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  1. Serum IgE levels in Malaysian infants and children with gastrointestinal disease
    Yadav, M., Iyngkaran, N.
    Malaysian Journal of Child Health, 1991;3(1):7-10.
    MyJurnal
    The total serum IgE levels in infants and children was quantitated by the radioimmunoassay technique. The serum levels increased from about 300 IUlml in the 2-3 month old infants to about 8000 1U/m1 in the 10-year-old children who were probably infected with intestinal helminths. The total serum IgE levels in infants with cow's milk protein-sensitive entero-pathy were similar in level to those in normal infants. Infants and children with acute gastroenteritis, giardia infection and malnutrition had elevated levels of serum IgE levels. The high serum I gE levels noted in Malaysian children are probably indicative of the pattern in the tropics. (Copied from article).
  2. Active human Herpesvirus-6 infections and associated diseases
    Yadav, M.
    Malaysian Journal of Child Health, 1991;3(1):11-22.
    MyJurnal
    Human Herpesvirus-6 (HHV-6) infections are ubiquitous in human populations with an antibody prevalence of 30-85 percent in normal adults. The virus in vivo infects T-lympho-cytes, at various stages of differentiation and is cytopathic to host cell during productive infection. In culture the virus is pleiotropic for several established cell lines including T and B lymphocytes, macrophages and neural cells. Primary viral infection occurs mostly in early childhood. The saliva is the primary source of infection. The infection remains clinically silent in majority but it establishes a lifelong latent presence. However, in about 30 percent of infants, probably a varient HHV-6, causes exanthem subitum (roseola infantum). If the primary infection of HHV-6 is delayed until adolescence it is accompanied by clinical manifestation of an Epstein-Barr virus like infectious mononucleosis in some individuals. Depressed host immune functions may reactivate the latent HHV-6 infection and further aggravation of the primary disease. Since the virus is cytopathic to the host cell the presence of HHV-6 in AIDS patients and other lympholiferative disorders may increase the severity and pathogenicity of the primary disease. Antibodies to the HHV-6 are enhanced in autoimmune disorders, chronic fatigue syndrome, progressive lymphoroliferative disorders and organ transplant patients on immunosuppressive drugs therapy. While considerable basic immunovirological information has been obtained in the last 4 years, large gaps in knowledge still exist on the biologic interaction of HHV-6 with the host.
  3. Childhood rhinitis is predominantly associated with mite allergens
    Yadav, M., Harnam, S.
    Malaysian Journal of Child Health, 1998;10(1):19-27.
    MyJurnal
    The total and allergen-specific IgE response of patients with rhinitis, rhinoconjunctivities, rhinitis with asthma and rhinitis with dermatitis was analyzed to a panel of twelve high risk airborne and food allergens. It has been found that this panel will detect 96 percent of the allergen-causing diseases in children. It was found that 26 (76%) of the 34 young patients had a family history for atopy suggesting a high frequency of inheritance of allergic disorders. Elevated total IgE was found in most patients with allergic disease. Positive IgE antibody response to two species of Dermatophagoides mite-allergens was found in 7/12 (58%) patients with rhinitis, 11/11 (100%) patients with rhinoconjunctivitis, 7/9 (78%) cases ofrhinitis with asthma and 3/3 (100%) cases of rhinitis with dermatitis. Some of the patients also responded to food allergens. Food allergy was noted in 4/12 (33%) cases of rhinitis, 11/11 (100%) cases of rhinoconjunctivitis, 4/9 (44%) cases of rhinitis with asthma and 1/3 (33%) cases of rhinitis with dermatitis. Patients with rhinoconjunctivitis who tested positive at high titres for mites invariably had enhanced response for cockroaches, shrimps and crabs suggesting invertebrate antigen cross-reactivity. A few patients however, did not show this type of cross-reactivity although they had high titres of anti-mite IgE antibodies indicating that they responded to non cross-reacting allergen epitopes. Response to multiple allergens appears to be a common feature of most patients with respiratory or skin allergic diseases. The prevalence of multiple target-organ allergy to wide variety offood and environmental allergens complicates the long term management ofpatients with such allergic disorders.
