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Biomedical subjects

A Ng

Publications and source records attributed to A Ng.

At least 73 records · Page 4Linked to original sources
PubMed1997

Abnormal prostate development in C3(1)-bcl-2 transgenic mice.

BACKGROUND: Recent hypotheses to explain the etiology of abnormal growth associated with prostate disease have invoked perturbations in the rate of apoptosis as an important contributor to the onset and progression of these diseases. For this reason, the apoptosis suppressing oncoprotein bcl-2 has come under scrutiny with regards to its role in prostate diseases. In order to evaluate the role of bcl-2 in human prostate disease and to develop an animal model to test anti-bcl-2 therapies, we generated transgenic mice in which bcl-2 expression is targeted to the mouse prostate gland. METHODS: Mouse embryos were microinjected with recombinant DNA constructed by fusing a modified rat C3(1) promotor element to cDNA encoding human bcl-2. Presence of the C3(1)-bcl-2 transgene in progeny was identified by Southern blot and polymerase chain reaction (PCR) analysis. RNase protection assays were used to analyze RNA from 15 organs of these mice. Western blot assays and immunohistochemical staining were used to confirm the tissue-specific protein expression of human bcl-2 and its cellular localization. RESULTS: Three lines of C3(1)-bcl-2 transgenic mice were established. Founder mice carried 2-20 copies of the transgene. Expression of human bcl-2 from the transgene was limited to the prostate gland and testis of males as well as the uterus of females. In the prostate gland, human bcl-2 protein was found only in prostatic epithelial cells. Microscopic analysis of prostate glands from individual males (three lines) showed that these glands were often abnormal, with increased accumulation of cells in the prostatic stroma as well as the epithelium. CONCLUSIONS: These transgenic mice appear to provide a novel animal model for studying neoplastic development of the prostate, with particular emphasis on the bcl-2 protein and the role of apoptosis regulation in such development.

Animals↗
PubMed1997

D-Cbl, the Drosophila homologue of the c-Cbl proto-oncogene, interacts with the Drosophila EGF receptor in vivo, despite lacking C-terminal adaptor binding sites.

The c-Cbl proto-oncogene encodes a multidomain phosphoprotein that has been demonstrated to interact with a wide range of signalling proteins. The biochemical function of c-Cbl in these complexes is, however, unclear. Recent studies with the C. elegans Cbl homologue, sli-1, have suggested that Cbl proteins may act as negative regulators of EGF receptor (EGFR) signalling. As the EGFR and other protein tyrosine kinase receptor signalling pathways are highly conserved between insects and vertebrates, we sought a Drosophila homologue of c-Cbl for a detailed genetic analysis. We report here that Drosophila melanogaster has a single gene, D-cbl, that is homologous to c-cbl. We find that D-cbl encodes a 52 kDa protein that has a high degree of similarity to c-Cbl and SLI-1 across novel phosphotyrosine-binding (PTB) and RING finger domains. Surprisingly, however, D-Cbl is C-terminally truncated relative to c-Cbl and SLI-1 and consequently is unable to bind SH3-domain containing adaptor proteins, including the Drosophila Grb2 homologue, Drk. Although the D-Cbl protein lacks Drk binding sites it can nevertheless associate with a tyrosine phosphorylated protein, or is itself tyrosine phosphorylated in an DER dependent manner and associates with activated Drosophila EGF receptors (DER) in vivo. Consistent with a role for D-Cbl in DER dependent patterning in the embryo and adult, D-Cbl is expressed at a high level in early embryos and throughout the imaginal discs in third instar larvae. This study forms the basis for future genetic analysis of D-Cbl, aimed at gaining insights into the role of Cbl proteins in signal transduction.

Amino Acid Sequence↗
PubMed1997

Atomic force microscopy of plant cell walls, plant cell wall polysaccharides and gels.

Methods developed for the routine imaging of polysaccharides by atomic force microscopy (AFM) have been used to image plant polysaccharides from higher plants (pectin) and algae (carrageenan). These methods have been extended to image K-carrageenan association in hydrated films. Finally, AFM has been used to image polysaccharide architecture in moist plant cell walls. Simple experimental and image processing methods have been used to enhance molecular structure in 'rough' cell wall surfaces.

