The clinical response and the histological changes in the mucosa of the small bowel in response to continued feeding with cows' milk protein were assessed over a period of 2-6 weeks in 24 infants who had shown histological changes without immediate clinical symptoms after challenge with a diet containing cows' milk protein. Twenty of the 24 infants (83%) thrived well on cows' milk protein. Jejunal biopsy specimens taken six to eight weeks after the initial biopsy showed histological improvement in all 20 infants compared with biopsy specimens taken soon after the challenge, which had shown mucosal damage. The mucosa had returned to normal in 12, was mildly abnormal in seven, and moderately abnormal in one. Corresponding improvements in the activities of mucosal enzymes were seen. In four of the 24 infants (17%) symptoms developed between three and six weeks. Histological examination of the jejunal biopsy specimens showed that mucosal damage had progressed in two, and remained the same in two; moreover, the disaccharidase activities remained depressed. The present study shows that most infants with enteropathy caused by sensitivity to cows' milk protein but without clinical symptoms develop tolerance to the protein and the mucosa returns to normal despite continued feeding with cows' milk protein.
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.
Serum samples from healthy adults in four geographic/ethnic groups (Ghanaian Blacks, Malaysian Chinese, Malaysian Indians and United States Caucasians) were tested under code for antibodies to human herpesvirus-6 (HHV-6). The prevalence and titer of HHV-6 antibody in the healthy Ghanaians were significantly higher than in the Malaysian Chinese; United States Caucasians and Malaysian Indians had intermediate prevalence and titer of antibodies. Thus far, no specific differences in HHV-6-associated diseases have been noted between geographic/ethnic groups with these marked variations in antibody patterns.
A series of 31 infants, 28 with cow's milk protein sensitive enteropathy (CMPSE) and 3 controls, was studied for severity and extent of mucosal damage of the upper small bowel in relation to the development of clinical symptoms. Following challenge with the offending cow's milk, 18 infants (Group 1) developed severe mucosal changes at both the proximal and distal small bowel mucosa and all of these infants presented with clinical symptoms. The other 10 infants (Group 2) who did not develop clinical symptoms following the challenge had less severe damage to the distal small bowel mucosa as compared to the proximal region. The histological score of both the proximal and distal postchallenge biopsies were significantly lower in Group 2 as compared to Group 1 infants. The mucosal disaccharidase and alkaline phosphatase levels were depleted in both the proximal and distal biopsies following challenge but the depletion was greater in the proximal than the distal biopsies. It is suggested that the extent and severity of mucosal damage to the proximal duodenum and jejunum have a critical bearing on the development of clinical symptoms.
Serum immunoglobulin G, A, M, D and E levels were determined in the forest-dwelling Orang Asli of age group 8 to 64 years. The levels are higher than observed for urban Malaysians and comparable to levels reported for populations residing in the tropics. There was no significant difference in serum levels of all the immunoglobulins studied in both sexes. The elevated serum immunoglobulins levels are discussed in terms of the nature of the immune defence developed in the Orang Asli to contend with the many parasites prevalent in their environment.
The present study was undertaken to evaluate the prevalence of HPV in formalin-fixed, paraffin-embedded cervical carcinoma tissues using PCR followed by non-radioactive Southern hybridization with type-specific oligonucleotides for HPV 16 and 18. In addition, the tissue sections were immunohistochemically screened with two monoclonal antibodies, for expression of HPV 16 L1 and HPV 18 E6 proteins. A total of 57 of 60 cervical carcinomas (95.0%) were found with HPV using both techniques. HPV 16 and HPV 18 were present in equal proportions. Results of both DNA hybridization and immunohistochemistry were in agreement for the majority of the cases. HPV 16 and 18 DNA and virus-encoded antigens, L1 and E6 were found highly prevalent in these cervical carcinomas. Due to the high prevalence of HPV with cervical carcinoma in Malaysia, the implementation of routine diagnosis for the virus in cervical biopsies would be clinically useful.
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.
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.
