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1.
J Eur Acad Dermatol Venereol ; 35(3): 712-720, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32896010

ABSTRACT

BACKGROUND: There is increasing use of anti-osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)-SCAR. OBJECTIVE: To characterize patients with AOA-SCAR and investigate the HLA association and utility of in vitro diagnostic methods. METHODS: We enrolled 16 cases with AOA-cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens-Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA-SCAR, and tolerability to alternative drugs. We further performed literature review and meta-analysis on the HLA association of AOA-SCAR. RESULTS: Our data showed strontium ranelate is the most common causality of AOA-SCAR in Asian populations. There was no cross-hypersensitivity of SR-SCAR with other AOA. HLA genotyping showed that SR-SJS was most significantly associated with HLA-A*33:03 (Pc = 5.17 × 10-3 , OR: 25.97, 95% CI: 3.08-219.33). Meta-analysis showed that HLA-A*33:03 was associated with SR-SJS (P = 5.01 × 10-5 ; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR-SJS was 83.3%. CONCLUSIONS: Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA-A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR-SCAR in patients whose reaction developed while taking multiple drugs.


Subject(s)
Stevens-Johnson Syndrome , Alleles , Anticonvulsants , Asian People , HLA-B Antigens/genetics , Hong Kong , Humans , Taiwan
2.
Epidemiol Psychiatr Sci ; 27(2): 176-185, 2018 Apr.
Article in English | MEDLINE | ID: mdl-27974084

ABSTRACT

AIMS: Poor insight is prevalent in patients with schizophrenia and has been associated with acute illness severity, medication non-adherence and poor treatment outcomes. Paradoxically, high insight has been associated with various undesirable outcomes, including low self-esteem, depression and low subjective quality of life (QoL) in patients with schizophrenia. Despite the growing body of studies conducted in Western countries supporting the pernicious effects of improved insight in psychosis, which bases on the level of self-stigma, the effects are unclear in non-Western societies. The current study examined the role of self-stigma in the relationship between insight and psychosocial outcomes in a Chinese population. METHODS: A total of 170 outpatients with schizophrenia spectrum disorders were recruited from two general university hospitals. Sociodemographic data and clinical variables were recorded and self-report scales were employed to measure self-stigma, depression, insight, self-esteem and subjective QoL. Structural equation modelling (SEM) was used to analyse the cross-sectional data. RESULTS: High levels of self-stigma were reported by 39% of the participants (n = 67). The influences of insight, self-stigma, self-esteem and depression on subjective QoL were confirmed by the SEM results. Our model with the closest fit to the data (χ 2 = 33.28; df = 20; p = 0.03; χ 2/df = 1.66; CFI = 0.98; TLI = 0.97; RMSEA = 0.06) demonstrated that self-stigma might fully mediate the association of insight with low self-esteem, depression and poor subjective QoL. High insight into illness contributed to self-stigma, which caused low self-esteem and depression and, consequently, low QoL. Notably, insight did not directly affect self-esteem, depression or QoL. Furthermore, the association of insight with poor psychosocial outcomes was not moderated by self-stigma. CONCLUSIONS: Our findings support the mediating model of insight relevant to the poor psychosocial outcomes of individuals diagnosed with schizophrenia in non-Western societies, in which self-stigma plays a pivotal role. These findings elucidate the direct and indirect effects of insight on psychosocial outcomes and imply that identifying and correcting self-stigma in people with schizophrenia could be beneficial. Additional studies are required to identify whether several other neurocognitive or psychosocial variables mediate or moderate the association of insight with self-esteem, depression and QoL in patients with schizophrenia. Studies with detailed longitudinal assessments are necessary to confirm our findings.


