PubMed Health⌕ Search

Biomedical subjects

D Fong

Publications and source records attributed to D Fong.

At least 19 recordsLinked to original sources

Ep-CAM expression in pancreatic and ampullary carcinomas: frequency and prognostic relevance.

AIMS: Pancreatic adenocarcinoma is an aggressive gastrointestinal malignancy with only a few long-term survivors even after radical surgery. Patients with ampullary cancer have a better prognosis but adjuvant therapy needs further improvement. Epithelial cell adhesion molecule (Ep-CAM) is strongly expressed in a variety of epithelial cancers and represents a promising target for immunological tumour therapy. Thus, the aim of this study was to investigate Ep-CAM expression and its potential prognostic impact in pancreatic and ampullary carcinomas. METHODS: Ep-CAM expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumour tissue samples from a series of consecutive patients with pancreatic (n = 153) and ampullary cancer (n = 34). RESULTS: Ep-CAM overexpression was observed in 85 of 153 pancreatic cancer specimens (56%) and in 29 of 34 ampullary cancer samples (85%). Overall, Ep-CAM failed to be an independent prognostic marker. However, subgroup analyses showed that Ep-CAM overexpression correlated with shorter overall survival among patients with ampullary cancer and advanced stage pancreatic cancer. In the latter subgroup, survival gradually worsened with increasing Ep-CAM scores. Furthermore, in ampullary cancer, Ep-CAM overexpression was found to correlate with tumour stage. CONCLUSIONS: Ep-CAM overexpression was detectable in the majority of cases with pancreatic and ampullary cancer. Therefore, Ep-CAM represents an attractive target for immune-based therapeutic interventions in these tumour entities. However, the prognostic value of Ep-CAM overexpression remains undetermined.

Adenocarcinoma↗

Deep Impact: observations from a worldwide Earth-based campaign.

On 4 July 2005, many observatories around the world and in space observed the collision of Deep Impact with comet 9P/Tempel 1 or its aftermath. This was an unprecedented coordinated observational campaign. These data show that (i) there was new material after impact that was compositionally different from that seen before impact; (ii) the ratio of dust mass to gas mass in the ejecta was much larger than before impact; (iii) the new activity did not last more than a few days, and by 9 July the comet's behavior was indistinguishable from its pre-impact behavior; and (iv) there were interesting transient phenomena that may be correlated with cratering physics.

Cosmic Dust↗

Aberrant tetranectin expression in human breast carcinomas as a predictor of survival.

AIMS: Tetranectin (TN), a plasminogen kringle 4 binding protein, is thought to play a prominent role in the regulation of proteolytic processes via binding to plasminogen. The aim of this study was to evaluate the expression of TN in human breast cancer and adjacent normal breast tissue and to determine the impact of this expression on survival. METHODS: A retrospective analysis was performed on 189 patients with breast cancer, with a median follow up time of 10.6 years. The expression of TN was assessed in tumour tissue and adjacent normal breast tissue by immunohistochemistry, and the prognostic relevance of its expression in tumour cells was evaluated. RESULTS: TN was highly expressed in connective tissue fibres surrounding normal breast epithelium, but not in normal epithelial cells. High expression of TN in tumour cells was found in 131 (69%) of the tumour samples. By western blot analysis, no significant difference in the amount and molecular weight of TN was seen between tumour tissue and normal tissue. Strong TN immunoreactivity in tumour tissue was predictive of poor disease free and tumour specific overall survival. By multivariate analysis, high TN expression in cancer cells was an independent prognostic factor for disease free and tumour specific overall survival. CONCLUSIONS: Our results demonstrate differential TN expression in normal and malignant breast tissue and a prognostic impact of TN protein expression in breast carcinoma tissue. These data suggest a possible role of TN in invasiveness and the metastatic spread of human breast cancer.

Adult↗

Correlation of COX-2 and Ep-CAM overexpression in human invasive breast cancer and its impact on survival.

Recent studies have demonstrated cyclooxygenase 2 (COX-2) overexpression in various human malignancies, especially in breast cancer, where COX-2 turned out to be a predictor of poor survival. To evaluate the relation of COX-2 and Ep-CAM overexpression and its prognostic significance, we performed a retrospective study on 212 breast cancer patients with a median follow-up time of 10.5 years. Overexpression of COX-2 in tumour tissue samples was assessed by immunohistochemistry. COX-2 overexpression was found in 48.6% of the tumour samples and was predictive for poor disease-free and overall survival. Univariate analysis revealed a strong correlation between COX-2 and Ep-CAM overexpression (P=0.009). Concurrent COX-2 and Ep-CAM overexpression was present in 21.7% of tumour specimens and had an additive negative impact on disease-free and overall survival. Determination of both tumour markers should help in guiding new therapeutic strategies in patients with invasive breast cancer.