Inhibition of tumour promotion by various vitamin E compounds (tocopherols and tocotrienols) and some of their dimers was examined by an in vitro assay utilizing the activation of Epstein-Barr virus (EBV) early antigen (EA) expression in EBV-genome-carrying human lymphoblastoid cells. The results reveal that gamma- and delta-tocotrienols derived from palm oil exhibit a strong activity against tumour promotion by inhibiting EBV EA expression in Raji cells induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). However, alpha- and gamma-tocopherols and dimers of gamma-tocotrienol or gamma-tocopherol lack this activity.
The relationship between immunoglobulin allotypes and risk of developing nasopharyngeal carcinoma was examined in a comparative study of 50 Chinese cases and 140 Chinese controls and 50 Malay cases and 79 Malay controls residing in Malaysia. Although the most common Gm phenotype was elevated in both Chinese and Malay nasopharyngeal carcinoma patients compared to their controls, there were no significant differences between cases and controls in the distribution of Gm haplotypes in either population. There were no differences between cases and controls in the distribution of Km alleles in either population. Thus a previously reported association of Km(1) with increased nasopharyngeal carcinoma risk in Tunisia is not confirmed in two Mongoloid populations in Malaysia.
Some infants intolerant to cow's milk protein (CMP) are often also intolerant to other food proteins including soy protein (SP). The effect of CMP and SP in infants recovering from diarrhoeal disease was studied in 22 infants who were maintained on an hypo-allergenic formula for 4-6 weeks. The infants were then challenged successively, initially with SP, followed 24 h later with CMP and then rechallenged with SP 24 h after CMP provocation. Three groups were recognized on the basis of clinical symptoms and mucosal changes following SP challenge. Group 1 comprised four infants who developed clinical and histological reactions on SP challenge. The subsequent CMP challenge, 24 h after the initial SP challenge, resulted in clinical symptoms in three of the four infants, and they developed increased mucosal injury. Rechallenge with SP in the three infants caused development of severe clinical symptoms. Group 2 comprised 12 infants who developed histological reaction but had no clinical symptoms to initial SP challenge. The subsequent CMP challenge caused further progression in mucosal pathology in 11 of the 12 infants and six also had associated clinical symptoms. Rechallenge with SP in the latter six infants resulted in development of clinical symptoms in three and tolerance to SP in three infants. Group 3 comprised six infants who tolerated SP and CMP but one of these infants developed mild histological changes to CMP. The progression of mucosal injury following SP and CMP challenge was associated with a significant decrease in mucosal disaccharidases, alkaline phosphatase levels and presence of reducing sugar in the stools. The 1 h blood xylose level continued to decrease significantly following the pre-SP, post-SP, and post-CMP challenge. It appears that the small bowel mucosa of young infants recovering from diarrhoeal disease remains sensitive not only to CMP but also to SP. The feeding of these proteins in rapid successive sequence to infants with mucosal damage might result in further progression of the mucosal injury. Thus, the exclusion for a variable period of time of antigenic food proteins like CMP and SP from the diet of young infants recovering from diarrhoea might reduce the risk of inducing mucosal sensitivity to these proteins in susceptible infants.
