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Incidence of acute atherosis in complete molar pregnancy

Hayati AR, Azizah A, Wahidah A

Malays J Pathol, 1998 Dec;20(2):113-4.
PMID: 10879273

A clinicohistological study of acute atherosis in molar pregnancy was undertaken. Maternal decidual vessels in currettage samples of 38 histologically confirmed complete hydatidiform moles were examined histologically for acute atherosis, recognised as fibrinoid necrosis of the smooth muscle wall with a perivascular mononuclear cell infiltrate, with or without lipophages. Acute atherosis was detected in eight of 38 cases, an incidence of 18.4%. All the patients were normotensive. The significance of acute atherosis in molar pregnancy remains to be clarified.
An immunohistochemical study of CD1a and CD83-positive infiltrating dendritic cell density in cervical neoplasia

Hayati AR, Zulkarnaen M

Int J Gynecol Pathol, 2007 Jan;26(1):83-8.
PMID: 17197902

Cervical carcinoma is the second leading cancer in women in Malaysia, after breast cancer. Human papillomavirus (HPV) has been implicated in the development of dysplasia or cervical intraepithelial neoplasia and progression to squamous cell carcinoma. Because of the confinement of the human papillomavirus infection within the epithelial layer, the presence of dentritic cells or Langerhans cells in epithelial layer of the ectocervix is paramount in producing immune response. The mature dentritic cells express CD83 and high CD40/80/86, whereas the immature cells express CD1a and low CD40/80/86. By identifying CD1a and CD83, theoretically, both immature and mature dentritic cell populations can be studied. In view of the facts, we investigated the infiltrating cell density of mature and immature dentritic cells in cervical neoplasia.
Clinicopathologic and immunohistochemical differences in complete and partial hydatidiform moles in a multiracial Malaysian population

Hayati AR, Tan GC

Int J Gynecol Pathol, 2005 Jul;24(3):277-85.
PMID: 15968205
Fulltext Management and short-term outcome of persistent hyperinsulinaemic hypoglycaemia of infancy (nesidioblastosis)

Rahmah R, Hayati AR, Kuhnle U

Singapore Med J, 1999 Mar;40(3):151-6.
PMID: 10402893

Persistent hyperinsulinaemic hypoglycaemia is a rare metabolic disorder of glucose regulation. It is however the most common cause of persistent hypoglycaemia in the neonatal period. Various drugs have been used with generally poor results, but diazoxide and a long-acting somatostatin analogue, octreotide, have been found to be rather successful. When medical therapy fails, early pancreatectomy is recommended to maintain euglycaemia. Since pancreatectomy seems to carry the long-term risk of diabetes mellitus, some authors recommend long-term medical therapy as an alternative to surgery. The outcome of treatment seems to correlate with neurological status prior to surgery. Even in early recognised and treated patients, publications suggest that a subtle neurological deficit may be present despite apparently normal intelligence. In view of the varying recommendations on treatment and the variations in outcome, we reviewed our experience over a period of three years (1992-1995) to determine whether we could formulate a rational approach to the management.
Fulltext An immunohistochemical study of Toll-like receptors 2 and 4 in placenta with and without infection

Hayati AR, Mohamed AE, Tan GC

Malays J Pathol, 2010 Jun;32(1):13-9.
PMID: 20614721 MyJurnal

The placenta constitutes a physical and immunological barrier against infectious agents. Toll-like receptors (TLRs) are essential components for the induction of innate immunity responses in different human tissues including the placenta. We investigated the expressions of TLR2 and TLR4 in the decidua and amniotic cells in non-inflamed placenta and placenta with infection.
The usefulness of limited placental sampling in stillbirths

Hayati AR, Khong TY, Zainul R

Malays J Pathol, 1998 Dec;20(2):99-102.
PMID: 10879270

144 placentas were sampled from all cases of stillbirth weighing 500 g and above seen over a period of thirteen months in the UKM Unit of the Maternity Hospital, Kuala Lumpur. Sampling was limited to 1-3 blocks per placenta for histological study. Placental abnormalities were found in 121 (85%) placentas, 78 of which had definite lesions known to contribute to foetal death while the remainder showed lesions suggestive of an underlying disease. This study supports the usefulness of limited sampling of the placenta in the face of unavailability of complete placental examination and autopsy for assessment of the cause of stillbirth.
Fulltext Diffuse neonatal haemangiomatosis: a rare cause of haemorrhagic shock and refractory coagulopathy in the newborn