  4. Development of immunity to Epstein-Barr virus in Malaysian children
    Yadav MS, Malliga N, Ablashi DV
    Microbiologica, 1987 Jan;10(1):29-35.
    PMID: 3033449
    The pattern of seroconversion to Epstein-Barr virus (EBV) was determined in 98 Malaysian children aged 2 weeks to 12 years. Maternal IgG antibodies to EBV viral capsid antigen, ranging between 1:10 to 1:160 titer, were found in 70.6 percent of infants less than three months old, and dropped to 26 percent by seven to nine months. Primary infection, as denoted by emergence of EBV-IgM antibody, occurred at 4 to 6 months, and by eight years all children were seropositive. Maternal antibody titers to EBV nuclear antigen were detected in 52.9 percent of infants less than 3 months old, declined to undetectable levels by 4 to 12 months, and then increased to 40 percent by the age of 12 years. The IgA antibody to viral capsid antigen was absent in all but one infant aged one year; the child also had IgG anti-early antigen, The IgG antibody to EBV early antigen were present in 17.7 percent of the infants aged 3 months or less. This seroconversion to EBV in early life explains the absence of infectious mononucleosis in the Malaysian population. The data suggest that a subunit vaccine to protect against EBV-associated diseases, most notably nasopharyngeal carcinoma, commonly observed in Malaysians would have to be administered to infants 6-12 months of age.
  5. Detection of human herpesvirus 7 in salivary glands
    Yadav M, Nambiar S, Khoo SP, Yaacob HB
    Arch Oral Biol, 1997 Aug;42(8):559-67.
    PMID: 9347118
    The prevalence and cellular distribution of human herpesvirus 7 (HHV-7) in archival labial salivary glands was analysed for virus-specific DNA sequences by polymerase chain reaction (PCR) and in situ hybridization signals. In addition, the cellular expression of HHV-7-encoded protein was detected by immunohistochemical staining with a virus-specific monoclonal antibody. Eleven of 20 samples were positive for the HHV-7 DNA sequence by PCR. Eighteen of 20 tissues analysed by in situ hybridization showed signals in ductal, serous and mucous cells. Some nuclei of these cells and also the myoepithelial population were positive. In immunolocalization studies, all 20 salivary glands consistently showed HHV-7-expressed protein in the cytoplasm of ductal cuboidal and columnar cells. The protein was also found in the cytoplasm of mucous and serous acinar cells that were immunopositive for HHV-7. The observations are consistent with the suggestion that the labial salivary gland is a site for virus replication, potential persistence and a source of infective HHV-7 in saliva.
  6. Dual detection of human herpesvirus-6 and human papillomavirus type 16 and 18 in cervical carcinoma
    Yadav M, Padmanathan A, Arivananthan M
    J Obstet Gynaecol, 1997 Jan;17(1):86-7.
    PMID: 15511780
    Introduction It is widely accepted that certain 'high risk' human papillomavirus (HPV) genotypes, particularly HPV 16 and 18 are aetiological agents in the development of neoplasia of the uterine cervix. The long latent period between initial HPV infection and emergence of carcinoma suggests that HPV alone is insufficient for malignant transformation and additional factors are required for the progression of HPV infected cells to a neoplastic phenotype. Cells with integrated HPV express viral E6 and E7 oncoproteins which are crucial for immortalisation of epithelial cells via their action on host p53 protein. It is therefore of particular interest to elucidate the molecular mechanisms that alter the expression of E6/E7 proteins during HPV-associated tumorigenesis. Recently, human herpesvirus-6 (HHV-6) has been shown to infect a HPV-immortalised cervical epithelial cell line and transactivate HPV 18 promoters, upregulating gene expression of E6 and E7 HPV oncoproteins (Chen et al., 1994; DiPaolo et al., 1994). HHV-6, first isolated from peripheral blood mononuclear cells of patients with AIDS and lymphoproliferative disorders, is the causative agent of exanthem subitum, heterophile-negative infectious mononucleosis and other febrile illnesses. HHV-6 has recently been detected in oral carcinomas (Yadav et al., 1994). HHV-6 also contains DNA sequences which can transform epithelial cells in culture.