Subject(s)
Quality of Life/psychology , Schizophrenic Psychology , Self Concept , Social Stigma , Adolescent , Adult , Cross-Sectional Studies , Depression/etiology , Female , Humans , Latent Class Analysis , Male , Middle Aged , Outpatients , Schizophrenia/diagnosis , Self Report , Young Adult
3.
Oncogene ; 37(5): 589-600, 2018 02 01.
Article in English | MEDLINE | ID: mdl-28991224

ABSTRACT

Growing evidence indicates that resistin-an obesity-related cytokine-is upregulated in breast cancer patients, yet its impact on breast cancer behavior remains to be ascertained. Similarly, Toll-like receptor 4 (TLR4) has been implicated in breast cancer progression, however, its clinically relevant endogenous ligand remains elusive. In this study, we observed that high serum resistin levels in breast cancer patients positively correlated with tumor stage, size and lymph node metastasis. These findings were replicated in animal models of breast cancer tumorigenesis and metastasis. Resistin was found to promote epithelial-mesenchymal transition and stemness in breast cancer cells-mechanisms critical to tumorigenesis and metastasis-through a TLR4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/signal transducer and activator of transcription 3 (STAT3) signaling pathway and negated by TLR4-specific antibody and antagonist. These findings provide clear evidence that resistin is a clinically relevant endogenous ligand for TLR4, which promotes tumor progression via TLR4/NF-κB/STAT3 signaling, providing insights into a novel therapeutic target in breast cancer.


Subject(s)
Breast Neoplasms/pathology , Epithelial-Mesenchymal Transition , Neoplastic Stem Cells/pathology , Resistin/metabolism , Toll-Like Receptor 4/metabolism , Animals , Breast/pathology , Breast Neoplasms/blood , Carcinogenesis/pathology , Cell Line, Tumor , Disease Progression , Female , Humans , Lymphatic Metastasis , Middle Aged , NF-kappa B , Neoplasm Staging , Resistin/blood , STAT3 Transcription Factor/metabolism , Signal Transduction , Up-Regulation , Xenograft Model Antitumor Assays , Zebrafish
4.
Genet Mol Res ; 15(3)2016 Sep 16.
Article in English | MEDLINE | ID: mdl-27706730

ABSTRACT

Long-term radiation exposure is hazardous to health; late-onset effects of exposure to ionizing radiation (IR) pose risks to the lens, and are associated with other non-cancerous diseases. Individuals occupationally exposed to low-dose IR are prone to developing eye cataracts. Cytogenetic evaluations suggest that IR is associated with chromosomal aberrations in occupationally exposed individuals. However, data regarding the association between chromosomal aberrations in cataract patients and occupational exposure to IR is scarce. Therefore, we aimed to report the characteristics of chromosomal aberrations in cataract patients from a Chinese population, occupationally exposed to IR. We found that the average age and frequency of numerical chromosomal aberrations were significantly lower in the exposed patients as compared with that in the non-exposed patients. In addition, the frequencies of dicentric and acentric chromosomes were significantly higher in the exposed patients as compared with those in the non-exposed patients. Therefore, chronic occupational exposure to IR affects cataract development in the Chinese population. The age of cataract patients exposed to IR was significantly lower than the age of cataract onset in normal individuals. Based on this study, we suggest that there is an urgent need for improved radiation safety and eye protection in individuals exposed to IR in the work place.


Subject(s)
Cataract/genetics , Chromosome Aberrations/radiation effects , Lens, Crystalline/radiation effects , Occupational Exposure , Aged , Cataract/etiology , Cataract/pathology , China , Dose-Response Relationship, Radiation , Female , Humans , Lens, Crystalline/pathology , Male , Middle Aged , Radiation, Ionizing
5.
Genet Mol Res ; 15(1)2016 Mar 22.
Article in English | MEDLINE | ID: mdl-27050976

ABSTRACT

Long-term radiation exposure affects human health. Ionizing radiation has long been known to raise the risk of cancer. In addition to high doses of radiation, low-dose ionizing radiation might increase the risk of cardiovascular disease, lens opacity, and some other non-cancerous diseases. Low- and high-dose exposures to ionizing radiation elicit different signaling events at the molecular level, and may involve different response mechanisms. The health risks arising from exposure to low doses of ionizing radiation should be re-evaluated. Health workers exposed to ionizing radiation experience low-dose radiation and have an increased risk of hematological malignancies. Reproductive function is sensitive to changes in the physical environment, including ionizing radiation. However, data is scarce regarding the association between occupational radiation exposure and risk to human fertility. Sperm DNA integrity is a functional parameter of male fertility evaluation. Hence, we aimed to report sperm quality and DNA damage in men from Jilin Province, China, who were occupationally exposed to ionizing radiation. Sperm motility and normal morphology were significantly lower in the exposed compared with the non-exposed men. There was no statistically significant difference in sperm concentration between exposed and non-exposed men. The sperm DNA fragmentation index was significantly higher in the exposed than the non-exposed men. Chronic long-term exposure to low doses of ionizing radiation could affect sperm motility, normal morphology, and the sperm DNA fragmentation index in the Chinese population. Sperm quality and DNA integrity are functional parameters that could be used to evaluate occupational exposure to ionizing radiation.