Rohana J, Boo NY, Hayati AR, Baizura J

Med J Malaysia, 2002 Sep;57(3):364-7.
PMID: 12440278

A term newborn infant developed hypovolaemic shock shortly after birth. She was pale with gross hepatomegaly. She required multiple boluses of intravenous fluids, blood products as well as inotropic support. Blood investigations showed persistent thrombocytopenia, anaemia and disseminated intravascular coagulopathy (DIC). She also developed heart failure. She finally succumbed on the eleventh day of life. Autopsy revealed haemangiomatosis involving the liver, lungs, gastrointestinal tract, kidneys and adrenals.
Fulltext Large bowel cancer in a young adult presenting as an acute intussusception--a case report

Jasmi AY, Zain AR, Hayati AR

Med J Malaysia, 1992 Dec;47(4):316-9.
PMID: 1338918

A 14 year old Malay boy with an adenocarcinoma of the transverse colon is reported. A lesion was discovered early when he presented with an uncommon complication in the form of a bowel intussusception. Emergency segmental colonic resection was performed, followed later by an extended left hemicolectomy following histological confirmation of the disease. Benign adenomatous polyp is believed to be the predisposing condition. Both ralities, colorectal cancer in young adults and adult intussusception, are discussed.
Fine needle aspiration cytology of the breast: an analysis of 1,094 aspirates

Sharifah NA, Hayati AR, Meah F, al-Rashid Z

Malays J Pathol, 1993 Jun;15(1):53-8.
PMID: 8277791

Our experience with 1,094 consecutive fine needle aspirations (FNAs) of the breast in 918 cases is presented. Correlation between the FNA cytology and subsequent histology of the lesions was available in 211 cases. FNA had a sensitivity rate of 87.3%, a specificity rate of 99.3% and a positive predictive value of 98.2%. A false negative diagnosis rate of 5.1% occurred. The overall diagnostic accuracy rate was 95.7%.
Low perinatal autopsy rate in Malaysia: time for a change

Tan GC, Hayati AR, Khong TY

Pediatr Dev Pathol, 2010 Sep-Oct;13(5):362-8.
PMID: 20367214 DOI: 10.2350/09-03-0623-OA.1

Our objectives were to determine the perinatal autopsy rate in a tertiary hospital in Malaysia and to quantify the value of the perinatal autopsy. All stillbirths, miscarriages, therapeutic abortions, and neonatal deaths between January 1, 2004, and August 31, 2009, were identified from the archives. The autopsy findings were compared with the clinical diagnoses. The autopsy reports were also reviewed to determine if it would be possible to improve the quality of the autopsies. There were 807 perinatal deaths, of which 36 (4.5%) included an autopsy. There were ethnic differences in the rate of autopsy, with the lowest rate among the Malays. The autopsy provided the diagnosis, changed the clinical diagnosis, or revealed additional findings in 58.3% of cases. Ancillary testing, such as microbiology, chromosomal analysis, and biochemistry, could improve the quality of the autopsy. This study provides further data on the perinatal autopsy rate from an emerging and developing country. It reaffirms the value of the perinatal autopsy. Attempts must be made to improve on the low autopsy rate while recognizing that the performance of autopsies can be enhanced through the use of ancillary testing.
Fulltext Tracheal agenesis: a rare cause of unsuccessful tracheal intubation during resuscitation

Iszuari M, Mazita A, Tan GC, Hayati AR, Shareena I, Cheah FC

Med J Malaysia, 2010 Dec;65(4):317-8.
PMID: 21901957

Tracheal agenesis is a rare congenital airway anomaly that usually results in a fatal outcome. The diagnosis is usually made through post-mortem examination. In the current literature, there has been no reported long-term survival although a few reports claimed prolongation of life of several hours to days. This condition is commonly associated with premature birth, polyhydramnios and a male predominance. In 90% of the cases, it is associated with multiple cardiovascular, gastrointestinal and genitourinary tract anomalies which are incompatible with life. We report a case of a premature newborn with severe respiratory distress, absent cry and cyanosis soon after birth. Attempts at endotracheal intubation failed as it was no possible to negotiate the tube beyond the vocal cords. Needle cricothyrotomy and attempted tracheostomy also failed to secure the airway. The diagnosis was confirmed at post-mortem examination.
Fulltext Metastatic penile cancer presenting as hypercalcemia and pathological fracture of the humerus: a rare event

