Histopathological diagnoses on pleural biopsy specimens over a 15-year period at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa: A retrospective review.

BACKGROUND: Pleural effusions are a common reason for presentation to healthcare facilities. Blind closed pleural biopsy can be a useful tool to diagnose their cause, especially in resource-limited settings. OBJECTIVES: To determine the aetiology, frequency and change in profile of histopathological diagnoses made at Chris Hani Baragwanath Academic Hospital (CHBAH), Johannesburg, South Africa, over the period 1 January 2001 - 31 December 2015. METHODS: Pleural biopsies performed at CHBAH and analysed by histopathologists from the National Health Laboratory Service at the hospital over the study period were retrospectively reviewed by accessing reports from two databases (DISA and TrakCare). The subjects' ages, genders, HIV status and histopathological diagnoses as well as adenosine deaminase and Ziehl-Neelsen results were recorded. RESULTS: A total of 1 013 samples were included in the study, with 780 considered adequate for assessment. The most common diagnosis was granulomatous inflammation (48.1%, n=375), with the most common type being necrotising granulomatous inflammation (73.6%, n=276). Ten percent of biopsies (n=78) showed malignancy, most commonly adenocarcinoma, with 46.2% (n=36) metastatic and 23.1% (n=18) primary lung adenocarcinoma. The odds of being diagnosed with malignancy showed increasing statistical significance above the age of 40 years: 40 - 49 years odds ratio (OR) 8.7, 95% confidence interval (CI) 1.1 - 66.9 (p=0.038); 50 - 59 years OR 12.4, 95% CI 1.6 - 95.0 (p=0.015); ≥60 years OR 23.0, 95% CI 3.1 - 171.3 (p=0.002). HIV seropositivity was associated with lower odds of being diagnosed with malignancy compared with HIV-negative patients (OR 0.5, 95% CI 0.2 - 0.9; p=0.040), with greater odds of a 'non-cancer' diagnosis in HIV-positive patients (including granulomatous inflammation and pleuritis (OR 2.16, 95% CI 1.03 - 4.51; p=0.040)). CONCLUSIONS: Blind closed pleural biopsy has a role to play in the diagnosis of exudative pleural effusions in resource-limited settings, particularly for patients suspected to have tuberculosis (TB) or malignancy. TB remains a common cause of exudative pleural effusions. Patients aged >40 years presenting with an exudative pleural effusion should routinely have pleural biopsy performed. However, this study showed a high frequency of inadequate specimens from closed pleural biopsy. Training in the performance of this procedure to increase diagnostic rates is recommended.

Valproic acid enhances neuronal differentiation of sympathoadrenal progenitor cells.

The antiepileptic drug valproic acid (VPA) has been shown to influence the neural differentiation and neurite outgrowth of neural stem cells. Sympathoadrenal progenitor cells share properties with neural stem cells and are considered a potential cell source in the treatment of neurodegenerative diseases. The present study therefore aims at modulating the neural differentiation potential of these cells by treatment with the histone deacetylase inhibitor VPA. We studied the epigenetic effects of VPA in two culture conditions: suspension conditions aimed to expand adrenomedullary sympathoadrenal progenitors within free-floating chromospheres and adherent cell cultures optimized to derive neurons. Treatment of chromospheres with VPA may launch neuronal differentiation mechanisms and improve their neurogenic potential upon transplantation. However, also transplantation of differentiated functional neurons could be beneficial. Treating chromospheres for 7 days with clinically relevant concentrations of VPA (2 mm) revealed a decrease of neural progenitor markers Nestin, Notch2 and Sox10. Furthermore, VPA initiated catecholaminergic neuronal differentiation indicated by upregulation of the neuronal marker ß-III-tubulin, the dopaminergic transcription factor Pitx3 and the catecholaminergic enzymes TH and GTPCH. In adherent neural differentiation conditions, VPA treatment improved the differentiation of sympathoadrenal progenitor cells into catecholaminergic neurons with significantly elevated levels of nor- and epinephrine. In conclusion, similar to neural stem cells, VPA launches differentiation mechanisms in sympathoadrenal progenitor cells that result in increased generation of functional neurons. Thus, data from this study will be relevant to the potential use of chromaffin progenitors in transplantation therapies of neurodegenerative diseases.

