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Microscopic colitis: a histopathological study of nine cases

Jayalakshmi P, Malik AK, Wong NW

Malays J Pathol, 1994 Dec;16(2):145-50.
PMID: 9053563

A retrospective histological analysis of colonic biopsies received by the Department of Pathology, University of Malaya during the 4-year-period between 1990 and 1993 revealed nine cases of microscopic colitis (MC). The ages of the patients ranged from 18 to 53 years. Seven patients were females with a female to male ratio of 3.5 :1. The main clinical symptom was chronic diarrhoea of duration varying from 4 months to 5 years. None of the patients had any systemic illness or were on any prior medication. Colonoscopy and barium enema observations in all the subjects were essentially normal. Colonic biopsies showed diffuse plasmacytic infiltration of the lamina propria, intraepithelial lymphocytic infiltration and normal crypt pattern. To the best of our knowledge, this is the first documented report on MC from Malaysia. It is envisaged that better recognition of this condition by histopathologists would reduce the numbers in the often diagnosed category of "nonspecific colitis".
Chromoblastomycosis in Malaysia

Jayalakshmi P, Looi LM, Soo-Hoo TS

Mycopathologia, 1990 Jan;109(1):27-31.
PMID: 2325747

Nine cases of histologically diagnosed chromoblastomycosis are reported from Malaysia. All the patients were males and ranged in age from 56 to 65 years. The duration of symptoms varied from 5 months to 13 years. All the lesions were noted in the lower limbs. Malignancy was suspected clinically in 5 cases. The diagnosis was established by finding characteristic brown muriform cells in the tissue sections.
Fulltext Impaired hypothalamic-pituitary-gonadal axis function in men with diabetes mellitus

Maneesh M, Jayalakshmi H, Singh TA, Chakrabarti A

Indian J Clin Biochem, 2006 Mar;21(1):165-8.
PMID: 23105591 DOI: 10.1007/BF02913088

In view of association of diabetes mellitus and male infertility, present study was designed to investigate the functional status of hypothalamic pituitary gonadal (HPG) axis in diabetic men. Thirty-five diabetic men (BMI 22.24±0.21) in the age group 20-40 (30.6±4.7) years were selected. Twenty-five healthy men (BMI 23.85±0.25), in the same age group (29.5±4.8) served as control. Blood samples were collected for hormonal and biochemical estimations. Diabetic men had significantly low serum testosterone with low LH and FSH, hypercholesterolemia, hypertriglyceridemia, hypoalbuminemia and increased oxidative stress. Low serum testosterone in diabetic men was accompanied by low LH and FSH; the inability of the pituitary gland to respond appropriately to a decline in testosterone implying central effect of high serum glucose on the interaction between the nervous and endocrine system. Nutritional deficiency, increased oxidative stress and increased aromatase activity due to excessive body fat might have also contributed to low serum testosterone.
Fulltext Intra-articular haemangioma of the knee in the skeletally immature

Wong KA, Singh VA, Pailoor J

Singapore Med J, 2013 Nov;54(11):e228-9.
PMID: 24276110

Intra-articular haemangioma is a rare and uncommon condition that sometimes presents in infants. The lesion can be a diagnostic challenge, with misdiagnosis often leading to delayed diagnosis and treatment. It is essential to establish and treat the condition early, as intra-articular haemangioma can lead to destruction of the joint and secondary arthrosis. Herein, we report the case of a five-year-old boy who presented with intra-articular haemangioma and discuss the management of his condition.
Fulltext Granular cell tumour: malignant or benign?