Adult↗

Diffuse axonal injury: detection of changes in anisotropy of water diffusion by diffusion-weighted imaging.

Myelinated axons of white matter demonstrate prominent directional differences in water diffusion. We performed diffusion-weighted imaging on ten patients with head injury to explore the feasibility of using water diffusion anisotropy for quantitating diffuse axonal injury. We showed significant decrease in diffusion anisotropy indices in areas with or without signal abnormality on T2 and T2*-weighted images. We conclude that the water diffusion anisotropy index a potentially useful, sensitive and quantitative way of diagnosing and assessing patients with diffuse axonal injury.

Adult↗

Digital subtraction in gadolinium-enhanced MR imaging of the brain: a method to reduce contrast dosage.

The aim of the study was to investigate the feasibility of using digital subtraction in contrast-enhanced MR imaging of the brain to reduce the MR contrast dosage without jeopardizing patient care. Fifty-two patients with intracranial lesions, either intra-axial or extra-axial, detected by computerized tomography were selected for contrast-enhanced MR imaging with half-dose and full-dose of gadopentetate dimeglumine. The half-dose unsubtracted, full-dose unsubtracted, and half-dose subtracted MR images were visually assessed by counting the number of enhancing brain lesions in the images and quantitatively analyzed by computing their lesion contrast-to-background ratios (CBR). The visual conspicuity of the half-dose subtracted MR images was comparable to that of the full-dose unsubtracted MR images ( p>0.05), whereas the CBR of the half-dose subtracted images was approximately two to three times higher than that of the full-dose unsubtracted images. The half-dose subtracted T1-weighted spin-echo images might be able to replace the conventional standard-dose T1-weighted spin-echo images in MR imaging of the brain.

Brain↗

Syphilitic myelitis with diffuse spinal cord abnormality on MR imaging.

Syphilitic myelitis is a very rare manifestation of neurosyphilis. The MRI appearance of syphilitic myelitis is not well documented and only a few cases have been reported. We present a 52-year-old woman with acute onset of paraplegia. Magnetic resonance imaging of the spine showed diffuse high signal intensity in the whole spinal cord on T2-weighted images. Focal enhancement was observed in the dorsal aspect of the thoracic cord on T1-weighted gadolinium-enhanced images. To our knowledge, diffuse spinal cord abnormality in syphilitic myelitis has not been reported in the international literature. Disappearance of the diffuse high-signal lesions with residual focal enhancement was noted after antibiotic therapy. The patient suffered significant neurological deficit despite improvement in the MR images. In this article we present the imaging findings and review the literature of this rare condition.

China↗

Spontaneous intracranial hypotension with diffuse dural enhancement of the spinal canal and transient enlargement of the pituitary gland.

Spontaneous intracranial hypotension is a rare phenomenon characterized by postural headache, neck rigidity, nausea and vomiting. Imaging findings on magnetic resonance imaging (MRI) is characteristic with diffuse intracranial pachymeningeal thickening and enhancement following intravenous gadolinium. We present a case of spontaneous intracranial hypotension with two unusual imaging findings; pachymeningeal enhancement of the spinal canal and enlargement of the pituitary gland in addition to the diffuse intracranial pachymeningeal enhancement. In this case report, we will discuss the clinical features, MRI findings and underlying pathophysiology of this rare condition.

Adult↗

Late temporal lobe necrosis in patients with nasopharyngeal carcinoma: evaluation with combined multi-section diffusion weighted and perfusion weighted MR imaging.

Late temporal lobe necrosis is a well-known and serious complication in patients with nasopharyngeal carcinoma (NPC) following radiotherapy. Owing to the close proximity to the skull base, the medial temporal lobes are inevitably included in the target volume of irradiation. Patients with NPC provide a unique opportunity in study of delay radiation effect in normal human brain. The objective of this study was to evaluate late temporal lobe radiation injury by combined multi-section diffusion weighted and perfusion weighted MR imaging. We prospectively studied 16 patients with typical clinical symptoms of late temporal lobe necrosis or other abnormalities in the temporal lobes incidentally detected by conventional MR imaging. All patients had a previous history of radiotherapy for histologically proven NPC. Conventional T1- and T2-weighted images, fast gradient echo with echo-planar diffusion-weighted and perfusion-weighted MR imaging were performed. Apparent diffusion coefficient (ADC) map and relative cerebral blood volume (rCBV) map were computed via commercially available software. MR diffusion and perfusion images were then analyzed and graded by two independent observers with focusing on the diffusion and perfusion mismatch. The temporal lobe lesions displayed marked high diffusion on the ADC map. The rCBV map also revealed marked hypoperfusion in these temporal lobe lesions in all patients. The areas of abnormality on the rCBV map were significantly larger than the lesions on the ADC map in 14 patients (observer 1) and 13 patients (observer 2). Since late temporal lobe necrosis is probably caused by damage of the endothelium of vessels and ischemia, perfusion and diffusion mismatch might imply injured tissue but potentially salvageable brain tissue. A mismatch may be potentially used to predict the response to treatment in-patients with late temporal lobe necrosis.