Ho CC, Nazri J, Zulkifli MZ, Sritharan S, Hayati AR

Med J Malaysia, 2006 Oct;61(4):503-5.
PMID: 17243535 MyJurnal

Distant haematogenous metastasis in penile cancer is rare. A patient who had total penectomy and bilateral inguinal lymphadenectomy for penile cancer but later presented with hypercalcemia of malignancy and pathological fracture of the humerus is reported.
Chronic histiocytic intervillositis in consecutive miscarriages: A potential pitfall in routine examination of conceptus

Mohd Fuad SK, Adznan N, Hayati AR, Virasamy V, Rahim NS

Malays J Pathol, 2020 Dec;42(3):439-444.
PMID: 33361726

INTRODUCTION: Chronic histiocytic intervillositis (CHI) is a rare placental lesion strongly associated with recurrent miscarriages and fetal losses. It requires histopathological diagnosis and can only be made after delivery of the products of conception (POC). We describe a case of CHI in a 41-yearold lady with a 16-year history of thirteen recurrent consecutive first trimester miscarriages.
CASE REPORT: The patient is a 41-year-old lady who suffered first trimester miscarriages in all her thirteen pregnancies. The relevant clinical investigations revealed neither significant nor helpful findings in determining the cause of recurrent miscarriages. Histological findings in each except one of the submitted conceptual tissue showed similar features of histiocytic aggregates primarily within the intervillous spaces, a characteristic description of CHI. One of the samples showed degenerative changes.
DISCUSSION: Practicing pathologists are not familiar with the histological features of CHI and this may be a potential pitfall in routine examination of POCs. Recognising this entity allows for accurate diagnosis and hence better management. The aetiology remains unclear, although an immunopathological basis are being explored.
Insulin-like growth factor-1 receptor expression in the placentae of diabetic and normal pregnancies

Hayati AR, Cheah FC, Tan AE, Tan GC

Early Hum Dev, 2007 Jan;83(1):41-6.
PMID: 16750336 DOI: 10.1016/j.earlhumdev.2006.04.002

BACKGROUND: Septal hypertrophic cardiomyopathy (sHCM) is a characteristic anomaly of the infant of diabetic mother (IDM). Insulin-like growth factor-1 (IGF-1) has been identified as a mediator of tissue overgrowth and we have previously shown that maternal IGF-1 levels were significantly elevated among neonates with asymmetrical sHCM. IGF-1 does not cross the placenta; it exerts physiologic action through binding to the IGF-1 receptor (IGF-1R). Localisation and expression of IGF-1R in term diabetic pregnancies are largely unclear. We have studied IGF-1R in the placentae of diabetic and normal pregnancies and this receptor expression in association with neonates with sHCM.
METHODS: IGF-1R localization and expression in the placentae of six diabetic pregnancies associated with neonatal sHCM were compared with six each of randomly selected diabetic and normal pregnancies without neonatal sHCM by immunohistochemistry. The staining for IGF-1R in the deciduas, cytotrophoblasts, syncytiotrophoblasts and villous endothelium for these 18 samples were assessed and scored by two pathologists who were blinded to the respective diagnoses.
RESULTS: Placental IGF-1R staining was negative in the villous endothelium for all three groups. IGF-1R staining was present in deciduas, cytotrophoblasts and syncytiotrophoblasts but the staining was weaker in the entire group of infants with sHCM compared to those without sHCM.
CONCLUSIONS: IGF-1R is localized in all cell types of the placenta except in villous endothelium. Weaker placental IGF-1R staining in the placentae of diabetic pregnancies associated with sHCM suggests reduced expression of IGF-1R. This may be a down-regulatory response to elevated maternal IGF with neonatal sHCM outcome.
Fulltext Pro-angiogenic potential of human chorion-derived stem cells: in vitro and in vivo evaluation

Fariha MM, Chua KH, Tan GC, Lim YH, Hayati AR

J Cell Mol Med, 2013 May;17(5):681-92.
PMID: 23551495 DOI: 10.1111/jcmm.12051

Human chorion-derived stem cells (hCDSC) were previously shown to demonstrate multipotent properties with promising angiogenic characteristics in monolayer-cell culture system. In our study, we investigated the angiogenic capability of hCDSC in 3-dimensional (3D) in vitro and in vivo angiogenic models for the purpose of future application in the treatment of ischaemic diseases. Human CDSC were evaluated for angiogenic and endogenic genes expressions by quantitative PCR. Growth factors secretions were quantified using ELISA. In vitro and in vivo vascular formations were evaluated by histological analysis and confocal microscopic imaging. PECAM-1(+) and vWF(+) vascular-like structures were observed in both in vitro and in vivo angiogenesis models. High secretions of VEGF and bFGF by hCDSC with increased expressions of angiogenic and endogenic genes suggested the possible angiogenic promoting mechanisms by hCDSC. The cooperation of hCDSC with HUVECS to generate vessel-like structures in our systems is an indication that there will be positive interactions of hCDSC with existing endothelial cells when injected into ischaemic tissues. Hence, hCDSC is suggested as the novel approach in the future treatment of ischaemic diseases.
Effects of epidermal growth factor on the proliferation and cell cycle regulation of cultured human amnion epithelial cells