Singh VA, Gunasagaran J, Pailoor J

Singapore Med J, 2015 Sep;56(9):513-7.
PMID: 26451054 DOI: 10.11622/smedj.2015136

Granular cell tumours (GrCTs) are uncommon soft tissue tumours that are usually benign (approximately 0.5%-2.0% have been reported as malignant). They are very rarely found at the extremities. Differentiating a malignant GrCT from a benign one is important as the former is aggressive and has a poor prognosis, whereas the latter, after surgical resection, has excellent outcomes. A malignant lesion can be suspected on clinical presentation and confirmed via histopathological examination using the Fanburg-Smith criteria.
Fulltext Splenic lymphoma with hypersplenism--a case report

Ng SC, Kuperan P, Jayalakshmi P, Chua CT

Singapore Med J, 1990 Feb;31(1):80-2.
PMID: 2185555

A 47-year old man had hypersplenism from massive splenomegaly, the cause of which was undetermined for 2 years. He was initially asymptomatic though there was mild pancytopenia. However, 18 months after presentation he manifested both clinical and haematological deterioration, almost succumbing to sepsis. Splenectomy finally provided a definite diagnosis of follicular lymphoma and also restored his blood counts to within normal range.
Overexpression of S100A4 as a biomarker of metastasis and recurrence in oral squamous cell carcinoma

Natarajan J, Hunter K, Mutalik VS, Radhakrishnan R

J Appl Oral Sci, 2014 12 4;22(5):426-33.
PMID: 25466476

S100A4, a biomarker of epithelial mesenchymal transition (EMT), plays an important role in invasion and metastasis by promoting cancer cell motility. In oral squamous cell carcinoma (OSCC), metastasis results in 90% of cancer associated mortality.
OBJECTIVE: To investigate the role of S100A4 expression as an important component of the epithelial mesenchymal transition (EMT) program in oral squamous cell carcinoma (OSCC).
MATERIAL AND METHODS: S100A4 protein expression was assessed semi-quantitatively by immunohistochemistry in 47 histologically confirmed cases of oral squamous cell carcinoma (OSCC) and 10 normal oral mucosal biopsies. The association between the S100A4 overexpression and the aggressive features of OSCC were analyzed by X2 test.
RESULTS: Moderate to strong cytoplasmic expression of S100A4 was observed in 30 out of 47 specimens of OSCC (64%). Overexpression of S100A4 was significantly associated with the clinical stage, lymph node involvement, metastases, pattern of invasion and recurrence (p<0.05).
CONCLUSION: S100A4 expression represents an important biomarker of prognostic significance that may be used to identify a subset of patients at high risk of invasion and metast.
Pattern of tissue expression of CA-125 and HE4 in primary epithelial ovarian tumours and correlation with serum CA-125 levels

Devan SM, Pailoor J, Sthaneshwar P, Narayanan V

Asian Pac J Cancer Prev, 2013;14(8):4545-8.
PMID: 24083699

The objective of this study is to assess tissue expression of CA-125 and HE4 protein in primary benign and malignant epithelial tumours of the ovary and correlate with serum CA-125 levels. A total of 100 formalin-fixed, paraffin embedded sections of ovarian tumours which included serous adenoma (11), mucinous adenoma (42), serous carcinoma (20), mucinous carcinoma (12) and endometrioid carcinoma (15), histologically diagnosed between 1st January 2004 to 31st December 2012 at the University Malaya Medical Centre, were stained for HE4 (rabbit polyclonal antibody, Abcam, UK) and CA-125 (mouse monoclonal antibody clone: OC125, Cell Marque Corporation, Rocklin, California, USA). Pre-operative serum CA-125 levels were obtained from the laboratory information system. Immunoscore (I score) for HE4 and CA-125 was given based on the intensity of staining and percentage of positive tumour cells and considered significant when it was >50 (intensity of staining multiplied by percentage of positive tumour cells). Serum CA-125 levels were compared with the I score of HE4 and CA-125 in tissues. We noted that the CA-125 levels in serum and tissues were significantly raised in malignant compared to benign ovarian tumours (p value<0.05). Tissue expression of HE4 protein was also significantly raised in malignant tumours compared to benign tumours (p value<0.05). We conclude that HE4 can be a useful tissue immunomarker in addition to CA-125.
Fulltext Low prevalence of 'classical' microscopic colitis but evidence of microscopic inflammation in Asian irritable bowel syndrome patients with diarrhoea