Subject(s)
DNA Fragmentation/radiation effects , Occupational Exposure/adverse effects , Radiation, Ionizing , Sperm Motility/radiation effects , Spermatozoa/radiation effects , Adult , Case-Control Studies , China , Humans , Male
7.
Neotrop Entomol ; 43(3): 209-17, 2014 Jun.
Article in English | MEDLINE | ID: mdl-27193616

ABSTRACT

Two new species of the tetrigid genus Xistra Bolivar from China, namely Xistra oculata Li, Deng et Zheng n. sp. and Xistra brachynota Li, Deng et Zheng n. sp. are described. An updated key to all known species of the genus is given.


Subject(s)
Orthoptera/classification , Animals , China
8.
Neurology ; 77(23): 2025-33, 2011 Dec 06.
Article in English | MEDLINE | ID: mdl-22116946

ABSTRACT

OBJECTIVE: Ethnicity has been shown to be a contributing risk factor regarding antiepileptic drug (AED)-induced severe cutaneous adverse drug reactions (SCARs). To increase the clinical and epidemiologic information in Asians, we investigated the characteristics, outcome, and tolerability toward alternative drugs for AED-induced SCARs. METHODS: A total of 154 patients with AED-induced SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), were analyzed for demographic characteristics, causative AEDs, latent period, organ involvement, complications, and mortality. Tolerability toward alternative AEDs was followed for patients after AED-SCARs episodes. RESULTS: Carbamazepine (CBZ) and phenytoin (PHT) were the most common causative AEDs for SJS/TEN (67.8%) and DRESS (43.6%), respectively. No SCARs case was caused by nonaromatic AEDs, e.g., valproic acid (VPA) and topiramate (TPM). The liver was the most frequently involved internal organ in AED-DRESS, whereas ocular complications were more commonly seen in AED-SJS/TEN. The mortality of AED-SJS/TEN and -DRESS was 6.1% and 7.7%, respectively. By following alternative AED usage of patients after AED-SCARs episodes, we noted that most patients were tolerant of nonaromatic AEDs. One case of oxcarbazepine-SJS had cross-hypersensitivity to lamotrigine (LTG) and further developed into DRESS. CONCLUSION: CBZ, PHT, and LTG were the major causative AEDs for SCARs. The mortality of PHT-SCARs was higher than CBZ-SCARs due to complicated comorbidity in patients. Nonaromatic AEDs were safe alternatives for patients with aromatic AED-induced SCARs.


Subject(s)
Anticonvulsants/adverse effects , Carbamazepine/adverse effects , Phenytoin/adverse effects , Stevens-Johnson Syndrome/chemically induced , Stevens-Johnson Syndrome/etiology , Triazines/adverse effects , Adult , Asian People/ethnology , Exanthema/chemically induced , Exanthema/mortality , Female , Follow-Up Studies , Humans , Lamotrigine , Male , Middle Aged , Retrospective Studies , Risk Factors , Severity of Illness Index , Stevens-Johnson Syndrome/ethnology , Stevens-Johnson Syndrome/mortality , Taiwan/epidemiology
9.
Eur J Pediatr Surg ; 21(5): 304-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21751122

