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Biomedical subjects

T Ng

Publications and source records attributed to T Ng.

At least 19 recordsLinked to original sources
PubMed2003

Integrin-protein kinase C relationships.

The integrins have an ability to interact with extracellular matrix proteins to confer adhesive and motile properties on cells. The means by which these activities operate and the manner in which they are integrated with cell functions is of particular relevance to many biological processes. In the present paper, the developing understanding of the bi-directional relationship between the protein kinase C family of signal transducers and integrins is discussed.

Amino Acid Sequence↗
PubMed2002

Intraperitoneal rituximab: an effective measure to control recurrent abdominal ascites due to non-Hodgkin's lymphoma.

We report a patient with an advanced stage low-grade small lymphocytic lymphoma who required regular drainage of malignant ascites for symptomatic relief despite intensive treatment. The administration of rituximab via the intraperitoneal route successfully controlled the ascites. The patient tolerated well with this unusual route of administration and has not required any further ascitic drainage for at least 8 months. In view of its simplicity, good tolerability and effectiveness to control recurrent ascites secondary to low-grade non-Hodgkin's lymphoma (NHL), this novel route of administration of rituximab is worth exploring.

Abdomen↗
PubMed2002

Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria.

The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimer's disease but low agreement for cases with possible Alzheimer's disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 20 cases. Inter-rater reliability for the diagnosis of Alzheimer's disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted.

Alzheimer Disease↗
PubMed2001

Ezrin is a downstream effector of trafficking PKC-integrin complexes involved in the control of cell motility.

Protein kinase C (PKC) alpha has been implicated in beta1 integrin-mediated cell migration. Stable expression of PKCalpha is shown here to enhance wound closure. This PKC-driven migratory response directly correlates with increased C-terminal threonine phosphorylation of ezrin/moesin/radixin (ERM) at the wound edge. Both the wound migratory response and ERM phosphorylation are dependent upon the catalytic function of PKC and are susceptible to inhibition by phosphatidylinositol 3-kinase blockade. Upon phorbol 12,13-dibutyrate stimulation, green fluorescent protein-PKCalpha and beta1 integrins co-sediment with ERM proteins in low-density sucrose gradient fractions that are enriched in transferrin receptors. Using fluorescence lifetime imaging microscopy, PKCalpha is shown to form a molecular complex with ezrin, and the PKC-co-precipitated endogenous ERM is hyperphosphorylated at the C-terminal threonine residue, i.e. activated. Electron microscopy showed an enrichment of both proteins in plasma membrane protrusions. Finally, overexpression of the C-terminal threonine phosphorylation site mutant of ezrin has a dominant inhibitory effect on PKCalpha-induced cell migration. We provide the first evidence that PKCalpha or a PKCalpha-associated serine/threonine kinase can phosphorylate the ERM C-terminal threonine residue within a kinase-ezrin molecular complex in vivo.

Amino Acid Substitution↗
PubMed2001

Varied tropism of HIV-1 isolates derived from different regions of adult brain cortex discriminate between patients with and without AIDS dementia complex (ADC): evidence for neurotropic HIV variants.

A number of infected individuals develop neuropathological disorders, such as AIDS dementia complex (ADC), as a consequence of HIV/AIDS. The biological features governing HIV entry and tropism in different brain cell types remain unclear, as do the genetics of the virus regulating these events and the neuropathogenic processes within the brain tissues. HIV-1 was isolated from the right and left parietal, occipital, and frontal lobes of the brain cortex of three HIV-1-infected patients: two with ADC and one without. The viral strains were studied from the innate tissues and various primary cell cultures. The kinetics and tropism of viral strains from different brain regions showed clear differences on various primary cell types (monocytes, monocyte-derived macrophages, and T cells), which could discriminate between biological behavior of HIV-1 strains from patients with and without ADC. The variable effect of different donor cells on tropism was also clearly evident. The majority (with a few exceptions) of isolates from different brain regions of all three patients used CCR5 as coreceptor for entry. The consistent CCR5 use, macrophage tropism, and non-syncytium-inducing phenotype were the main characteristics of the brain-derived HIV-1 strains from all three patients. Importantly, viral strains derived directly from innate brain tissue of the patient without ADC showed some differences from the cultured variants of the same patient, whereas those from brain tissue of the patients with ADC were more similar to the culture-adapted strains. This suggests that the emergence of primary cell type-adapted isolates during ADC may play a crucial role in the development and progression of the neuropathology associated with ADC. The different genotypes residing in different areas of brain combined with their differential tropism and coreceptor use suggest that neurotropic variants exist that may be governing the neurological manifestation of HIV disease in infected patients.