Neutrophil gelatinase-associated lipocalin in dogs with naturally occurring renal diseases.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is released from renal tubular cells after injury and serves in humans as a real-time indicator of active kidney damage, including acute kidney injury (AKI) and chronic kidney disease (CKD). However, NGAL concentrations in dogs with naturally occurring AKI or CKD rarely have been explored in detail. HYPOTHESIS/OBJECTIVES: The goal of this study was to evaluate whether NGAL can serve as a useful biomarker in dogs with naturally occurring renal disease. ANIMALS: Client-owned dogs with renal disease (57) and control dogs without any disease (12) were examined. METHODS: Serum NGAL (sNGAL) and urine NGAL (uNGAL) concentrations were measured in each animal by a newly developed ELISA system. Demographic, hematologic, and serum biochemical data were recorded. Survival attributable to AKI and CKD was evaluated at 30 days and 90 days, respectively. RESULTS: Serum and urine NGAL concentrations in azotemic dogs were significantly higher than in nonazotemic dogs and were highly correlated with serum creatinine concentration (P < .05). Among CKD dogs, death was associated with significantly higher sNGAL and uNGAL concentrations compared with survivors. Receiver-operating characteristic curve (ROC) analysis showed that sNGAL was better than serum creatinine concentration when predicting clinical outcomes for CKD dogs (P < .05). The best cutoff point for sNGAL was 50.6 ng/mL, which gave a sensitivity and a specificity of 76.9 and 100%, respectively. Furthermore, dogs that had higher concentrations of sNGAL survived for a significantly shorter time. CONCLUSION: sNGAL is a useful prognostic marker when evaluating dogs with CKD.

Lipidomic profiling before and after Roux-en-Y gastric bypass in obese patients with diabetes.

Bariatric surgery is a well-established approach to improve metabolic disease in morbidly obese patients with high cardiovascular risk. The post-operative normalization of lipid metabolism has a central role in the prevention of future cardiovascular events. The aim of the present study therefore was to characterize changes of plasma lipidomic patterns, consisting of 229 lipid species of 13 lipid classes, 3 months after Roux-en-Y gastric bypass (RYGB) in morbidly obese patients with and without diabetes. RYGB resulted in a 15-32% decrease of body mass index, which was associated with a significant reduction of total cholesterol (TC, -28.3%; P=0.02), LDL-cholesterol (LDL-C, -26.8%; P=0.03) and triglycerides (TGs, -63.0%; P=0.05) measured by routine clinical chemistry. HDL-cholesterol remained unchanged. The effect of RYGB on the plasma lipidomic profile was characterized by significant decreases of 87 lipid species from triacylglycerides (TAGs), cholesterol esters (CholEs), lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), phosphatidylethanolamine ethers (PEOs), phosphatidylinositols (PIs) and ceramides (Cers). The total of plasma lipid components exhibited a substantial decline of 32.6% and 66 lipid species showed a decrease by over 50%. A direct correlation with HbA1C values could be demonstrated for 24 individual lipid species (10 TAG, three CholE, two LPC, one lysophosphatidylcholine ethers (LPCO) (LPC ether), one PC, two phosphatidylcholine ethers (PCO) and five Cer). Notably, two lipid species (TAG 58:5 and PEO 40:5) were inversely correlated with HbA1C. LPCO, as single whole lipid class, was directly related to HbA1C. These data indicate that RYGB-induced modulation of lipidomic profiles provides important information about post-operative metabolic adaptations and might substantially contribute to improvements of glycemic control. These striking changes in the human plasma lipidome may explain acute, weight independent and long-term effects of RYGB on the cardiovascular system, mental status and immune regulation.

Prevalence of tobacco smoking in adults with tuberculosis in South Africa.

We conducted a tobacco prevalence survey among 707 in-patients diagnosed with tuberculosis (TB) at the Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. Current smoking status was expanded to include both patients who self-reported at the time of TB diagnosis and patients who stopped smoking in the 2-month period before diagnosis. Six per cent reported current smoking at the time of TB diagnosis, 26% within 2 months before TB diagnosis. Human immunodeficiency virus status (73% positive) was not associated with current smoking. Classifying current smoking status among newly diagnosed TB patients should be extended to include smoking at time of the onset of TB symptoms.

Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters.