Cell Wall↗
PubMed1997

Defining the roles of high dose rate endobronchial brachytherapy and laser resection for recurrent bronchial malignancy.

Endobronchial therapy is commonly used in the palliative management of malignant disease, but the optimal combinations of treatment modalities (laser, brachytherapy, external beam radiotherapy) have not been defined. We have undertaken a prospective analysis of symptom response, duration of response, and prognostic factors for 117 patients treated with brachytherapy at a single centre, to identify hypotheses suitable for prospective randomised studies. All but one patient had received previous treatment. The percentage of patients with scores of 0 or 1 (none or mild) for each symptom pre-treatment and at 3 months were as follows: cough 62% to 77% (43% improving by at least one grade, N.S.); dyspnoea 32% to 56% (50% improvement by at least one grade, P = 0.0063); haemoptysis 78% to 97%; performance status 65% to 84% (54% by at least one grade, P = 0.0417). An actuarial risk of fatal haemoptysis at 2 years of 20% was associated with prior laser resection (P = 0.048). Death before 2 months was associated with dyspnoea scores of 3 or 4. Suggestions for randomised studies are made to address some of the uncertainties revealed by the analysis.

Brachytherapy↗
PubMed1997

Laryngeal mask insertion following inhalational induction in children: a comparison between halothane and sevoflurane.

The aim of this study was to compare laryngeal mask insertion conditions following inhalational induction with either halothane or sevoflurane. Fifty-eight healthy children scheduled for dental extraction were randomly assigned to receive nitrous oxide 66% in oxygen and 3.0 MAC of either halothane or sevoflurane introduced in a stepwise fashion. The laryngeal masks were inserted when an adequate depth of anaesthesia was attained and the reactions and time to insertion noted. Inhalational induction was smooth in both halothane and sevoflurane groups. Induction time and time to laryngeal mask insertion were significantly faster with sevoflurane. The conditions for laryngeal mask insertion were generally good with 86.2% and 89.2% in the halothane and sevoflurane groups respectively having had no reactions to insertion. The complications to laryngeal mask insertion encountered were mild. The emergence time from the anaesthetic was found to be shorter for sevoflurane but the difference was not statistically significant.

Anesthesia, Dental↗
PubMed1996

Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells.

Many cytokines exert their biological effect through members of the hemopoietin receptor family. Using degenerate oligonucleotides to the common WSXWS motif, we have cloned from human hemopoietic cell cDNA libraries various forms of the receptor that was recently shown to bind the obesity hormone, leptin. mRNAs encoding long and short forms of the human leptin receptor were found to be coexpressed in a range of human and murine hemopoietic organs, and a subset of cells from these tissues bound leptin at the cell surface. Ectopic expression in murine Ba/F3 and M1 cell lines revealed that the long, but not the short, form of the leptin receptor can signal proliferation and differentiation, respectively. In cultures of murine or human marrow cells, human leptin exhibited no capacity to stimulate cell survival or proliferation, but it enhanced cytokine production and phagocytosis of Leishmania parasites by murine peritoneal macrophages. Our data provide evidence that, in addition to its role in fat regulation, leptin may also be able to regulate aspects of hemopoiesis and macrophage function.

Amino Acid Sequence↗
PubMed1996

Visualization of plant cell walls by atomic force microscopy.

Atomic force microscopy has been used to visualize the ultrastructure of hydrated plant cell wall material from prepared apple (Malus pumila MILL; Cox orange pippin), water chestnut (Eleocharis dulcis L.), potato (Solanum tuberosum L.; Bintje), and carrot (Daucus carota L.; Amsterdamse bak) parenchyma. Samples of cell wall material in aqueous suspension were deposited onto freshly cleaved mica. Excess water was blotted away and the moist samples were imaged in air at ambient temperature and humidity. The three-dimensional images obtained highlighted the layered structure of the plant cell walls and revealed features interpreted as individual cellulose microfibrils and plasmodesmata.

Biophysical Phenomena↗
PubMed1996

Exercise 201Tl/rest 99Tcm-tetrofosmin myocardial perfusion imaging: a convenient protocol for the assessment of coronary disease.