AIDS Dementia Complex↗
PubMed2001

Suppression of cell cycle progression by a fungal lectin: activation of cyclin-dependent kinase inhibitors.

The antiproliferative activity of a fungal lectin (VVL) isolated from the mushroom, Volvariella volvacea, was studied using a battery of cultured tumor cell lines. It was revealed that [(3)H]thymidine incorporation into the cell lines was markedly reduced at 0.32 microM VVL. When S180 mouse sarcoma cells were incubated for 48 hr with doses of VVL ranging from 0.32 to 0.8 microM, prominent blebs on the cell surface and large vacuoles in the cytoplasm, but not apoptotic bodies, were observed under a fluorescence microscopy. VVL did not exert ribosome-inactivating activity or induce any changes in the expression of cyclins A, D1, and E. However, it did activate the expression of cyclin kinase inhibitors, namely p21, p27, p53, and Rb, in a dose-dependent manner. Flow cytometric analysis demonstrated an accumulation of cells in the G2/M phase in a time- and dose-dependent manner, indicating that VVL arrested cell proliferation by blocking cell cycle progression in the G2/M phase.

Agaricales↗
PubMed2001

Esophageal perforation: a rare complication of Zollinger-Ellison syndrome.

Spontaneous perforation of the esophagus is a rare manifestation of Zollinger-Ellison syndrome (ZES). Failure to recognize its existence can lead to an unsuccessful treatment of the esophageal perforation. We present a rare case of reflux esophagitis-induced esophageal perforation in a patient with ZES. Presence of a gastrinoma should be considered when recurrent or complicated reflux esophagitis is encountered.

Barium Sulfate↗
PubMed2001

Warfarin-induced skin necrosis associated with Factor V Leiden and protein S deficiency.

Thrombotic events are rare complications during anticoagulation therapy. The thrombosis varies from localized cutaneous involvement to catastrophic thromboembolism and is usually associated with an underlying thrombophilia. We describe a patient who developed skin necrosis during warfarin treatment for a pulmonary thromboembolism. The management was complicated by the development of heparin-induced thrombocytopenia and further thrombotic events. Thrombophilia screen demonstrated the presence of protein S deficiency and Factor V Leiden as the prothrombotic factors, together with the demonstration of antiplatelet factor 4 antibodies, which confirms the diagnosis of heparin-induced thrombocytopenia (type II). Reinstitution of warfarin at a low loading dose was successful without the recurrence of skin lesions nor any further thrombosis.

Adult↗
PubMed2001

Haemangiopericytoma of the trigeminal nerve.

A 41-year-old man presented with a 4-year history of progressive right-sided diplopia on lateral gaze and right nasolabial paraesthesia. A CT revealed minor bone erosion of Meckel's cave and of the right petrous apex by a uniformly enhancing lesion at the base of the skull. Magnetic resonance imaging on three occasions over 2 years showed tumour, measuring 4 cm in diameter, with features suggestive of a trigeminal neuroma. At surgery the lesion had the macroscopic appearance of a giant schwannoma. Histopathological findings were that of a meningeal haemangiopericytoma (HPC) of the trigeminal nerve. Intracranial HPC are rare and aggressive tumours of the central nervous system. They usually arise from the falx, tentorium and dural sinuses. The present case is unique as it originates from a cranial nerve.

Adult↗
PubMed2001

Lipid rafts act as specialized domains for tetanus toxin binding and internalization into neurons.

Tetanus (TeNT) is a zinc protease that blocks neurotransmission by cleaving the synaptic protein vesicle-associated membrane protein/synaptobrevin. Although its intracellular catalytic activity is well established, the mechanism by which this neurotoxin interacts with the neuronal surface is not known. In this study, we characterize p15s, the first plasma membrane TeNT binding proteins and we show that they are glycosylphosphatidylinositol-anchored glycoproteins in nerve growth factor (NGF)-differentiated PC12 cells, spinal cord cells, and purified motor neurons. We identify p15 as neuronal Thy-1 in NGF-differentiated PC12 cells. Fluorescence lifetime imaging microscopy measurements confirm the close association of the binding domain of TeNT and Thy-1 at the plasma membrane. We find that TeNT is recruited to detergent-insoluble lipid microdomains on the surface of neuronal cells. Finally, we show that cholesterol depletion affects a raft subpool and blocks the internalization and intracellular activity of the toxin. Our results indicate that TeNT interacts with target cells by binding to lipid rafts and that cholesterol is required for TeNT internalization and/or trafficking in neurons.

