBsAg) in the serum (P = 0.004), and Ki-67 (P = 0.038) but not with age, tumor size, alpha-fetoprotein, TP53, and copy number of TOP2A gene and chromosome 17 centromere. In conclusion, TOP2A overexpression in HCC was not secondary to gene amplification. In addition, neither HER2 amplification nor overexpression could be used as prognostic and predictive marker in HCC.


Subject(s)
Antigens, Neoplasm/genetics , Carcinoma, Hepatocellular/genetics , DNA Topoisomerases, Type II/genetics , DNA-Binding Proteins/genetics , Gene Amplification/genetics , Gene Expression Regulation, Neoplastic/genetics , Liver Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Female , Gene Dosage/genetics , Humans , Male , Middle Aged , Poly-ADP-Ribose Binding Proteins , Receptor, ErbB-2/genetics , Tumor Suppressor Protein p53/genetics
7.
Appl Immunohistochem Mol Morphol ; 20(4): 367-74, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22417858

ABSTRACT

Gains of chromosome 17 centromere (CEP17) may be accompanied by gains of chromosome 17q. To evaluate the effect of CEP17 gains (CEP17>3 copies per tumor nucleus) on the expression of the HER2 gene, which is located on chromosome 17q12-21.32, we analyzed HER2 amplification and expression in breast carcinomas with and without CEP17 gains. We isolated tumor nuclei from frozen tissues of 37 breast carcinomas for analysis of the HER2 gene and CEP17 by fluorescence in situ hybridization. HER2 expression was detected by immunohistochemistry (IHC) performed on formalin-fixed, paraffin-embedded sections of the corresponding tumors. Tumors with amplified HER2 as determined by both HER2 copy number and HER2/CEP17 ratio were detected in 29.7% (11/37). CEP17 gains were significantly associated with HER2 amplification (P=0.005) but not associated with estrogen receptor status, tumor grade, and lymph node status (P>0.05). In contrast, HER2 amplification was significantly associated with estrogen receptor negativity (P=0.020) but not with tumor grade and lymph node status (P>0.05). IHC analysis was performed in 7 HER2-amplified tumors and all of these were IHC 3+, which were used as positive controls. Among HER2-non-amplified tumors with CEP17 gains, only 1 tumor (1/8, 12.5%) was IHC 3+. However, none of the HER2-non-amplified tumors without CEP17 gains was IHC 3+. In HER2-non-amplified tumors, there was no significant association between HER2 protein expression as detected by IHC and CEP17 or HER2 copy number (P=0.999, P=0.785, respectively). These findings indicate that in the absence of HER2 amplification, CEP17 gains do not have a significant effect on HER2 protein expression.


Subject(s)
Breast Neoplasms/diagnosis , Carcinoma/diagnosis , Chromosomes, Human, Pair 17/genetics , Receptor, ErbB-2/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carcinoma/genetics , Carcinoma/pathology , Centromere/genetics , Chromosome Aberrations/statistics & numerical data , Female , Gene Amplification , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Receptors, Estrogen/metabolism
8.
J Med Assoc Thai ; 94(10): 1276-80, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22145516

ABSTRACT

UNLABELLED: Hereditary tyrosinemia type I (HT-I) is an autosomal recessive inborn error of tyrosine metabolism, caused by mutation(s) in the gene encoding for fumarylacetoacetate hydrolase (FAH) enzyme. The authors report a Thai boy who presented at two months of age with liver failure. HT-I was diagnosed based on the presence of succinylacetone in urine and homozygous R237X mutations of FAH gene. He was started on tyrosine and phenylalanine restricted diet immediately. Due to a limitation of 2-(2-nitro-4-trifluoromethyl benzoyl)-1,3-cyclohexanedione (NTBC) therapy in Thailand, it was commenced at eight months old and used as a bridging therapy before liver transplantation. He had a good response to NTBC therapy with an improvement in liver chemistries and synthetic functions. Subsequently, living donor liver transplantation (LDLT) was performed at 15 months old Long-term follow-up for 6.3 years following LDLT revealed normal growth, good school performance, normal liver, renal tubular, and glomerular functions, and without urinary excretion of succinylacetone. CONCLUSION: Liver transplantation is a promising treatment for patients with HT-1 when NTBC is unavailable, resulting in a good long-term outcome.