ABSTRACT

OBJECTIVE: Aim of the study was to further evaluate the role of caspase 8 and death receptors (DR) in the TRAIL-induced apoptosis of neuroblastoma (NB) cell lines. METHODS: Caspase 8 mRNA expression was monitored by RT-PCR. Caspase 8, DR5 and DR4 protein expression were monitored by Western blot analysis. The effects of IFNγ, TRAIL, IFNγ+TRAIL, caspase 8 inhibitor+TRAIL and IFNγ+chemotherapeutic agents+TRAIL on the growth and apoptosis of NB cells were detected with MTT and flow cytometry. The relative caspase 8 activity was measured with colorimetric assay. RESULTS: Caspase 8 expression was induced by IFNγ in the NB cell line SKNDZ. TRAIL alone did not induce apoptosis compared with controls but a combination of IFNγ+TRAIL and IFNγ+chemotherapeutic agents+TRAIL significantly induced cell apoptosis in SY5Y cells. Etoposide and doxorubicin induced DR5 but not DR4 in NB cell lines. SKNDZ cells expressing caspase 8 after treatment with IFNγ were still resistant to TRAIL but sensitive to TRAIL after the induction of DR5. CONCLUSIONS: Sensitization of NB cells to TRAIL may be mediated by the upregulation of caspase 8 with IFNγ and DR5 with chemotherapeutic agents. This suggests that caspase 8 and death receptors play a very important role in TRAIL-induced apoptosis of NB cells and a combination of IFNγ, TRAIL and chemotherapeutic agents may be a new and interesting anticancer treatment strategy for NB.


Subject(s)
Antineoplastic Agents/pharmacology , Caspase 8/biosynthesis , Interferon-gamma/pharmacology , Neuroblastoma/drug therapy , Receptors, TNF-Related Apoptosis-Inducing Ligand/biosynthesis , Apoptosis/drug effects , Cell Line, Tumor , Doxorubicin/pharmacology , Etoposide/pharmacology , Humans , RNA, Messenger , TNF-Related Apoptosis-Inducing Ligand/metabolism , Up-Regulation
10.
Transplant Proc ; 40(8): 2525-6, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18929788

ABSTRACT

Hepatic arterial thrombosis is a critical complication in living donor liver transplantation (LDLT). Two separate branches of the right hepatic artery (RHA) are sometimes observed and addressed by anastomosis of the larger branch first, then checking backflow from the smaller branch. If not good, the smaller branch must be reconstructed. We used the cystic artery as a conduit for the reconstruction. Meticulous dissection was performed to identify all branches of the hepatic artery in the donor operation. The length of cystic artery preserved was as long as possible. The cystic arterial stump was anastomosed to the stump of the posterior branch the of RHA under microscopic guidance on the back table. Patency was checked through the stump of the anterior branch of the RHA. With this technique, only one orifice, the stump of right anterior hepatic artery, was used for hepatic artery reconstruction. We have performed this technique in two patients. Both had good arterial flow after living donor liver transplantation. This innovative technique is easy and safe, and requires only one anastomosis, which, in theory, decreases the adds of developing hepatic arterial thrombosis.


Subject(s)
Hepatic Artery/surgery , Liver Transplantation/methods , Living Donors , Plastic Surgery Procedures , Anastomosis, Surgical , Dissection/methods , Functional Laterality , Hepatic Artery/anatomy & histology , Humans , Postoperative Complications/pathology , Thrombosis/pathology
11.
J Med Genet ; 43(8): 653-9, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16571646

ABSTRACT

BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare inherited disorder, characterised by periodic paralysis, cardiac dysarrhythmias, and dysmorphic features, and is caused by mutations in the gene KCNJ2, which encodes the inward rectifier potassium channel, Kir2.1. This study sought to analyse KCNJ2 in patients with familial ATS and to determine the functional characteristics of the mutated gene. METHODS AND RESULTS: We screened a family with inherited ATS for the mutation in KCNJ2, using direct DNA sequencing. A missense mutation (T75R) of Kir2.1, located in the highly conserved cytoplasmic N-terminal domain, was identified in three affected members of this family. Using the Xenopus oocyte expression system and whole cell voltage clamp analyses, we found that the T75R mutant was non-functional and possessed a strong dominant negative effect when co-expressed with the same amount of wild type Kir2.1. Transgenic (Tg) mice expressing the mutated form of Kir2.1 in the heart had prolonged QTc intervals compared with mice expressing the wild type protein. Ventricular tachyarrhythmias were observed in 5 of 14 T75R-Tg mice compared with 1 of 7 Wt-Tg and none of 6 non-transgenic littermates. In three of five T75R-Tg mice with ventricular tachycardia, their ECG disclosed bidirectional tachycardia as in our proband. CONCLUSIONS: The in vitro studies revealed that the T75R mutant of Kir2.1 had a strong dominant negative effect in the Xenopus oocyte expression system. It still preserved the ability to co-assemble and traffic to the cell membrane in mammalian cells. For in vivo studies, the T75R-Tg mice had bidirectional ventricular tachycardia after induction and longer QT intervals.