Overexpression of c-myc protein and amplification of c-myc were investigated by immunohistochemistry and differential polymerase chain reaction (dPCR) in 440 formalin-fixed primary breast carcinoma tissues, respectively. Overexpression of c-myc was detected in 45% (199/440) and amplification of c-myc was observed in 25% (112/440) of the primary breast carcinomas. Immunolocalization of c-myc oncoprotein was demonstrated in 35% (8/23) of the comedo subtype, 17% (3/18) of the non-comedo subtype, 37% (15/41) of the comedo DCIS and 49% (20/41) of the adjacent invasive ductal carcinomas, 21% (4/19) of the non-comedo DCIS and 37% (7/19) of the adjacent invasive lesions, 49% (133/270) of the invasive ductal carcinomas, 33% (11/33) of the invasive lobular carcinomas, 29% (6/21) of the colloid carcinomas and 47% (7/15) of the medullary carcinomas. C-myc was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 24% (10/41) of the adjacent invasive ductal carcinomas, 30% (82/270) of the invasive ductal carcinomas, 21% (7/33) of the invasive lobular carcinomas, 14% (3/21) of the colloid carcinomas and 24% (4/15) of the medullary carcinomas. Amplification of c-myc was noted in 16% (3/9) of the invasive ductal carcinomas but not in the adjacent non-comedo DCIS lesions. A significant association (P<0.05) was observed between in situ components and adjacent invasive lesions for c-myc expression and amplification. Overexpression of c-myc protein was significantly correlated with poorly differentiated (P<0.05) and high proliferation index (Ki-67) (P<0.05) tumors but not with lymph node metastases (P>0.05), patient age (P>0.05) and estrogen receptor status (P>0.05). Significant relationship was also noted between amplification of c-myc and absence of estrogen receptor (P<0.05), high histological grade (P<0.05) and high proliferation index (Ki-67) (P<0.05). No relationship was seen with nodal status (P>0.05) and patient age (P>0.05). Majority of the Malaysian female patients are from younger age group (<50 years old) but overexpression and amplification of c-myc was not statistically associated with patient age (P>0.05) indicating that these alterations may be independent events of patient age. The above observations suggest that overexpression and amplification of c-myc could play an important role in tumor progression from non-invasive to invasive and, also, it may have the potential as a marker of poor prognosis of breast cancer.
Amplification of int-2/FGF-3 gene was investigated by differential polymerase chain reaction (dPCR) in 440 archival primary breast carcinoma tissues. Of these, 23 were comedo ductal carcinoma in situ (DCIS), 18 were non-comedo DCIS, 41 were comedo DCIS with adjacent invasive ductal carcinomas, 19 were non-comedo DCIS with adjacent invasive ductal carcinomas, 270 were invasive ductal carcinomas, 33 were invasive lobular carcinomas, 21 were colloid carcinomas and 15 were medullary carcinomas. Int-2 was amplified in 22% (96/440) of the primary breast carcinomas. It was shown that int-2 was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 29% (12/41) of the adjacent invasive ductal carcinomas, 26% (71/270) of the invasive ductal carcinomas, 18% (6/33) of the invasive lobular carcinomas, 10% (2/21) of the colloid carcinomas and 13% (2/15) of the medullary carcinomas. In contrast, int-2 was not amplified in non-comedo DCIS and invasive ductal carcinomas with adjacent non-comedo DCIS lesions. A significant association was observed between int-2 amplification in the in situ components and adjacent invasive lesion (P<0.05). All tumors with int-2 amplification in the in situ lesions (7/7) also demonstrated same degree of amplification in the adjacent invasive components. However, 9% (5/53) of the tumors with no amplified int-2 gene in the in situ components showed int-2 amplification in the adjacent invasive lesions. A significant relationship was noted between amplification of int-2 and lymph node metastases (P<0.05) and poorly differentiated tumors (P<0.05) but not with estrogen receptor status (P>0.05) and proliferation index (Ki-67 and PCNA) (P>0.05). In Malaysia, majority of the patients belong to younger age group (<50 years old) but a comparison of the age groups showed that the amplification of int-2 was not statistically associated with patient age (P>0.05). These observations indicate that amplification of int-2 tends to strengthen the view that int-2 may have the potential to be an indicator of poor prognosis regardless of the age of the patient. Moreover, the presence of int-2 amplification in preinvasive, preinvasive and adjacent invasive lesions, and invasive carcinomas suggest that int-2 could be a marker of genetic instability occurring in early and late stages of tumor development.