Roux-en-Y gastric bypass (RYGB) has become a prominent therapeutic option for long-term treatment of morbid obesity and type 2 diabetes mellitus (T2D). Cross talk and pathogenetic consequences of RYGB-induced profound effects on metabolism and gut microbiome are poorly understood. The aim of the present study therefore was to characterize intra-individual changes of gut microbial composition before and 3 months after RYGB by metagenomic sequencing in morbidly obese patients (body mass index (BMI)>40 kg m(-)(2)) with T2D. Subsequently, metagenomic data were correlated with clinical indices. Based on gene relative abundance profile, 1061 species, 729 genera, 44 phyla and 5127 KO (KEGG Orthology) were identified. Despite high diversity, bacteria could mostly be assigned to seven bacterial divisions. The overall metagenomic RYGB-induced shift was characterized by a reduction of Firmicutes and Bacteroidetes and an increase of Proteobacteria. Twenty-two microbial species and 11 genera were significantly altered by RYGB. Using principal component analysis, highly correlated species were assembled into two common components. Component 1 consisted of species that were mainly associated with BMI and C-reactive protein. This component was characterized by increased numbers of Proteobacterium Enterobacter cancerogenus and decreased Firmicutes Faecalibacterium prausnitzii and Coprococcus comes. Functional analysis of carbohydrate metabolism by KO revealed significant effects in 13 KOs assigned to phosphotransferase system. Spearmen's Rank correlation indicated an association of 10 species with plasma total- or low-density lipoprotein cholesterol, and 5 species with triglycerides. F. prausnitzii was directly correlated to fasting blood glucose. This is the first clinical demonstration of a profound and specific intra-individual modification of gut microbial composition by full metagenomic sequencing. A clear correlation exists of microbiome composition and gene function with an improvement in metabolic and inflammatory parameters. This will allow to develop new diagnostic and therapeutic strategies based on metagenomic sequencing of the human gut microbiome.

Prediction of susceptibility to major depression by a model of interactions of multiple functional genetic variants and environmental factors.

Major depressive disorder (MDD) is the most common psychiatric disorder and the second overall cause of disability. Even though a significant amount of the variance in the MDD phenotype is explained by inheritance, specific genetic variants conferring susceptibility to MDD explain only a minimal proportion of MDD causality. Moreover, genome-wide association studies have only identified two small-sized effect loci that reach genome-wide significance. In this study, a group of Mexican-American patients with MDD and controls recruited for a pharmacogenetic study were genotyped for nonsynonymous single-nucleotide polymorphisms (nsSNPs) and used to explore the interactions of multiple functional genetic variants with risk-classification tree analysis. The risk-classification tree analysis model and linkage disequilibrium blocks were used to replicate exploratory findings in the database of genotypes and phenotypes (dbGaP) for major depression, and pathway analysis was performed to explore potential biological mechanisms using the branching events. In exploratory analyses, we found that risk-classification tree analysis, using 15 nsSNPs that had a nominal association with MDD diagnosis, identified multiple increased-MDD genotype clusters and significant additive interactions in combinations of genotype variants that were significantly associated with MDD. The results in the dbGaP for major depression disclosed a multidimensional dependent phenotype constituted of MDD plus significant modifiers (smoking, marriage status, age, alcohol abuse/dependence and gender), which then was used for the association tree analysis. The reconstructed tree analysis for the dbGaP data showed robust reliability and replicated most of the genes involved in the branching process found in our exploratory analyses. Pathway analysis using all six major events of branching (PSMD9, HSD3B1, BDNF, GHRHR, PDE6C and PDLIM5) was significant for positive regulation of cellular and biological processes that are relevant to growth and organ development. Our findings not only provide important insights into the biological pathways underlying innate susceptibility to MDD but also offer a predictive framework based on interactions of multiple functional genetic variants and environmental factors. These findings identify novel targets for therapeutics and for translation into preventive, clinical and personalized health care.

A qualitative study on HPV vaccination from a nursing perspective in Hong Kong.

OBJECTIVE: To identify the perception on human papillomavirus (HPV) vaccination among female nursing students in Hong Kong. DATA SOURCES: Data were collected through focus group discussions and semi-structured in-depth interviews. All participants (n=28) were female nursing students of a university in Hong Kong. Tape recordings of individual interviews and focus group discussions were transcribed verbatim in Chinese, translated into English, and analyzed according to Colaizzi's phenomenological analysis. STUDY DESIGN: Four major themes emerged from the data: nursing students' understanding about HPV vaccine, nursing students' attitude on HPV vaccine, nursing students' perspective on HPV vaccination promotion, and nursing role on HPV vaccination. CONCLUSIONS: Government should take initiative in promotion with vaccine suppliers. The awareness and knowledge of HPV and HPV vaccination among women should be increased in order to raise the positive attitude of women towards HPV vaccination and prevention of cervical cancer. Health professionals should work together on HPV promotion among women and increase the HPV vaccination rates. Moreover, further studies regarding attitude and awareness of HPV vaccination among women in different age groups are needed in order to identify more associated factors affecting their perceptions towards HPV vaccination.

