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Biomedical subjects

J J Ho

Publications and source records attributed to J J Ho.

At least 19 recordsLinked to original sources
PubMed2006

Loss of human leucocyte antigen class I and gain of class II expression are early events in carcinogenesis: clues from a study of Barrett's oesophagus.

BACKGROUND: Human leucocyte antigen (HLA) expression is altered in oesophageal carcinomas compared with normal tissue. It is unclear, however, whether this phenotype precedes malignant transformation or results as a consequence of it. AIM: To investigate HLA class I and II expression in Barrett's oesophagus and normal squamous oesophageal tissue. METHODS: Asian patients with Barrett's oesophagus (n = 64) and a control group (n = 60) with a normal oesophagus but without reflux symptoms were recruited using endoscopic and histopathological criteria. Tissue samples were stained with monoclonal antibodies specific for HLA-ABC, HLA-DR alpha chain or HLA-DP/DQ/DR, and scored semiquantitatively. The results of immunohistochemical staining were correlated with clinical and histopathological characteristics of patients. RESULTS: Marked expression of HLA-ABC was observed in 50% of Barrett's oesophagus sections as compared with 68.3% of controls (p = 0.038). HLA-DR staining was seen in 51.6% of Barrett's oesophagus samples versus 11.7% of controls (p<0.001). Expression of HLA-DP/DQ/DR was evident in 73.4% of oesophageal intestinal metaplasia tissue as opposed to 18.3% of controls (p<0.001). Importantly, a total loss of HLA-ABC and a concomitant gain of HLA-DP/DQ/DR expression were seen in 37.5% of patients with Barrett's oesophagus but in none of the controls (p<0.001). Interestingly, this phenotype was associated positively with dysplasia (adjusted p, p* = 0.031) but negatively with non-steroidal anti-inflammatory drug use (p* = 0.004). CONCLUSIONS: HLA class I expression is down regulated and class II expression is up regulated in Barrett's oesophagus. As these changes predate malignant transformation, altered major histocompatibility complex expression may be a key event in disease progression, possibly in facilitating evasion from immune surveillance.

Adult↗
PubMed2005

Human leucocyte antigen determinants of susceptibility to Barrett's oesophagus in Asians--a preliminary study.

BACKGROUND: Characteristic immune profiles have been demonstrated in gastro-oesophageal reflux disease. However, the genetic basis of gastro-oesophageal reflux disease remains unclear. AIM: To investigate whether certain human leucocyte antigen genes are associated with Barrett's oesophagus. METHODS: Asian patients of Malay, Chinese and Indian descent with Barrett's oesophagus (n = 59) and those without reflux symptoms and a normal oesophagus (n =60) were recruited prospectively using endoscopic and histopathological criteria. Human leucocyte antigen class I and II typing was performed using a polymerase chain reaction sequence-specific primers method. RESULTS: The HLA-B7 allele was present in 17% (10 of 59) of patients with Barrett's oesophagus when compared with 0% (zero of 60) of controls [P = 0.0006, corrected P = 0.0171, OR = 25.67]. Subgroup analysis revealed that the HLA-B7 allele was confined almost exclusively to Indians with Barrett's oesophagus, 43% (nine of 21) vs. 0% (zero of 19) Indian controls (P = 0.0014, corrected P = 0.0406, OR = 29.64). No class II associations, protective human leucocyte antigens or extended haplotypes for disease susceptibility were identified. CONCLUSIONS: Barrett's oesophagus in Asians, particularly Indians, is strongly positively associated with HLA-B7; reinforcing a genetic component to gastro-oesophageal reflux disease. A larger sample size and different ethnic populations should be genotyped to further confirm this association and identify possible additional risk factors in the human leucocyte antigen locus.

Asian People↗
PubMed2004

Folic acid in the prevention of neural tube defect--a programme for Malaysia?

There is good evidence that folic acid is safe and efficacious for reducing neural tube defect (NTD). All women capable of becoming pregnant should take 400 microgram daily. This can be given in the form of a daily vitamin supplement, by food fortification, or by increasing natural dietary folates. Compulsory grain fortification has been shown to reduce NTD in a population but supplementation and dietary advice have not. Malaysia should work towards a programme of grain fortification and use alternative strategies to reach sections of the population that would not be covered but several research questions need to be answered before a programme could be implemented in Malaysia.

Female↗
PubMed2002

Early versus delayed initiation of continuous distending pressure for respiratory distress syndrome in preterm infants.