Subject(s)
Andersen Syndrome/genetics , Genetic Predisposition to Disease , Mutation/genetics , Potassium Channels, Inwardly Rectifying/genetics , Adolescent , Animals , DNA Mutational Analysis , Electrocardiography , Electrophysiology , Female , Humans , Mice , Mice, Transgenic , Myocardium/cytology , Myocardium/pathology , Myocytes, Cardiac/cytology , Xenopus
12.
J Virol ; 75(9): 4357-66, 2001 May.
Article in English | MEDLINE | ID: mdl-11287584

ABSTRACT

The function of the N terminus of the murine leukemia virus (MuLV) surface (SU) protein was examined. A series of five chimeric envelope proteins (Env) were generated in which the N terminus of amphotropic 4070A was replaced by equivalent sequences from ecotropic Moloney MuLV (M-MuLV). Viral titers of these chimeras indicate that exchange with homologous sequences could be tolerated, up to V17eco/T15ampho (crossover III). Constructs encoding the first 28 amino acids (aa) of ecotropic M-MuLV resulted in Env expression and binding to the receptor; however, the virus titer was reduced 5- to 45-fold, indicating a postbinding block. Additional exchange beyond the first 28 aa of ecotropic MuLV Env resulted in defective protein expression. These N-terminal chimeras were also introduced into the AE4 chimeric Env backbone containing the amphotropic receptor binding domain joined at the hinge region to the ecotropic SU C terminus. In this backbone, introduction of the first 17 aa of the ecotropic Env protein significantly increased the titer compared to that of its parental chimera AE4, implying a functional coordination between the N terminus of SU and the C terminus of the SU and/or transmembrane proteins. These data functionally dissect the N-terminal sequence of the MuLV Env protein and identify differential effects on receptor-mediated entry.


Subject(s)
Leukemia Virus, Murine/physiology , Viral Envelope Proteins/physiology , Amino Acid Sequence , Animals , Cell Line , Dogs , Leukemia Virus, Murine/genetics , Mice , Molecular Sequence Data , Viral Envelope Proteins/genetics
13.
Acta Paediatr Taiwan ; 42(1): 46-8, 2001.
Article in English | MEDLINE | ID: mdl-11270186

ABSTRACT

A very low-birth-weight neonate developed chylus-like urine after receiving parenteral nutrition (PN) via percutaneous central venous catheters (CVC) for 7 weeks. A perirenal fluid collection could be seen under sonography. This kind of complication has not been described in literature. After withdrawing the CVC for 5 cm, the urine cleared up. For patients under prolonged PN via CVC and repeated change dressing of the CVC, close monitoring and regular evaluation of the position of the catheter tip are warranted.


Subject(s)
Catheterization, Central Venous/adverse effects , Chyle , Parenteral Nutrition/adverse effects , Humans , Infant, Newborn , Male , Urine
14.
Pacing Clin Electrophysiol ; 23(10 Pt 1): 1564-6, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11060880

ABSTRACT

We report on 16-year-old, female identical twins who both have atrioventricular reentrant tachycardia caused by the same left lateral atrioventricular accessory pathway. The Kent pathway in twin A was a unidirectional retrograde accessory pathway. A manifest Kent pathway was demonstrated in twin B. Both pathways were successfully ablated by radiofrequency (RF) energy and without recurrence. In addition, innocent dual AV nodal pathways were shown in both patients. These findings suggest that genetic factors may play a role in the pathogenesis of the formation of accessory atrioventricular pathways and dual AV nodal pathways.