Haemoglobin in normal and neoplastic canine mammary glands.

Four types of globins for oxygen transport are known in vertebrates, and the haemoglobin is responsible for carrying oxygen in blood. In this study, we found that haemoglobin was also expressed in canine mammary glands. Samples were taken from 26 malignant mammary tumors, 16 normal mammary glands and 10 other normal tissues. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting and mass spectrometry were used to investigate haemoglobin in mammary tissues. The results indicated that normal canine mammary glands expressed high levels of haemoglobin protein as shown by Coomassie blue staining. The identity of haemoglobin was confirmed by immunoblotting and mass spectrometry, and the mass spectrometry data revealed that both alpha-haemoglobin and beta-haemoglobin were expressed. Relative to normal mammary glands, the levels of haemoglobin expression in mammary tumors were lower. Our results also indicated that the haemoglobin was endogenously produced in mammary gland tissues and was not derived from the erythroid cells.

Framingham Risk Scores and Anthropometric Measurements in Predicting Cardiovascular Risks among Malay Men.

Framingham Risk Scores is an established method to predict an individual's 10-year risk for coronary heart disease (CHD). It provides a more precise delineation of risk which might lead to appropriate selection of therapy and opportunities for patient education and motivation. A Healthy Lifestyle Project was initiated to decrease the modifiable risk factors for CHD in a worksite in Kuala Lumpur. The participants were Malay men (n=186) working as security guards in a public university. Their mean age was 46.6 + 6.6 years. The majority had secondary education and were married. The participants' 10-year risks based on the Framingham Risk Scores were 55.4%, 39.8% and 4.8% respectively for categories of low (< 10%), intermediate (10 to 20%) and high (>20%) risk. Their Framingham Risk Scores were then correlated with anthropometric measurements such as the Body Mass Index (BMI), waist circumference and waist-hip-ratio (WHR). All the anthropometric measurements had weak but significant correlation with the Framingham Risk Scores (WHR: r=0.26; waist circumference: r=0.23; BMI: r=0.16). In conclusion, 44.6% of our participants had more than 10% risk in developing CHD in the coming ten years. Hence, they are suitable target candidates for the promotion of a healthy lifestyle such as smoking cessation, weight control, healthy dietary patterns and increased physical activities. Indicators of abdominal obesity like WHR or waist circumference may be used to complement the Framingham Risk Scores for the prediction of CHD risk in this population.

Id-1 and Id-2 are markers for metastasis and prognosis in oesophageal squamous cell carcinoma.

Id protein family consists of four members namely Id-1 to Id-4. Different from other basic helix-loop-helix transcription factors, they lack the DNA binding domain. Id proteins have been shown to be dysregulated in many different cancer types and their prognostic value has also been demonstrated. Recently, Id-1 has been shown to be upregulated in oesophageal squamous cell carcinoma (ESCC). However, the prognostic implications of Id proteins in ESCC have not been reported. We examined the expression of the Id proteins in ESCC cell lines and clinical ESCC specimens and found that Id protein expressions were dysregulated in both the ESCC cell lines and specimens. By correlating the expression levels of Id proteins and the clinicopathological data of our patient cohort, we found that M1 stage tumours had significantly higher nuclear Id-1 expression (P=0.012) while high nuclear Id-1 expression could predict development of distant metastasis within 1 year of oesophagectomy (P=0.005). In addition, high levels of Id-2 expression in both cytoplasmic and nuclear regions predicted longer patient survival (P=0.041). Multivariate analysis showed that high-level expression of Id-2 in both cytoplasmic and nuclear regions and lower level of nuclear Id-1 expression were independent favourable predictors of survival in our ESCC patients. Our results suggest that Id-1 may promote distant metastasis in ESCC, and both Id-1 and Id-2 may be used for prognostication for ESCC patients.

