Cryptococcus neoformans is an encapsulated basidiomycetous yeast commonly associated with pigeon droppings and soil. The opportunistic pathogen infects humans through the respiratory system and the metabolic implications of C. neoformans infection have yet to be explored. Studying the metabolic profile associated with the infection could lead to the identification of important metabolites associated with pulmonary infection. Therefore, the aim of the study was to simulate cryptococcal infection at the primary site of infection, the lungs, and to identify the metabolic profile and important metabolites associated with the infection at low and high multiplicity of infections (MOI). The culture supernatant of lung epithelial cells infected with C. neoformans at MOI of 10 and 100 over a period of 18 hours were analysed using gas chromatography mass spectrometry. The metabolic profiles obtained were further analysed using multivariate analysis and the pathway analysis tool, MetaboAnalyst 2.0. Based on the results from the multivariate analyses, ten metabolites were selected as the discriminatory metabolites that were important in both the infection conditions. The pathways affected during early C. neoformans infection of lung epithelial cells were mainly the central carbon metabolism and biosynthesis of amino acids. Infection at a higher MOI led to a perturbance in the β-alanine metabolism and an increase in the secretion of pantothenic acid into the growth media. Pantothenic acid production during yeast infection has not been documented and the β-alanine metabolism as well as the pantothenate and CoA biosynthesis pathways may represent underlying metabolic pathways associated with disease progression. Our study suggested that β-alanine metabolism and the pantothenate and CoA biosynthesis pathways might be the important pathways associated with cryptococcal infection.
A consecutive series of 2,277 patients presenting for upper gastrointestinal endoscopy was analysed. The following groups of patients were studied with reference to sex, race and dialect groups: those presenting with dyspepsia but no haemorrhage, those presenting with upper gastrointestinal haemorrhage, those with non-ulcer dyspepsia, gastric ulcer and duodenal ulcer. Males out-numbered females in all diagnostic groups. Male and female Malays were under-represented in all diagnostic groups when compared to the Singapore population. Amongst female Chinese, there was an excess of Cantonese patients and an under-representation of Teochew patients in most diagnostic groups. These dialect differences were not remarkable amongst male Chinese. The possible reasons for these differences and their significance are discussed.
In Malaysia, homosexuality is illegal; little is known about access to HIV prevention services among Malaysian men who have sex with men (MSM). We analysed PT Foundation outreach data to describe the profiles among MSM who accessed PT Foundation services and to examine factors associated with being aware of PT Foundation and having visited the organization. A survey was administered during weekly outreach throughout Kuala Lumpur from March-December 2012. Pearson's Chi square tests were used to compare demographic and behavioural characteristics of participants who were and were not aware of the PT Foundation. Binary logistic regression was used to identify correlates of MSM visiting the PT Foundation among those who had heard of the organization. Of 614 MSM, this study found significantly higher awareness of the PT Foundation among MSM who perceived they had "good" HIV knowledge (p = .026) and participants who reported always using condoms (p = .009). MSM who reported being paid for sex were 2.81 times as likely to visit the PT Foundation compared to men who did not. A subgroup of MSM known to be at high risk for HIV infection is accessing prevention services. Future studies should uncover motivations and barriers of accessing these services among MSM in Malaysia.