Subject(s)
Liver Failure/therapy , Tyrosinemias/diagnosis , Tyrosinemias/genetics , Asian People , Diet Therapy , Heptanoates/urine , Humans , Hydrolases/genetics , Infant , Liver Failure/etiology , Liver Transplantation , Living Donors , Male , Mutation , Phenylalanine/metabolism , Thailand , Treatment Outcome , Tyrosine/metabolism , Tyrosinemias/therapy
9.
Am J Infect Control ; 39(6): 525-8, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21612842

ABSTRACT

We aimed to report the coverage and safety of the influenza A (H1N1) 2009 monovalent vaccination (Panenza; Sanofi Pasteur, Val de Reuil Cedex, France) among health care personnel (HCP) in a university hospital setting in Thailand. The hospital set up a system to vaccinate HCP and did surveillance of the adverse effects (AEs). During a 4-week period, 6,210 (78.7%) HCP were vaccinated. There were 82 reported nonserious AEs among 32 HCP. The most common AE was fatigue/uncomfortable feeling (24%).


Subject(s)
Health Personnel , Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines/administration & dosage , Influenza Vaccines/adverse effects , Influenza, Human/prevention & control , Vaccination/adverse effects , Vaccination/statistics & numerical data , Adult , Fatigue/chemically induced , Fatigue/epidemiology , Female , Humans , Influenza, Human/virology , Male , Middle Aged , Thailand
10.
J Med Assoc Thai ; 90(8): 1654-6, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17926998

ABSTRACT

Acute renal failure (ARF) is common among patients with liver failure awaiting liver transplantation due to the increased waiting time for available liver grafts and extended survival from improved intensive care. The role of combined liver and kidney transplantation (LKT) in this situation is quite controversial. A case of acute liver failure (ALF) complicated with ARF is reported. Non-A, non-B hepatitis was the cause of ALF. He had hemodialysis for one month before transplantation. Combined LKT was performed because of prolonged pre-transplant hemodialysis and the potential of irreversible renal failure. Severe impairment of both native kidneys was confirmed by renal scan at 6 months after transplantation. Combined LKT may be needed for patients with acute liver failure complicated with prolonged acute renal failure.


Subject(s)
Acute Kidney Injury/surgery , Kidney Transplantation , Liver Failure, Acute/surgery , Liver Transplantation , Acute Kidney Injury/complications , Humans , Liver Failure, Acute/complications , Male , Middle Aged
11.
J Med Assoc Thai ; 90(2): 363-8, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17375644

ABSTRACT

BACKGROUND: Genetic analysis using the fluorescence in situ hybridization (FISH) method applied to intact tissue sections of formalin-fixed paraffin embedded (FFPE) tissue is well known to be relatively difficult. The frequent technical problems include unsuccessful hybridization as a result of poor probe penetration, excessive probe requirement, excessive background, auto-fluorescence, and overlapping or incomplete nuclei. These problems lead to absence or insufficiency of fluorescent signals, resulting in an inaccurate analysis. Formalin-fixed paraffin embedded tissue can be analyzed either as intact tissue sections or as a suspension of disaggregated, but intact, nuclei. Intact tissue sections have the advantage of preserved tissue architecture and morphology but have the intrinsic disadvantage of poor probe penetration, overlapping or incomplete nuclei and auto-fluorescence, accordingly reducing the accuracy of fluorescent signals evaluation. OBJECTIVE: To present the effective FISH method applied to isolated of single nuclei and the procedures for isolation of a single nuclei from formalin-fixed paraffin embedded tissues of hepatocellular carcinoma. MATERIAL AND METHOD: Ten paraffin-embedded blocks of hepatocellular carcinoma tissues from the department of pathology, Ramathibodi hospital, Thailand were studied. Isolated single nuclei were extracted from 10-microm sections of paraffin-embedded blocks of hepatocellular carcinoma tissue and hybridized with alpha-satellite centromeric DNA enumeration probes for chromosomes X (CEP X, spectrum green) and satellite III for chromosomes Y (CEP Y spectrum orange). The signal of at least, 200 interphase nuclei were counted from each specimen. RESULTS: The efficacy of this method has been evaluated in 10 formalin-fixed paraffin embedded tissue of hepatocellular carcinoma. The results showed bright, planar and an easy to score signal. CONCLUSION: FISH procedure described here is particularly suitable for retrospective studies of genetic aberration applied to formalin-fixed paraffin embedded tissues.