Adult↗

Synergy between ethanol and grape polyphenols, quercetin, and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway.

In atherosclerosis and tumor initiation, inducible nitric oxide synthase (iNOS) has been implicated in the damage of vascular walls and DNA, respectively. Moderate consumption of red wine has been ascribed as a preventive for coronary heart disease; however, there has been much debate over whether the beneficial effect is from grape polyphenolic components or ethanol. We studied the interaction of grape compounds on nitric oxide (NO) production by macrophages, mediators of blood vessel damage in atherosclerosis. For the murine macrophage cell line RAW 264.7, stimulation with lipopolysaccharide and interferon-gamma led to expression of the iNOS gene and production of NO. The polyphenols quercetin and resveratrol at a micromolar range suppressed iNOS gene expression and NO production, as determined by reverse transcription-polymerase chain reaction and nitrite assay. The polyphenols were also found to be scavengers of NO in an acellular system using sodium nitroprusside under physiological conditions. Ethanol, at a moderate level, did not produce any appreciable level of reduction of iNOS or NO activity. However, its presence at 0.1 to 0.75% enhanced the effect of grape polyphenols concentration-dependently. Thus, the interaction between these components plays a significant role in the health effects of red wine, especially with respect to their effect on the NO pathway.

Animals↗

The inhibition of spontaneous and tumor necrosis factor-alpha induced neutrophil apoptosis by crystals of calcium pyrophosphate dihydrate and monosodium urate monohydrate.

OBJECTIVE: Spontaneous neutrophil apoptosis may be inhibited by various proinflammatory stimuli. which may result in prolonged lifetimes and responses of these phagocytic cells with the potential for extended inflammation. We investigated the effect of short term incubation of opsonized crystals of monosodium urate monohydrate (MSUM) or calcium pyrophosphate dihydrate (CPPD) on both spontaneous and tumor necrosis factor-alpha (TNF-alpha) induced neutrophil apoptosis. METHODS: Peripheral neutrophils were incubated with plasma opsonized crystals of CPPD or MSUM in the presence or absence of TNF-alpha for 4 h at 37 degrees C. Apoptosis was determined using 3 separate assays: (1) an agarose DNA fragmentation assay, (2) a cytoplasmic histone associated DNA fragmentation assay, and (3) a caspase 3 fluorometric assay. RESULTS: All 3 assays showed similar results. Both MSUM and CPPD crystals inhibited spontaneous apoptosis in neutrophils. TNF-alpha induced high levels of apoptosis in neutrophils. However, co-incubation of the cells with TNF-alpha and crystals resulted in the inhibition of apoptosis to levels below those of control cells. Pretreatment of neutrophils with the protein synthesis inhibitor cycloheximide prevented the inhibition of apoptosis by crystals. CONCLUSION: These data support the concept of crystal induced inhibition of neutrophil apoptosis as part of the pathophysiology of the diseases collectively known as crystal induced arthritis.

Apoptosis↗

A PCR-ELISA Method for Direct Detection of the Oyster Pathogen Haplosporidium nelsoni.

: A rapid method, utilizing both polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), was developed for detection of oyster MSX disease. The technique included using Haplosporidium nelsoni pathogen-specific PCR primers (based on ribosomal RNA genes), a Chelex resin (for rapid DNA extraction from oyster mantle tissues), and cloned H. nelsoni rRNA plasmid DNA (for use as a capture probe). Digoxigenin was incorporated into the pathogen-specific PCR products, which were captured by the coated probe in a fast hybridization reaction and then detected by ELISA. The sensitivity of PCR amplification on cloned plasmid DNA was 10 fg for detection by stained agarose gel, and increased to 0.01 fg for ELISA. Positive signals were observed in infected oysters using the PCR-ELISA technique. This method may be applicable to early detection of infection.

Journal Article↗

The shaken baby syndrome: review of 10 cases.

OBJECTIVE: To study the characteristics of the shaken baby syndrome from 10 cases in Hong Kong. DESIGN: Retrospective study. SETTING: Regional public hospital, Hong Kong. PATIENTS: Six boys and four girls (mean age, 0.54 years; range, 0.18-1.42 years) in whom the shaken baby syndrome was diagnosed between January 1994 and June 1998. MAIN OUTCOME MEASURES: Clinical features at presentation, radiological findings, management, and outcome. RESULTS: All 10 patients presented with coma: the mean score on the Glasgow coma scale was 4.8 (range, 3-10). In all 10 cases, the history provided by the carers were incompatible with the patient's presentation. Nine patients presented with seizures. Retinal haemorrhages were detected in all patients, but peripheral signs of bruising were observed in only three. Acute subdural haematoma was found in eight patients; one of the remaining two children had subarachnoid and subdural haemorrhages, whereas the other had subarachnoid and intracerebral haemorrhages. Skeletal fractures were detected in two patients. The suspected abusers included either or both parents (n=3), childminders (n=3), and maids (n=2); the identity of the abusers were unknown in two cases. Prosecution by the police was initiated in three cases and two abusers were found to be guilty. Three children died of the abuse; the seven survivors had significant neurological handicaps. CONCLUSION: Medical practitioners should be alert to the occurrence of abusive head injury in children. Peripheral signs are uncommon and a high degree of suspicion is needed for the management to be successful.