BACKGROUND: The application of a continuous distending pressure (CDP) has been shown to have some benefits in the treatment of pre-term infants with respiratory distress syndrome (RDS). CDP has the potential to reduce lung damage, particularly if applied early before atelectasis has occurred. Early application of CDP may better conserve an infant's own surfactant stores and consequently be more effective than CDP applied later in the course of RDS. OBJECTIVES: In pre-term infants with RDS to determine if early compared with delayed initiation of CDP results in lower mortality and reduced need for intermittent positive pressure ventilation. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register (Issue 1, 2002), MEDLINE (1966-2001), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, journal hand searching mainly in the English language. SELECTION CRITERIA: Trials among pre-term infants with respiratory distress syndrome spontaneously breathing at trial entry, which used random or quasi-random allocation to either early or delayed CDP. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and its Neonatal Review Group were used, including independent assessment of trial quality and extraction of data by two authors. MAIN RESULTS: In six studies on a total of 165 infants, early CDP was associated with a significant reduction in subsequent use of intermittent positive pressure ventilation, typical RR 0.55, RD -0.16, NNT 6, but there was no evidence of effect on overall mortality. There was no evidence of effect on the rates of pneumothorax (five studies) or bronchopulmonary dysplasia (one study). Early CDP resulted in a reduction in duration of oxygen therapy in the single study reporting this outcome. REVIEWER'S CONCLUSIONS: Early application of CDP has a clinical benefit in the treatment of RDS in that it reduces subsequent use of IPPV and thus may be useful in preventing the adverse effects of this treatment. However, many of the trials were done in the 1970s and 1980s and re-evaluation of the strategy of early CDP in the era of antenatal steroid use and early surfactant administration is indicated.

Humans↗
PubMed2001

Late onset infection in very low birth weight infants in Malaysian Level 3 neonatal nurseries. Malaysian Very Low Birth Weight Study Group.

BACKGROUND: The purpose of this study was to examine the rate and mortality from late onset infection occurring in very low birth weight infants admitted to Malaysian nurseries. METHODS: Data on all infants 1500 g or below admitted to the 20 participating Level 3 nurseries were analyzed for late onset infection (clinical infection and positive blood or cerebrospinal fluid culture occurring after 48 h of life). RESULTS: The overall survival of the 962 study infants was 69%. The rate of late onset infection was 19.3%. The mortality in those with late onset infection was 30.8%. The most common infecting organism was Klebsiella pneumoniae, accounting for 38.3% of infections and 46.9% of deaths in infants with infection, followed by coagulase-negative staphylocci, 17.6 and 12.2%, respectively. On logistic regression analysis risk factors for late onset gram-negative compared with gram-positive infection were endotracheal intubation at birth and blood transfusion. Hypoglycemia was associated with gram-positive infection. CONCLUSION: The late onset infection rate in Malaysian very low birth weight infants does not differ from that reported from developed countries, but the mortality is higher. This could be because of an excess of gram-negative infections.

Humans↗
PubMed2001

Recurrent ocular herpes simplex keratitis following excimer laser photorefractive keratectomy in a rabbit model.

PURPOSE: Reactivation of latent herpes simplex virus (HSV) by excimer laser photorefractive keratectomy(PRK) has been reported previously in the literature. This study evaluates the extent of such HSV reactivation and determines whether corneal de-epithelialization prior to PRK or the laser treatment itself induces this response. METHODS: Twenty three normal 1.5-2.5 kg New Zealand white rabbits were infected on the surface of the cornea with HSV-1, strain RE. The animals were monitored until resolution and then divided into two treatment groups: 1) de-epithelialization alone, and 2) de-epithelialization plus laser. Animals were evaluated in a masked fashion by clinical examination and viral cultures twice a week through day 28. RESULTS: The reactivation rate for group 1 (de-epithelization alone) was 0.0%, and for group 2 (PRK) was 67% by slit lamp biomicroscopy. Viral culture positivity rate matched these findings. CONCLUSIONS: Excimer laser (193 nm) treatment can trigger viral shedding and reactivation of herpetic ocular disease in the latently infected rabbit. De-epithelialization alone is not sufficient to cause such viral reactivation or keratitis. Our findings suggest that patients with a history of herpetic keratitis undergoing PRK are at increased risk of HSV reactivation as a result of exposure to the excimer laser.

Animals↗
PubMed2001

Use of the Griffiths Mental Scales in normal 2 year old Malaysian children.