Subject(s)
Carcinoma, Hepatocellular/pathology , In Situ Hybridization, Fluorescence/methods , Feasibility Studies , Female , Humans , Male , Paraffin
12.
J Med Assoc Thai ; 90(12): 2638-43, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18386714

ABSTRACT

OBJECTIVE: To compare the results of laparoscopic adrenalectomy with those of open adrenalectomy in Ramathibodi Hospital. MATERIAL AND METHOD: Medical charts of 41 laparoscopic and 39 open adrenalectomy patients were reviewed Baseline characteristics and outcomes of treatment were compared between these two patient groups, using univariable statistical tests and multivariable statistical procedures. RESULTS: There were significant baseline differences between the two groups in terms of gender, body mass index, ASA class, and preoperative diagnosis. The outcomes operative time, estimated blood loss and length of hospital stay were also significantly different. After adjusting for the effects of baseline differences, laparoscopic adrenalectomy was associated with a significant reduction of length of hospital stay by 40%. CONCLUSION: Laparoscopic adrenalectomy is a safe and effective procedure and should help hasten postoperative recovery and may save the costs of hospitalization.


Subject(s)
Adrenal Glands/surgery , Adrenalectomy/methods , Laparoscopy/methods , Treatment Outcome , Adrenalectomy/instrumentation , Body Mass Index , Cushing Syndrome/surgery , Female , Hospitals, Public , Humans , Hyperaldosteronism/surgery , Length of Stay , Male , Middle Aged , Retrospective Studies , Thailand
13.
Parasitol Int ; 55(3): 187-93, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16793328

ABSTRACT

Due to chronic morbidity, the risk of increasing drug resistance and the existence of the hypnozoite stage in Plasmodium vivax malaria, there is a need to find out how hosts develop immunity to compromise the malaria parasites. Here we focused on an in vitro model for immunotherapy and vaccine development. Immunosuppressive mechanisms in malaria include inhibition of T cell response and suppression of dendritic cell function. Using in vitro activation of lymphocytes by malaria antigen-pulsed dendritic cells could overcome the limitation of antigen presentation during acute infections. Here we showed that the sporozoite-pulsed dendritic cell could elicit cytotoxicity against liver stage of P. vivax. Analysis using immunophenotypic markers showed maturation of the dendritic cells and stimulation of cytotoxic T cells. Functional assay of the in vitro-activated cytotoxic T cells showed enhancement of specific killing of the P. vivax exoerythrocytic stages within infected hepatocytes. This model may be useful for vaccine development against human malaria.


Subject(s)
Dendritic Cells/immunology , Hepatocytes/parasitology , Lymphocyte Activation , Plasmodium vivax/immunology , T-Lymphocytes, Cytotoxic/immunology , Animals , Anopheles/parasitology , Antigens, Protozoan , Cell Line , Cytotoxicity, Immunologic , Dendritic Cells/cytology , Female , Humans , Sporozoites/immunology , T-Lymphocyte Subsets/immunology
14.
Am J Trop Med Hyg ; 74(5): 708-15, 2006 May.
Article in English | MEDLINE | ID: mdl-16687667

ABSTRACT

Our understanding of the biology of malaria parasite liver stages is limited because of the lack of efficient in vitro systems that support the exo-erythrocytic (EE) development of the parasite. We report the development of a new hepatocyte line (HC-04) from normal human liver cells. The HC-04 cells have proliferated in hormone-free medium for more than 200 passages. The cells were hyperdiploid, resembled liver parenchymal cells, and synthesized major liver-specific proteins and enzymes. Using Plasmodium falciparum and P. vivax sporozoites harvested from salivary glands of infected mosquitoes, we showed that HC-04 cells supported the complete EE development of these two most prevalent human malaria parasites. The EE parasites attained full maturation as shown by their infectivity to human erythrocytes. The infection rates of the liver cells were estimated to be 0.066% and 0.041% for P. falciparum and P. vivax, respectively. As the first human hepatocyte line known to support complete EE development of both P. falciparum and P. vivax, HC-04 will provide an experimental model that can be used for studying the biology of liver stage malaria parasites.