Subject(s)
Diseases in Twins , Tachycardia, Atrioventricular Nodal Reentry/genetics , Tachycardia, Paroxysmal/genetics , Tachycardia, Supraventricular/genetics , Adolescent , Catheter Ablation , Electrocardiography , Electrophysiologic Techniques, Cardiac , Female , Humans , Tachycardia, Atrioventricular Nodal Reentry/diagnosis , Tachycardia, Paroxysmal/diagnosis , Tachycardia, Paroxysmal/surgery , Tachycardia, Supraventricular/diagnosis , Tachycardia, Supraventricular/surgery , Wolff-Parkinson-White Syndrome/genetics
15.
Int J Cardiol ; 72(3): 221-7, 2000 Feb 15.
Article in English | MEDLINE | ID: mdl-10716130

ABSTRACT

From 1993 to 1998, a total of 100 consecutive pediatric patients with tachycardia (45 male and 55 female, aged 1 year 10 months to 17 years, 11+/-4 year) who underwent electrophysiological study were reviewed. Eleven of them were younger than 5 years. Two had tachycardia-related cerebrovascular accident. Congenital heart disease was found in 12 patients. After propofol anesthesia, the clinical tachycardia could not be induced in three (two atrial tachycardia and one AV nodal re-entrant tachycardia) and became nonsustained in five (atrial tachycardia). Mechanical ablation occurred in three and two had subsequent recurrences. Among the 85 cases who received radiofrequency ablation, the overall final success rate of RF ablation for all diagnoses was 94% with a diagnosis-specific success rate ranging from 100 to 57%. Tachycardia cardiomyopathy was noted in four (three atrial tachycardia and one junctional ectopic tachycardia) and all regressed after successful ablation. Success in two patients with left posterioseptal accessory pathway could only be achieved by delivering the energy at the middle cardiac vein. Two patients with right atrial isomerism had an 'AV nodal-to-AV nodal tachycardia' which was eliminated by ablation. Total recurrence rate was 13% but final success was achieved in all during re-study except the three patients who refused re-intervention. The atrial tachycardia developed in postoperative congenital heart disease was associated with the lowest success rate (57%) and highest recurrence rate (25%). Procedure-related complications occurred in four; two with transient brachial palsy, one with first-degree AV block and one with blood loss requiring blood transfusion. In conclusion, the experience of this single center confirmed the efficacy and safety of radiofrequency catheter ablation in treating pediatric arrhythmias, but the limitations in postoperative arrhythmias and the effects of propofol on tachycardia induction (especially the atrial tachycardia) need to be improved.


Subject(s)
Catheter Ablation , Heart Defects, Congenital , Tachycardia/surgery , Anesthetics, Intravenous , Cardiac Pacing, Artificial , Case-Control Studies , Child , Electrophysiology , Female , Heart Defects, Congenital/complications , Humans , Male , Propofol , Recurrence , Retrospective Studies , Tachycardia/etiology
16.
J Biomed Sci ; 5(2): 101-10, 1998.
Article in English | MEDLINE | ID: mdl-9662069

ABSTRACT

Protein kinases play key roles in cellular functions. They are involved in many cellular functions including; signal transduction, cell cycle regulation, cell division, and cell differentiation. Alterations of protein kinase by gene amplification, mutation or viral factors often induce tumor formation and tumor progression toward malignancy. The identification and cloning of kinase genes can provide a better understanding of the mechanisms of tumorigenesis as well as diagnostic tools for tumor staging. In this study, we have used degenerated polymerase-chain-reaction primers according to the consensus catalytic domain motifs to amplify protein kinase genes (protein-tyrosine kinase, PTK, and protein-serine/threonine kinase, PSK) from human stomach cancer cells. Following amplification, the protein kinase molecules expressed in the gastric cancer cells were cloned into plasmid vectors for cloning and sequencing. Sequence analysis of polymerase-chain-reaction products resulted in the identification of 25 protein kinases, including two novel ones. Expression of several relevant PTK/PSK genes in gastric cancer cells and tissues was further substantiated by RT-PCR using gene-specific primers. The identification of protein kinases expressed or activated in the gastric cancer cells provide the framework to understand the oncogenic process of stomach cancer.