The Griffiths Scales for Mental Development were used to assess a group of 60 normal 2-year old Malaysian children (25 Indian, 23 Malay and 12 Chinese). The mean GQ was 104.2 (SD 9.3). This was significantly higher than the test mean of 100, p < 0.001. The mean score for Malaysian children was significantly higher on the locomotor, personal social, performance and practical reasoning subscales while they were significantly lower on the hand eye subscale and did not differ from the test mean on the hearing and speech subscale. There was a significant correlation between GQ and social class, r = -0.39, p < 0.05. Scores were lower than those currently obtained on British children, p < 0.001. Minor difficulties due to language and cultural factors arose over the interpretation of several items but with standardisation of these items the test is useful in Malaysian children.

Child Development↗
PubMed2001

Mortality from congenital abnormality in Malaysia 1991-1997: the effect of economic development on death due to congenital heart disease.

An analysis was done of available data from the Department of Statistics Malaysia, on the type of congenital abnormality contributing to death, to determine whether progress in health care over recent years was associated with any decline in mortality from congenital abnormality. A significant decline in death due to congenital abnormality was observed between 1991 and 1996. This was attributable to a decline in deaths due to congenital heart disease occurring because of improvements in cardiac surgical services for infants. In 1997 death due to congenital heart disease increased significantly. This could be attributed to improvements in the diagnosis of congenital heart disease in the neonate.

Congenital Abnormalities↗
PubMed2000

Neuroprotective potential of a viral vector system induced by a neurological insult.

Gene transfer into neurons via viral vectors for protection against acute necrotic insults has generated considerable interest. Most studies have used constitutive vector systems, limiting the ability to control transgene expression in a dose-dependent, time-dependent, or reversible manner. We have constructed defective herpes simplex virus vectors designed to be induced by necrotic neurological insults themselves. Such vectors contain a synthetic glucocorticoid-responsive promoter, taking advantage of the almost uniquely high levels of glucocorticoids-adrenal stress steroids-secreted in response to such insults. We observed dose-responsive and steroid-specific induction by endogenous and synthetic glucocorticoids in hippocampal cultures. Induction was likely to be rapid enough to allow transgenic manipulation of relatively early steps in the cascade of necrotic neuron death. The protective potential of such a vector was tested by inclusion of a neuroprotective transgene (the Glut-1 glucose transporter). Induction of this vector by glucocorticoids decreased glutamatergic excitotoxicity in culture. Finally, both exogenous glucocorticoids and excitotoxic seizures induced reporter gene expression driven from a glucocorticoid-responsive herpes simplex virus vector in the hippocampus in vivo.

Animals↗
PubMed2000

Continuous distending airway pressure for respiratory distress syndrome in preterm infants.

BACKGROUND: Respiratory distress syndrome (RDS) is the single most important cause of morbidity and mortality in preterm infants (Greenough 1998, Bancalari 1992). Intermittent positive pressure ventilation (IPPV) with surfactant is the standard treatment for the condition. The major difficulty with IPPV is that it is invasive, resulting in airway and lung injury and contributing to the development of chronic lung disease. OBJECTIVES: In spontaneously breathing preterm infants with RDS, to determine if continuous distending airway pressure (CDAP) reduces the need for IPPV and associated morbidity without adverse effects. SEARCH STRATEGY: The standard search strategy of the Neonatal Review group was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, journal hand searching mainly in the English language. SELECTION CRITERIA: All trials using random or quasi-random patient allocation of newborn infants with RDS were eligible. Interventions were continuous distending airway pressure including continuous positive airway pressure (CPAP) by mask, nasal prong, nasopharnygeal tube, or endotracheal tube, or continuous negative pressure (CNDP) via a chamber enclosing the thorax and lower body, compared with standard care. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and its Neonatal Review Group, including independent assessment of trial quality and extraction of data by each author, were used. MAIN RESULTS: CDAP is associated with a lower rate of failed treatment (death or use of assisted ventilation), overall mortality, and mortality in infants with birthweights above 1500 g. The use of CDAP is associated with an increased rate of pneumothorax. REVIEWER'S CONCLUSIONS: In preterm infants with RDS the application of CDAP either as CPAP or CNDP is associated with some benefits, particularly in infants with birthweights over 1500 gms. The extent of this benefit is difficult to assess given the outdated methods to administer CDAP, low use of antenatal corticosteroids, non-availability of surfactant and the intensive care setting of the 1970's in which these trials were done. Where resources are limited, such as in developing countries, CPAP for RDS may have a clinical role. Further research is required to determine the best mode of administration and its role in modern intensive care settings

Humans↗
PubMed2000

Long-term expression driven by herpes simplex virus type-1 amplicons may fail due to eventual degradation or extrusion of introduced transgenes.