Subject(s)
Hepatocytes/parasitology , Malaria, Falciparum/parasitology , Malaria, Vivax/parasitology , Plasmodium falciparum/physiology , Plasmodium vivax/physiology , Albumins/metabolism , Animals , Cells, Cultured , Hepatocytes/enzymology , Hepatocytes/metabolism , Humans , Transferrin/metabolism , alpha-Fetoproteins/metabolism
15.
J Med Assoc Thai ; 88(4): 473-7, 2005 Apr.
Article in English | MEDLINE | ID: mdl-16146250

ABSTRACT

BACKGROUND: Surgical venous stripping (SVS) is a standard treatment for varicose veins (VV) due to greater saphenous vein incompetence (GSVI) but there are some disadvantages to and risks. Endovascular laser (EVL) has been introduced to overcome these disadvantages. The present study was designed to determine the effectiveness of EVL treatment for these patients. MATERIAL AND METHOD: The patients with VV due to GSVI diagnosed by duplex scan were recruited in the present study. The EVL-procedure was percutaneously approached guiding by ultrasound under monitor anesthetic care (MAC). Postoperative clinical and imaging assessment was assessed. RESULTS: There were 17 limbs with symptomatic VVs in 11 patients. Two patients were admitted for a reason not related to surgery. The others were day cases. There was no postoperative complication except a large echymosis in one case. At 3-month follow-up, no recanalization or recurrence was detected. CONCLUSION: The authors' early results demonstrated that EVL could obliterate VVs due to GSVI and further showed some benefits over SVS. More studies with a longer period of follow-up are needed to further confirm the efficacy of EVL.


Subject(s)
Laser Therapy/methods , Saphenous Vein/surgery , Varicose Veins/surgery , Venous Insufficiency/surgery , Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Prospective Studies , Thailand , Time Factors , Treatment Outcome , Varicose Veins/etiology , Venous Insufficiency/complications
16.
J Med Assoc Thai ; 87(3): 304-9, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15117048

ABSTRACT

Transplant renal artery stenosis (TRAS) is one of the common vascular complications post kidney transplantation. A retrospective study of TRAS among transplant recipients at a single transplant center in Thailand was performed from February 1986 to December 2002. Among 750 cases, 16 cases (2.1%) of TRAS were identified. Twelve cases (3.3%) were from cadaveric donors and four cases (1%) were from living-related donors (p-value = 0.034). Most cases presented with progressive deterioration of kidney graft with or without refractory hypertension. Doppler ultrasonography was used for initial screening followed by renal angiography. Fifteen cases were treated by Percutaneous Transluminal Angioplasty (PTA) with a 73 per cent success rate. Five cases underwent surgical revascularization with an 80 per cent success rate. Two cases (13%) of successful PTA showed recurrent stenosis with 46 months follow-up which were successfully treated by repeated PTA with stents.


Subject(s)
Kidney Transplantation , Postoperative Complications/epidemiology , Renal Artery Obstruction/epidemiology , Angiography , Angioplasty , Female , Humans , Incidence , Male , Middle Aged , Renal Artery Obstruction/diagnosis , Renal Artery Obstruction/therapy , Retrospective Studies , Risk Factors , Thailand/epidemiology , Tissue Donors , Ultrasonography, Doppler
17.
Transpl Int ; 17(4): 163-8, 2004 May.
Article in English | MEDLINE | ID: mdl-15107973

ABSTRACT

Arterial complications after orthotopic liver transplantation (OLT), including hepatic artery thrombosis (HAT), are important causes of early graft failure. The use of an arterial conduit is an accepted alternative to the utilisation of native recipient hepatic artery for specific indications. This study aims to determine the efficacy of arterial conduits and the outcome in OLT. We retrospectively reviewed 1,575 cadaveric adult OLTs and identified those in which an arterial conduit was used for hepatic revascularisation. Data on the primary disease, indication for using arterial conduit, type of vascular graft, operative technique and outcome were obtained. Thirty-six (2.3%) patients underwent OLT in which arterial conduits were used for hepatic artery (HA) revascularisation. Six of these were performed on the primary transplant, while the rest (n=30) were performed in patients undergoing re-transplantation, including six who had developed hepatic artery aneurysms. The incidence of arterial conduits was 0.4% (6/1,426 cases) in all primary OLTs and 20.1% (30/149 cases) in all re-transplants. Twenty-nine procedures utilised iliac artery grafts from the same donor as the liver, six used iliac artery grafts from a different donor, and a single patient underwent a polytetrafluoroethylene (PTFE) graft. Two techniques were used: infra-renal aorto-hepatic artery conduit and interposition between the donor and recipient native HAs, or branches of the HAs. The 30-day mortality rate for operations using an arterial conduit was 30.6%. Three conduits thrombosed at 9, 25 and 155 months, respectively, but one liver graft survived without re-transplantation. The arterial conduits had 1- and 5-year patency rates of 88.5% and 80.8%. The 1- and 5-year patient survival rates were 66.7% and 44%. We can thus conclude that an arterial conduit is a viable alternative option for hepatic revascularisation in both primary and re-transplantation. Despite a lower patency rate than that of native HA in the primary OLT group, the outcomes of arterial conduit patency and patient survival rates are both acceptable at 1 and 5 years, especially in the much larger re-OLT group.