Mammary carcinoma with sebaceous differentiation in a dog.

This report describes an invasive mammary carcinoma with a rare distinctive feature characterized by sebaceous differentiation of tumor cells. This tumor occurred in a 10-year-old female mixed breed dog. The patient had two masses in the left fifth mammary gland. Grossly, the masses were firm, whitish to light brown, and superficially ulcerated. On cut surface, they were multilobulated with foci of necrosis. Microscopically, the tumors were composed of two distinctive neoplastic components, intraductal papillary adenocarcinoma and sebaceous carcinoma. The regions of sebaceous tumor were clumped separately, contained well-developed sebaceous cells and keratinized epithelial cells, and were surrounded by few to several layers of basaloid cells. The cells with abundant foamy cytoplasm that resembled sebaceous cells were also found within the intraductal papillary-like nests of mammary carcinoma, providing evidence of sebaceous metaplasia. Sebaceous differentiation in a mammary gland tumor is possible, because skin appendages and ductal apparatus of the mammary gland share a common anlagen. This tumor had an aggressive behavior with lymphatic metastasis. Consequentially, the dog had a poor prognosis.

Cryptococcal pneumonia in African miners at autopsy.

SETTING: Deceased miners from South Africa whose cardiorespiratory organs were submitted for autopsy for compensation for occupational lung diseases from 1996 to 2000. OBJECTIVES: To 1) calculate the prevalence of cryptococcal pneumonia in 8421 autopsied miners, a population with a high prevalence of human immunodeficiency virus (HIV) infection; 2) document the association of cryptococcal pneumonia with other pulmonary infection; 3) document the association of cryptococcal pneumonia with a clinical diagnosis of cryptococcal meningitis; and 4) determine the accuracy of the clinical diagnosis of cryptococcal pneumonia. DESIGN: Case series of 589 black miners with histological evidence of cryptococcal pneumonia at autopsy, defined as the presence of cryptococcal organisms in the lung parenchyma, identified by staining of the mucinous capsule. RESULTS: The incidence of cryptococcal pneumonia at autopsy was 7%. Ninety-seven of the 589 cases (16.5%) had a concomitant respiratory infection, most commonly Pneumocystis jirovecii pneumonia (51.5%), followed by mycobacterial infection (42.3%). In life, cryptococcal meningitis was diagnosed in 46.9% and cryptococcal pneumonia in only 2.7%. CONCLUSION: Although tuberculosis remains the most common HIV-associated respiratory disease in Africa, it is important to consider the diagnosis of cryptococcal pneumonia in acquired immune-deficiency syndrome (AIDS) patients, and to bear in mind the possibility of dual pathology.

The major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formation.

Identification of tumor suppressor genes (TSG) silenced by methylation uncovers mechanisms of tumorigenesis and identifies new epigenetic tumor markers for early cancer detection. Both nasopharyngeal carcinoma (NPC) and esophageal carcinoma are major tumors in Southern China and Southeast Asia. Through expression subtraction of NPC, we identified Deleted in Liver Cancer 1 (DLC1)/ARHGAP7 (NM_006094)--an 8p22 TSG as a major downregulated gene. Although expressed in all normal tissues, DLC1 was silenced or downregulated in 11/12 (91%) NPC, 6/15 (40%) esophageal, 5/8 (63%) cervical and 3/9 (33%) breast carcinoma cell lines. No genetic deletion of DLC1 was detected in NPC although a hemizygous deletion at 8p22-11 was found by 1-Mb array-CGH in some cell lines. We then located the functional DLC1 promoter by 5'-RACE and promoter activity assays. This promoter was frequently methylated in all downregulated cell lines and in a large collection of primary tumors including 89% (64/72) NPC (endemic and sporadic types), 51% (48/94) esophageal, 87% (7/8) cervical and 36% (5/14) breast carcinomas, but seldom in paired surgical marginal tissues and not in any normal epithelial tissue. The transcriptional silencing of DLC1 could be reversed by 5-aza-2'-deoxycytidine or genetic double knock-out of DNMT1 and DNMT3B. Furthermore, ectopic expression of DLC1 in NPC and esophageal carcinoma cells strongly inhibited their colony formation. We thus found frequent epigenetic silencing of DLC1 in NPC, esophageal and cervical carcinomas, and a high correlation of methylation with its downregulation, suggesting a predominant role of epigenetic inactivation. DLC1 appears to be a major TSG implicated in the pathogenesis of these tumors, and should be further tested as a molecular biomarker in patients with these cancers.