Expression of the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNA 1 to 6) and membrane-associated protein (LMP) was investigated by immunoblotting in 83 nasopharyngeal carcinoma (NPC) biopsies and 25 other tumor and normal tissue specimens from the head and neck region. Fifty-eight of the 83 NPC biopsies were large enough to yield parallel data on virus DNA and viral expression. All 16 cases of clinically diagnosed and histologically confirmed NPCs from North Africa contained EBV DNA and expressed EBNA-1. Of 31 clinically diagnosed NPCs from China, 29 contained EBV DNA and 25 of these expressed EBNA-1. One control tissue biopsy from the oropharynx of NPC patients contained EBV DNA, but none expressed EBNA-1. The latent membrane protein (LMP) was detected in 22/31 of the Chinese and in 10/16 of the North African NPC biopsies. None of the NPC biopsies or control tissues expressed detectable amounts of EBNA 2 or any of the other 4 nuclear antigens which are invariably expressed in EBV-transformed B cells. A smaller number of tumors from Malaysia and East Africa exhibited a similar pattern of expression. EBV was rescued from a nude-mouse-passaged North African NPC tumor by co-cultivation of the tumor cells with umbilical cord blood lymphocytes. The tumor expressed EBNA 1 and LMP, but not EBNA 2 or the other 4 EBNAs. The resulting LCLs expressed all 6 nuclear antigens, EBNA 1 to 6 and LMP. Our data suggest that expression of the EBV genome is regulated in a tissue-specific fashion.
The effect of soy protein on the small bowel mucosa of 18 infants with acute gastroenteritis was studied. The infants were maintained on a protein hydrolysate formula for 6-8 weeks, following which they were readmitted for soy protein challenge studies. Jejunal biopsy was performed before and 24 h after challenge. On the basis of the clinical and histological reaction to soy protein challenge, three groups were identified. Group 1 consisted of three infants who had clinical and histological reaction. There was associated depletion of mucosal enzymes, lactase, sucrase, malatase, alkaline phosphatase, and blood xylose levels. Group 2 consisted of seven infants who had histological reaction but no clinical symptoms. Two of these seven infants, however, developed clinical reaction when rechallenged with soy protein 2 and 90 days later. Following challenge, mucosal enzymes and blood xylose levels were depressed in five of the seven infants tested. Group 3 consisted of eight infants who did not have either a clinical or a histological reaction. The mucosal enzymes and blood xylose levels were not depressed in four infants tested. The present study shows that the small bowel mucosa of some young infants recovering from acute gastroenteritis remains sensitive to soy protein for a variable period of time. The feeding of soy protein to these infants may result in the persistence of mucosal damage and perpetuation of diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS)
Artificial intelligence (AI) and machine learning (ML) are currently used in several areas. The applications of AI and ML based models are also reported for monitoring and design of biological wastewater treatment systems (WWTS). The available information is reviewed and presented in terms of bibliometric analysis, model's description, specific applications, and major findings for investigated WWTS. Among the applied models, artificial neural network (ANN), fuzzy logic (FL) algorithms, random forest (RF), and long short-term memory (LSTM) were predominantly used in the biological wastewater treatment. These models are tested by predictive control of effluent parameters such as biological oxygen demand (BOD), chemical oxygen demand (COD), nutrient parameters, solids, and metallic substances. Following model performance indicators were mainly used for the accuracy analysis in most of the studies: root mean squared error (RMSE), mean square error (MSE), and determination coefficient (DC). Besides, outcomes of various models are also summarized in this study.
Seroprevalence of HHV-8 has been studied in Malaysia, India, Sri Lanka, Thailand, Trinidad, Jamaica and the USA, in both healthy individuals and those infected with HIV. Seroprevalence was found to be low in these countries in both the healthy and the HIV-infected populations. This correlates with the fact that hardly any AIDS-related Kaposi's sarcoma has been reported in these countries. In contrast, the African countries of Ghana, Uganda and Zambia showed high seroprevalences in both healthy and HIV-infected populations. This suggests that human herpes virus-8 (HHV-8) may be either a recently introduced virus or one that has extremely low infectivity. Nasopharyngeal and oral carcinoma patients from Malaysia, Hong Kong and Sri Lanka who have very high EBV titres show that only 3/82 (3.7%) have antibody to HHV-8, demonstrating that there is little, if any, cross-reactivity between antibodies to these two gamma viruses.