In gene therapy applications employing herpes simplex virus amplicon-based vectors, a prevailing problem is the down-regulation of transgene expression over time. We have applied a combined immunocytochemistry and fluorescent in situ hybridization method to determine whether down-regulation of transgene expression at the single-cell level correlates with loss of vector DNA from the host cell nucleus. Utilizing separate fluorescent labels (i.e., rhodamine, fluorescein, and 4',6'-diamidino-2-phenlindole), we were able to simultaneously detect transgenes, their products, and their locations relative to the nuclear compartment of a single cell. Detection of the reporter gene lacZ and its encoded protein beta-galactosidase (beta-gal) was accomplished in in vivo experiments of the dentate gyrus of rats. A time course study of the expression of the transgene post-stereotactic microinfusion up to 60 days was made. Expression reached maximal levels within 12-24 h after infection, and lacZ presence was reduced to less than 3% of its maximal levels within 36 h after infection. In comparing days 1 and 60 post-stereotactic microinfusion, only one-fifth of the original DNA was observed in the area of a 100-mm radius around the site of microinfusion at day 60. Moreover, by comparing the locations of the reporter gene in cells that expressed the encoded protein versus those that did not, we found that introduced transgenes were preferentially localized in the nuclear periphery of down-regulated host cells, compared to expressing host cells. These results suggest that nuclear compartmentalization may play a role in the down-regulation of our reporter gene by means of peripheralization, extrusion, and/or degradation.

Animals↗
PubMed2000

Forskolin and phorbol ester have opposite effects on the expression of mucin-associated sialyl-Lewis(a) in pancreatic cancer cells.

The carbohydrate antigen sialyl-Lewis(a) is important to pancreatic tumour biology because the circulating antigen is used in serological tests for malignancy and because cell surface antigen is involved in tumour cell binding to the endothelial adhesion molecule, E-selectin, in extravasation. In this study, we examined the effects of the adenylyl cyclase activator, forskolin, and the diacylglycerol analogue, phorbol 12-myristate 13-acetate (PMA), on the expression and release of sialyl-Lewis(a) in human pancreatic cancer cells. Increases in the release of sialyl-Lewis(a) from SW1990 cells produced by forskolin and PMA were associated with increases in the activities of protein kinases A and C, respectively, and could be blocked by inhibitors specific for these enzymes. Immunoprecipitation experiments showed that sialyl-Lewis(a) was associated with MUC1 mucin. Forskolin also increased the cellular content of antigen and MUC1 mRNA. Actinomycin D and a protein kinase A inhibitor, H8, blocked these effects. In contrast, PMA reduced cellular antigen and MUC1 mRNA levels, although it produced a temporary increase in release of the antigen. The effects of PMA were blocked by the protein kinase C inhibitor, H7. PMA also reduced cell binding to the adhesion molecule E-selectin. In summary, PKA and PKC alter cell MUC1-associated sialyl-Lewis(a) in opposite directions. These changes may have clinical utility in the diagnosis of pancreatic cancer and the prevention of metastases.

Blotting, Western↗
PubMed2000

Antibody-dependent cytotoxicity mediated by chimeric monoclonal antibody Nd2 and experimental immunotherapy for pancreatic cancer.

In a previous study, mouse monoclonal antibody (MoAb) Nd2 (m-Nd2, mouse IgG1) labeled with (131)I exhibited efficacy in in vivo radioimmunotherapy against pancreatic cancer. In this study we prepared mouse / human chimeric antibody Nd2 (c-Nd2, human IgG1) for clinical use and examined whether c-Nd2 induced antibody-dependent cell-mediated cytotoxicity (ADCC). Cytotoxicity to pancreatic cancer (PC) cell lines, including Nd2 antigen-positive (SW1990, RWP-1, Capan-1) and Nd2 antigen-negative (Panc-1, MiaPaca-2, Capan-2) lines, was evaluated by mixed human leukocyte and tumor cell culture (MLTC) at an effector cell to target cell (E / T) ratio of 50 with or without Nd2. Cytotoxicities to SW1990 with no antibody, m-Nd2 and c-Nd2 (1 microg / ml) were 26.7%, 38.0% and 55%, respectively; to RWP-1, 28%, 41% and 70%; to Capan-1, 26%, 30% and 52%; to Panc-1, 24%, 28% and 30%; to MiaPaca-2, 18%, 20% and 27% and to Capan-2, 29. 7%, 35.0% and 40.6%. Cytotoxic capacity during MLTC with c-Nd2 was significantly higher than during MLTC with m-Nd2 or with no antibody. These findings indicated that cytotoxicity to Nd2-positive PC cells during MLTC is induced by ADCC. Intraperitoneal injection of c-Nd2 inhibited the tumor growth of SW1990 xenografted subcutaneously in nude mice and prolonged the survival of nude mice in which SW1990 tumor was transplanted orthotopically at the tail of the pancreas. These findings suggested that, because of its ability to induce ADCC, c-Nd2 may be clinically useful for the immunotherapeutic treatment of pancreatic cancer.