Hilmi I, Hartono JL, Pailoor J, Mahadeva S, Goh KL

BMC Gastroenterol, 2013;13:80.
PMID: 23651739 DOI: 10.1186/1471-230X-13-80

There is increasing evidence for the role of microscopic inflammation in patients with IBS. We aimed to examine the prevalence of microscopic colitis and inflammation in Malaysian IBS patients with diarrhoea (IBS-D).
Fulltext P53 expression in invasive pancreatic adenocarcinoma and precursor lesions

Norfadzilah MY, Pailoor J, Retneswari M, Chinna K, Noor LM

Malays J Pathol, 2011 Dec;33(2):89-94.
PMID: 22299208 MyJurnal

Patients with pancreatic adenocarcinoma are known to have a high mortality rate. The 5-year survival rate still remains low even now compared to that of the 1960's despite new advances in management including surgery, chemotherapy, pathological classification and molecular diagnostic technologies. Precursors to invasive pancreatic adenocarcinoma have been identified in the last ten years that include mucinous cystic neoplasm, intraductal papillary mucinous neoplasm and pancreatic intraepithelial neoplasia. p53 protein accumulation in the nuclei is a common molecular event in most human neoplasms. Our objective is to investigate p53 expression in pancreatic adenocarcinoma and precursor lesions and their significance. The selected study material encompassed 31 invasive ductal adenocarcinoma, 15 mucinous cystic neoplasm and papillary mucinous neoplasm, and 27 cases of pancreatic intraepithelial neoplasia including grade 1, 2 and 3. Immunoscore was given for each case based on intensity of staining and percentage of cells positive and compared between precursor lesions and invasive adenocarcinoma. A score of 50 and above was considered significant. The results showed that p53 expression increased progressively and significantly with the grade of pancreatic intraepithelial neoplasia and adenocarcinoma (p-value < 0.001). These findings support the concept of multistep carcinogenesis in pancreatic adenocarcinoma and suggest that p53 inactivation occurs in the progression of precursors to pancreatic adenocarcinoma.
Fulltext Which is the best method of sterilization of tumour bone for reimplantation? A biomechanical and histopathological study

Singh VA, Nagalingam J, Saad M, Pailoor J

Biomed Eng Online, 2010;9:48.
PMID: 20831801 DOI: 10.1186/1475-925X-9-48

Sterilization and re-usage of tumour bone for reconstruction after tumour resection is now gaining popularity in the East. This recycle tumour bone needs to be sterilized in order to eradicate the tumour cells before re-implantation for limb salvage procedures. The effect of some of these treatments on the integrity and sterility of the bone after treatment has been published but there has yet been a direct comparison between the various methods of sterilization to determine the one method that gives the best tumour kill without compromising the bone's structural integrity.
Follicular dendritic cell sarcoma of inguinal lymph node--a case report

Pailoor J, Iyengar KR, Chan KS, Sumithra S

Malays J Pathol, 2008 Dec;30(2):115-9.
PMID: 19291921

Follicular dendritic cell sarcomas (FDCS) are rare neoplasms that involve lymph nodes or extranodal sites. They show varied histological features and thus can be mistaken for carcinoma or sarcoma. Correct identification is important for further management. A 43-year-old Indian female presented with a three-month history of progressive swelling at the right inguinal region. It was excised completely and was reported as lymph node with metastatic poorly differentiated carcinoma based on Haematoxylin and eosin (H&E) stain findings. Computerized tomography (CT) scans of thorax, abdomen and pelvis were normal and did not reveal a primary site. Following this, the case was referred to one of the authors. The slides were reviewed and a variety of immunocytochemical markers were done. The tumour cells were negative for epithelial, melanocytic, neural, leucocyte and soft tissue tumour markers. They were immunopositive for CD21, CD35 and negative for CD68. Based on the immunocytochemical findings, a final diagnosis of FDCS was made. This case highlights the histological and immunophenotypical profile of a rare tumour which requires a high index of suspicion for diagnosis.
Disseminated histoplasmosis presenting as penile ulcer