Fatimah SS, Tan GC, Chua KH, Tan AE, Hayati AR

J Biosci Bioeng, 2012 Aug;114(2):220-7.
PMID: 22578596 DOI: 10.1016/j.jbiosc.2012.03.021

Human amnion epithelial cells (HAECs) hold great promise in tissue engineering for regenerative medicine. Large numbers of HAECs are required for this purpose. Hence, exogenous growth factor is added to the culture medium to improve epithelial cells proliferation. The aim of the present study was to determine the effects of epidermal growth factor (EGF) on the proliferation and cell cycle regulation of cultured HAECs. HAECs at P1 were cultured for 7 days in medium containing an equal volume mix of HAM's F12: Dulbecco's Modified Eagles Medium (1:1) supplemented with different concentrations of EGF (0, 5, 10, 20, 30 and 50 ng/ml EGF) in reduced serum. Morphology, growth kinetics and cell cycle analysis using flow cytometry were assessed. Quantitative gene expression for cell cycle control genes, pluripotent transcription factors, epithelial genes and neuronal genes were also determined. EGF enhanced HAECs proliferation with optimal concentration at 10 ng/ml EGF. EGF significantly increased the proportion of HAECs at S- and G2/M-phase of the cell cycle compared to the control. At the end of culture, HAECs remained as diploid cells under cell cycle analysis. EGF significantly decreased the mRNA expression of p21, pRb, p53 and GADD45 in cultured HAECs. EGF also significantly decreased the pluripotent genes expression: Oct-3/4, Sox2 and Nanog; epithelial genes expression: CK14, p63, CK1 and Involucrin; and neuronal gene expression: NSE, NF-M and MAP 2. The results suggested that EGF is a strong mitogen that promotes the proliferation of HAECs through cell cycle regulation. EGF did not promote HAECs differentiation or pluripotent genes expression.
Value of human amniotic epithelial cells in tissue engineering for cornea

Fatimah SS, Ng SL, Chua KH, Hayati AR, Tan AE, Tan GC

Hum. Cell, 2010 Nov;23(4):141-51.
PMID: 21166885 DOI: 10.1111/j.1749-0774.2010.00096.x

Human amniotic epithelial cells (hAECs) are potentially one of the key players in tissue engineering due to their easy availability. The aim of the present study was to develop an optimal isolation and transportation technique, as well as to determine the immunophenotype and epithelial gene expression of hAECs. Amnion was mechanically peeled off from the chorion and digested with trypsin-ethylenediaminetetraacetic acid. The isolated hAECs were cultured in medium containing 10 ng/mL epidermal growth factor until P4. The epithelial gene expression, cell surface antigen and protein expression of hAECs were analyzed by quantitative polymerase chain reaction, flow cytometry and immunocytochemistry. hAECs were also cultured in adipogenic, osteogenic and neurogenic induction media. The best cell yield of hAECs was seen in the digestion of 15 pieces of amnion (2 × 2 cm) and isolated 30 min after digestion with trypsin. F12:Dulbecco's modified eagle medium was the best medium for short term storage at 4 °C. hAECs expressed CD9, CD44, CD73 and CD90, and negligibly expressed CD31, CD34, CD45 and CD117. After serial passage, CK3, CK19 and involucrin gene expressions were upregulated, while p63, CK1 and CK14 gene expressions were downregulated. Sustained gene expressions of integrin β1 and CK18 were observed. At initial culture, these cells might have stem-like properties. However, they differentiated after serial passage. Nonetheless, hAECs have epithelial stem cell characteristics and have the potential to differentiate into corneal epithelial cells. Further investigations are still needed to elucidate the mechanism of differentiation involved and to optimize the culture condition for long term in vitro culture.
Human chorion-derived stem cells: changes in stem cell properties during serial passage

Fariha MM, Chua KH, Tan GC, Tan AE, Hayati AR

Cytotherapy, 2011 May;13(5):582-93.
PMID: 21231803 DOI: 10.3109/14653249.2010.549121