  7. Fulltext Polymerase chain reaction detection and restriction enzyme typing of human papillomavirus in cervical carcinoma
    Yadav M, Nurhayati ZA, Padmanathan A, Abdul Aziz Y, Norhanom AW
    Med J Malaysia, 1995 Mar;50(1):64-71.
    PMID: 7752979
    Specific human papillomavirus (HPV) types have been implicated in the development of cervical carcinoma worldwide. Novel molecular techniques have facilitated the detection and typing of HPV in cervical lesions. DNA preparations from a series of 23 histopathologically confirmed cervical carcinoma patients were analyzed by polymerase chain reaction (PCR) using degenerate primers for the presence of HPV DNA sequences. A total of 22 of 23 cases studied (95.7%) were found positive for HPV DNA sequences. Further studies by DNA hybridization with viral specific probe and restriction enzyme analysis demonstrated the presence of HPV 16 in 73.9% (17/23) and HPV 18 in 65.2% (15/23) of the cases examined. Interestingly, the uncommon HPV 31 and 33 were also found but with a lower percentage (16.9%). It was noted that HPV 16 frequency in the carcinoma increased with age but HPV 18 was evenly present at all ages investigated. We found that HPV was frequently associated with the majority of the cervical carcinomas, and in all but one case, oncogenic high risk HPV genotypes were present. We conclude that HPV infection of the genital tract has an important role in the development of the disease in Malaysia.
  8. Human herpesvirus-6 (HHV-6) DNA and virus-encoded antigen in oral lesions
    Yadav M, Arivananthan M, Chandrashekran A, Tan BS, Hashim BY
    J Oral Pathol Med, 1997 Oct;26(9):393-401.
    PMID: 9385576
    Archival oral tissues comprising 51 squamous cell carcinomas, 18 non-malignant lesions and 7 normal mucosa samples were investigated for human herpesvirus-6 (HHV-6)-encoded antigens and HHV-6 DNA. The virus-specific antigens were detected by an immunohistochemical method using monoclonal antibodies. Two further techniques used for HHV-6 DNA detection included the polymerase chain reaction (PCR) with virus-specific primers and in situ hybridization using digoxigenin-labelled oligonucleotides specific for HHV-6A and HHV-6B genotypes. A high proportion (79-80%) of the squamous cell carcinomas were positive for HHV-6 with the various detection methods. In cases of lichen planus and leukoplakia a high prevalence rate (67-100%) was noted with in situ hybridization and immunohistochemical techniques but a lower proportion (22-33%) was detected with the PCR method. All 7 normal tissues tested were negative for HHV-6. The HHV-6 variant B was found in 60% of the oral carcinoma tissues analysed. The study demonstrates the frequent presence of HHV-6 in neoplastic and non-malignant lesions of the oral cavity. While the role of HHV-6 in oral mucosal tissues remains to be determined, the in vitro tumorigenic potential of the virus suggests a possible role in the etiopathogenesis of oral lesions.
  9. HHV-6 antigen and viral DNA detected in cervical cells from archived tissue using histochemical staining and hybridization
    Yadav M, Arivananthan M, Kumar S
    Clin Diagn Virol, 1996 Oct;7(1):23-33.
    PMID: 9077427
    BACKGROUND: Human herpesvirus type 6 (HHV-6), an ubiquitous virus, is the causative agent for exanthem subitum. The virus is frequently associated with lymphoproliferative disorders and other diseases. Recently, we have reported the frequent presence of HHV-6 in oral carcinoma and the present study extends the observation to cervical carcinoma.

    OBJECTIVE: To examine the presence of HHV-6 in cervical carcinoma.