Utility of the Health Belief Model in predicting compliance of screening in patients with chronic hepatitis B.

BACKGROUND: Regular surveillance is recommended for patients with chronic hepatitis B, to select candidates for anti-viral therapy and detect early complications. However, factors that determine compliance are not well studied. AIM: To determine the utility of the Health Belief Model in explaining non-compliance, among a group of chronic hepatitis B patients for screening. METHODS: A total of 192 chronic hepatitis B patients who responded to advertisement for free screening took part in a telephonic interview study. Subjects were asked about the five constructs of the Health Belief Model, and factors associated with recent screening were analysed. RESULTS: The mean age of the subjects was 42.1 +/- 0.7 years; 77% white male, and 97% Chinese. About 108 patients (56%) had recent screening. At multivariate analysis, only the ability to remember date of follow-up (OR: 4.37; 95% CI: 2.07-9.17) and the perception of having to wait a long time for venepuncture (OR: 0.38; 95% CI: 0.19-0.79) were significantly associated with recent screening. CONCLUSION: Future public health measures should include improving the logistics of follow-up procedures and providing reminders for screening to improve compliance.

Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma.

BACKGROUND: Identification of risk factors for the development of hepatocellular carcinoma (HCC) is important for HCC surveillance in chronic hepatitis B virus (HBV) infection. Our aim was to study the independent risk factors and effect of HBV genotypes on HCC development in a prospective longitudinal cohort of chronic hepatitis B patients. PATIENTS AND METHODS: Chronic hepatitis B patients recruited since 1997 were prospectively followed up for the development of HCC. HCC was diagnosed by a combination of alpha fetoprotein, imaging, and histology. Liver cirrhosis was defined as ultrasonic features of cirrhosis together with hypersplenism, ascites, varices, and/or encephalopathy. RESULTS: In total, 426 patients were followed up for 1664 person years; median 225 (range 12-295) weeks. Forty nine (11%) patients had underlying clinical liver cirrhosis. A total of 242 (57%) and 179 (42%) patients had HBV genotypes C and B, respectively. Twenty five patients developed HCC in a median follow up of 121 (range 14-236) weeks. The overall incidence of HCC was 1502 cases per 100 000 person years. On multivariate analysis, clinical liver cirrhosis and HBV genotype C infection were independently associated with HCC development, with an adjusted relative risk of 10.24 (95% confidence interval (CI) 4.39-23.89; p<0.001) and 2.84 (95% CI 1.05-7.72; p = 0.040), respectively. Patient age, sex, hepatitis B e antigen (HBeAg) status, alanine aminotransferase (ALT) levels, and basal core promoter mutations did not predict HCC development. Patients infected with HBV genotype C tended to have persistently positive HBeAg or fluctuating HBeAg status and higher ALT levels during the follow up period. CONCLUSION: Genotype C HBV infection is an independent risk factor for HCC development in addition to liver cirrhosis.

Bupropion in the management of apathy.

We report on three males with prominent apathy as part of the symptom complex of depression or organic brain disease. Significant clinical responses were observed following treatment with bupropion, an antidepressant with dopamine (DA) reuptake activity. We present clinical evidence in support of the hypothesis that remission in these patients occurred as a consequence of bupropion-induced increases in central DA neurotransmission.

Expression of recombinant envelope protein of Japanese encephalitis virus YL strain in Escherichia coli possesses hemagglutination activity.

The nucleotide sequence of glycoprotein E of YL vaccine strain was cloned, sequenced and expressed in E. coli. Phylogenetic analysis of envelope (E) amino acid sequences of 18 JEVs in GenBank showed that the vaccine strain YL closer to the virulent strain HVI which is a Taiwanese isolate. We found only two amino acid mutations (K-138 and G-389) of E protein might lead viral attenuation in YL. In this study, we used pRSET vector system to construct three recombinant plasmids (pRSET/F1R1, pRSET/F2R2 and pRSET/F1R2), which encoded and expressed different or overlapping amino acid region of E protein. The antigenicity and hemagglutination activity of these recombinant proteins were examined by western blotting and hemagglutination test, respectively. Our results demonstrated that the recombinant protein of pRSET/F1R2 possesses predominant antigenicity and hemagglutination activity.