BACKGROUND AIMS: Fetal membrane from human placenta tissue has been described as a potential source of stem cells. Despite abundant literature on amnion stem cells, there are limited studies on the stem cell properties of chorion-derived stem cells.
METHODS: The main aim was to determine the stemness properties of serial-passaged human chorion-derived stem cells (hCDSC). Quantitative polymerase chain reaction (PCR) was performed to reveal the following stemness gene expression in serial-passaged hCDSC: Oct-4, Sox-2, FGF-4, Rex-1, TERT, Nanog (3), Nestin, FZD-9, ABCG-2 and BST-1. Cell growth rate was evaluated from passage (P) 1 until P5. The colony-forming unit-fibroblast (CFU-F) frequency of P3 and P5 cells and multilineage differentiation potential of P5 cells were determined. The immunophenotype of hCDSC was compared using the surface markers CD9, CD31, CD34, CD44, CD45, CD73, CD90, CD117, HLA-ABC and HLA-DR, -DP and -DQ. Immunostaining for trophoblast markers was done on P0, P1, P3 and P5 cells to detect the contamination of trophoblasts in culture, while chromosomal abnormality was screened by cytogenetic analysis of P5 cells.
RESULTS: The surface markers for mesenchymal lineage in hCDSC were more highly expressed at P5 compared with P3 and P0, indicating the increased purity of these stem cells after serial passage. Indeed, all the stemness genes except TERT were expressed at P1, P3 and P5 hCDSC. Furthermore, human chorion contained high clonogenic precursors with a 1:30 CFU-F frequency. Successful adipogenic, chondrogenic and osteogenic differentiation demonstrated the multilineage potential of hCDSC. The karyotyping analysis showed hCDSC maintained chromosomal stability after serial passage.
CONCLUSIONS: hCDSC retain multipotent potential even at later passages, hence are a promising source for cell therapy in the future.
Fulltext MTHFR C677T polymorphism as a risk factor of neural tube defects in Malay: a case control study

Hayati AR, Zainal AI, Tan GC, Ong LC, Khoo TB

Med J Malaysia, 2008 Dec;63(5):379-83.
PMID: 19803295 MyJurnal

Major congenital malformations occur in about 3% of newborn. Several studies have suggested that homozygosity for the C677T methylenetetrahydrofolate reductase (MTHFR) variant is a potential risk factor for neural tube defects (NTDs). It has been hypothesized that the maternal folic acid supplementation prevents NTDs by partially correcting reduced MTHFR activity associated with the variant form of the enzyme. This association has not been found in some ethnic groups. In this study, we attempted to assess the association between NTDs and MTHFR C677T in Malaysian Malay population. Results show that MTHFR 677TT genotype was absent in both patient and control groups.
Effects of keratinocyte growth factor on skin epithelial differentiation of human amnion epithelial cells

Fatimah SS, Tan GC, Chua K, Tan AE, Nur Azurah AG, Hayati AR

Burns, 2013 Aug;39(5):905-15.
PMID: 23273814 DOI: 10.1016/j.burns.2012.10.019

The aim of the present study was to determine the effects of KGF on the differentiation of cultured human amnion epithelial cells (HAECs) towards skin keratinocyte. HAECs at passage 1 were cultured in medium HAM's F12: Dulbecco's Modified Eagles Medium (1:1) supplemented with different concentrations of KGF (0, 5, 10, 20, 30 and 50 ng/ml KGF). Dose-response of KGF on HAECs was determined by morphological assessment; growth kinetic evaluation; immunocytochemical analysis; stemness and epithelial gene expression quantification with two step real time RT-PCR. KGF promotes the proliferation of HAECs with maximal effect observed at 10 ng/ml KGF. However, KGF decreased the stemness genes expression: Oct-3/4, Sox-2, Nanog3, Rex-1, FGF-4, FZD-9 and BST-1. KGF also down-regulates epithelial genes expression: CK3, CK18, CK19, Integrin-β1, p63 and involucrin in cultured HAECs. No significant difference on the gene expression was detected for each Nestin, ABCG-2, CK1 and CK14 in KGF-treated HAECs. Immunocytochemical analysis for both control and KGF-treated HAECs demonstrated positive staining against CK14 and CK18 but negative staining against involucrin. The results suggested that KGF stimulates an early differentiation of HAECs towards epidermal cells. Differentiation of KGF-treated HAECs to corneal lineage is unfavourable. Therefore, further studies are needed to elucidate the roles of KGF in the differentiation of HAECs towards skin keratinocytes.

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