Standard exercise thallium-201 (201Tl)-redistribution protocols for the detection of coronary artery disease take about 4 h to complete. This is inconvenient for both patients and staff. The higher energy technetium-99m (99Tcm) emissions permit immediate imaging after 201Tl with minimal crosstalk. This study assessed exercise gated planar 201Tl scintigraphy (55 MBq) followed by rest gated planar 99Tcm-tetrofosmin scintigraphy (250 MBq) in 32 patients. The results showed a high sensitivity for the detection of coronary disease (100%) in this highly selective group of patients. In order to diagnose myocardial infarction accurately, it was necessary to view the gated 201Tl images and assess regional wall motion in a defect zone. This gave a specificity of 88% and a sensitivity of 71% for the prediction of myocardial infarction on the angiographic ventriculogram. Stress 201Tl/rest 99Tcm-tetrofosmin is a useful short protocol for patients unable to complete the full 4-h exercise 201Tl-redistribution study.

Adult↗
PubMed1996

Characterization and partial purification of microsomal casein kinase II from osteoblast-like cells: an enzyme that phosphorylates osteopontin and phosphophoryn.

Microsomal casein kinase II (mCKII) is a membrane-bound enzyme present in the microsomal fractions of ROS 17/2.8 osteoblast-like cells. It phosphorylates acidic matrix phosphoproteins such as phosphophoryn and osteopontin. Addition of 1.0% Nonidet P-40 facilitates extraction of the optimum amount of detergent-solubilized and -activated enzyme from microsomal fractions. mCKII was partially purified over 3000-fold by sequential chromatography over DEAE-cellulose and heparin-agarose. SDS-polyacrylamide gels, showed that mCKII contained 43 kDa and 31 kDa polypeptides, corresponding to the alpha- and beta-subunits of the enzyme, respectively. The alpha subunit was identified by anti-CKII antiserum and the beta subunit, by its ability to undergo autophosphorylation. The enzyme was inhibited by 50% with 0.4 micrograms/ml heparin and stimulated by 100% with 1.0 mM spermine when casein was used as a substrate. The phosphorylation of phosphophoryn was reduced to 50% by 0.8 micrograms/ml heparin, but was increased to 2-2.5 fold by 5 to 15 mM spermine, which may be due to substrate-directed effects. Kinetic analysis showed that the apparent Km values for phosphophoryn (0.39 microM) and for osteopontin (2.1 microM) were lower than that for casein (21.3 microM). Vmax values of phosphophoryn and osteopontin were 2.2-fold and 4.6-fold higher than that of casein. Using the ratio Vmax/Km as a measure of kinetic specificity, osteopontin and phosphophoryn appear to be the more specific substrates than casein for mCKII. Thus, both proteins can be considered as physiological substrates for mCKII.

Animals↗
PubMed1996

Diagnosis and Treatment of Early-Stage Non-Small Cell Lung Cancer.

Current recommendations for the diagnostic work-up and treatment of early-stage non-small cell lung cancer are presented, and the rationale behind these recommendations is reviewed. Early-stage disease is found in approximately 30% of patients at initial presentation. Surgeons continue to be uncertain with regard to how extensively they should look for metastatic disease, especially in asymptomatic patients with newly diagnosed lung cancer. While it is generally agreed that surgery is an important component of treatment for stage I and II non-small cell lung cancer, the role of adjuvant therapies in early-stage disease merits further study. Stage IIIa lung cancer is evolving as a disease for which multimodality therapy is likely to play a role, but the timing and sequence of treatment is an area of intense investigation. The recommendations made in this article are based upon the results of randomized clinical trials whenever possible.

Journal Article↗
PubMed1996

Safety and efficacy of percutaneous Inoue-balloon mitral commissurotomy.