Jayalakshmi P, Goh KL, Soo-Hoo TS, Daud A

Aust N Z J Med, 1990 Apr;20(2):175-6.
PMID: 2344324

A 59-year-old Chinese man presented with a three month history of penile ulcers and abdominal pain. Syphilis and a gastric malignancy were diagnosed clinically. Biopsy of the genital and stomach ulcers revealed histiocytic granulomata containing numerous intracellular fungal bodies. Histoplasma capsulatum was subsequently cultured from the penile ulcer. Antifungal therapy was instituted. However the patient's general condition deteriorated rapidly and he died within two weeks of admission. A post-mortem liver biopsy showed numerous intracellular fungi.
Fulltext Sub-Acute Toxicity Study of Tiger Milk Mushroom Lignosus tigris Chon S. Tan Cultivar E Sclerotium in Sprague Dawley Rats

Kong BH, Tan NH, Fung SY, Pailoor J

Front Pharmacol, 2016;7:246.
PMID: 27555822 DOI: 10.3389/fphar.2016.00246

Lignosus also known as "Tiger Milk Mushroom," is classified in the family Polyporaceae and mainly consumed for its medicinal properties in Southeast Asia and China. The sclerotium is known as the part with medicinal value and often used by the natives to treat a variety of ailments. Lignosus tigris Chon S. Tan, one of the species of the Malaysia Tiger Milk mushroom, has recently been successfully cultivated in laboratory. Earlier studies have demonstrated the L. tigris cultivar E sclerotia exhibited beneficial biomedicinal properties. This study evaluated the potential toxicity of L. tigris E sclerotia in a 28-day sub-acute oral administration in Sprague Dawley (SD) rats. L. tigris E sclerotial powder was administered orally at three different doses of 250, 500, and 1000 mg/kg to the SD rats once daily, consecutively for 28-days. Body weight of the rats was recorded and general behavior, adverse effects, and mortality were observed daily throughout the experimental period. At the end of the experiment, blood hematology and biochemistry, relative organ weights, and histopathological analysis were performed. Results showed that there were no mortality nor signs of toxicity throughout the 28-day sub-acute toxicity study. Oral administration of the L. tigris E sclerotial powder at daily dose up to 1000 mg/kg had no significant effects in body weight, relative organ weight, blood hematological and biochemistry, gross pathology, and histopathology of the organs. L. tigris E sclerotial powder did not cause any treatment-related adverse effect in the rats at different treatment dosages up to 1000 mg/kg. As the lethal dose for the rats is above 1000 mg/kg, the no-observed-adverse-effect level (NOAEL) dose is more than 1000 mg/kg.
Safety assessment of cultivated fruiting body of Ophiocordyceps sinensis evaluated through subacute toxicity in rats

Fung SY, Lee SS, Tan NH, Pailoor J

J Ethnopharmacol, 2017 Jul 12;206:236-244.
PMID: 28587826 DOI: 10.1016/j.jep.2017.05.037