Animals↗
PubMed2001

Pilomatrix carcinoma: case report and review of literature.

We report the case of a 57-year-old immunocompromised man with a pilomatrix carcinoma in his left forearm. Pilomatrix carcinoma is the rare malignant counterpart of pilomatrixoma. It has a potential for local recurrence and can metastasise to distant sites. We discuss the differential diagnosis of this rare tumour, and the difficulty in distinguishing this lesion from an atypical proliferating pilomatrixoma. Ultrastructural features of pilomatrix carcinoma are also discussed.

Carcinoma↗
PubMed2000

Esophageal histology does not provide additional useful information over clinical assessment in identifying reflux patients presenting for esophagogastroduodenoscopy.

We prospectively evaluated the value of histology in identifying gastroesophageal reflux disease (GERD) in consecutive patients enrolled for upper endoscopy. GERD was defined as heartburn occurring at least weekly. Macroscopic esophagitis was graded and an esophageal biopsy was taken 2 cm above the gastroesophageal junction. Histological esophagitis was identified by: (1) basal cell hyperplasia >15%, (2) increased papillary length >66%, and (3) infiltration by leukocytes/eosinophils. The sensitivity, specificity, and positive and negative predictive value of histological esophagitis in patients with and without typical reflux symptoms, with and without endoscopic changes, or both were evaluated. Of 178 patients, reflux symptoms were present in 59% (N = 105) and esophageal erosions in 19% (N = 34); 75 patients had reflux symptoms but no erosions. While the specificity of histology was adequate (78%), it was insensitive (30%). The positive and negative predictive values were 67% and 44%, respectively. No single individual parameter was better than any other. Thus, histology appears to be of no additional value in identifying GERD.

Endoscopy, Digestive System↗
PubMed2000

Colchicine: an effective treatment for refractory malignant pericardial effusion.

We report a patient with AL amyloidosis and chemo-resistant light-chain multiple myeloma who developed a progressive malignant pericardial effusion leading to cardiac tamponade. Despite pericardiocentesis and surgical intervention, the pericardial effusion failed to resolve. The administration of oral colchicine produced symptomatic relief within 5 days, with the resolution of pericardial effusion after 14 days of treatment. As the administration of colchicine is simple and the side-effect is usually minimal, further studies are warranted to establish the feasibility of using colchicine to treat malignant pericardial effusion.

Adult↗
PubMed2000

Non-caseating granulomata associated with hypocellular myelodysplastic syndrome.

Non-caseating granuloma (NCG) remains a histopathological hallmark for sarcoidosis. Although the exact mechanism for NCG formation is unknown, the pathogenesis may involve a disordered antigen presentation in the monocyte/macrophage system, functional abnormalities in activated T-lymphocytes and uncontrolled cytokine production. Similar immunological dysfunction has been described in myelodysplastic syndrome (MDS). However, the association of NCG and MDS is rarely documented. We report a case of hypocellular MDS associated with generalized NCG. Despite treatment for both sarcoidosis and tuberculosis, the patient failed to respond. A clonal myeloid disorder which was initially suppressed by T-cell immunosurveillance evolved after treatment with anti-thymocyte globulin. Although the coexistence of sarcoidosis remains a possibility, the lack of supportive clinical evidence of sarcoidosis, the abnormal appearances of the bone marrow, together with the failure to improve on high-dose steroid favour the clonal myeloid disorder as the sole pathology.

Adult↗
PubMed1999

PKCalpha regulates beta1 integrin-dependent cell motility through association and control of integrin traffic.

Protein kinase C (PKC) has been implicated in integrin-mediated spreading and migration. In mammary epithelial cells there is a partial co-localization between beta1 integrin and PKCalpha. This reflects complexes between these proteins as demonstrated by fluorescense resonance energy transfer (FRET) monitored by fluorescence lifetime imaging microscopy and also by coprecipitation. Constitutive complexes are observed for the intact PKCalpha and also form with the regulatory domain in an activation-dependent manner. Expression of PKCalpha causes upregulation of beta1 integrin on the cell surface, whereas stimulation of PKC induces internalization of beta1 integrin. The integrin initially traffics to an endosomal compartment in a Ca(2+)/PI 3-kinase/dynamin I-dependent manner and subsequently enters an endocytic recycling pathway. This induction of endocytosis by PKCalpha is a function of activity and is not observed for the regulatory domain. PKCalpha, but not PKCalpha regulatory domain expression stimulates migration on beta1 integrin substrates. This PKCalpha-enhanced migratory response is inhibited by blockade of endocytosis.

Calcium↗