Serum levels were determined in urban Chinese, Malays and Indians and in the forest-residing Orang Asli of age group 11 to 50. There was no difference in the IgM levels in the Chinese, Indians and Malays, but the serum IgG was elevated (p less than 0.05) in the Malays and the serum IgA level (p less than 0.01) in the Indians, when compared to the other two races. In contrast to the three other races there was a significant elevation of all three immunoglobulins in the Orang Asli. The mean immunoglobulin levels of the urban Malaysians are comparable to those reported for Caucasians residing in temperate countries. However, in the Orang Asli, the immunoglobulin levels were higher than observed for populations of the temperate regions but are comparable to the levels reported for several other populations of the tropical regions. Females had higher IgM levels than males in the Chinese, Indian and Malays but in the Orang Asli there was no sex difference in the immunoglobulin levels.
Dengue fever (DF) which is caused by four serotypes of dengue virus may in some cases progress into a life threatening situation of dengue haemorrhage fever (DHF) and dengue shock syndrome (DSS). It has been suggested that sequential infection with different dengue virus serotypes predisposes the patient towards DHF/DSS. We report here a primary dengue infection in a 10-year-old boy progressing from DF to DSS while under clinical observation. The report provides unequivocal evidence for the development of DSS in primary dengue infection caused by virus serotype 4. The close relationship between sequential changes in the levels of tumour necrosis factor (TNF), Interleukin 1 and 6 (IL-1 and IL-6) in the serum, to the clinical progression of the disease from DF to DHF/DSS and then to full recovery implicates a pathogenetic role for the inflammatory cytokines. The child also manifested clinical features consistent with Reye's syndrome and this suggests a common pathogenetic origin for DSS and the Reye-like syndrome induced by dengue virus.
Immunoglobulin G, A and M levels were determined in paired maternal and cord sera of premature, full term and postmature newborns of urban dwelling Chinese, Indian, Malay and full term newborn of the forest dwelling Orang Asli (Malaysian aborigines). The mean serum IgC level in the full term Orang Asli newborns (1254±441 mg per 100 mil is comparable to that of the Indians (1211±282 mg per 100 ml) and Malays (1169±286 mg per 100 ml) but these levels are higher than those of the Chinese
newborns (1092±270 mg per 100 ml). Statistical analysis indicates a significant dependence of cord serum IgG level on maternal serum IgG level in the . Chinese, Indians and Malays. In addition, in Indians the cord serum IgG was significantly dependent at 5% level on the gestation age. The fetomaternal serum IgG level ratios at term were equal to or just less than one. The cord serum IgM levels of the Chinese, Indian, Malay and Orang Asli newborns at term were 11.6.±. 6.5, 12.5.±. 7.3, 10.9.±. 5.8 and
16.7±6.9 mg per 100 ml respectively. Statistical analysis showed absence of correlation between cord serum IgM level and birthweight, gestation age or maternal serum IgM level in Chinese and Malays. In Indians the cord sera IgM level showed a dependence on the birthweight. Immunoglobulin A was present in 34.6%, 40.5%, 31.6% and 62.5% of full term Chinese, Indian, Malay and Orang Asli newborns respectively. These observations are discussed in relation to the immunoglobulin levels observed in populations residing in temperate and other tropical regions.
Human herpesvirus-6 exists in two forms, HHV-6A which has not been clearly associated with any disease, and HHV-6B, the causative agent of exanthem subitum. The two variants have been distinguished by techniques such as dot blotting and restriction fragment length polymorphism of PCR products. This study aims to establish the prevalence of HHV-6A and HHV-6B in carcinoma tissues using variant-specific oligonucleotide probes. A total of 73 archived carcinoma biopsies from the oral, salivary gland, larynx, breast and cervix were obtained with seven histologically normal controls. In situ hybridization was carried out with nonradioactively labelled variant-specific probes. Samples that hybridized with both variant A and B probes were subjected further to nested PCR and digested with HindIII to distinguish the variants. A hybridization signal was observed in 76.2% of oral carcinoma tissue and 75.0% of salivary gland carcinoma tissue. In contrast, only 33.3% of cervical carcinoma tissue were positive for HHV-6 DNA. A hybridization signal was noted in all 4 laryngeal carcinoma tissues studied. However, the 10 breast carcinoma tissues studied were negative, as was the histologically normal tissue. The virus possesses tumourigenic potential and demonstrates virus transactivating properties. The frequency of HHV-6 variants in certain tumours suggest a cofactorial role in multistep carcinogenesis. While PCR amplifies selectively the predominant variant in a sample, this was not seen by in situ hybridization. The in situ hybridization technique allowed the localization of both HHV-6A and HHV-6B in the nuclei of transformed regions.
Zingiberaceae rhizomes commonly used in the Malaysian traditional medicine were screened for anti-tumour promoter activity using the short-term assay of inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) in Raji cells. The inhibition of TPA-induced EBV-EA was detected using the indirect immunofluorescence assay (IFA) and Western blot technique. The indirect IFA detected the expression/inhibition of EBV-EA-D (diffused EA antigen), whereas the Western blot technique detected the expression/inhibition of both EBV-EA-D and EA-R (restricted EA antigen). Seven rhizomes were found to possess inhibitory activity towards EBV activation, induced by TPA; they are: Curcuma domestica, C. xanthorrhiza, Kaempferia galanga, Zingiber cassumunar, Z. officinale, Z. officinale (red variety), and Z. zerumbet. A cytotoxicity assay was carried out to determine the toxicity of the Zingiberaceae rhizome extracts. The rhizome extracts that exhibited EBV activation inhibitory activity had no cytotoxicity effect in Raji cells. Therefore, the present study shows that several Zingiberaceae species used in Malaysian traditional medicine contain naturally occurring non-toxic compounds that inhibit the EBV activation, which, if further investigated, could contribute in the development of cancer prevention methods at the tumour-promoting stage.