    STUDY DESIGN: Formalin-fixed, paraffin-embedded cervical carcinoma tissues were examined for the presence of HHV-6 by immunohistochemistry using two monoclonal antibodies that react to HHV-6-encoded p41/38 and gp116/64/54. In situ hybridization with variant-specific probes were used to type the HHV-6 DNA sequences present.

    RESULTS: A total of 14/26 (53.9%) carcinoma tissue specimens and 5/8 (62.5%) normal tissue specimens were positive for viral antigens. In situ hybridization studies revealed the presence of HHV-6 DNA sequences in 10/26 (38.5%) carcinoma tissue specimens and 1/8 (12.5%) normal tissue specimens. In the normal tissue, the HHV-6 was present in the endocervical ciliated columnar-epithelial cells and some cells in the subepithelial mucosa but in the carcinoma, the transformed cells were positive for the virus.

    CONCLUSIONS: HHV-6 viral proteins and DNA were found in more than one third of the cervical tissue examined suggesting possible viral expression in these tumours. The significance of the distribution and role of the HHV-6 in cervical tissue remains unclear. Since HHV-6 has an oncogenic potential, the virus may cooperate with other transforming agents for the progression of the disease.

  10. Frequent detection of human herpesvirus 6 in oral carcinoma
    Yadav M, Chandrashekran A, Vasudevan DM, Ablashi DV
    J Natl Cancer Inst, 1994 Dec 07;86(23):1792-4.
    PMID: 7966419
  11. Antibody reactivity with two strains of human herpesvirus-6 in Malaysians
    Yadav M, Umamaheswari S, Ablashi D
    J Med Virol, 1991 Apr;33(4):236-9.
    PMID: 1649908
    A total of 234 sera from healthy Malaysians of diverse ethnic origins were tested for antibody to the Z29 and prototype GS strains of HHV-6. The prevalence in the races ranged from 58 to 80% for the GS strain and 49 to 76% for the Z29 strain. The highest prevalence was in Malays with semi-urban cultural lifestyles and lowest was in the indigenous rural tribes (Ibans, Kadazans, Bidayuhs, and Orang Asli). The antibody titres to GS and Z29 virus capsid antigens differed in 11 (4.7%) samples by more than 2 dilutions. In 9 of the 11 sera the titres to GS strain were higher than to the Z29 strain. The differences in the antibody titres between strains of HHV-6 may reflect subtle changes in antigen structure of the virus recognised by some individuals.
  12. Nasopharyngeal carcinoma in Malaysians under the age of 20 years
    Yadav M, Tan MK, Singh P, Dharmalingam SK
    Clin Oncol, 1984 Dec;10(4):353-61.
    PMID: 6509817
    A total of 52 cases of NPC were found in a five-year survey from 1978 to 1982 in Malaysia. The annual rate of occurrence was 3.4, 3.0, 2.4 and 1.8 for Chinese, Malays, Kadazans and Sarawakians, respectively. The age-specific incidence rates per 100 000 were highest for Kadazans (2.34 to 7.59) in comparison to the other races (0.11 to 1.24). The proportion of NPC in young Malaysians formed 1.2% in Chinese, 7.2% in Malays and 6.9% for others. A sexual bias was present in Chinese (male:female = 2.2) and Sarawakians (1.7) but not in Kadazans and Malays (0.9). In most Chinese, the primary tumour histologically is of the poorly differentiated characteristic and this type is the predominant tumour in the country. The Kadazans presented with well differentiated primary tumour and the Malays with all three histological types i.e. well-, poorly- and undifferentiated. At first examination enlarged lymph nodes were found in 95.7% of the patients and 65.2% had epistaxis and growth in the postnasal space. Antibodies to IgA anti-VCA were present in half of the 6 patients serologically studied.
  13. Fulltext Transudation of immunoglobulins into duodenal juice of infants with cow's milk protein sensitive enteropathy
    Yadav M, Iyngkaran N
    Med J Malaysia, 1982 Sep;37(3):239-44.