Subject(s)
Protein Serine-Threonine Kinases/genetics , Protein-Tyrosine Kinases/genetics , Stomach Neoplasms/enzymology , Stomach Neoplasms/genetics , Amino Acid Sequence , Base Sequence , DNA Primers/genetics , Gene Expression , Humans , Molecular Sequence Data , Polymerase Chain Reaction , Stomach Neoplasms/etiology , Tumor Cells, Cultured
18.
J Gastroenterol Hepatol ; 9(6): 592-6, 1994.
Article in English | MEDLINE | ID: mdl-7865718

ABSTRACT

Single total paracentesis (4.8-11 L) was performed in 23 patients with hepatitis B surface antigen (HBsAg)-positive cirrhosis and massive ascites and its effects on systemic and hepatic haemodynamics and renal function were examined over 5 days. Severe hypotension occurred in six (26.1%) patients from 6 to 54 h after paracentesis. In the remaining 17 patients, compared to the baseline, there was an increase in the cardiac output (6.1 +/- 0.3 vs 6.7 +/- 0.3 L/min, P < 0.001) and a decrease in right atrial pressure (8.8 +/- 0.8 vs 4.3 +/- 0.7 mmHg, P < 0.001), systemic vascular resistance (1160 +/- 61 vs 976 +/- 50 dyne.s.cm-5, P < 0.001), and wedged hepatic venous pressure 30 min after completion of paracentesis. After 5 days, right atrial pressure, systemic vascular resistance and wedged hepatic venous pressure returned to baseline, while the cardiac output dropped to a level lower than the baseline (5.7 +/- 0.7 L/min, P < 0.05). Hepatic venous pressure gradient had returned to baseline after 5 days. Serial tests of serum creatinine level showed an increase from day 3 (1.34 +/- 0.14 vs 1.04 +/- 0.10 mg/dL, P < 0.05). On day 5, creatinine clearance (55.7 +/- 5.4 vs 41.9 +/- 5.3 mL/min, P < 0.05) and effective renal plasma flow (351 +/- 32 vs 293 +/- 29 mL/min, P < 0.05) were decreased, compared to the baseline. Based on these data, infusion of a volume expander may be necessary for total paracentesis to avoid systemic haemodynamic complications in non-alcoholic cirrhosis.


Subject(s)
Ascites/therapy , Hemodynamics/physiology , Kidney/physiopathology , Liver Circulation/physiology , Liver Cirrhosis/complications , Ascites/etiology , Drainage/methods , Female , Hepatitis B Surface Antigens/analysis , Humans , Hypotension/etiology , Liver Cirrhosis/physiopathology , Liver Cirrhosis/virology , Male , Middle Aged , Plasma Substitutes/therapeutic use , Punctures , Time Factors
19.
J Gastroenterol Hepatol ; 9(4): 396-400, 1994.
Article in English | MEDLINE | ID: mdl-7948823

ABSTRACT

To determine the clinical value of tumour markers in the diagnosis of malignancy-related ascites (not including hepatocellular carcinoma), serum and ascitic fluid levels of carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 19-9, tissue polypeptide antigen and serum-ascites albumin gradient were determined in 66 patients with cirrhotic ascites, 28 patients with hepatocellular carcinoma and ascites, and 29 patients with malignancy-related ascites. Three tumour markers and serum-ascites albumin gradient showed significant difference between patients with malignancy-related ascites and those without: serum carcinoembryonic antigen (26.4 +/- 31.5 vs 4.8 +/- 4.6 ng/mL, P < 0.01), ascitic fluid carcinoembryonic antigen (118.4 +/- 196.5 vs 2.0 +/- 1.4 ng/mL, P < 0.01), ascitic fluid carbohydrate antigen 19-9 (12,933 +/- 25,496 vs 23 +/- 67 U/mL, P < 0.01) and serum-ascites albumin gradient (1.1 +/- 0.4 vs 2.0 +/- 0.4 g/dL, P < 0.01). At the best cut-off levels chosen from near 95% of the data in those without malignancy-related ascites, the sensitivity, specificity and accuracy to diagnose malignancy-related ascites were, respectively, 65.5%, 93.6%, 87.0% using serum carcinoembryonic antigen > or = 10 ng/mL; 69.0%, 94.7%, 88.6% using ascitic fluid carcinoembryonic antigen > or = 5 ng/mL; 65.5%, 93.6%, 87.0% using ascitic fluid carbohydrate antigen 19-9 > or = 50 U/mL; 62.1%, 98.9%, 90.2% using serum-ascites albumin gradient < 1.1 g/dL. Although serum-ascites albumin gradient offered the best diagnostic accuracy and specificity, its sensitivity was not good enough. Our study indicates that serum-ascites albumin gradient and tumour markers are not sensitive parameters in the diagnosis of malignancy-related ascites.