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiocordyceps sinensis (Berk.) G.H. Sung, J.M. Sung, Hywel-Jones & Spatafora is one of the most renowned traditional Chinese medicine used as tonic, renal, respiratory and reproductive health, promote longevity and overall improvement in quality of life. Natural production of O. sinensis is limited due to its extreme specificity in host range and confined geographic distribution. Therefore, cultivation of the fungus was developed to meet high demand for commercialization as nutraceutical. O. sinensis fruiting body has recently been successfully cultivated in large scale using rice based solid medium, providing wider source options for consumers and scientific researchers.
AIMS OF THE STUDY: The present study aims to establish safety profile for the consumption of cultivated fruiting body of O. sinensis (FBOS) by 28-days sub-acute toxicity study in Sprague Dawley rats.
MATERIALS AND METHODS: Rats were orally administered with cultivated FBOS at three graded doses (250, 500 and 1000mg/kg), once daily for 28 consecutive days. Control group received distilled water. General observations (gross behavioral changes and toxic symptoms) and body weight of each animal were monitored daily. Haematological, serum biochemical and histopathological analysis were carried out at the end of the experiment (Day 29).
RESULTS: No behavioral changes, toxic symptoms or death was observed in rats throughout the dosing period. Cultivated FBOS treatment up to 1000mg/kg did not cause any adverse effect on the growth of the animals. Results from haematology and serum biochemistry revealed no toxic effect following cultivated FBOS treatment at three graded doses for 28 days. In addition, no treatment related histopathological changes were noted in heart, spleen, kidney, lung and liver of the animals.
CONCLUSION: The present study revealed that oral administration of cultivated FBOS for 28 days, at dosage up to 1000mg/kg did not pose toxicological concern in rats. Therefore, the no-observed-adverse-effect level (NOAEL) dose of cultivated FBOS in 28-days subacute toxicity study is higher than 1000mg/kg.
Safety Evaluation of Sclerotium from a Medicinal Mushroom, Lignosus cameronensis (Cultivar): Preclinical Toxicology Studies

Lee SS, Tan NH, Pailoor J, Fung SY

Front Pharmacol, 2017;8:594.
PMID: 28919858 DOI: 10.3389/fphar.2017.00594

Twenty-eight days subacute toxicity studies performed in rats using sclerotial powder of Lignosus cameronensis cultivar was conducted to assess its safety for consumption prior to other scientific investigations on its medicinal benefits, nutraceutical or pharmaceutical application of the mushroom. The study was conducted at 250, 500, and 1000 mg/kg sclerotial powder of L. cameronensis cultivar (n = 5 for each respective dose, on both male and female groups) while control groups received only distilled water. At the end of the study (29th day), the animals were sacrificed followed by blood and organs collection for analysis. Subacute toxicity studies done shows that sclerotial powder of L. cameronensis cultivar at 250, 500, and 1000 mg/kg did not induce treatment related changes on behavioral patterns, gross physical appearance, growth pattern, body weight gain, values of hematological and clinical biochemical panels as well as histopathological findings on kidney, spleen, heart, lung and liver of the experimental rats. The no-observed-adverse-effect level dose for sclerotial powder of L. cameronensis cultivar in 28-days sub-acute toxicity study is determined to be 1000 mg/kg.
The significance of CD14 in clear cell renal cell carcinoma progression and survival prognosis

Yap NY, Ong TA, Pailoor J, Gobe G, Rajandram R

Biomarkers, 2023 Feb;28(1):24-31.
PMID: 36315054 DOI: 10.1080/1354750X.2022.2142292

Purpose: CD14-positive tumour and immune cells have been implicated in cancer progression. This study evaluated the prognostic significance of CD14 immunostaining in clear cell renal cell carcinoma (ccRCC) compared to the adjacent non-cancer kidney, and serum soluble CD14 (sCD14) levels in patients versus controls.Methods: Immunohistochemistry was performed for CD14 on ccRCC and the corresponding adjacent non-cancer kidney tissue from 88 patients. Staining intensity was determined using Aperio ImageScope morphometry. Serum sCD14 was evaluated for 39 ccRCC patients and 38 non-cancer controls using ELISA. CD14 levels were compared with tumour characteristics and survival status.Results: CD14 overall and nuclear immunostaining was higher in ccRCC compared to the adjacent non-cancer kidney tissue. CD14 nuclear immunostaining in the adjacent non-cancer kidney was significantly associated with advanced stage and adverse RCC survival prognosis. Serum sCD14 concentration was elevated in ccRCC patients compared to non-cancer controls and was also significantly associated with tumour stage and worse survival prognosis. Higher CD14 expression, in particular CD14 positive immune cell infiltrates found in the adjacent non-RCC kidney tissue, were associated with tumour progression and poorer prognosis.Conclusion: The levels of CD14 in non-RCC adjacent kidney and serum could be potential prognostic indicators.
Anaplastic lymphoma kinase (ALK) mutations in patients with adenocarcinoma of the lung

Mohamad N, Jayalakshmi P, Rhodes A, Liam CK, Tan JL, Yousoof S, et al.