    PMID: 7177005
    Eighteen infants clinically suspected to be intolerant of cow's milk were placed on a milk-free formula and six to eight weeks later were orally challenged with cow's milk. Following challenge three groups were recognised. Group A: Four infants tolerated oral feeds ofcow's milk and lacked mucosal abnormality or clinical symptoms. Group B: Seven infants had mucosal deterioration but lacked clinical symptoms and tolerated cow's milk. Group C: Seven infants had mucosal abnormality, developed clinical symptoms and were intolerant of cow's milk. The intestinal transudation of IgA was increased in Group A and unchanged in Group Band C : the IgM levels in the duodenal juice was increased in Group A and B but unchanged in Group C : the IgG levels in the juice were increased in all Groups following challenge. It appears that increased transmission of IgA and IgM or IgM alone in the duodenal juice is associated with lack of development of clinical symptoms. Symptoms are present in infants in whom the IgA and IgM levels in duodenal juice remained unchanged after challenge. It is suggested that patients responding to cow's millt challenge with intestinal production of IgA and IgM (or IgM alone) are able to counter balance the deleterious mechanisms leading to clinical cow's milk intolerance whereas those who, for some unknown reason, do not mount a secretory immune response become ill.
  14. Changes in complement C3 levels following treatment of patients with Brugia malayi infection
    Yadav M
    Southeast Asian J. Trop. Med. Public Health, 1989 Jun;20(2):183-7.
    PMID: 2609207
    Serum IgG levels and complement C3 levels were assayed on Day 0, 1, 3-4, 7 and 56-70 post-treatment with diethylcarbamizine citrate (DEC) in a series to 26 patients with Brugia malayi infection and 6 volunteers without infection. On treatment, the microfilariae were cleared from the blood within 24 hours. The eosinophils decreased dramatically on Day 1 post-treatment but increased rapidly by Day 4 to 7 and then dropped to normal levels in 45 days. The serum IgG mean levels decreased briefly following treatment with DEC but then returned to original levels. However, the complement C3 levels gradually increased over the 2 months period of study reaching statistical significance levels (p less than 0.01) in patients with initial high blood microfilariae. The observation suggests that Brugia malayi infection probably induces a high rate of synthesis of complement C3 and this process continued in the post-treatment phase. Since, DEC treatment did not cause a decrease in complement C3 with the elimination of blood microfilariae, it would appear that the complement C3 is consumed following antibody attachment to the microfilariae as they enter the blood circulation.
  15. Precocious puberty after surgery for craniopharyngioma
    Yadav M, Nagappan N, Iyngkaran N
    J Pediatr, 1980 Mar;96(3 Pt 1):515-6.
    PMID: 7359251
  16. Fulltext Dengue haemorrhagic fever and dengue shock syndrome: are they tumour necrosis factor-mediated disorders?
    Yadav M, Kamath KR, Iyngkaran N, Sinniah M
    FEMS Microbiol Immunol, 1991 Dec;4(1):45-9.
    PMID: 1815710 DOI: 10.1111/j.1574-6968.1991.tb04969.x
    A consecutive series of 24 patients with clinical features of primary dengue infection and 22 controls (14 patients with viral fever of unknown origin and 8 healthy subjects) were assayed for serum levels of tumour necrosis factor (TNF). The acute sera of the 24 patients with clinical dengue infection were positive for dengue virus-specific IgM antibody. Clinically, 8 had dengue fever (DF), 14 dengue haemorrhagic fever (DHF) and 2 dengue shock syndrome (DSS). All 16 patients with DHF/DSS had significantly elevated serum TNF levels but the 8 DF patients had TNF levels equivalent to that in the 22 controls. A case is made for augmented TNF production having a role for the pathophysiological changes observed in DHF/DSS and mediator modulation as a possible therapeutic approach to treatment.
  17. Endogenous tumor necrosis factor-alpha in patients with nasopharyngeal carcinoma
    Yadav M
    Southeast Asian J. Trop. Med. Public Health, 1991 Mar;22(1):123-6.