The effect of cow's milk protein (CMP) challenge on the levels of alkaline phosphatase (ALP) in the upper jejunal mucosa and the serum were studied in 25 infants clinically suspected to have cow's milk allergy. Following CMP provocation 3 groups were identified. Group 1 consisted of 10 infants who had clinical and histological reaction to CMP challenge. All 10 infants had significant depletion in the levels of tissue and serum ALP. Group 2 consisted of 5 infants who had histological reaction but no clinical reaction. Tissue ALP was depressed in 3 but not in 2 following CMP challenge. Serum ALP were essentially unaltered in all 5. Group 3 consisted of 10 infants who clinically and histologically tolerated CMP challenge. Tissue and serum ALP were not depressed in any. Estimation of sucrase levels in the mucosa and xylose absorption before and after CMP challenge were also performed for comparison with changes of tissue and serum ALP levels. The clinical significance of the changes in serum ALP level is discussed.
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.
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.
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.
Eleven infants who were suspected clinically of having cows' milk protein sensitive enteropathy were fed with a protein hydrolysate formula for six to eight weeks, after which they had jejunal and rectal biopsies taken before and 24 hours after challenge with cows' milk protein. When challenged six infants (group 1) developed clinical symptoms and five did not (group 2). In group 1 the lesions developed in both the jejunal mucosa (four infants at 24 hours and one at three days), and the rectal mucosa, and the injury was associated with depletion of alkaline phosphatase activity. Infants in group 2 were normal. It seems that rectal injury that develops as a direct consequence of oral challenge with the protein in reactive infants may be used as one of the measurements to confirm the diagnosis of cows' milk protein sensitive enteropathy. Moreover, ingestion of such food proteins may injure the distal colonic mucosa without affecting the proximal small gut in some infants.
Enterokinase has a critical role in initiating proteolytic digestion by hydrolysing the conversion of pancreatic trypsinogen into trypsin. The enzyme is synthesised by enterocytes of the proximal small intestine and initially incorporated into the brush border from where it is released into the intestinal lumen by the action of pancreatic secretions. The aim of the study was to analyse enterokinase activity in the duodenal mucosa of infants with diarrhoeal disease including cow's milk protein-sensitive enteropathy. Our observations show that the mean depletion of enterokinase was only 17% compared to 60-80% for other brush border enzymes like disaccharidases, peptidases and alkaline phosphatases in infants with diarrhoea. This suggests that enterokinase activity in the small bowel enteropathies may be dependent not only on the degree of mucosal damage specifically but also on the extent of damage to the goblet cell population where the enzyme is synthesised. Thus the enterokinase activity was reduced in acute and chronic diarrhoea with marked mucosal damage where significant reduction of goblet cell population was evident but the enzyme was relatively little affected when the mucosa was damaged mildly.
Expression of c-erbB3 protein was investigated in 104 primary breast carcinomas comprising nine comedo ductal carcinoma in situ (DCIS), 91 invasive ductal carcinomas and four invasive lobular carcinomas using two monoclonal antibodies, RTJ1 and RTJ2. Of the 91 invasive ductal carcinomas, seven contained the comedo DCIS component adjacent to the invasive component. An immunohistochemical technique was used to evaluate the association between expression of c-erbB3 and clinical parameters and tumour markers such as epidermal growth factor receptor (EGFR), c-erbB2, cathepsin-D and p53 in archival formalin-fixed paraffin-embedded tumour tissues. Our results indicated that RTJ1 and RTJ2 gave identical staining patterns and concordant results. It was found that the overexpression of c-erbB3 protein was observed in 67% (6/9) of comedo DCIS, 52% (44/84) of invasive ductal carcinomas, 71% (5/7) of carcinomas containing both the in situ and invasive lesions and 25% (1/4) of invasive lobular carcinomas. A significant relationship (P < 0.05) was observed between strong immunoreactivity of c-erbB3 protein and histological grade, EGFR and cathepsin-D, but not with expression of c-erbB2, p53, oestrogen receptor status, lymph node metastases or age of patient. However, we noted that a high percentage of oestrogen receptor-negative tumours (59%), lymph node-positive tumours (63%) and c-erbB2 (63%) were strongly positive for c-erbB3 protein. We have also documented that a high percentage of EGFR (67%), c-erbB2 (67%), p53 (75%) and cathepsin-D-positive DCIS (60%) were strongly positive for c-erbB3. These observations suggest that overexpression of c-erbB3 protein could play an important role in tumour progression from non-invasive to invasive and, also, that it may have the potential to be used as a marker for poor prognosis of breast cancer.
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.
Expression of p53 protein was investigated by immunohistochemical techniques in archival cases of 134 primary breast carcinomas comprising 13 comedo ductal carcinoma in situ (DCIS), 105 invasive ductal carcinomas, 7 contained the comedo DCIS component adjacent to the invasive ductal component, 5 invasive lobular carcinomas, three colloid carcinomas and one medullary carcinoma. Overexpression of p53 gene product was studied to determine the association with clinico-pathological parameters and also its relationship to c-erbB2. Overexpression of p53 protein was observed in 31% (4/13) of comedo DCIS, 37% (39/105) of invasive ductal carcinomas, 57% (4/7) of carcinomas containing both the in situ and invasive lesions and all medullary carcinomas. A significant relationship (p < 0.05) was observed between strong immunoreactivity of p53 protein and absence of estrogen receptor, histological grade and c-erbB2 but not with lymph node metastases or age of patient. These observations suggest that overexpression of p53 protein may play an important role in tumor progression from noninvasive to invasive in some breast carcinomas and may have potential as an indicator for poorer prognosis.
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.