Subject(s)
Ascites/etiology , Ascitic Fluid/chemistry , Biomarkers, Tumor/analysis , Peritoneal Neoplasms/complications , Peritoneal Neoplasms/diagnosis , Serum Albumin/analysis , Ascites/diagnosis , Carcinoma, Hepatocellular/complications , Diagnosis, Differential , Female , Humans , Immunoradiometric Assay , Liver Cirrhosis/complications , Liver Neoplasms/complications , Male , Middle Aged , Peritoneal Neoplasms/secondary , Predictive Value of Tests , Sensitivity and Specificity
20.
Zhonghua Yi Xue Za Zhi (Taipei) ; 53(2): 71-6, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8167991

ABSTRACT

BACKGROUND: The clinical value of ascitic fluid pH or lactate in the diagnosis of spontaneous bacterial peritonitis was debated in alcoholic cirrhosis. It was rarely discussed in hepatitis B-related cirrhosis. We investigated the best rapid diagnostic method in spontaneous bacterial peritonitis of patients with hepatitis B-related cirrhosis. METHODS: Ascitic fluid polymorphonuclear cell count, ascitic fluid pH, arterial-ascitic fluid pH gradient, ascitic fluid lactate, and arterial-ascitic fluid lactate gradient were analyzed in 79 patients with sterile portal hypertension-related ascites, 31 patients with spontaneous bacterial peritonitis, 16 patients with hepatocellular carcinoma, 15 patients with malignancy-related ascites and 9 patients with other miscellaneous diseases. RESULTS: The sensitivity, specificity and accuracy of the diagnosis of spontaneous bacterial peritonitis were 100, 94 and 95% with the cut-off value of an ascitic fluid polymorphonuclear cell count > or = 250 cells/mm3, and were 86, 98 and 96% with that value > or = 500 cells/mm3, respectively. The sensitivity, specificity and accuracy were 29, 92, 80% using ascitic fluid pH < or = 7.35 as a cut-off value; 38, 91, 82% using arterial-ascitic fluid pH gradient > or = 0.1 as a cut-off value; 52, 92, 85% using ascitic fluid lactate > or = 32 mg/dL as a cut-off value, and 38, 96, 85% using arterial-ascitic fluid lactate gradient > or = 20 mg/dL as a cut-off value. CONCLUSIONS: The sensitivity of ascitic fluid pH or lactate was too low to aid in a diagnosis of spontaneous bacterial peritonitis in hepatitis B-related cirrhosis in spite of the acceptable specificity. An ascitic fluid polymorphonuclear cell count > or = 250 cells/mm3 or > or = 500 cells/mm3 was the major and appropriate aids in the rapid diagnosis of spontaneous bacterial peritonitis.


Subject(s)
Ascitic Fluid/cytology , Bacterial Infections/diagnosis , Hepatitis B/complications , Lactates/analysis , Liver Cirrhosis, Alcoholic/complications , Peritonitis/diagnosis , Adult , Aged , Aged, 80 and over , Ascitic Fluid/metabolism , Female , Humans , Hydrogen-Ion Concentration , Lactates/blood , Lactic Acid , Leukocyte Count , Male , Middle Aged , Neutrophils
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