Br J Biomed Sci, 2017 Oct;74(4):176-180.
PMID: 28705139 DOI: 10.1080/09674845.2017.1331520

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death. Approximately 2-16% of NSCLC patients with wild-type epidermal growth factor receptor (EGFR) harbour anaplastic lymphoma kinase (ALK) mutations. Both EGFR and ALK mutations occur most commonly in Asian patients with NSCLC. As targeted therapy is available for NSCLC patients with these mutations, it is important to establish reliable assays and testing strategies to identify those most likely to benefit from this therapy.
MATERIALS AND METHODS: Patients diagnosed with adenocarcinoma of the lung between 2010 and 2014 were tested for EGFR mutations. Of these, 92 cases were identified as EGFR wild type and suitable candidates for ALK testing utilising immunohistochemistry and the rabbit monoclonal antibody D5F3. The reliability of the IHC was confirmed by validating the results against those achieved by fluorescence in situ hybridisation (FISH) to detect ALK gene rearrangements.
RESULTS: Twelve (13%) cases were positive for ALK expression using immunohistochemistry. Of the 18 evaluable cases tested by FISH, there was 100% agreement with respect to ALK rearrangement/ALK expression between the assays, with 11 cases ALK negative and 7 cases ALK positive by both assays. ALK tumour expression was significantly more common in female compared to male patients (29.6% vs. 6.2%, P
Nephrotoxicity of hump-nosed pit viper (Hypnale hypnale) venom in mice is preventable by the paraspecific Hemato polyvalent antivenom (HPA)

Tan CH, Tan NH, Sim SM, Fung SY, Jayalakshmi P, Gnanathasan CA

Toxicon, 2012 Dec 1;60(7):1259-62.
PMID: 22975088 DOI: 10.1016/j.toxicon.2012.08.012

Mice experimentally envenomed with Hypnale hypnale venom (1× and 1.5×LD₅₀) developed acute kidney injury (AKI) principally characterized by raised blood urea and creatinine. Prolonged blood clotting time and hemorrhage in lungs implied bleeding tendency. Pallor noted in most renal cortices was suggestive of renal ischemia secondary to consumptive coagulopathy. Intravenous infusion of Hemato polyvalent antivenom following experimental envenoming effectively prevented death and AKI in all mice, supporting its potential therapeutic use in envenoming cases.
Fulltext Exacerbation of colon carcinogenesis by Blastocystis sp

Kumarasamy V, Kuppusamy UR, Jayalakshmi P, Samudi C, Ragavan ND, Kumar S

PLoS One, 2017;12(8):e0183097.
PMID: 28859095 DOI: 10.1371/journal.pone.0183097

Colorectal cancer (CRC) is one the most commonly diagnosed cancers worldwide and the number is increasing every year. Despite advances in screening programs, CRC remains as the second leading cause of cancer deaths in the United States. Oxidative stress plays an important role in the molecular mechanisms of colorectal cancer (CRC) and has been shown to be associated with Blastocystis sp., a common intestinal microorganism. In the present study, we aimed to identify a role for Blastocystis sp. in exacerbating carcinogenesis using in vivo rat model. Methylene blue staining was used to identify colonic aberrant crypt foci (ACF) and adenomas formation in infected rats whilst elevation of oxidative stress biomarker levels in the urine and serum samples were evaluated using biochemical assays. Histological changes of the intestinal mucosa were observed and a significant number of ACF was found in Blastocystis sp. infected AOM-rats compared to the AOM-controls. High levels of urinary oxidative indices including advanced oxidative protein products (AOPP) and hydrogen peroxide were observed in Blastocystis sp. infected AOM-rats compared to the uninfected AOM-rats. Our study provides evidence that Blastocystis sp. has a significant role in enhancing AOM-induced carcinogenesis by resulting damage to the intestinal epithelium and promoting oxidative damage in Blastocystis sp. infected rats.

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