    PMID: 1948253
    Serum tumor necrosis factor alpha (TNF) concentration was assayed in 105 patients with nasopharyngeal carcinoma using a sensitive ELISA technique with detection level of 10 pg/ml. The TNF levels were detectable in 45 of 63 (71.4%) patients newly diagnosed for the malignancy and 29 of 42 (69%) patients in remission following treatment with radiotherapy. In 25 normal controls the TNF were less than 10 pg/ml. While TNF may be present in the majority of the patients with the malignant disease, the TNF concentration appeared to have no clinical significance in diagnosis or prognosis of the patients.
  18. Malaria antibody levels in patients with nasopharyngeal carcinoma
    Yadav M, Prasad U
    Southeast Asian J. Trop. Med. Public Health, 1984 Jun;15(2):234-7.
    PMID: 6095462
    The antibody titres to P. falciparum and Epstein-Barr Virus-associated antigens were assayed in 22 patients with NPC and 43 controls. All, but one patient had antimalarial titres; 14 had titres greater than 80 and 4 patients greater than 640. Compared to controls the mean anti-malarial titre for most age groups were higher in the patients. Those patients with high anti-malarial titres also had high IgA anti-VCA titre, an antibody which has been demonstrated to be diagnostic for NPC. The peak anti-VCA (IgG) and anti-EA (IgG) antibody titres were associated with anti-falciparum titres of 320-640 and 80-160, respectively. The results are discussed in relation to the possible association between malarial infection and etiology of NPC.
  19. Low prevalence of antibody to human herpesvirus-6 (HHV-6) in Kadazans
    Yadav M, Umamaheswari S, Ablashi DV
    Southeast Asian J. Trop. Med. Public Health, 1990 Jun;21(2):259-63.
    PMID: 2173152
    The prevalence of antibody to human herpesvirus type 6 (HHV-6) and Epstein-Barr virus (EBV) viral capsid antigens (VCA) were analysed in sera from Kadazans of Sabah, North Borneo. At a serum dilution of 10, about 34% were positive for HHV-6 antibody but in contrast all 95 individuals studied were positive for EBV VCA antibody. The study shows that HHV-6 and EBV infection occur independently. The low frequency of seropositive individuals in this community suggests that other than socioeconomic factors are responsible for the spread of the virus.
  20. Fulltext Absence of milk-specific IgE in infants with cow's milk protein-sensitive enteropathy
    Yadav M, Iyngkaran N, Seow IKG
    Med J Malaysia, 1983 Dec;38(4):266-71.
    PMID: 6599980
    Infants, one to 56-weeks-old, presenting with persistent diarrhoea were placed on a diet free of cow's milk protein which improved their clinical condition. Six weeks later, 67 infants were challenged with a low-lactose cow's milk formula and jejunal biopsy was taken before and 24-hours after challenge. On the basis of histological changes in the intestinal mucosa and development of clinical symptoms the infants were categorised into three groups: Group 1 (n = 16) with no clinical or mucosal abnormality, Group 2 (n = 20) with mucosal abnormality but lacking clinical symptoms, and Group 3 (n 31) with manifestation of mucosal abnormality and clinical symptoms. In addition to the total IgE the radioallergosorbent test (RAST) was performed on sera from the infants taken before and after milk provocation. The mean total serum IgE level ranged from 288 to 560 IU/ml. In Groups 2 and 3 the prechallenge serum IgE levels were significantly higher than the postchallenge levels but in Group 1 the levels remained unchanged on challenge. A positive RAST to milk proteins was observed in five infants (7.4%), that is, one in Group 2 and four in Group 3, of 67 infants studied. In a survey of 405 consecutive paediatric-age patients admitted for a variety of symptoms, 90 were positive for RAST specific for milk proteins. Interestingly the majority of the patients positive for RAST presented with gastrointestinal ailments. The measurement of specific IgE appears not to be a useful adjunct in the diagnosis of CMPSE in Malaysian children.
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