Animals↗
PubMed2000

Mucins in the diagnosis and therapy of pancreatic cancer.

Mucins are large glycoproteins that form a protective layer along the lumens of the organs of the gastrointestinal and reproductive tracts. Frequently in tumors of the pancreas there are changes in the structure of mucin carbohydrates and/or levels of apomucin types. Originally mucins were of interest clinically because diagnostic tests could be based on their levels in circulation. More recently mucin directed monoclonal antibodies have been used to target tumors with cytotoxic agents. There is now a considerable literature on the development of mucin-based vaccines. Both monoclonal antibodies and vaccines could be powerful tools to specifically target tumor cells in distant metastases. Gene therapy based upon the MUC1 gene promoter is being investigated to target therapeutic genes to MUC1 expressing cells. The carbohydrates of mucins on the surface of tumor cells have been reported to inhibit cells of the immune system. These carbohydrates also act as ligands during the process of tumor cell metastasis. Another approach to therapy is to block interactions between the ligands and their receptors.

Animals↗
PubMed2000

Forskolin increases the expression of the pancreatic tumor antigen, Nd2, and uptake of Nd2 antibody.

Nd2 antibody recognizes an antigen that is tumor specific in pancreas. It has been used successfully in clinical radioimmunodetection studies to identify exocrine pancreatic tumors. In the present study we show that the uptake of radiolabeled Nd2 antibody by SW1990 pancreatic carcinoma cells was increased by the adenyl cyclase activator, forskolin. Dibutyryl cyclic AMP and forskolin were both effective in increasing the level of Nd2 antigen in SW1990 cells. Immunoprecipitation studies showed that the Nd2 epitope is associated with MUC1 mucin. Forskolin increased Nd2/MUC1 antigen in both a membrane fraction and a high buoyant density mucin-like fraction. Nd2 immunoreactivity was reduced by treatment of mucins with proteases and beta-mercaptoethanol. Immunohistochemical studies showed that periodate catalyzed beta-elimination greatly reduced Nd2 immunoreactivity. These results suggest that the Nd2 epitope is unusual in having characteristics of both a peptide and a carbohydrate, protease and conformation sensitivities and involvement of O-linked oligosaccharides. Nd2 antibody does not react with several known pancreatic cancer antigens. In summary, activation of the cyclic AMP pathway increased cellular uptake of Nd2 antibody and the cellular expression of the tumor-specific, mucin-associated Nd2 antigen. These results suggest a means of improving the effectiveness of monoclonal antibodies in targeting tumor antigens for the diagnosis and treatment of malignancy.

Amino Acid Sequence↗
PubMed1999

Phorbol ester reduces phosphorylation of epidermal growth factor receptor in pancreatic cancer cells by activation of a tyrosine phosphatase.

In this study we report that phorbol 12-myristate 13-acetate (PMA) transiently reduced the level of EGF receptor tyrosine phosphorylation in three pancreatic cancer cell lines (HPAC, SW1990, and UCVA-1) in response to EGF. The effect was maximal at 40-90 min. Pretreatment with the protein kinase C inhibitor GF 109203X reduced the PMA effect. Flow cytometry experiments showed that PMA produced only a slight reduction in the surface expression of EGF-R. The phosphotyrosine phosphatase inhibitor bpV(phen) returned phosphorylation to almost control levels. Moreover, homogenates of PMA treated pancreatic cells reduced the phosphorylation of activated receptor that was immunoprecipitated from A431 epidermoid cells. A combination of orthovanadate and NaF or bpV(phen) inhibited the effect of the homogenates. These results suggest that PMA activates a phosphotyrosine phosphatase activity that reduces the steady-state level of tyrosine phosphorylation of the receptor that is induced by EGF.

Cell Membrane↗