BACKGROUND: Although percutaneous transvenous mitral commissurotomy (PTMC) is currently accepted as the first-line treatment modality for selected patients with mitral stenosis, technical failures and the potential risk of inadvertent cardiac perforation with tamponade, resultant severe mitral regurgitation and death associated with the procedure continue to be important issues of concern. OBJECTIVES: The purpose of this study was to assess the safety profile and acute results of Inoue-balloon PTMC in a consecutive series of 50 patients with symptomatic significant mitral stenosis who underwent the procedure between January 1993 and August 1994. RESULTS: PTMC was successfully completed in all patients without encountering cardiac perforation, cardioembolism, severe (> or = grade 3+) angiographic mitral regurgitation or death. The mitral valve area increased from 0.8 +/- 0.2 cm2 to 1.7 +/- 0.4 cm2 (p = 0.0001) as assessed echocardiographically. Optimal results defined as a valve area improvement of > or = 50% and/or a final valve area of > or = 1.5 cm2 without significant mitral regurgitation (> or = 2 grade increase in mitral regurgitation or a final regurgitation > or = 3+) was obtained in 94% of patients. CONCLUSION: We confirm that Inoue-balloon PTMC is a safe and highly effective procedure as reflected by the absence of cardiac perforation, cardioembolism, severe mitral regurgitation or death and the excellent enlargement in mitral valve area. Furthermore, in our study the clinical restenosis rate was low with the majority of patients maintaining their improved functional status over a 14-month follow-up period.

Adult↗
PubMed1995

Intracoronary stenting in the treatment of acute or threatened closure in angiographically small coronary arteries (< 3.0 mm) complicating percutaneous transluminal coronary angioplasty.

The effect of the Flex-Stent on immediate and long-term angiographic and clinical results for acute and threatened closure was evaluated in 42 consecutive patients with coronary arterial segments < 3.0 mm in diameter after percutaneous transluminal coronary angioplasty (PTCA). Forty-two consecutive patients were treated with Flex-Stent (2.0 or 2.5 mm) for acute or threatened closure complicating PTCA. Ten patients (24%) had acute closure and 32 (76%) had threatened closure with a residual luminal stenosis of > 50%. Successful stent deployment was achieved in 40 patients (95%) with a primary clinical success rate of 90% (freedom from myocardial infarction, coronary artery surgery, and death). In-hospital complications occurred in 5 patients (some patients fell into more than one category): 3 (7.1%) had coronary bypass surgery, 1 (2.4%) had acute stent thrombosis, 1 (2.4%) had subacute stent thrombosis, 2 (4.8%) had myocardial infarction, and 1 (2.4%) had dextran allergy. There was no hospital death. Clinical follow-up was complete at a mean of 14.8 +/- 7.6 months, and recurrence of angina was noted in 20 of 38 eligible patients (53%). Angiographic restenosis was found in 19 of 29 patients (66%) (76.3% of eligible patients) on follow-up angiography (mean 5.9 +/- 4.6 months). Fourteen patients (74%) underwent successful repeat PTCA at the stented site, 4 of 38 patients (11%) had bypass surgery. Intracoronary stenting in the treatment of acute or threatened closure in arteries < 3.0 mm is effective in improving the acute clinical outcome and is a viable nonsurgical alternative for this subset of patients.

Acute Disease↗
PubMed1995

Characteristics of diaphragm muscle fibre types in hibernating squirrels.

Muscle samples from the diaphragms of 7 full-awake (FA), 10 winter-awake (WA), and 8 hibernating (H) squirrels (Spermophilus lateralis) were quick frozen, sectioned and processed for NADH-TR reaction end-product and myofibrillar-ATPase. Both WA and H squirrels showed small increases in diaphragm weight, reductions in body weight, and hence, significant increases in the diaphragm weight to body weight ratio compared to FA squirrels. They also showed increases in muscle fibre type cross-sectional areas and in the oxidative capacity of type 2b fibres as well as a reduction in capillary density. Furthermore, there also was an increase in the proportion of type 2b fibres in the diaphragm of the H squirrels. Thus, despite the dramatically reduced ventilation associated with hibernation, H squirrels exhibited (1) hypertrophy of the diaphragm which may represent an adaptive response that enables them to work against a stiffer chest wall, and (2) an increased oxidative capacity which enables them to fuel this with fat.

Animals↗
PubMed1995

A rare cause of an acute abdomen in late pregnancy.

A case is presented where spontaneous rupture of a uterine arteriovenous malformation into the peritoneal cavity presented as an acute abdomen with fetal distress in late pregnancy. This is thought to be the first reported case of its type.

Abdomen, Acute↗