Journal Article↗

Selective posterior rhizotomy: results of five pilot cases.

We report on two patients with spastic quadriplegia and three patients with spastic diplegia who underwent selective posterior rhizotomy. The mean period of follow-up was 15 months (range, 12-21 months). The patients were assessed preoperatively and at 2 weeks, 3 months, 6 months, and 1 year after surgery. Tests included those for muscle tone (using a modified Ashworth scale), range of passive movement, functional status, and gait pattern. Muscle tone was reduced substantially after the procedure, and the range of passive movement was increased. Both the dependent and independent ambulators showed an increment in their walking velocity and stride length. There were no postoperative complications apart from mild fever and the treatment was well tolerated by both patients and parents. There was no return of spasticity in any of the patients during follow-up. The reduced spasticity resulted in better motor performance, and patients felt more comfortable with their daily activities. We conclude that selective posterior rhizotomy should be considered for those patients who have cerebral palsy and are disabled by spasticity.

Journal Article↗

In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties.

Curcumin is a naturally occurring, dietary polyphenolic phytochemical that is under preclinical trial evaluation for cancer preventive drug development and whose working pharmacological actions include anti-inflammation. With respect to inflammation, in vitro, it inhibits the activation of free radical-activated transcription factors, such as nuclear factor kappaB (NFkappaB) and AP-1, and reduces the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF alpha), interleukin-1beta (IL-1beta), and interleukin-8. Inducible nitric oxide synthase (iNOS) is an inflammation-induced enzyme that catalyzes the production of nitric oxide (NO), a molecule that may lead to carcinogenesis. Here, we report that in ex vivo cultured BALB/c mouse peritoneal macrophages, 1-20 microM of curcumin reduced the production of iNOS mRNA in a concentration-dependent manner. Furthermore, we demonstrated that, in vivo, two oral treatments of 0.5 mL of a 10-microM solution of curcumin (92 ng/g of body weight) reduced iNOS mRNA expression in the livers of lipopolysaccharide(LPS)-injected mice by 50-70%. Although many hold that curcumin needs to be given at dosages that are unattainable through diet to produce an in vivo effect, we were able to obtain potency at nanomoles per gram of body weight. This efficacy is associated with two modifications in our preparation and feeding regimen: 1) an aqueous solution of curcumin was prepared by initially dissolving the compound in 0.5 N NaOH and then immediately diluting it in PBS; and 2) mice were fed curcumin at dusk after fasting. Inhibition was not observed in mice that were fed ad lib., suggesting that food intake may interfere with the absorption of curcumin.

Animals↗

Inhibition of inducible nitric oxide synthase gene expression and enzyme activity by epigallocatechin gallate, a natural product from green tea.

Chronic inflammation has been implicated as the underlying factor in the pathogenesis of many disorders. In the past decade, inflammation-related endogenous production of reactive nitrogen species, similar to oxygen free radicals, has also been suggested as a risk factor for cancer, in addition to the well-studied exogenous nitroso compounds. Epidemiological, in vitro, and animal model studies have implicated green tea to be protective against nitroso compound-induced and inflammation-related cancer. Therefore, we investigated the effect of epigallocatechin-3-gallate (EGCG), one of the known biologically active catechins contained in green tea, on the production of nitric oxide (NO.). We have shown previously that EGCG reduces NO. production as measured by nitrite accumulation in the culture medium. Expanding on this finding, in this report we show that EGCG may do so by two mechanisms: reduction of inducible nitric oxide synthase (iNOS) gene expression and inhibition of enzyme activity. Addition of 1-10 microM EGCG to lipopolysaccharide- and interferon-gamma-activated mouse peritoneal cells reduced iNOS mRNA expression concentration dependently, to 82-14%, as measured by relative reverse transcription-polymerase chain reaction. Addition of 50-750 microM EGCG, in a concentration-dependent manner, inhibited the enzyme activity of iNOS, to 85-14%, and neuronal nitric oxide synthase (nNOS), to 93-56%, as measured by citrulline formation. EGCG competitively inhibited binding of arginine and tetrahydrobiopterin, and the gallate structure is important for this action.

Animals↗