Subject(s)
Graft Rejection/etiology , Hepatic Artery/physiopathology , Iliac Artery/transplantation , Liver Transplantation/adverse effects , Thrombosis/etiology , Thrombosis/surgery , Vascular Surgical Procedures/methods , Adult , Anastomosis, Surgical , Blood Vessel Prosthesis , Female , Humans , Liver Circulation , Male , Middle Aged , Polytetrafluoroethylene , Reoperation , Retrospective Studies , Time Factors , Transplantation, Homologous , Treatment Outcome , Vascular Patency
18.
Transpl Int ; 16(4): 257-61, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12730806

ABSTRACT

Hepatic artery aneurysm (HAA) is a rare vascular complication, but has a high mortality rate in liver transplant recipients. This study reports the precipitating factors, clinical manifestation, pre-operative diagnosis, related micro-organism, management, and outcome, in a series of HAAs that developed after adult orthotopic liver transplantation (OLT). Data on the primary disease as well as on the above were obtained from a prospective database, and all case records were reviewed. There were eight (0.5%) HAAs in 1,575 adult cadaveric OLTs between 1982 and March 2001. All were pseudo-aneurysms around the native hepatic-artery (HA) anastomosis, and all occurred in whole-organ OLTs. There were three types of clinical presentations: sudden hypotension (n=4), gastrointestinal (GI) bleeding (n=2), and abnormal liver-function tests (LFTs) (n=2). The majority (n=7) presented within the first 2 months (median: 27.5 days, range: 12-760 days) following OLT. A pre-operative diagnosis of HAA was not determined in five cases. The sensitivity of abdominal ultrasound scan (USS), computed tomography (CT) scan and angiography for detection of HAAs was 3 of 5, 1 of 2 and 3 of 4, respectively. Micro-organisms could be identified in six patients (bacteria n=4 and fungi n=3). All patients underwent urgent operations (excision of HAA in six and ligation in two cases). Immediate reconstruction of the HA was carried out, two different methods being used: repair of native arteries (n=2) and arterial conduit (interposition n=3 and aortic conduit n=2). Two patients died peri-operatively, two died within 2 months, and the remaining four patients are alive at between 8.6 and 12.8 years after repair. HAA following OLT is unpredictable in its presentation, and the sensitivity of clinical and radiological detection is low. A high index of suspicion is required, and urgent surgery with immediate re-vascularisation and use of appropriate antibiotic/anti-fungal agents is recommended.


Subject(s)
Aneurysm/surgery , Hepatic Artery/surgery , Liver Transplantation/adverse effects , Adult , Hepatic Artery/transplantation , Humans , Retrospective Studies , Transplantation, Homologous
19.
Liver Transpl ; 8(7): 612-4, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12089715

ABSTRACT

Right-lobe graft has been used most frequently for living donor liver transplantation in adult patients; however, some donors cannot donate their right lobe (according to the Healey and Scroy's terminology) because the remaining residual liver would be too small. A recent study suggested the possibility of right posterior segment graft in these donors. The purpose of this study was to evaluate the feasibility of right lobe or right posterior segment graft with a volumetric analysis. Liver volumetry by computed tomography was performed in 155 consecutive donors, and the volume of each liver segment was calculated. To confirm the reliability of volumetric examination, the estimated graft volume and the actual weight were compared. The average volume ratios of the left lateral segment, left medial segment, caudate lobe, right anterior segment, and right posterior segment were 17%, 14%, 2%, 37%, and 30%, respectively. In 39 donors (25%), the volume ratio of the right lobe was over 70%. Of these donors, 72% had a larger (difference in volume ratio greater than 5%) right posterior segment than left lobe with caudate lobe. The relationship between the estimated volume and actual weight was linear. The present results suggest that right lobectomy carries a potential risk and that the right posterior segment may be useful as an alternative graft from the point of donor's safety.


Subject(s)
Liver Transplantation/methods , Liver/anatomy & histology , Living Donors , Adolescent , Adult , Child , Child, Preschool , Feasibility Studies , Humans , Infant , Middle Aged
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