Human toxocariasis which is caused mainly by the larvae of Toxocara canis and Toxocara cati, is a worldwide zoonotic disease that can be a potentially serious human infection. The enzyme-linked immunosorbent assay (ELISA) using T. canis excretory-secretory (TES) antigens harvested from T. canis larvae is currently the serological test for confirming toxocariasis. An alternative to producing large amounts of Toxocara TES and improved diagnosis for toxocariasis is through the development of highly specific recombinant antigens such as the T. canis second stage larva excretory-secretory 30 kDa protein (recTES-30). The aim of this study was to evaluate the sensitivity and specificity of a rapid diagnostic kit (RDT, named as iToxocara kit) in comparison to recTES-30 ELISA in Serendah Orang Asli village in Selangor, Malaysia. A total of 133 subjects were included in the study. The overall prevalence rates by ELISA and RDT were 29.3% and 33.1%, respectively, with more positive cases detected in males than females. However, no association was found between toxocariasis and gender or age. The percentage sensitivity, specificity, positive predictive value and negative predictive value of RDT were 85.7%, 90.1%, 80% and 93.2%, respectively. The prevalence for toxocariasis in this population using both ELISA and RDT was 27.1% (36/133) and the K-concordance test suggested good agreement of the two tests with a Cohen's kappa of 0.722, P<0.01. In addition, the followed-up Spearman rank correlation showed a moderately high correlation at R=0.704 and P<0.01. In conclusion, the RDT kit was faster and easier to use than an ELISA and is useful for the laboratory diagnosis of hospitalized cases of toxocariasis.
Thirty-one patients with endoscopically proven chronic gastric ulcer completed a randomised double-blind trial comparing the effects of cimetidine and placebo on ulcer healing. Seventeen patients received cimetidine 400 mg bid and 14 patients received placebo. Repeat endoscopy at six weeks showed that the ulcer had healed in 12 patients (71%) receiving cimetidine and in four patients (29%) receiving placebo (p=O.032). Non-smokers healed their ulcers better than smokers (83% vs 35%, p=O.023). The use of cimetidine was not associated with any adverse effects.
Peptic ulcer occurs with different frequencies in the three main racial groups in Singapore. This study aimed firstly to determine the prevalence of Helicobacter pylori in peptic ulcer and non-ulcer dyspepsia patients of the different races and secondly, to assess the relation between H pylori, histological gastritis, patient diagnosis, and race. Gastric antral biopsy specimens from 1502 patients undergoing gastroduodenoscopy were studied and 892 (59%) were positive for H pylori. H pylori was strongly associated with gastritis: 873 of 1197 (73%) patients with gastritis were positive compared with 19 of 305 (6%) without gastritis (p less than 0.0001). The prevalences of H pylori and gastritis were similar in peptic ulcer patients of different races. Malay patients with non-ulcer dyspepsia, however, were less likely to be positive for H pylori (10 of 46 (22%] or to have antral gastritis (17 of 46 (37%] than Chinese (292 of 605 (48%) were positive for H pylori and 421 of 605 (70%) had gastritis) and Indians (35 of 61 (57%) were H pylori positive and 42 of 61 (69%) had gastritis). Patients with duodenal ulcer were more likely to be positive for H pylori than those with non-ulcer dyspepsia, even when subjects with gastritis were considered separately. While our results do not help to explain the observed racial differences in peptic ulcer frequency it may be that the pathophysiology of non-ulcer dyspepsia is different in the different races in Singapore.
p53 is the most frequently mutated tumor-suppressor gene in human cancers. Unlike other tumor-suppressor genes, p53 mutations mainly occur as missense mutations within the DNA-binding domain, leading to the expression of full-length mutant p53 protein. Mutant p53 proteins not only lose their tumor-suppressor function, but may also gain new oncogenic functions and promote tumorigenesis. Here, we showed that silencing of endogenous p53-R273H contact mutant, but not p53-R175H conformational mutant, reduced AKT phosphorylation, induced BCL2-modifying factor (BMF) expression, sensitized BIM dissociation from BCL-XL and induced mitochondria-dependent apoptosis in cancer cells. Importantly, cancer cells harboring endogenous p53-R273H mutant were also found to be inherently resistant to anoikis and lack BMF induction following culture in suspension. Underlying these activities is the ability of p53-R273H mutant to suppress BMF expression that is dependent on constitutively active PI3K/AKT signaling. Collectively, these findings suggest that p53-R273H can specifically drive AKT signaling and suppress BMF expression, resulting in enhanced cell survivability and anoikis resistance. These findings open the possibility that blocking of PI3K/AKT will have therapeutic benefit in mutant p53-R273H expressing cancers.